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

  • Ruzica Kravljanac
    Correspondence
    Corresponding author. University of Belgrade, Faculty of Medicine Institute for Mother and Child Healthcare of Serbia Head of Neurology Department, Pediatric Clinic, Str Radoje Dakić 6-8, 11070, Belgrade, Serbia.
    Affiliations
    University of Belgrade, Faculty of Medicine, Serbia

    Institute for Mother and Child Healthcare of Serbia, Belgrade, Serbia
    Search for articles by this author
  • Biljana Vucetic Tadic
    Affiliations
    University of Belgrade, Faculty of Medicine, Serbia

    Institute for Mother and Child Healthcare of Serbia, Belgrade, Serbia
    Search for articles by this author

      Highlights

      • Diagnosis delay is longer in CLN2 patients with the first provoked seizure.
      • Red flags are focal, atonic, prolonged, onset >3 years of the first provoked seizures.
      • Provoked seizures associated with language and behavior problems requires caution.

      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.

      Keywords

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