Hereditary form of parkinsonism--dementia

• Published in: Annals of neurology Vol. 43; no. 6; p. 768
• Main Authors: Muenter, M D, Forno, L S, Hornykiewicz, O, Kish, S J, Maraganore, D M, Caselli, R J, Okazaki, H, Howard, Jr, F M, Snow, B J, Calne, D B
• Format: Journal Article
• Language: English
• Published: United States 01-06-1998
• Subjects: Adult; Antiparkinson Agents - administration & dosage; Choline O-Acetyltransferase - analysis; Dementia - diagnostic imaging; Dementia - drug therapy; Dementia - genetics; Dopamine - analysis; Family Health; Female; Genes, Dominant; Hippocampus - chemistry; Hippocampus - enzymology; Hippocampus - pathology; Homovanillic Acid - analysis; Humans; Levodopa - administration & dosage; Lewy Bodies - pathology; Locus Coeruleus - chemistry; Locus Coeruleus - pathology; Male; Middle Aged; Neostriatum - chemistry; Neostriatum - pathology; Nerve Degeneration - pathology; Neuropsychological Tests; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Pedigree; Substantia Innominata - chemistry; Substantia Innominata - pathology; Substantia Nigra - chemistry; Substantia Nigra - pathology; Temporal Lobe - chemistry; Temporal Lobe - enzymology; Temporal Lobe - pathology; Tomography, Emission-Computed
• DOI: 10.1002/ana.410430612
• ISSN: 0364-5134

In four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa-responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.