A role for the substantia nigra pars reticulata in the gaze palsy of progressive supranuclear palsy

• Published in: Brain (London, England : 1878) England : 1878), 2000-04, Vol.123 (4), p.724-732
• Main Authors: Halliday, G. M., Hardman, C. D., Cordato, N. J., Hely, M. A., Morris, J. G. L.
• Format: Article
• Language: English
• Subjects: Aged; Basal Ganglia - pathology; Biological and medical sciences; Cell Death; Diseases of striated muscles. Neuromuscular diseases; Female; gaze palsy; globus pallidus; GPe = external globus pallidus; GPi = internal globus pallidus; Humans; Male; Medical sciences; Middle Aged; Nerve Degeneration - pathology; Neurofibrillary Tangles - pathology; Neurology; neuronal cell loss; NFT = neurofibrillary tangles; Ocular Motility Disorders - pathology; Ocular Motility Disorders - physiopathology; Prospective Studies; PSP = progressive supranuclear palsy; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; STN = subthalamic nucleus; substantia nigra; Substantia Nigra - physiopathology; subthalamic nucleus; Supranuclear Palsy, Progressive - pathology; Supranuclear Palsy, Progressive - physiopathology
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/123.4.724

We examined the topography and degree of cell loss within basal ganglia structures commonly involved in progressive supranuclear palsy in order to identify any relationship between degeneration in these nuclei and gaze palsy. Serial section analyses and unbiased quantitative techniques were applied to brain tissue from six cases with progressive supranuclear palsy (four with gaze palsy and two without) and six controls with no neurological or neuropathological abnormalities. The total number of nucleolated neurons within the substantia nigra pars compacta (SNc) and reticulata (SNr), the subthalamic nucleus, and the internal and external segments of the globus pallidus was determined for all subjects and the data expressed as percentages of control values to compare degeneration across these basal ganglia structures. The density of neurofibrillary tangles was also evaluated within these structures. Despite significant subcortical neurofibrillary tangle formation in all cases, there was considerable variability in the degree of neuronal cell loss in all basal ganglia regions, except the SNc which was consistently affected. There was no correlation between the ranked density of neurofibrillary tangles and the degree of neuronal cell loss in any basal ganglia region. Comparisons between cases with and without gaze palsy revealed a 40% greater decrease in the number of SNr neurons in cases with gaze palsy (75 ± 8% loss) compared with those without (35 ± 14% loss). This was the largest difference between these cases. As the SNr projects to the superior colliculus, degeneration of this basal ganglia structure may disrupt eye movements in progressive supranuclear palsy.