Clinical and pathological features of corticobasal degeneration.
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Aged↗
Biomedical subjects
W R Gibb
Publications and source records attributed to W R Gibb.
Prevalence of Lewy bodies in Alzheimer's disease.
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The evolution and distribution of morphological changes in the nervous system of the common marmoset following the acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Six young adult marmosets received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in multiple doses (total 8-16 mg/kg over 2-13 days) sufficient to produce a parkinsonian syndrome and were killed up to 3.5 months later. Cellular changes were found in the substantia nigra, ventral tegmental area, and hypothalamus. The earliest histological abnormalities were axonal swellings in proximal parts of nigrostriatal axons. Subsequent changes in the substantia nigra were reduced Nissl staining, reduced cell volume, and aggregation and loss of melanin granules. Other effects were reduced nuclear and nucleolar volumes, depletion of cells, and hyperplasia of glial cells. Shrunken cytoplasm and nuclei stained uniformly with eosin, and no cells showed cytoplasmic swellings or inclusions. These cellular alterations, with nuclear changes resembling karyolysis, do not occur in Parkinson's disease, which is characterised by Lewy body inclusions and signs of chromatolysis. The rapid appearance of axonal swellings, disruption of Nissl substance, and cell shrinkage suggest an insult to energy producing mechanisms. In this study, the absence of histological evidence of toxicity in the locus coeruleus and also in the substantia innominata and in serotonergic cell groups is unlike the more widespread degenerative changes of Parkinson's disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Treatment with a selective MAO B inhibitor prevents loss of dopamine in the nucleus accumbens of MPTP-treated common marmosets.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced motor deficits, associated with a marked decrease in the uptake of [3H]dopamine into synaptosomes in the putamen and a reduction in the content of dopamine in both caudate nucleus and nucleus accumbens. Histological analysis showed a marked loss of dopamine-containing cells in the zona compacta of the substantia nigra and less loss in the ventral tegmental area. Treatment of animals with the selective monoamine oxidase (MAO) B inhibitor, MDL 72145 (0.5 or 2.0 mg/kg) prior to, during and following administration of MPTP partially protected animals from the motor abnormalities induced by administration of MPTP alone. Both doses inhibited the onset of akinesia but only the large dose of MDL 72145 prevented the occurrence of other motor abnormalities. Moreover, while MDL 72145 (2.0 mg/kg) prevented the loss in uptake of [3H]dopamine into synaptosomes of the putamen, this was only partly prevented using the smaller dose. Similarly, while MDL 72145 (2.0 mg/kg) prevented loss of dopamine in the caudate, only partial protection was afforded by the smaller dose. However, in the nucleus accumbens, both doses of MDL 72145 prevented the depletion of dopamine, occurring in this region. Histological examination of the substantia nigra showed little or no cell loss in animals receiving the larger dose of MDL 72145 but a moderate cell loss in animals receiving the smaller dose. No damage was observed in the ventral tegmental area of animals treated with MDL 72145 (2.0 mg/kg) and only mild cell loss in those receiving the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Corticobasal degeneration.
Three patients with clinical and pathological features of corticobasal degeneration are described. They presented with a progressive disease bearing some clinical resemblance to Steele-Richardson-Olszewski syndrome and displaying some pathological features of Pick's disease. Their illness began at the age of 59 to 66 yrs with focal dystonia and myoclonus of an arm, the 'alien hand' sign, or an akinetic-rigid syndrome. They developed a supranuclear gaze palsy, parkinsonian features and mild cerebellar signs. Two patients showed constructional dyspraxia when using the arms. The duration of disease to death was 4 to 6 yrs. Pathological examination showed frontoparietal atrophy with cortical cell loss, gliosis and Pick cells, but there was no significant hippocampal disease or Pick bodies in this region. There was nerve cell loss and gliosis in the thalamus, lentiform nucleus, subthalamic nucleus, red nucleus, midbrain tegmentum, substantia nigra and locus coeruleus. Neuronal inclusions in the substantia nigra, termed corticobasal inclusions, were reminiscent of the globose neurofibrillary tangle of Steele-Richardson-Olszewski syndrome, and other pale inclusions resembled the pale body of Parkinson's disease, but Lewy bodies and neurofibrillary tangles were generally absent. Some nigral inclusions were similar to those in Pick's disease. Despite some pathological similarities to Pick's disease we suggest that the distribution of nerve cell loss and the corticobasal inclusion are unique to corticobasal degeneration.
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Asymmetry of substantia nigra neuronal loss in Parkinson's disease and its relevance to the mechanism of levodopa related motor fluctuations.
A pathological study of 21 patients with Parkinson's disease of asymmetrical onset revealed significant asymmetry of degeneration of the substantia nigra with greater neuronal loss contralateral to the initially affected body side. It has previously been suggested that decline in duration of effectiveness of levodopa doses in Parkinsonian patients with motor oscillations is caused by loss of nigro-striatal dopaminergic terminals with consequent reduction in striatal dopamine storage capacity. If this is true, duration of levodopa motor response should be shorter on the more severely affected body side in patients with asymmetrical disease, as loss of contralateral striatal dopamine storage capacity should be greater. Serial motor evaluations in 20 patients with asymmetrical Parkinson's disease failed to reveal any such asymmetry of duration of motor response to levodopa. It is suggested that striatal dopamine storage is not an important determinant of duration of clinical response to levodopa doses.
Adult↗
Cortical Lewy body dementia: clinical features and classification.
Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology.
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The substantia nigra and ventral tegmental area in Alzheimer's disease and Down's syndrome.
Degenerative changes in the substantia nigra and ventral tegmental area were investigated in 104 cases of Alzheimer's disease and 13 cases of Down's syndrome. Frequencies of tangles in three groups of patients with Alzheimer's disease were 86%, 44% and 46% (54% overall) respectively. About half of those with tangles, but no Lewy bodies, had excess nigral cell loss, and 16% had moderate or severe neuronal fallout, but none had a Parkinsonian syndrome. Cases with nigral tangles were younger, tended to have more hippocampal and cortical tangles and plaques, and lower activities of cortical choline acetyltransferase. In most cases of Alzheimer's disease degeneration in nigral and tegmental areas was greater than controls, and tangles were evenly distributed. All the cases of Down's syndrome had tangles in the nigra and eight showed mild cell loss. Mild degenerative changes accompanied by tangles in the substantia nigra and ventral tegmental area are common in Alzheimer's disease, but severe cell loss is rare. When a Parkinsonian syndrome occurs in Alzheimer's disease it is likely to be due to Lewy body pathology.
Adult↗
A pathological study of the association between Lewy body disease and Alzheimer's disease.
The possibility of an association between Parkinson's disease and Alzheimer's disease has been examined by studying the age-specific prevalence of Lewy bodies in the substantia nigra in a group of 273 control cases without Parkinson's disease and 121 cases of Alzheimer's disease. The substantia nigra was also studied in 14 cases of Down's syndrome, 13 of which had cortical Alzheimer pathology. Twelve (7.8%) of the controls aged over 60 years showed nigral Lewy bodies. There was mild nerve cell degeneration and/or an extranigral distribution of Lewy bodies, suggestive of presymptomatic Parkinson's disease. Twenty five (22.5%) of the Alzheimer's disease cases over 60 years showed Lewy bodies, but only 14 (14.0%) of these had mild nigral cell loss consistent with presymptomatic Parkinson's disease. No case of Down's syndrome had Lewy bodies. Counts of tangles and plaques in hippocampus, frontal and temporal cortex were lower in cases of Alzheimer's disease with Lewy bodies compared with those without, but cortical choline acetyltransferase (ChAT) activities were similar. This suggests that Lewy body degeneration in the nucleus basalis of Meynert contributes to the deficit of cortical ChAT, but not to the cortical Alzheimer pathology. The relatively small difference in the prevalence of Lewy bodies between controls and Alzheimer's disease could be explained by the additive effects of Lewy body and tangle pathology causing dementia, rather than a greater than chance association between Parkinson's disease and Alzheimer's disease.
Adult↗
Neuropathology in movement disorders.
This review concentrates on the definition and classification of degenerative movement disorders in which Parkinsonian symptoms are often prominent. The pathological spectrum and clinical manifestations of Lewy body disease are described, and associations with Alzheimer's disease and motor neuron disease are explored. A classification of pallidonigral degenerations is based on clinical features, distribution of pathology, and morphological abnormalities; some of these patients have mild nigral degeneration and no Parkinsonian features. Many other juvenile and familial Parkinsonian cases are not included among the pallidonigral degenerations. Most of these latter syndromes have been organised into preliminary groups, in particular, autosomal dominant dystonia-Parkinson syndrome, juvenile Parkinsonian disorder and autosomal dominant Lewy body disease.
Brain↗
Dementia and Parkinson's disease.
Recent research into the dementia of Parkinson's disease has exposed a complex area in which it has not always been possible to match clinical and pathological observations. Certain neuropsychological deficits result from a disruption of basal ganglia and frontal lobe interactions. These are unrelated to a global dementia, the prevalence of which exceeds twice that in the normal population. The associated pathological lesions comprise cortical pathology, either Alzheimer's disease or Lewy bodies, in combination with moderate degeneration of the subcortical, cholinergic, basal nucleus of Meynert.
Alzheimer Disease↗
Tendency to late recurrence following rheumatic chorea.
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A conus tuberculoma mimicking an intramedullary tumour: a case report and review of the literature.
Tuberculomas of the spinal cord are rare. They usually present as mass lesions with little evidence of systemic illness. We report a case where the diagnosis was only made histologically, emphasising the need to consider infection as a cause of neurological illness in patients from under-developed countries.
Adult↗
The histological effects of intracerebral injection or infusion of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (1-methyl-4-phenylpyridinium) in rat and mouse.
Bilateral infusion of MPTP into the substantia nigra, ventral tegmental area or putamen of the rat brain provoked accumulation of leucocytes, but the periphery of nigral lesions showed no significant nerve cell loss. Tyrosine hydroxylase labelling of dopaminergic perikarya showed a normal staining pattern. In contrast, MPP+ was more destructive. After one day there was local degeneration of neuronal and glial elements. After one month there was tissue necrosis and central cavitation, but, like MPTP, there was no evidence of selective nigral cell loss. Striatal injection of MPP+ also failed to produce retrograde nigral damage. It is concluded that the toxicity of MPP+ applied directly to the dopamine system is a consequence of a severe non-selective necrotic lesion.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Pathological report of four patients presenting with cranial dystonias.
Secondary dystonias and experimental models of dystonia suggest that mechanisms responsible for primary dystonias may lie in the basal ganglia or brainstem. A histological study has been done in three patients with cranial dystonia (blepharospasm with oromandibular dystonia in two, blepharospasm alone in one), and one patient with craniocervical dystonia (oromandibular dystonia with retrocollis). In the patient with blepharospasm alone, an angioma, 0.5 mm in diameter, was found in the dorsal pons at the site of the central tegmental tract, confirming that some patients presenting with primary dystonias may have longstanding lesions in the brainstem. In the three other cases, the striatum, pallidum, thalamus, and brainstem were examined and cell populations in the putamen, substantia nigra, and inferior olives were compared with age-matched controls, but no significant abnormality was found.
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The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.
Adolescent↗
Accuracy in the clinical diagnosis of parkinsonian syndromes.
This review of Parkinson's disease and related disorders emphasizes the difficulties of distinguishing between variants of the parkinsonian syndrome. Characteristic clinical features may remain absent for many months, but accuracy of diagnosis may be improved by considering certain presenting symptoms and signs. The main characteristics of various parkinsonian syndromes are reviewed and their major distinguishing features are emphasized. Future improvement in the precision of clinical diagnosis, especially early in the course of parkinsonian syndromes, will depend on selecting out patients with Parkinson's disease using positive diagnostic criteria.
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