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Washington University Experience | NEURODEGENERATION | Huntington Disease | 18C2 (Case 18) N2 1C2 H&E 40X
Immunohistochemistry with an anti-polyglutamine antibody (1C2) highlights intranuclear inclusions within many striatal neurons and a few globus pallidus neurons, and also shows granular nuclear and paranuclear reactivity. (1C2 IHC) ---- Not shown: H&E stained sections of the frontal, occipital, and cingulate cortices show mild neuronal loss and associated mild gliosis. Alzheimer type II astrocytosis is widespread. Bielschowsky silver staining reveals rare amyloid plaques in the anterior cingulate and parahippocampal gyri, without convincing neuritic plaques or neurofibrillary tangles. ---- Neuro Diagnosis Comment: Postmortem examination finds macroscopic atrophy, neuronal loss and gliosis within the striatum (moderate) and cortex (mild), and neuronal polyglutamine-bearing inclusions within the basal ganglia. These gross and microscopic features support the diagnosis of Huntington disease; the severity of the findings in this case are consistent with Grade 2 (range 0-to-4; normal-to-severe) in the Huntington's Disease Neuropathological Grading Scheme of Vonsattel et al. (PMID: 9596408)]. In addition to the features of Huntington disease, this case demonstrates very rare amyloid plaques in the neocortex, without neuritic plaques or neurofibrillary tangles. Technically, by the most recent NIA-AA criteria, this finding supports a diagnosis of ‘Alzheimer disease neuropathologic change’ (A1B0C0), but is inconsistent with any significant contribution to the patient’s cognitive impairment, and does not support a neuropathological diagnosis of Alzheimer disease by Khachaturian, CERAD, NIA-Reagan or NIA-AA schemes. This case shows evidence of widespread Alzheimer type II astrocytes, reflecting a cytomorphological change that is consistent with hyperammonemia (and is unrelated to Alzheimer disease). The etiology of this finding in this case is unclear.
