Search

Two aspects of the neuropathology of early Huntington disease (HD) are examined. Neurons of the neostriatum are counted to determine relative loss in striosomes versus matrix at early stages, including for the first time in preclinical cases. An immunohistochemical procedure is described that tentatively distinguishes early HD from HD mimic disorders in postmortem brains. Counts of striatal projection neurons (SPNs) in striosomes defined by calbindin immunohistochemistry versus counts in the surrounding matrix are reported for 8 Vonsattel grade 0 (including 5 premanifest), 8 grade 1, 2 grade 2 HD, and for 8 control postmortem brains. Mean counts of striosome and matrix SPNs were significantly lower in premanifest grade 0 versus controls, with striosome counts significantly lower than matrix. In 8 grade 1 and 2 grade 2 brains, no striosomes with higher SPN counts than in the surrounding matrix were observed. Comparing dorsal versus ventral neostriatum, SPNs in dorsal striosomes and matrix declined more than ventral, making clear the importance of the dorsoventral site of tissue selection for research studies. A characteristic pattern of expanded polyglutamine-immunopositive inclusions was seen in all HD cases. Inclusions were always present in some SPNs and some pontine nucleus neurons and were absent in Purkinje cells, which showed no obvious cell loss.

Abstract: Detailed neuropathologic examination was performed on a 47.5-year-old man with an unusual adult-onset dementing illness. His initial symptoms were those of depression, memory loss, and personality change. He developed progressive cognitive decline with prominent psychiatric symptoms. Seizures began approximately 11 months prior to death and he died 5.5 years after onset of symptoms. Pathologic examination of the brain at autopsy revealed organizing necrosis of the hippocampi, felt to be the result of his seizures. More significant was the finding of widespread microscopic nodular cortical dysplasia. The dysplastic nodules were composed of clusters of abnormal cells with enlarged, pleomorphic, vesicular nuclei, many of which contained nucleoli and had ballooned cytoplasm. There were no mitoses. Cortical dysplasia is most commonly associated with childhood-onset seizures. It has not, to our knowledge, been reported as a cause of dementia. Whether or not the dysplasia was the basis of the patient’s dementia is difficult to say with certainty, but we discuss possible pathoetiologic mechanisms of dementia due to cortical dysplasia.