Prevalence of multiple system atrophy.
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Aged↗
Biomedical subjects
F Tison
Publications and source records attributed to F Tison.
Toward a primate model of L-dopa-unresponsive parkinsonism mimicking striatonigral degeneration.
We developed a primate model of striatonigral degeneration (SND), the neuropathology underlying levodopa-unresponsive parkinsonism associated with multiple systemic atrophy (MSA-P), by sequential systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3NP) in a Macaca fascicularis monkey. L-Dopa-responsive parkinsonian features emerged after MPTP injections. Subsequent chronic 3NP administration aggravated the motor symptoms and abolished the L-dopa response. In vivo magnetic resonance imaging revealed bilateral striatal lesions. Histopathologically, there was severe dopaminergic cell loss in the substantia nigra pars compacta compared with the control monkey. Furthermore, we observed circumscribed areas of severe neuronal degeneration in the motor striatum. These changes were absent in the control monkey, and they were associated with diffuse metabolic failure as demonstrated by cytochrome oxidase histochemistry. The striatal pathology predominantly involved output pre-pro-enkephalin A- and substance P-containing cells, whereas somatostatin (NADPH-diaphorase)-containing interneurons were relatively spared. Our model therefore reproduced levodopa-unresponsive parkinsonism and SND-like pathologic changes characteristic of MSA-P. The double-lesion primate model of SND may serve as a preclinical test-bed for the evaluation of novel therapeutic strategies in MSA-P.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
The value of external anal sphincter electromyography for the diagnosis of multiple system atrophy.
OBJECTIVE: To assess the value of external anal sphincter electromyography (ASEMG) for the diagnosis of multiple system atrophy (MSA) among various causes of parkinsonism. ASEMG denervation profiles have previously been proposed as a diagnosis test for MSA, but their specificity is disputed. METHODS: ASEMG variables of 52 parkinsonian patients were analyzed according to the clinical diagnosis: MSA (n = 31) or no MSA (n = 21). Mean motor unit potential duration, percentage of polyphasicity, and the electromyographer's interpretation were analyzed according to clinical diagnosis, disease duration, genitourinary symptoms, gender, parity, and history of pelvic surgery. RESULTS: All patients with MSA showed ASEMG denervation. Mean motor unit potential duration was the most discriminant variable. No patient with MSA had a mean duration less than 12 ms and no patient without MSA had one greater than 16 ms. ASEMG discriminates between patients with MSA and Parkinson's disease. Using a threshold of 13 ms, the sensitivity was 80% and specificity was almost 70% (positive predictive value, 80%) for the diagnosis of MSA. Age, history of pelvic surgery, and to a lesser extent, female gender, parity, disease duration, and presence of urinary symptoms increased the likelihood of abnormal ASEMG. CONCLUSION: ASEMG was highly sensitive and rather specific for the diagnosis of MSA.
Adult↗
Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy).
This study characterizes paw reaching, stepping and balance abnormalities in a double lesion rat model of striatonigral degeneration, the core pathology underlying levodopa unresponsive parkinsonism associated with multiple system atrophy. Extensive unilateral nigral or striatal lesions induced by 6-hydroxydopamine or quinolinic acid, respectively, produced a similarly marked contralateral paw reaching deficit without further deterioration following a secondary (complementary) lesion of ipsilateral striatum or substantia nigra. Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions without further deterioration following the secondary striatal lesion. In contrast, initial unilateral striatal quinolinic acid injections induced bilateral stepping deficits that significantly worsened contralaterally following the secondary nigral lesion. Contralateral sidefalling rates were significantly increased following primary nigral and striatal lesions. Secondary nigral but not secondary striatal lesions worsened contralateral sidefalling rates. Histological studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia nigra pars compacta and variable degrees of striatal degeneration depending on the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed significantly larger residual striatal surface areas following the secondary striatal quinolinic acid lesion compared to animals with primary striatal quinolinic acid lesions (P<0.001). These findings are in line with previous experimental studies demonstrating that striatal dopamine depletion confers neuroprotection against subsequent excitotoxic injury. Whether loss of dopaminergic neurons protects against the striatal disease process occurring in multiple system atrophy (Parkinson-type) remains to be elucidated. In summary, this is the first experimental study to investigate spontaneous motor behaviour in a unilateral double lesion rat model. Our observations are consistent with a complex interaction of nigral and striatal lesions producing distinct behavioural and histological changes depending on the lesion sequence. Tests of forelimb akinesia and complex motor behaviour appear to provide a reliable tool that will be helpful for monitoring the effects of interventional strategies such as embryonic neuronal transplantation in the rat model of striatonigral degeneration.
Animals↗
[Contribution and limitations of evaluation scales in Parkinson's disease].
Rating scales in Parkinson's disease (PD) are generally reliable but are not widely used in practice. UPDRS is the core assessment of PD, its metrologic properties are well known, and it is simple to use after training. However, cognitive and psychic disorders need complementary approaches. For example, MATTIS seems to be more appropriate in assessing the cognitive deficit and MADRS the depressive symptoms. A patient diary best appreciates motor fluctuations. Activities of daily living rated by the UPDRS allow a global assessment of the patient handicap that may be completed by "the patient's own point of view" through quality of life scales (SF36, PDQ39). For clinical research purposes, time tests and dyskinesia scales following the CAPIT or CAPSIT procedure are required.
Humans↗
[Changes in clinical diagnostic criteria for multiple system atrophy].
Multiple system atrophy (MSA) is a clinical and pathological entity characterized by the variable combination of autonomic failure, parkinsonism, cerebellar and pyramidal signs and by cell loss with gliosis and oligodendroglial cytoplasmic inclusions in the nigrostriatal, olivopontocerebellar systems and the spinal cord. Beyond nosology there has been a need for reliable clinical diagnosis criteria for MSA. Such criteria should ideally combine good sensitivity and specificity to diagnose MSA at different stages and should be good predictors (high positive predictive value) of the pathological diagnosis. Difficulties encountered in establishing MSA clinical diagnosis criteria were, among others, the variable expression of the disease, the definition of autonomic failure, of the cerebellar syndrome and of the poor levodopa response of parkinsonism. Quinn in 1989 proposed 3 sets of criteria (revised in 1994) to diagnose "possible", "probable" and "definite" MSA. These criteria are quite simple and partially validated. More recently these criteria evolved towards consensus criteria in which autonomic failure had a more central position. The consensus conference, held in 1998, proposed a precise definition of the various clinical domains and the combination needed for the clinical diagnosis, as well as exclusion criteria. In this article, we review and comment the different criteria for the clinical diagnosis of MSA.
Autonomic Nervous System Diseases↗
Parkinsonism as a result of a giant aneurysm.
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Basal Ganglia↗
Stimulus-sensitive spinal segmental myoclonus improved with injections of botulinum toxin type A.
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Adult↗
Effect of the alpha 2 adrenoreceptor antagonist, idazoxan, on motor disabilities in MPTP-treated monkey.
1. The motor effect of the alpha 2 adrenoreceptor antagonist, idazoxan, was compared to that of L-dopa in MPTP-treated monkeys. 2. Idazoxan 2.0 mg/kg improved parkinsonian motor abnormalities which was comparable to the effects of a minimal effective dose of L-dopa. 3. At 2.0 and 5.0 mg/kg, the parkinsonian rigidity was the item most frequently alleviated by idazoxan (respectively 63.6% and 68.2%). 4. These findings provide support for the therapeutic utility of alpha 2 antagonists in the treatment of Parkinson's disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia.
Familial hemiplegic migraine (HM) is an autosomal dominant migraine with aura. In 20% of HM families, HM is associated with a mild permanent cerebellar ataxia (PCA). The CACNA1A gene encoding the alpha1A subunit of P/Q-type voltage-gated calcium channels is involved in 50% of unselected HM families and in all families with HM/PCA. Four CACNA1A missense mutations have been identified in HM: two in pure HM and two in HM/PCA. Different CACNA1A mutations have been identified in other autosomal dominant conditions: mutations leading to a truncated protein in episodic ataxia type 2 (EA2), small expansions of a CAG trinucleotide in spinocerebellar ataxia type 6 and also in three families with EA2 features, and, finally, a missense mutation in a single family suffering from episodic ataxia and severe progressive PCA. We screened 16 families and 3 nonfamilial case patients affected by HM/PCA for specific CACNA1A mutations and found nine families and one nonfamilial case with the same T666M mutation, one new mutation (D715E) in one family, and no CAG repeat expansion. Both T666M and D715E substitutions were absent in 12 probands belonging to pure HM families whose disease appears to be linked to CACNA1A. Finally, haplotyping with neighboring markers suggested that T666M arose through recurrent mutational events. These data could indicate that the PCA observed in 20% of HM families results from specific pathophysiologic mechanisms.
Calcium Channels↗
Brain stem infiltration by mixed Langerhans cell histiocytosis and Chester-Erdheim disease: more than just an isolated case?
Langerhans cell histiocytosis is classically considered as totally different from Chester-Erdheim's disease which consists in the infiltration of various parenchymas by macrophagic CD68-positive histiocytes. We report the case of a 46-year-old woman with a long history of diabetes insipidus who presented typical lesions of Langerhans cell histiocytosis on vulvar and skin biopsies as well as bony cellular infiltrates characteristic of Chester-Erdheim's disease. A few months later she presented cerebellar disorders and died after an 18-month course. At autopsy the pons was enlarged, due to numerous cellular infiltrates which were also scattered in the middle cerebellar pedoncles, dentate nuclei, midbrain and hypothalamus. There were S100-protein positive Langerhans cells intermingled with numerous ovoid CD68-positive histiocytes. There are a few reported cases of Chester-Erdheim's disease presenting foci of Langerhans cells histiocytosis in other parenchymas. In addition, there are 10 reported cases with diabetes insipidus and bilateral infiltration of the brain stem and cerebellum, considered as presenting either one type of histiocytosis or the other. Our case demonstrates that both histiocytoses may coexist in the brain and thus correspond in fact to the same pathology in certain particular cases.
Biopsy↗
[Langerhans-cell histiocytosis and Erdheim-Chester disease: probably not a fortuitous association].
BACKGROUND: Erdheim Chester disease (MEC) is a rare non-Langerhans cell histiocytosis characterized by multi-visceral involvement. We report a case of MEC associated with Langerhans cell histiocytosis (HCL). CASE REPORT: A 46-year-old women presented skin and vulvar localization of HCL associated with typical MEC bone involvement. Despite chemotherapy (vinblastine) and prednisone, the disease progressed to involve the central nervous system, leading to fatal outcome. Post-mortem examination showed HCL in skin, MEC in bones and central nervous system, and intermediate histiocytic proliferation in the encephalon. DISCUSSION: Usually, MEC and HCL are considered as distinct entities. MEC is characterized by a xanthogranulomatous proliferation of CD 68+ foamy histiocytes nested in fibrosis, and HCL by a proliferation of PS 100+ and CD1a+ Langerhans cells. However, our observation, as well as previous reports, suggests that MEC is part of the HCL spectrum.
Bone Diseases↗
[Study of cortical atrophy with magnetic resonance imaging in corticobasal degeneration].
Corticobasal degeneration (C.B.D.) is a neurodegenerative disorder characterized mainly by an asymmetrical a kineto-rigid syndrome associated with fronto-parietal cortical signs, particularly apraxia. Conventional imaging even magnetic resonance imaging (M.R.I.) has often been considered as poorly contributive for the diagnosis of C.B.D. We retrospectively studied routinely performed M.R.I. scans of 15 patients presenting a clinical and metabolic (P.E.T/S.P.E.C.T.) syndrome characteristic of probable C.B.D. M.R.I. scans were assessed by 3 investigators, not aware of the clinically most affected side, taking into account M.R.I. technical parameters. We quantified, on each side, the cortical atrophy (frontal, parietal and temporal) and the white matter changes, by using the semi-quantified method of Victoroff et al. (1994). Abnormalities were considered if observed by at least 2 of the 3 investigators. Abnormalities were then correlated with the side initially and most severely affected. The most contributive findings were the asymmetric parietal atrophy (clinically correlated in 93 p. 100 of cases), asymmetric frontal atrophy (clinically correlated in 60 p. 100) and asymmetric dilatation of the lateral ventricles (clinically correlated in 60 p. 100). 80 p. 100 of affected subjects displayed at least 2 of these M.R.I. abnormalities. These results are in accordance with the metabolic and pathologic features of C.B.D. This study demonstrates that M.R.I. evaluation of the cortical atrophy asymmetry may contribute to the diagnosis of C.B.D.
Age of Onset↗
[Fulminant orthochromatic leukodystrophy in an adult].
A 27-year-old man from Marocco developed a progressive dementia leading within a year to a mutic akinetic state. The course of the disease was also marked by epileptic seizures. MRI revealed diffuse white matter involvement. A frontal white matter brain biopsy was consistent with the diagnosis of orthochromatic leucodystrophy, i.e: presence of sudanophilic lipids and pigmented cells associated with myelin loss. Adult forms of orthochromatic leucodystrophy are very rare. Our case was characterized by a fulminant course.
Adult↗
[Propriospinal myoclonus induced by relaxation and drowsiness].
Propriospinal myoclonus is a subtype of spinal myoclonus characterized by axial flexion or extension jerks, arrhythmic and prolonged muscle bursts with a pattern of activation consistent with a slow conduction within the propriospinal pathways. We describe a new idiopathic case of flexion propriospinal myoclonus occurring upon relaxation and drowsiness. This syndrome is to be added to the spectrum of movement disorders occurring during drowsiness.
Anticonvulsants↗
Multiple system atrophy: a review of 203 pathologically proven cases.
We report the clinicopathological features of 203 cases of pathologically proven multiple system atrophy (MSA) from 108 publications up to February 1995. The majority of patients showed symptoms in their early fifties, and men were more commonly affected than women (ratio of 1.3:1). Most patients suffered from some degree of autonomic failure (74%). Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). The response to levodopa was poor in most patients, but there was a subgroup with a good response, who also often developed axial levodopa-induced dyskinesias. Other characteristic features included severe dysarthria, stridor, and, in a few patients, contractures and dystonia (antecollis). Mild or moderate intellectual impairment occurred in some cases, but severe dementing illness was most unusual. The main pathological change comprised cell loss and gliosis in the putamen, caudate nucleus, external pallidum, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, and intermediolateral cell columns of the spinal cord. However, other neuronal populations were also involved to varying degrees, such as the thalamus, vestibular nucleus, dorsal vagal nucleus, corticospinal tracts, and anterior horn cells. Characteristic glial and/or neuronal cytoplasmic inclusions were identified in all cases in which they were sought, irrespective of clinical presentation. Akinesia correlated with the degree of nigral and putaminal cell loss, whereas rigidity was related only to the later. Tremor was unrelated to cell loss at any site. Ataxia correlated with the degree of olivopontocerebellar atrophy. Pyramidal signs were associated with pyramidal tract pallor. Our analysis also confirmed an association of postural hypotension with intermediolateral cell column degeneration.
Aged↗
Dependency in Parkinson's disease: a population-based survey in nondemented elderly subjects.
Little epidemiological data are available on the dependency status of elderly patients with Parkinson's disease (PD) living in the community. This study assessed the activities of daily living (ADL), the instrumental activities of daily living (IADL), and mobility in a representative sample of elderly nondemented PD subjects (n = 20), compared to a control population (n = 2,697). We found a significantly higher level of dependency in the PD sample based on ADL, IADL, and mobility scales. Half of the PD subjects were dependent for ADL (versus 13.2% for controls), 80% were dependent for IADL (versus 28% for controls), and 20% had their mobility restricted to their home (versus 1.5% for controls). The proportion of PD patients tended to be higher in those more depressed or with more severe motor symptoms. PD patients were not found to be more isolated socially or from family than was the control group and, in any case, dependency seemed not to be associated with isolation. When adjusting for age, sex, depressive symptoms, Mini Mental Status examination score, and dyspnea, PD remained significantly associated with dependency. PD thus constitutes a significant factor of dependency in elderly subjects living at home. Institutionalization occurred over four times more frequently in the PD group than in the general population, but no specific factor of institutionalization was noted.
Activities of Daily Living↗
A historical case of probable corticobasal degeneration?
In 1925, Jean Lhermitte and colleagues published a work on spatial representation in apraxic patients, based on two illustrative cases. One of these displayed a clinical picture that would nowadays be clinically classified as probable corticobasal degeneration.
Apraxias↗