Alexander Disease Diagnosed in an Obstetrics Patient: A Case Report and Review of the Literature

Alexander disease (AxD) is a rare autosomal dominant leukodystrophy due to pathogenic variants in glial fibrillary acidic protein ( GFAP) . Adult-onset AxD type II presents with heterogeneous neurologic and neuropsychiatric symptoms. We report a unique case diagnosed in the postpartum period that mimicked posterior reversible encephalopathy syndrome (PRES). A 33-year-old gravida 2 para 1 at 36 weeks gestation presented with 10 days of progressive restlessness, delusions, insomnia, dysarthria, weight loss with inability to feed herself, and urinary/fecal incontinence. She underwent induction of labor due to concern for severe pre-eclampsia (elevated liver enzymes and creatine kinase, elevated blood pressure), received magnesium sulfate, and required emergent cesarean delivery for non-reassuring fetal status. However, her symptoms persisted postpartum. Brain magnetic resonance imaging revealed extensive bifrontal, periventricular, and pontine non-enhancing hyperintensities. Cerebrospinal fluid analysis was normal including negative infectious, autoimmune, and paraneoplastic studies. Electroencephalography showed mild background slowing but no epileptiform activity. Empiric methylprednisolone and acyclovir had limited effects. Given the imaging findings, a leukodystrophy panel was ordered, which identified a heterozygous pathogenic GFAP variant (Arg79Leu), confirming a diagnosis of AxD type II. She improved with rehabilitation, with mild residual dysarthria at the 2-month follow-up. This is the first case report to describe an onset of AxD in the peripartum period. In peripartum patients with neurological symptoms whose course and MRI findings are atypical for PRES or other more common disorders, adult-onset neurogenetic disorders such as AxD should be considered. This diagnosis has important reproductive implications and warrants genetic counseling.