Inflammatory neuropathology of infantile Alexander disease: A case report.

BACKGROUND: Alexander disease (AxD) is a rare fatal leukodystrophy caused by a dominant missense mutation in the glial fibrillary acidic protein. In a mouse model of AxD, the pathological astrocyte causes a pronounced immune response. The inflammatory environment in the brain might play an important role in the neuronal dysfunction of AxD. CASE: A 3-month-old girl diagnosed with infantile AxD presented with severe intractable seizures and a deteriorated neurological state. Steroid pulse therapy was effective at preventing the epileptic activity and progressive white matter abnormalities on magnetic resonance images, but the effect was temporary. Levels of interleukin (IL)-6, IL-8, and macrophage chemotactic protein 1 (MCP-1) in the cerebrospinal fluid were high at onset and reduced transiently after steroid pulse therapy. DISCUSSION: These results suggest that inflammatory responses of astrocyte and microglia can contribute to the neuropathology of AxD. Robust immunomodulation that targets activated astrocytes and microglia may be a novel therapeutic strategy to improve neurological prognosis in AxD.