An adult case of leukoencephalopathy with intracranial calcifications and cysts

Leukoencephalopathies are generally volume-losing processes, although several variants, such as Alexander disease and Canavan disease, may cause megalencephaly. Leukoencephalopathies that generate severe edema, are mass producing, and mimic neoplasms are rare. In 1996, a new cerebral disorder was described in three unrelated children who had onset in early infancy to adolescence of slowed cognitive performance, seizures, and extrapyramidal, cerebellar, and pyramidal signs.(1) Neuroimaging studies demonstrated a striking triad of findings: progressive calcifications in the basal ganglia, cerebellar nuclei, and deep white matter; diffuse abnormal signal on MRI in the white matter; and large, space-occupying parenchymal brain cysts generating mass effect. 1 Neuropathologic examination of surgically resected material from one patient revealed "angiomatous-like rearrangements of the microvessels..." that "suggest a constitutional, diffuse cerebral microangiopathy..."(1) Profuse numbers of Rosenthal fibers were identified around the "pseudoangiomatous" blood vessels. The disease did not fit descriptions for any previously known phakomatosis or dysgenetic syndrome. A descriptive name was given to this new syndrome, which was initially thought to be a leukodystrophy. Three more patients were subsequently reported, all of whom also had onset in childhood between the ages 9 and 14 years.(2) More extensive neuroimaging studies suggested that the white matter abnormalities were due to "increased water content rather than a demyelinating process," consistent with a leukoencephalopathy, rather than a leukodystrophy. We now present an adult patient with clinical and pathologic findings nearly identical to these six previously reported children. Because this disorder seemed somewhat similar to adult-onset Alexander disease and was associated with apparent microangiopathy, we also searched for polymorphisms in glial fibrillary acidic protein (GFAP) and cerebral cavernous malformation (CCM) genes.