Seizures in childhood cerebral adrenoleukodystrophy

Abstract

Leukodystrophies are a group of genetic conditions causing white matter degeneration in the brain. X-linked adrenal leukodystrophy (X-ALD) is the most common leukodystrophy. Approximately one-third of young males with X-ALD develop severe brain disease in childhood, which is known as childhood cerebral X-ALD (CCALD). Young males with CCALD can experience seizures that lead to diagnosis or after the disease is diagnosed and has progressed.

In this study we aimed to describe how often seizures occur in patients with CCALD and how seizures relate to disease severity. We included patients seen at two leukodystrophy centers (Massachusetts General Hospital and Nationwide Children's Hospital) between 2008 and 2024. Ours is the largest study of young males with CCALD and seizures and provides new information regarding when seizures occur in CCALD.

We found that X-ALD without brain disease does not increase the risk of seizures. Seizure severity increases as brain disease progresses. Seizure severity correlated with worse functional status and magnetic resonance imaging/Loes score; no seizures occurred with Loes scores less than 6. This is important because treatment with stem cell transplant or gene therapy is especially effective for Loes scores less than or equal to 9.

Of the 86 young males with CCALD in our study, 25 (29%) experienced seizures. Of these 25, 22 were diagnosed with CCALD after seizures started, and 10 of these were diagnosed directly as a result of their seizure(s). Electroencephalogram in patients with CCALD with seizures was more likely to show diffuse slowing than epileptiform discharges (73.3% vs 26.7% respectively), making clinical symptoms the most important factor in diagnosing seizures or epilepsy in these patients. All seizures in CCALD in our study were motor seizures. But staring spells should still be discussed with neurologists as they could be a result of inattention related to processing disorders or a sign of seizures.