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Results for “Multiple System Atrophy”

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PubMed2001

No functional effects of embryonic neuronal grafts on motor deficits in a 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy).

Intrastriatal injection of 3-nitropropionic acid results in secondary excitotoxic local damage and retrograde neuronal cell loss in substantia nigra pars compacta, thus mimicking salient features of striatonigral degeneration, the core pathology underlying Parkinsonism associated with multiple system atrophy. We used 3-nitropropionic acid to create a rat model of advanced striatonigral degeneration in order to assess the effects of embryonic allografts upon rotational and complex-motor behavioural abnormalities. Following stereotaxic intrastriatal administration of 500nmol 3-nitropropionic acid in male Wistar rats we observed consistent amphetamine- and apomorphine-induced ipsiversive rotation. Furthermore, there were marked deficits of contralateral paw reaching. Subsequently, animals received intrastriatal implantations of either E14 mesencephalic or striatal or mixed embryonic cell suspensions. In addition, one group received sham injections. Grafted rats were followed for up to 21 weeks and repeated behavioural tests were obtained during this period. Drug-induced rotation asymmetries and complex motor deficits measured by paw reaching tests were not compensated by embryonic grafts. Persistence of drug-induced rotations and of paw reaching deficits following transplantation probably reflects severe atrophy of adult striatum, additional nigral degeneration as well as glial demarcation of embryonic grafts. We suggest that dopamine rich embryonic grafts fail to induce functional recovery in a novel 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy).

Animals↗

PubMed1995

Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise for trade off between sensitivity and specificity was a cut off value at a score of 3. The sensitivity and specificity of the individual pointers considered to predict fully symptomatic MSA varied considerably, and no single item could predict whether patients presenting with just parkinsonian signs went on during the two year follow up period to develop fully symptomatic MSA. Instead, the number of abnormalities offered a predictive value for the clinical prognosis of these parkinsonian patients.

Adult↗

PubMedDate not supplied

Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France.

We investigated the prevalence of multiple system atrophy (MSA) in Gironde, France, through a network of 120 public and private specialists and assessed the relationship between some environmental factors and MSA in a case-control study involving 50 MSA patients, 50 Parkinson's disease (PD) patients and 50 healthy controls. The occupational exposure to pesticides was evaluated through a job-exposure matrix. On prevalence day (November 1, 1998), the crude prevalence of MSA in Gironde was 1.94/100,000 inhabitants. We found no significant relationship between occupational exposure to pesticides and MSA. PD patients were significantly less frequently ever-smokers than controls and the same tendency was observed for MSA patients. We also described the clinical features that heralded the disease among this nonselected population.

Adolescent↗

PubMed2001

Increased growth hormone response to apomorphine in Parkinson disease compared with multiple system atrophy.

BACKGROUND: Parkinson disease (PD) is often difficult to distinguish from parkinsonian syndromes of other causes in early stages of the disease. In search of a suitable endocrinologic challenge test, we investigated dopaminergic sensitivity in patients with de novo parkinsonian syndromes. OBJECTIVE: We measured the growth hormone (GH) response to a subthreshold dose of the dopamine 1-dopamine 2 receptor agonist apomorphine hydrochloride to differentiate parkinsonian syndromes from PD. PATIENTS AND METHODS: Seventeen patients with a clinical diagnosis of PD, 16 patients with a clinical diagnosis of multiple system atrophy, and 11 healthy controls. The GH response to a subthreshold dosage of apomorphine and to somatorelin (GH-releasing factor) was tested in a randomized order; on the third day the protocol was repeated with a clinically effective dose of apomorphine. RESULTS: The GH response to the low dose of apomorphine was significantly increased in patients with PD when compared with patients with multiple system atrophy or the control subjects (multivariate analyses of covariance; univariate F test, all P<.05). In contrast, there were no significant group differences with use of the higher dose of apomorphine or in the somatorelin-induced GH release. CONCLUSIONS: The GH response to a subthreshold dose of apomorphine appears to be a useful tool to identify patients with PD vs multiple system atrophy. The enhanced GH response to a subthreshold dopaminergic stimulus may reflect a hypersensitivity of the extrastriatal dopamine receptors in PD.

Adrenocorticotropic Hormone↗

PubMed2001

Comparison of natural histories of progressive supranuclear palsy and multiple system atrophy.

In order to identify early clinical features and survival predictors of supranuclear palsy (PSP) and multiple system atrophy (MSA), we compared the disease course of patients consecutively referred between 1987 and 1999 and followed to December 1999. Thirty-nine PSP and 74 MSA patients were diagnosed according to commonly accepted clinical criteria. Length of survival was ascertained from death certificates or by contacting relatives. Ten-year survival after disease onset was 29% for both disorders. Median survival was 7.0 years (PSP) and 7.5 (MSA). Neither age, symptoms at onset, or disability at diagnosis predicted survival. At diagnosis, all PSP patients had oculomotor palsy, whereas 89% of MSA patients had dysautonomia; bradykinesia and falls were the most frequent common signs. Distinctive early signs were palilalia, cognitive impairment and hyperreflexia in PSP; hypophonia, anterocollis and dysautonomia in MSA. MSA patients responded better to levodopa. Attention to early distinctive features can improve differential diagnosis and inform subsequent management.

Aged↗

PubMed2001

Pathogenesis of laryngeal narrowing in patients with multiple system atrophy.

1. We do not fully understand the pathogenesis of nocturnal laryngeal stridor in patients with multiple system atrophy (MSA). Recent studies suggest that inspiratory thyroarytenoid (TA) muscle activation has a role in the development of the stridor. 2. The breathing pattern and firing timing of TA muscle activation were determined in ten MSA patients, anaesthetized with propofol and breathing through the laryngeal mask airway, while the behaviour of the laryngeal aperture was being observed endoscopically. 3. Two distinct breathing patterns, i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the measurements. During IFL, significant laryngeal narrowing was observed leading to an increase in laryngeal resistance and end-tidal carbon dioxide concentration. Development of IFL was significantly associated with the presence of phasic inspiratory activation of TA muscle. Application of continuous positive airway pressure suppressed the TA muscle activation. 4. The results indicate that contraction of laryngeal adductors during inspiration narrows the larynx leading to development of inspiratory flow limitation accompanied by stridor in patients with MSA under general anaesthesia.

Aged↗

PubMed2000

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↗

PubMed2002

Sleep disorders and their determinants in multiple system atrophy.

OBJECTIVES: To evaluate the incidence, types, determinants, and consequences of sleep disorders in patients with multiple system atrophy (MSA) and determine whether their characteristics are similar to those of patients with Parkinson's disease (PD). METHODS: Information about sleep disorders was collected using a standardised questionnaire in an unselected group of 57 patients with MSA and in 62 patients with PD matched as a group for age, sex distribution, and disease duration. RESULTS: Seventy percent of patients with MSA complained of sleep disorders compared with 51% of patients with PD (p=0.03). The most commonly reported sleep disorders were sleep fragmentation (52.5%), vocalisation (60%), REM sleep behaviour disorder (47.5%), and nocturnal stridor (19%). Except for sleep fragmentation, the incidence of these disorders was significantly higher than in PD. Sleep problems tended to be associated with more severe motor symptoms, longer disease duration, depression, and longer duration of levodopa treatment. Half of patients with MSA with sleep disorders complained of daytime somnolence compared with 30% of patients with PD. Daytime somnolence was significantly associated with disease severity in MSA. CONCLUSION: This study shows that sleep disorders are more common in patients with MSA than in those with PD after the same duration of the disease, reflecting the more diffuse underlying pathological process in MSA.

Aged↗

PubMed1993

Dopa resistance in multiple-system atrophy: loss of postsynaptic D2 receptors.

Postmortem autoradiography was used to explore the mechanisms underlying L-dopa resistance in 2 patients with multiple-system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H-mazindol, 3H-SCH 23390, and 125I-sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple-system atrophy, resistance to L-dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.

Aged↗

PubMed2004

Asymmetrical awake bruxism associated with multiple system atrophy.

We describe a 51-year-old man who developed awake bruxism during the course of multiple system atrophy. Electromyographic studies revealed side-to-side amplitude asymmetry of the bursts of motor activity. The bruxism responded favourably to low-dose levodopa-carbidopa therapy. Possible mechanisms of this rare association are discussed.

Bruxism↗

PubMed2002

Observations on haematological and cardiovascular effects of erythropoietin treatment in multiple system atrophy with sympathetic failure.

Symptomatic autonomic neuropathy and in particular sympathetic failure mediated postural hypotension often accompanies Multiple System Atrophy (MSA). Release of erythropietin is under sympathetic control and we and others have previously reported that severe autonomic failure may be associated with a normocytic normochromic anaemia and erythopietin (EPO) deficiency. In this paper we describe the haematological, cardiovascular and clinical observations on a patient with MSA and severe symptomatic autonomic neuropathy who had haematological and clinical improvement (substantial increase in standing blood pressure) following subcutaneous EPO treatment.

Aged↗

PubMed2001

Irresistible onset of sleep during acute levodopa challenge in a patient with multiple system atrophy (MSA): placebo-controlled, polysomnographic case report.

A 67-year-old male patient with clinically probable multiple system atrophy developed severe reproducible sleepiness and irresistible onset of sleep during an acute levodopa (L-dopa) challenge. In a placebo-controlled, double-blind study of acute L-dopa challenge, videopolysomnography revealed multiple episodes of non-rapid eye movement sleep 60 minutes after L-dopa and none following placebo. These observations suggest the irresistible sleep can also be induced by L-dopa and also in patients with atypical parkinsonism.

Aged↗

PubMed2003

The effect of intranasal desmopressin on nocturnal waking in urination in multiple system atrophy patients with nocturnal polyuria.

Nocturnal waking in urination (nocturia) is a common feature in patients with multiple system atrophy (MSA). Degeneration of arginine vasopressin (AVP) neurons in the suprachiasmatic nucleus in this disorder may lead to nocturnal polyuria, which has been treated with intramuscular desmopressin. We also prescribed 5 microg of intranasal desmopressin once a night in 3 MSA patients, who had nocturnal polyuria with abnormal circadian rhythm of the plasma AVP. During the treatment, all patients showed an improvement in their nocturia without serious adverse effects.

Administration, Intranasal↗

PubMed2001

Nocturnal body core temperature falls in Parkinson's disease but not in Multiple-System Atrophy.

OBJECTIVE: To evaluate whether the circadian rhythm of body core temperature (CRT degrees ) can differentiate Multiple-System Atrophy (MSA) from Idiopathic Parkinson's disease (IPD). METHODS: We evaluated 14 patients with probable MSA, seven with IPD, and eight controls. After a preliminary evaluation of cardiovascular autonomic function, rectal temperature and sleep-wake cycle were monitored continuously for 48 hours in a temperature-controlled room, at constant bed rest with controlled food intake and fixed light-dark schedule. RESULTS: MSA patients showed cardiovascular autonomic sympathetic and parasympathetic failure. IPD had normal cardiovascular autonomic function. A 24-hour rhythm of body core temperature (BcT degrees ) was present in all subjects. IPD had CRT degrees comparable to controls. In MSA the mesor was higher and mean BcT degrees of each hour was significantly higher from 11 p.m. to 7 a.m. The analysis of mean BcT degrees during the different sleep phases showed significantly higher values during both NREM (1--2, 3--4) and REM sleep stages in MSA. CONCLUSIONS: The physiological nocturnal fall of BcT degrees is blunted in MSA patients mainly because BcT degrees did not decrease during sleep. This CRT degrees pattern is not justified by differences in sleep structure and may reflect an impairment of central sympathetic nervous system function.

Adult↗

PubMed2004

Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy.

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.

Aged↗

PubMed2004

Annular alpha-synuclein species from purified multiple system atrophy inclusions.

Oligodendroglial cytoplasmic inclusions composed of alpha-synuclein filamentous aggregates are the pathological hallmark of multiple system atrophy (MSA). We found that cortical tissue from MSA cases contains increased detergent-resistant high-molecular-weight alpha-synuclein species. To analyse these species, we immunopurified alpha-synuclein aggregates from pathological samples and examined their ultrastructures using scanning electron and atomic force microscopies. Purified aggregates consisted of bundles of filaments. After treatment with 1% sarcosine or 2% 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propanesulfonate (CHAPS) detergents, we observed frequent 30-50 nm annular particles, probably released from pathological aggregates due to the dissociation of filaments by the detergents. Antibody recognition imaging using a specific anti-alpha-synuclein antibody confirmed that the annular structures were positive for alpha-synuclein. In contrast to pathological alpha-synuclein, detergent treatment of recombinant alpha-synuclein yielded only smaller, 10-18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA alpha-synuclein aggregates, but not recombinant alpha-synuclein, yields discrete alpha-synuclein-positive species with annular morphologies. The ability of the pathological alpha-synuclein to form annular aggregates may be an important factor contributing to the toxicity of the protein in disease that may have implications in designing therapeutic strategies aimed at detoxifying alpha-synuclein aggregates.

Brain Chemistry↗

PubMed1994

Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy.

Slit-hyperintensity in the outer margin of the putamen on T2 weighted MRI was found in 17 out of 28 patients with clinically diagnosed multiple system atrophy. Thirteen of these 17 patients showed extrapyramidal signs. Five patients had only unilateral slit-hyperintensity; four of them had contralateral rigidity; and one had bradykinesia. Despite mild rigidity, one case showed no slit-hyperintensity. One of the 14 cases with parkinsonism showed no hyperintensity, and four of the 14 cases without parkinsonism showed hyperintensity. On the other hand, slit-hyperintensity was not seen in any of 25 patients with clinically diagnosed Parkinson's disease. Putaminal slit-hyperintensity is a useful MRI feature in the differential diagnosis between Parkinson's disease and multiple system atrophy predominantly affecting the extrapyramidal system.

Aged↗

PubMed2002

Magnetization transfer measurements of brain structures in patients with multiple system atrophy.

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.

Aged↗