2023 American Academy of Neurology Abstract Website

Objective:

To describe seizure burden in Alexander disease (AxD)

Background:

Seizures in AxD contribute to both burden of disease and neurologic deterioration. Patients with provoked seizures at presentation are often not initiated on anti-seizure medication (ASM) in the setting of delayed recognition of AxD. Improved understanding of seizure burden over time in AxD may aid in diagnosis, anticipatory guidance, and management.

Design/Methods:

Medical records and structured interviews of AxD participants in a natural history study (1/2016–9/2022) were reviewed for occurrence of seizures and presence of provoking factors (illnesses with or without fever, ingestions, head trauma). Descriptive statistics were used to quantify seizure burden over time.

Results:

Of 81 patients with a median age at last follow-up of 10.1 years (IQR11.3), 46 (57%) had ≥1 seizure. First seizure occurred at a mean age of 29.9 months (SD45.6) overall, with no significant difference between patients whose first seizure was provoked vs unprovoked (22.4 months, SD18.0 vs 45.3 months, SD75.0, p=0.3). Overall, 96% of patients had additional seizures; of these 87% had multiple unprovoked seizures. Only 9% had exclusively provoked seizures. Excluding two outliers, first seizure preceded the diagnosis of AxD by a mean of 20.8 months (SD41.5). EEG abnormalities (generalized or focal slowing, epileptiform discharges) were similarly common prior to diagnosis. Of these patients, 63% had their first seizure, provoked or unprovoked, prior to 2 years of age. At this same age 94% of the cohort had already demonstrated developmental delay.

Conclusions:

Provoked seizures are common in patients with AxD, often occurring concurrently with developmental delays and prior to the diagnosis of underlying leukodystrophy. Provoked seizures in the setting of developmental delays, even when mild, should prompt additional evaluation. Given high incidence of unprovoked seizures over time as well as associated risk of neurologic regression, provoked seizures in patients with AxD should prompt consideration of ASM.