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Washington University Experience | NEURODEGENERATION | Progressive Supranuclear Palsy (PSP) | 9E Case 9 Denouement
Final Neuropathologic Diagnoses: Progressive supranuclear palsy; Alzheimer disease neuropathologic change; TDP-43-immunoreactive inclusions in the medial temporal lobe and dentate gyrus; Hippocampal sclerosis; Small vessel disease with infarcts in the basal ganglia, cerebellum, and anterior pituitary; Arteriolosclerosis (moderate); Atherosclerosis (moderate) ---- Neuro Diagnosis Comment: This case shows the stereotypic features of progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome: degeneration including widespread neuronal loss, gliosis, and tau-positive neuronal and glial cytoplasmic inclusions, especially tufted astrocytes, in cortical and subcortical nuclei. ---- In addition to the tauopathy of PSP, histological slides of representative neocortical areas show frequent beta-amyloid plaques, only few neocortical neuritic plaques, and relatively abundant neurofibrillary tangles. These findings indicate the presence of Alzheimer's disease (AD) by Khachaturian, 'possible' AD by CERAD criteria, and a 'low probability of dementia caused by AD' according to the NIA-Reagan Institute criteria for neuropathological diagnosis of AD. ---- Sparse TDP-43-immunoreactive cytoplasmic inclusions, indicative of another disease process called TDP-43 proteinopathy, were also present in medial temporal lobe structures. These inclusions were few in number and unlikely to have impacted on the cognitive state to any significant extent. ---- Only equivocal Lewy body-like structures were identified focally in the midbrain; the limited number and distribution, and inconclusive nature of these alpha-synuclein-containing structures excludes a neuropathological diagnosis of Parkinson's disease. ---- Vascular pathology in the form of moderate arteriolosclerosis, hippocampal sclerosis, and infarcts in the basal ganglia, cerebellum and anterior pituitary are also features of this brain. The microinfarcts and hippocampal sclerosis are significant and are likely to have contributed to cognitive impairment. ---- Neurofibrillary tangles were also observed in small numbers within neurons of the spinal cord; the significance of this finding, if any, is unclear, as these are reported in a number of disease states, including progressive supranuclear palsy, as well as in individuals of advanced age without defined neurodegenerative disease. No other neurodegenerative diseases are identified. ---- In conclusion, the motor and cognitive deficits experienced during life may be explained by progressive supranuclear palsy, Alzheimer's disease, and vascular pathology in the form of hippocampal sclerosis and infarcts of the basal ganglia and cerebellum, with a modest contribution from TDP-43 proteinopathy. (Comment by Nigel Cairns, PhD)
