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Globus pallidus degeneration and clinicopathological features of Huntington disease
Author(s) -
SinghBains Malvindar K.,
Tippett Lynette J.,
Hogg Virginia M.,
Synek Beth J.,
Roxburgh Richard H.,
Waldvogel Henry J.,
Faull Richard L. M.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24694
Subject(s) - globus pallidus , neurodegeneration , huntington's disease , atrophy , neuroscience , psychology , stereology , putamen , white matter , degenerative disease , pathology , soma , chorea , basal ganglia , medicine , central nervous system disease , disease , magnetic resonance imaging , central nervous system , radiology
Objective Numerous studies have focused on striatal neurodegeneration in Huntington disease (HD). In comparison, the globus pallidus (GP), a main striatal output nucleus, has received less focus in HD research. This study characterizes the pattern of neurodegeneration in 3 subdivisions of the human GP, and its relation to clinical symptomatology. Methods Stereology was used to measure regional atrophy, neuronal loss, and soma neuronal atrophy in 3 components of the GP—the external segment (GPe), internal segment (GPi), and ventral pallidum (VP)—in 8 HD cases compared with 7 matched control cases. The findings in the HD patients were compared with HD striatal neuropathological grade, and symptom scores of motor impairment, chorea, cognition, and mood. Results Relative to controls, in the HD patients the GPe showed a 54% overall volume decline, 60% neuron loss, and 34% reduced soma volume. Similarly, the VP was reduced in volume by 31%, with 48% neuron loss and 64% reduced soma volume. In contrast, the GPi was less affected, with a 38% reduction in overall volume only. The extent of GP neurodegeneration correlated with increasing striatal neuropathological grade. Decreasing GPe and VP volumes were associated with poorer cognition and increasing motor impairments, but not chorea. In contrast, decreasing GPi volumes were associated with decreasing levels of irritability. Interpretation The HD gene mutation produces variable degrees of GP segment degeneration, highlighting the differential vulnerability of striato‐GP target projections. The relationship established between clinical symptom scores and pallidal degeneration provides a novel contribution to understanding the clinicopathological associations in HD. Ann Neurol 2016;80:185–201