Neurocognitive decline in Alexander disease

Alexander disease is a neurological condition associated with prominent white matter deterioration. Its rarity and relatively rapid disease course have provided limited understanding into the cognitive effects of the illness. We report the serial neuropsychological findings of a 21-year-old with normal development and no medical history until age 9, when he experienced refractory sinusitis, stabbing headaches with vertigo, disorientation, and decline in academic and social settings. An MRI scan of the brain found acute demyelinating encephalomyelitis, with a preponderance of white matter degeneration in the bilateral frontal lobes. Interval MRIs showed continued degeneration. Confirmation of Alexander disease was made at age 20 through genetic testing. Four evaluations completed from ages 15 to 21 showed impairment across all cognitive domains. Cognitive deficits were most prominent in new learning and recent memory, executive functions, and fine motor dexterity, and less apparent in information processing and visual scanning speed. These results present evidence for a particular cognitive pattern in individuals with juvenile-onset Alexander disease. Despite extensive white matter degeneration in the frontal lobes, certain tasks associated with frontal lobe integrity were relatively preserved. Further research into the neuropsychological presentation of the subtypes of Alexander disease can enhance diagnostic clarity and treatment planning.