Huntington's disease like‐2 neuropathology

Abstract Huntington's disease like‐2 (HDL‐2) neurodegeneration is a recently described autosomal dominant disorder with features similar to Huntington's disease (HD). Only one case report has described neuropathology from an affected patient. We describe the clinical presentation and illustrate the pathology in two additional molecularly confirmed patients, compare these with the previously published case, and contrast them with HD. We examined two patients with HDL‐2. Their charts were reviewed, their brains were examined using standard neuropathology techniques, including immunoperoxidase stains, and their diagnoses were confirmed with a PCR‐based assay for repeat length. The first patient presented with obsessive suspiciousness, while the second had depression and decreased visual acuity. Both patients developed increased tone and cogwheel rigidity, but neither developed choreoathetosis. Extensive degeneration affected the caudate nucleus and putamen, especially dorsally and laterally. In addition, the first patient showed lateral temporal, lateral frontal, and orbitofrontal cortical atrophy, while the second patient displayed marked degeneration in the occipital and parietal cortices. Neither patient showed significant changes in the cerebellum or brainstem. Both cases had ubiquitin‐immunoreactive neuronal intranuclear inclusions (NII). The patients with of HDL‐2 reviewed here were remarkable for significant frontal inhibition with parkinsonism, a lack of choreiform movements, and African ancestry. Pathologically, HDL‐2 is similar to HD in its effect on the neostriatum but may differ, at least in some cases, in its degree of focal cortical involvement, including the occipital lobe.