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Results for “Multiple System Atrophy”

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PubMed1996

Large neurons in the tuberomammillary nucleus in patients with Parkinson's disease and multiple system atrophy.

To investigate whether the histaminergic neurons degenerate in Parkinson's disease (PD) and multiple system atrophy (MSA), we studied the number of large-sized neurons in the tuberomammillary nucleus in patients with PD, patients with MSA, and age-matched controls. The number of large-sized neurons in the tuberomammillary nucleus in PD patients was not altered compared with controls, and Lewy bodies were rarely present in the tuberomammillary nucleus. In contrast, the number of large-sized neurons in the tuberomammillary nucleus in MSA patients was significantly decreased compared with controls. Thus, the central histaminergic neurons are affected in MSA and preserved in PD.

Aged↗

PubMed1993

[Dysphagia in multiple system atrophy--radiological and manometric study].

Clinical, radiological and manometric studies on 27 patients with multiple system atrophy (MSA) were performed to investigate the characteristics of dysphagia. Patients of MSA were divided into 4 groups: 9 patients of OPCA I (duration < 5 years), 6 patients of OPCA II (duration > or = 5 years), 8 patients of SDS (duration < 5 years) and 4 patients of SND (duration < 5 years). A clinical history was taken to distinguish the two types of dysphagia, that is to say, swallowing disturbance in a narrow sense and passage disturbance. In the radiological study, each phase of swallowing was observed by X-rays with contrast medium (Dionosil). In the manometric study, intraluminal resting pressure in the esophagus and pressure of esophageal contraction after swallowing were measured. The results were as follows: 13 patients (OPCA I 2, OPCA II 6, SDS 2, SND 3) experienced the sensation of swallowing disturbance in a narrow sense and 4 patients (OPCA I 1, OPCA II 1, SDS 1, SND 1) had the feeling of passage disturbance. X-ray studies showed 6 patients (OPCA I 0, OPCA II 1, SDS 1, SND 4) had disturbance of lingual movements, 11 patients (OPCA I 1, OPCA II 5, SDS 3, SND 2) had pooling in piriformis sinus and 14 patients (OPCA I 3, OPCA II 4, SDS 5, SND 2) had slight dilatation of the lower esophagus. In the manometric study, 12 patients (OPCA I 4, OPCA II 4, SDS 3, SND 1) were shown to have low intraluminal resting pressure of the upper esophageal sphincter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

Nocturnal decrease in vasopressin secretion into plasma in patients with multiple system atrophy.

To determine whether the nocturnal decrease in arginine vasopressin (AVP) secretion into the plasma, found in a patient with multiple system atrophy (MSA) reported previously, is a usual finding in MSA, the plasma AVP concentrations in 13 patients with MSA were measured every 4 hours during a 24 hour period. The plasma AVP concentrations in these patients showed significant daily variations and were the lowest during the night. This finding indicates that patients with MSA often exhibit nocturnal decrease in AVP secretion into the plasma. The results suggest the possibility that the system responsible for the daily variations in AVP secretion is involved in MSA.

Aged↗

PubMedDate not supplied

Multiple system atrophy.

Most doctors have vague and imprecise notions of what is meant by the terms olivopontocerebellar atrophy, Shy-Drager syndrome, striatonigral degeneration, multiple system atrophy and multisystem degenerations. This article attempts to tame this nosological jungle.

Atrophy↗

PubMed2004

Sphincter electromyography in diagnosis of multiple system atrophy: technical issues.

Possible technical reasons for the controversy over the role of sphincter electromyography (EMG) in the diagnosis of multiple system atrophy (MSA) were analyzed. In a review of the literature, a high sensitivity (>60%) was found reported in 11 studies that included late components, and no value of the test was found in 4 studies that excluded them. This was also corroborated in a pilot study of 5 patients with probable MSA. With late components included, the mean motor unit potential (MUP) duration was prolonged in all 4 patients with an adequate single-MUP analysis sample and, with late components excluded, in 2 of 5 patients on multi-MUP analysis. At least in diagnostic EMG of MSA patients, late components should be included in the measurement of MUP duration.

Action Potentials↗

PubMed2003

Involvement of precerebellar nuclei in multiple system atrophy.

In this semiquantitative study based on 26 post-mortem cases, we describe the involvement of precerebellar nuclei in multiple system atrophy (MSA), a progressive degenerative disorder of the human central nervous system characterized by abnormal, argyrophilic and alpha-synuclein immunopositive intracellular inclusions within selectively vulnerable oligodendrocytes and nerve cells. The Campbell-Switzer silver-pyridine technique with alpha-synuclein immunoreactions using 100-microm thick sections is recommended over more conventional methods, thereby permitting visualization of the pertinent lesions in greater detail and facilitating post-mortem diagnosis of MSA specimens. Affected oligodendrocytes occur in specific fibre tracts and grey matters, with most pathology being observed in projections from the precerebellar nuclei to the cerebellum (ponto-cerebellar, olivo-cerebellar, reticulo-cerebellar tracts) and in descending/ascending fibre tracts of the motor system (cortico-pontine, cortico-bulbar, cortico-spinal, spino-reticular, spino-olivary, spino-cerebellar tracts). Three types of abnormal intraneuronal aggregations occur: (i) a loosely woven network within the cell nucleus; (ii) a latticework accumulating in peripheral portions of the cell body; and (iii) irregularly outlined patches of compact, intensely argyrophilic material usually located within deposits of lipofuscin granules. Counter-staining for the presence of extraneuronal lipofuscin can aid neuropathologists in the recognition of lost existent neurones in MSA. Neurones with inclusion bodies occur in the inferior olivary nuclear complex, lateral reticular nucleus, external cuneate nucleus, conterminal nucleus, interfascicular nucleus, nucleus of Roller, dorsal paramedian reticular nucleus, subventricular nucleus, arcuate nucleus, pontobulbar body and pontine grey. The lateral reticular nucleus and accessory nuclei of the inferior olive sustain the most damage and reveal prominent neuronal loss, followed by the pontobulbar body and arcuate nucleus. The uniformly bilateral damage and, in some cases, even obliteration of the nuclei studied, supply additional evidence for the pathoanatomical substrata of the cerebellar dysfunction that reportedly emerges in the clinical course of MSA.

Aged↗

PubMed1999

No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy.

To determine whether mutations in the coding region of the alpha-synuclein gene are relevant in cases of multiple system atrophy (MSA), detailed nucleotide sequence analysis of the alpha-synuclein gene was performed using total RNA obtained from autopsied brain specimens of 11 pathologically confirmed cases of MSA. The brain specimens used in this study contained both gray and white matter, which were dissected from the frontal, temporal or occipital lobe. No nucleotide alterations were found in the entire coding region of the alpha-synuclein gene in any of the cases. While mutations in the regulatory or intronic regions of the gene were not ruled out, our results suggest that mutations in the coding region of the alpha-synuclein gene are unlikely to contribute to the pathogenesis of MSA.

Aged↗

PubMed2002

Increased brain histamine levels in Parkinson's disease but not in multiple system atrophy.

We investigated histamine concentration in post-mortem brain samples of patients with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and age-matched controls (n = 27). Histamine concentrations were significantly increased in the putamen (to 159% of the control mean), substantia nigra pars compacta (to 201%), internal globus pallidus (to 234%) and external globus pallidus (to 200%), i.e. in areas which play a crucial role in the motor behaviour and which show typical functional alterations in PD. In MSA no significant differences were seen. Tele-methylhistamine (histamine metabolite) concentrations were unchanged in PD. These results indicate that histamine concentration, but not its metabolism is increased in PD, but not in MSA. This finding may have implications in developing new drug therapies for PD and in differential diagnosis between PD and MSA.

Aged↗

PubMed2006

Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy.

The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson's disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82% of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson's disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2% (1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2% (1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5% (3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson's disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and ponto-cerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes. We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.

Aged↗

PubMed2005

Swallowing function in patients with multiple-system atrophy with a clinical predominance of cerebellar symptoms (MSA-C).

We investigated the swallowing function of 21 patients with multiple system atrophy with a clinical predominance of cerebellar symptoms (MSA-C) by videofluoroscopy (VF). Twenty-six VF examinations were performed at various time points, and they were divided into three groups according to the duration following disease onset: Group A had 1 to 3 years following disease onset (the early stage of the disease), group B had 4 to 6 years following disease onset (the middle stage of the disease), and group C had more than 7 years following disease onset (the late stage of the disease). Swallowing function in the oral phase became gradually disturbed over the progression of MSA. Delayed bolus transport from the oral cavity to the pharynx was already seen in 50% of the patients in group A, and it was seen in more than 85% of the patients in group C. Bolus holding in the oral cavity was slightly disturbed in group A, but it was seen in 57% of the patients in group C. Our study shows that parkinsonism is related to swallowing dysfunction in MSA, but cerebellar dysfunction also affects coordination of the tongue; bolus transport in the oral cavity was disturbed in the early stage of disease. Progression of cerebellar dysfunction and overlapped parkinsonism will worsen tongue movement, and in the late stage of the disease, swallowing function of the oral phase (bolus transport and bolus holding) was remarkably disturbed. Swallowing function in the pharyngeal phase was not significantly correlated to the duration of the disease; however, our study showed that swallowing function in the pharyngeal phase was not assessed fully by VF examination in MSA-C only. Combination with other examinations, such as manometry and electromyography, may be useful, especially in the late stage of the disease. In addition, an analysis concerning the relationship between aspiration seen on VF examination and a history of aspiration pneumonia in MSA-C patients suggested that the sensory system at the larynx and trachea should also be assessed in patients in the late stage of MSA-C.

Aged↗

PubMed2006

Hemodynamic effects of clonidine in two contrasting models of autonomic failure: multiple system atrophy and pure autonomic failure.

We assessed the effects of clonidine on blood pressure (BP) and heart rate (HR) in multiple system atrophy (MSA), where the autonomic nervous system lesion site is preganglionic, and in pure autonomic failure (PAF), where it is postganglionic. In normal subjects, intravenous infusion of the selective alpha2-adrenoceptor agonist clonidine reduces BP and plasma noradrenaline (NA) levels by means of central alpha2-adrenoceptor action, as well as inducing growth hormone (GH) release. Clonidine-induced GH release is impaired in MSA but spared in PAF. However, the hemodynamic effects of clonidine have not been studied extensively in these disorders. We examined intravenous clonidine test results (performed in our autonomic laboratories using the London Autonomic Units protocol) in 58 patients: 39 with probable MSA and 19 with PAF. Systolic BP (SBP), diastolic BP (DBP), HR, and NA levels were measured supine at baseline and for up to 60 minutes after clonidine. Clonidine resulted in a significant BP fall in MSA patients, which occurred earlier (within 15 minutes of clonidine) and to a greater extent than seen in PAF patients. MSA and PAF patients showed reduction in HR after clonidine administration, although this finding was significantly greater in MSA than in PAF patients. NA levels decreased significantly after clonidine administration in both groups. Although basal NA levels were lower in PAF than in MSA patients, there was no difference in NA reduction relative to baseline between groups. MSA patients showed significant negative correlation between basal NA levels and BP response to clonidine. Clonidine infusion reduces BP and HR in both MSA and PAF groups but to a greater extent in MSA patients. The greater vasodepressor action of clonidine in MSA patients suggests that there is partial preservation of brainstem sympathetic outflow pathways in MSA and may reflect its action at sites in the brainstem and spinal cord that were in part functionally preserved in MSA. Despite similar degrees of NA reduction after clonidine administration, the vasodepressor effect of clonidine was attenuated in PAF compared with MSA patients. This attenuation in PAF patients may reflect greater peripheral alpha2-adrenoceptor denervation supersensitivity due to the postganglionic lesion site. These BP differences, thus, may reflect the underlying lesion site in MSA and PAF, and the hemodynamic data after clonidine infusion may help differentiate these conditions.

Adrenergic alpha-Agonists↗

PubMed2000

Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). alpha1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective alpha1 blocker) and moxisylyte (an alpha1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than -30 mmHg at trial entry (P<0.05). Modulation of alpha1-receptors may function in the management of lower urinary tract dysfunction in MSA.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Hyperintensity of the middle cerebellar peduncles on fluid-attenuated inversion recovery imaging: variation with age and implications for the diagnosis of multiple system atrophy.

BACKGROUND AND PURPOSE: T2 hyperintensity of the middle cerebellar peduncle (MCP) is described in a number of diseases, including multiple system atrophy (MSA). We hypothesize that mild MCP hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging can be a normal finding. To our knowledge, a detailed study of the prevalence of this finding in various age groups with the FLAIR sequence has not been described. METHODS: One hundred twenty-two patients underwent an axial FLAIR examination of the brain as part of either a hearing loss or tinnitus work-up (ie, to exclude an acoustic neuroma or a retrocochlear cause). Subjects aged 15-78 years were included to reflect an even spread through the decades and were divided into 6 age groups. A radiologist and an MR imaging fellow graded the examinations subjectively, blinded to age: 0 for normal or 1 for the presence of MCP hyperintensity if the increased signal intensity was greater than that of adjacent pons and cerebellar white matter. Spearman rank correlation test of MCP hyperintensity with age and analysis of variance (ANOVA) were performed. RESULTS: Of 122 patients, we identified 17 with MCP FLAIR hyperintensity. None of these patients had a clinical condition that could cause MCP hyperintensity. MCP hyperintensity did not show a statistically significant correlation with age (r = 0.05, P = .62). Patients were divided into 6 age groups, and ANOVA showed no statistically significant difference in the incidence of MCP hyperintensity between different age groups (P = .95). However, results were highly reproducible with excellent interobserver correlation (r = 0.97, P < .001). CONCLUSIONS: Mild MCP FLAIR hyperintensity can occur normally, and this finding shows no relationship with age.

Adolescent↗

PubMed2002

Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction.

Activities of Daily Living↗

PubMed2002

[Multiple system atrophy with a-/hypo-ceruloplasminemia: distribution of iron in brains of 2 autopsy cases].

OBJECTIVE: We presented first two cases of multiple system atrophy (MSA) with a-/hypo-ceruloplasminemia (hypo-Cp). To know whether hypo-Cp was a cause of MSA, we investigated distribution of iron in brains. METHODS: Investigating history, neurological sings and symptoms, neuroimagings, and neuropathological findings of the 2 cases, we demonstrate that these 2 cases were typical MSA. Serum ceruloplasmin (Cp) values of two cases were investigated, as well as those of 14 MSA patients diagnosed after the 2 cases. In the 2 cases, we compared distribution of lesions and distribution of iron depositions revealed by Berlin blue stain (iron stain). Further, we compared depositions of iron in substantia nigra, putamen, and dentate nucleus of the 2 cases with those of 4 control MSA, 2 Parkinson's disease (PD), 2 amyotrophic lateral sclerosis (ALS), and 3 controls. RESULTS: Case 1 was 68-year-old man who developed gait disturbance, and had anti-Parkinson disease drugs after diagnosis of PD. Parkinsonism was progressed, and became bed-ridden after 6 years when he died. Neuropathological finding was typical MSA from distribution of lesions, as well as existence of GCIs and NCIs. Case 2 was 61-year-old man who developed parkinsonism. After 9 years, he had tracheostomy, and after 11 years died of renal failure. Neuropathological finding was typical MSA. With an investigation of serum Cp values of clinically diagnosed 14 MSA patients, we found 2 other cases of MSA with hypo-Cp. Iron stain of the 2 brains revealed that iron depositions were found in substantia nigra and putamen, but were not found neither in pontine base, cerebellum, nor inferior olive. Iron depositions were also seen in substantia nigra and putamen of control MSA cases as same degree as MSA with hypo-Cp, but iron depositions were fewer in PD, ALS and controls. CONCLUSION: Clinico-pathological findings of the the 2 cases were those of typical MSA, but were not same as those of previously reported hypo-Cp. Previous reports suggested iron depositions as a cause of brain lesions, but, we concluded that, in the 2 cases, iron depositions were not a direct cause of MSA lesions. However, high incidence of association of hypo-Cp and MSA shown in our study suggests a relation between hypo-Cp and MSA.

Aged↗

PubMed2003

Coordination of fingertip forces during precision grasping in multiple system atrophy.

While the pathology and autonomic nervous system components of multiple system atrophy (MSA) have been well described, little is known about the associated motor dysfunction. One prominent feature of MSA is parkinsonism, although ataxias and pyramidal tract signs are frequently present. To investigate the nature of motor deficits in MSA, a natural grip-lift movement requiring a precision grasp was used to examine force coordination. Subjects were asked to grasp an instrumented object using the fingertips of the thumb and index finger and lift it 10 cm above the table surface. Subjects with MSA demonstrated a prolonged duration between object contact and initiation of the lifting drive that increased with the weight of the object. During this period these subjects produced large grasping forces generating a significant portion of the eventual grip force employed to hold the object. In contrast, control subjects generated grip and load forces in parallel after establishing contact with the object. Therefore, subjects with MSA showed a disrupted performance on both the sequential (grasp, then lift) and simultaneous (grip and load force development) portions of this task. Only after initiation of the vertical lifting drive did subjects with MSA generate forces in a similar manner to control subjects. These findings demonstrate that subjects with MSA exhibit a disrupted coordination of grasp and could suggest a general deficit in motor control resulting from multi-focal neural degeneration.

Adaptation, Physiological↗

PubMed1998

Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Antiparkinson Agents↗

PubMed1999

Phosphorus magnetic resonance spectroscopy in multiple system atrophy and Parkinson's disease.

We performed in vivo phosphorus magnetic resonance spectroscopy on the occipital lobes of 15 patients with multiple system atrophy (MSA; eight with olivopontocerebellar atrophy [OPCA] and seven with the striatonigral degeneration variant [SND]), 13 patients with idiopathic Parkinson's disease (PD), and 16 age-matched healthy subjects. The MSA group showed significantly reduced phosphocreatine (PCr), increased inorganic phosphate (Pi), and unchanged cytosolic free [Mg2+], and pH. We did not find any significant difference between the OPCA and SND variants. However, patients with PD showed significantly increased content of Pi, decreased cytosolic free [Mg2+], and unchanged [PCr] and pH. Comparing the MSA and PD groups, [PCr] was significantly lower in MSA than in PD, whereas cytosolic free [Mg2+] was significantly lower in PD. Despite a certain degree of overlap of [PCr] and [Mg2+] values between the two groups, by considering both variables at the same time it was possible to classify correctly 93% of cases by discriminant analysis. We conclude that phosphorus magnetic resonance spectroscopy discloses abnormal phosphate metabolite and ion contents in both MSA and PD, respectively, and may provide noninvasive diagnostic help to differentiate MSA from PD.

Adult↗