Globus pallidus degeneration and clinicopathological features of Huntington disease

This study characterizes the pattern of neurodegeneration in 3 subdivisions of the human GP, and its relation to clinical symptomatology. MethodsStereology 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. ResultsRelative 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. InterpretationThe 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 clinicopatho...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research