Neuropathological Classification of Huntingtonʼs Disease

TLDR

Postmortem analysis of 163 Huntington’s disease cases revealed marked variation in striatal neuropathology. The authors developed a five‑grade (0–4) system based on macroscopic and microscopic criteria to quantify striatal pathology severity. The grading system correlated with clinical disability, with grade 0 showing no pathology, grade 1 limited microscopic changes and 50 % neuron loss, and grade 4 marked by 95 % neuron loss and astrocytosis, indicating that early disease affects medial caudate and dorsal putamen while later stages involve widespread astrocytic proliferation.

Abstract

In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0–4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2–4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1–2, these regions would reflect early cellular and biochemical changes in HD.