Provoked seizures at the onset of progressive disease contribute to diagnosis delay - A tertiary center experience in a cohort of 22 children with CLN2.

ABSTRACT

PURPOSE: The evaluation of epilepsy features and factors with impact to diagnosis delay in children with CLN2. METHOD: The study included children with CLN2 treated from 2000 to 2020. Diagnosis was confirmed by TPP1 deficiency and/or TPP1 gene mutation or pathognomonic electron microscopy findings. The seizure features were evaluated the age of onset, provocation, semiology and EEG. The disease severity was assessed by CLN2 Clinical Rating Scale (CLN2-CRS). Statistical analysis included T test, chi-square test, Wilcoxon-Mann-Whitney test, using SPSS statistics 25. RESULT: The study included 22 children with CLN2. Seizures were experienced by all cases at the early stage of disease, preceded by language delay in 18, and behavior problems in 14 pts. The first seizure was provoked in 9 children at mean age of 33.8 ± 4.6 months, and unprovoked in 13 at mean age of 34.6 ± 2.7 months. In patients with provoked first seizure, the average period from the first seizure to diagnosis was longer (35.1 months), with lower CLN2-CRS, then in those with unprovoked (23.8 months) first seizures (p < 0.008). Initial seizures were generalized tonic-clonic (Pampiglione and Harden, 1973 Feb) [8], atonic (Pampiglione and Harden, 1973 Feb) [8], and focal (Beltrán et al., 2018 Aug) [4], with recurrence within two months. With progression, the patients experienced multiple seizure types, and 1/3 suffered status epilepticus. CONCLUSIONS: Provoked seizures at the onset of CLN2 have impact to diagnosis delay. The red flags are preceding language delay and behavior problems, later FS onset comparing to the typical age, atonic, focal and long-lasting seizure, and recurrence of seizures within two months.