Seizure phenotype in CLN3 disease and its relation to other neurologic outcome measures
| Autor: | Gina Norato, William H. Theodore, Audrey Thurm, An N Dang Do, Sara K. Inati, Eva H. Baker, Myriam Abdennadher, Bibiana Bielekova, Ariane Soldatos, Ruturaj R. Masvekar, Luca Bartolini, Forbes D. Porter |
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| Rok vydání: | 2021 |
| Předmět: |
Male
In vivo magnetic resonance spectroscopy medicine.medical_specialty Batten disease Adolescent Electroencephalography Severity of Illness Index Gastroenterology Cohort Studies 03 medical and health sciences Neuronal Ceroid-Lipofuscinoses Seizures Internal medicine Genetics medicine Humans Tonic (music) Child Genetics (clinical) 030304 developmental biology 0303 health sciences Membrane Glycoproteins medicine.diagnostic_test business.industry 030305 genetics & heredity Glutamate receptor medicine.disease Glutamine Phenotype CLN3 Child Preschool Cohort Female business Biomarkers Molecular Chaperones |
| Zdroj: | Journal of Inherited Metabolic Disease. 44:1013-1020 |
| ISSN: | 1573-2665 0141-8955 |
| Popis: | CLN3 disease is a pediatric neurodegenerative condition wherein seizures are common. The most common disease-causing variant is an ~1-kb 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-3), glutamate+glutamine+GABA and N-acetylaspartate+N-acetylaspartyl glutamate (MR spectroscopy), and CSF neurofilament light chain (NEFL) levels. In 20 participants, median age was 10.7 years (IQR = 7.8). Eighteen completed baseline EEG; 12 had a 1-year follow-up. Seizures were reported in 14 (8 1-kb deletion homozygotes), with median age at onset of 10.0 (IQR = 6.8). Epileptiform discharges were noted in 15 (9 homozygotes). Bilateral tonic clonic (n = 11) and nonmotor seizures (n = 7) were most common. UBDRS seizure score correlated with age (rp = 0.50; [0.08,0.77]; P = .02), UBDRS capability (rp = -0.57; [-0.81,-0.17]; P = .009) and ABC (rp = -0.66; [-0.85,-0.31]; P = .001) scores, glutamate+glutamine+GABA (rp = -0.54; [-0.80,-0.11]; P = .02) and N-acetylaspartate+N-acetylaspartyl glutamate (rp = -0.54; [-0.80,-0.11]; P = .02), and CSF NEFL (rp = 0.65; [0.29,0.85]; P = .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 years 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. |
| Databáze: | OpenAIRE |
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