Huntington disease is characterized clinically by chorea, motor impairment, psychiatric manifestations and dementia. Atrophy of the striatum is the neuropathological hallmark of Huntington disease and previous studies have suggested that striatal atrophy correlates more closely with motor impairment than with chorea. Motor impairment, as measured by motor impairment score, correlates with functional disability in Huntington patients, but chorea does not. In this study, we investigate the relation between neuronal loss and these motor features.
We conducted neuropathological and stereologic assessments of neurons in putamen and subthalamic nuclei in Huntington patients and age-matched controls. In putamen, we estimated the total number and volume of medium spiny neurons labeled with dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP32). In subthalamic nuclei, we estimated the total number of neurons on Hematoxylin/Eosin -Luxol/Fast Blue stains.
In putamen of Huntington disease, immunohistochemistry showed DARPP 32 neuronal atrophy with extensive disruption of neurites and neuropil; stereologic studies found significant decreases in both the number and size of DARPP32 neurons; we also detected a significant reduction of overall putamen volume in Huntington patients compared with controls. In subthalamic nuclei, there was a mild but significant neuronal loss in Huntington group. The loss of neurons in putamen and subthalamic nuclei and the putaminal atrophy were significantly correlated with the severity of motor impairment, but not with chorea.
Our findings suggest that neuronal loss and atrophy in striatum and neuronal loss in subthalamic nuclei contribute specifically to the motor impairment of Huntington, but not to chorea.