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Results for “Multiple System Atrophy”

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PubMed1992

Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions.

Neuronal alterations in five cases of multiple system atrophy (MSA) were investigated histologically, immunocytochemically and ultrastructurally. Argentophilic neuronal cytoplasmic inclusions (NCIs) were observed in all cases. They were distributed, in order of decreasing frequency, in the pontine nucleus, striatum, subiculum, amygdala, hippocampus, dentate fascia, substantia nigra and inferior olivary nucleus. Anti-ubiquitin antibodies visualized many thickened neurites in the degenerating gray matter as well as NCIs. Some NCIs were also recognized by anti-phosphorylated neurofilament antibodies. Ultrastructurally, NCIs consisted of a meshwork of granule-associated filaments, the diameter ranging from 18 to 28 nm, that were mixed with neurofilaments. The granule-associated filaments were also present in the axoplasm of myelinated fibers. Our studies demonstrate widespread distribution of NCIs in the central nervous system of MSA. The same pathological process that forms the granule-associated filaments in axons may also be responsible for the formation of ubiquitin-positive thickened neurites. These axonal alterations, as well as neuronal perikaryal changes, may play an important role in the impaired neuronal function in MSA.

Adult↗

PubMed1993

Multiple system atrophy. Clinical and MR observations on 42 cases.

Probable or possible multiple system atrophy (MSA) was diagnosed on strict clinical criteria in 42 patients: 20 with combined parkinsonism and cerebellar ataxia, 9 with striatonigral degeneration (SND) and 13 with olivopontocerebellar atrophy (OPCA). All patients were then studied with 0.5 and/or 1.5 Tesla magnetic resonance (MR) units. MR imaged putaminal abnormalities in all 9 patients with SND and posterior fossa abnormalities consistent with OPCA in all 13 patients with this diagnosis. Of the 20 patients with parkinsonism and cerebellar involvement, classified as probable MSA, 7 presented putaminal abnormalities only, 3 abnormalities consistent with OPCA only and 10 a combination of both. These findings show strong MRI support for the clinical diagnosis of MSA.

Adult↗

PubMed1996

Depression in multiple system atrophy and in idiopathic Parkinson's disease: a pilot comparative study.

Multiple system atrophy (MSA) is a disease causing parkinsonism in which response to levodopa is classically absent, poor, or transient. Idiopathic Parkinson's disease (IPD) itself, which responds favorably to levodopa, has been associated with the development of disease-related depression. Over and above the clinical and pathological characteristics of IPD, MSA causes additional, more widespread, clinical and pathological deficits. We have compared motor disability and mood in 12 patients with MSA and 12 with IPD. There was more severe motor disability, but no clinical evidence of depression among the MSA patients studied, and their Beck Depression Inventory scores did not differ significantly from the group with IPD. We conclude that depression does not appear to be more common in MSA than in IPD.

Activities of Daily Living↗

PubMed1996

Paroxysmal staring and masticatory automatisms during postural hypotension in a patient with multiple system atrophy.

PURPOSE: We studied a 51-year-old man with multiple system atrophy and autonomic insufficiency. He had repeated episodes of loss of contact, staring, and masticatory automatisms. METHODS: Blood pressure during these events documented a systolic pressure of 60 mm Hg. Cardiovascular reflex tests provided evidence of autonomic failure. Head computed tomography (CT) revealed moderate, diffuse cortical and cerebellar atrophy. RESULTS: These events were strictly related to blood pressure decreases and could be reproduced consistently by having the patient sit up after a meal. Ictal polygraphic recordings showed EEG changes consistent with anoxia, preceded by sudden hypotension with fixed heart rate. CONCLUSIONS: Cerebral anoxia during a syncopal attack may therefore precipitate transient, sudden neurologic dysfunction that closely mimics complex partial seizures. Masticatory automatisms may represent a release phenomenon resulting from inactivation of neocortical structures by cerebral anoxia or reticular disconnection.

Automatism↗

PubMed1992

[Loss of catecholaminergic neuron in the hypothalamus of multiple system atrophy].

Autonomic failure is one of the primary clinical features of multiple system atrophy (MSA); while the hypothalamus is thought to be a higher center regulating the autonomic nervous system. In the hypothalamus, catecholamine depletion had been confirmed by neurochemical studies but no marked changes had yet been demonstrated by pathological studies. Using three MSA and three control cases, we evaluated the quantitative changes of catecholamine (CA)-containing neurons in the hypothalamus. As markers of CA neurons, neuromelanin (NM)- and tyrosin hydroxylase (TH)-containing neurons were stained by Fontana-Masson and the immunohistochemical technique alternatively. Serial coronal sections, 10 microns thick, were evaluated every tenth section for NM neurons, while two sections were evaluated for TH neurons. The distributions of NM and TH neurons were almost identical; most of them were clustered in the periventricular and arcuate nuclei. The mean numbers of NM and TH neurons per slice were significantly lower in MSAs than in the controls (T test, p less than 0.01); the former were 21.0, 31.6, and 13.7 in MSAs and 78.4, 54.1, and 84.3 in the controls, while the latter were 1.5, 15.5, and 20.5 in MSAs and 48.0, 62.0, and 50.5 in the controls. The clinico-pathological correlation was suggested by the significant differences in the number of TH neurons between two MSA cases: a case with severe orthostatic hypotension and a case with a milder one. The ratio of TH and NM neurons, as obtained from the adjusted sections, was constant in all MSA cases, and there was a positive statistical correlation, but it altered in each control case.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1995

[Multiple system atrophy (MSA)].

The clinical and pathological features of 47 cases of multiple system atrophy (MSA) were analyzed. The mean age of onset was 56.7 (range 40 to approximately 76) years and mean survival was 5.7 (range 1.5 to approximately 12) years. Parkinsonism occurred in 31 cases. Helpful early points to the diagnosis included rigid-akinetic type, rapid progression, failure to respond to L-DOPA and other signs such as autoromic dysfunction, cerebellar ataxia and pyramidal signs, but these were not always present. T2 weighted MR images demonstrated decreased signal in the putamen and/or slit-hyperintensity in the outer margin of the putamen. These clinical and MRI findings are useful in the differential diagnosis between Parkinson's disease and MSA. Glial cytoplasmic inclusions (GCIs) were found in all 21 cases, but not in control brains. Several types of neuroral inclusion were also observed; large neuroral cytoplasmic, small neuroral cytoplasmic and nuclear inclusions. GCIs were labeled by antiubiquitin, anti-alpha and beta-tubulin and antitau antibodies. Large neuronal cytoplasmic inclusions (NCIs) observed in the pontine nuclei were positive with only antiubiquitin antibody.

Adult↗

PubMed2005

alpha-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy.

We immunohistochemically examined the sympathetic ganglia (SG) and brains of 26 patients with multiple system atrophy (MSA), 19 age-matched controls, and 25 patients with amyotrophic lateral sclerosis (ALS). alpha-Synuclein-immunoreactive structures were found in the neuronal cytoplasm and processes of the SG in 11 of the 26 MSA cases (42.3%) and 1 of the 25 ALS cases (4%), but not in the 19 controls. No alpha-synuclein-immunoreactive structures were found in Schwann cells or the neuronal nucleus. Mean disease duration of MSA cases with alpha-synuclein-immunoreactive structures was significantly longer than that of MSA cases without alpha-synuclein-immunoreactive structures. alpha-Synuclein-immunoreactive structures in 4 cases proved to be Lewy bodies (LB) based on hematoxylin-eosin staining. A few LB were also found in the brains of 3 of these 4 cases. In the other 7 MSA cases, diffuse or focal neuronal cytoplasmic aggregates and swollen neurites were detected with alpha-synuclein immunostaining, but not with hematoxylin-eosin staining. However, a few LB-like structures with ring-like staining were observed in those aggregates, which suggested those aggregates had progressed to form LB. Immunoelectron microscopically, those aggregates were composed of filaments and granular materials which closely resembled the ultrastructural features of LB. We inferred that alpha-synuclein aggregates found in the SG in our study evidenced LB-related pathologies. MSA, a type of synucleinopathy, is characterized by glial cytoplasmic inclusions in oligodendrocytes, but also frequently develops LB pathology in the late stage, especially in the SG.

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PubMed1998

Twenty-four-hour blood pressure profile and blood pressure responses to head-up tilt tests in Parkinson's disease and multiple system atrophy.

OBJECTIVE: To investigate the 24 h blood pressure profile in patients with Parkinson's disease with intact autonomic function or with autonomic failure and patients with multiple system atrophy (MSA), and to assess whether these patients exhibit posture-related variations in blood pressure. PATIENTS AND METHODS: We studied 24 patients with Parkinson's disease (11 with autonomic failure) and 13 patients with MSA (all with autonomic failure). Autonomic failure was determined by autonomic tests. An oscillometric recorder was used for ambulatory blood pressure monitoring. Tilt-table tests were performed with a head-up tilt position of 60 degrees. RESULTS: An alteration in the normal 24 h blood pressure profile was observed in 82% of Parkinson's disease patients with autonomic failure and in 85% of those with multiple system atrophy, but not in the patients with intact autonomic function. Head-up tilt tests revealed a significantly higher supine blood pressure in Parkinson's disease patients with autonomic failure and in those with MSA than in Parkinson's disease patients with intact autonomic function. Tilting resulted in a marked fall in blood pressure in patients with MSA; in Parkinson's disease patients with autonomic failure, the fall was comparatively slighter. CONCLUSIONS: We conclude that autonomic failure contributes to the alterations in the day-night blood pressure profile that may possibly be ascribed to postural dysregulation of blood pressure. We hypothesize that nocturnal hypertension is a risk factor in the development of additional cerebrovascular disease in patients with Parkinson's disease or MSA who are affected by autonomic failure.

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PubMed2002

Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes.

We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation.

Brain↗

PubMed2004

Comparison of magnetic resonance imaging in subtypes of multiple system atrophy.

Some abnormal findings in routine MRI have been proposed as helpful discriminators for distinguishing multiple system atrophy (MSA) from Parkinson's disease (PD). However, what the most distinguishing MRI findings for MSA-p (parkinsonism dominant) or MSA-c (cerebellar dominant) are separately has not been systematically analyzed. To determine what the most helpful discriminators for MSA-p or MSA-c are and whether those findings are correlated with the presence of parkinsonism or cerebellar dysfunction, we compared 10 previously reported MRI findings in 36 patients with probable MSA-p, 27 patients with probable MSA-c and 30 patients with PD separately. In our results, hyperintense rim and putaminal atrophy among supratentorial parameters and the parameters of infratentorial atrophy were significantly prominent in MSA-p comparing to PD. Hyperintense rim showed the highest specificity in MSA-p patients (90.0%) with relatively suboptimal sensitivity (72.2%). In MSA-c, all infratentorial parameters had strong discriminating power comparing to PD. Signal increase in the middle cerebellar peduncle showed the highest specificity (100%) and had fair sensitivity (85.2%) in MSA-c. Compared between MSA-p and MSA-c, supratentorial parameters were not valid to differentiate MSA-c from MSA-p except for putaminal atrophy. On the contrary, infratentorial parameters were good for distinguishing MSA-c from MSA-p except dilatation of the fourth ventricle. Parkinsonism was not correlated with a hyperintense rim, but cerebellar symptoms were correlated with signal increase in the middle cerebellar peduncle. Our findings suggest the characteristic MRI can be helpful for differentiating MSA-p and MSA-c from PD, respectively, although they do not reflect the presence or lateralization of parkinsonism.

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PubMed1999

Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study.

BACKGROUND: The prevalence of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) in the general population is unknown. Clinicopathological studies of patients diagnosed as having Parkinson's disease suggest that the two disorders may be underdiagnosed. We investigated the population prevalence of these disorders. METHODS: We screened computerised records of 15 general practices in London, UK, for patients with specific diagnostic labels suggestive of Parkinson's disease or parkinsonism and all patients who had ever received antiparkinsonian medication. We assessed eligible patients by review of records, interview, physical examination, and video recordings of neurological signs for independent diagnostic confirmation. We diagnosed parkinsonian disorders according to published criteria and further reviewed patients with atypical features after 1 year. FINDINGS: The participation rate was 84%. The age-adjusted prevalence for PSP was 6.4 per 100,000 (five probable and one possible case [95% CI 2.3-10.6]) and for MSA 4.4 per 100,000 (two probable and two possible cases [1.2-7.6]). An additional four atypical patients were identified at 1 year but did not fulfil criteria for PSP or MSA. INTERPRETATION: Our results suggest that the true prevalence of PSP and MSA has been underestimated, since many patients in the community remain undiagnosed or misdiagnosed.

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PubMed1998

Multiple system atrophy with severe involvement of the motor cortical areas and cerebral white matter.

We report multiple system atrophy (MSA) of 14 years' duration in a 75-year-old woman. Postmortem examination revealed pathological changes typical of MSA. Furthermore, neuronal loss with astrocytosis in the primary motor and premotor cortices, especially in the fifth and sixth layers, and extensive myelin and axonal loss in the frontal and parietal white matter were evident. There were numerous ubiquitin-positive oligodendroglial inclusions, which are characteristic of MSA, in these cortical and white matter lesions. These findings suggest that the motor cortical areas and cerebral white matter are sites of significant involvement in the MSA disease process and that inclusion-bearing oligodendroglial alterations contribute to the white matter degeneration.

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PubMed2004

Alpha-synuclein immunoreactivity in neuronal nuclear inclusions and neurites in multiple system atrophy.

We examined neuronal and oligodendroglial nuclear inclusions and neurites in the pontine base of multiple system atrophy brains using an antibody to alpha-synuclein. Immunohistochemistry showed alpha-synuclein positive inclusions in the nuclei of some neurons and oligodendroglia. Immunoelectron microscopy showed that the labeled inclusions were composed of bundles of tightly packed straight filaments with a diameter of 10-20 nm. The filaments were similar, if not identical, in morphology and immunoreactivity, to those found in the soma of neurons and oligodendrocytes with glial cytoplasmic inclusions. In addition, similar immuno-positive filaments were found in dendrites or unmyelinated axons, but not in myelinated axons. The functional significance of these inclusions in terms of transcriptional and axonal dysfunction is unknown.

Actin Cytoskeleton↗

PubMed2025

Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.

To investigate transcriptomic signatures of Parkinson's disease (PD) and the Parkinsonian subtype of Multiple System Atrophy (MSA-P) in substantia nigra pars compacta (SNpc), we conducted transcriptome analysis using in-situ hybridization on paraffin-embedded SNpc tissues from post-mortem brains. The study included 2 MSA-P patients, 2 PD patients, and 2 healthy controls (HC), with 12 regions of interest (ROIs) selected from the dorsal to ventral and medial to lateral aspects of the SNpc. A total of 72 ROIs from 6 participants were analyzed, and differentially expressed genes (DEGs) were identified by comparing MSA-P, PD and HC groups. The MSA-P group showed 88 upregulated DEGs and 326 downregulated DEGs (adjusted 𝑝<0.05) compared to HC. The downregulated DEGs were significantly enriched in pathways related to ribosomal translation, immune processes, mitochondrial function, and autophagy. Notably, the dorsomedial quadrant was uniquely linked to antigen presentation, while other quadrants showed downregulation of protein synthesis. The PD group exhibited 165 upregulated DEGs and 350 downregulated DEGs (adjusted 𝑝<0.05) compared to HC, with downregulated DEGs associated with ribosomal translation, mitochondrial function, and the ubiquitin-proteasome system. In both MSA-P and PD, the upregulated DEGs were not associated with any pathways or biological process in gene enrichment analysis. In network propagation analysis, amyloid precursor protein was the most significant network hub among DEGs in both MSA-P and PD. Comparing the transcriptomic signatures of SNpc between MSA-P and PD, we found immune/inflammation, mitochondrial function and neural signaling related genes were significantly downregulated in MSA-P compared to PD. Overall, the transcriptomic signature of the SNpc in MSA-P and PD revealed overlapping but distinct features, including alterations in protein synthesis, immune processes, mitochondrial function, and protein degradation systems. Future studies with larger cohorts and functional validation are needed to further elucidate these findings.

Humans↗

PubMed2003

Reciprocal accumulation of beta-synuclein in alpha-synuclein lesions in multiple system atrophy.

Alpha-Synuclein is a major component of neuronal and glial cytoplasmic inclusions in multiple system atrophy (MSA), one of the alpha-synucleinopathies. Recent studies have shown that beta-synuclein, a homolog of alpha-synuclein, inhibits alpha-synuclein aggregation in vitro. We immunohistochemically examined the MSA brain, using specific antibodies against alpha-synuclein and beta-synuclein. alpha-synuclein-positive filamentous aggregates were frequently found in neurons in the pontine and inferior olivary nuclei. No abnormal accumulation of alpha-synuclein was noted in Purkinje cells. In contrast, beta-synuclein accumulation occurred extensively in Purkinje cells, and only minimally in pontine and olivary neurons. Thus, neuronal alpha-synuclein inclusions appear to occur only rarely in neurons in which beta-synuclein accumulates. These findings support the possibility that beta-synuclein is a negative regulator of alpha-synuclein aggregation.

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PubMed1999

[Neuronal kinases in glial cytoplasmic inclusions in patients with multiple system atrophy].

Glial cytoplasmic inclusions (GCI) occur characteristically in the cytoplasms of oligodendrocytes of brains with multiple system atrophy. We examined whether proline-directed protein kinases, which have been found in several neuronal inclusion bodies such as neurofibrillary tangles and Lewy bodies, are associated with GCI. We unexpectedly have observed cdk 5 and MAPK in GCI. These kinases were not immunolabeled in coiled bodies which are oligodendroglial inclusion bodies in brains with progressive supsranuclear palsy and Alzheimer's disease. We also found microtubule-associated protein 2 in oligodendrocytes in brains with MSA, which have not been observed in normal controls or neurological disease controls. Cdk 5 and MAP 2 are principally neuronal proteins. MAPK have been found in neuronal somata and some astrocytes, but not in oligodendrocytes. Thus, the present results suggest that oligodendrocytes in MSA harbor an abnormal phenotypic nature in terms of the aberrant expressions of the principally neuronal proteins.

Brain↗

PubMed2002

Abnormalities of rate-corrected QT intervals in Parkinson's disease-a comparison with multiple system atrophy and progressive supranuclear palsy.

A number of patients with Parkinson's disease (PD) and multiple system atrophy (MSA), in whom sudden death does occur occasionally, have QT or rate-corrected QT (QTc) interval prolongation on electrocardiogram (ECG). Although these QT or QTc interval abnormalities are likely related to autonomic dysfunction, the pathophysiology remains unknown. The aim of this study was to compare the degree of QTc interval prolongation among akinetic-rigid syndromes, namely PD and related disorders, and to evaluate the relationship between QTc prolongation and severity of autonomic dysfunction. Thirty-four patients with PD, 22 with MSA, 11 with progressive supranuclear palsy (PSP) and 30 healthy controls underwent standard autonomic function tests, and electrocardiography variables (RR, QT and QTc intervals) were measured by an ECG recorder with an automated analyzer. The relationship between QTc interval and cardiovascular reflex tests were also analyzed. Orthostatic hypotension and decreased heart rate in response to respiratory stimuli were prominent in MSA, while these were relatively mild in PD. Unlike the RR and QT intervals, the QTc interval significantly differed among all groups (p<0.01). The QTc interval was significantly prolonged in PD (409+/-17 ms; p<0.001) and MSA (404+/-14 ms; p<0.05) compared with healthy controls (394+/-19 ms). Neither autonomic dysfunction nor QTc interval prolongation was evident in PSP. QTc intervals and cardiovascular reflexes did not correlate, except for Valsalva ratio. The QTc interval was obviously prolonged in PD patients to an extent that could not be accounted for simply by autonomic dysfunction levels. MSA patients showed slightly prolonged QTc intervals in spite of marked cardiovascular autonomic dysfunction. Abnormalities of the QTc may reflect the degeneration of cardioselective sympathetic and parasympathetic neurons that cannot be fully captured by cardiovascular autonomic function tests.

Adult↗

PubMed2005

When is Onuf's nucleus involved in multiple system atrophy? A sphincter electromyography study.

BACKGROUND: External anal sphincter (EAS) electromyography (EMG) abnormalities can distinguish multiple system atrophy (MSA) from Parkinson's disease in the first five years after disease onset. However, the prevalence of the abnormalities in the early stages of MSA is unknown. OBJECTIVES: To present EAS-EMG data in the various stages of MSA. METHODS: 84 patients with "probable" MSA were recruited (42 men, 42 women; mean age 62 years (range 47 to 78); mean disease duration 3.2 years (0.5 to 8.0; <1 year in 25%); 50 cerebellar form (MSA-C), 34 parkinsonian form (MSA-P)). EAS motor unit potential (MUP) analysis and EMG cystometry were carried out in all patients. RESULTS: The overall prevalence of neurogenic change of the EAS MUP was 62%-52% in the first year after disease onset, increasing to 83% by the fifth year (p<0.05); it also increased with severity of gait disturbance (p<0.05), storage and voiding disorders, and detrusor sphincter dyssynergy (NS). The neurogenic change was not correlated with sex, age, MSA-P/C, postural hypotension, constipation, erectile dysfunction in men, underactive or acontractile detrusor, or detrusor overactivity. In 17 incontinent patients without detrusor overactivity or low compliance, urinary incontinence was more severe in those with neurogenic change than in those without (p<0.05). CONCLUSIONS: Involvement of Onuf's nucleus in MSA is time dependent. Before the fifth year of illness, the prevalence of neurogenic change does not seem to be high, so a negative result cannot exclude the diagnosis of MSA.

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