Background/Purpose: Juvenile neuronal ceroid lipofuscinosis or CLN3 disease is a pediatric neurodegenerative
disorder characterized by visual loss, epilepsy, and psychomotor deterioration. No
approved treatment for CLN3 is currently available. Patients may present with significant
phenotypic variability, which complicates the evaluation of potential therapies. Biomarkers
as surrogates to measure disease progression are needed to assess the efficacy of
experimental therapies. This study evaluates EEG findings as a potential early biomarker
for CLN3 disease.
Methods: A total of 7 CLN3 patients with two annual EEG recordings obtained prior to the first
onset of seizures were enrolled in this study. Their EEGs were retrospectively analyzed,
and findings correlated with the patients’ respective juvenile NCL score (JNCL score)
at the time. EEGs were screened for slow background activity, intermittent slowing,
absence of anterior-posterior gradient, absence of Berger's sign, and epileptiform
discharges. Results were statistically analyzed by rating the presence of each item
as 1 point and grading the frequency of epileptiform discharges from 1 (mild) to 3
(severe).
Results: Median patients’ age at EEG recordings was 8.5 years. All patients already suffered
from visual loss, three patients had mild speech difficulties, and two patients had
mild intellectual impairment. Per the inclusion criteria, no patient had an onset
of seizures yet. EEGs of all patients showed abnormal findings, most commonly a lack
of anterior-posterior gradient and intermittent slow theta activity. After 1 year
of follow-up, EEG abnormalities significantly increased (p = 0.0008), especially slow background activity and intermittent delta activity, still
without any reported seizures in the selected CLN3 cases. No correlation was found
between JNCL score and EEG abnormalities.
Conclusion: EEG changes in CLN3 disease are present already prior to the onset of seizures and
can serve as a potential early biomarker to monitor disease progression.
