Globus pallidus degeneration and clinico-pathological features of Huntington’s Disease

Abstract

Globus pallidus degeneration and clinico-pathological features of Huntington’s disease M.K. Singh-Bains1,2, L.J. Tippett2,3, V.M Hogg2,3, B.J. Synek2,4, R.H. Roxburgh2,5,H.J. Waldvogel1,2, R.L.M. Faull1,2 1Department of Anatomy with Radiology, 2Centre for Brain Research, 3Department of Psychology, University of Auckland, Auckland, New Zealand; 4Department of Forensic Pathology, 5Department of Neurology, Auckland City Hospital, Auckland, New Zealand Numerous studies have focused on striatal neurodegeneration in Huntington’s disease (HD). In comparison, the globus pallidus (GP), a main striatal output nucleus, has received less focus in HD research. The objective of this research is to characterize the pattern of neurodegeneration in three subdivisions of the human globus pallidus, and its relation to clinical symptomatology. Stereology was used to measure regional atrophy, neuronal loss, and soma neuronal atrophy in three components of the GP - the external segment (GPe), internal segment (GPi) and ventral pallidum (VP) - in eight HD cases compared with seven 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. 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, increasing motor impairments, but not chorea. In contrast, decreasing GPi volumes were associated with decreasing levels of irritability. These results indicate that the HD gene mutation produces variable degrees of GP segment degeneration, highlighting the differential vulnerability of striatal-GP target projections. The relationship established between clinical symptom scores and pallidal degeneration provides a novel contribution to understanding the clinical-pathological associations in HD. Support: Health Research Council of New Zealand; Neurological Foundation of New Zealand; The University of Auckland.