Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine cases of multiple system atrophy and 1 case of autosomal dominant olivopontocerebellar atrophy (neuropathological diagnosis) were retrospectively examined for the presence of oligodendroglial inclusions. Clinical diagnosis in the first 9 cases had been: olivopontocerebellar atrophy (3 cases), atypical Parkinson's disease (2 cases), Shy-Drager syndrome (2 cases) and multiple system atrophy (1 case); one of the patients could not be included in any of the above mentioned groups. The oligodendroglial inclusions were argyrophilic and located in the cytoplasm around the nucleus. They were revealed by Bodian's method in all cases of multiple system atrophy. They were not found in the case of autosomal dominant olivopontocerebellar atrophy. They were labelled by anti-ubiquitin antibodies, and were negative with anti-tau antibodies. At electron microscopy, they consisted of rectilinear profiles coated with a fuzzy material (diameter: 20-33 nm); this aspect was compatible with microtubules. Oligodendroglial inclusions were prominent in regions selectively vulnerable in multiple system atrophy (tegmentum pontis, putamen, inferior olives, substantia nigra and cerebellar white matter), even in those areas where neuronal loss or fascicular atrophy were minimal or absent. They were also observed in regions considered to be spared in multiple system atrophy, such as the motor cortex and the corpus callosum. Argyrophilic oligodendroglial inclusions are an early and specific marker of multiple system atrophy. It is suggested that autosomal dominant olivopontocerebellar atrophy lacking oligodendroglial inclusions does not belong to multiple system atrophy.
 ...
PMID:[Oligodendroglial inclusions, a marker of multisystemic atrophies]. 133 74

The clinical expressions of primary autonomic nervous system failure are more or less numerous, orthostatic hypotension being only one of them. Clinical analysis reveals 3 categories of manifestations: pure progressive dysautonomia, dysautonomia associated with Parkinson's disease, and dysautonomia associated with multiple system atrophy of the nervous system also known as Shy-Drager syndrome. Neuropathological studies show that lesions of the efferent autonomic nervous system (tractus intermediolateralis, sympathetic ganglia) are frequently associated with lesions of the central nervous system the role of which in dysautonomia is still imperfectly known. Lesions of the central nervous system may present as genuine Parkinson's disease with Lew bodies or as multiple systemic atrophy with its two best individualized aspects: striatonigral atrophy and olivopontocerebellar atrophy. These various neurological aspects have their counterpart in biochemical abnormalities, prognosis and response to treatment.
 ...
PMID:[Dysautonomia and multi-systemic atrophy of the nervous system (Shy-Drager's syndrome)]. 153 7

The enzymatic activity of acetylcholinesterase (AchE) in the cerebrospinal fluid (CSF) is considered to be a marker of central cholinergic neuron integrity. Then, we evaluated CSF AchE activity in 90 cases of neurological diseases involving cholinergic system and their related disease, and 28 control cases without central organic lesions or abnormal findings in routine CSF study. AchE activity was evaluated according to Ellman's method using acetylthiocholine iodide as a substrate and tetraisopropyl-pyrophosphoramide, a specific inhibitor of butyrylocholinesterase. CSF AchE of Alzheimer type dementia (AD/SDAT, N = 12: 21.9 +/- 4.7 nmol/ml/min) showed no significant change from those of both control group (22.1 +/- 3.9) and vascular dementia (9: 21.7 +/- 6.7). In extrapyramidal diseases, reduction of the activity was observed in Huntington's chorea (HC, 4: 16.3 +/- 1.4) and progressive supranuclear palsy (PSP, 4: 17.6 +/- 1.7), whereas normal activity was shown in Parkinson's disease (PD, 19: 22.5 +/- 4.6), dentatorubropallidoluysian atrophy (DRPLA, 4: 22.6 +/- 4.2) and striatonigral degeneration (SND, 4: 20.4 +/- 4.3). In olivopontocerebellar atrophy (OPCA, N = 16), we disclosed reduced CSF AchE activity (15.8 +/- 2.4) which had significant correlations with the atrophy of the pontine base (r = 0.6017, p less than 0.02) and cerebellar vermis (r = 0.5450, p less than 0.05) in MRI. AchE activity in cerebellar cortical atrophy (CCA, 5: 20.6 +/- 2.2) remained within the control values. Normal activity was demonstrated in both amyotrophic lateral sclerosis (6: 24.3 +/- 7.3) and spinal muscular atrophy (4: 22.9 +/- 3.9).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[CSF acetylcholinesterase activity in central neurological diseases involving cholinergic systems]. 162 49

The dopamine receptor agonist apomorphine has been used successfully to treat on-off swings in Parkinson's disease. Its value as a predictor of dopa responsiveness in idiopathic Parkinson's disease (IPD) was assessed and its potential role in differentiating IPD from the Parkinsonian plus syndromes (PPS) of multisystem atrophy, progressive supranuclear palsy and olivopontocerebellar atrophy was investigated. The response to an injection of apomorphine was observed in 20 patients with IPD and eight with PPS after being off levodopa for 12 hours. Patients were reassessed after taking levodopa for one month. Nineteen of the 20 patients (95%) with IPD showed a positive response to apomorphine and 18 (90%) to oral levodopa. In the PPS group, two patients (25%) responded to the apomorphine injection but not to oral levodopa. Apomorphine produced severe drowsiness in the PPS patients. It is suggested that the test can predict dopa responsiveness in IPD and may be of help in confirming a doubtful diagnosis. It has potential value in differentiating IPD from PPS.
 ...
PMID:The apomorphine test in parkinsonian syndromes. 174 40

Based on 45 normal cases aged from 32 to 106 years of age, a morphometric study revealed that, despite decrease in the number of both pigmented neurons (PN) and the non-pigmented neurons (NN) with advancing age, the ratio (PN/NN) did not change (4.8). It is well-known that both the substantia nigra and the striatum send fibers to each other. McGee demonstrated that the ratio of the number of large neurons to that of small neurons was constant, irrespective of different ages, although number of both neurons decreased with ageing. It was therefore apparent that this phenomenon in the putamen was the same as in the substantia nigra. It could be considered that "balanced depopulation of different neurons" in the nucleus of the strio-nigral circuit contribute to support normal extrapyramidal functions. Additionally, the centenarian cases showed larger numbers of both PN and NN than younger case. It was likely that they could be classified as so-called "excellent" centenarians. On the other hand, idiopathic Parkinson's disease (15 cases) showed that while the same number of NN remained as in age-matched controls, PN showed marked depopulation. Olivopontocerebellar atrophy of the sporadic type (OPCA, 10 cases) and progressive supranuclear palsy (PSP, 5 cases) showed a decrease in number of both PN and NN. However, NN in PSP showed much more decrease than OPCA. NN sends fibers to the pontine tegmentum as well as the thalamus, and PSP shows marked atrophy of the brainstem tegmentum. In this connection, it was considered that marked decrease of NN in PSP could be related to tegmental atrophy.
 ...
PMID:[Pigmented neuron/non-pigmented neuron ratio of the substantia nigra in relation to ageing and pathological conditions]. 189 29

Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 years experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M-50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.
 ...
PMID:Accuracy of clinical diagnosis in parkinsonism--a prospective study. 191 60

The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe a patient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D2 dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson's disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson's disease, nor does it exclude multiple-system, atrophy-related parkinsonism.
 ...
PMID:Presynaptic parkinsonism in olivopontocerebellar atrophy: clinical, pathological, and neurochemical evidence. 195 31

We measured the binding of the vesicular acetylcholine transport blocker [3H]vesamicol (2-[4-phenylpiperidino] cyclohexanol; AH-5183) to autopsied frontal cortex and amygdala of patients from 4 disorders having a marked brain cholinergic reduction, namely Alzheimer's disease, Parkinson's disease with dementia, dominantly inherited olivopontocerebellar atrophy and Down's syndrome. Although mean activity of the specific cholinergic marker enzyme choline acetyltransferase (ChAT) was markedly reduced by about 60% in frontal cortex in the 4 patient groups and by 80% or greater in amygdala of the Alzheimer's and Down's syndrome patients, [3H]vesamicol binding density was, on average, either normal or only slightly reduced as compared with the controls. This discrepancy suggests that in human brain [3H]vesamicol binding is either not preferentially localized to cholinergic nerve endings or, in these cholinergic deficiency syndromes, a substantial proportion of the vesamicol binding sites persist on cholinergic nerve terminals despite loss of ChAT activity.
 ...
PMID:[3H]vesamicol binding in human brain cholinergic deficiency disorders. 215 Dec 94

The discovery of a specific association between nerve growth factor (NGF) and basal forebrain cholinergic neurons (BFCNs) marks the beginning of a new era of research into neurodegenerative diseases such as Alzheimer disease (AD). Degeneration of BFCNs appears to be one of the earliest and most prominent neuropathological features of a broad range of diseases of the human brain that give rise to loss of memory and dementia (including, in addition to Alzheimer disease, Parkinson disease, Lewy body dementia, progressive supranuclear palsy, dementia pugilistica, olivopontocerebellar atrophy, and Wernicke-Korsakoff syndrome). Selective localization of NGF receptors on BFCN, the relatively high levels of NGF mRNA in BFCN target areas, and numerous effects of exogenous NGF in vivo and in vitro provide overwhelming evidence that the structure and function of BFCNs in the adult brain are dependent on this molecule. The question then arises as to how this special relationship is disturbed in the diseased human brain? Initial investigations in AD have already indicated a normality of NGF mRNA and retention of receptors in the basal forebrain region. Interpretation of these results and the therapeutic relevance of NGF obviously depend upon future developments in understanding the role of NGF in the normal and pathological brain.
 ...
PMID:Nerve growth factor and the basal forebrain cholinergic system: a link in the etiopathology of neurodegenerative dementias? 218 Apr 39

We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.
 ...
PMID:Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients. 235 20


1 2 3 4 5 6 Next >>