Research Publications

Browse scientific publications from the NIH-funded RDCRN network and its 20 consortia or research teams to find information about rare disease research and read rare disease publications. Publications are sorted by consortium and year.

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A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis. Galeffi F, Snellings DA, Wetzel-Strong SE, Kastelic N, Bullock J, Gallione CJ, North PE, Marchuk DA. Angiogenesis. 2022 May 30. doi: 10.1007/s10456-022-09841-w. Epub ahead of print. PMID: 35635655.

Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel development in the brain, eyes, and skin at birth. A hallmark feature is capillary malformation, also known as a port-wine birthmark (a red, pink, or purple facial birthmark). SWS and capillary malformations are both caused by mutations in the GNAQ gene. In this study, researchers sequenced skin biopsies of capillary malformations from nine patients. They identified the same type of GNAQ mutation (R183Q) in nearly all samples. However, one sample exhibited a new type of GNAQ mutation (Q209R). To explore its effects, the team compared this new mutation with other GNAQ mutations. The authors found that although the different mutations varied in signaling strength, they all had the same effects in cells. Since some of these same mutations are also found in cancer, pharmaceutical companies are working on inhibiting the effects of this gene. Thus, drugs that may work for certain cancers with GNAQ mutations may also work for SWS.

A single-cell atlas of the normal and malformed human brain vasculature. Winkler EA, Kim CN, Ross JM, Garcia JH, Gil E, Oh I, Chen LQ, Wu D, Catapano JS, Raygor K, Narsinh K, Kim H, Weinsheimer S, Cooke DL, Walcott BP, Lawton MT, Gupta N, Zlokovic BV, Chang EF, Abla AA, Lim DA, Nowakowski TJ. Science. 2022 Mar 4;375(6584):eabi7377. doi: 10.1126/science.abi7377. Epub 2022 Mar 4.

Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence. Sheth KN, Anderson CD, Biffi A, Dlamini N, Falcone GJ, Fox CK, Fullerton HJ, Greenberg SM, Hemphill JC, Kim A, Kim H, Ko NU, Roland JL, Sansing LH, van Veluw SJ, Rosand J. Stroke. 2022 Mar;53(3):1020-1029. doi: 10.1161/STROKEAHA.121.036197. Epub 2022 Feb 3.

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways. Cannavicci A, Zhang Q, Faughnan ME, Kutryk MJB. Genes (Basel). 2022 Apr 9;13(4):665. doi: 10.3390/genes13040665.

Neurovascular Complications and Pulmonary Arteriovenous Malformation Feeding Artery Size. Ananiadis T, Faughnan ME, Clark D, Prabhudesai V, Kim H, Lawton MT, Vozoris NT; Brain Vascular Malformation Consortium HHT Investigator Group. Ann Am Thorac Soc. 2022 Apr 20. doi: 10.1513/AnnalsATS.202202-130RL. Online ahead of print.

Quantification metrics for telangiectasia using optical coherence tomography. Cardinell JL, Ramjist JM, Chen C, Shi W, Nguyen NQ, Yeretsian T, Choi M, Chen D, Clark DS, Curtis A, Kim H, Faughnan ME, Yang VXD; Brain Vascular Malformation Consortium HHT Investigator Group. Sci Rep. 2022 Feb 2;12(1):1805. doi: 10.1038/s41598-022-05272-1.

Robotics for neuroendovascular intervention: Background and primer. Narsinh KH, Paez R, Mueller K, Caton MT, Baker A, Higashida RT, Halbach VV, Dowd CF, Amans MR, Hetts SW, Norbash AM, Cooke DL. Neuroradiol J. 2022 Feb;35(1):25-35. doi: 10.1177/19714009211034829. Epub 2021 Aug 16.

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation. Choksi F, Weinsheimer S, Nelson J, Pawlikowska L, Fox CK, Zafar A, Mabray MC, Zabramski J, Akers A, Hart BL, Morrison L, McCulloch CE, Kim H. Mol Genet Genomic Med. 2021 Sep 7:e1794. doi: 10.1002/mgg3.1794. Online ahead of print.

Cerebral cavernous malformations (CCMs) are collections of small blood vessels in the brain that are enlarged and irregular in structure, leading to altered blood flow. While approximately 25 percent of individuals with CCMs never experience any related medical problems, other people with CCMs may experience serious symptoms such as headaches, seizures, paralysis, hearing or vision deficiencies, and cerebral hemorrhage. In addition to lesions in the brain, familial cases have lesions present on the skin. Interestingly, similar appearing skin lesions have been reported in another inherited vascular disease called capillary malformation-arteriovenous malformation (CM-AVM), which is caused by mutations in RASA1 and EPHB4. In this study, researchers investigated whether common variants in the EPHB4 and RASA1 genes are associated with familial CCM disease severity, including intracranial hemorrhage (ICH), total lesions, and large lesion counts. They found that EPHB4 variants were not associated with CCM severity, but a common RASA1 variant may be associated with ICH and large lesion count. These findings could improve understanding of the natural history of CCM, leading to better predictions of disease course and new medical therapies for treatment.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention. Narsinh KH, Kilbride BF, Mueller K, Murph D, Copelan A, Massachi J, Vitt J, Sun CH, Bhat H, Amans MR, Dowd CF, Halbach VV, Higashida RT, Moore T, Wilson MW, Cooke DL, Hetts SW. Radiology. 2021 Apr;299(1):167-176. doi: 10.1148/radiol.2021202750. Epub 2021 Feb 9.

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations. Sabeti S, Ball KL, Bhattacharya SK, Bitrian E, Blieden LS, Brandt JD, Burkhart C, Chugani HT, Falchek SJ, Jain BG, Juhasz C, Loeb JA, Luat A, Pinto A, Segal E, Salvin J, Kelly KM. Pediatr Neurol. 2021 Aug;121:59-66. doi: 10.1016/j.pediatrneurol.2021.04.013. Epub 2021 May 6.

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation. Keränen S, Suutarinen S, Mallick R, Laakkonen JP, Guo D, Pawlikowska L, Jahromi BR, Rauramaa T, Ylä-Herttuala S, Marchuk D, Krings T, Koivisto T, Lawton M, Radovanovic I, Kim H, Faughnan ME, Frösen J. Acta Neurochir (Wien). 2021 Sep;163(9):2503-2514. doi: 10.1007/s00701-021-04895-z. Epub 2021 Jun 29.

Brain ateriovenous malformations (bAVM) are rare vascular anomalies that may bleed causing epilepsy, neurological deficits, or death. Cyclo-oxygenase-2 (COX2) is an enzyme that plays a key role in promoting inflammation. Researchers examined tissue samples from surgery of 139 patients with bAVMs and compared them to 21 normal samples. They were seeking to determine if COX2 is expressed in bAVMs and whether it associates with inflammation and hemorrhage in these lesions. They concluded that COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodeling and ongoing inflammation. Authors suggest that COX2 may be a target for drug therapy stabilizing bAVMs.  

Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells. Zhang Q, Wang C, Cannavicci A, Faughnan ME, Kutryk MJB. Transl Res. 2021 Sep;235:129-143. doi: 10.1016/j.trsl.2021.04.005. Epub 2021 Apr 22.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of the blood vessels that can cause excessive bleeding. People with HHT can develop abnormal blood vessels called arteriovenous malformations (AVMs) in several areas of the body, including the skin, brain, lungs, liver, or intestines. Endoglin (ENG) is one of the genes commonly mutated in this autosomal dominant disease. In this study, researchers sought to investigate the interplay of the ENG gene with several other genes in endothelial cells. They found that ENG deficiency alters the vascular endothelial growth factor (VEGF)/VEGFR2 pathway, which may play a role in the development of HHT.

Identification of a Mosaic Activating Mutation in GNA11 in Atypical Sturge-Weber Syndrome. Thorpe J, Frelin LP, McCann M, Pardo CA, Cohen BA, Comi AM, Pevsner J. J Invest Dermatol. 2021 Mar;141(3):685-688. doi: 10.1016/j.jid.2020.03.978. Epub 2020 Aug 7.

Intracranial hemorrhage due to central venous occlusion from hemodialysis access: A case report. Mirza MH, Schwertner A, Kohlbrenner R, Dowd CF, Narsinh KH. Interdiscip Neurosurg. 2021 Jun;24:101081. doi: 10.1016/j.inat.2020.101081. Epub 2021 Jan 4.

Intrasaccular flow disruption (WEB) of a large wide-necked basilar apex aneurysm using PulseRider-assistance. Narsinh KH, Caton MT, Mahmood NF, Higashida RT, Halbach VV, Hetts SW, Amans MR, Dowd CF, Cooke DL. Interdiscip Neurosurg. 2021 Jun;24:101072. doi: 10.1016/j.inat.2020.101072. Epub 2020 Dec 29.

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome. Smegal LF, Sebold AJ, Hammill AM, Juhász C, Lo WD, Miles DK, Wilfong AA, Levin AV, Fisher B, Ball KL, Pinto AL, Comi AM; National Institutes of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2021 Jun;119:3-10. doi: 10.1016/j.pediatrneurol.2021.02.006. Epub 2021 Mar 5.

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Wetzel-Strong SE, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.

Vascular malformations are growths composed of blood vessels involving arteries, veins, capillaries, and lymphatics. Patients with vascular malformations in the central nervous system may experience a range of debilitating or life-threatening symptoms including seizures, headaches, and increased risk of cerebral hemorrhage. Due to their inaccessible location, these malformations are difficult to monitor and treat. Therefore, biomarkers from a non-invasive tissue source, such as blood, may aid in predicting disease severity and outcomes. In this study, researchers compared circulating biomarker levels in plasma from patients with sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformations (CCM), and hereditary hemorrhagic telangiectasia (HHT). They found that biomarkers may be unique to each type of vascular malformation, indicating potential usefulness in assessing phenotypic traits of vascular malformations.

Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Thompson KP, Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2021 Jan 6;16(1):12. doi: 10.1186/s13023-020-01579-2.

Quantitative EEG improves prediction of Sturge-Weber syndrome in infants with port-wine birthmark. Gill RE, Tang B, Smegal L, Adamek JH, McAuliffe D, Lakshmanan BM, Srivastava S, Quain AM, Sebold AJ, Lin DDM, Kossoff EH, Caffo B, Comi AM, Ewen JB. Clin Neurophysiol. 2021 Oct;132(10):2440-2446. doi: 10.1016/j.clinph.2021.06.030. Epub 2021 Aug 5.

Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations. Fox CK, Nelson J, McCulloch CE, Weinsheimer S, Pawlikowska L, Hart B, Mabray M, Zafar A, Morrison L, Zabramski JM, Akers A, Kim H. Neurology. 2021 Aug 13;97(12):e1210-6. doi: 10.1212/WNL.0000000000012569. Online ahead of print.

Sirolimus Treatment in Sturge-Weber Syndrome. Sebold AJ, Day AM, Ewen J, Adamek J, Byars A, Cohen B, Kossoff EH, Mizuno T, Ryan M, Sievers J, Smegal L, Suskauer SJ, Thomas C, Vinks A, Zabel TA, Hammill AM, Comi AM. Pediatr Neurol. 2021 Feb;115:29-40. doi: 10.1016/j.pediatrneurol.2020.10.013. Epub 2020 Nov 2.

Systemic and CNS manifestations of inherited cerebrovascular malformations. Hart BL, Mabray MC, Morrison L, Whitehead KJ, Kim H. Clin Imaging. 2021 Jul;75:55-66. doi: 10.1016/j.clinimag.2021.01.020. Epub 2021 Jan 20.

Review paper examines imaging and clinical features of cerebrovascular malformations with a genetic basis, summarizing the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia. Thompson KP, Nelson J, Kim H, Weinsheimer SM, Marchuk DA, Lawton MT, Krings T, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2021 Sep 19;16(1):390. doi: 10.1186/s13023-021-02012-y.

Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture. Copelan A, Drocton G, Caton MT, Smith ER, Cooke DL, Nelson J, Abla AA, Fox C, Amans MR, Dowd CF, Halbach VV, Higashida RT, Lawton MT, Kim H, Fullerton HJ, Gupta N, Hetts SW; UCSF Center For Cerebrovascular Research and UCSF Pediatric Brain Center. Stroke. 2020 Oct;51(10):2990-2996. doi: 10.1161/STROKEAHA.120.030135. Epub 2020 Sep 11.

Clinical outcomes after revascularization for pediatric moyamoya disease and syndrome: A single-center series. Morshed RA, Abla AA, Murph D, Dao JM, Winkler EA, Burkhardt JK, Colao K, Hetts SW, Fullerton HJ, Lawton MT, Gupta N, Fox CK. J Clin Neurosci. 2020 Sep;79:137-143. doi: 10.1016/j.jocn.2020.07.016. Epub 2020 Aug 19.

Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome. Isikbay M, Narsinh KH, Arroyo S, Smith WS, Cooke DL, Higashida RT, Amans MR. J Vasc Surg Cases Innov Tech. 2020 Oct 27;7(1):171-175. doi: 10.1016/j.jvscit.2020.10.010. eCollection 2021 Mar.

Cutaneous findings of familial cerebral cavernous malformation syndrome due to the common Hispanic mutation. Manole AK, Forrester VJ, Zlotoff BJ, Hart BL, Morrison LA. Am J Med Genet A. 2020 May;182(5):1066-1072. doi: 10.1002/ajmg.a.61519. Epub 2020 Feb 26.

Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial. Mabray MC, Caprihan A, Nelson J, McCulloch CE, Zafar A, Kim H, Hart BL, Morrison L. Transl Stroke Res. 2020 Jun;11(3):319-321. doi: 10.1007/s12975-019-00737-4. Epub 2019 Oct 23.

Genome-wide Genotyping of Cerebral Cavernous Malformation Type 1 Individuals to Identify Genetic Modifiers of Disease Severity. Choquet H, Kim H. Methods Mol Biol. 2020;2152:77-84. doi: 10.1007/978-1-0716-0640-7_6.

Genotype-Phenotype Correlations in Children with HHT. Kilian A, Latino GA, White AJ, Clark D, Chakinala MM, Ratjen F, McDonald J, Whitehead K, Gossage JR, Lin D, Henderson K, Pollak J, McWilliams JP, Kim H, Lawton MT, Faughnan ME; the Brain Vascular Malformation Consortium HHT Investigator Group. J Clin Med. 2020 Aug 22;9(9):2714. doi: 10.3390/jcm9092714.

High Prevalence of Spinal Cord Cavernous Malformations in the Familial Cerebral Cavernous Malformations Type 1 Cohort. Mabray MC, Starcevich J, Hallstrom J, Robinson M, Bartlett M, Nelson J, Zafar A, Kim H, Morrison L, Hart BL. AJNR Am J Neuroradiol. 2020 Jun;41(6):1126-1130. doi: 10.3174/ajnr.A6584. Epub 2020 May 28.

Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs. Narsinh KH, Mueller K, Nelson J, Massachi J, Murph DC, Copelan AZ, Hetts SW, Halbach VV, Higashida RT, Abla AA, Amans MR, Dowd CF, Kim H, Cooke DL. AJNR Am J Neuroradiol. 2020 Dec;41(12):2303-2310. doi: 10.3174/ajnr.A6846. Epub 2020 Oct 29.

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia. Cannavicci A, Zhang Q, Kutryk MJB. J Clin Med. 2020 Oct 17;9(10):3333. doi: 10.3390/jcm9103333.

Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA. Nat Commun. 2020 May 27;11(1):2659. doi: 10.1038/s41467-020-16436-w.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software. Copelan AZ, Smith ER, Drocton GT, Narsinh KH, Murph D, Khangura RS, Hartley ZJ, Abla AA, Dillon WP, Dowd CF, Higashida RT, Halbach VV, Hetts SW, Cooke DL, Keenan K, Nelson J, Mccoy D, Ciano M, Amans MR. AJNR Am J Neuroradiol. 2020 Dec;41(12):2235-2242. doi: 10.3174/ajnr.A6908. Epub 2020 Nov 19.

Subjective Cognitive Concerns and Attitudes toward Genetic Testing Are Associated with Depressive Symptoms and Quality of Life after Genetic Testing for the Cerebral Cavernous Malformation Common Hispanic Mutation (CCM1). Campbell R, Petranovich CL, Cheek S, Morrison L, Hart B. J Behav Brain Sci. 2020 Feb;10(2):118-127. doi: 10.4236/jbbs.2020.102007. Epub 2020 Feb 25.

The Expanding Cell Diversity of the Brain Vasculature. Ross JM, Kim C, Allen D, Crouch EE, Narsinh K, Cooke DL, Abla AA, Nowakowski TJ, Winkler EA. Front Physiol. 2020 Dec 3;11:600767. doi: 10.3389/fphys.2020.600767. eCollection 2020.

Vertebral Intraosseous Vascular Malformations in a Familial Cerebral Cavernous Malformation Population: Prevalence, Histologic Features, and Associations With CNS Disease. Tandberg SR, Bocklage T, Bartlett MR, Morrison LA, Nelson J, Hart BL. AJR Am J Roentgenol. 2020 Feb;214(2):428-436. doi: 10.2214/AJR.19.21492. Epub 2019 Dec 11.

A theory for polymicrogyria and brain arteriovenous malformations in HHT. Klostranec JM, Chen L, Mathur S, McDonald J, Faughnan ME, Ratjen F, Krings T. Neurology. 2019 Jan 1;92(1):34-42. doi: 10.1212/WNL.0000000000006686.

Angiopoietin-2 predicts morbidity in adults with Fontan physiology. Shirali AS, Lluri G, Guihard PJ, Conrad MB, Kim H, Pawlikowska L, Boström KI, Iruela-Arispe ML, Aboulhosn JA. Sci Rep. 2019 Dec 4;9(1):18328. doi: 10.1038/s41598-019-54776-w.

Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia (1). Cannavicci A, Zhang Q, Dai SC, Faughnan ME, Kutryk MJB. Can J Physiol Pharmacol. 2019 Jun;97(6):562-569. doi: 10.1139/cjpp-2018-0508. Epub 2018 Dec 4.

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. Tang AT, Sullivan KR, Hong CC, Goddard LM, Mahadevan A, Ren A, Pardo H, Peiper A, Griffin E, Tanes C, Mattei LM, Yang J, Li L, Mericko-Ishizuka P, Shen L, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Roedel CJ, Li N, Zhu Q, Whitehead KJ, Zheng X, Akers A, Morrison L, Kim H, Bittinger K, Lengner CJ, Schwaninger M, Velcich A, Augenlicht L, Abdelilah-Seyfried S, Min W, Marchuk DA, Awad IA, Kahn ML. Sci Transl Med. 2019 Nov 27;11(520):eaaw3521. doi: 10.1126/scitranslmed.aaw3521.

Familial Cerebral Cavernous Malformations. Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL, Mabray MC, Vigil C, Tang AT, Kahn ML, Yonas H, Lawton MT, Kim H, Morrison L. Stroke. 2019 May;50(5):1294-1301. doi: 10.1161/STROKEAHA.118.022314.

Gαq and hyper-phosphorylated ERK expression in Sturge-Weber syndrome leptomeningeal blood vessel endothelial cells. Wellman RJ, Cho SB, Singh P, Tune M, Pardo CA, Comi AM; BVMC Sturge–Weber syndrome Project Workgroup. Vasc Med. 2019 Feb;24(1):72-75. doi: 10.1177/1358863X18786068. Epub 2018 Aug 16.

Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset. Day AM, Hammill AM, Juhász C, Pinto AL, Roach ES, McCulloch CE, Comi AM; National Institutes of Health Sponsor: Rare Diseases Clinical Research Network (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2019 Jan;90:8-12. doi: 10.1016/j.pediatrneurol.2018.04.009. Epub 2018 Nov 24.

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome. Day AM, McCulloch CE, Hammill AM, Juhász C, Lo WD, Pinto AL, Miles DK, Fisher BJ, Ball KL, Wilfong AA, Levin AV, Thau AJ, Comi AM; National Institute of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group, Koenig JI, Lawton MT, Marchuk DA, Moses MA, Freedman SF, Pevsner J. Pediatr Neurol. 2019 Jul;96:30-36. doi: 10.1016/j.pediatrneurol.2018.12.002. Epub 2018 Dec 20.

Quality of Life in Children With Sturge-Weber Syndrome. Harmon KA, Day AM, Hammill AM, Pinto AL, McCulloch CE, Comi AM; National Institutes of Health Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2019 Dec;101:26-32. doi: 10.1016/j.pediatrneurol.2019.04.004. Epub 2019 Apr 24.

Sturge-Weber Syndrome Patient Registry: Delayed Diagnosis and Poor Seizure Control. Cho S, Maharathi B, Ball KL, Loeb JA, Pevsner J. J Pediatr. 2019 Dec;215:158-163.e6. doi: 10.1016/j.jpeds.2019.08.025. Epub 2019 Oct 3.

A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. De la Torre AJ, Luat AF, Juhász C, Ho ML, Argersinger DP, Cavuoto KM, Enriquez-Algeciras M, Tikkanen S, North P, Burkhart CN, Chugani HT, Ball KL, Pinto AL, Loeb JA. Pediatr Neurol. 2018 Jul;84:11-20. doi: 10.1016/j.pediatrneurol.2018.04.005. Epub 2018 Apr 18.

A user-guided tool for semi-automated cerebral microbleed detection and volume segmentation: Evaluating vascular injury and data labelling for machine learning. Morrison MA, Payabvash S, Chen Y, Avadiappan S, Shah M, Zou X, Hess CP, Lupo JM. Neuroimage Clin. 2018 Aug 4;20:498-505. doi: 10.1016/j.nicl.2018.08.002. eCollection 2018.

Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia. Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Mol Genet Genomic Med. 2018 May;6(3):350-356. doi: 10.1002/mgg3.377. Epub 2018 Mar 6.

Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing. Walcott BP, Winkler EA, Zhou S, Birk H, Guo D, Koch MJ, Stapleton CJ, Spiegelman D, Dionne-Laporte A, Dion PA, Kahle KT, Rouleau GA, Lawton MT. Hum Genome Var. 2018 Mar 8;5:18001. doi: 10.1038/hgv.2018.1. eCollection 2018.

Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study. Meybodi AT, Kim H, Nelson J, Hetts SW, Krings T, terBrugge KG, Faughnan ME, Lawton MT; Brain Vascular Malformation Consortium HHT Investigator Group. Neurosurgery. 2018 Jan 1;82(1):35-47. doi: 10.1093/neuros/nyx168.

Arterial Ischemic Stroke in Children and Young Adults. Lo WD, Kumar R. Continuum (Minneap Minn). 2017 Feb;23(1, Cerebrovascular Disease):158-180. doi: 10.1212/CON.0000000000000438.

Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Zou X, Hart BL, Mabray M, Bartlett MR, Bian W, Nelson J, Morrison LA, McCulloch CE, Hess CP, Lupo JM, Kim H. Neuroradiology. 2017 Jul;59(7):685-690. doi: 10.1007/s00234-017-1845-8. Epub 2017 May 22.

Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N, Girard R, Zeineddine HA, Lightle R, Moore T, Cao Y, Shenkar R, Chen M, Mericko P, Yang J, Li L, Tanes C, Kobuley D, Võsa U, Whitehead KJ, Li DY, Franke L, Hart B, Schwaninger M, Henao-Mejia J, Morrison L, Kim H, Awad IA, Zheng X, Kahn ML. Nature. 2017 May 18;545(7654):305-310. doi: 10.1038/nature22075. Epub 2017 May 10.

Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome. Pilli VK, Chugani HT, Juhász C. Neurology. 2017 Jan 3;88(1):103-105. doi: 10.1212/WNL.0000000000003455. Epub 2016 Nov 18.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Strickland CD, Eberhardt SC, Bartlett MR, Nelson J, Kim H, Morrison LA, Hart BL. Radiology. 2017 Aug;284(2):443-450. doi: 10.1148/radiol.2017161127. Epub 2017 Mar 20.

Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia. Kasthuri RS, Montifar M, Nelson J, Kim H, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Am J Hematol. 2017 Jun 22:10.1002/ajh.24832. doi: 10.1002/ajh.24832. Online ahead of print.

Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome. Offermann EA, Sreenivasan A, DeJong MR, Lin DDM, McCulloch CE, Chung MG, Comi AM; National Institute of Health Sponsor; Rare Disease Clinical Research Consortium (RDCRN); Brain and Vascular Malformation Consortium (BVMC); National Sturge-Weber Syndrome Workgroup. Pediatr Neurol. 2017 Sep;74:15-23.e5. doi: 10.1016/j.pediatrneurol.2017.04.026. Epub 2017 May 8.

Size of Facial Port-Wine Birthmark May Predict Neurologic Outcome in Sturge-Weber Syndrome. Dymerska M, Kirkorian AY, Offermann EA, Lin DD, Comi AM, Cohen BA. J Pediatr. 2017 Sep;188:205-209.e1. doi: 10.1016/j.jpeds.2017.05.053. Epub 2017 Jul 12.

Anticonvulsant Efficacy in Sturge-Weber Syndrome. Kaplan EH, Kossoff EH, Bachur CD, Gholston M, Hahn J, Widlus M, Comi AM. Pediatr Neurol. 2016 May;58:31-6. doi: 10.1016/j.pediatrneurol.2015.10.015. Epub 2016 Jan 11.

Brainstem cavernous malformations: Natural history versus surgical management. Walcott BP, Choudhri O, Lawton MT. J Clin Neurosci. 2016 Oct;32:164-5. doi: 10.1016/j.jocn.2016.03.021. Epub 2016 Jun 16.

Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1. Choquet H, Trapani E, Goitre L, Trabalzini L, Akers A, Fontanella M, Hart BL, Morrison LA, Pawlikowska L, Kim H, Retta SF. Free Radic Biol Med. 2016 Mar;92:100-109. doi: 10.1016/j.freeradbiomed.2016.01.008. Epub 2016 Jan 19.

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research. Comi AM, Sahin M, Hammill A, Kaplan EH, Juhász C, North P, Ball KL, Levin AV, Cohen B, Morris J, Lo W, Roach ES; 2015 Sturge-Weber Syndrome Research Workshop. Pediatr Neurol. 2016 May;58:12-24. doi: 10.1016/j.pediatrneurol.2015.11.009. Epub 2016 Mar 16.

Molecular, Cellular, and Genetic Determinants of Sporadic Brain Arteriovenous Malformations. Walcott BP, Winkler EA, Rouleau GA, Lawton MT. Neurosurgery. 2016 Aug;63 Suppl 1(Suppl 1 CLINICAL NEUROSURGERY):37-42. doi: 10.1227/NEU.0000000000001300.

Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms. Walcott BP, Reinshagen C, Stapleton CJ, Choudhri O, Rayz V, Saloner D, Lawton MT. J Cereb Blood Flow Metab. 2016 Jun;36(6):998-1003. doi: 10.1177/0271678X16641125. Epub 2016 Mar 23.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

[Formula: see text]Intellectual and adaptive functioning in Sturge-Weber Syndrome. Kavanaugh B, Sreenivasan A, Bachur C, Papazoglou A, Comi A, Zabel TA. Child Neuropsychol. 2016;22(6):635-48. doi: 10.1080/09297049.2015.1028349. Epub 2015 May 8.

Armies of pestilence: CNS infections as potential weapons of mass destruction. Hart BL, Ketai L. AJNR Am J Neuroradiol. 2015 Jun;36(6):1018-25. doi: 10.3174/ajnr.A4177. Epub 2014 Dec 4.

Current Therapeutic Options in Sturge-Weber Syndrome. Comi A. Semin Pediatr Neurol. 2015 Dec;22(4):295-301. doi: 10.1016/j.spen.2015.10.005. Epub 2015 Nov 11.

Genetics of cerebral cavernous malformations: current status and future prospects. Choquet H, Pawlikowska L, Lawton MT, Kim H. J Neurosurg Sci. 2015 Sep;59(3):211-20. Epub 2015 Apr 22.

Hemorrhage rates from brain arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia. Kim H, Nelson J, Krings T, terBrugge KG, McCulloch CE, Lawton MT, Young WL, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Stroke. 2015 May;46(5):1362-4. doi: 10.1161/STROKEAHA.114.007367. Epub 2015 Apr 9.

Increased number of white matter lesions in patients with familial cerebral cavernous malformations. Golden MJ, Morrison LA, Kim H, Hart BL. AJNR Am J Neuroradiol. 2015 May;36(5):899-903. doi: 10.3174/ajnr.A4200. Epub 2015 Jan 2.

Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations. Krings T, Kim H, Power S, Nelson J, Faughnan ME, Young WL, terBrugge KG; Brain Vascular Malformation Consortium HHT Investigator Group. AJNR Am J Neuroradiol. 2015 May;36(5):863-70. doi: 10.3174/ajnr.A4210. Epub 2015 Jan 8.

Sensitivity of patients with familial cerebral cavernous malformations to therapeutic radiation. Golden M, Saeidi S, Liem B, Marchand E, Morrison L, Hart B. J Med Imaging Radiat Oncol. 2015 Feb;59(1):134-6. doi: 10.1111/1754-9485.12269. Epub 2015 Jan 7.

Sturge-Weber syndrome. Comi AM. Handb Clin Neurol. 2015;132:157-68. doi: 10.1016/B978-0-444-62702-5.00011-1.

The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with ENG mutations, but not in patients with ACVRL1 mutations. Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Young WL, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Am J Med Genet A. 2015 Jun;167(6):1262-7. doi: 10.1002/ajmg.a.36936. Epub 2015 Apr 2.

Association of cardiovascular risk factors with disease severity in cerebral cavernous malformation type 1 subjects with the common Hispanic mutation. Choquet H, Nelson J, Pawlikowska L, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H. Cerebrovasc Dis. 2014;37(1):57-63. doi: 10.1159/000356839. Epub 2013 Dec 21.

Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. Cheng KH, Mariampillai A, Lee KK, Vuong B, Luk TW, Ramjist J, Curtis A, Jakubovic H, Kertes P, Letarte M, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group, Yang VX. J Biomed Opt. 2014 Aug;19(8):086015. doi: 10.1117/1.JBO.19.8.086015.

Polymorphisms in inflammatory and immune response genes associated with cerebral cavernous malformation type 1 severity. Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study. Cerebrovasc Dis. 2014;38(6):433-40. doi: 10.1159/000369200. Epub 2014 Dec 3.

Preliminary reliability and validity of a battery for assessing functional skills in children with Sturge-Weber syndrome. Reidy TG, Suskauer SJ, Bachur CD, McCulloch CE, Comi AM. Childs Nerv Syst. 2014 Dec;30(12):2027-36. doi: 10.1007/s00381-014-2573-6. Epub 2014 Oct 26.

Severity score for hereditary hemorrhagic telangiectasia. Latino GA, Kim H, Nelson J, Pawlikowska L, Young W, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2014 Dec 29;9:188. doi: 10.1186/s13023-014-0188-3.

Stimulant use in patients with sturge-weber syndrome: safety and efficacy. Lance EI, Lanier KE, Zabel TA, Comi AM. Pediatr Neurol. 2014 Nov;51(5):675-80. doi: 10.1016/j.pediatrneurol.2013.11.009. Epub 2013 Nov 21.

Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. Lance EI, Sreenivasan AK, Zabel TA, Kossoff EH, Comi AM. J Child Neurol. 2013 Feb;28(2):213-8. doi: 10.1177/0883073812463607. Epub 2012 Oct 30.

Brain Vascular Malformation Consortium: Overview, Progress and Future Directions. Akers AL, Ball KL, Clancy M, Comi AM, Faughnan ME, Gopal-Srivastava R, Jacobs TP, Kim H, Krischer J, Marchuk DA, McCulloch CE, Morrison L, Moses M, Moy CS, Pawlikowska L, Young WL. J Rare Disord. 2013 Apr 1;1(1):5.

Case report of subdural hematoma in a patient with Sturge-Weber syndrome and literature review: questions and implications for therapy. Lopez J, Yeom KW, Comi A, Van Haren K. J Child Neurol. 2013 May;28(5):672-5. doi: 10.1177/0883073812449514. Epub 2012 Jul 17.

Dynamic contrast-enhanced MRI evaluation of cerebral cavernous malformations. Hart BL, Taheri S, Rosenberg GA, Morrison LA. Transl Stroke Res. 2013 Oct;4(5):500-6. doi: 10.1007/s12975-013-0285-y. Epub 2013 Sep 21.

Importance of utilizing a sensitive free thyroxine assay in Sturge-Weber syndrome. Siddique L, Sreenivasan A, Comi AM, Germain-Lee EL. J Child Neurol. 2013 Feb;28(2):269-74. doi: 10.1177/0883073812463606. Epub 2012 Oct 30.

Increased choroidal thickness in patients with Sturge-Weber syndrome. Arora KS, Quigley HA, Comi AM, Miller RB, Jampel HD. JAMA Ophthalmol. 2013 Sep;131(9):1216-9. doi: 10.1001/jamaophthalmol.2013.4044.

Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. N Engl J Med. 2013 May 23;368(21):1971-9. doi: 10.1056/NEJMoa1213507. Epub 2013 May 8.

Sturge-weber syndrome. Bachur CD, Comi AM. Curr Treat Options Neurol. 2013 Oct;15(5):607-17. doi: 10.1007/s11940-013-0253-6.

Urine vascular biomarkers in Sturge-Weber syndrome. Sreenivasan AK, Bachur CD, Lanier KE, Curatolo AS, Connors SM, Moses MA, Comi AM. Vasc Med. 2013 Jun;18(3):122-8. doi: 10.1177/1358863X13486312.

Brain arteriovenous malformation multiplicity predicts the diagnosis of hereditary hemorrhagic telangiectasia: quantitative assessment. Bharatha A, Faughnan ME, Kim H, Pourmohamad T, Krings T, Bayrak-Toydemir P, Pawlikowska L, McCulloch CE, Lawton MT, Dowd CF, Young WL, Terbrugge KG. Stroke. 2012 Jan;43(1):72-8. doi: 10.1161/STROKEAHA.111.629865. Epub 2011 Oct 27.

Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schrum SD, James M, Quinnine N, Bharatha A, Terbrugge KG, White RI Jr. Am J Med Genet A. 2012 Nov;158A(11):2829-34. doi: 10.1002/ajmg.a.35622. Epub 2012 Sep 18.

Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Lo W, Marchuk DA, Ball KL, Juhász C, Jordan LC, Ewen JB, Comi A; Brain Vascular Malformation Consortium National Sturge-Weber Syndrome Workgroup. Dev Med Child Neurol. 2012 Mar;54(3):214-23. doi: 10.1111/j.1469-8749.2011.04169.x. Epub 2011 Dec 23.

Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Comi AM. Neurologist. 2011 Jul;17(4):179-84. doi: 10.1097/NRL.0b013e318220c5b6.

Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype. Petersen TA, Morrison LA, Schrader RM, Hart BL. AJNR Am J Neuroradiol. 2010 Feb;31(2):377-82. doi: 10.3174/ajnr.A1822. Epub 2009 Oct 15.

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta. Rodriguez Celin M, Kruger KM, Caudill A, Murali CN, Nagamani SCS, Members Of The Brittle Bone Disorders Consortium Bbdc, Smith PA, Harris GF. Am J Med Genet A. 2022 Oct 22. doi: 10.1002/ajmg.a.63009. Epub ahead of print. PMID: 36271817.

Osteogenesis imperfecta (OI) is a group of rare, inherited disorders caused by gene mutations resulting in fragile bones that break easily. Symptoms include skeletal and joint deformities, hearing loss, a bluish tint to the sclerae (whites of the eyes), dental problems, respiratory problems, and chronic pain. In this study, researchers aimed to describe pain characteristics and treatments used in individuals with varying severity of OI, as well as investigate variables associated with pain. Using data from a natural history study of OI conducted by the Brittle Bone Disorders Consortium (BBDC), the team analyzed the prevalence, characteristics, treatments, and predictors of chronic pain. Among 861 individuals with OI, results showed that 41.8% had chronic pain, which was most frequently located in the back. Predictors of chronic pain for all OI types included age, use of a wheelchair, and number of fractures per year. Compared to participants without chronic pain, participants with chronic pain missed more days from school or work per year and performed worse in all mobility metrics. The most common treatments were nonsteroidal anti-inflammatory drugs and bisphosphonates. These results show that chronic pain is prevalent in OI across all types, affects mobility, and interferes with participation.

Targeting TGF-β for treatment of osteogenesis imperfecta. Song IW, Nagamani SC, Nguyen D, Grafe I, Sutton VR, Gannon FH, Munivez E, Jiang MM, Tran A, Wallace M, Esposito P, Musaad S, Strudthoff E, McGuire S, Thornton M, Shenava V, Rosenfeld S, Huang S, Shypailo R, Orwoll E, Lee B. J Clin Invest. 2022 Apr 1;132(7):e152571. doi: 10.1172/JCI152571.

Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta. Nicol LE, Coghlan RF, Cuthbertson D, Nagamani SCS, Lee B, Olney RC, Horton W; Members of the Brittle Bone Disease Consortium, Orwoll E. Bone. 2021 Aug;149:115990. doi: 10.1016/j.bone.2021.115990. Epub 2021 Apr 28.

Osteogenesis imperfecta is a genetic disorder characterized by bone fragility, abnormal bone growth, and short stature. In this study, researchers sought to better understand the mechanisms by which abnormalities in collagen contribute to growth plate dysfunction. Growth plates are the areas of new bone growth in children and teens, which are made up of cartilage. Researchers examined the presence of Type X collagen (CXM), which has been found to be a reliable marker for new bone formation in cartilage, in blood samples of 187 subjects ages 8 months to 40 years with OI compared with control subjects. All subjects had higher levels of CXM early in life and during puberty, but there was greater variability for the OI cohort and a weaker relationship with growth velocity. The ratio of CXM level to growth velocity was elevated in children with type III/IV OI compared to controls. Results suggest that the relationship between growth plate and the end point of skeletal growth is disrupted in OI. 

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay. Marom R, Burrage LC, Venditti R, Clément A, Blanco-Sánchez B, Jain M, Scott DA, Rosenfeld JA, Sutton VR, Shinawi M, Mirzaa G, DeVile C, Roberts R, Calder AD, Allgrove J, Grafe I, Lanza DG, Li X, Joeng KS, Lee YC, Song IW, Sliepka JM, Batkovskyte D, Washington M, Dawson BC, Jin Z, Jiang MM, Chen S, Chen Y, Tran AA, Emrick LT, Murdock DR, Hanchard NA, Zapata GE, Mehta NR, Weis MA, Scott AA, Tremp BA, Phillips JB, Wegner J, Taylor-Miller T, Gibbs RA, Muzny DM, Jhangiani SN, Hicks J, Stottmann RW, Dickinson ME, Seavitt JR, Heaney JD, Eyre DR; Undiagnosed Diseases Network, Westerfield M, De Matteis MA, Lee B. Am J Hum Genet. 2021 Sep 2;108(9):1710-1724. doi: 10.1016/j.ajhg.2021.08.002. Epub 2021 Aug 26.

Vesicle coat proteins help cells sort and transport or “traffic” proteins and lipids. Pathogenic variants (mutations) in genes that encode subunits of coat complexes called coatomers are believed to contribute to a number of genetic disorders called coatopathies that can affect the skeletal and central nervous systems. In this study, researchers examined loss-of-function variants in the gene COPB2, which encodes for a protein in the coatomer complex, in six individuals from five unrelated families who have osteoporosis or osteopenia (brittle bones that may fracture easily) and variable degree of developmental delay. Researchers also used zebrafish and mouse models to further study the effect of COPB2 deficiency on collagen trafficking because of the critical role of collagen secretion in bone development. The authors conclude that COPB2 haploinsufficiency (meaning only 50% of the normal active form of a particular protein is expressed) is a cause of this form of coatopathy. They also tested ascorbic acid supplementation as a potential treatment and found that it had a beneficial effect on animal models.

Health-related quality of life in adults with osteogenesis imperfecta. Murali CN, Slater B, Musaad S, Cuthbertson D, Nguyen D, Turner A, Azamian M, Tosi L, Rauch F, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SCS. Clin Genet. 2021 Jun;99(6):772-779. doi: 10.1111/cge.13939. Epub 2021 Feb 22.

Missing and unerupted teeth in osteogenesis imperfecta. Taqi D, Moussa H, Schwinghamer T, Vieira AR, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC. Bone. 2021 Sep;150:116011. doi: 10.1016/j.bone.2021.116011. Epub 2021 May 18.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and craniofacial and dental abnormalities. It is believed that OI patients have missing or unerupted teeth at a rate twice the general population. To better understand the factors influencing missing and unerupted teeth, researchers studied 144 OI patients. They examined clinical phenotype (OI type), the genetic variant type, the tooth type and the onset of biophosphonate treatment, which slows bone loss. They found that the presence of missing and unerupted teeth varied according to the nature of the collagen variants and OI type. These findings highlight the role of collagen in tooth development and eruption.

Osteogenesis imperfecta tooth level phenotype analysis: Cross-sectional study. Taqi D, Moussa H, Schwinghamer T, Ducret M, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC. Bone. 2021 Jun;147:115917. doi: 10.1016/j.bone.2021.115917. Epub 2021 Mar 16.

Pregnancy in women with osteogenesis imperfecta: pregnancy characteristics, maternal, and neonatal outcomes. Rao R, Cuthbertson D, Nagamani SCS, Sutton VR, Lee BH, Krischer J, Krakow D. Am J Obstet Gynecol MFM. 2021 Jul;3(4):100362. doi: 10.1016/j.ajogmf.2021.100362. Epub 2021 Mar 26.

Women with rare diseases considering pregnancy often lack data regarding outcomes, specific risks, and management strategies. The Brittle Bone Disorders Consortium established an Osteogenesis Imperfecta Pregnancy Registry to collect data on pregnancy, maternal, and neonatal outcomes in women with osteogenesis imperfecta (OI), or brittle bone disease. A total of 132 participants with OI completed a cross-sectional, survey-based study. Of respondents, 34% had moderate to severe OI. Researchers compared self-reported information on pregnancy and maternal and neonatal outcomes of women with OI with data on the general population, referenced by literature-based standards. Results indicated that women with OI had higher rates than the general population of diabetes in pregnancy, cesarean delivery, need for blood transfusion, and fractures before or after delivery. Individuals with moderate or severe OI reported higher maternal hospitalization and delivery rates than those with mild OI. Babies born to women with OI had higher rates of neonatal intensive care unit admissions and higher neonatal mortality, regardless of neonatal OI status. Study authors say that patients and providers should be aware of these findings, particularly the need for blood products (hemorrhage) and the increased rate of fractures, low birthweight infants, and neonatal mortality. They suggest that survey results can support both preconception counseling and proactive measures to reduce harm and recognize modifiable risk factors related to pregnancy.

A Multicenter Study of Intramedullary Rodding in Osteogenesis Imperfecta. Rodriguez Celin M, Kruger KM, Caudill A, Nagamani SCS; Brittle Bone Disorders Consortium (BBDC); Linked Clinical Research Centers (LCRC), Harris GF, Smith PA. JB JS Open Access. 2020 Sep 11;5(3):e20.00031. doi: 10.2106/JBJS.OA.20.00031. eCollection 2020 Jul-Sep.

Assessment of longitudinal bone growth in osteogenesis imperfecta using metacarpophalangeal pattern profiles. Rauch D, Robinson ME, Seiltgens C, Sutton VR, Lee B, Glorieux F, Rauch F. Bone. 2020 Nov;140:115547. doi: 10.1016/j.bone.2020.115547. Epub 2020 Jul 27.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study. Machol K, Hadley TD, Schmidt J, Cuthbertson D, Traboulsi H, Silva RC, Citron C, Khan S, Citron K, Carter E, Brookler K, Shapiro JR, Steiner RD, Byers PH, Glorieux FH, Durigova M, Smith P, Bober MB, Sutton VR, Lee BH; Members of the BBD Consortium, Nagamani SCS, Raggio C. Am J Med Genet A. 2020 Apr;182(4):697-704. doi: 10.1002/ajmg.a.61464. Epub 2019 Dec 26.

Malocclusion traits and oral health-related quality of life in children with osteogenesis imperfecta: A cross-sectional study. Najirad M, Madathil SA, Rauch F, Sutton VR, Lee B, Retrouvey JM; Members of the Brittle Bone Diseases Consortium, Esfandiari S. J Am Dent Assoc. 2020 Jul;151(7):480-490.e2. doi: 10.1016/j.adaj.2020.03.040.

Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta. Murali CN, Cuthbertson D, Slater B, Nguyen D, Turner A, Harris G, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SCS. Genet Med. 2020 Mar;22(3):581-589. doi: 10.1038/s41436-019-0688-6. Epub 2019 Nov 27.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta. Bains JS, Carter EM, Citron KP, Boskey AL, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sliepka JM, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SC, Raggio CL. JBMR Plus. 2019 Jan 7;3(5):e10118. doi: 10.1002/jbm4.10118. eCollection 2019 May.

Assessing Disease Experience across the Life Span for Individuals with Osteogenesis Imperfecta: Challenges and Opportunities for Patient-Reported Outcomes (PROs) Measurement. Tosi LL, Floor MK, Dollar CM, Gillies AP; Members of the Brittle Bone Disease Consortium, Hart TS, Cuthbertson DD, Sutton VR, Krischer JP. Orphanet Journal of Rare Diseases. 2019. 14:23. https://doi.org/10.1186/s13023-019- 1004-x. PMID: 30696467

Caries Prevalence and Experience in Individuals with Osteogenesis Imperfecta. Ma MS, Najirad M, Taqi D, Retrouvey JM, Tamimi F, Dagdeviren D, Glorieux FH, Lee B, Sutton VR, Rauch F, Esfandiari S. Spec Care Dentist. 2019 Mar;39(2):214-219. Epub 2019 Feb 13. https://doi.org/10.1101/418806. PMID: 30758072

Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in IFITM5. Dagdeviren D, Tamimi F, Lee B, Sutton R, Rauch F, Retrouvey JM. Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in IFITM5. Dagdeviren D, Tamimi F, Lee B, Sutton V, Rauch F, Retrouvey JM. Am J Med Genet A. 2018 Oct 5. doi: 10.1002/ajmg.a.40383. PMID: 30289614

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study. Jain M, Tam A, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Mullins M, Bellur S, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Lee B, Sutton VR; , Members of the Brittle Bone Disorders Consortium*,, Nagamani SCS. Genet Med. 2018 Jul 4. doi: 10.1038/s41436-018-0045-1. PMID: 29970925

Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells. Ortinau LC, Wang H, Lei K, Deveza L, Jeong Y, Hara Y, Grafe I, Rosenfeld SB, Lee D, Lee B, Scadden DT, Park D. Cell Stem Cell. 2019 Dec 5;25(6):784-796.e5. doi: 10.1016/j.stem.2019.11.003.

Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community. Swezey T, Reeve BB, Hart TS, Floor MK, Dollar CM, Gillies AP, Tosi LL. Osteoporos Int. 2019 Feb;30(2):507-511. doi: 10.1007/s00198-018-4690-7. Epub 2018 Sep 6. PMID:30191258

Mobility in Osteogenesis Imperfecta: A Multicenter North American Study. Kruger KM, Caudill A, Rodriguez Celin M, Nagamani SCS, Shapiro JR, Steiner RD, Bober MB, Hart T, Cuthbertson D, Krischer J, Byers PH, Durigova M, Glorieux FH, Rauch F, Sutton VR, Lee B, Rush ET, Smith PA, Harris GF. Genet Med. 2019 Mar 28. doi: 10.1038/s41436-019-0491-4. PMID: 30918359

Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V. Retrouvey JM, Taqi D, Tamimi F, Dagdeviren D, Glorieux FH, Lee B, Hazboun R, Krakow D, Sutton VR; Members of the BBD Consortium. Eur J Med Genet. 2019 Dec;62(12):103606. doi: 10.1016/j.ejmg.2018.12.011. Epub 2018 Dec 26.

Osteogenesis imperfecta: advancements in genetics and treatment. Rossi V, Lee B, Marom R. Curr Opin Pediatr. 2019 Dec;31(6):708-715. doi: 10.1097/MOP.0000000000000813.

A Multicenter Study to Evaluate Pulmonary Function in Osteogenesis Imperfecta. Tam A, Chen S, Schauer E, Grafe I, Bandi V, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Mullins M, Byers PH, Sandhaus RA, Durigova M, Glorieux FH, Rauch F, Reid Sutton V, Lee B; Members of the Brittle Bone Disorders Consortium, Rush ET, Nagamani SCS. Clin Genet. 2018 Dec;94(6):502-511. doi: 10.1111/cge.13440. Epub 2018 Sep 24. PMID: 30152014

Cone‐Beam Computed Tomography of Osteogenesis Imperfecta Types III and IV: Three‐Dimensional Evaluation of Craniofacial Features and Upper Airways. Reznikov N, Dagdeviren D, Tamimi F, Glorieux F, Rauch F, Retrouvey JM. JBMR Plus, Epub November 16, 2018; doi: 10.1002/jbm4.10124

Heterozygous WNT1 variant causing a variable bone phenotype. Alhamdi S, Lee YC, Chowdhury S, Byers PH, Gottschalk M, Taft RJ, Joeng KS, Lee BH, Bird LM. Am J Med Genet A. 2018 Nov;176(11):2419-2424. doi: 10.1002/ajmg.a.40347. Epub 2018 Sep 24.

Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta. Bains JS, Carter EM, Citron KP, Boskey AL, Shapiro JR, Steiner RD, Smith PA, Bober MA, Hart T, Cuthbertson D, Krischer J, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sliepka JM, Sutton VR, Lee B, “Members of the BBD Consortium”, Nagamani SC, Raggio CL. JBMR Plus, Epub October 23, 2018; doi: 10.1002/jbm4.10118

Oral Health-Related Quality of Life in Children and Adolescents with Osteogenesis Imperfecta: cross- sectional study. Najirad M, Ma MS, Rauch F, Sutton VR, Lee B, Retrouvey JM; Members of the BBD, Esfandiari S. Orphanet J Rare Dis. 2018 Oct 25;13(1):187. doi: https://doi.org/10.1101/424812. PMID: 30359278

Osteogenesis imperfecta: potential therapeutic approaches. Rousseau M, Retrouvey JM; Members of the Brittle Bone Disease Consortium. PeerJ. 2018 Aug 17;6:e5464. doi: 10.7717/peerj.5464. eCollection 2018. PMID: 30128210

Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment. Bi X, Grafe I, Ding H, Flores R, Munivez E, Jiang MM, Dawson B, Lee B, Ambrose CG. J Bone Miner Res. 2017 Feb;32(2):347-359. doi: 10.1002/jbmr.2997. Epub 2016 Oct 20.

Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone. Lietman CD, Lim J, Grafe I, Chen Y, Ding H, Bi X, Ambrose CG, Fratzl-Zelman N, Roschger P, Klaushofer K, Wagermaier W, Schmidt I, Fratzl P, Rai J, Weis M, Eyre D, Keene DR, Krakow D, Lee BH. J Bone Miner Res. 2017 Jun;32(6):1354-1367. doi: 10.1002/jbmr.3108. Epub 2017 Mar 20.

Genetic causes and mechanisms of Osteogenesis Imperfecta. Lim J, Grafe I, Alexander S, Lee B. Bone. 2017 Sep;102:40-49. doi: 10.1016/j.bone.2017.02.004. Epub 2017 Feb 15.

Orthodontic chart documentation. Abdelkarim A, Jerrold L. Am J Orthod Dentofacial Orthop. 2017 Jul;152(1):126-130. doi: 10.1016/j.ajodo.2017.03.018.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta. Bellur S, Jain M, Cuthbertson D, Krakow D, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Krischer J, Mullins M, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SC. Genet Med. 2016 Jun;18(6):570-6. doi: 10.1038/gim.2015.131. Epub 2015 Oct 1. PMID: 26426884

Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta. Grafe I, Alexander S, Yang T, Lietman C, Homan EP, Munivez E, Chen Y, Jiang MM, Bertin T, Dawson B, Asuncion F, Ke HZ, Ominsky MS, Lee B. J Bone Miner Res. 2016 May;31(5):1030-40. doi: 10.1002/jbmr.2776. Epub 2016 Feb 12.

A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation. Lietman CD, Marom R, Munivez E, Bertin TK, Jiang MM, Chen Y, Dawson B, Weis MA, Eyre D, Lee B. J Bone Miner Res. 2015 Mar;30(3):489-98. doi: 10.1002/jbmr.2363.

Characteristics of serum neurofilament light chain as a biomarker in hereditary spastic paraplegia type 4. Kessler C, Serna-Higuita LM, Wilke C, Rattay TW, Hengel H, Reichbauer J, Stransky E, Leyva-Gutiérrez A, Mengel D, Synofzik M, Schöls L, Martus P, Schüle R. Ann Clin Transl Neurol. 2022 Mar;9(3):326-338. doi: 10.1002/acn3.51518. Epub 2022 Feb 16. PMID: 35171517; PMCID: PMC8935322.

Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by muscle weakness and tightness (spasticity) in the legs. Easily accessible fluid biomarkers are lacking in spastic paraplegia type 4 (SPG4), the most prevalent form of HSP. In this study, researchers investigated serum neurofilament light chain (sNfL) as a potential therapy response, diagnostic, monitoring, and prognostic biomarker in SPG4. The team assessed sNfL levels in 93 patients with SPG4 and 60 healthy controls. They found that sNfL levels are not suitable to monitor disease progression in SPG4, but may be valuable as a therapy response biomarker. Authors note that because sNfL levels appear to be most dynamic around the onset of SPG4, the ability to detect a therapy response is especially promising in younger patients, matching the need to initiate treatment in early disease stages.

Defining cognitive impairment in amyotrophic lateral sclerosis: an evaluation of empirical approaches. McMillan CT, Wuu J, Rascovsky K, Cosentino S, Grossman M, Elman L, Quinn C, Rosario L, Stark JH, Granit V, Briemberg H, Chenji S, Dionne A, Genge A, Johnston W, Korngut L, Shoesmith C, Zinman L; Canadian ALS Neuroimaging Consortium (CALSNIC), Kalra S, Benatar M. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Mar 7:1-10. doi: 10.1080/21678421.2022.2039713. Online ahead of print.

Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: a new diagnostic entity. Benatar M, Granit V, Andersen PM, Grignon AL, McHutchison C, Cosentino S, Malaspina A, Wuu J. Brain. 2022 May 20:awac185. doi: 10.1093/brain/awac185. Epub ahead of print. PMID: 35594156.

Amyotrophic lateral sclerosis (ALS) is traditionally regarded as a clinical syndrome. Emerging biomarker evidence of disease prior to clinical manifestations of disease, however, have fostered the view that ALS should be considered a biological entity with pre-symptomatic and clinically manifest stages of disease. New data from Pre-fALS, a natural history and biomarker study of people at genetic risk for ALS, now indicate that pre-symptomatic should not necessarily be taken to mean “clinically silent.” Systematic clinical characterization of 20 phenoconverters–pre-symptomatic gene mutation carriers who have been followed from the pre-symptomatic to the clinically manifest stages of disease–reveals evidence of a prodromal state of mild motor impairment (MMI). MMI is characterized by symptoms, signs, or electromyographic findings that represent a departure from normal, but which are insufficiently severe or widespread to clearly indicate ALS. The duration of prodromal MMI varies among carriers of different genetic mutations. Based on these findings, the authors conclude that in three of the most common genetic forms of ALS, MMI is an observable state that is prodromal to clinically manifest disease. The authors hypothesize that this may also be true for all genetic ALS and non-genetic forms of ALS as well. Importantly, MMI is considered both an intermediate (transitional) and an indeterminate state, as not everyone with MMI will progress to develop ALS. As a new diagnostic label, MMI should generate fresh urgency for developing diagnostic biomarkers that might permit earlier therapeutic intervention.

Occupational lead exposure and survival with amyotrophic lateral sclerosis. Wang TW, Wuu J, Cooley A, Yeh TS, Benatar M, Weisskopf M. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Apr 9;1-8. doi: 10.1080/21678421.2022.2059379. Online ahead of print.

Environmental risk factors are thought to play a role in ALS risk but may also impact the rate of disease progression and survival. Lead, given its known neurotoxicity, is one such exposure. Prior studies that have relied on biomarkers of lead exposure have yielded conflicting results. In this study, researchers evaluated the relationship between occupational lead exposure prior to onset of ALS on the one hand, and disease progression and survival following onset of ALS on the other hand. Lead exposure was determined using a job-exposure matrix based on occupations held prior to onset of ALS. This approach avoids the potential for reverse causation bias that may result from reliance on lead biomarkers after disease onset. The impact on disease progression was quantified through both survival analysis and estimation of the rate of functional decline. Results suggest that lead exposure before onset of ALS is associated with more rapid functional decline and shorter survival following onset of ALS, even after adjusting for other factors known to influence disease progression.

Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; First International Pre-Symptomatic ALS Workshop. Brain. 2022 Mar 29;145(1):27-44. doi: 10.1093/brain/awab404. PMID: 34677606; PMCID: PMC8967095.

Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis (ALS). Much is still unknown, however, and advances in other neurodegenerative diseases—including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), spinal muscular atrophy (SMA), and frontotemporal dementia (FTD)—highlight opportunities for discovery in ALS. This article builds on discussions at the First International Pre-Symptomatic ALS Workshop (January 2020, Miami, Florida). Lessons from AD illustrate the importance of conceptualizing neurodegenerative diseases as biological entities. PD and HD, respectively, highlight the value of prodromal clinical markers and the value of tools to predict age of onset. FTD elucidates nuanced differences in pre-symptomatic disease based on genotype, and SMA underscores the value of early therapeutic intervention. The authors discuss a conceptual framework for pre-symptomatic ALS that includes clinically silent and prodromal stages of disease. They also provide recommendations for the study of motor, cognitive, and behavioral manifestations of early ALS; emphasize the critical importance of biomarkers; discuss the challenges of genetic and biomarker counseling as well as a range of ethical, legal, and social issues relevant to pre-symptomatic disease. Last, but not least, they present ideas about the design of early intervention and disease prevention clinical trials. Ultimately, the authors present a road map to early intervention—and perhaps even disease prevention—for all forms of ALS.

Rates of longitudinal change in (18) F-flortaucipir PET vary by brain region, cognitive impairment, and age in atypical Alzheimer's disease. Phillips JS, Nitchie FJ 4th, Da Re F, Olm CA, Cook PA, McMillan CT, Irwin DJ, Gee JC, Dubroff JG, Grossman M, Nasrallah IM; Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2022 Jun;18(6):1235-1247. doi: 10.1002/alz.12456. Epub 2021 Sep 13.

Amyotrophic Lateral Sclerosis Survival Associates With Neutrophils in a Sex-specific Manner. Murdock BJ, Goutman SA, Boss J, Kim S, Feldman EL. Neurol Neuroimmunol Neuroinflamm. 2021 Feb 2;8(2):e953. doi: 10.1212/NXI.0000000000000953. Print 2021 Mar.

Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations. Lingor P, Koch JC, Statland JM, Hussain S, Hennecke C, Wuu J, Langbein T, Ahmed R, Günther R, Ilse B, Kassubek J, Kollewe K, Kuttler J, Leha A, Lengenfeld T, Meyer T, Neuwirth C, Tostmann R, Benatar M. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug;22(5-6):419-425. doi: 10.1080/21678421.2021.1879866. Epub 2021 Feb 3.

Epigenetic small moleculars rescue nucleocytoplasmic transport and DNA damage phenotypes in C9ORF72 ALS/FTD. Melina Ramic, Nadja S Andrade, Matthew J Rybin, Rustam Esanov, Claes Wahlestedt, Michael Benatar, Zane Zeier . Brain Sci. 2021 Nov 20;11(11):1543. doi: 10.3390/brainsci11111543. PMID: 34827542

FGF23, a novel muscle biomarker detected in the early stages of ALS. Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. Sci Rep. 2021 Jun 8;11(1):12062. doi: 10.1038/s41598-021-91496-6.

Harnessing the power of the electronic health record for ALS research and quality improvement: CReATe CAPTURE-ALS and the ALS Toolkit. Granit V, Grignon AL, Wuu J, Katz J, Walk D, Hussain S, Hernandez J, Jackson C, Caress J, Yosick T, Smider N, Benatar M. Muscle Nerve. 2022 Feb;65(2):154-161. doi: 10.1002/mus.27454. Epub 2021 Nov 16. PMID: 34730240; PMCID: PMC8752483.

Effective use of electronic health record (EHR) data for research purposes has been a long-standing goal of physicians caring for patients with amyotrophic lateral sclerosis (ALS). Several barriers, however, have impeded progress toward this goal, including the limited quality and completeness of clinical documentation, as well as the burden of duplicative entry of clinical data into a research database. To address these barriers, researchers developed the ALS Toolkit, a set of interactive digital forms integrated into the EHR. Used routinely during clinic visits, the ALS Toolkit enables seamless, structured and consistent collection of data elements relevant to ALS patient care, with the expectation that these will also be suitable for research purposes. Since it incorporates AAN quality measures for the care of ALS patients, the ALS Toolkit may also be used to facilitate quality improvement initiatives. CReATe’s Clinical Procedures to Support Research in ALS (CAPTURE-ALS) study utilizes the ALS Toolkit to facilitate multi-center aggregation of data collected at the point of clinical care, empowering research and driving quality improvement. With the goal of collecting data from all patients receiving care through multidisciplinary clinics, CAPTURE-ALS will yield data that reflects the true diversity of populations affected by ALS, rather than the restricted subset of patients currently participating in dedicated research studies.

Humoral response to neurofilaments and dipeptide repeats in ALS progression. Puentes F, Lombardi V, Lu CH, Yildiz O, Fratta P, Isaacs A, Bobeva Y, Wuu J; ALS Biomarker Consortium; CReATe Consortium, Benatar M, Malaspina A. Ann Clin Transl Neurol. 2021 Sep;8(9):1831-1844. doi: 10.1002/acn3.51428. Epub 2021 Jul 27.

Neurofilaments, both light chain (NfL) and phosphorylated neurofilament heavy (pNfH), are structural components of axons. Both NfL and pNfH are known to increase during the pre-symptomatic and early symptomatic phases of disease and then to reach a stable but elevated plateau despite continued progression of disease. Although these proteins, most notably NfL, have emerged as the most promising prognostic and potential pharmacodynamic biomarkers, it remains unclear why neurofilament levels do not change as disease progresses. The current study focused on the immune response to neurofilaments (and dipeptide repeat proteins in patients with the C9orf72 genetic form of ALS), quantifying levels of antibodies and immune complexes that represent the humeral response to the release of these proteins. The investigators observed a trend towards increasing concentrations of NfL antibodies and immune complexes over the course of longitudinal follow among patients with faster progressing disease, raising the possibility that the immune response is partially responsible for clearing NfL and stabilizing plasma levels of this protein despite increased production as neurodegeneration progresses.

Long-read targeted sequencing ucnovers clinicopathological associations for Cr0rf72-linked diseases. DeJesus-Hernandez M, Aleff RA, Jackson JL, Finch NA, Baker MC, Gendron TF, Murray ME, McLaughlin IJ, Harting JR, Graff-Radford NR, Oskarsson B, Knopman DS, Josephs KA, Boeve BF, Petersen RC, Fryer JD, Petrucelli L, Dickson DW, Rademakers R, Ebbert MTW, Wieben ED, van Blitterswijk M. . Brain. 2021 May 7;144(4):1082-1088. doi: 10.1093/brain/awab006. PMID: 33889947

Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis. Placek K, Benatar M, Wuu J, Rampersaud E, Hennessy L, Van Deerlin VM, Grossman M, Irwin DJ, Elman L, McCluskey L, Quinn C, Granit V, Statland JM, Burns TM, Ravits J, Swenson A, Katz J, Pioro EP, Jackson C, Caress J, So Y, Maiser S, Walk D, Lee EB, Trojanowski JQ, Cook P, Gee J, Sha J, Naj AC, Rademakers R; CReATe Consortium, Chen W, Wu G, Paul Taylor J, McMillan CT. EMBO Mol Med. 2020 Dec 3;e12595. PMID: 3327098

NK cells associate with ALS in a sex- and age-dependent manner. Murdock BJ, Famie JP, Piecuch CE, Raue KD, Mendelson FE, Pieroni CH, Iniguez SD, Zhao L, Goutman SA, Feldman EL. JCI Insight. 2021 Jun 8;6(11):e147129. doi: 10.1172/jci.insight.147129.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia. Kessler C, Serna-Higuita LM, Rattay TW, Maetzler W, Wurster I, Hayer S, Wilke C, Hengel H, Reichbauer J, Armbruster M, Schöls L, Martus P, Schüle R. Ann Clin Transl Neurol. 2021 May;8(5):1122-1131. doi: 10.1002/acn3.51358. Epub 2021 Apr 5.

Repeat expansions in ATXN2, NOP56, NIPA1 and ATXN1 are not associated with ALS in Africans. Nel M, Mavundla T, Gultig K, Botha G, Mulder N, Benatar M, Wuu J, Cooley A, Myers J, Rampersaud E, Wu G, Heckmann JM. . IBRO Neurosci Rep. 2021 Feb 10;10:130-135. doi: 10.1016/j.ibneur.2021.02.002. PMID: 34179866

Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis. Shepheard SR, Karnaros V, Benyamin B, Schultz DW, Dubowsky M, Wuu J, Chataway T, Malaspina A, Benatar M, Rogers ML. Eur J Neurol. 2021 Dec 29. doi: 10.1111/ene.15237. Epub ahead of print. PMID: 34967083.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that leads to progressive muscle weakness. There are currently no meaningfully effective treatments for ALS, which is invariably fatal. Biomarkers that are suitably fit-for-purpose have great potential to enhance therapy development efforts. A research team led by Dr. Mary Louise-Rogers at Flinders University in Australia has found that urinary neopterin, a marker of an underlying pro-inflammatory state, is elevated in ALS compared to age-matched controls, and progressively increases as the disease advances. In addition to its potential utility as a biomarker of disease progression, neopterin might also have potential as a predictive biomarker, identifying a subset of patients who may stand to benefit from therapeutics that target inflammatory pathways.

Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD. Andrade N, Ramic M, Esanov R, et al. Mol Neurodegener. 2020; 15: 13. PMCID:PMC7041170, PMID: 32093728

Disentangling Heterogeneity in Alzheimer's Disease and Related Dementias Using Data-Driven Methods. Habes M, Grothe MJ, Tunc B, McMillan C, Wolk DA, Davatzikos C. Biol Psychiatry. 2020 Jul 1;88(1):70-82. doi: 10.1016/j.biopsych.2020.01.016. Epub 2020 Jan 31.

Metabolite Profiling Reveals Predictive Biomarkers and the Absence of β-Methyl Amino-l-alanine in Plasma from Individuals Diagnosed with Amyotrophic Lateral Sclerosis. Bereman MS, Kirkwood KI, Sabaretnam T, Furlong S, Rowe DB, Guillemin GJ, Mellinger AL, Muddiman DC. J Proteome Res. 2020 Aug 7;19(8):3276-328. PMID: 32418425

Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice. Figueroa-Romero C,1, Guo K,2, Murdock BJ, et al. Dis Model Mech. 2020 Feb 1; 13(2). PMCID: PMC6906635, PMID: 31597644

The potential of neurofilaments analysis using dry-blood and plasma spots. Lombardi V, Carassiti D, Giovannoni G, Lu CH, Adiutori R, Malaspina A. Sci Rep. 2020 Jan 9;10(1):97. PMID: 31919375, PMCID: PMC6952412

Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, Swenson A, Ravits J, Jackson C, Burns TM, Trivedi J, Pioro EP, Caress J, Katz J, McCauley JL, Rademakers R, Malaspina A, Ostrow LW, Wuu J; CReATe Consortium. Neurology. 2020 Jul 7;95(1):e59-e69. PMID: 32385188, PMCID: PMC7371380

Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study. Aladesuyi Arogundade O, Stauffer JE, Saberi S, Diaz-Garcia S, Malik S, Basilim H, Rodriguez MJ, Ohkubo T, Ravits J. Acta Neuropathol. 2019. PMID: 30666413

Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Farhan SMK, Howrigan DP, Abbott LE, Klim JR, Topp SD, Byrnes AE, Churchhouse C, Phatnani H, Smith BN, Rampersaud E, Wu G, Wuu J, Shatunov A, Iacoangeli A, Al Khleifat A, Mordes DA, Ghosh S; ALSGENS Consortium; FALS Consortium; Project MinE Consortium; CReATe Consortium, Eggan K, Rademakers R, McCauley JL, Schüle R, Züchner S, Benatar M, Taylor JP, Nalls M, Gotkine M, Shaw PJ, Morrison KE, Al-Chalabi A, Traynor B, Shaw CE, Goldstein DB, Harms MB, Daly MJ, Neale BM. Nat Neurosci. 2019 Dec; 22(12): 1966–1974. PMCID: PMC6919277, PMID: 31768050

Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants. Edmonson MN, Patel AN, Hedges DJ, Wang Z, Rampersaud E, Kesserwan CA, Zhou X, Liu Y, Newman S, Rusch MC, McLeod CL, Wilkinson MR, Rice SV, Soussi T, Taylor JP, Benatar M, Becksfort JB, Nichols KE, Robison LL, Downing JR, Zhang J.. Genome Res. 2019 Sep;29(9):1555-1565. doi: 10.1101/gr.250357.119. Epub 2019 Aug 22. PMID: 31439692

UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis. Placek K, Baer GM, Elman L, McCluskey L, Hennessy L, Ferraro PM, Lee EB, Lee VMY, Trojanowski JQ, Van Deerlin VM, Grossman M, Irwin DJ, McMillan CT. Neurobiol Aging. 2019; 73:190-199. PMID:30368160, PMCID: PMC6251755

G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo. Simone R, Balendra R, Moens TG, et al. EMBO Mol Med. 2018;10(1):22-31. PMID: 29113975, PMCID: PMC5760849

GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Eidhof I, Baets J, Kamsteeg EJ, Deconinck T, van Ninhuijs L, Martin JJ, Schüle R, Züchner S, De Jonghe P, Schenck A, van de Warrenburg BP. Brain. 2018 Sep 1;141(9):2592-2604. doi: 10.1093/brain/awy198.

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, et al. Neuron. 2018;97(6):1268-1283.e1266. PMID: 29566793, PMCID: PMC5867896

Identification of compound heterozygous variants in OPTN in an ALS-FTD patient from the CReATe consortium: a case report. Pottier C, Rampersaud E, Baker M, Wu G, Wuu J, McCauley JL, Zuchner S, Schule R, Bermudez C, Hussain S, Cooley A, Wallace M, Zhang J, Taylor JP, Benatar M, Rademakers R. Amyotrophic lateral sclerosis & frontotemporal degeneration. 2018:1-3. PMID: 29558868

Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brožková DŠ, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Am J Hum Genet. 2018;102(3):505-514. PMID: 29499166, PMCID: PMC5985288

Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS/FTD. Moens TG, Mizielinska S, Niccoli T, et al. Acta Neuropathol. 2018;135(3):445-457. PMID:29380049

Serum neurofilament light chain is increased in hereditary spastic paraplegias. Wilke C, Rattay TW, Hengel H, Zimmermann M, Brockmann K, Schöls L, Kuhle J, Schüle R, Synofzik M. Annals of clinical and translational neurology. 2018;5(7):876-882. PMID:30009206, PMCID: PMC6043776

Using automated electronic medical record data extraction to model ALS survival and progression. Karanevich AG, Weisbrod LJ, Jawdat O, Barohn RJ, Gajewski BJ, He J, Statland JM. BMC Neurol. 2018;18(1):205. PMID:30547800, PMCID: PMC6295028

A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD. Esanov R, Cabrera GT, Andrade NS, Gendron TF, Brown RH Jr, Benatar M, Wahlestedt C, Mueller C, Zeier Z. Mol Neurodegener. 2017;12(1):46. PMID: 28606110, PMCID: PMC5468954

Abnormal expression of homeobox genes and transthyretin in C9ORF72 expansion carriers. Finch NA, Wang X, Baker MC, Heckman MG, Gendron TF, Bieniek KF, Wuu J, DeJesus-Hernandez M, Brown PH, Chew J, Jansen-West KR, Daughrity LM, Nicholson AM, Murray ME, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Petrucelli L, Boeve BF, Graff-Radford NR, Asmann YW, Dickson DW, Benatar M, Bowser R, Boylan KB, Rademakers R, van Blitterswijk M. Neurology Genetics. 2017;3(4):e161. PMID: 28660252, PMCID. PMC5479438

Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Strong MJ, Abrahams S, Goldstein LH, Woolley S, Mclaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, HortobáGyi T, Rosenfeld J, Silani V, Ince PG, Turner MR. Amyotrophic lateral sclerosis & frontotemporal degeneration. 2017;18(3-4):153-174. PMID: 28054827

Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression. Murdock BJ, Zhou T, Kashlan SR, Little RJ, Goutman SA, Feldman EL. JAMA neurology. 2017. PMID: 28973548, PMCID: PMC5822195

Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Jacquier A, Delorme C, Belotti E, Juntas-Morales R, Solé G, Dubourg O, Giroux M, Maurage CA, Castellani V, Rebelo A, Abrams A, Züchner S, Stojkovic T, Schaeffer L, Latour P. Acta neuropathologica communications. 2017;5(1):55. PMID: 28709447, PMCID: PMC5513089

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Schols L, Rattay TW, Martus P, et al. Brain. 2017;140(12):3112-3127. PMID:29126212, PMCID: PMC5841036

In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers. DeJesus-Hernandez M, Finch NA, Wang X, Gendron TF, Bieniek KF, Heckman MG, Vasilevich A, Murray ME, Rousseau L, Weesner R, Lucido A, Parsons M, Chew J, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Graff-Radford NR, de Boer J, Asmann YW, Petrucelli L, Boylan KB, Dickson DW, van Blitterswijk M, Rademakers R. Acta Neuropathol. 2017;134(2):255-269. PMID: 28508101, PMCID: PMC5508036

Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF; C9ORF72 Neurofilament Study Group, Daughrity LM, Heckman MG, Diehl NN, Wuu J, Miller TM, Pastor P, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Benatar M, Silani V, Glass JD, Floeter MK, Jeromin A, Boylan KB, Petrucelli L. Ann Neurol. 2017;82(1):139-146. PMID: 28628244, PMCID: PMC5676468

Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O'Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L. Sci Transl Med. 2017;9(383). PMID: 28356511, PMCID: PMC5576451

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients. Prudencio M, Gonzales PK, Cook CN, Gendron TF, Daughrity LM, Song Y, Ebbert MTW, van Blitterswijk M, Zhang YJ, Jansen-West K, Baker MC, DeTure M, Rademakers R, Boylan KB, Dickson DW, Petrucelli L, Link CD. Hum Mol Genet. 2017;26(17):3421-3431. PMID: 28637276

Research Toolkit: Capturing clinical data to advance ALS research. Michael Benatar, Jonathan Katz, David Walk CReATe Consortium ALS Association Muscular Dystrophy Association (MDA). Capturing clinical data to advance ALS research. https://galaxy.epic.com/Redirect.aspx?DocumentID=3701881&Version=Epic 2017, EpicCare Ambulatory, 2017

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, Annu K, Baker M, Perkerson RB, Kurti A, Matchett BJ, Mittag T, Temirov J, Hsiung GR, Krieger C, Murray ME, Kato M, Fryer JD, Petrucelli L, Zinman L, Weintraub S, Mesulam M, Keith J, Zivkovic SA, Hirsch-Reinshagen V, Roos RP, Züchner S, Graff-Radford NR, Petersen RC, Caselli RJ, Wszolek ZK, Finger E, Lippa C, Lacomis D, Stewart H, Dickson DW, Kim HJ, Rogaeva E, Bigio E, Boylan KB, Taylor JP, Rademakers R. Neuron. 2017;95(4):808-816.e809. PMID: 28817800, PMCID: PMC5576574

Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Shepheard SR, Wuu J, Cardoso M, Wiklendt L, Dinning PG, Chataway T, Schultz D, Benatar M, Rogers ML. Neurology. 2017;88(12):1137-1143. PMID: 28228570, PMCID: PMC5373786

ALS biomarkers for therapy development: State of the field and future directions. Benatar M, Boylan K, Jeromin A, Rutkove SB, Berry J, Atassi N, Bruijn L. Muscle Nerve. Feb 2016;53(2):169-182. PMID: 26574709, PMCID: PMC4718795

C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD. Liu Y, Pattamatta A, Zu T, et al. Neuron. 2016;90(3):521-534. PMID: 27112499

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells. Esanov R, Belle KC, van Blitterswijk M, Belzil VV, Rademakers R, Dickson DW, Petrucelli L, Boylan KB, Dykxhoorn DM, Wuu J, Benatar M, Wahlestedt C, Zeier Z. Exp Neurol. Mar 2016;277:171-177. PMID: 26746986, PMCID: PMC4761318

Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Rebelo AP, Abrams AJ, Cottenie E, Horga A, Gonzalez M, Bis DM, Sanchez-Mejias A, Pinto M, Buglo E, Markel K, Prince J, Laura M, Houlden H, Blake J, Woodward C, Sweeney MG, Holton JL, Hanna M, Dallman JE, Auer-Grumbach M, Reilly MM, Zuchner S. Am J Hum Genet. 2016; 98(4):597-614. PMID: 27040688, PMCID: PMC4833435

Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis. Murdock BJ, Bender DE, Kashlan SR, et al. Neurology(R) neuroimmunology & neuroinflammation. 2016;3(4):e242. PMID: 27308304, PMCID: PMC4897983

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers. Gendron TF, van Blitterswijk M, Bieniek KF, Daughrity LM, Jiang J, Rush BK, Pedraza O, Lucas JA, Murray ME, Desaro P, Robertson A, Overstreet K, Thomas CS, Crook JE, Castanedes-Casey M, Rousseau L, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Graff-Radford NR, Rademakers R, Lagier-Tourenne C, Edbauer D, Cleveland DW, Dickson DW, Petrucelli L, Boylan KB. Acta Neuropathol. Oct 2015;130(4):559-573. PMID: 26350237, PMCID: PMC4575385

Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis. Turner MR, Benatar M. Muscle Nerve. Jan 2015;51(1):14-18. PMID: 25288265, PMCID: PMC4270289

Neurodegenerative disease: C9orf72 repeats compromise nucleocytoplasmic transport. van Blitterswijk M, Rademakers R. Nature reviews. Neurology. Dec 2015;11(12):670-672. PMID: 26526532

Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72. van Blitterswijk M, Gendron TF, Baker MC, DeJesus-Hernandez M, Finch NA, Brown PH, Daughrity LM, Murray ME, Heckman MG, Jiang J, Lagier-Tourenne C, Edbauer D, Cleveland DW, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Petrucelli L, Boeve BF, Graff-Radford NR, Boylan KB, Dickson DW, Rademakers R. Acta Neuropathol. Oct 5 2015. PMID: 26437865, PMCID: PMC4655160

Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Brain. Feb 2015;138(Pt 2):293-310. PMID: 25497877, PMCID: PMC4306822

2021 year in review: Spotlight on eosinophils. Dunn JLM, Rothenberg ME. J Allergy Clin Immunol. 2022 Feb;149(2):517-524. doi: 10.1016/j.jaci.2021.11.012. Epub 2021 Nov 25.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. Gastroenterology. 2022 Jul;163(1):59-76. doi: 10.1053/j.gastro.2022.03.025. Epub 2022 May 20. PMID: 35606197; PMCID: PMC9233087.

For patients with eosinophilic esophagitis (EoE), an allergic inflammatory disease that damages the esophagus, therapeutic options and management are dictated by disease severity. However, the process for determining severity varies among practitioners. Reducing this variability could help improve clinicians’ ability to monitor EoE in an office setting. In this study, researchers aimed to create an international consensus severity scoring index for EoE. First, a group of adult and pediatric EoE researchers and clinicians—as well as non-EoE allergy immunology and gastroenterology experts—reviewed existing literature on EoE in the context of progression and severity. Next, a steering committee reached consensus on important features of severity. These features were then distilled to categorize patients with EoE as having inactive, mild, moderate, or severe disease. This new simplified scoring system, called the Index of Severity for Eosinophilic Esophagitis (I-SEE), can be completed at routine clinic visits. The system can help guide practitioners in EoE management by standardizing features of disease severity beyond eosinophil counts. To increase its utilization and functionality, authors note that I-SEE should be validated and refined using data from future clinical trials and routine clinical practice.

A survey examining the impact of COVID-19 on food protein-induced enterocolitis syndrome. Trogen B, Jin H, Cianferoni A, Chehade M, Schultz F, Chavez A, Warren C, Nowak-Wegrzyn AH. J Allergy Clin Immunol Pract. 2022 Jan;10(1):312-314.e3. doi: 10.1016/j.jaip.2021.10.053. Epub 2021 Nov 2.

CD73(+) Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis. Hara T, Kasagi Y, Wang J, Sasaki M, Aaron B, Karami A, Shimonosono M, Shimonosono R, Maekawa H, Dolinsky L, Wilkins B, Klein J, Wei J, Nunes K, Lynch K, Spergel JM, Hamilton KE, Ruffner MA, Karakasheva TA, Whelan KA, Nakagawa H, Muir AB. Cell Mol Gastroenterol Hepatol. 2022;13(5):1449-1467. doi: 10.1016/j.jcmgh.2022.01.018. Epub 2022 Jan 30.

Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study. Greuter T, Straumann A, Fernandez-Marrero Y, Germic N, Hosseini A, Yousefi S, Simon D, Collins MH, Bussmann C, Chehade M, Dellon ES, Furuta GT, Gonsalves N, Hirano I, Moawad FJ, Biedermann L, Safroneeva E, Schoepfer AM, Simon HU. Allergy. 2022 Aug;77(8):2520-2533. doi: 10.1111/all.15233. Epub 2022 Feb 17. PMID: 35094416

Eosinophilic esophagitis (EoE) is an allergic condition characterized by inflammation in the esophagus that causes a range of symptoms. Patients can have symptoms of esophageal dysfunction without meeting the classical diagnostic criteria. To characterize and classify the range of variants, an international team of researchers studied 69 patients with EoE variants. They identified and described three histological subtypes. Study authors concluded that EoE variants appear to be part of a disease spectrum, with classical EoE as the most common and apparent phenotype.

Close follow-up is associated with fewer stricture formation and results in earlier detection of histological relapse in the long-term management of eosinophilic esophagitis. Bon L, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Vavricka SR, Schoepfer AM, McCright-Gill T, Simon HU, Straumann A, Chehade M, Greuter T. United European Gastroenterol J. 2022 Apr;10(3):308-318. doi: 10.1002/ueg2.12216. Epub 2022 Apr 5. PMID: 35384368.

Eosinophilic esophagitis (EoE) is characterized by immune cells called eosinophils building up in the esophagus, which may cause polyps, tissue break down, inflammation, and ulcers. The follow-up schedule for maintenance treatment of EoE varies, possibly due to a lack of a recommended schedule. In this study, researchers analyzed "close follow-up" (less than 18 months between maintenance visits) and "non-close follow-up" (greater than or equal to 18 months between maintenance visits) for steroid treatment of EoE. They found that close follow-up was associated with less stricture formation (abnormal narrowing) and earlier detection of EoE relapse by histology. Authors note that regular assessment of EoE disease activity (every 12-18 months) may be beneficial in detecting relapsing disease as early as possible, therefore potentially minimizing the risk for EoE complications.

Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.

Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis. Hiremath G, Sun L, Correa H, Acra S, Collins MH, Bonis P, Arva NC, Capocelli KE, Falk GW, King E, Gonsalves N, Gupta SK, Hirano I, Mukkada VA, Martin LJ, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME, Koyama T, Dellon ES. Am J Gastroenterol. 2022 Feb 1;117(2):272-279. doi: 10.14309/ajg.0000000000001587.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS). COREOS Collaborators:, Ma C, Schoepfer AM, Dellon ES, Bredenoord AJ, Chehade M, Collins MH, Feagan BG, Furuta GT, Gupta SK, Hirano I, Jairath V, Katzka DA, Pai RK, Rothenberg ME, Straumann A, Aceves SS, Alexander JA, Arva NC, Atkins D, Biedermann L, Blanchard C, Cianferoni A, Ciriza de Los Rios C, Clayton F, Davis CM, de Bortoli N, Dias JA, Falk GW, Genta RM, Ghaffari G, Gonsalves N, Greuter T, Hopp R, Hsu Blatman KS, Jensen ET, Johnston D, Kagalwalla AF, Larsson HM, Leung J, Louis H, Masterson JC, Menard-Katcher C, Menard-Katcher PA, Moawad FJ, Muir AB, Mukkada VA, Penagini R, Pesek RD, Peterson K, Putnam PE, Ravelli A, Savarino EV, Schlag C, Schreiner P, Simon D, Smyrk TC, Spergel JM, Taft TH, Terreehorst I, Vanuytsel T, Venter C, Vieira MC, Vieth M, Vlieg-Boerstra B, von Arnim U, Walker MM, Wechsler JB, Woodland P, Woosley JT, Yang GY, Zevit N, Safroneeva E. J Allergy Clin Immunol. 2022 Feb;149(2):659-670. doi: 10.1016/j.jaci.2021.07.001. Epub 2021 Jul 6.

Diagnostic merits of the Eosinophilic Esophagitis Diagnostic Panel from a single esophageal biopsy. Min S, Shoda T, Wen T, Rothenberg ME. J Allergy Clin Immunol. 2022 Feb;149(2):782-787.e1. doi: 10.1016/j.jaci.2021.07.032. Epub 2021 Aug 8.

Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry. Zevit N, Chehade M, Leung J, Marderfeld L, Dellon ES. J Allergy Clin Immunol Pract. 2022 Jan;10(1):143-149.e9. doi: 10.1016/j.jaip.2021.10.019. Epub 2021 Oct 22.

Eosinophilic gastrointestinal diseases make a name for themselves: A new consensus statement with updated nomenclature. Wright BL, Schwartz JT, Ruffner MA, Furuta GT, Gonsalves N, Dellon ES, Aceves SS. J Allergy Clin Immunol. 2022 Aug;150(2):291-293. doi: 10.1016/j.jaci.2022.05.012. Epub 2022 May 29. PMID: 35649464; PMCID: PMC9378528

Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. Consensus recommendations have been developed for diagnosis of eosinophilic esophagitis (EoE), the most common EGID. However, there are currently no consensus guidelines for diagnosis of non-EoE EGIDs. Standardization of EGID terminology is one of the first priorities for developing these guidelines. In this study, a large group of researchers and clinicians aimed to reach international consensus for EGID nomenclature. The team used multiple rounds of surveys to develop a new tiered framework for EGID terms. Authors note that this revision of terms could advance both clinical care and research in EGIDs. Next steps include selection of specific disease markers and thresholds, definition of symptoms, exclusion of alternative diagnoses, and duration of disease.

Evaluating Eosinophilic Colitis as a Unique Disease using Colonic Molecular Profiles: A Multi-Site Study. Shoda T, Collins MH, Rochman M, Wen T, Caldwell JM, Mack LE, Osswald GA, Besse JA, Haberman Y, Aceves SS, Arva NC, Capocelli KE, Chehade M, Davis CM, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Klion A, Menard-Katcher C, Leung J, Mukkada V, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Denson LA, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR). Gastroenterology. 2022 Jan 24:S0016-5085(22)00038-5. doi: 10.1053/j.gastro.2022.01.022. Epub ahead of print. PMID: 35085569.

Eosinphilic colitis (EoC) has been a poorly understood condition with uncertainty whether it is a distinct disease or a manifestation of eosinophilic gastrointestinal disease or inflammatory bowel disease. Researchers from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) seeking to better understand the condition analyzed samples from more than 60 people treated at multiple medical centers v. controls to compare this rare disease to other conditions. They identified and analyzed 987 differentially expressed genes, established EoC transcriptomic profiles, identified mechanistic pathways, and compared findings with related conditions. They concluded that EoC is a distinct disease, establishing a basis for improved diagnosis and treatment.

Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field. Rothenberg ME, Hottinger SKB, Gonsalves N, Furuta GT, Collins MH, Talley NJ, Peterson K, Menard-Katcher C, Smith M, Hirano I, Genta RM, Chehade M, Gupta SK, Spergel JM, Aceves SS, Dellon ES. J Allergy Clin Immunol. 2022 Mar;149(3):844-853. doi: 10.1016/j.jaci.2021.12.768. Epub 2021 Dec 22.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature. Dellon ES, Gonsalves N, Abonia JP, Alexander JA, Arva NC, Atkins D, Attwood SE, Auth MKH, Bailey DD, Biederman L, Blanchard C, Bonis PA, Bose P, Bredenoord AJ, Chang JW, Chehade M, Collins MH, Di Lorenzo C, Dias JA, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox AT, Genta RM, Greuter T, Gupta SK, Hirano I, Hiremath GS, Horsley-Silva JL, Ishihara S, Ishimura N, Jensen ET, Gutiérrez-Junquera C, Katzka DA, Khoury P, Kinoshita Y, Kliewer KL, Koletzko S, Leung J, Liacouras CA, Lucendo AJ, Martin LJ, McGowan EC, Menard-Katcher C, Metz DC, Miller TL, Moawad FJ, Muir AB, Mukkada VA, Murch S, Nhu QM, Nomura I, Nurko S, Ohtsuka Y, Oliva S, Orel R, Papadopoulou A, Patel DA, Pesek RD, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Ruffner MA, Safroneeva E, Schreiner P, Schoepfer A, Schroeder SR, Shah N, Souza RF, Spechler SJ, Spergel JM, Straumann A, Talley NJ, Thapar N, Vandenplas Y, Venkatesh RD, Vieira MC, von Arnim U, Walker MM, Wechsler JB, Wershil BK, Wright BL, Yamada Y, Yang GY, Zevit N, Rothenberg ME, Furuta GT, Aceves SS. Clin Gastroenterol Hepatol. 2022 Feb 16:S1542-3565(22)00143-4. doi: 10.1016/j.cgh.2022.02.017. Online ahead of print.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis. Safroneeva E, Pan Z, King E, Martin LJ, Collins MH, Yang GY, Capocelli KE, Arva NC, Abonia JP, Atkins D, Bonis PA, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Schoepfer AM, Spergel JM, Wershil BK, Rothenberg ME, Aceves SS, Furuta GT; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Clin Gastroenterol Hepatol. 2022 Apr;20(4):766-775.e4. doi: 10.1016/j.cgh.2021.05.049. Epub 2021 May 29.

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort. Hirano I, Collins MH, King E, Sun Q, Chehade M, Abonia JP, Bonis PA, Capocelli KE, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Leung J, Katzka D, Menard-Katcher P, Khoury P, Klion A, Mukkada VA, Peterson K, Rudman-Spergel AK, Spergel JA, Yang GY, Rothenberg ME, Aceves SS, Furuta GT. Am J Gastroenterol. 2022 Jan 20. doi: 10.14309/ajg.0000000000001625. Epub ahead of print. PMID: 35080202.

Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach that occurs when certain white blood cells known as eosinophils gather in large numbers in the stomach, causing injury and irritation. In this study, researchers aimed to better understand the endoscopic manifestations of EG and develop a standardized instrument for investigations. Using data prospectively collected as part of CEGIR, the team evaluated endoscopic features of children and adults with EG recorded with the EG Endoscopic Reference System (EG-REFS). Researchers identified a strong correlation between EG-REFS scores and physician global assessment of endoscopy severity. EG-REFS severity was significantly correlated with active histology and a tendency for the gastric antrum (lower portion of the stomach). The authors note that further development of EG-REFS should improve its utility in clinical studies.

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study. Seibold MA, Moore CM, Everman JL, Williams BJM, Nolin JD, Fairbanks-Mahnke A, Plender EG, Patel BB, Arbes SJ, Bacharier LB, Bendixsen CG, Calatroni A, Camargo CA Jr, Dupont WD, Furuta GT, Gebretsadik T, Gruchalla RS, Gupta RS, Khurana Hershey GK, Murrison LB, Jackson DJ, Johnson CC, Kattan M, Liu AH, Lussier SJ, O'Connor GT, Rivera-Spoljaric K, Phipatanakul W, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Fulkerson PC, Hartert TV; HEROS study team. J Allergy Clin Immunol. 2022 Aug;150(2):302-311. doi: 10.1016/j.jaci.2022.05.014. Epub 2022 Jun 1. PMID: 35660376; PMCID: PMC9155183

Children and people with asthma or other allergic diseases are typically known as high-risk groups for many respiratory viruses. However, it is currently unknown whether these groups are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection. In this study, researchers aimed to determine the incidence of SARS-CoV-2 infection in households with children, as well as whether self-reported asthma or other allergic diseases are associated with infection and household transmission. Participants included allergic disease patients from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), which provided an accessible cohort for the study. For six months, the team collected biweekly nasal swabs and weekly surveys to calculate the probabilities of infection and transmission. Researchers then used regression analyses to determine associated risk factors. Results suggest that asthma does not increase the risk of SARS-CoV-2 infection. Food allergy was associated with lower infection risk, while body mass index was associated with increased infection risk. Authors note that understanding how these factors modify infection risk may offer new avenues for preventing infection.

What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities. Chang JW, Chen VL, Rubenstein JH, Dellon ES, Wallner LP, De Vries R. Dis Esophagus. 2022 Jun 15;35(6):doab073. doi: 10.1093/dote/doab073. PMID: 34718475.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that damages the esophagus. Little is known about how patients with EoE experience their symptoms, receive care, and cope with their disease. Often, patients seek peer support from online communities. As an unfiltered source of patient perspectives, these communities can provide insights on unmet needs and barriers to care. In this study, researchers performed a qualitative analysis of electronic health forums to characterize patient-to-patient conversations about EoE symptoms and the experience of disease. The team analyzed a random sample of conversation threads from three publicly accessible electronic health forums hosting EoE communities. Results showed that patients with EoE interpret their disease as sporadic events and lack reliable sources of knowledge, which may influence how they prioritize treatment. Authors note that providers should equip themselves with evidence-based knowledge, engage in shared decision-making, and look outside of clinical settings in order to recognize barriers to disease management.

A Gut-Wrenching Case of Hypereosinophilia. Melethil S, Abonia JP. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3524-3525. doi: 10.1016/j.jaip.2021.05.039. PMID: 34507713.

In a case study of hypereosinophilia, an allergic inflammatory condition in which white blood cells called eosinophils are at high levels in the body, a pediatric patient had recurrent gastrointestinal symptoms and histology showing elevated eosinophils in biopsy specimens. After excluding secondary causes of gastrointestinal eosinophilia, the clinicians diagnosed the patient with eosinophilic gastroenteritis (EGE). Eosinophilic gastritis (EG) and EGE are a heterogeneous group of rare disorders due to selective eosinophilic infiltration causing inflammation in the stomach and small intestine, in the absence of other secondary causes of eosinophilia. The exact incidence is unknown but is more commonly diagnosed in children younger than 5 years. In adults, the peak age of diagnosis is in the third decade of life. Authors say this case exemplifies two key points for healthcare providers: 1) Refer patients presenting with peripheral eosinophilia and recurrent or persistent gastrointestinal (GI) symptoms for evaluation for an intestinal biopsy and 2) Recognize that eosinophilic gastrointestinal diseases can be diagnosed only after other secondary causes of eosinophilia like parasitic infections or drug-induced causes are ruled out.

A Single-Food Milk Elimination Diet Is Effective for Treatment of Eosinophilic Esophagitis in Children. Wechsler JB, Schwartz S, Arva NC, Kim KA, Chen L, Makhija M, Amsden K, Keeley K, Mohammed S, Dellon ES, Kagalwalla AF. Clin Gastroenterol Hepatol. 2021 Apr 3:S1542-3565(21)00384-0. doi: 10.1016/j.cgh.2021.03.049. Online ahead of print.

Comorbid Diagnosis of Eosinophilic Esophagitis and Inflammatory Bowel Disease in the Pediatric Population. Moore H, Wechsler J, Frost C, Whiteside E, Baldassano R, Markowitz J, Muir AB. J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):398-403. doi: 10.1097/MPG.0000000000003002.

Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee. Zimmermann N, Abonia JP, Dreskin SC, Akin C, Bolton S, Happel CS, Geller M, Larenas-Linnemann D, Nanda A, Peterson K, Wasan A, Wechsler J, Zhang S, Bernstein JA. J Allergy Clin Immunol. 2021 Oct;148(4):964-983. doi: 10.1016/j.jaci.2021.06.030. Epub 2021 Aug 9. PMID: 34384610.

In human tissue biopsies, mast cells and eosinophils are commonly found. However, for several clinical conditions, there are knowledge gaps in determining diagnostic thresholds and how samples are processed, interpreted, and reported. These discrepancies can delay the correct diagnosis of a patient’s condition. A work group of pathology, allergy, dermatology, hematology/oncology, and gastroenterology stakeholders assembled to address this need. Together, the group developed a standardized approach for assessing mast cells and eosinophils in skin, gastrointestinal, and bone marrow pathologic specimens for the benefit of clinical practice and patients.

Diagnosis of Pediatric Non-Esophageal Eosinophilic Gastrointestinal Disorders by Eosinophil Peroxidase Immunohistochemistry. Hasan SH, Taylor S, Garg S, Buras MR, Doyle AD, Bauer CS, Wright BL, Schroeder S. Pediatr Dev Pathol. 2021 Nov-Dec;24(6):513-522. doi: 10.1177/10935266211024552. Epub 2021 Jun 28.

Distance to pediatric gastroenterology providers is associated with decreased diagnosis of eosinophilic esophagitis in rural populations. McGowan EC, Keller JP, Muir AB, Dellon ES, Peng R, Keet CA, Jensen ET. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4489-4492.e2. doi: 10.1016/j.jaip.2021.08.034. Epub 2021 Sep 14. PMID: 34534720; PMCID: PMC8671202.

Eosinophilic esophagitis (EoE) is characterized by immune cells called eosinophils building up in the esophagus, which may cause polyps, tissue break down, inflammation, and ulcers. In this cross-sectional study, researchers examined data from children enrolled in Medicaid 2012. They found that the apparent lower prevalence of eosinophilic esophagitis in rural communities was attenuated when adjusting for distance to provider. These results suggest that diagnostic disparities likely exist for eosinophilic esophagitis among children residing in rural areas.

Do rural health disparities affect prevalence data in pediatric eosinophilic esophagitis?. Sabet C, Klion AD, Bailey D, Jensen E, Chehade M, Abonia JP, Rothenberg ME, Furuta GT, Muir AB; CEGIR Investigator Group. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2549-2551. doi: 10.1016/j.jaip.2021.03.027.

Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood. Dellon ES, Shaheen O, Koutlas NT, Chang AO, Martin LJ, Rothenberg ME, Jensen ET. Dis Esophagus. 2021 Feb 10;34(2):doaa074. doi: 10.1093/dote/doaa074.

Effect of topical swallowed steroids on the bacterial and fungal esophageal microbiota in eosinophilic esophagitis. Benitez AJ, Tanes C, Mattei L, Hofstaedter CE, Kim DK, Gross J, Ruffner MA, Albenberg L, Spergel J, Bittinger K, Muir AB. Allergy. 2021 May;76(5):1549-1552. doi: 10.1111/all.14602. Epub 2020 Oct 19.

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies. Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ, Pavord ID, Akuthota P, Roufosse F, Rothenberg ME. Annu Rev Immunol. 2021 Apr 26;39:719-757. doi: 10.1146/annurev-immunol-093019-125918. Epub 2021 Mar 1.

Eosinophilic Esophagitis: A Review. Muir A, Falk GW. JAMA. 2021 Oct 5;326(13):1310-1318. doi: 10.1001/jama.2021.14920.

Researchers affiliated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) have published a new review paper examining eosinophilic esophagitis (EoE), an allergic inflammatory disease. EoE is characterized by elevated eosinophils (a type of disease-fighting white blood cell) in the esophagus (the tube connecting the mouth to the stomach). It affects an estimated 34.4/100,000 people in Europe and North America, including both children and adults. To diagnose the disease and evaluate treatment efficacy, a doctor inserts a thin, flexible tube with a light and camera at the end through a patient’s mouth, into the stomach, and sometimes into the upper intestine and collects tissue samples. In this paper, researchers discuss symptoms of the disease along with genetic and environmental factors associated with it. They also examine several current therapies, including proton pump inhibitors, topical steroid preparations, dietary therapy, and endoscopic dilation, and summarize recent systematic reviews of therapy trials.

Eosinophilic esophagitis may persist after discontinuation of oral immunotherapy. Hamant L, Freeman C, Garg S, Wright BL, Schroeder S. Ann Allergy Asthma Immunol. 2021 Mar;126(3):299-302. doi: 10.1016/j.anai.2020.12.007. Epub 2020 Dec 17.

How to approach adult patients with asymptomatic esophageal eosinophilia. Schreiner P, Biedermann L, Greuter T, Wright BL, Straumann A. Dis Esophagus. 2021 Jan 11;34(1):doaa105. doi: 10.1093/dote/doaa105.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk. Shoda T, Wen T, Caldwell JM, Ben-Baruch Morgenstern N, Osswald GA, Rochman M, Mack LE, Felton JM, Abonia JP, Arva NC, Atkins D, Bonis PA, Capocelli KE, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Putnam PE, Rudman Spergel AK, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group. Gastroenterology. 2022 Feb;162(2):439-453. doi: 10.1053/j.gastro.2021.10.016. Epub 2021 Oct 21. PMID: 34687736; PMCID: PMC8792211.

Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated immunologic disease that can progress to fibrostenosis, but the molecular pathogenesis of fibrostenotic EoE is not well understood. This study found that endothelial TSPAN12 contributes to fibrostenotic EoE and is the first molecular correlate of esophageal diameter. These findings provide new insight into previously underrecognized roles of the endothelium in disease pathogenesis. Anti–IL-13 therapy may improve fibrostenotic EoE through normalizing TSPAN12 levels.

Motivations, Barriers, and Outcomes of Patient-Reported Shared Decision Making in Eosinophilic Esophagitis. Chang JW, Rubenstein JH, Mellinger JL, Kodroff E, Strobel MJ, Scott M, Mack D, Book W, Sable K, Kyle S, Paliana A, Dellon ES. Dig Dis Sci. 2021 Jun;66(6):1808-1817. doi: 10.1007/s10620-020-06438-5. Epub 2020 Jul 3.

Moving FORWARD Toward Racial Equity in Food Allergy. Davis CM. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2874-2875. doi: 10.1016/j.jaip.2021.04.066.

Noninvasive biomarkers identify eosinophilic esophagitis: A prospective longitudinal study in children. Wechsler JB, Ackerman SJ, Chehade M, Amsden K, Riffle ME, Wang MY, Du J, Kleinjan ML, Alumkal P, Gray E, Kim KA, Wershil BK, Kagalwalla AF. Allergy. 2021 Apr 27. doi: 10.1111/all.14874. Online ahead of print.

Patients with eosinophilic gastrointestinal disorders have lower in-hospital mortality rates related to COVID-19. Qeadan F, Chehade M, Tingey B, Egbert J, Dellon ES, Peterson KA. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4473-4476.e4. doi: 10.1016/j.jaip.2021.09.022. Epub 2021 Sep 23. PMID: 34563741; PMCID: PMC8459462.

Little is known about eosinophilic gastrointestinal disease (EGID) and COVID-19 outcomes. By reducing viral entry into cells, the mucosal responses of patients with EGID may protect against severe effects of COVID-19. In this study, researchers compared hospitalization rates, ventilator dependence, and death between patients with and without EGID. When compared with non–EGID COVID-19 positive patients, they found that EGID COVID-19 positive individuals stayed longer in the hospital, yet had lower rates of inpatient mortality. This analysis suggests that EGID may provide a protective effect against severe COVID-19 outcomes. In future studies, researchers plan to further explore the protective role of reduced expression of ACE2/TMPRSS2 and the eosinophilic disease itself in COVID-19 mortality.

RNA sequencing identifies global transcriptional changes in peripheral CD4(+) cells during active oesophagitis and following epicutaneous immunotherapy in eosinophilic oesophagitis. Ruffner MA, Zhang Z, Maurer K, Muir AB, Cianferoni A, Sullivan KE, Spergel JM. Clin Transl Immunology. 2021 Jul 22;10(7):e1314. doi: 10.1002/cti2.1314. eCollection 2021.

Treatment of Eosinophilic Esophagitis: Diet or Medication?. Chehade M, Aceves SS. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3249-3256. doi: 10.1016/j.jaip.2021.07.029. PMID: 34507706.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease characterized by elevated eosinophils (white blood cells) in the esophagus (the tube connecting the mouth to the stomach). The prevalence of EoE is increasing in children and adults. As a chronic condition currently without a cure, EoE must be carefully managed to prevent complications, such as food impactions in the esophagus or narrowing of the lumen. In this paper, researchers discuss the current approaches for dietary and pharmacologic management of EoE and the need for future clinical trials to help tailor therapies to individual patients with this chronic disease.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders. Chiang AWT, Duong LD, Shoda T, Nhu QM, Ruffner M, Hara T, Aaron B, Joplin E, Manresa MC, Abonia JP, Dellon ES, Hirano I, Gonsalves N, Gupta SK, Furuta GT, Rothenberg ME, Lewis NE, Muir AB, Aceves SS; CEGIR Investigator Group. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):718-722. doi: 10.1097/MPG.0000000000003032.

Eosinophilic gastrointestinal disorders are inflammatory conditions caused by chronic type 2 (T2) inflammation. In this study, researchers sought to better understand the impact of this T2 inflammation on susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus-induced disease 2019 (COVID-19). Researchers analyzed gene expression data in pediatric eosinophilic esophagitis, eosinophilic gastritis, and in normal adults using publicly available datasets. They concluded that eosinophilic gastrointestinal diseases are not risk factors for COVID-19. and that T2 immunity & pediatric age could be protective for SARS-CoV-2 infection in the GI tract.

Unsedated transnasal esophagoscopy with virtual reality distraction enables earlier monitoring of dietary therapy in eosinophilic esophagitis. Friedlander JA, Fleischer DM, Black JO, Levy M, Rothenberg ME, Smith C, Nguyen N, Pan Z, Furuta GT. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3494-3496. doi: 10.1016/j.jaip.2021.06.030. Epub 2021 Jul 2. PMID: 34224927; PMCID: PMC8459391.

Eosinophilic esophagitis is a chronic, inflammatory disease of the esophagus often treated with an elimination diet, where patients avoid specific foods that are triggering the disease. The current standard of care for diagnosis and symptom monitoring requires repeated sedated endoscopy procedures over time. After the initial diagnostic endoscopy, many assessments may be needed to establish the correct diet. For patients, these repeated diagnostic procedures raise issues of risk, cost, and lost time from school and/or work. They also extend the time patients must wait to reintroduce foods. In this study, researchers seeking to address these concerns tested the use of an emerging technology, less invasive monitoring approach compared with standard endoscopy—unsedated transnasal esophagoscopy (TN-Eso) with virtual reality distraction. Although this was a pilot study involving only five patients, the researchers found that TN-Eso was well-tolerated and preferred by patients and families. Tests using the new technology detected the return of esophagitis as soon as two weeks after single-food exposure, suggesting that the timing of food reintroductions could be shortened by 50% to 75%, compared with the traditional endoscopies (which typically occur at 12-week intervals). Study authors say these findings support a shortened challenge period with the use of TN-Eso, which may lead to faster identification of a suitable treatment. The study also demonstrates that food allergen-induced eosinophilic esophagitis occurs within two weeks following exposure to the triggering food.

Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis. Joshi S, Rubenstein JH, Dellon ES, Worthing N, Stefanadis Z, Chang JW. Am J Gastroenterol. 2021 Jun 1;116(6):1336-1338. doi: 10.14309/ajg.0000000000001170.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Hirano I, Chan ES, Rank MA, Sharaf RN, Stollman NH, Stukus DR, Wang K, Greenhawt M, Falck-Ytter YT; AGA Institute Clinical Guidelines Committee; Joint Task Force on Allergy-Immunology Practice Parameters. Ann Allergy Asthma Immunol. 2020 May;124(5):416-423. doi: 10.1016/j.anai.2020.03.020.

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Aceves S, Collins MH, Rothenberg ME, Furuta GT, Gonsalves N; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jan;145(1):28-37. doi: 10.1016/j.jaci.2019.11.012. Epub 2019 Nov 20.

Antifibrotic Effects of the Thiazolidinediones in Eosinophilic Esophagitis Pathologic Remodeling: A Preclinical Evaluation. Nhu QM, Hsieh L, Dohil L, Dohil R, Newbury RO, Kurten R, Moawad FJ, Aceves SS. Clin Transl Gastroenterol. 2020 Apr;11(4):e00164. doi: 10.14309/ctg.0000000000000164.

Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. Hirano I, Furuta GT. Gastroenterology. 2020 Mar;158(4):840-851. doi: 10.1053/j.gastro.2019.09.052. Epub 2019 Dec 10.

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders. Pesek RD, Reed CC, Collins MH, Muir AB, Fulkerson PC, Menard-Katcher C, Falk GW, Kuhl J, Magier AZ, Ahmed FN, Demarshall M, Gupta A, Gross J, Ashorobi T, Carpenter CL, Krischer JP, Gonsalves N, Hirano I, Spergel JM, Gupta SK, Furuta GT, Rothenberg ME, Dellon ES; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Dig Dis Sci. 2020 Jul;65(7):2024-2035. doi: 10.1007/s10620-019-05961-4. Epub 2019 Nov 26.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study. Greuter T, Godat A, Ringel A, Almonte HS, Schupack D, Mendoza G, McCright-Gill T, Dellon ES, Hirano I, Alexander J, Chehade M, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Schoepfer AM, Straumann A, Katzka DA. Clin Gastroenterol Hepatol. 2020 Aug 13:S1542-3565(20)31136-8. doi: 10.1016/j.cgh.2020.08.027. Online ahead of print.

Elimination diets for eosinophilic esophagitis: making the best choice. Chehade M, Brown S. Expert Rev Clin Immunol. 2020 Jul;16(7):679-687. doi: 10.1080/1744666X.2020.1801419. Epub 2020 Aug 4.

Emerging therapies for eosinophilic esophagitis. Greuter T, Hirano I, Dellon ES. J Allergy Clin Immunol. 2020 Jan;145(1):38-45. doi: 10.1016/j.jaci.2019.10.027. Epub 2019 Nov 6.

EoE disease monitoring: Where we are and where we are going. Godwin B, Wilkins B, Muir AB. Ann Allergy Asthma Immunol. 2020 Mar;124(3):240-247. doi: 10.1016/j.anai.2019.12.004. Epub 2019 Dec 9.

Eosinophilic Esophagitis: Existing and Upcoming Therapies in an Age of Emerging Molecular and Personalized Medicine. Slack IF, Schwartz JT, Mukkada VA, Hottinger S, Abonia JP. Curr Allergy Asthma Rep. 2020 Jun 6;20(8):30. doi: 10.1007/s11882-020-00928-2.

Eosinophilic gastrointestinal disease below the belt. Pesek RD, Rothenberg ME. J Allergy Clin Immunol. 2020 Jan;145(1):87-89.e1. doi: 10.1016/j.jaci.2019.10.013. Epub 2019 Oct 24.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Doyle AD, Masuda MY, Kita H, Wright BL. Front Immunol. 2020 Dec 1;11:603295. doi: 10.3389/fimmu.2020.603295. eCollection 2020.

Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort. Dunn JLM, Shoda T, Caldwell JM, Wen T, Aceves SS, Collins MH, Dellon ES, Falk GW, Leung J, Martin LJ, Menard-Katcher P, Rudman-Spergel AK, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jun;145(6):1629-1640.e4. doi: 10.1016/j.jaci.2020.01.051. Epub 2020 Mar 19.

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases. Jensen ET, Aceves SS, Bonis PA, Bray K, Book W, Chehade M, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Katzka DA, Kyle S, Mack D, Kodroff E, Leung J, Mukkada VA, Scott M, Paliana A, Sable K, Spergel JM, Strobel MJ, Krischer J, Rothenberg ME, Abonia P; CEGIR Investigator group. J Pediatr Gastroenterol Nutr. 2020 Oct;71(4):524-529. doi: 10.1097/MPG.0000000000002817.

Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Bolton SM, Kagalwalla AF, Arva NC, Wang MY, Amsden K, Melin-Aldana H, Dellon ES, Bryce PJ, Wershil BK, Wechsler JB. Am J Gastroenterol. 2020 Feb;115(2):224-233. doi: 10.14309/ajg.0000000000000474.

Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in adults. Greuter T, Straumann A. Allergy. 2020 Mar;75(3):727-730. doi: 10.1111/all.14112. Epub 2019 Dec 5.

Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in children. Spergel JM, Brown-Whitehorn TA, Muir A, Liacouras CA. Allergy. 2020 Jun;75(6):1522-1524. doi: 10.1111/all.14188. Epub 2020 Jan 31.

Modeling Epithelial Homeostasis and Reactive Epithelial Changes in Human and Murine Three-Dimensional Esophageal Organoids. Nakagawa H, Kasagi Y, Karakasheva TA, Hara T, Aaron B, Shimonosono M, Kijima T, Giroux V, Bailey D, Wilkins B, Abrams JA, Falk GW, Aceves SS, Spergel JM, Hamilton KE, Whelan KA, Muir AB. Curr Protoc Stem Cell Biol. 2020 Mar;52(1):e106. doi: 10.1002/cpsc.106.

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study. Shoda T, Wen T, Caldwell JM, Collins MH, Besse JA, Osswald GA, Abonia JP, Arva NC, Atkins D, Capocelli KE, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Mukkada VA, Putnam PE, Sheridan RM, Rudman Spergel AK, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jan;145(1):255-269. doi: 10.1016/j.jaci.2019.11.007. Epub 2019 Nov 16.

Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis. Whelan KA, Godwin BC, Wilkins B, Elci OU, Benitez A, DeMarshall M, Sharma M, Gross J, Klein-Szanto AJ, Liacouras CA, Dellon ES, Spergel JM, Falk GW, Muir AB, Nakagawa H. Clin Gastroenterol Hepatol. 2020 Jun;18(7):1475-1482.e1. doi: 10.1016/j.cgh.2019.08.055. Epub 2019 Sep 6.

Technical review on the management of eosinophilic esophagitis: a report from the AGA institute and the joint task force on allergy-immunology practice parameters. Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES; AGA Institute Electronic address: clinicalpractice@gastroorg; Joint Task Force on Allergy-Immunology Practice Parameters collaborators Electronic address: drdanawallace@gmailcom; AGA Institute; Joint Task Force on Allergy-Immunology Practice Parameters collaborators. Ann Allergy Asthma Immunol. 2020 May;124(5):424-440.e17. doi: 10.1016/j.anai.2020.03.021.

The genetic etiology of eosinophilic esophagitis. Kottyan LC, Parameswaran S, Weirauch MT, Rothenberg ME, Martin LJ. J Allergy Clin Immunol. 2020 Jan;145(1):9-15. doi: 10.1016/j.jaci.2019.11.013.

The potential for malignancy from atopic disorders and allergic inflammation: A systematic review and meta-analysis. Muir AB, Whelan KA, Dougherty MK, Aaron B, Navarre B, Aceves SS, Dellon ES, Jensen ET. Clin Exp Allergy. 2020 Feb;50(2):147-159. doi: 10.1111/cea.13537. Epub 2019 Dec 20.

The role of eosinophils in immunotherapy. Cafone J, Ruffner MA, Spergel JM. Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):329. doi: 10.1097/ACI.0000000000000617.

Unanswered questions in eosinophilic esophagitis. Nhu QM, Aceves SS. Ann Allergy Asthma Immunol. 2020 Mar;124(3):227-228. doi: 10.1016/j.anai.2019.12.003. Epub 2019 Dec 9.

Validation of self-reported diagnosis of eosinophilic gastrointestinal disorders patients enrolled in the CEGIR contact registry. Hiremath G, Krischer JP, Rothenberg ME, Dellon ES. Clin Res Hepatol Gastroenterol. 2020 Nov 5:101555. doi: 10.1016/j.clinre.2020.10.001. Online ahead of print.

A Comparative Analysis of Eating Behavior of School-Aged Children with Eosinophilic Esophagitis and Their Caregivers' Quality of Life: Perspectives of Caregivers. Hiremath G, Rogers E, Kennedy E, Hemler J, Acra S. Dysphagia. 2019 Aug;34(4):567-574. doi: 10.1007/s00455-019-09984-x. Epub 2019 Feb 2.

A Conceptual Approach to Understanding Treatment Response in Eosinophilic Esophagitis. Dellon ES, Gupta SK. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2149-2160. doi: 10.1016/j.cgh.2019.01.030. Epub 2019 Jan 30.

Climbing New Mountains: How Antibodies Blocking α4β7 Integrins Tamed Eosinophilic Inflammation of the Intestinal Tract. Olbrich CL, Simerly L, de Zoeten EF, Furuta GT, Spencer LA. Dig Dis Sci. 2019 Aug;64(8):2068-2071. doi: 10.1007/s10620-019-05706-3.

Consortium of Eosinophilic Gastrointestinal Disease Researchers: Advancing the Field of Eosinophilic GI Disorders Through Collaboration. Gupta SK, Falk GW, Aceves SS, Chehade M, Collins MH, Dellon ES, Gonsalves N, Hirano I, Mukkuda VA, Peterson KA, Spergel J, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Gastroenterology. 2019 Mar;156(4):838-842. doi: 10.1053/j.gastro.2018.10.057. Epub 2018 Nov 17.

Cost-effective care in eosinophilic esophagitis. Dellon ES. Ann Allergy Asthma Immunol. 2019 Aug;123(2):166-172. doi: 10.1016/j.anai.2019.04.010. Epub 2019 Apr 19.

Editorial: the evolving epidemiology of EoE-up, up, and away?. Dellon ES. Aliment Pharmacol Ther. 2019 Jun;49(11):1448-1449. doi: 10.1111/apt.15252.

Eosinophil progenitor levels correlate with tissue pathology in pediatric eosinophilic esophagitis. Schwartz JT, Morris DW, Collins MH, Rothenberg ME, Fulkerson PC. J Allergy Clin Immunol. 2019 Mar;143(3):1221-1224.e3. doi: 10.1016/j.jaci.2018.10.036. Epub 2018 Nov 9.

Eosinophilic esophagitis during sublingual and oral allergen immunotherapy. Cafone J, Capucilli P, Hill DA, Spergel JM. Curr Opin Allergy Clin Immunol. 2019 Aug;19(4):350-357. doi: 10.1097/ACI.0000000000000537.

Eosinophilic esophagitis: early diagnosis is the key. Muir AB, Brown-Whitehorn T, Godwin B, Cianferoni A. Clin Exp Gastroenterol. 2019 Aug 15;12:391-399. doi: 10.2147/CEG.S175061. eCollection 2019.

Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis. Masterson JC, Biette KA, Hammer JA, Nguyen N, Capocelli KE, Saeedi BJ, Harris RF, Fernando SD, Hosford LB, Kelly CJ, Campbell EL, Ehrentraut SF, Ahmed FN, Nakagawa H, Lee JJ, McNamee EN, Glover LE, Colgan SP, Furuta GT. J Clin Invest. 2019 Jul 2;129(8):3224-3235. doi: 10.1172/JCI126744. eCollection 2019 Jul 2.

Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis. Muir AB, Wang JX, Nakagawa H. J Gastroenterol. 2019 Jan;54(1):10-18. doi: 10.1007/s00535-018-1498-3. Epub 2018 Aug 12.

Feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders. Chehade M, Meyer R, Beauregard A. Ann Allergy Asthma Immunol. 2019 Jun;122(6):603-609. doi: 10.1016/j.anai.2019.03.020. Epub 2019 Mar 26.

Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α. Kasagi Y, Dods K, Wang JX, Chandramouleeswaran PM, Benitez AJ, Gambanga F, Kluger J, Ashorobi T, Gross J, Tobias JW, Klein-Szanto AJ, Spergel JM, Cianferoni A, Falk GW, Whelan KA, Nakagawa H, Muir AB. J Allergy Clin Immunol. 2019 Jul;144(1):171-182. doi: 10.1016/j.jaci.2018.10.067. Epub 2018 Dec 20.

Histologic similarities in children with eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. Nguyen N, Baumgarten A, Wright BL, Capocelli KE, Pan Z, Lee JJ, Furuta GT, Masterson JC. J Allergy Clin Immunol. 2019 Mar;143(3):1237-1240.e2. doi: 10.1016/j.jaci.2018.10.047. Epub 2018 Nov 14.

How to Advance Research, Education, and Training in the Study of Rare Diseases. Groft SC, Gopal-Srivastava R, Dellon ES, Gupta SK. Gastroenterology. 2019 Oct;157(4):917-921. doi: 10.1053/j.gastro.2019.08.010. Epub 2019 Aug 8.

Illuminating Elimination Diets: Controversies Regarding Dietary Treatment of Eosinophilic Esophagitis. Cotton CC, Durban R, Dellon ES. Dig Dis Sci. 2019 Jun;64(6):1401-1408. doi: 10.1007/s10620-019-05602-w.

Immunology of the ancestral differences in eosinophilic esophagitis. Kottyan L, Spergel JM, Cianferoni A. Ann Allergy Asthma Immunol. 2019 May;122(5):443-444. doi: 10.1016/j.anai.2018.10.026. Epub 2018 Nov 7.

Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium. Pesek RD, Reed CC, Muir AB, Fulkerson PC, Menard-Katcher C, Falk GW, Kuhl J, Martin EK, Magier AZ, Ahmed F, Demarshall M, Gupta A, Gross J, Ashorobi T, Carpenter CL, Krischer JP, Gonsalves N, Spergel JM, Gupta SK, Furuta GT, Rothenberg ME, Dellon ES; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Am J Gastroenterol. 2019 Jun;114(6):984-994. doi: 10.14309/ajg.0000000000000228.

Mechanisms of gastrointestinal allergic disorders. Azouz NP, Rothenberg ME. J Clin Invest. 2019 Mar 11;129(4):1419-1430. doi: 10.1172/JCI124604. eCollection 2019 Mar 11.

Minimally symptomatic patients with eosinophilic esophagitis should still be actively treated-PRO. Muir A, Moore H, Spergel JM. Ann Allergy Asthma Immunol. 2019 Jun;122(6):572-573. doi: 10.1016/j.anai.2018.09.468. Epub 2018 Oct 5.

New Developments in the Diagnosis and Treatment of Eosinophilic Esophagitis. Nhu QM, Moawad FJ. Curr Treat Options Gastroenterol. 2019 Mar;17(1):48-62. doi: 10.1007/s11938-019-00216-7.

No Maintenance, No Gain in Long-term Treatment of Eosinophilic Esophagitis. Dellon ES. Clin Gastroenterol Hepatol. 2019 Feb;17(3):397-399. doi: 10.1016/j.cgh.2018.07.038.

Overestimation of the diagnosis of eosinophilic colitis with reliance on billing codes. Muir AB, Jensen ET, Wechsler JB, Menard-Katcher P, Falk GW, Aceves SS, Furuta GT, Dellon ES, Rothenberg ME, Spergel JM. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2434-2436. doi: 10.1016/j.jaip.2019.03.020. Epub 2019 Mar 25.

Prevalence of eosinophilic colitis and the diagnoses associated with colonic eosinophilia. DiTommaso LA, Rosenberg CE, Eby MD, Tasco A, Collins MH, Lyles JL, Putnam PE, Mukkada VA, Rothenberg ME. J Allergy Clin Immunol. 2019 May;143(5):1928-1930.e3. doi: 10.1016/j.jaci.2018.12.1002. Epub 2019 Jan 14.

Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis. Lyles J, Rothenberg M. Curr Opin Immunol. 2019 Oct;60:46-53. doi: 10.1016/j.coi.2019.04.004. Epub 2019 May 25.

Screening children for eosinophilic esophagitis: allergic and other risk factors. Ruffner MA, Capucilli P, Hill DA, Spergel JM. Expert Rev Clin Immunol. 2019 Apr;15(4):315-318. doi: 10.1080/1744666X.2019.1579643. Epub 2019 Feb 20.

The Salivary Microbiome Is Altered in Children With Eosinophilic Esophagitis and Correlates With Disease Activity. Hiremath G, Shilts MH, Boone HH, Correa H, Acra S, Tovchigrechko A, Rajagopala SV, Das SR. Clin Transl Gastroenterol. 2019 Jun;10(6):e00039. doi: 10.14309/ctg.0000000000000039.

Toll-like receptor 2 stimulation augments esophageal barrier integrity. Ruffner MA, Song L, Maurer K, Shi L, Carroll MC, Wang JX, Muir AB, Spergel JM, Sullivan KE. Allergy. 2019 Dec;74(12):2449-2460. doi: 10.1111/all.13968. Epub 2019 Jul 25.

Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus. Bailey DD, Zhang Y, van Soldt BJ, Jiang M, Suresh S, Nakagawa H, Rustgi AK, Aceves SS, Cardoso WV, Que J. Development. 2019 Dec 4;146(23):dev178855. doi: 10.1242/dev.178855.

A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia. Godwin B, Liacouras C, Mehta V, Eisenberg J, Agawu A, Brown-Whitehorn T, Ruffner MA, Verma R, Cianferoni A, Spergel JM, Muir AB. Front Pediatr. 2018 Jun 20;6:173. doi: 10.3389/fped.2018.00173. eCollection 2018.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites. Aceves SS, King E, Collins MH, Yang GY, Capocelli KE, Abonia JP, Atkins D, Bonis PA, Carpenter CL, Dellon ES, Eby MD, Falk GW, Gonsalves N, Gupta SK, Hirano I, Kocher K, Krischer JP, Leung J, Lipscomb J, Menard-Katcher P, Mukkada VA, Pan Z, Spergel JM, Sun Q, Wershil BK, Rothenberg ME, Furuta GT; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2018 Jul;142(1):130-138.e1. doi: 10.1016/j.jaci.2018.05.014. Epub 2018 May 29.

Allergic components of eosinophilic esophagitis. Spergel J, Aceves SS. J Allergy Clin Immunol. 2018 Jul;142(1):1-8. doi: 10.1016/j.jaci.2018.05.001.

Assessing Adherence and Barriers to Long-Term Elimination Diet Therapy in Adults with Eosinophilic Esophagitis. Wang R, Hirano I, Doerfler B, Zalewski A, Gonsalves N, Taft T. Dig Dis Sci. 2018 Jul;63(7):1756-1762. doi: 10.1007/s10620-018-5045-0. Epub 2018 Apr 2.

Authors' response. Spergel JM, Dellon ES, Liacouras CA, Hirano I, Molina-Infante J, Bredenoord AJ, Furuta GT. Ann Allergy Asthma Immunol. 2018 Dec;121(6):747-748. doi: 10.1016/j.anai.2018.10.015. Epub 2018 Oct 13.

Biological therapies for eosinophilic gastrointestinal diseases. Wechsler JB, Hirano I. J Allergy Clin Immunol. 2018 Jul;142(1):24-31.e2. doi: 10.1016/j.jaci.2018.05.018. Epub 2018 May 31.

Clinical Implications of Pediatric Colonic Eosinophilia. Mark J, Fernando SD, Masterson JC, Pan Z, Capocelli KE, Furuta GT, de Zoeten EF. J Pediatr Gastroenterol Nutr. 2018 May;66(5):760-766. doi: 10.1097/MPG.0000000000001784.

Clinical tolerance in eosinophilic esophagitis. Ruffner MA, Brown-Whitehorn TF, Verma R, Cianferoni A, Gober L, Shuker M, Muir AB, Liacouras CA, Spergel JM. J Allergy Clin Immunol Pract. 2018 Mar-Apr;6(2):661-663. doi: 10.1016/j.jaip.2017.06.035. Epub 2017 Aug 12.

Commentary: Individuals affected by Eosinophilic Gastrointestinal Disorders Have Complex Unmet Needs and Experience Barriers to Care. Hiremath G, Dellon ES. J Rare Dis Res Treat. 2018;3(2):34-36. doi: 10.29245/2572-9411/2018/2.1155. Epub 2018 Jul 17.

Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis- Current Concepts and Perspectives for Steroid Use. Greuter T, Alexander JA, Straumann A, Katzka DA. Clin Transl Gastroenterol. 2018 Dec;9(12):e212. doi: 10.1038/s41424-018-0074-8.

Emerging drugs for eosinophilic esophagitis. Pesek RD, Gupta SK. Expert Opin Emerg Drugs. 2018 Jun;23(2):173-183. doi: 10.1080/14728214.2018.1483335. Epub 2018 Jun 8.

Environmental factors and eosinophilic esophagitis. Jensen ET, Dellon ES. J Allergy Clin Immunol. 2018 Jul;142(1):32-40. doi: 10.1016/j.jaci.2018.04.015. Epub 2018 May 2.

Eosinophilic Esophagitis. Wright BL, Spergel JM. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1799-1801. doi: 10.1016/j.jaip.2018.06.019.

Eosinophilic Esophagitis Is a Late Manifestation of the Allergic March. Hill DA, Grundmeier RW, Ramos M, Spergel JM. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1528-1533. doi: 10.1016/j.jaip.2018.05.010. Epub 2018 Jun 25.

Eosinophilic Esophagitis Reference Score Accurately Identifies Disease Activity and Treatment Effects in Children. Wechsler JB, Bolton SM, Amsden K, Wershil BK, Hirano I, Kagalwalla AF. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1056-1063. doi: 10.1016/j.cgh.2017.12.019. Epub 2017 Dec 15.

Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and Management. Steinbach EC, Hernandez M, Dellon ES. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1483-1495. doi: 10.1016/j.jaip.2018.06.012. Epub 2018 Jul 3.

Eosinophilic Esophagitis: an Important Comorbid Condition of Asthma?. Durrani SR, Mukkada VA, Guilbert TW. Clin Rev Allergy Immunol. 2018 Aug;55(1):56-64. doi: 10.1007/s12016-018-8670-7.

Eosinophilic Gastroenteritis and Colitis: Not Yet Ready for the Big Leagues. Zevit N, Furuta GT. J Pediatr Gastroenterol Nutr. 2018 Jul;67(1):1-2. doi: 10.1097/MPG.0000000000001998.

Eosinophilic Gastrointestinal Disorders Pathology. Collins MH, Capocelli K, Yang GY. Front Med (Lausanne). 2018 Jan 15;4:261. doi: 10.3389/fmed.2017.00261. eCollection 2017.

Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. Martin LJ, He H, Collins MH, Abonia JP, Biagini Myers JM, Eby M, Johansson H, Kottyan LC, Khurana Hershey GK, Rothenberg ME. J Allergy Clin Immunol. 2018 May;141(5):1690-1698. doi: 10.1016/j.jaci.2017.09.046. Epub 2017 Nov 10.

Eosinophilic esophagitis: Time to classify into endotypes?. Ferguson AE, Fulkerson PC. J Allergy Clin Immunol. 2018 Jul;142(1):71-72. doi: 10.1016/j.jaci.2018.04.025. Epub 2018 May 8.

Eosinophilic esophagitis: pathophysiology and its clinical implications. Inage E, Furuta GT, Menard-Katcher C, Masterson JC. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G879-G886. doi: 10.1152/ajpgi.00174.2018. Epub 2018 Sep 13.

Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study. Shoda T, Wen T, Aceves SS, Abonia JP, Atkins D, Bonis PA, Caldwell JM, Capocelli KE, Carpenter CL, Collins MH, Dellon ES, Eby MD, Gonsalves N, Gupta SK, Falk GW, Hirano I, Menard-Katcher P, Kuhl JT, Krischer JP, Leung J, Mukkada VA, Spergel JM, Trimarchi MP, Yang GY, Zimmermann N, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Lancet Gastroenterol Hepatol. 2018 Jul;3(7):477-488. doi: 10.1016/S2468-1253(18)30096-7. Epub 2018 May 3.

Epidemiology and Natural History of Eosinophilic Esophagitis. Dellon ES, Hirano I. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.

Epithelial acid imbalance in patients with eosinophilic esophagitis. Hill DA, Spergel JM. J Allergy Clin Immunol. 2018 Dec;142(6):1757-1758. doi: 10.1016/j.jaci.2018.09.026. Epub 2018 Oct 10.

Epithelial origin of eosinophilic esophagitis. Rochman M, Azouz NP, Rothenberg ME. J Allergy Clin Immunol. 2018 Jul;142(1):10-23. doi: 10.1016/j.jaci.2018.05.008.

Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine. Whelan KA, Muir AB, Nakagawa H. Cell Mol Gastroenterol Hepatol. 2018 Jan 31;5(4):461-478. doi: 10.1016/j.jcmgh.2018.01.011. eCollection 2018.

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis. Fahey LM, Chandramouleeswaran PM, Guan S, Benitez AJ, Furuta GT, Aceves SS, Wang ML, Liacouras CA, Muir AB, Sleiman PM, Hakonarson H, Spergel JM, Cianferoni A. Clin Transl Gastroenterol. 2018 Mar 6;9(3):139. doi: 10.1038/s41424-018-0003-x.

Histologic improvement after 6 weeks of dietary elimination for eosinophilic esophagitis may be insufficient to determine efficacy. Philpott H, Dellon E. Asia Pac Allergy. 2018 Apr 25;8(2):e20. doi: 10.5415/apallergy.2018.8.e20. eCollection 2018 Apr.

Increased GATA-3 and T-bet expression in eosinophilic esophagitis versus gastroesophageal reflux disease. Wright BL, Nguyen N, Shim KP, Masterson JC, Jacobsen EA, Ochkur SI, Lee JJ, Furuta GT. J Allergy Clin Immunol. 2018 May;141(5):1919-1921.e5. doi: 10.1016/j.jaci.2017.12.993. Epub 2018 Jan 31.

Individuals affected by eosinophilic gastrointestinal disorders have complex unmet needs and frequently experience unique barriers to care. Hiremath G, Kodroff E, Strobel MJ, Scott M, Book W, Reidy C, Kyle S, Mack D, Sable K, Abonia P, Spergel J, Gupta SK, Furuta TG, Rothenberg ME, Dellon ES. Clin Res Hepatol Gastroenterol. 2018 Oct;42(5):483-493. doi: 10.1016/j.clinre.2018.03.003. Epub 2018 Mar 31.

Is eosinophilic esophagitis a member of the atopic march?. Hill DA, Spergel JM. Ann Allergy Asthma Immunol. 2018 Feb;120(2):113-114. doi: 10.1016/j.anai.2017.10.003.

Latest Insights on the Relationship Between Symptoms and Biologic Findings in Adults with Eosinophilic Esophagitis. Safroneeva E, Straumann A, Schoepfer AM. Gastrointest Endosc Clin N Am. 2018 Jan;28(1):35-45. doi: 10.1016/j.giec.2017.08.001.

Management of Esophageal Food Impaction Varies Among Gastroenterologists and Affects Identification of Eosinophilic Esophagitis. Hiremath G, Vaezi MF, Gupta SK, Acra S, Dellon ES. Dig Dis Sci. 2018 Jun;63(6):1428-1437. doi: 10.1007/s10620-018-4972-0. Epub 2018 Feb 20.

New Developments in the Diagnosis, Therapy, and Monitoring of Eosinophilic Esophagitis. Patel RV, Hirano I. Curr Treat Options Gastroenterol. 2018 Mar;16(1):15-26. doi: 10.1007/s11938-018-0167-1.

New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting. Spergel JM, Aceves SS, Kliewer K, Gonsalves N, Chehade M, Wechsler JB, Groetch M, Friedlander J, Dellon ES, Book W, Hirano I, Muir AB, Cianferoni A, Spencer L, Liacouras CA, Cheng E, Kottyan L, Wen T, Platts-Mills T, Rothenberg ME. J Allergy Clin Immunol. 2018 Jul;142(1):48-53. doi: 10.1016/j.jaci.2018.05.005. Epub 2018 May 24.

Nonesophageal Eosinophilic Gastrointestinal Disorders: Clinical Care and Future Directions. Naramore S, Gupta SK. J Pediatr Gastroenterol Nutr. 2018 Sep;67(3):318-321. doi: 10.1097/MPG.0000000000002040.

Pathophysiology of Eosinophilic Esophagitis. O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.

Pediatric Eosinophilic Esophagitis Endotypes: Are We Closer to Predicting Treatment Response?. Ferguson AE, Mukkada VA, Fulkerson PC. Clin Rev Allergy Immunol. 2018 Aug;55(1):43-55. doi: 10.1007/s12016-017-8658-8.

Pediatric eosinophilic esophagitis: updates for the primary care setting. Ruffner MA, Spergel JM. Curr Opin Pediatr. 2018 Dec;30(6):829-836. doi: 10.1097/MOP.0000000000000698.

Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research. Chehade M, Jones SM, Pesek RD, Burks AW, Vickery BP, Wood RA, Leung DYM, Furuta GT, Fleischer DM, Henning AK, Dawson P, Lindblad RW, Sicherer SH, Abonia JP, Sherrill JD, Sampson HA, Rothenberg ME. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1534-1544.e5. doi: 10.1016/j.jaip.2018.05.038. Epub 2018 Aug 1.

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). Khoury P, Akuthota P, Ackerman SJ, Arron JR, Bochner BS, Collins MH, Kahn JE, Fulkerson PC, Gleich GJ, Gopal-Srivastava R, Jacobsen EA, Leiferman KM, Francesca LS, Mathur SK, Minnicozzi M, Prussin C, Rothenberg ME, Roufosse F, Sable K, Simon D, Simon HU, Spencer LA, Steinfeld J, Wardlaw AJ, Wechsler ME, Weller PF, Klion AD. J Leukoc Biol. 2018 Jul;104(1):69-83. doi: 10.1002/JLB.5MR0118-028R. Epub 2018 Apr 19.

Summary of the updated international consensus diagnostic criteria for eosinophilic esophagitis: AGREE conference. Spergel JM, Dellon ES, Liacouras CA, Hirano I, Molina-Infante J, Bredenoord AJ, Furuta GT; participants of AGREE. Ann Allergy Asthma Immunol. 2018 Sep;121(3):281-284. doi: 10.1016/j.anai.2018.05.035. Epub 2018 Jul 18.

TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis. Nguyen N, Fernando SD, Biette KA, Hammer JA, Capocelli KE, Kitzenberg DA, Glover LE, Colgan SP, Furuta GT, Masterson JC. Mucosal Immunol. 2018 Mar;11(2):415-426. doi: 10.1038/mi.2017.72. Epub 2017 Aug 23.

The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes. Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. Cell Mol Gastroenterol Hepatol. 2018 Jan 3;5(3):333-352. doi: 10.1016/j.jcmgh.2017.12.013. eCollection 2018 Mar.

The Occasional Ebb and Flow between Eosinophilic Esophagitis and IgE-Mediated Food Allergy. Atkins D. J Allergy Clin Immunol Pract. 2018 Mar-Apr;6(2):651-652. doi: 10.1016/j.jaip.2017.11.011.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses. Azouz NP, Ynga-Durand MA, Caldwell JM, Jain A, Rochman M, Fischesser DM, Ray LM, Bedard MC, Mingler MK, Forney C, Eilerman M, Kuhl JT, He H, Biagini Myers JM, Mukkada VA, Putnam PE, Khurana Hershey GK, Kottyan LC, Wen T, Martin LJ, Rothenberg ME. Sci Transl Med. 2018 Jun 6;10(444):eaap9736. doi: 10.1126/scitranslmed.aap9736.

The atopic march: Critical evidence and clinical relevance. Hill DA, Spergel JM. Ann Allergy Asthma Immunol. 2018 Feb;120(2):131-137. doi: 10.1016/j.anai.2017.10.037.

The role of maintenance therapy in eosinophilic esophagitis: who, why, and how?. Philpott H, Dellon ES. J Gastroenterol. 2018 Feb;53(2):165-171. doi: 10.1007/s00535-017-1397-z. Epub 2017 Oct 10.

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ. Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.

What Is the Relationship Between Eosinophilic Esophagitis (EoE) and Aeroallergens? Implications for Allergen Immunotherapy. Egan M, Atkins D. Curr Allergy Asthma Rep. 2018 Jun 16;18(8):43. doi: 10.1007/s11882-018-0798-2.

Aeroallergens in Eosinophilic Esophagitis: Significant Triggers or Noise in the System?. Atkins D. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):1-2. doi: 10.1097/MPG.0000000000001268.

Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Whelan KA, Merves JF, Giroux V, Tanaka K, Guo A, Chandramouleeswaran PM, Benitez AJ, Dods K, Que J, Masterson JC, Fernando SD, Godwin BC, Klein-Szanto AJ, Chikwava K, Ruchelli ED, Hamilton KE, Muir AB, Wang ML, Furuta GT, Falk GW, Spergel JM, Nakagawa H. Gut. 2017 Jul;66(7):1197-1207. doi: 10.1136/gutjnl-2015-310341. Epub 2016 Feb 16.

Clarifying misunderstandings and misinterpretations about proton pump inhibitor-responsive oesophageal eosinophilia. Molina-Infante J, Hirano I, Spechler SJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Gut. 2017 Jun;66(6):1173-1174. doi: 10.1136/gutjnl-2016-312851. Epub 2016 Sep 13.

Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel. Wen T, Rothenberg ME. Front Med (Lausanne). 2017 Jul 14;4:108. doi: 10.3389/fmed.2017.00108. eCollection 2017.

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Cheng K, Gupta SK, Kantor S, Kuhl JT, Aceves SS, Bonis PA, Capocelli KE, Carpenter C, Chehade M, Collins MH, Dellon ES, Falk GW, Gopal-Srivastava R, Gonsalves N, Hirano I, King EC, Leung J, Krischer JP, Mukkada VA, Schoepfer A, Spergel JM, Straumann A, Yang GY, Furuta GT, Rothenberg ME. Transl Sci Rare Dis. 2017 Dec 18;2(3-4):141-155. doi: 10.3233/TRD-170016.

Diet and Stress in Pediatric Eosinophilic Esophagitis. Case C, Furuta GT, Atkins D, Pan Z, Robinson J. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):281-284. doi: 10.1097/MPG.0000000000001481.

Dilation of Pediatric Eosinophilic Esophagitis: Adverse Events and Short-term Outcomes. Menard-Katcher C, Furuta GT, Kramer RE. J Pediatr Gastroenterol Nutr. 2017 May;64(5):701-706. doi: 10.1097/MPG.0000000000001336.

Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis. Pesek RD, Rettiganti M, O'Brien E, Beckwith S, Daniel C, Luo C, Scurlock AM, Chandler P, Levy RA, Perry TT, Kennedy JL, Chervinskiy S, Vonlanthen M, Casteel H, Fiedorek SC, Gibbons T, Jones SM. Ann Allergy Asthma Immunol. 2017 Aug;119(2):177-183. doi: 10.1016/j.anai.2017.06.006. Epub 2017 Jul 1.

Eosinophilic Esophagitis: A Primary Disease of the Esophageal Mucosa. Abonia JP, Spergel JM, Cianferoni A. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):951-955. doi: 10.1016/j.jaip.2017.02.004. Epub 2017 Mar 28.

Eosinophilic esophagitis phenotypes: Ready for prime time?. Atkins D, Furuta GT, Liacouras CA, Spergel JM. Pediatr Allergy Immunol. 2017 Jun;28(4):312-319. doi: 10.1111/pai.12715. Epub 2017 May 4.

Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a Pediatric Cohort. Menard-Katcher C, Benitez AJ, Pan Z, Ahmed FN, Wilkins BJ, Capocelli KE, Liacouras CA, Verma R, Spergel JM, Furuta GT, Muir AB. Am J Gastroenterol. 2017 Sep;112(9):1466-1473. doi: 10.1038/ajg.2017.131. Epub 2017 May 16.

Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis. Eluri S, Book WM, Kodroff E, Strobel MJ, Gebhart JH, Jones PD, Menard-Katcher P, Ferris ME, Dellon ES. J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):53-57. doi: 10.1097/MPG.0000000000001415.

Management of refractory eosinophilic oesophagitis. Dellon ES. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):479-490. doi: 10.1038/nrgastro.2017.56. Epub 2017 May 24.

Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, Pentiuk S, Putnam PE, Abonia JP, Mukkada VA, Franciosi JP, Rothenberg ME. Dis Esophagus. 2017 Feb 1;30(3):1-8. doi: 10.1111/dote.12470.

Novel immunologic mechanisms in eosinophilic esophagitis. Caldwell JM, Paul M, Rothenberg ME. Curr Opin Immunol. 2017 Oct;48:114-121. doi: 10.1016/j.coi.2017.08.006. Epub 2017 Sep 29.

Propofol Use in Pediatric Patients With Food Allergy and Eosinophilic Esophagitis. Mehta P, Sundaram SS, Furuta GT, Pan Z, Atkins D, Markowitz S. J Pediatr Gastroenterol Nutr. 2017 Apr;64(4):546-549. doi: 10.1097/MPG.0000000000001291.

Proton pump inhibitor-responsive oesophageal eosinophilia: too early to change clinical practice. Muir AB, Wang ML, Metz D, Falk G, Markowitz J, Spergel JM, Liacouras CA. Gut. 2017 May;66(5):979-980. doi: 10.1136/gutjnl-2016-312601. Epub 2016 Jul 26.

Sticky Steroids: In Search of an Approved Treatment for Eosinophilic Esophagitis. Nguyen N, Furuta GT, Menard-Katcher C. J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):172-173. doi: 10.1097/MPG.0000000000001326.

The National Biome Initiative: An allergy perspective. Furuta GT, Aceves SS. J Allergy Clin Immunol. 2017 Apr;139(4):1131-1134. doi: 10.1016/j.jaci.2017.02.008. Epub 2017 Feb 28.

The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy. Hill DA, Dudley JW, Spergel JM. J Allergy Clin Immunol Pract. 2017 Mar-Apr;5(2):369-375. doi: 10.1016/j.jaip.2016.11.020. Epub 2016 Dec 30.

Toward More Efficient Dietary Elimination Therapy for Eosinophilic Esophagitis: The Fantastic 4?. Eluri S, Dellon ES. Clin Gastroenterol Hepatol. 2017 Nov;15(11):1668-1670. doi: 10.1016/j.cgh.2017.07.022. Epub 2017 Jul 26.

White Paper AGA: Drug Development for Eosinophilic Esophagitis. Hirano I, Spechler S, Furuta G, Dellon ES. Clin Gastroenterol Hepatol. 2017 Aug;15(8):1173-1183. doi: 10.1016/j.cgh.2017.03.016. Epub 2017 Mar 22.

2015 David Y. Graham Lecture: The First Two Decades Of Eosinophilic Esophagitis-From Acid Reflux To Food Allergy. Hirano I. Am J Gastroenterol. 2016 Jun;111(6):770-6. doi: 10.1038/ajg.2016.136. Epub 2016 Apr 12.

Advances in the endoscopic evaluation of eosinophilic esophagitis. Kia L, Hirano I. Curr Opin Gastroenterol. 2016 Jul;32(4):325-31. doi: 10.1097/MOG.0000000000000278.

Deeper Than the Epithelium: Role of Matrix and Fibroblasts in Pediatric and Adult Eosinophilic Esophagitis. Nguyen N, Furuta GT, Masterson JC. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):168-9. doi: 10.1097/MPG.0000000000001183.

Diets for diagnosis and management of food allergy: The role of the dietitian in eosinophilic esophagitis in adults and children. Venter C, Fleischer DM. Ann Allergy Asthma Immunol. 2016 Nov;117(5):468-471. doi: 10.1016/j.anai.2016.08.003. Epub 2016 Aug 31.

Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis. Morris DW, Stucke EM, Martin LJ, Abonia JP, Mukkada VA, Putnam PE, Rothenberg ME, Fulkerson PC. J Allergy Clin Immunol. 2016 Sep;138(3):915-918.e5. doi: 10.1016/j.jaci.2016.03.027. Epub 2016 May 16.

Eosinophilic Esophagitis-Associated Chemical and Mechanical Microenvironment Shapes Esophageal Fibroblast Behavior. Muir AB, Dods K, Henry SJ, Benitez AJ, Lee D, Whelan KA, DeMarshall M, Hammer DA, Falk G, Wells RG, Spergel J, Nakagawa H, Wang ML. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):200-9. doi: 10.1097/MPG.0000000000001100.

Eosinophilic Gastrointestinal Disorders Affect More Than Just the Esophagus. Gonsalves N, Furuta GT, Atkins D. J Pediatr Gastroenterol Nutr. 2016 Jan;62(1):1-2. doi: 10.1097/MPG.0000000000000993.

Eosinophilic esophagitis: search for noninvasive techniques for long-term monitoring. Watts A, Alexander JA, Gupta SK. Gastrointest Endosc. 2016 Feb;83(2):307-8. doi: 10.1016/j.gie.2015.07.006.

Eosinophils, probiotics, and the microbiome. Rosenberg HF, Masterson JC, Furuta GT. J Leukoc Biol. 2016 Nov;100(5):881-888. doi: 10.1189/jlb.3RI0416-202R. Epub 2016 Aug 22.

Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30.

Mechanisms of Disease of Eosinophilic Esophagitis. Davis BP, Rothenberg ME. Annu Rev Pathol. 2016 May 23;11:365-93. doi: 10.1146/annurev-pathol-012615-044241. Epub 2016 Feb 24.

Microbiome and its impact on gastrointestinal atopy. Muir AB, Benitez AJ, Dods K, Spergel JM, Fillon SA. Allergy. 2016 Sep;71(9):1256-63. doi: 10.1111/all.12943. Epub 2016 Jun 23.

Narrow-caliber esophagus of eosinophilic esophagitis: difficult to define, resistant to remedy. Carlson DA, Hirano I. Gastrointest Endosc. 2016 Jun;83(6):1149-50. doi: 10.1016/j.gie.2016.01.034.

Non-IgE-mediated food allergy syndromes. Ruffner MA, Spergel JM. Ann Allergy Asthma Immunol. 2016 Nov;117(5):452-454. doi: 10.1016/j.anai.2016.04.014. Epub 2016 Oct 24.

Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE). Chandramouleeswaran PM, Shen D, Lee AJ, Benitez A, Dods K, Gambanga F, Wilkins BJ, Merves J, Noah Y, Toltzis S, Yearley JH, Spergel JM, Nakagawa H, Malefyt Rd, Muir AB, Wang ML. PLoS One. 2016 Mar 18;11(3):e0150968. doi: 10.1371/journal.pone.0150968. eCollection 2016.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Straumann A, Lucendo AJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Gut. 2016 Mar;65(3):524-31. doi: 10.1136/gutjnl-2015-310991. Epub 2015 Dec 18.

Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Cavagnero K, Miyanohara A, Dohil R, Kurten RC, Aceves SS. J Allergy Clin Immunol. 2016 Apr;137(4):1270-1272.e1. doi: 10.1016/j.jaci.2015.09.020. Epub 2015 Nov 2.

Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?. Kliewer KL, Venter C, Cassin AM, Abonia JP, Aceves SS, Bonis PA, Dellon ES, Falk GW, Furuta GT, Gonsalves N, Gupta SK, Hirano I, Kagalwalla A, Leung J, Mukkada VA, Spergel JM, Rothenberg ME. J Allergy Clin Immunol. 2016 Apr;137(4):1011-1014. doi: 10.1016/j.jaci.2015.10.040. Epub 2015 Dec 24.

Substantial Variability in Biopsy Practice Patterns Among Gastroenterologists for Suspected Eosinophilic Gastrointestinal Disorders. Dellon ES, Collins MH, Bonis PA, Leung J, Capocelli KE, Dohil R, Falk GW, Furuta GT, Menard-Katcher C, Gupta SK, Hirano I, Hiremath GS, Kagalwalla AF, Wershil BK, Liacouras CA, Muir AB, Mukkada VA, Putnam PE, Schoepfer AM, Straumann A, Wo JM, Yang GY, Rothenberg ME, Gonsalves N. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1842-1844. doi: 10.1016/j.cgh.2016.04.025. Epub 2016 Apr 22.

TGF-β1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. Rawson R, Yang T, Newbury RO, Aquino M, Doshi A, Bell B, Broide DH, Dohil R, Kurten R, Aceves SS. J Allergy Clin Immunol. 2016 Sep;138(3):791-800.e4. doi: 10.1016/j.jaci.2016.02.028. Epub 2016 Apr 8.

The Immunologic Mechanisms of Eosinophilic Esophagitis. Hill DA, Spergel JM. Curr Allergy Asthma Rep. 2016 Feb;16(2):9. doi: 10.1007/s11882-015-0592-3.

The Regulatory Function of Eosinophils. Wen T, Rothenberg ME. Microbiol Spectr. 2016 Oct;4(5):10.1128/microbiolspec.MCHD-0020-2015. doi: 10.1128/microbiolspec.MCHD-0020-2015.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Topical glucocorticoid vs. diet therapy in eosinophilic esophagitis: the need for better treatment options. Imam T, Gupta SK. Expert Rev Clin Immunol. 2016 Aug;12(8):797-9. doi: 10.1080/1744666X.2016.1191947. Epub 2016 Jun 13.

Allergic mechanisms of Eosinophilic oesophagitis. Leung J, Beukema KR, Shen AH. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):709-720. doi: 10.1016/j.bpg.2015.09.012. Epub 2015 Sep 11.

An allergist's perspective to the evaluation of Eosinophilic Esophagitis. Spergel JM. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):771-781. doi: 10.1016/j.bpg.2015.06.011. Epub 2015 Jul 8.

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies. Kia L, Hirano I. Nat Rev Gastroenterol Hepatol. 2015 Jul;12(7):379-386. doi: 10.1038/nrgastro.2015.75. Epub 2015 May 19.

Environmental and infectious factors in eosinophilic esophagitis. Jensen ET, Dellon ES. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):721-729. doi: 10.1016/j.bpg.2015.06.008. Epub 2015 Jul 17.

Eosinophilic Esophagitis. Furuta GT, Katzka DA. N Engl J Med. 2015 Oct 22;373(17):1640-8. doi: 10.1056/NEJMra1502863.

Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections. Mehta P, Furuta GT. Immunol Allergy Clin North Am. 2015 Aug;35(3):413-37. doi: 10.1016/j.iac.2015.04.003. Epub 2015 Jun 17.

From genetics to treatment of eosinophilic esophagitis. Cianferoni A, Spergel JM. Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):417-25. doi: 10.1097/ACI.0000000000000200.

Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, Wang ML. Microbiome. 2015 Jun 1;3:23. doi: 10.1186/s40168-015-0085-6. eCollection 2015.

Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches. Kochar B, Dellon ES. Expert Rev Gastroenterol Hepatol. 2015;9(11):1359-69. doi: 10.1586/17474124.2015.1088384. Epub 2015 Sep 12.

Molecular, genetic, and cellular bases for treating eosinophilic esophagitis. Rothenberg ME. Gastroenterology. 2015 May;148(6):1143-57. doi: 10.1053/j.gastro.2015.02.002. Epub 2015 Feb 7.

Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: more similarities than differences. Eluri S, Dellon ES. Curr Opin Gastroenterol. 2015 Jul;31(4):309-15. doi: 10.1097/MOG.0000000000000185.

Recent advances in the pathological understanding of eosinophilic esophagitis. Cianferoni A, Spergel JM, Muir A. Expert Rev Gastroenterol Hepatol. 2015;9(12):1501-10. doi: 10.1586/17474124.2015.1094372. Epub 2015 Oct 15.

Recognition and Assessment of Eosinophilic Esophagitis: The Development of New Clinical Outcome Metrics. Nguyen N, Furuta GT, Menard-Katcher C. Gastroenterol Hepatol (N Y). 2015 Oct;11(10):670-4.

The TGFβ1 Promoter SNP C-509T and Food Sensitization Promote Esophageal Remodeling in Pediatric Eosinophilic Esophagitis. Rawson R, Anilkumar A, Newbury RO, Bafna V, Aquino M, Palmquist J, Hoffman HM, Mueller JL, Dohil R, Broide DH, Aceves SS. PLoS One. 2015 Dec 14;10(12):e0144651. doi: 10.1371/journal.pone.0144651. eCollection 2015.

Therapeutic strategies in eosinophilic esophagitis: Induction, maintenance and refractory disease. Sodikoff J, Hirano I. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):829-839. doi: 10.1016/j.bpg.2015.09.002. Epub 2015 Sep 11.

A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Srivastava S, Jo B, Zhang B, Frazier T, Gallagher AS, Peck F, Levin AR, Mondal S, Li Z, Filip-Dhima R, Geisel G, Dies KA, Diplock A, Eng C, Hanna R, Sahin M, Hardan A; Developmental Synaptopathies Consortium. Hum Mol Genet. 2022 Oct 10;31(20):3393-3404. doi: 10.1093/hmg/ddac111. PMID: 35594551.

PTEN hamartoma tumor syndrome (PHTS) is a complex neurodevelopmental disorder characterized by overactivity of the mechanistic target of rapamycin (mTOR) pathway, which serves as a major regulator of growth. Limited data suggest that mTOR inhibitors may be therapeutic for patients with PHTS. However, no placebo-controlled studies have explored the effects of mTOR inhibition on cognition and behavior in PHTS patients with or without autism. In this study, researchers conducted a phase II, placebo-controlled trial to examine the safety and efficacy of everolimus, an mTOR inhibitor, in patients with PHTS. The team measured cognitive and behavioral outcomes in addition to biomarkers of electroencephalography (measurement of electrical activity in different parts of the brain). Results show that everolimus was well tolerated in individuals with PHTS. Electroencephalography supported engagement of the drug target in the brain, and some of the secondary (but not primary) outcome measures moved in the direction of improvement. Although this trial provides early evidence that everolimus is safe for use in patients with PHTS, authors note that further study is needed.

Distinct metabolic profiles associated with autism spectrum disorder versus cancer in individuals with germline PTEN mutations. Yehia L, Ni Y, Sadler T, Frazier TW, Eng C.. NPJ Genom Med. 2022 Mar 3;7(1):16. doi: 10.1038/s41525-022-00289-x. PMID: 35241692; PMCID: PMC8894426.

Strong evidence for genotype-phenotype correlations in Phelan-McDermid syndrome: results from the developmental synaptopathies consortium. Levy T, Foss-Feig JH, Betancur C, Siper PM, Trelles-Thorne MDP, Halpern D, Frank Y, Lozano R, Layton C, Britvan B, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Srivastava S, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Hum Mol Genet. 2022 Feb 21;31(4):625-637. doi: 10.1093/hmg/ddab280. PMID: 34559195; PMCID: PMC8863417.

Visual Evoked Potential Abnormalities in Phelan-McDermid Syndrome. Siper PM, Rowe MA, Guillory SB, Rouhandeh AA, George-Jones JL, Tavassoli T, Lurie S, Zweifach J, Weissman J, Foss-Feig J, Halpern D, Trelles MP, Mulhern MS, Brittenham C, Gordon J, Zemon V, Buxbaum JD, Kolevzon A. J Am Acad Child Adolesc Psychiatry. 2022 Apr;61(4):565-574.e1. doi: 10.1016/j.jaac.2021.07.006. Epub 2021 Jul 22. PMID: 34303785; PMCID: PMC8782912.

A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations. Hardan AY, Jo B, Frazier TW, Klaas P, Busch RM, Dies KA, Filip-Dhima R, Snow AV, Eng C, Hanna R, Zhang B, Sahin M. Contemp Clin Trials Commun. 2021 Feb 6;21:100733. doi: 10.1016/j.conctc.2021.100733. eCollection 2021 Mar.

Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders. Anderson NC, Chen PF, Meganathan K, Afshar Saber W, Petersen AJ, Bhattacharyya A, Kroll KL, Sahin M; Cross-IDDRC Human Stem Cell Working Group. Stem Cell Reports. 2021 Jun 8;16(6):1446-1457. doi: 10.1016/j.stemcr.2021.03.025. Epub 2021 Apr 15. PMID: 33861989; PMCID: PMC8190574

Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations. Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. J Autism Dev Disord. 2021 Feb 17. doi: 10.1007/s10803-021-04881-5. Online ahead of print.

Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Frazier TW, Jaini R, Busch RM, Wolf M, Sadler T, Klaas P, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Mol Autism. 2021 Jan 28;12(1):5. doi: 10.1186/s13229-020-00406-6.

Although PTEN is a well-established risk gene for autism spectrum disorder (ASD), little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). In this study, researchers evaluated the influence of PTEN mutation and ASD diagnostic status on relevant pathway protein levels in peripheral blood. They also examined the associations between protein levels and neurobehavioral functions. They found that several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. These results show that protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. The team notes that future longitudinal analyses are needed to replicate these findings and evaluate relationships between protein and neurobehavioral measures.

Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex. Ihnen SKZ, Capal JK, Horn PS, Griffith M, Sahin M, Bebin EM, Wu JY, Northrup H, Krueger DA; TACERN study group. Pediatr Neurol. 2021 Oct;123:1-9. doi: 10.1016/j.pediatrneurol.2021.06.012. Epub 2021 Jul 6.

Tuberous sclerosis complex (TSC) is a multi-system genetic disease that causes benign tumors to grow in vital organs including the brain, kidneys, heart, eyes, lungs, and skin. Epilepsy in TSC typically presents with early onset, multiple seizure types, and intractability. However, this varies among individual patients. In this study, researchers aimed to define epilepsy profiles in the TSC population. The team prospectively collected detailed individual data on seizure characteristics in children aged zero to 36 months. Caregivers kept daily seizure diaries, including onset and daily counts, for each seizure type. Researchers then compared developmental outcomes at 36 months between subgroups. Epilepsy was seen in 79 percent of participants. Hierarchical clustering based on six metrics of seizure burden—age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches—revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Within each group, subpopulations showed clinically meaningful differences in seizure burden, and groups with higher burden had worse developmental outcomes at 36 months. These findings indicate that early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders-a Keystone Symposia report. Cable J, Purcell RH, Robinson E, Vorstman JAS, Chung WK, Constantino JN, Sanders SJ, Sahin M, Dolmetsch RE, Shah BM, Thurm A, Martin CL, Bearden CE, Mulle JG. Ann N Y Acad Sci. 2021 Dec;1506(1):5-17. doi: 10.1111/nyas.14658. Epub 2021 Aug 2. PMID: 34342000; PMCID: PMC8688183.

Neurodevelopmental neuropsychiatric disorders—such as autism spectrum disorder and schizophrenia—have strong genetic risk components, but researchers are still deciphering the underlying mechanisms. Rare variants could help us better understand the biological mechanisms for more common idiopathic diseases and reveal new therapeutic targets. This review summarizes insights from the 2021 Keystone eSymposium "Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants.” Experts describe progress in genomic discovery and human phenotyping, as well as raise consistent issues.

Interplay Between Class II HLA Genotypes and the Microbiome and Immune Phenotypes in Individuals With PTEN Hamartoma Tumor Syndrome. Jia M, Sangwan N, Tzeng A, Eng C.. JCO Precis Oncol. 2021 Feb 9;5:PO.20.00374. doi: 10.1200/PO.20.00374. PMID: 34250407; PMCID: PMC8232567.

Multivariate data analysis identifies natural clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND). de Vries PJ, Leclezio L, Gardner-Lubbe S, Krueger D, Sahin M, Sparagana S, De Waele L, Jansen A. Orphanet J Rare Dis. 2021 Oct 24;16(1):447. doi: 10.1186/s13023-021-02076-w. PMID: 34689816; PMCID: PMC8543869.

Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome. Srivastava S, Condy E, Carmody E, Filip-Dhima R, Kapur K, Bernstein JA, Berry-Kravis E, Powell CM, Soorya L, Thurm A, Buxbaum JD, Sahin M, Kolevzon AL; Developmental Synaptopathies Consortium. J Neurodev Disord. 2021 Nov 5;13(1):53. doi: 10.1186/s11689-021-09398-7. PMID: 34740315; PMCID: PMC8570010.

Repetitive behaviors are often seen in individuals with autism spectrum disorder as well as intellectual disability. Due to the association of these diagnoses with Phelan-McDermid syndrome (PMS), researchers characterized the severity and profile of repetitive behaviors in PMS relative to previously published scores in other neurodevelopmental disorders. The team used the Repetitive Behavior Scale-Revised (RBS-R) as a parent-report measure of what was collected as part of a natural history study of PMS through the Developmental Synaptopathies Consortium (DSC). Researchers demonstrated that individuals with PMS in this cohort had lower rates of repetitive behaviors compared to previous studies of individuals with autism spectrum disorder and Fragile X syndrome. They also showed that more severe motor repetitive behaviors (e.g., body rocking, finger movements) were associated with lower IQ scores in PMS, but this relationship was not present between IQ and other types of repetitive behaviors. These findings indicate that repetitive behaviors may be milder overall in PMS compared to previous studies characterizing autism spectrum disorder and other genetic conditions. Stereotyped motor behaviors may be related to level of cognitive functioning, and not an autism spectrum disorder diagnosis, in PMS. Authors note the need to better understand these findings by continuing to study repetitive behaviors in PMS using objective measures.

Profile of Autism Spectrum Disorder in Tuberous Sclerosis Complex: Results from a Longitudinal, Prospective, Multisite Study. Capal JK, Williams ME, Pearson DA, Kissinger R, Horn PS, Murray D, Currans K, Kent B, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA; TACERN Study Group. Ann Neurol. 2021 Dec;90(6):874-886. doi: 10.1002/ana.26249. Epub 2021 Oct 29. PMID: 34668231; PMCID: PMC8639652.

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that causes noncancerous tumors to develop in many parts of the body. It is highly associated with autism spectrum disorder (ASD). Researchers seeking to characterize autistic features in young children with TSC evaluated 138 children from ages 3 to 36 months. They used both development and autism-specific assessments. One in four children in the study had been diagnosed with ASD by 36 months. Many individuals with TSC without an autism diagnosis also exhibited a range of autistic behaviors that were below the diagnostic threshold. Study authors report a broader autism phenotype (set of characteristics) that can be identified in young children with TSC, offering an opportunity for early, targeted treatments.

Psychiatric Characteristics Across Individuals With PTEN Mutations. Steele M, Uljarević M, Rached G, Frazier TW, Phillips JM, Libove RA, Busch RM, Klaas P, Martinez-Agosto JA, Srivastava S, Eng C, Sahin M, Hardan AY. Front Psychiatry. 2021 Aug 17;12:672070. doi: 10.3389/fpsyt.2021.672070. eCollection 2021.

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome. Mariscal MG, Berry-Kravis E, Buxbaum JD, Ethridge LE, Filip-Dhima R, Foss-Feig JH, Kolevzon A, Modi ME, Mosconi MW, Nelson CA, Powell CM, Siper PM, Soorya L, Thaliath A, Thurm A, Zhang B, Sahin M, Levin AR; Developmental Synaptopathies Consortium. Mol Autism. 2021 Apr 28;12(1):29. doi: 10.1186/s13229-020-00411-9.

Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study. Guillory SB, Baskett VZ, Grosman HE, McLaughlin CS, Isenstein EL, Wilkinson E, Weissman J, Britvan B, Trelles MP, Halpern DB, Buxbaum JD, Siper PM, Wang AT, Kolevzon A, Foss-Feig JH. J Neurodev Disord. 2021 Dec 4;13(1):58. doi: 10.1186/s11689-021-09400-2. PMID: 34863106.

Phelan-McDermid Syndrome (PMS) is a rare genetic disorder characterized by intellectual disability and motor delays. It is also one of the most common genetic causes of autism spectrum disorder (ASD). Social deficits are a core feature of ASD. In order to characterize social attention and recognition memory, researchers tested a group of patients with PMS and another group of patients with idiopathic (no cause identified) ASD on a visual paired-comparison task. They analyzed the behavior of test subjects looking at a novel image versus a previously viewed, familiar image. Researchers found differences in attention and memory for social stimuli in the PMS group v. the idiopathic ASD group. Study authors say that these unique patterns could both clarify underlying mechanistic alterations and inform treatment targets for PMS. They could also help stratify individuals with idiopathic ASD and potentially apply knowledge gained in PMS to those individuals.

Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous PTEN mutations. Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. Am J Med Genet A. 2021 Aug 23. doi: 10.1002/ajmg.a.62458. Online ahead of print.

Mutations in the PTEN gene are an important genetic risk factor for autism spectrum disorder (ASD). PTEN mutations are identified in 2% of all ASD cases and 17-20% of cases with both ASD and macrocephaly (larger than typical head size). Restricted and repetitive behaviors (RRB) are a core diagnostic symptom of ASD and one of the earlier predictors of a subsequent ASD diagnosis. RRBs include repetitive motor behaviors (RMB), insistence on sameness (IS), and circumscribed interests (CI). Researchers believe these symptom domains, which have a significant negative impact on affected individuals and their families, likely have distinct mechanisms and might therefore require different treatments. Seeking to develop a more nuanced understanding of RRB in individuals with PTEN mutations, researchers compared RMB, IS, and CI symptoms captured by two different measures across three groups: 38 individuals with PTEN mutations with ASD, 23 with PTEN mutations without ASD, and 25 with ASD and macrocephaly but without PTEN mutations. After adjusting for age and full-scale intelligence quotient (FSIQ) scores, the researchers found that differences between the three study groups were not statistically significant. However, all three symptom domains showed distinct association patterns with sex, age, and FSIQ. Study authors conclude that their findings highlight the importance of comprehensively assessing RRB in people with PTEN mutations. Their findings further support the hypothesis that RMB, IS, and CI are indeed distinct RRB domains that might, therefore, require different treatment approaches in this population. They recommend that future studies are needed to further understand mechanisms behind specific RRB subdomains and inform most optimal strategies for individuation of treatment options. This research offers the largest, most comprehensive comparison of distinct RRB domains in individuals with PTEN mutations to date.

Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network. Cohen AL, Mulder BPF, Prohl AK, Soussand L, Davis P, Kroeck MR, McManus P, Gholipour A, Scherrer B, Bebin EM, Wu JY, Northrup H, Krueger DA, Sahin M, Warfield SK, Fox MD, Peters JM; Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group. Ann Neurol. 2021 Apr;89(4):726-739. doi: 10.1002/ana.26015. Epub 2021 Jan 21.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

Copy Number Variation and Clinical Outcomes in Patients With Germline PTEN Mutations. Yehia L, Seyfi M, Niestroj LM, Padmanabhan R, Ni Y, Frazier TW, Lal D, Eng C. JAMA Netw Open. 2020 Jan 3;3(1):e1920415. doi: 10.1001/jamanetworkopen.2019.20415.

Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome. Bassell J, Srivastava S, Prohl AK, Scherrer B, Kapur K, Filip-Dhima R, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Buxbaum JD, Kolevzon A, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Pediatr Neurol. 2020 May;106:24-31. doi: 10.1016/j.pediatrneurol.2020.01.006. Epub 2020 Jan 31.

Editorial: Biomarkers to Enable Therapeutics Development in Neurodevelopmental Disorders. Sahin M, Sweeney JA, Jones SR. Front Integr Neurosci. 2020 Nov 12;14:616641. doi: 10.3389/fnint.2020.616641. PMID: 33262695; PMCID: PMC7686575.

Epilepsy Risk Prediction Model for Patients With Tuberous Sclerosis Complex. Farach LS, Richard MA, Lupo PJ, Sahin M, Krueger DA, Wu JY, Bebin EM, Au KS, Northrup H; TACERN Study Group. Pediatr Neurol. 2020 Dec;113:46-50. doi: 10.1016/j.pediatrneurol.2020.07.015. Epub 2020 Jul 29.

LEARNING TO DETECT BRAIN LESIONS FROM NOISY ANNOTATIONS. Karimi D, Peters JM, Ouaalam A, Prabhu SP, Sahin M, Krueger DA, Kolevzon A, Eng C, Warfield SK, Gholipour A. Proc IEEE Int Symp Biomed Imaging. 2020 Apr;2020:1910-1914. doi: 10.1109/isbi45749.2020.9098599. Epub 2020 May 22.

Language predictors of autism spectrum disorder in young children with tuberous sclerosis complex. Schoenberger A, Capal JK, Ondracek A, Horn PS, Murray D, Byars AW, Pearson DA, Williams ME, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA. Epilepsy Behav. 2020 Feb;103(Pt A):106844. doi: 10.1016/j.yebeh.2019.106844. Epub 2019 Dec 18.

Lesion-Constrained Electrical Source Imaging: A Novel Approach in Epilepsy Surgery for Tuberous Sclerosis Complex. Peters JM, Hyde DE, Chu CJ, Boom M, Scherrer B, Madsen JR, Stone SS, Ouaalam H, Prabhu SP, Sahin M, Warfield SK. J Clin Neurophysiol. 2020 Jan;37(1):79-86. doi: 10.1097/WNP.0000000000000615.

PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation?. Yehia L, Eng C. Hum Mol Genet. 2020 Oct 20;29(R2):R150-R157. doi: 10.1093/hmg/ddaa127.

More than 400 hereditary cancer syndromes have been described to date and account for 5-10% of all cancers. PTEN hamartoma tumour syndrome (PHTS) is an umbrella term for subsets of four syndromes associated with germline (inherited) PTEN mutations. However, many patients with phenotypes similar to those in PHTS do not carry germline PTEN mutations. This paper reviews gene discovery efforts over the last decade to identify alterations in cancer-predisposing genes in order to facilitate gene-informed molecular diagnosis, cancer risk assessment, and gene-specific clinical management. Authors conclude that validating these discoveries is critical to bringing these patients specific gene-informed risk assessment and subsequent management.

Polymicrogyria is Associated With Pathogenic Variants in PTEN. Shao DD, Achkar CM, Lai A, Srivastava S, Doan RN, Rodan LH, Chen AY; Brain Development Study Group, Poduri A, Yang E, Walsh CA. Ann Neurol. 2020 Dec;88(6):1153-1164. doi: 10.1002/ana.25904. Epub 2020 Oct 8.

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome. Kohlenberg TM, Trelles MP, McLarney B, Betancur C, Thurm A, Kolevzon A. J Neurodev Disord. 2020 Feb 12;12(1):7. doi: 10.1186/s11689-020-9309-6.

Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome. Gergoudis K, Weinberg A, Templin J, Farmer C, Durkin A, Weissman J, Siper P, Foss-Feig J, Del Pilar Trelles M, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Autism Res. 2020 Aug;13(8):1383-1396. doi: 10.1002/aur.2299. Epub 2020 May 14.

Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms. Nariai H, Hussain SA, Bernardo D, Motoi H, Sonoda M, Kuroda N, Asano E, Nguyen JC, Elashoff D, Sankar R, Bragin A, Staba RJ, Wu JY. Clin Neurophysiol. 2020 Nov;131(11):2527-2536. doi: 10.1016/j.clinph.2020.08.013. Epub 2020 Sep 3.

The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex. Scherrer B, Prohl AK, Taquet M, Kapur K, Peters JM, Tomas-Fernandez X, Davis PE, M Bebin E, Krueger DA, Northrup H, Y Wu J, Sahin M, Warfield SK. Cereb Cortex. 2020 Apr 14;30(4):2199-2214. doi: 10.1093/cercor/bhz233.

A unified circuit for social behavior. Modi ME, Sahin M. Neurobiol Learn Mem. 2019 Nov;165:106920. doi: 10.1016/j.nlm.2018.08.010. Epub 2018 Aug 24.

Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer. Smith IN, Thacker S, Seyfi M, Cheng F, Eng C. Am J Hum Genet. 2019 May 2;104(5):861-878. doi: 10.1016/j.ajhg.2019.03.009. Epub 2019 Apr 18.

Distinct Alterations in Tricarboxylic Acid Cycle Metabolites Associate with Cancer and Autism Phenotypes in Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome. Yehia L, Ni Y, Feng F, Seyfi M, Sadler T, Frazier TW, Eng C. Am J Hum Genet. 2019 Oct 3;105(4):813-821. doi: 10.1016/j.ajhg.2019.09.004. Epub 2019 Sep 26.

Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes. Smith IN, Thacker S, Jaini R, Eng C. J Biomol Struct Dyn. 2019 Apr;37(7):1766-1782. doi: 10.1080/07391102.2018.1465854. Epub 2018 May 14.

Incontinence in Phelan-McDermid Syndrome. Witmer C, Mattingly A, DʼSouza P, Thurm A, Hadigan C. J Pediatr Gastroenterol Nutr. 2019 Aug;69(2):e39-e42. doi: 10.1097/MPG.0000000000002342.

Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex. Davis PE, Kapur K, Filip-Dhima R, Trowbridge SK, Little E, Wilson A, Leuchter A, Bebin EM, Krueger D, Northrup H, Wu JY, Sahin M, Peters JM; Tuberous Sclerosis Autism Centers of Excellence Research Network. Epilepsia. 2019 Aug;60(8):1721-1732. doi: 10.1111/epi.16284. Epub 2019 Jul 12.

Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex. Peters JM, Prohl A, Kapur K, Nath A, Scherrer B, Clancy S, Prabhu SP, Sahin M, Franz DN, Warfield SK, Krueger DA. Pediatr Neurol. 2019 Jan;90:24-30. doi: 10.1016/j.pediatrneurol.2018.10.005. Epub 2018 Oct 18.

Motion-robust diffusion compartment imaging using simultaneous multi-slice acquisition. Marami B, Scherrer B, Khan S, Afacan O, Prabhu SP, Sahin M, Warfield SK, Gholipour A. Magn Reson Med. 2019 May;81(5):3314-3329. doi: 10.1002/mrm.27613. Epub 2018 Nov 16.

Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN. Busch RM, Srivastava S, Hogue O, Frazier TW, Klaas P, Hardan A, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Transl Psychiatry. 2019 Oct 8;9(1):253. doi: 10.1038/s41398-019-0588-1.

Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature. Kolevzon A, Delaby E, Berry-Kravis E, Buxbaum JD, Betancur C. Mol Autism. 2019 Dec 24;10:50. doi: 10.1186/s13229-019-0291-3. eCollection 2019.

PTEN-opathies: from biological insights to evidence-based precision medicine. Yehia L, Ngeow J, Eng C. J Clin Invest. 2019 Feb 1;129(2):452-464. doi: 10.1172/JCI121277. Epub 2019 Jan 7.

The tumor suppressor phosphatase and tensin homolog (PTEN) classically counteracts the PI3K/AKT/mTOR signaling cascade. Germline pathogenic PTEN mutations cause PTEN hamartoma tumor syndrome (PHTS), featuring various benign and malignant tumors, as well as neurodevelopmental disorders such as autism spectrum disorder. Germline and somatic mosaic mutations in genes encoding components of the PI3K/AKT/mTOR pathway downstream of PTEN predispose to syndromes with partially overlapping clinical features, termed the "PTEN-opathies." Experimental models of PTEN pathway disruption uncover the molecular and cellular processes influencing clinical phenotypic manifestations. Such insights not only teach us about biological mechanisms in states of health and disease, but also enable more accurate gene-informed cancer risk assessment, medical management, and targeted therapeutics. Hence, the PTEN-opathies serve as a prototype for bedside to bench, and back to the bedside, practice of evidence-based precision medicine.

Prospective observational study: Fast ripple localization delineates the epileptogenic zone. Nariai H, Hussain SA, Bernardo D, Fallah A, Murata KK, Nguyen JC, Rajaraman RR, Rao LM, Matsumoto JH, Lerner JT, Salamon N, Elashoff D, Sankar R, Wu JY. Clin Neurophysiol. 2019 Nov;130(11):2144-2152. doi: 10.1016/j.clinph.2019.08.026. Epub 2019 Sep 17.

Resting-State fMRI Networks in Children with Tuberous Sclerosis Complex. Ahtam B, Dehaes M, Sliva DD, Peters JM, Krueger DA, Bebin EM, Northrup H, Wu JY, Warfield SK, Sahin M, Grant PE; TACERN Study Group. J Neuroimaging. 2019 Nov;29(6):750-759. doi: 10.1111/jon.12653. Epub 2019 Jul 14.

Tuberous Sclerosis Complex Genotypes and Developmental Phenotype. Farach LS, Pearson DA, Woodhouse JP, Schraw JM, Sahin M, Krueger DA, Wu JY, Bebin EM, Lupo PJ, Au KS, Northrup H; TACERN Study Group. Pediatr Neurol. 2019 Jul;96:58-63. doi: 10.1016/j.pediatrneurol.2019.03.003. Epub 2019 Mar 13.

Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome. Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Pediatr Neurol. 2019 Jan;90:37-43. doi: 10.1016/j.pediatrneurol.2018.09.008. Epub 2018 Sep 21.

White matter mean diffusivity correlates with myelination in tuberous sclerosis complex. Peters JM, Struyven RR, Prohl AK, Vasung L, Stajduhar A, Taquet M, Bushman JJ, Lidov H, Singh JM, Scherrer B, Madsen JR, Prabhu SP, Sahin M, Afacan O, Warfield SK. Ann Clin Transl Neurol. 2019 Jul;6(7):1178-1190. doi: 10.1002/acn3.793. Epub 2019 Jun 23.

A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). de Vries PJ, Wilde L, de Vries MC, Moavero R, Pearson DA, Curatolo P. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):309-320. doi: 10.1002/ajmg.c.31637. Epub 2018 Aug 16.

Assessing the validity of the approximation of diffusion-weighted-MRI signals from crossing fascicles by sums of signals from single fascicles. Rensonnet G, Scherrer B, Warfield SK, Macq B, Taquet M. Magn Reson Med. 2018 Apr;79(4):2332-2345. doi: 10.1002/mrm.26832. Epub 2017 Jul 16.

Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex. Baumer FM, Peters JM, Clancy S, Prohl AK, Prabhu SP, Scherrer B, Jansen FE, Braun KPJ, Sahin M, Stamm A, Warfield SK. Cereb Cortex. 2018 Oct 1;28(10):3665-3672. doi: 10.1093/cercor/bhx247.

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Mol Autism. 2018 Apr 27;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018.

Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels. Frazier TW, Klingemier EW, Parikh S, Speer L, Strauss MS, Eng C, Hardan AY, Youngstrom EA. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):858-866. doi: 10.1016/j.jaac.2018.06.023. Epub 2018 Sep 13.

Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder. Curtin P, Austin C, Curtin A, Gennings C, Arora M; (for the Emergent Dynamical Systems Group), Tammimies K, Willfors C, Berggren S, Siper P, Rai D, Meyering K, Kolevzon A, Mollon J, David AS, Lewis G, Zammit S, Heilbrun L, Palmer RF, Wright RO, Bölte S, Reichenberg A. Sci Adv. 2018 May 30;4(5):eaat1293. doi: 10.1126/sciadv.aat1293. eCollection 2018 May.

Framework for assessing individuals with rare genetic disorders associated with profound intellectual and multiple disabilities (PIMD): the example of Phelan McDermid Syndrome. Soorya L, Leon J, Trelles MP, Thurm A. Clin Neuropsychol. 2018 Aug-Oct;32(7):1226-1255. doi: 10.1080/13854046.2017.1413211. Epub 2017 Dec 21.

Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Peron A, Au KS, Northrup H. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):281-290. doi: 10.1002/ajmg.c.31651. Epub 2018 Sep 26.

High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex. Hussain SA, Schmid E, Peters JM, Goyal M, Bebin EM, Northrup H, Sahin M, Krueger DA, Wu JY; Tuberous Sclerosis Complex Autism Center of Excellence Network. Epilepsy Res. 2018 Dec;148:1-7. doi: 10.1016/j.eplepsyres.2018.09.016. Epub 2018 Oct 2.

Interrater reliability in visual identification of interictal high-frequency oscillations on electrocorticography and scalp EEG. Nariai H, Wu JY, Bernardo D, Fallah A, Sankar R, Hussain SA. Epilepsia Open. 2018 Nov 2;3(Suppl Suppl 2):127-132. doi: 10.1002/epi4.12266. eCollection 2018 Dec.

Prospective longitudinal overnight video-EEG evaluation in Phelan-McDermid Syndrome. Khan OI, Zhou X, Leon J, Kessler R, Gaughan T, D'Souza P, Gropman A, Cohen N, Rennert O, Buckley A, Inati S, Thurm A. Epilepsy Behav. 2018 Mar;80:312-320. doi: 10.1016/j.yebeh.2017.11.034. Epub 2018 Feb 3.

Removing high-frequency oscillations: A prospective multicenter study on seizure outcome.. Jacobs J, Wu JY, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, Gotman J. Neurology. 2018 Sep 11;91(11):e1040-e1052. doi: 10.1212/WNL.0000000000006158. Epub 2018 Aug 17. PMID: 30120133; PMCID:PMC6140372

The Way Forward for Mechanism-Based Therapeutics in Genetically Defined Neurodevelopmental Disorders. Modi ME, Sahin M. Clin Pharmacol Ther. 2018 Oct;104(4):603-606. doi: 10.1002/cpt.1181. Epub 2018 Aug 12.

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome. Farach LS, Little ME, Duker AL, Logan CV, Jackson A, Hecht JT, Bober M. Am J Med Genet A. 2018 Feb;176(2):465-469. doi: 10.1002/ajmg.a.38581. Epub 2017 Dec 19.

The microbiome in PTEN hamartoma tumor syndrome. Byrd V, Getz T, Padmanabhan R, Arora H, Eng C. Endocr Relat Cancer. 2017. PMID: 29233840

Tuberous sclerosis complex. Peron A, Northrup H. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):274-277. doi: 10.1002/ajmg.c.31657. Epub 2018 Oct 16.

Vigabatrin for Epileptic Spasms and Tonic Seizures in Tuberous Sclerosis Complex. van der Poest Clement EA, Sahin M, Peters JM. J Child Neurol. 2018 Jul;33(8):519-524. doi: 10.1177/0883073818768309. Epub 2018 Apr 24.

Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex. Bernardo D, Nariai H, Hussain SA, Sankar R, Salamon N, Krueger DA, Sahin M, Northrup H, Bebin EM, Wu JY; UCLA Pediatric Epilepsy Group; TACERN Study Group. Clin Neurophysiol. 2018 Jul;129(7):1458-1466. doi: 10.1016/j.clinph.2018.03.010. Epub 2018 Apr 3.

A Meta-Analysis of Gaze Differences to Social and Nonsocial Information Between Individuals With and Without Autism. Frazier TW, Strauss M, Klingemier EW, Zetzer EE, Hardan AY, Eng C, Youngstrom EA. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):546-555. doi: 10.1016/j.jaac.2017.05.005. Epub 2017 May 11.

A clinician-administered observation and corresponding caregiver interview capturing DSM-5 sensory reactivity symptoms in children with ASD. Siper PM, Kolevzon A, Wang AT, Buxbaum JD, Tavassoli T. Autism Res. 2017 Jun;10(6):1133-1140. doi: 10.1002/aur.1750. Epub 2017 Mar 11.

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. Srivastava S, Sahin M. Srivastava S, Sahin M. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord. 2017;9:23. PMID: 28649286, PMCID: PMC5481888

Influence of seizures on early development in tuberous sclerosis complex. Capal JK, Bernardino-Cuesta B, Horn PS, et al. Epilepsy Behav. 2017;70(Pt A):245-252. PMID: 28457992, PMCID: PMC5497719

Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena. Hussain SA, Mathern GW, Hung P, Weng J, Sankar R, Wu JY. Epilepsy Res. 2017;135:79-86. PMID: 28644979, PMCID: PMC5568451

Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder. Rankine J, Li E, Lurie S, Rieger H, Fourie E, Siper PM, Wang AT, Buxbaum JD, Kolevzon A. J Autism Dev Disord. 2017 Jun;47(6):1605-1617. doi: 10.1007/s10803-017-3082-8.

Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants. Davis PE, Filip-Dhima R, Sideridis G, Peters JM, Au KS, Northrup H, Bebin EM, Wu JY, Krueger D, Sahin M; Tuberous Sclerosis Complex Autism Center of Excellence Research Network. Pediatrics. 2017;140(6). PMID: 29101226, PMCID: PMC5703775

The genomic landscape of tuberous sclerosis complex. Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE, Sisson KA, Koeman J, Weisenberger DJ, Cottingham SL, DeRoos ST, Devinsky O, Winn ME, Cherniack AD, Shen H, Northrup H, Krueger DA, MacKeigan JP. Nat Commun. 2017 Jun 15;8:15816. doi: 10.1038/ncomms15816.

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex. Capal JK, Horn PS, Murray DS, Byars AW, Bing NM, Kent B, Bucher LA, Williams ME, O'Kelley S, Pearson DA, Sahin M, Krueger DA; TACERN Study Group. Pediatr Neurol. 2017;75:80-86. PMID: 28844798, PMCID: PMC5610103

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference. Sahin M, Henske EP, Manning BD, Ess KC, Bissler JJ, Klann E, Kwiatkowski DJ, Roberds SL, Silva AJ, Hillaire-Clarke CS, Young LR, Zervas M, Mamounas LA; Tuberous Sclerosis Complex Working Group to Update the Research Plan. Pediatr Neurol. 2016;60:1-12. PMID: 27267556, PMCID: PMC4921275

Altered Structural Brain Networks in Tuberous Sclerosis Complex. Im K, Ahtam B, Haehn D, Peters JM, Warfield SK, Sahin M, Ellen Grant P. Cereb Cortex. 2016;26(5):2046-2058. PMID: 25750257, PMCID: PMC4830286

Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND). Scherrer B, Schwartzman A, Taquet M, Sahin M, Prabhu SP, Warfield SK. Magn Reson Med. Sep 12 2015. PMID: 26362832

Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism. Ebrahimi-Fakhari D, Saffari A, Wahlster L, Lu J, Byrne S, Hoffmann GF, Jungbluth H, Sahin M. Brain. 2016;139(Pt 2):317-337. PMID: 26715604

Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders. Markowitz LA, Reyes C, Embacher RA, Speer LL, Roizen N, Frazier TW. Autism. 2016 Oct;20(7):832-44. doi: 10.1177/1362361315611382. Epub 2015 Dec 10.

Development of an Objective Autism Risk Index Using Remote Eye Tracking. Frazier TW, Klingemier EW, Beukemann M, Speer L, Markowitz L, Parikh S, Wexberg S, Giuliano K, Schulte E, Delahunty C, Ahuja V, Eng C, Manos MJ, Hardan AY, Youngstrom EA, Strauss MS. J Am Acad Child Adolesc Psychiatry. Apr 2016;55(4):301-309. PMID: 27015721, PMCID: PMC4808563

Editorial: Essential Pathways and Circuits of Autism Pathogenesis. Dölen G, Sahin M. Front Neurosci. 2016 Apr 26;10:182. doi: 10.3389/fnins.2016.00182. eCollection 2016.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis. Krueger DA, Wilfong AA, Mays M, Talley CM, Agricola K, Tudor C, Capal J, Holland-Bouley K, Franz DN. Neurology. 2016 Dec 6;87(23):2408-2415. doi: 10.1212/WNL.0000000000003400. Epub 2016 Nov 4. PMID: 27815402; PMCID: PMC5177677

Motion-Robust Diffusion-Weighted Brain MRI Reconstruction Through Slice-Level Registration-Based Motion Tracking. Marami B, Scherrer B, Afacan O, Erem B, Warfield SK, Gholipour A. IEEE Trans Med Imaging. 2016;35(10):2258-2269. PMID: 27834639, PMCID: PMC5108524

Siper PM. Siper PM, Zemon V, Gordon J, et al. PLoS ONE. 2016;11(10):e0164422. PMID: 27716799, PMCID: PMC5055293

Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Keppler-Noreuil KM, Parker VE, Darling TN, Martinez-Agosto JA. Am J Med Genet C Semin Med Genet. 2016;172(4):402-421. PMID: 27860216, PMCID: PMC5592089

The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis. Key negative regulators of the PI3K-AKT signaling pathway include PTEN and TSC1/TSC2 and germline loss-of function mutations of these genes are established to cause PTEN Hamartoma Tumor Syndrome and Tuberous Sclerosis Complex. Mosaic forms of these conditions lead to increased activation of PI3K and mTOR at affected sites and there is phenotypic overlap between these conditions. All are associated with significant morbidity with limited options for treatment other than symptomatic therapies and surgeries. As dysregulation of the PI3K/AKT/mTOR pathway has been implicated in cancer, several small molecule inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are under clinical investigation. The development of these therapies brings closer the prospect of targeting treatment for somatic PI3K/AKT/mTOR-related overgrowth syndromes. This review describes the clinical findings, gene function and pathogenesis of these mosaic overgrowth syndromes, and presents existing and future treatment strategies to reduce or prevent associated complications of these disorders. © 2016 Wiley Periodicals, Inc.

The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Costales J, Kolevzon A. Neurosci Biobehav Rev. 2016;63:207-222. PMID: 26780584, PMCID: PMC4790729

Autism and the synapse: emerging mechanisms and mechanism-based therapies. Ebrahimi-Fakhari D, Sahin M. Curr Opin Neurol. Apr 2015;28(2):91-102. PMID: 25695134

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder. Tilot AK, Frazier TW 2nd, Eng C. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):609-619. PMID: 25916396, PMCID: PMC4489960

Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex. Sundberg M, Sahin M. J Child Neurol. Aug 24 2015. PMID: 26303409, PMCID: PMC4644486

Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits. He X, Thacker S, Romigh T, Yu Q, Frazier TW Jr, Eng C. Mol Autism. 2015 Nov 17;6:63. doi: 10.1186/s13229-015-0056-6. eCollection 2015.

Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Sahin M, Sur M. Science. Nov 20 2015;350(6263). PMID: 26472761, PMCID: PMC4739545

Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity. Hussain SA, Kwong G, Millichap JJ, Mytinger JR, Ryan N, Matsumoto JH, Wu JY, Lerner JT, Sankar R. Epilepsia. 2015 Jan;56(1):77-81. doi: 10.1111/epi.12861. Epub 2014 Nov 10.

Improved fidelity of brain microstructure mapping from single-shell diffusion MRI. Taquet M, Scherrer B, Boumal N, Peters JM, Macq B, Warfield SK. Med Image Anal. Dec 2015;26(1):268- 286. PMID: 26529580, PMCID: PMC4679640

Longitudinal changes in diffusion properties in white matter pathways of children with tuberous sclerosis complex. Baumer FM, Song JW, Mitchell PD, Pienaar R, Sahin M, Grant PE, Takahashi E. Pediatr Neurol. Jun 2015;52(6):615-623. PMID: 25817702, PMCID: PMC4442035

Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. Tyburczy ME, Dies KA, Glass J, Camposano S, Chekaluk Y, Thorner AR, Lin L, Krueger D, Franz DN, Thiele EA, Sahin M, Kwiatkowski DJ. PLoS Genet. 2015 Nov 5;11(11):e1005637. doi: 10.1371/journal.pgen.1005637. eCollection 2015 Nov.

Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families. Frazier TW, Youngstrom EA, Hardan AY, Georgiades S, Constantino JN, Eng C. Mol Autism. 2015 Oct 27;6:58. doi: 10.1186/s13229-015-0050-z. eCollection 2015.

Therapeutic Advances in Autism and Other Neurodevelopmental Disorders. Neul JL, Sahin M. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):519-520. PMID: 26076992, PMCID: PMC4489958

Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism. Davis PE, Peters JM, Krueger DA, Sahin M. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):572-583. PMID: 25986747, PMCID: PMC4489948

The neurology of mTOR. Lipton JO, Sahin M. Neuron. Oct 22 2014;84(2):275-291. PMID: 25374355, PMCID: PMC4223653

The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.

Clinical features, pathophysiology, treatment, and controversies of tremor in dystonia. Panyakaew P, Jinnah HA, Shaikh AG. J Neurol Sci. 2022 Apr 15;435:120199. doi: 10.1016/j.jns.2022.120199. Epub 2022 Feb 22. PMID: 35259651.

Dystonia is a general term for a group of movement disorders characterized by uncontrollable, sometimes painful, involuntary muscle contractions, resulting in repetitive shaking, turning, and twisting of affected body parts. Dystonia is a rare disorder, but it often coexists with a more common disorder, tremor. The reasons for the frequent co-occurrence of dystonia and tremor are not clear. In this review article, researchers outline the differences in definitions, subtypes, and pathophysiology of dystonia and tremor. They outline some controversial topics, such as whether these two problems share a similar pathophysiology.

Diagnosis and classification of blepharospasm: Recommendations based on empirical evidence. Defazio G, Hallett M, Berardelli A, Ferrazzano G, Belvisi D, Klein C, Bäumer T, Weissbach A, Perlmutter JS, Feuerstein J, Jinnah HA; Dystonia Coalition Investigators. J Neurol Sci. 2022 Aug 15;439:120319. doi: 10.1016/j.jns.2022.120319. Epub 2022 Jun 10. PMID: 35716653; PMCID: PMC9357089

Blepharospasm is a rare disorder characterized by spasms of muscles surrounding both eyes with excessive blinking and squinting. It is the second most common form of dystonia (involuntary muscle twitching) and often spreads to other regions of the body. Currently, guidelines for diagnosis and classification are ambiguous. In this study, researchers aimed to provide more specific recommendations for diagnosis and classification of blepharospasm. Data were obtained from the Dystonia Coalition for patients diagnosed with all types of isolated dystonia. The team evaluated these data to determine how examinations recorded by movement disorder specialists were used to classify blepharospasm as focal, segmental, or multifocal. Results showed much variability in expert opinion regarding the diagnosis of blepharospasm, which was often inconsistent with existing guidelines for the diagnosis and classification of focal blepharospasm. This study highlights the need for more specific guidelines, which are provided in the publication.

Hold that pose: capturing cervical dystonia's head deviation severity from video. Zhang Z, Cisneros E, Lee HY, Vu JP, Chen Q, Benadof CN, Whitehill J, Rouzbehani R, Sy DT, Huang JS, Sejnowski TJ, Jankovic J, Factor S, Goetz CG, Barbano RL, Perlmutter JS, Jinnah HA, Berman BD, Richardson SP, Stebbins GT, Comella CL, Peterson DA. Ann Clin Transl Neurol. 2022 Mar 25. doi: 10.1002/acn3.51549. Epub ahead of print. PMID: 35333449.

Cervical dystonia (CD) is a movement disorder resulting in characteristic, sustained, or tremor-like involuntary muscle contractions of the neck. It is characterized by excessive pulling of the muscles of the neck and shoulder, which causes the head to turn or tilt involuntarily. Typically, head posture severity is quantified with clinical rating scales that are susceptible to variability, reducing their sensitivity as outcome measures. Previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. In this study, researchers evaluated a novel software system—the Computational Motor Objective Rater (CMOR)—to quantify multi-axis directionality and severity of head posture in CD using only conventional video camera recordings. They found that CMOR’s metrics for head posture severity correlated with clinical rating scales. Authors note that CMOR’s reliance upon only conventional video recordings supports its future potential for large-scale multisite clinical trials.

Microstructural white matter abnormalities in Lesch-Nyhan disease. Del Bene VA, Crawford JL, Gómez-Gastiasoro A, Vannorsdall TD, Buchholz A, Ojeda N, Harris JC, Jinnah HA, Schretlen DJ. Eur J Neurosci. 2022 Jan;55(1):264-276. doi: 10.1111/ejn.15512. Epub 2021 Dec 6.

The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes. Albanese A, Jinnah HA. Curr Opin Neurol. 2022 Aug 1;35(4):502-509. doi: 10.1097/WCO.0000000000001076. Epub 2022 Jul 5. PMID: 35856917; PMCID: PMC9309988.

The dystonias are a group of movement disorders characterized by uncontrollable, sometimes painful, involuntary muscle contractions, resulting in repetitive shaking, turning, and twisting of affected body parts. As new genetic causes continue to be discovered, researchers have found that these different genetic forms share unexpectedly common underlying mechanisms. In this review article, authors explore the phenotypic diversity and shared mechanisms across dystonia syndromes. They also describe how these mechanisms can give rise to motor performance dysfunctions with a clinical aspect of dystonia. Authors state that this relationship between dystonia genes could revolutionize current dystonia classification systems. In the future, these advances could have promising effects on mechanism-based therapeutic approaches.

A Multi-center Genome-wide Association Study of Cervical Dystonia. Sun YV, Li C, Hui Q, Huang Y, Barbano R, Rodriguez R, Malaty IA, Reich S, Bambarger K, Holmes K, Jankovic J, Patel NJ, Roze E, Vidailhet M, Berman BD, LeDoux MS, Espay AJ, Agarwal P, Pirio-Richardson S, Frank SA, Ondo WG, Saunders-Pullman R, Chouinard S, Natividad S, Berardelli A, Pantelyat AY, Brashear A, Fox SH, Kasten M, Krämer UM, Neis M, Bäumer T, Loens S, Borsche M, Zittel S, Maurer A, Gelderblom M, Volkmann J, Odorfer T, Kühn AA, Borngräber F, König IR, Cruchaga C, Cotton AC, Kilic-Berkmen G, Freeman A, Factor SA, Scorr L, Bremner JD, Vaccarino V, Quyyumi AA, Klein C, Perlmutter JS, Lohmann K, Jinnah HA. Mov Disord. 2021 Jul 28. doi: 10.1002/mds.28732. Online ahead of print.

Cervical dystonia is a painful condition in which a patient’s neck muscles contract involuntarily, causing the head to twist or turn to one side. In this multi-center international study, researchers conducted a Genome-Wide Association Study (GWAS) using samples from the Dystonia Coalition Biorepository. They compared 919 cervical dystonia patients with 1491 controls, seeking to identify genetic loci—fixed positions on a chromosome where a particular gene or genetic marker is located—related to the disorder. They identified one genome-wide significant variant that was however not replicated in an independent sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia. One low-frequency variant located within the GABBR2 gene on chromosome 9 was associated with lower age-at-onset. Authors concluded that the genetic underpinnings of cervical dystonia are heterogeneous and likely consist of multiple distinct variants of small effect sizes, rather than one gene that is responsible for many cases. Larger GWAS sample sizes may be needed to understand the genetic causes of cervical dystonia.

Cervical Dystonia Is Associated with Aberrant Inhibitory Signaling Within the Thalamus. Groth CL, Brown M, Honce JM et al. Front Neurol. 2021; 11: 575879. PMCID: PMC7900407

Current Guidelines for Classifying and Diagnosing Cervical Dystonia: Empirical Evidence and Recommendations. Kilic-Berkmen G, Pirio Richardson S, Perlmutter JS et al. MDCP, Nov 2021. https://doi.org/10.1002/mdc3.13376. PMCID: in progress

Deep brain stimulation in Lesch-Nyhan disease: outcomes from the patient's perspective. Visser JE, Cotton AC, Schretlen DJ, Bloch J, Tedroff K, Schechtmann G, Radu Djurfeldt D, Gonzalez V, Cif L, Jinnah HA. Dev Med Child Neurol. 2021 Mar 10. doi: 10.1111/dmcn.14852. Online ahead of print.

Diagnostic criteria for blepharospasm: A multicenter international study. Defazio G, Jinnah HA, Berardelli A, Perlmutter JS, Berkmen GK, Berman BD, Jankovic J, Bäumer T, Comella C, Cotton AC, Ercoli T, Ferrazzano G, Fox S, Kim HJ, Moukheiber ES, Richardson SP, Weissbach A, Wrigth LJ, Hallett M. Parkinsonism Relat Disord. 2021 Oct;91:109-114. doi: 10.1016/j.parkreldis.2021.09.004. Epub 2021 Sep 8. PMID: 34583301.

Blepharospasm (BSP) is a form of focal dystonia that manifests with eyelid spasms, involuntary eyelid closures, and spontaneous blinking. To date, there are no widely accepted criteria to diagnose BSP. In this study, researchers validate the use of new diagnostic criteria for BSP in a diverse international population. “This was a huge, multicenter effort aimed at establishing internationally acceptable diagnostic criteria for BSP,” says H. A. Jinnah, MD, PhD, principal investigator of the DC. “Such criteria did not exist before. What we do in the USA with RDCRN funding must ultimately go to the rest of the world.”

Does raising the arms modify head tremor severity in cervical dystonia?. Cisneros E, Vu JP, Lee HY et al. Tremor and Other Hyperkinetic Movements. 2021. doi: 10.5334/tohm.623. PMCID: PMC8231450.

Dystonia and Tremor: A Cross-Sectional Study of the Dystonia Coalition Cohort. Shaikh AG, Beylergil SB, Scorr L, Kilic-Berkmen G, Freeman A, Klein C, Junker J, Loens S, Brüggemann N, Münchau A, Bäumer T, Vidailhet M, Roze E, Bonnet C, Jankovic J, Jimenez-Shahed J, Patel N, Marsh L, Comella C, Barbano RL, Berman BD, Malaty I, Wagle Shukla A, Reich SG, Ledoux MS, Berardelli A, Ferrazzano G, Stover N, Ondo W, Pirio Richardson S, Saunders-Pullman R, Mari Z, Agarwal P, Adler C, Chouinard S, Fox SH, Brashear A, Truong D, Suchowersky O, Frank S, Factor S, Perlmutter J, Jinnah HA. Neurology. 2021 Jan 26;96(4):e563-e574. doi: 10.1212/WNL.0000000000011049. Epub 2020 Oct 12.

Feedback-dependent neuronal properties make focal dystonias so focal. Sedov A, Usova S, Popov V, Tomskiy A, Jinnah HA, Shaikh AG. Eur J Neurosci. 2021 Apr;53(7):2388-2397. doi: 10.1111/ejn.14933. Epub 2020 Aug 31.

Seeking to better understand the neuron activity responsible for dystonia, researchers tested the hypothesis that focal dystonia (a condition that causes abnormal movements in a single body part) may be associated with specific vs broad neuronal abnormalities. They measured the activity of individual neurons of the basal ganglia during deep brain stimulation surgery in 12 patients with dystonia limited to the neck. They found abnormal neuronal activity for both neck and hand neurons, even though the hand was unaffected. These results imply abnormalities of neuronal activity are not restricted to neurons associated with the affected body region, but appear to be more widespread. Symptoms may appear in only in specific body regions, such as the neck, when a second abnormality is added, such as sensory feedback from the affected region.

Functional Connectivity of Vermis Correlates with Future Gait Impairments in Parkinson's Disease. Maiti B, Rawson KS, Tanenbaum AB, Koller JM, Snyder AZ, Campbell MC, Earhart GM, Perlmutter JS. Mov Disord. 2021 Nov;36(11):2559-2568. doi: 10.1002/mds.28684. Epub 2021 Jun 10.

Head tremor and pain in cervical dystonia. Vu JP, Lee HY, Chen Q, Cisneros E, Barbano RL, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Berman BD, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. J Neurol. 2021 May;268(5):1945-1950. doi: 10.1007/s00415-020-10378-5. Epub 2021 Jan 8.

To determine how head tremor and pain are associated with cervical dystonia, researchers undertook a retrospective review of severity and pain rating scales from 188 patients. They examined associations of head trauma and pain with age at onset, disease duration, and head tremor subtype, finding that head tremor severity was associated with longer disease duration while pain severity was associated with younger age at onset. Researchers said these associations further characterize the heterogeneity of cervical dystonia’s clinical presentation and suggest similarly heterogenous underlying mechanisms.

Induced pluripotent stem cells from subjects with Lesch-Nyhan disease. Sutcliffe DJ, Dinasarapu AR, Visser JE, Hoed JD, Seifar F, Joshi P, Ceballos-Picot I, Sardar T, Hess EJ, Sun YV, Wen Z, Zwick ME, Jinnah HA. Sci Rep. 2021 Apr 19;11(1):8523. doi: 10.1038/s41598-021-87955-9.

Is Levodopa Response a Valid Indicator of Parkinson's Disease?. Martin WRW, Miles M, Zhong Q, Hartlein J, Racette BA, Norris SA, Ushe M, Maiti B, Criswell S, Davis AA, Kotzbauer PT, Cairns NJ, Perrin RJ, Perlmutter JS. Mov Disord. 2021 Apr;36(4):948-954. doi: 10.1002/mds.28406. Epub 2020 Nov 30.

Neuropathology of blepharospasm. Fagan M, Scorr L, Bernhardt D, Hess EJ, Perlmutter JS, Pardo CA, Jinnah HA. Exp Neurol. 2021 Dec;346:113855. doi: 10.1016/j.expneurol.2021.113855. Epub 2021 Aug 28. PMID: 34464652; PMCID: PMC8490317.

The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal repetitive movements or postures. Blepharospasm is a subtype of dystonia characterized by overactive facial muscles. Previous brain imaging studies have implied subtle structural changes in blepharospasm, but the nature of these changes is not well understood. In this study, researchers found subtle loss of cerebellar Purkinje neurons in histopathological studies of brains from blepharospasm cases. These findings are similar to those reported for subjects with cervical dystonia. “To focus on what we should be looking for in blepharospasm, we used what we learned about cervical dystonia published in 2013 in a prior funding cycle,” says H. A. Jinnah, MD, PhD, principal investigator of the DC. “Thus, the RDCRN strategy of combining similar disorders under the same research umbrella is successful in facilitating both the research questions and methodologies.”

Non-motor phenotypic subgroups in adult-onset idiopathic, isolated, focal cervical dystonia. Megan E Wadon, Grace A Bailey, Zehra Yilmaz, Emily Hubbard, Meshari AlSaeed, Amy Robinson, Duncan McLauchlan, Richard L Barbano, Laura Marsh, Stewart A Factor, Susan H Fox, Charles H Adler, Ramon L Rodriguez, Cynthia L Comella, Stephen G Reich, William L Severt, Christopher G Goetz, Joel S Perlmutter, Hyder A Jinnah, Katharine E Harding, Cynthia Sandor, Kathryn J Peall. Brain and Behavior. 11,e2292. https://doi.org/10.1002/brb3.2292

Adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD) is a disorder characterized by involuntary muscle contractions that cause repetitive movements or abnormal postures. These movements can be painful and cause considerable disability. Although patients most commonly present to clinical services due to their motor symptoms, increasing evidence suggests a significant non-motor phenotype to be associated with most forms of dystonia, including AOIFCD. Improved understanding of these non-motor symptoms is needed to better target therapeutic interventions. In this study, researchers examined non-motor phenotypic features to identify possible AOIFCD subgroups. Non-motor symptoms were assessed in participants with AOIFCD, including psychiatric symptoms, pain, sleep disturbance, and quality of life. To investigate the relationship between these symptoms and determine phenotypic subgroups, researchers used Cluster and Bayesian multiple mixed model phenotype analyses. They identified two phenotypic subgroups of non-motor symptoms accompanying AOIFCD, with differences in psychiatric symptoms, pain catastrophizing, sleep quality, and quality of life. Researchers say that improved understanding of these symptom groups will enable better targeted pathophysiological investigation and future therapeutic intervention.

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases. Scorr LM, Factor FA, Parra SP et al and Jinnah HA for the Dystonia Coalition Investigators. Front Neurol. 2021. https://doi.org/10.3389/fneur.2021.700714. PMCID: in progress

Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia. Sedov A, Popov V, Gamaleya A, Semenova U, Tomskiy A, Jinnah HA, Shaikh AG. Clin Neurophysiol 2021; 132: 3190-3196. PMCID: in progress

Predictive modeling of spread in adult-onset isolated dystonia: key properties and effect of tremor inclusion. Wang M, Sajobi T, Morgante F, Adler C, Agarwal P, Bäumer T, Berardelli A, Berman BD, Blumin J, Borsche M, Brashear A, Deik A, Duque K, Espay AJ, Ferrazzano G, Feuerstein J, Fox S, Frank S, Hallett M, Jankovic J, LeDoux MS, Leegwater-Kim J, Mahajan A, Malaty IA, Ondo W, Pantelyat A, Pirio-Richardson S, Roze E, Saunders-Pullman R, Suchowersky O, Truong D, Vidailhet M, Shukla AW, Perlmutter JS, Jinnah HA, Martino D.. European Journal of Neurology. 2021 Dec;28(12):3999-4009. doi: 10.1111/ene.15031. Epub 2021 Aug 4. PMID: 34296504; PMCID: PMC9100858.

Quality of life in isolated dystonia: non-motor manifestations matter. Junker J, Berman BD, Hall J, Wahba DW, Brandt V, Perlmutter JS, Jankovic J, Malaty IA, Wagle Shukla A, Reich SG, Espay AJ, Duque KR, Patel N, Roze E, Vidailhet M, Jinnah HA, Brüggemann N. J Neurol Neurosurg Psychiatry 2021 Feb 9; jnnp-2020-325193. doi: 10.1136/jnnp-2020-325193. Online ahead of print. PMCID: PMC8356023.

Rational Design of Novel Therapies for Pantothenate Kinase-Associated Neurodegeneration. Thakur N, Klopstock T, Jackowski S, Kuscer E, Tricta F, Videnovic A, Jinnah HA. Mov Disord. 2021 Sep;36(9):2005-2016. doi: 10.1002/mds.28642. Epub 2021 May 18.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurogenetic disorder in which specific regions of the central nervous system progressively degenerate, causing progressive, abnormal, involuntary movements. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in enzyme activity. This disruption allows iron to accumulate in the brain. Increased understanding of the molecular and biochemical mechanisms of the disease has allowed researchers to use these insights to begin designing new therapeutics for the disorder. Study authors review the results of recent clinical trials and pre-clinical studies of several compounds currently being evaluated. They say that these trials have helped improve trial designs and allowed the development of PKAN-specific measures to monitor outcomes. They conclude that PKAN provides a good model for targeted drug development and clinical trial design for rare disorders.

Resting-State Functional Connectivity Predicts STN DBS Clinical Response. Younce JR, Campbell MC, Hershey T, Tanenbaum AB, Milchenko M, Ushe M, Karimi M, Tabbal SD, Kim AE, Snyder AZ, Perlmutter JS, Norris SA. Mov Disord. 2021 Mar;36(3):662-671. doi: 10.1002/mds.28376. Epub 2020 Nov 19.

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies. Kilic-Berkmen G, Wright LJ, Perlmutter JS, Comella C, Hallett M, Teller J, Pirio Richardson S, Peterson DA, Cruchaga C, Lungu C, Jinnah HA. Front Neurol. 2021. 8;12:660909. doi: 10.3389/fneur.2021.660909. PMCID: PMC8060489. [Review]

A metabolomic study of cervical dystonia. Liu C, Scorr L, Kilic-Berkmen G, Cotton A, Factor SA, Freeman A, Tran V, Liu K, Uppal K, Jones D, Jinnah HA, Sun YV. Parkinsonism Relat Disord. 2021 Jan;82:98-103. doi: 10.1016/j.parkreldis.2020.11.020. Epub 2020 Nov 26. PMID: 33271463; PMCID: PMC7856090.

Cervical dystonia is the most common adult-onset focal dystonia. Researchers currently believe that cervical dystonia may be caused by a combination of genetic and environmental factors. Although genetic factors have been studied extensively, other factors have not. To identify potentially abnormal metabolites or altered biological pathways, researchers conducted an exploratory metabolomics analysis of cervical dystonia. The team compared plasma samples from 100 idiopathic cervical dystonia patients and 100 controls. Results showed that altered biological pathways may relate to carbohydrate and lipid metabolism. Study authors say this may provide novel insights into the biology of cervical dystonia.

Clinical and Demographic Characteristics of Upper Limb Dystonia. Norris SA, Jinnah HA, Klein C, Jankovic J, Berman BD, Roze E, Mahajan A, Espay AJ, Murthy AV, Fung VSC, LeDoux MS, Chang FCF, Vidailhet M, Testa C, Barbano R, Malaty IA, Bäumer T, Loens S, Wright LJ, Perlmutter JS. Mov Disord. 2020 Nov;35(11):2086-2090. doi: 10.1002/mds.28223. Epub 2020 Aug 26.

Hemodynamic responses are abnormal in isolated cervical dystonia. Berman BD, Groth CL, Shelton E, Sillau SH, Sutton B, Legget KT, Tregellas JR. J Neurosci Res. 2020 Apr;98(4):692-703. doi: 10.1002/jnr.24547. Epub 2019 Nov 6.

It's tricky: Rating alleviating maneuvers in cervical dystonia. Cisneros E, Stebbins GT, Chen Q, Vu JP, Benadof CN, Zhang Z, Barbano RL, Fox SH, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Adler CH, Factor SA, Reich SG, Rodriguez R, Severt LL, Stover NP, Berman BD, Comella CL, Peterson DA. J Neurol Sci. 2020 Dec 15;419:117205. doi: 10.1016/j.jns.2020.117205. Epub 2020 Nov 1.

Medical and Surgical Treatments for Dystonia. Jinnah HA. Neurol Clin. 2020 May;38(2):325-348. doi: 10.1016/j.ncl.2020.01.003. Epub 2020 Mar 2.

Pallidal Activity in Cervical Dystonia with and Without Head Tremor. Sedov A, Usova S, Semenova U, Gamaleya A, Tomskiy A, Beylergil SB, Jinnah HA, Shaikh AG. Cerebellum. 2020 Jun;19(3):409-418. doi: 10.1007/s12311-020-01119-5.

Postural Directionality and Head Tremor in Cervical Dystonia. Chen Q, Vu JP, Cisneros E, Benadof CN, Zhang Z, Barbano RL, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. Tremor Other Hyperkinet Mov (N Y). 2020 Jan 20;10. doi: 10.7916/tohm.v0.745. eCollection 2020.

Regional, not global, functional connectivity contributes to isolated focal dystonia. Norris SA, Morris AE, Campbell MC, Karimi M, Adeyemo B, Paniello RC, Snyder AZ, Petersen SE, Mink JW, Perlmutter JS. Neurology. 2020 Oct 20;95(16):e2246-e2258. doi: 10.1212/WNL.0000000000010791. Epub 2020 Sep 10.

Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. Berman BD, Groth CL, Sillau SH, Pirio Richardson S, Norris SA, Junker J, Brüggemann N, Agarwal P, Barbano RL, Espay AJ, Vizcarra JA, Klein C, Bäumer T, Loens S, Reich SG, Vidailhet M, Bonnet C, Roze E, Jinnah HA, Perlmutter JS. J Neurol Neurosurg Psychiatry. 2020 Mar;91(3):314-320. doi: 10.1136/jnnp-2019-321794. Epub 2019 Dec 17.

Soft Nanomembrane Sensors and Flexible Hybrid Bioelectronics for Wireless Quantification of Blepharospasm. Mahmood M, Kwon S, Berkmen GK, Kim YS, Scorr L, Jinnah HA, Yeo WH. IEEE Trans Biomed Eng. 2020 Nov;67(11):3094-3100. doi: 10.1109/TBME.2020.2975773. Epub 2020 Feb 21.

The Influence of Linguistic Demand on Symptom Expression in Adductor Spasmodic Dysphonia. Laura LO Froeschke. Journal of Voice. 2020; 34: 807.e11-807.e21. PMCID: In Progress

Gravity-Independent Upbeat Nystagmus in Syndrome of Anti-GAD Antibodies. Feldman D, Otero-Millan J, Shaikh AG. Cerebellum. 2019 Apr;18(2):287-290. doi: 10.1007/s12311-018-0972-z.

Head tremor at disease onset: an ataxic phenotype of cervical dystonia. Merola A, Dwivedi AK, Shaikh AG, Tareen TK, Da Prat GA, Kauffman MA, Hampf J, Mahajan A, Marsili L, Jankovic J, Comella CL, Berman BD, Perlmutter JS, Jinnah HA, Espay AJ. J Neurol. 2019 Aug;266(8):1844-1851. doi: 10.1007/s00415-019-09341-w. Epub 2019 Apr 26.

Involuntary Thumb Flexion on Neurological Examination: An Unusual Form of Upper Limb Dystonia in the Faroe Islands. Kim CY, Petersen MS, Eliasen EH et al. Tremor Other Hyperkinet Mov. 2019; 20: 9. PMCID: PMC6702791. [Research Support]

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. Fernandez HH, Stamler D, Davis MD, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Woods SW, Bega D, LeDoux MS, Shprecher DR, Anderson KE. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1317-1323. doi: 10.1136/jnnp-2018-319918. Epub 2019 Jul 10.

Naming Genes for Dystonia: DYT-z or Ditzy?. Mencacci NE and Jinnah HA. Tremor Other Hyperkinet Mov. 2019; 28: 9. PMCID: PMC6714488. [Research Support]

Past and Present of Eye Movement Abnormalities in Ataxia-Telangiectasia. Tang SY, Shaikh AG. Cerebellum. 2019 Jun;18(3):556-564. doi: 10.1007/s12311-018-0990-x.

Progressive Encephalomyelitis with Rigidity and Myoclonus Syndrome Presenting as Catatonia. Witek N, Hebert C, Gera A, Comella C. Psychosomatics. 2019; 60: 83-87. PMCID: In Progress.

Relationship between jerky and sinusoidal oscillations in cervical dystonia. Beylergil SB, Singh AP, Zee DS, Jinnah HA, Shaikh AG. Parkinsonism Relat Disord. 2019 Sep;66:130-137. doi: 10.1016/j.parkreldis.2019.07.024. Epub 2019 Jul 20.

Sensory Tricks Are Associated with Higher Sleep-Related Quality of Life in Cervical Dystonia. Benadof CN, Cisneros E, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. Tremor Other Hyperkinet Mov (N Y). 2019 Jun 17;9. doi: 10.7916/4q53-vt23. eCollection 2019.

Soft Material-Enabled, Active Wireless, Thin-Film Bioelectronics for Quantitative Diagnostics of Cervical Dystonia. Kwon YT, Lee Y, Berkmen GK, Lim HR, Scorr L, Jinnah HA, Yeo WH. Adv Mater Technol. 2019 Oct;4(10):1900458. doi: 10.1002/admt.201900458. Epub 2019 Aug 16.

The Dystonias. Jinnah HA. Continuum (Minneap Minn). 2019 Aug;25(4):976-1000. doi: 10.1212/CON.0000000000000747.

The role of pallidum in the neural integrator model of cervical dystonia. Sedov A, Usova S, Semenova U, Gamaleya A, Tomskiy A, Crawford JD, Corneil B, Jinnah HA, Shaikh AG. Neurobiol Dis. 2019 May;125:45-54. doi: 10.1016/j.nbd.2019.01.011. Epub 2019 Jan 22.

Tremor in chronic inflammatory demyelinating polyneuropathy: Proof of unifying network model for dystonia. Pyatka N, Sedov A, Walter BL et al. Prog Brain Res. 2019; 249: 285-294. PMCID: In progress.

A strategy for managing flu-like symptoms after botulinum toxin injections. George EB, Cotton AC, Shneyder N, Jinnah HA. J Neurol. 2018 Aug;265(8):1932-1933. doi: 10.1007/s00415-018-8934-4. Epub 2018 Jun 20.

Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia. Popa T, Hubsch C, James P et al. Nat Sci Rep. 2018; 8: 2263. PMCID: PMC5797249.

Cervical dystonia and substance abuse. Mahajan A, Jankovic J, Marsh L, Patel A, Jinnah HA, Comella C, Barbano R, Perlmutter J, Patel N; members of the Dystonia Coalition. J Neurol. 2018 Apr;265(4):970-975. doi: 10.1007/s00415-018-8840-9. Epub 2018 Mar 22.

Consensus-Based Attributes for Identifying Patients With Spasmodic Dysphonia and Other Voice Disorders. Ludlow CL, Domangue R, Sharma D, Jinnah HA, Perlmutter JS, Berke G, Sapienza C, Smith ME, Blumin JH, Kalata CE, Blindauer K, Johns M, Hapner E, Harmon A, Paniello R, Adler CH, Crujido L, Lott DG, Bansberg SF, Barone N, Drulia T, Stebbins G. JAMA Otolaryngol Head Neck Surg. 2018 Aug 1;144(8):657-665. doi: 10.1001/jamaoto.2018.0644.

Dysfunction in emotion processing underlies functional (psychogenic) dystonia. Espay AJ, Maloney T, Vannest J et al. Mov Disord. 2018; 33: 136-145. PMCID: PMC5767134.

Effects of deep brain stimulation on eye movements and vestibular function. Shaikh AG, Antoniades C, Fitzgerald J et al. Front Neurol. 2018; 9: 444. PMCID: PMC6005881.

Evolving concepts in the pathogenesis of dystonia. Jinnah HA, Hess EJ. Parkinsonism Relat Disord. 2018 Jan;46 Suppl 1(Suppl 1):S62-S65. doi: 10.1016/j.parkreldis.2017.08.001. Epub 2017 Aug 2.

Expert Opinion vs Patient Perspective in Treatment of Rare Disorders: Tooth Removal in Lesch-Nyhan Disease as an Example. Cotton AC, Bell RB, Jinnah HA. JIMD Rep. 2018;41:25-27. doi: 10.1007/8904_2017_80. Epub 2017 Dec 15.

Eye movement research in the twenty-first century-a window to the brain, mind, and more. Shaikh AG, Zee DS. Cerebellum. 2018; 17: 252-258. [Review] 

Functional imaging in dystonia. Norris SA, Perlmutter JS. In Treatment of Dystonia, ed Dressler, Altenmuller, & Krauss, Cambridge University Press, Cambridge, UK, June 2018, ISBN: 9781107132863. [Chapter]

In Vivo Characterization of Two (18)F-Labeled PDE10A PET Radioligands in Nonhuman Primate Brains. Liu H, Jin H, Luo Z, Yue X, Zhang X, Flores H, Su Y, Perlmutter JS, Tu Z. ACS Chem Neurosci. 2018 May 16;9(5):1066-1073. doi: 10.1021/acschemneuro.7b00458. Epub 2018 Feb 19.

Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?. Jinnah HA, Comella CL, Perlmutter J, Lungu C, Hallett M; Dystonia Coalition Investigators. Toxicon. 2018 Jun 1;147:89-95. doi: 10.1016/j.toxicon.2017.09.004. Epub 2017 Sep 6.

Minimal clinically important change in the Toronto Western Spasmodic Torticollis Rating Scale. Espay AJ, Trosch R, Suarez G et al. Parkinsonism Relat Disord. 2018; 52: 94-97. PMCID: In Progress.

Paraneoplastic seesaw nystagmus and opsoclonus provides evidence for hyperexcitable reciprocally innervating mesencephalic network. Rizvi MT, Cameron L, Kilbane C, Shaikh AG. J Neurol Sci. 2018 Jul 15;390:239-245. doi: 10.1016/j.jns.2018.05.002. Epub 2018 May 3.

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia. Shi LL, Simpson CB, Hapner ER, Jinnah HA, Johns MM 3rd. J Voice. 2018 Mar;32(2):234-238. doi: 10.1016/j.jvoice.2017.05.004. Epub 2017 Jun 23.

Physiological effects of subthalamic nucleus deep brain stimulation surgery in cervical dystonia. Wagle Shukla A, Ostrem JL, Vaillancourt DE et al. J Neurol Neurosurg Psychiatry. 2018; 89: 1296-1300. PMCID: PMC7498178.

Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia. Scorr LM, Silver MR, Hanfelt J, Sperin E, Freeman A, Jinnah HA, Factor SA. Neurotherapeutics. 2018 Apr;15(2):452-458. doi: 10.1007/s13311-018-0620-9.

Predictors of alcohol responsiveness in dystonia. Junker J, Brandt V, BD B, Vidailhet M et al. Neurology 2018; 91: 2020-2026. PMCID: PMC6260199.

Quantitative, clinically relevant acoustic measurements of focal embouchure dystonia. Morris AE, Norris SA, Perlmutter JS, Mink JW. Mov Disord. 2018 Mar;33(3):449-458. doi: 10.1002/mds.27298. Epub 2018 Feb 20.

The motor network model for dystonia. Jinnah HA, Hess EJ. In Treatment of dystonia. Cambridge University Press. 1st Edition, 2018. [Book chapter]

Treatable inherited rare movement disorders. Jinnah HA, Albanese A, Bhatia KP, Cardoso F, Da Prat G, de Koning TJ, Espay AJ, Fung V, Garcia-Ruiz PJ, Gershanik O, Jankovic J, Kaji R, Kotschet K, Marras C, Miyasaki JM, Morgante F, Munchau A, Pal PK, Rodriguez Oroz MC, Rodríguez-Violante M, Schöls L, Stamelou M, Tijssen M, Uribe Roca C, de la Cerda A, Gatto EM; International Parkinson's Disease Movement Disorders Society Task Force on Rare Movement Disorders. Mov Disord. 2018 Jan;33(1):21-35. doi: 10.1002/mds.27140. Epub 2017 Sep 1.

Vergence and strabismus in neurodegenerative disorders. Kang SL, Shaikh AG, Ghasia FF. Front Neurol. 2018; 9: 299. PMCID: PMC5964131.

A Dynamic circuit hypothesis for the pathogenesis of blepharospasm. Peterson DA, Sejnowski TJ. Front Comput Neurosci. 2017; 11: 11. PMCID: PMC5340098 [Review]

Acquired pendular nystagmus. Kang S, Shaikh AG. J Neurol Sci. 2017 Apr 15;375:8-17. doi: 10.1016/j.jns.2017.01.033. Epub 2017 Jan 10.

Alterations of resting-state fMRI measurements in individuals with cervical dystonia. Li Z, Prudente CN, Stilla R, Sathian K, Jinnah HA, Hu X. Hum Brain Mapp. 2017 Aug;38(8):4098-4108. doi: 10.1002/hbm.23651. Epub 2017 May 15.

Basic and translational neuro-ophthalmology of visually guided saccades: disorders of velocity. Puri S, Shaikh AG. Expert Rev Ophthalmol. 2017;12(6):457-473. doi: 10.1080/17469899.2017.1395695. Epub 2017 Nov 28.

Blepharospasm 40 years later. Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. Mov Disord. 2017 Apr;32(4):498-509. doi: 10.1002/mds.26934. Epub 2017 Feb 10.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia. Shakkottai VG, Batla A, Bhatia K, Dauer WT, Dresel C, Niethammer M, Eidelberg D, Raike RS, Smith Y, Jinnah HA, Hess EJ, Meunier S, Hallett M, Fremont R, Khodakhah K, LeDoux MS, Popa T, Gallea C, Lehericy S, Bostan AC, Strick PL. Cerebellum. 2017 Apr;16(2):577-594. doi: 10.1007/s12311-016-0825-6.

Deep brain stimulation for dystonia: a novel perspective on the value of genetic testing. Jinnah HA, Alterman R, Klein C, Krauss JK, Moro E, Vidailhet M, Raike R. J Neural Transm (Vienna). 2017 Apr;124(4):417-430. doi: 10.1007/s00702-016-1656-9. Epub 2017 Feb 3.

Diffusion-Weighted Magnetic Resonance Imaging in Acute Retinal Pathology. Alsinaidi O, Shaikh AG. Neuroophthalmology. 2017 Oct 13;42(3):191-193. doi: 10.1080/01658107.2017.1354385. eCollection 2018 Jun.

Dystonia treatment: patterns of medication use in an international cohort. Pirio Richardson S, Wegele A, Skipper B et al. Neurology. 2017; 88: 543-550. PMCID: PMCID: 5304465

Fixational eye movements in Tourette syndrome. Shaikh AG, Finkelstein SR, Schuchard R, Ross G, Juncos JL. Neurol Sci. 2017 Nov;38(11):1977-1984. doi: 10.1007/s10072-017-3069-4. Epub 2017 Aug 16.

Fixational saccades are more disconjugate in adults than in children. Shaikh AG, Ghasia FF. PLoS One. 2017 Apr 13;12(4):e0175295. doi: 10.1371/journal.pone.0175295. eCollection 2017.

Increased blinking may be a precursor of blepharospasm: a longitudinal study. Conte A, Ferrazzano G, Defazio G et al. Mov Disord Clin Pract. 2017; 4: 733-736. PMCID: PMC5654574.

Motion Illusion-Evidence towards Human Vestibulo-Thalamic Projections. Shaikh AG, Straumann D, Palla A. Cerebellum. 2017 Jun;16(3):656-663. doi: 10.1007/s12311-017-0844-y.

Novel Eye Movement Disorders in Whipple's Disease-Staircase Horizontal Saccades, Gaze-Evoked Nystagmus, and Esotropia. Shaikh AG, Ghasia FF. Front Neurol. 2017 Jul 11;8:321. doi: 10.3389/fneur.2017.00321. eCollection 2017.

Physiology of midbrain head movement neurons in cervical dystonia. Sedov A, Popov V, Shabalov V, Raeva S, Jinnah HA, Shaikh AG. Mov Disord. 2017 Jun;32(6):904-912. doi: 10.1002/mds.26948. Epub 2017 Feb 20.

Psychiatric associations of adult-onset focal dystonia phenotypes. Berman BD, Junker J, Shelton E, Sillau SH, Jinnah HA, Perlmutter JS, Espay AJ, Jankovic J, Vidailhet M, Bonnet C, Ondo W, Malaty IA, Rodríguez R, McDonald WM, Marsh L, Zurowski M, Bäumer T, Brüggemann N. J Neurol Neurosurg Psychiatry. 2017 Jul;88(7):595-602. doi: 10.1136/jnnp-2016-315461. Epub 2017 Apr 24.

Reply: Contributions of visual and motor signals in cervical dystonia. Shaikh AG, Zee DS, Crawford JD et al. Brain. 2017; 140: e5. [Letter]

Research Priorities in Limb and Task-Specific Dystonias. Pirio Richardson S, Altenmüller E, Alter K, Alterman RL, Chen R, Frucht S, Furuya S, Jankovic J, Jinnah HA, Kimberley TJ, Lungu C, Perlmutter JS, Prudente CN, Hallett M. Front Neurol. 2017 May 3;8:170. doi: 10.3389/fneur.2017.00170. eCollection 2017.

Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and slow. Shaikh AG, Factor SA, Juncos J. Mov Disord Clin Pract. 2017 Sep-Oct;4(5):671-681. doi: 10.1002/mdc3.12491. Epub 2017 Aug 11.

The anatomical basis for dystonia: The motor network model. Jinnah HA, Neychev V, Hess EJ. Tremor Other Hyperkinet Mov (N Y). 2017; 7: 506. PMCID: PMC5673689. [Invited Review]

Using the shared genetics of dystonia and ataxia to unravel their pathogenesis. Nibbeling EA, Delnooz CC, de Koning TJ, Sinke RJ, Jinnah HA, Tijssen MA, Verbeek DS. Neurosci Biobehav Rev. 2017 Apr;75:22-39. doi: 10.1016/j.neubiorev.2017.01.033. Epub 2017 Jan 28.

"Complex" dystonia is not a category in the new 2013 consensus classification. Albanese A, Bhatia K, DeLong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Mink JW, Teller JK. Mov Disord. 2016 Nov;31(11):1758-1759. doi: 10.1002/mds.26764. Epub 2016 Sep 10.

Abnormal interhemispheric inhibition in musician's dystonia - Trait or state?. Bäumer T, Schmidt A, Heldmann M, Landwehr M, Simmer A, Tönniges D, Münte T, Lohmann K, Altenmüller E, Klein C, Münchau A. Parkinsonism Relat Disord. 2016 Apr;25:33-8. doi: 10.1016/j.parkreldis.2016.02.018. Epub 2016 Feb 20.

Blepharospasm in a multiplex African-American pedigree. Xiao J, Thompson MM, Vemula SR et al. J Neurol Sci. 2016; 362: 299-303. PMCID: PMC4779500.

Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes. Jinnah HA, Goodmann E, Rosen AR, Evatt M, Freeman A, Factor S. J Neurol. 2016 Jun;263(6):1188-94. doi: 10.1007/s00415-016-8136-x. Epub 2016 Apr 25.

Cervical dystonia: a neural integrator disorder. Shaikh AG, Zee DS, Crawford JD, Jinnah HA. Brain. 2016 Oct;139(Pt 10):2590-2599. doi: 10.1093/brain/aww141. Epub 2016 Jun 20.

Clinical and demographic characteristics related to onset site and spread of cervical dystonia. Norris SA, Jinnah HA, Espay AJ, Klein C, Brüggemann N, Barbano RL, Malaty IA, Rodriguez RL, Vidailhet M, Roze E, Reich SG, Berman BD, LeDoux MS, Richardson SP, Agarwal P, Mari Z, Ondo WG, Shih LC, Fox SH, Berardelli A, Testa CM, Cheng FC, Truong D, Nahab FB, Xie T, Hallett M, Rosen AR, Wright LJ, Perlmutter JS. Mov Disord. 2016 Dec;31(12):1874-1882. doi: 10.1002/mds.26817. Epub 2016 Oct 18.

Clinical and genetic features of cervical dystonia in a large multicenter cohort. LeDoux MS, Vemula SR, Xiao J, Thompson MM, Perlmutter JS, Wright LJ, Jinnah HA, Rosen AR, Hedera P, Comella CL, Weissbach A, Junker J, Jankovic J, Barbano RL, Reich SG, Rodriguez RL, Berman BD, Chouinard S, Severt L, Agarwal P, Stover NP. Neurol Genet. 2016 Apr 11;2(3):e69. doi: 10.1212/NXG.0000000000000069. eCollection 2016 Jun.

Clinimetric testing of the comprehensive cervical dystonia rating scale. Comella CL, Perlmutter JS, Jinnah HA, Waliczek TA, Rosen AR, Galpern WR, Adler CA, Barbano RL, Factor SA, Goetz CG, Jankovic J, Reich SG, Rodriguez RL, Severt WL, Zurowski M, Fox SH, Stebbins GT. Mov Disord. 2016 Apr;31(4):563-9. doi: 10.1002/mds.26534. Epub 2016 Mar 12.

Comparative effectiveness of propranolol and botulinum for the treatment of essential voice tremor. Justicz N, Hapner ER, Josephs JS, Boone BC, Jinnah HA, Johns MM 3rd. Laryngoscope. 2016 Jan;126(1):113-7. doi: 10.1002/lary.25485. Epub 2015 Jul 21.

Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?. Fraint A, Vittal P, Comella C. Ther Clin Risk Manag. 2016; 12: 147-54. PMCID: PMC4751901. [Review]

DYT1 dystonia increases risk taking in humans. Arkadir D, Radulescu A, Raymond D et al. eLife 2016;10.7554. PMCID: PMC4951192.

DYT6 Dystonia: A Neuropathological Study. Paudel R, Li A, Hardy J, Bhatia KP, Houlden H, Holton J. Neurodegener Dis. 2016;16(3-4):273-8. doi: 10.1159/000440863. Epub 2015 Nov 27.

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia. Bologna M, Paparella G, Fabbrini A, Leodori G, Rocchi L, Hallett M, Berardelli A. Clin Neurophysiol. 2016 Nov;127(11):3472-3479. doi: 10.1016/j.clinph.2016.09.008. Epub 2016 Sep 15.

Locus Pocus. Jinnah HA. Mov Disord. 2016 Nov;31(11):1759-1760. doi: 10.1002/mds.26765. Epub 2016 Aug 22.

Objective, computerized video-based rating of blepharospasm severity. Peterson DA, Littlewort GC, Bartlett MS, Macerollo A, Perlmutter JS, Jinnah HA, Hallett M, Sejnowski TJ. Peterson D, Littlewort G, Bartlett M et al. Objective, computerized, video-based rating of blepharospasm severity. Neurology. 2016; 87: 2146-2153. PMCID: PMC5109937.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

The role of polymyography in the treatment of cervical dystonia: the authors reply. Jinnah HA, Factor S. J Neurol. 2016 Aug;263(8):1665. doi: 10.1007/s00415-016-8222-0. Epub 2016 Jul 8.

Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism. Schottlaender LV, Polke JM, Ling H, MacDoanld ND, Tucci A, Nanji T, Pittman A, de Silva R, Holton JL, Revesz T, Sweeney MG, Singleton AB, Lees AJ, Bhatia KP, Houlden H. Neurobiol Aging. 2015 Feb;36(2):1221.e1-6. doi: 10.1016/j.neurobiolaging.2014.08.024. Epub 2014 Aug 27.

Central Nervous System Control of Voice and Swallowing. Ludlow CL. J Clin Neurophysiol. 2015 Aug;32(4):294-303. doi: 10.1097/WNP.0000000000000186.

Development and validation of a clinical scale for rating the severity of blepharospasm. Defazio G, Hallett M, Jinnah HA, Stebbins GT, Gigante AF, Ferrazzano G, Conte A, Fabbrini G, Berardelli A. Mov Disord. 2015 Apr;30(4):525-30. doi: 10.1002/mds.26156.

Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology. Comella CL, Fox SH, Bhatia KP, Perlmutter JS, Jinnah HA, Zurowski M, McDonald WM, Marsh L, Rosen AR, Waliczek T, Wright LJ, Galpern WR, Stebbins GT. Mov Disord Clin Pract. 2015 Jun;2(2):135-141. doi: 10.1002/mdc3.12131. Epub 2015 Apr 6.

Diagnosis and treatment of dystonia. Jinnah HA, Factor SA. Neurol Clin. 2015 Feb;33(1):77-100. doi: 10.1016/j.ncl.2014.09.002.

Diagnostic Delays in Spasmodic Dysphonia: A Call for Clinician Education. Creighton FX, Hapner E, Klein A, Rosen A, Jinnah HA, Johns MM. J Voice. 2015 Sep;29(5):592-4. doi: 10.1016/j.jvoice.2013.10.022. Epub 2015 Apr 11.

Dystonia: Five new things. Berman BD, Jinnah HA. Neurol Clin Pract. 2015 Jun;5(3):232-240. doi: 10.1212/CPJ.0000000000000128.

Laryngeal Reflexes: Physiology, Technique, and Clinical Use. Ludlow CL. J Clin Neurophysiol. 2015 Aug;32(4):284-93. doi: 10.1097/WNP.0000000000000187.

Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia. Kimberley TJ, Schmidt RL, Chen M et al. Front Hum Neurosci. 2015; 9: 385. PMCID: PMC4496570.

Neural Substrates for Head Movements in Humans: A Functional Magnetic Resonance Imaging Study. Prudente CN, Stilla R, Buetefisch CM, Singh S, Hess EJ, Hu X, Sathian K, Jinnah HA. J Neurosci. 2015 Jun 17;35(24):9163-72. doi: 10.1523/JNEUROSCI.0851-15.2015.

Ocular palatal tremor plus dystonia - new syndromic association. Shaikh AG, Ghasia FF, DeLong MR, Jinnah HA, Freeman A, Factor SA. Mov Disord Clin Pract. 2015 Sep 1;2(3):267-270. doi: 10.1002/mdc3.12193. Epub 2015 Jun 17.

Oscillatory head movements in cervical dystonia: Dystonia, tremor, or both?. Shaikh AG, Zee DS, Jinnah HA. Mov Disord. 2015 May;30(6):834-42. doi: 10.1002/mds.26231. Epub 2015 Apr 16.

Recent developments in dystonia. Jinnah HA, Teller JK, Galpern WR. Curr Opin Neurol. 2015 Aug;28(4):400-5. doi: 10.1097/WCO.0000000000000213.

Repetitive transcranial magnetic stimulation in cervical dystonia:  effect of site and repetition in a randomized pilot trial. Pirio Richardson S, Tinaz S, Chen R. PLoS One. 2015; 10: e0124937. PMCID: PMC4414555.

Secured web-based video repository for multicenter studies. Yan L, Hicks M, Winslow K, Comella C, Ludlow C, Jinnah HA, Rosen AR, Wright L, Galpern WR, Perlmutter JS. Parkinsonism Relat Disord. 2015 Apr;21(4):366-71. doi: 10.1016/j.parkreldis.2015.01.011. Epub 2015 Jan 20.

Short- and long-term outcome of chronic pallidal neurostimulation in monogenic isolated dystonia. Brüggemann N, Kühn A, Schneider SA, Kamm C, Wolters A, Krause P, Moro E, Steigerwald F, Wittstock M, Tronnier V, Lozano AM, Hamani C, Poon YY, Zittel S, Wächter T, Deuschl G, Krüger R, Kupsch A, Münchau A, Lohmann K, Volkmann J, Klein C. Neurology. 2015 Mar 3;84(9):895-903. doi: 10.1212/WNL.0000000000001312. Epub 2015 Feb 4.

Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation. Shaikh AG, Mewes K, DeLong MR, Gross RE, Triche SD, Jinnah HA, Boulis N, Willie JT, Freeman A, Alexander GE, Aia P, Butefisch CM, Esper CD, Factor SA. Parkinsonism Relat Disord. 2015 Feb;21(2):116-9. doi: 10.1016/j.parkreldis.2014.11.013. Epub 2014 Nov 20.

The neurobiology of dystonia. Jinnah HA, Prudente CN, Rose SJ et al. In Neurobiology of Disease, 2nd Ed, 2015. [Chapter]

The role of dopamine and dopaminergic pathways in dystonia: insights from neuroimaging. Karimi M, Perlmutter JS. Tremor Other Hyperkinet Mov (N Y). 2015 Jan 29;5:280. doi: 10.7916/D8J101XV. eCollection 2015.

When brawn benefits brain: physical activity and Parkinson's disease risk. Tanner CM, Comella CL. Brain. 2015 Feb;138(Pt 2):238-9. doi: 10.1093/brain/awu351.

Why are voluntary head movements in cervical dystonia slow?. Shaikh AG, Wong A, Zee DS, Jinnah HA. Parkinsonism Relat Disord. 2015 Jun;21(6):561-6. doi: 10.1016/j.parkreldis.2015.03.005. Epub 2015 Mar 14.

A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia. Vemula SR, Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Hedera P, Truong DD, Blitzer A, Rudzińska M, Momčilović D, Jinnah HA, Frei K, Pfeiffer RF, LeDoux MS. Mol Genet Genomic Med. 2014 May;2(3):261-72. doi: 10.1002/mgg3.67. Epub 2014 Feb 11.

Activation of upper airway muscles during breathing and swallowing. Fregosi RF, Ludlow CL. J Appl Physiol (1985). 2014 Feb 1;116(3):291-301. doi: 10.1152/japplphysiol.00670.2013. Epub 2013 Oct 3.

Alleviating manoeuvres (sensory tricks) in cervical dystonia. Patel N, Hanfelt J, Marsh L, Jankovic J; members of the Dystonia Coalition. J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):882-4. doi: 10.1136/jnnp-2013-307316. Epub 2014 May 14.

An ¹⁸F-FDG PET study of cervical muscle in parkinsonian anterocollis. Revuelta GJ, Montilla J, Benatar M, Freeman A, Wichmann T, Jinnah HA, Delong MR, Factor SA. J Neurol Sci. 2014 May 15;340(1-2):174-7. doi: 10.1016/j.jns.2014.03.023. Epub 2014 Mar 18.

Closed-loop brain-machine-body interfaces for noninvasive rehabilitation of movement disorders. Broccard FD, Mullen T, Chi YM, Peterson D, Iversen JR, Arnold M, Kreutz-Delgado K, Jung TP, Makeig S, Poizner H, Sejnowski T, Cauwenberghs G. Ann Biomed Eng. 2014 Aug;42(8):1573-93. doi: 10.1007/s10439-014-1032-6. Epub 2014 May 15.

Designing clinical trials for dystonia. Galpern WR, Coffey CS, Albanese A, Cheung K, Comella CL, Ecklund DJ, Fahn S, Jankovic J, Kieburtz K, Lang AE, McDermott MP, Shefner JM, Teller JK, Thompson JL, Yeatts SD, Jinnah HA. Neurotherapeutics. 2014 Jan;11(1):117-27. doi: 10.1007/s13311-013-0221-6.

Dystonia as a network disorder: what is the role of the cerebellum?. Prudente CN, Hess EJ, Jinnah HA. Neuroscience. 2014 Feb 28;260:23-35. doi: 10.1016/j.neuroscience.2013.11.062. Epub 2013 Dec 11.

Globus pallidus deep brain stimulation for adult-onset axial dystonia. Shaikh AG, Mewes K, Jinnah HA, DeLong MR, Gross RE, Triche S, Freeman A, Factor SA. Parkinsonism Relat Disord. 2014 Nov;20(11):1279-82. doi: 10.1016/j.parkreldis.2014.09.005. Epub 2014 Sep 16.

Loss of dopamine phenotype among midbrain neurons in Lesch-Nyhan disease. Göttle M, Prudente CN, Fu R, Sutcliffe D, Pang H, Cooper D, Veledar E, Glass JD, Gearing M, Visser JE, Jinnah HA. Ann Neurol. 2014 Jul;76(1):95-107. doi: 10.1002/ana.24191. Epub 2014 Jun 20.

Neuroimaging biomarkers for Parkinson disease: facts and fantasy. Perlmutter JS, Norris SA. Ann Neurol. 2014 Dec;76(6):769-83. doi: 10.1002/ana.24291. Epub 2014 Nov 7.

Neuropathological features of genetically confirmed DYT1 dystonia: investigating disease-specific inclusions. Paudel R, Kiely A, Li A, Lashley T, Bandopadhyay R, Hardy J, Jinnah HA, Bhatia K, Houlden H, Holton JL. Acta Neuropathol Commun. 2014 Nov 18;2:159. doi: 10.1186/s40478-014-0159-x.

New concepts for dystonia. Jinnah HA, Albanese A. Jinnah HA, Albanese A. New concepts for dystonia. Moving Along: The Official Newsletter of the International Parkinson and Movement Disorder Society. 2014; 18: 6-7. [Feature article]

Pathogenic variants in TUBB4A are not found in primary dystonia. Vemula SR, Xiao J, Bastian RW, Momčilović D, Blitzer A, LeDoux MS. Neurology. 2014 Apr 8;82(14):1227-30. doi: 10.1212/WNL.0000000000000294. Epub 2014 Mar 5.

Recent advances in the genetics of dystonia. Xiao J, Vemula SR, LeDoux MS. Curr Neurol Neurosci Rep. 2014 Aug;14(8):462. doi: 10.1007/s11910-014-0462-8.

Reply: dystonia after severe head injuries. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Mov Disord. 2014 Apr;29(4):578-9. doi: 10.1002/mds.25861. Epub 2014 Mar 3.

Smoking and Parkinson disease: where there is smoke there may not be fire. Hershey LA, Perlmutter JS. Neurology. 2014 Oct 14;83(16):1392-3. doi: 10.1212/WNL.0000000000000896. Epub 2014 Sep 12.

The New Classification System for the Dystonias: Why Was it Needed and How was it Developed?. Jinnah HA, Albanese A. Mov Disord Clin Pract. 2014 Dec 1;1(4):280-284. doi: 10.1002/mdc3.12100.

Treatment of myoclonus-dystonia syndrome with tetrabenazine. Luciano AY, Jinnah HA, Pfeiffer RF, Truong DD, Nance MA, LeDoux MS. Parkinsonism Relat Disord. 2014 Dec;20(12):1423-6. doi: 10.1016/j.parkreldis.2014.09.029. Epub 2014 Oct 5.

Treatment of restless legs syndrome. Comella CL. Neurotherapeutics. 2014 Jan;11(1):177-87. doi: 10.1007/s13311-013-0247-9.

Assessment of patients with isolated or combined dystonia: an update on dystonia syndromes. Fung VS, Jinnah HA, Bhatia K, Vidailhet M. Mov Disord. 2013 Jun 15;28(7):889-98. doi: 10.1002/mds.25549.

Cerebellar processing of sensory inputs primes motor cortex plasticity. Popa T, Velayudhan B, Hubsch C, Pradeep S, Roze E, Vidailhet M, Meunier S, Kishore A. Cereb Cortex. 2013 Feb;23(2):305-14. doi: 10.1093/cercor/bhs016. Epub 2012 Feb 20.

Defective cerebellar control of cortical plasticity in writer's cramp. Hubsch C, Roze E, Popa T, Russo M, Balachandran A, Pradeep S, Mueller F, Brochard V, Quartarone A, Degos B, Vidailhet M, Kishore A, Meunier S. Brain. 2013 Jul;136(Pt 7):2050-62. doi: 10.1093/brain/awt147.

Depression and Parkinson's disease: current knowledge. Marsh L. Curr Neurol Neurosci Rep. 2013 Dec;13(12):409. doi: 10.1007/s11910-013-0409-5.

Development and validation of a clinical guideline for diagnosing blepharospasm. Defazio G, Hallett M, Jinnah HA, Berardelli A. Neurology. 2013 Jul 16;81(3):236-40. doi: 10.1212/WNL.0b013e31829bfdf6. Epub 2013 Jun 14.

Dystonia rating scales: critique and recommendations. Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Mov Disord. 2013 Jun 15;28(7):874-83. doi: 10.1002/mds.25579.

Dystonia, facial dysmorphism, intellectual disability and breast cancer associated with a chromosome 13q34 duplication and overexpression of TFDP1: case report. Moscovich M, LeDoux MS, Xiao J, Rampon GL, Vemula SR, Rodriguez RL, Foote KD, Okun MS. BMC Med Genet. 2013 Jul 13;14:70. doi: 10.1186/1471-2350-14-70.

Genetics of dystonia: What's known? What's new? What's next?. Lohmann K, Klein C. Mov Disord. 2013; 28: 899-905. [Invited Review]

How long does it take to diagnose cervical dystonia?. Tiderington E, Goodman EM, Rosen AR, Hapner ER, Johns MM 3rd, Evatt ML, Freeman A, Factor S, Jinnah HA. J Neurol Sci. 2013 Dec 15;335(1-2):72-4. doi: 10.1016/j.jns.2013.08.028. Epub 2013 Aug 30.

Keeping your head on target. Shaikh AG, Wong AL, Zee DS, Jinnah HA. J Neurosci. 2013 Jul 3;33(27):11281-95. doi: 10.1523/JNEUROSCI.3415-12.2013.

Neuropathology of cervical dystonia. Prudente CN, Pardo CA, Xiao J, Hanfelt J, Hess EJ, Ledoux MS, Jinnah HA. Exp Neurol. 2013 Mar;241:95-104. doi: 10.1016/j.expneurol.2012.11.019. Epub 2012 Nov 27.

Phenomenology and classification of dystonia: a consensus update. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.

Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase. Ceballos-Picot I, Augé F, Fu R, Olivier-Bandini A, Cahu J, Chabrol B, Aral B, de Martinville B, Lecain JP, Jinnah HA. Mol Genet Metab. 2013 Nov;110(3):268-74. doi: 10.1016/j.ymgme.2013.08.016. Epub 2013 Sep 8.

Psychiatric comorbidities in dystonia: emerging concepts. Zurowski M, McDonald WM, Fox S, Marsh L. Mov Disord. 2013 Jun 15;28(7):914-20. doi: 10.1002/mds.25501.

Rating scales for musician's dystonia: the state of the art. Peterson DA, Berque P, Jabusch HC, Altenmüller E, Frucht SJ. Neurology. 2013 Aug 6;81(6):589-98. doi: 10.1212/WNL.0b013e31829e6f72. Epub 2013 Jul 24.

Secondary blepharospasm associated with structural lesions of the brain. Khooshnoodi MA, Factor SA, Jinnah HA. J Neurol Sci. 2013 Aug 15;331(1-2):98-101. doi: 10.1016/j.jns.2013.05.022. Epub 2013 Jun 6.

Special concerns in defining, studying, and treating dystonia in children. Mink JW. Mov Disord. 2013 Jun 15;28(7):921-5. doi: 10.1002/mds.25548.

The dystonias: past, present, and future. Jinnah HA, Delong MR, Hallett M. Mov Disord. 2013 Jun 15;28(7):849-50. doi: 10.1002/mds.25564.

The focal dystonias: current views and challenges for future research. Jinnah HA, Berardelli A, Comella C, Defazio G, Delong MR, Factor S, Galpern WR, Hallett M, Ludlow CL, Perlmutter JS, Rosen AR; Dystonia Coalition Investigators. Mov Disord. 2013 Jun 15;28(7):926-43. doi: 10.1002/mds.25567.

Translation of Oppenheim's 1911 paper on dystonia. Klein C, Fahn S. Mov Disord. 2013; 28: 851-862. PMCID: In Progress. [Translation from German]

Clinical subtypes of anterocollis in parkinsonian syndromes. Revuelta GJ, Benatar M, Freeman A, Wichmann T, Jinnah HA, DeLong MR, Factor SA. J Neurol Sci. 2012 Apr 15;315(1-2):100-3. doi: 10.1016/j.jns.2011.11.017. Epub 2011 Nov 30.

Coprevalence of anxiety and depression with spasmodic dysphonia: a case-control study. White LJ, Hapner ER, Klein AM, Delgaudio JM, Hanfelt JJ, Jinnah HA, Johns MM 3rd. J Voice. 2012 Sep;26(5):667.e1-6. doi: 10.1016/j.jvoice.2011.08.011. Epub 2011 Dec 29.

Dystonia: phenomenology. LeDoux MS. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1(Suppl 1):S162-4. doi: 10.1016/S1353-8020(11)70050-5.

Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases. LeDoux MS, Xiao J, Rudzińska M, Bastian RW, Wszolek ZK, Van Gerpen JA, Puschmann A, Momčilović D, Vemula SR, Zhao Y. Parkinsonism Relat Disord. 2012 Jun;18(5):414-25. doi: 10.1016/j.parkreldis.2012.02.001. Epub 2012 Feb 28.

Mutations in CIZ1 cause adult onset primary cervical dystonia. Xiao J, Uitti RJ, Zhao Y, Vemula SR, Perlmutter JS, Wszolek ZK, Maraganore DM, Auburger G, Leube B, Lehnhoff K, LeDoux MS. Ann Neurol. 2012 Apr;71(4):458-69. doi: 10.1002/ana.23547. Epub 2012 Mar 23.

Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia. Hedera P, Xiao J, Puschmann A, Momčilović D, Wu SW, LeDoux MS. BMC Neurol. 2012 Sep 18;12:93. doi: 10.1186/1471-2377-12-93.

Oromandibular and lingual dystonia associated with spinocerebellar ataxia type 8. Ushe M, Perlmutter JS. Mov Disord. 2012 Dec;27(14):1741-2. doi: 10.1002/mds.25295.

Prevalence, predictors, and perceived effectiveness of complementary, alternative and integrative medicine in adult-onset primary dystonia. Fleming BM, Schwab EL, Nouer SS, Wan JY, LeDoux MS. Parkinsonism Relat Disord. 2012 Sep;18(8):936-40. doi: 10.1016/j.parkreldis.2012.04.027. Epub 2012 May 25.

The genetics of dystonias. LeDoux MS. Adv Genet. 2012;79:35-85. doi: 10.1016/B978-0-12-394395-8.00002-5.

An African-American family with dystonia. Puschmann A, Xiao J, Bastian RW, Searcy JA, LeDoux MS, Wszolek ZK. Parkinsonism Relat Disord. 2011 Aug;17(7):547-50. doi: 10.1016/j.parkreldis.2011.04.019. Epub 2011 May 20.

Animal models of dystonia: Lessons from a mutant rat. LeDoux MS. Neurobiol Dis. 2011 May;42(2):152-61. doi: 10.1016/j.nbd.2010.11.006. Epub 2010 Nov 21.

Convergent mechanisms in etiologically-diverse dystonias. Thompson VB, Jinnah HA, Hess EJ. Expert Opin Ther Targets. 2011 Dec;15(12):1387-403. doi: 10.1517/14728222.2011.641533. Epub 2011 Dec 3.

Coprevalence of tremor with spasmodic dysphonia: a case-control study. White LJ, Klein AM, Hapner ER, Delgaudio JM, Hanfelt JJ, Jinnah HA, Johns MM 3rd. Laryngoscope. 2011 Aug;121(8):1752-5. doi: 10.1002/lary.21872.

Extreme task specificity in writer's cramp. Shamim EA, Chu J, Scheider LH, Savitt J, Jinnah HA, Hallett M. Mov Disord. 2011 Sep;26(11):2107-9. doi: 10.1002/mds.23827. Epub 2011 Jun 28.

In the wink of an eye: nature and nurture in blepharospasm. Jinnah HA, Hallett M. Neurology. 2011 Aug 16;77(7):616-7. doi: 10.1212/WNL.0b013e3182299f84. Epub 2011 Jul 20.

Needles in haystacks: the challenges of rare diseases. Jinnah HA. Dev Med Child Neurol. 2011 Jan;53(1):6-7. doi: 10.1111/j.1469-8749.2010.03791.x.

Spasmodic dysphonia: a laryngeal control disorder specific to speech. Ludlow CL. J Neurosci. 2011 Jan 19;31(3):793-7. doi: 10.1523/JNEUROSCI.2758-10.2011.

The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia. Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Blitzer A, Rudzińska M, Pfeiffer RF, Le C, LeDoux MS. Mov Disord. 2011 Feb 15;26(3):549-52. doi: 10.1002/mds.23551. Epub 2011 Mar 2.

The functional neuroanatomy of dystonia. Neychev VK, Gross RE, Lehéricy S, Hess EJ, Jinnah HA. Neurobiol Dis. 2011 May;42(2):185-201. doi: 10.1016/j.nbd.2011.01.026. Epub 2011 Feb 12.

Neuronal voltage-gated calcium channels: brief overview of their function and clinical implications in neurology. Hess EJ, Jen JC, Jinnah HA, Benarroch EE. Neurology. 2010 Sep 7;75(10):937; author reply 937-8. doi: 10.1212/WNL.0b013e3181eee9e8.

Novel THAP1 sequence variants in primary dystonia. Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Dev Batish S, Blitzer A, Pfeiffer RF, Gong S, LeDoux MS. Neurology. 2010 Jan 19;74(3):229-38. doi: 10.1212/WNL.0b013e3181ca00ca.

Treatment strategies for dystonia. Cloud LJ, Jinnah HA. Expert Opin Pharmacother. 2010 Jan;11(1):5-15. doi: 10.1517/14656560903426171.

Rodent models of dystonia. Hess EJ, Jinnah HA. In Animal models for movement disorders, LeDoux MS, Ed. Elsevier Academic Press, Amsterdam, 2005. [Book chapter]

A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants. Geiculescu I, Dranove J, Cosper G, Edmondson AC, Morava-Kozicz E, Carter LB. Am J Med Genet A. 2022 Jun 4. doi: 10.1002/ajmg.a.62859. Epub ahead of print. PMID: 35665995.

Achalasia is a disorder of the esophagus, the tube that carries food from the mouth to the stomach. It is characterized by enlargement of the esophagus, impaired ability of the esophagus to push food down toward the stomach (peristalsis), and failure of the ring-shaped muscle at the bottom of the esophagus (the lower esophageal sphincter) to relax. Because achalasia is rare in the pediatric population, clinicians should consider associated genetic disorders. This includes GMPPA-congenital disorder of glycosylation (CDG), a rare type of CDG that is caused by variants in the GMPPA gene. In this study, researchers describe a 9-month-old female with achalasia and alacrima (reduced or absent ability to produce tears). The patient was found to have two novel compound heterozygous variants in the GMPPA gene that are associated with GMPPA-CDG. Authors provide a brief review of GMPPA-CDG, including management of this condition.

ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines. Albokhari D, Ng BG, Guberinic A, Daniel EJP, Engelhardt NM, Barone R, Fiumara A, Garavelli L, Trimarchi G, Wolfe L, Raymond KM, Morava E, He M, Freeze HH, Lam C, Edmondson AC. J Inherit Metab Dis. 2022 Jun 18. doi: 10.1002/jimd.12527. Epub ahead of print. PMID: 35716054.

ALG8-congenital disorder of glycosylation (ALG8-CDG) is a rare, inherited disorder that affects multiple systems in the body. Patients with ALG8-CDG commonly present with decreased muscle tone, intestinal problems, and liver problems. In this study, researchers describe seven new individuals with ALG8-CDG, bringing the total to 26 individuals reported in medical literature. The team diagnosed these patients based on biochemical and molecular testing, identifying nine novel variants in ALG8. The cohort also includes the two oldest patients reported to date. This study expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder, and other neuropsychiatric symptoms. Researchers also expand the clinical features in a variety of organ systems. To improve clinical management, authors suggest a comprehensive evaluation and monitoring strategy.

CDG or not CDG. Freeze HH, Jaeken J, Matthijs G. J Inherit Metab Dis. 2022 May;45(3):383-385. doi: 10.1002/jimd.12498. Epub 2022 Apr 1. PMID: 35338706; PMCID: PMC9121739.

In this letter to the editor, an expert team of authors explores a consensus on which genetic conditions should be identified as congenital disorders of glycosylation (CDG). “They are aiming to be inclusive; CDG should be used as the correct nomenclature in any disorders where the synthesis of glycans, glycoproteins, or glycolipids—including oligosaccharide transfer, glycan maturation, or trafficking—is affected,” says Eva Morava-Kozicz, MD, PhD, principal investigator of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC). “This is demonstrated by abnormal glycosylation in functional studies, and should be called a CDG.”

Clinical and molecular characterization of a third patient with a milder and a predominantly movement disorder phenotype. Elsharkawi I, Wongkittichote P, Daniel EJP, Starosta RT, Ueda K, Ng BG, Freeze HH, He M, Shinawi M. DDOST-CDG. J Inherit Metab Dis. 2022 Oct 10. doi: 10.1002/jimd.12565. Epub ahead of print. PMID: 36214423.

DDOST-CDG is an ultra-rare type of congenital disorder of glycosylation (CDG) that is caused by mutations in the gene DDOST. The metabolic disorder was previously reported in just two patients, whose clinical features included severe developmental delay, failure to thrive, and hypotonia (low muscle tone). Both patients also had abnormal transferrin glycosylation. In this study, researchers describe a new patient with DDOST-CDG. The 18-year-old male presented with moderate developmental delay, progressive opsoclonus (involuntary, rapid eye movements), myoclonus (involuntary, sudden muscle spasms), ataxia (impaired balance or coordination), tremor, and dystonia (involuntary muscle contractions that cause repetitive or twisting movements). The team performed several tests, including biochemical studies, exome sequencing, plasma N-glycan profiling, and western blot analysis, to learn more about the patient’s clinical features. Authors state that these insights—including new findings on the clinical variability, phenotypes, and genotypes of DDOST-CDG—are essential for diagnosing and managing patients with DDOST-CDG.

Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1-congenital disorder of glycosylation) and response to l-fucose therapy: Insights from two new families and review of the literature. Tahata S, Raymond K, Quade M, Barnes S, Boyer S, League S, Kumanovics A, Abraham R, Jacob E, Menon P, Morava E. Am J Med Genet A. 2022 Mar 26. doi: 10.1002/ajmg.a.62737. Epub ahead of print. PMID: 35338746.

Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. Among a subset of patients with a milder presentation, descriptions have also included short stature and developmental delay with minimal immune and hematologic (relating to blood) features. While some patients with LAD II benefit from oral fucose therapy, this has not yet been studied in patients with milder disease. In this study, researchers describe three new patients from two separate families with the milder variant of LAD II and review the published literature. After 27 months of oral fucose supplementation, one patient showed improvements in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins. Authors note that these patients support classification of this disorder into distinct subtypes—a classical severe and an attenuated variant—and provide preliminary evidence of benefit of fucose therapy in the latter group.

Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement. Mahajan S, Ng BG, AlAbdi L, Earnest PDJ, Sosicka P, Patel N, Helaby R, Abdulwahab F, He M, Alkuraya FS, Freeze HH. J Med Genet. 2022 Nov 10:jmg-2022-108821. doi: 10.1136/jmg-2022-108821. Epub ahead of print. PMID: 36357165

Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Defects in Golgi enzymes, which play a critical role in N-glycan processing and brain development, are often defined as types of CDG. However, defects in the Golgi enzyme MAN2A2 have not been known to cause defects in glycosylation. In this study, researchers investigated the effects of variants in MAN2A2. In a family of affected individuals, the team performed exome sequencing, analyzed N-glycans, and designed a cell-based complementation assay to evaluate the disease-causing effects of the variant. Findings show that variants in MAN2A2 cause a new type of CDG, which is characterized by neurological involvement and facial dysmorphism. Authors note that the cell-based complementation assay designed in this study can also help diagnose patients with potentially pathogenic variants in a very similar enzyme, MAN2A1.

N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts. Budhraja R, Saraswat M, De Graef D, Ranatunga W, Ramarajan MG, Mousa J, Kozicz T, Pandey A, Morava E.. J Inherit Metab Dis. 2022 Sep 14. doi: 10.1002/jimd.12557. Epub ahead of print. PMID: 36102038

NGLY1-CDDG (congenital disorder of deglycosylation) is a multisystemic, inherited condition caused by a mutation in the NGLY1 gene. Although the NGLY1 enzyme plays an essential role in the process of deglycosylation, the effects of NGLY1 deficiency on protein glycosylation are not yet understood. In this study, researchers explored the hypothesis that NGLY1 deficiency leads to accumulation of misfolded glycoproteins. Using glycoproteomics and proteomics methods, the team analyzed fibroblasts from four patients with NGLY1 deficiency carrying different variants in NGLY1. Results showed no significant accumulation of glycoproteins in the NGLY1-deficient fibroblasts. However, researchers found distinct changes in specific glycoproteins. As the first study of its kind, authors note that these findings highlight new insights for understanding NGLY1-CDDG.

Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions. Sosicka P, Ng BG, Pepi LE, Shajahan A, Wong M, Scott DA, Matsumoto K, Xia ZJ, Lebrilla CB, Haltiwanger RS, Azadi P, Freeze HH. J Cell Biol. 2022 Oct 3;221(10):e202205038. doi: 10.1083/jcb.202205038. Epub 2022 Sep 2. PMID: 36053214.

Congenital disorders of glycosylation (CDG) are a group of inherited metabolic disorders that affect a process called glycosylation. This process uses monosaccharides (simple sugars) from multiple sources to produce nucleotide sugars (activated forms of monosaccharides). Since these sources of monosaccharides are assumed to contribute to one similar pool, their individual contributions are often overlooked. In this study, researchers explored the hypothesis that fucose (a type of monosaccharide) exists in multiple, distinct pools. The team measured the contribution of fucose from different sources. Findings show that cells identify and select from different pools of fucose for the process of glycosylation. Authors also present new perspectives on monosaccharide metabolism, which may have other applications beyond glycosylation.

A new D-galactose treatment monitoring index for PGM1-CDG. Perales-Clemente E, Liedtke K, Studinski A, Radenkovic S, Gavrilov D, Oglesbee D, Matern D, Rinaldo P, Tortorelli S, Morava E, Raymond K. J Inherit Metab Dis. 2021 Sep;44(5):1263-1271. doi: 10.1002/jimd.12406. Epub 2021 Jun 22.

ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. Alsharhan H, He M, Edmondson AC, Daniel EJP, Chen J, Donald T, Bakhtiari S, Amor DJ, Jones EA, Vassallo G, Vincent M, Cogné B, Deb W, Werners AH, Jin SC, Bilguvar K, Christodoulou J, Webster RI, Yearwood KR, Ng BG, Freeze HH, Kruer MC, Li D, Raymond KM, Bhoj EJ, Sobering AK. J Inherit Metab Dis. 2021 Mar 18. doi: 10.1002/jimd.12378. Online ahead of print.

Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings. Wilson MP, Garanto A, Pinto E Vairo F, Ng BG, Ranatunga WK, Ventouratou M, Baerenfaenger M, Huijben K, Thiel C, Ashikov A, Keldermans L, Souche E, Vuillaumier-Barrot S, Dupré T, Michelakakis H, Fiumara A, Pitt J, White SM, Lim SC, Gallacher L, Peters H, Rymen D, Witters P, Ribes A, Morales-Romero B, Rodríguez-Palmero A, Ballhausen D, de Lonlay P, Barone R, Janssen MCH, Jaeken J, Freeze HH, Matthijs G, Morava E, Lefeber DJ. Am J Hum Genet. 2021 Nov 4;108(11):2130-2144. doi: 10.1016/j.ajhg.2021.09.012. Epub 2021 Oct 14. PMID: 34653363; PMCID: PMC8595932.

Congenital disorders of glycosylation (CDGs) are a group of rare diseases characterized by hypoglycosylation. The STT3A gene plays an essential role in protein N-glycosylation. In this study, researchers identified 16 individuals from nine families who have variants in STT3A, leading to an autosomal-dominant CDG. They describe the features of these individuals including variable skeletal anomalies, short stature, large head, muscle cramps, and in some, intellectual disability. The authors also present data to support a dominant form of STT3A-CDG that is unusual among type I CDGs.

Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation. Polla DL, Edmondson AC, Duvet S, March ME, Sousa AB, Lehman A; CAUSES Study, Niyazov D, van Dijk F, Demirdas S, van Slegtenhorst MA, Kievit AJA, Schulz C, Armstrong L, Bi X, Rader DJ, Izumi K, Zackai EH, de Franco E, Jorge P, Huffels SC, Hommersom M, Ellard S, Lefeber DJ, Santani A, Hand NJ, van Bokhoven H, He M, de Brouwer APM. Am J Hum Genet. 2021 Jul 1;108(7):1342-1349. doi: 10.1016/j.ajhg.2021.05.010. Epub 2021 Jun 17.

D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial. Witters P, Andersson H, Jaeken J, Tseng L, van Karnebeek CDM, Lefeber DJ, Cassiman D, Morava E. Orphanet J Rare Dis. 2021 Mar 20;16(1):138. doi: 10.1186/s13023-020-01609-z.

Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation. Radenkovic S, Fitzpatrick-Schmidt T, Byeon SK, Madugundu AK, Saraswat M, Lichty A, Wong SYW, McGee S, Kubiak K, Ligezka A, Ranatunga W, Zhang Y, Wood T, Friez MJ, Clarkson K, Pandey A, Jones JR, Morava E. Mol Genet Metab. 2021 Jan;132(1):27-37. doi: 10.1016/j.ymgme.2020.10.007. Epub 2020 Oct 17.

Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG. Alsharhan H, Ng BG, Daniel EJP, Friedman J, Pivnick EK, Al-Hashem A, Faqeih EA, Liu P, Engelhardt NM, Keller KN, Chen J, Mazzeo PA; University of Washington Center for Mendelian Genomics (UW-CMG), Rosenfeld JA, Bamshad MJ, Nickerson DA, Raymond KM, Freeze HH, He M, Edmondson AC, Lam C. J Inherit Metab Dis. 2021 Feb 13. doi: 10.1002/jimd.12367. Online ahead of print.

Genotype-Phenotype Correlations in PMM2-CDG. Vaes L, Rymen D, Cassiman D, Ligezka A, Vanhoutvin N, Quelhas D, Morava E, Witters P Genotype-Phenotype Correlations in PMM2-CDG . Genes (Basel). 2021 Oct 21;12(11):1658. doi: 10.3390/genes12111658. PMID: 34828263; PMCID: PMC8620515.

PMM2-CDG is a rare disease that causes hypoglycosylation of multiple proteins. Direct genotype-phenotype correlations are not yet identified. In this paper, researchers carried out a retrospective cohort study on 26 PMM2-CDG patients. They collected the identified genotype, as well as variables indicating the disease severity and patients' phenotype. By studying the phenotypic effects of patients' genotype, researchers gained a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base. They concluded that specific pathogenic variants (p.Pro113Leu and p.Phe119Leu) have a significantly higher total NPCRS disease severity score which indicates a more severe clinical outcome. The Nijmegen Paediatric CDG Rating Scale (NPCRS) is a tool to objectively follow the clinical disease progression in clinical disorders of glycosylation (CDG). Pathogenic variants affecting the folding or stabilization domain of the PMM2 enzyme protein have a significantly lower total NPCRS and thus the genetic results could provide a good prognostic clinical outcome.

Immune dysfunction in MGAT2-CDG: A clinical report and review of the literature. Poskanzer SA, Schultz MJ, Turgeon CT, Vidal-Folch N, Liedtke K, Oglesbee D, Gavrilov DK, Tortorelli S, Matern D, Rinaldo P, Bennett JT, Thies JM, Chang IJ, Beck AE, Raymond K, Allenspach EJ, Lam C. Am J Med Genet A. 2021 Jan;185(1):213-218. doi: 10.1002/ajmg.a.61914. Epub 2020 Oct 12.

Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder. Morava E, Schatz UA, Torring PM, Abbott MA, Baumann M, Brasch-Andersen C, Chevalier N, Dunkhase-Heinl U, Fleger M, Haack TB, Nelson S, Potelle S, Radenkovic S, Bommer GT, Van Schaftingen E, Veiga-da-Cunha M. Am J Hum Genet. 2021 Jun 3;108(6):1151-1160. doi: 10.1016/j.ajhg.2021.04.017. Epub 2021 May 11.

Study authors describe a genetic syndrome due to PGM2L1 deficiency. The gene PGM2L1 is highly expressed in the brain. They report the identification of four children with PGM2L1 deficiency sharing a largely neurological phenotype. All four children had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Study authors concluded that, while analyses indicated PGM2L1 deficiency does not appear to be a glycosylation defect, the discovery of this developmental disorder highlights the importance of glucose-1,6-biophosphate in the brain.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management. Altassan R, Radenkovic S, Edmondson AC, Barone R, Brasil S, Cechova A, Coman D, Donoghue S, Falkenstein K, Ferreira V, Ferreira C, Fiumara A, Francisco R, Freeze H, Grunewald S, Honzik T, Jaeken J, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-da-Silva D, Pascoal C, Quelhas D, Raymond KM, Rymen D, Seroczynska M, Serrano M, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Voermans N, Witters P, Morava E. J Inherit Metab Dis. 2021 Jan;44(1):148-163. doi: 10.1002/jimd.12286. Epub 2020 Sep 15.

Is X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy a congenital disorder of glycosylation?. Berry GT, Freeze HH, Morava E. Epilepsia. 2021 Feb;62(2):335-336. doi: 10.1111/epi.16817. Epub 2021 Feb 11.

Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up. Starosta RT, Boyer S, Tahata S, Raymond K, Lee HE, Wolfe LA, Lam C, Edmondson AC, Schwartz IVD, Morava E. Orphanet J Rare Dis. 2021 Jan 7;16(1):20. doi: 10.1186/s13023-020-01630-2.

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?. Čechová A, Honzík T, Edmondson AC, Ficicioglu C, Serrano M, Barone R, De Lonlay P, Schiff M, Witters P, Lam C, Patterson M, Janssen MCH, Correia J, Quelhas D, Sykut-Cegielska J, Plotkin H, Morava E, Sarafoglou K. Mol Genet Metab. 2021 Aug;133(4):397-399. doi: 10.1016/j.ymgme.2021.06.003. Epub 2021 Jun 11.

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications. Ligezka AN, Radenkovic S, Saraswat M, Garapati K, Ranatunga W, Krzysciak W, Yanaihara H, Preston G, Brucker W, McGovern RM, Reid JM, Cassiman D, Muthusamy K, Johnsen C, Mercimek-Andrews S, Larson A, Lam C, Edmondson AC, Ghesquière B, Witters P, Raymond K, Oglesbee D, Pandey A, Perlstein EO, Kozicz T, Morava E. Ann Neurol. 2021 Dec;90(6):887-900. doi: 10.1002/ana.26245. Epub 2021 Oct 26.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study. Witters P, Edmondson AC, Lam C, Johnsen C, Patterson MC, Raymond KM, He M, Freeze HH, Morava E. Orphanet J Rare Dis. 2021 Feb 25;16(1):102. doi: 10.1186/s13023-021-01751-2.

Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy. Del Caño-Ochoa F, Ng BG, Abedalthagafi M, Almannai M, Cohn RD, Costain G, Elpeleg O, Houlden H, Karimiani EG, Liu P, Manzini MC, Maroofian R, Muriello M, Al-Otaibi A, Patel H, Shimon E, Sutton VR, Toosi MB, Wolfe LA, Rosenfeld JA, Freeze HH, Ramón-Maiques S. Genet Med. 2020 Oct;22(10):1598-1605. doi: 10.1038/s41436-020-0833-2. Epub 2020 May 28.

Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG. Witters P, Tahata S, Barone R, Õunap K, Salvarinova R, Grønborg S, Hoganson G, Scaglia F, Lewis AM, Mori M, Sykut-Cegielska J, Edmondson A, He M, Morava E. Genet Med. 2020 Jun;22(6):1102-1107. doi: 10.1038/s41436-020-0767-8. Epub 2020 Feb 27.

Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation. Čechová A, Altassan R, Borgel D, Bruneel A, Correia J, Girard M, Harroche A, Kiec-Wilk B, Mohnike K, Pascreau T, Pawliński Ł, Radenkovic S, Vuillaumier-Barrot S, Aldamiz-Echevarria L, Couce ML, Martins EG, Quelhas D, Morava E, de Lonlay P, Witters P, Honzík T. J Inherit Metab Dis. 2020 Jul;43(4):671-693. doi: 10.1002/jimd.12241. Epub 2020 Apr 21.

Defining a new immune deficiency syndrome: MAN2B2-CDG. Verheijen J, Wong SY, Rowe JH, Raymond K, Stoddard J, Delmonte OM, Bosticardo M, Dobbs K, Niemela J, Calzoni E, Pai SY, Choi U, Yamazaki Y, Comeau AM, Janssen E, Henderson L, Hazen M, Berry G, Rosenzweig SD, Aldhekri HH, He M, Notarangelo LD, Morava E. J Allergy Clin Immunol. 2020 Mar;145(3):1008-1011. doi: 10.1016/j.jaci.2019.11.016. Epub 2019 Nov 24.

Fetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype. Ferrer A, Starosta RT, Ranatunga W, Ungar D, Kozicz T, Klee E, Rust LM, Wick M, Morava E. Mol Genet Metab. 2020 Dec;131(4):424-429. doi: 10.1016/j.ymgme.2020.11.003. Epub 2020 Nov 7.

Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Zilmer M, Edmondson AC, Khetarpal SA, Alesi V, Zaki MS, Rostasy K, Madsen CG, Lepri FR, Sinibaldi L, Cusmai R, Novelli A, Issa MY, Fenger CD, Abou Jamra R, Reutter H, Briuglia S, Agolini E, Hansen L, Petäjä-Repo UE, Hintze J, Raymond KM, Liedtke K, Stanley V, Musaev D, Gleeson JG, Vitali C, O'Brien WT, Gardella E, Rubboli G, Rader DJ, Schjoldager KT, Møller RS. Brain. 2020 Apr 1;143(4):1114-1126. doi: 10.1093/brain/awaa063.

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions. Ng BG, Eklund EA, Shiryaev SA, Dong YY, Abbott MA, Asteggiano C, Bamshad MJ, Barr E, Bernstein JA, Chelakkadan S, Christodoulou J, Chung WK, Ciliberto MA, Cousin J, Gardiner F, Ghosh S, Graf WD, Grunewald S, Hammond K, Hauser NS, Hoganson GE, Houck KM, Kohler JN, Morava E, Larson AA, Liu P, Madathil S, McCormack C, Meeks NJL, Miller R, Monaghan KG, Nickerson DA, Palculict TB, Papazoglu GM, Pletcher BA, Scheffer IE, Schenone AB, Schnur RE, Si Y, Rowe LJ, Serrano Russi AH, Russo RS, Thabet F, Tuite A, Villanueva MM, Wang RY, Webster RI, Wilson D, Zalan A; Undiagnosed Diseases Network, University of Washington Center for Mendelian Genomics (UW-CMG), Wolfe LA, Rosenfeld JA, Rhodes L, Freeze HH. J Inherit Metab Dis. 2020 Nov;43(6):1333-1348. doi: 10.1002/jimd.12290. Epub 2020 Aug 5.

Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature. Qian Z, Van den Eynde J, Heymans S, Mertens L, Morava E. JIMD Rep. 2020 Aug 19;56(1):27-33. doi: 10.1002/jmd2.12160. eCollection 2020 Nov.