{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T20:46:47Z","timestamp":1775249207365,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["1ZICMH002961"],"award-info":[{"award-number":["1ZICMH002961"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CLN3 disease is a pediatric neurodegenerative condition wherein seizures are common. The most common disease\u2010causing variant is an ~1\u2010kb deletion in CLN3. We investigated seizure phenotype in relation to genotype and to adaptive behavior, MR spectroscopy and CSF biochemical markers in a CLN3 cohort. We performed seizure phenotyping using clinical history, EEG, and the Unified Batten Disease Rating Scale (UBDRS) seizure score. We assessed correlations of seizure severity with disease severity (UBDRS capability), adaptive behavior composite score (ABC; Vineland\u20103), glutamate+glutamine+GABA and N\u2010acetylaspartate+N\u2010acetylaspartyl glutamate (MR spectroscopy), and CSF neurofilament light chain (NEFL) levels. In 20 participants, median age was 10.7\u2009years (IQR\u00a0=\u00a07.8). Eighteen completed baseline EEG; 12 had a 1\u2010year follow\u2010up. Seizures were reported in 14 (8 1\u2010kb deletion homozygotes), with median age at onset of 10.0 (IQR\u00a0=\u00a06.8). Epileptiform discharges were noted in 15 (9 homozygotes). Bilateral tonic clonic (n\u00a0=\u00a011) and nonmotor seizures (n\u00a0=\u00a07) were most common. UBDRS seizure score correlated with age (rp\u00a0=\u00a00.50; [0.08,0.77]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02), UBDRS capability (rp\u00a0=\u00a0\u22120.57; [\u22120.81,\u22120.17]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.009) and ABC (rp\u00a0=\u00a0\u22120.66; [\u22120.85,\u22120.31]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) scores, glutamate+glutamine+GABA (rp\u00a0=\u00a0\u22120.54; [\u22120.80,\u22120.11]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02) and N\u2010acetylaspartate+N\u2010acetylaspartyl glutamate (rp\u00a0=\u00a0\u22120.54; [\u22120.80,\u22120.11]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02), and CSF NEFL (rp\u00a0=\u00a00.65; [0.29,0.85]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.002) levels. After controlling for age, correlations with ABC and CSF NEFL remained significant. In our CLN3 cohort, seizures and epileptiform discharges were frequent and often started by age 10\u2009years without significant difference between genotypes. ABC and CSF NEFL correlate with UBDRS seizure score, reflecting the role of seizures in the neurodegenerative process. Longitudinal evaluations in a larger cohort are needed to confirm these findings.<\/jats:p>","DOI":"10.1002\/jimd.12366","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T10:56:12Z","timestamp":1612695372000},"page":"1013-1020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Seizure phenotype in <scp>CLN3<\/scp> disease and its relation to other neurologic outcome measures"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-2560","authenticated-orcid":false,"given":"Myriam","family":"Abdennadher","sequence":"first","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"},{"name":"Department of Neurology, Boston Medical Center Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Inati","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariane","family":"Soldatos","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Norato","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva H.","family":"Baker","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences Department Clinical Center, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Thurm","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Bartolini","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"},{"name":"Division of Pediatric Neurology Hasbro Children's Hospital; The Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruturaj","family":"Masvekar","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Theodore","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibiana","family":"Bielekova","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An N.","family":"Dang Do","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90274-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210110801"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2016.0844"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420428"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/DNND.S111967"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000169019.41332.8a"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb04608.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12634"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.02.020"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000077"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000091"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100720070045"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2000.0458"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100720070044"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009454"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318237f649"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13670"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/21646821.2016.1245527"},{"key":"e_1_2_11_20_1","volume-title":"Vineland Adaptive Behavior Scales\u2013Third Edition (Vineland\u20103)","year":"2016"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.222"},{"issue":"2","key":"e_1_2_11_22_1","first-page":"313","article-title":"Utility of magnetic resonance spectroscopic imaging for human epilepsy","volume":"5","author":"Pan JW","year":"2015","journal-title":"Quant Imaging Med Surg"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01035-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01698-3"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9421-6"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.11.164"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291557.62706.d3"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.11.017"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb00226.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.07.033"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.07.043"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T15:50:09Z","timestamp":1692978609000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,15]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/jimd.12366"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12366","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,15]]},"assertion":[{"value":"2020-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}