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Studies on Brain Biopsies of Patients with Huntington's Chorea

Isabel Tellez-Nagel M.D., Anne B. Johnson M.D., Robert D. Terry M.D.
DOI: http://dx.doi.org/10.1097/00005072-197404000-00008 308-332 First published online: 1 April 1974

Abstract

Frontal cortex brain biopsies of four patients with Huntington's chorea were studied by histological, histochemical, and electron microscopic methods. The changes observed were evaluated in regard to the age of the patients and stage of the disease process. One of the most outstanding features was the large and generalized accumulation of lipofuscin in neurons and glial cells. This increase in lipofusein was detectable in paraffin sections, but was most striking in frozen sections examined for fluorescence and in acid-phosphatase preparations. Preliminary extractions of lipofusein demonstrated a higher content of the pigment in Huntington's chorea than in age-matched control brains. The glial lipofusein was associated with very high acid-phosphatase activity, which was found to be localized in the dense component of the granule.

At the fine structural level, neurons evidenced several abnormalities including proliferation of Golgi membranes and Golgi-associated vesicles, disorganization of the rough endoplasmic reticulum with shedding of membrane-bound ribosomes; abnormally dense mitochondria with sparse cristae, occasionally containing crystalline fibrillar arrays within the matrix; abnormal nuclei with chromatin condensed in numerous dense granules and with increased porosity of the nuclear membrane. Increased numbers of microglial cells in the neuropil and ear vessels, often containing remnants of neuronal cytoplasm with lipofuscin, suggest that active removal of irreversibly damaged neurons by phagocytosis is taking place. Astrocytes were proliferated and hypertrophic with a fair increase in glial filaments. They contained large quantities of lipopigment granules in their cell bodies and their processes. Neuronal death and axonal and synaptic degeneration account for the atrophy of the frontal cortex. The abnormalities found were present in all cases, and were of increasing severity with more prolonged disease.