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Results for “Multiple System Atrophy”

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PubMed2005

FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), a novel disorder in male carriers of premutations of the fragile X mental retardation 1 gene (FMR1), was recently described. The clinical presentation of FXTAS most closely resembles multiple system atrophy (MSA) because both disorders manifest with cerebellar ataxia, intention tremor, autonomic dysfunction, and parkinsonism. It has been proposed that FXTAS might be a common neurodegenerative disorder. OBJECTIVE: To determine whether FXTAS accounts for patients currently diagnosed as having MSA or a related clinical diagnosis. DESIGN: Patients with MSA or related phenotypes were examined by experienced movement disorders neurologists, and DNA samples were obtained for genetic study. SETTING: Salpêtrière Hospital. PATIENTS: Seventy-seven patients clinically diagnosed as having MSA, 19 as having olivopontocerebellar atrophy, and 27 as having cerebellar ataxia. MAIN OUTCOME MEASURE: The number of FMR1 repeats was determined in all patients by polymerase chain reaction. Alleles above 40 CGG repeats were controlled by Southern blot analysis. RESULTS: Two patients carried FMR1 premutations of 110 and 135 repeats: a man with a familial form of cerebellar ataxia and a woman diagnosed as having MSA-cerebellar type. In addition, 9 patients (7%) carried alleles in the intermediate size range, from 41 to 53 repeats. CONCLUSIONS: We confirm the recent initial description of FXTAS in women. Our data suggest that FXTAS is rare in MSA and indicate that FXTAS might be less prevalent than proposed.

Adult↗

PubMed1994

Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy.

We used positron emission tomography with [18F]fluorodeoxyglucose to study local cerebral metabolic rates for glucose (ICMRglc) in patients with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA) in comparison with normal control subjects. IN MSA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In sOPCA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In dOPCA, absolute lCMRglc was significantly decreased in the brainstem and cerebellum but not in the other structures. Examination of lCMRglc normalized to the cerebral cortex in comparison with normal controls revealed in MSA significant decreases in the brainstem, cerebellum, and putamen but, in both sOPCA and dOPCA, significant decreases only in the brainstem and cerebellum. The findings indicate that these three disorders all show a marked decrease of lCMRglc in the brainstem and cerebellum but differ in the degree of hypometabolism in forebrain and cerebral cortical structures. The results are consistent with the possibility that, in many cases, sOPCA will evolve into MSA. Moreover, positron emission tomography may provide helpful diagnostic information in these neurodegenerative diseases.

Adult↗

PubMed1999

Decreased striatal monoaminergic terminals in multiple system atrophy detected with positron emission tomography.

We examined the density of striatal presynaptic monoaminergic terminals, using a ligand for the type 2 vesicular monoamine transporter, (+)-[11C]dihydrotetrabenazine, with positron emission tomography in 7 normal control subjects, 8 multiple system atrophy (MSA) patients with predominantly parkinsonian features (MSA-P), 8 MSA patients with principally cerebellar dysfunction (MSA-C), and 6 sporadic olivopontocerebellar atrophy (sOPCA) patients. The findings were correlated with the results of neurological evaluations and magnetic resonance imaging studies. Specific binding was significantly reduced in the putamen of all patient groups in the order MSA-P < MSA-C < sOPCA, compared with controls. Mean blood-to-brain ligand transport (K1) was significantly decreased in the putamen of all patient groups and in the cerebellar hemispheres of MSA-C and sOPCA but not MSA-P groups, compared with controls. Significant negative correlations were found between striatal binding and the intensity of parkinsonian features and between cerebellar K1 and the intensity of cerebellar dysfunction. The results suggest fundamental differences between MSA-P and MSA-C groups reflecting differential severity of degeneration of nigrostriatal and cerebellar systems in these two forms of MSA. The findings also show that some sOPCA patients have subclinical nigrostriatal dysfunction and are at risk of developing MSA with disease progression.

Adult↗

PubMed1999

Affective symptoms in multiple system atrophy and Parkinson's disease: response to levodopa therapy.

The objective was to determine the extent to which psychiatric disturbances (especially mood disorders) generally considered poor prognostic factors, are present in patients with striatonigral (SND) type multiple system atrophy (MSA) compared with patients with idiopathic Parkinson's disease (IPD). The Hamilton depression scale (HAM-D), brief psychiatric rating scale (BPRS), and Unified Parkinson's disease rating scale (UPDRS) were administered to clinically probable non-demented patients with SND-type MSA and patients with IPD matched for age and motor disability, at baseline and after receiving levodopa. At baseline total HAM-D score was greater in patients with IPD. Overall, BPRS score did not differ between the two groups; however, patients with IPD scored higher on anxiety items of the BPRS, and patients with MSA had higher scores on the item indicating blunted affect. After levodopa, both groups improved significantly in UPDRS and HAM-D total scores (just significant for patients with MSA). Patients with IPD improved significantly in total BPRS score but patients with MSA did not. At baseline patients with IPD were more depressed and anxious than patients with MSA who, by contrast, showed blunted affect. After levodopa, depression and anxiety of patients with IPD improved significantly whereas the affective detachment of patients with MSA did not change. Major neuronal loss in the caudate and ventral striatum, which are part of the lateral orbitofrontal and limbic circuits, may be responsible for the blunted affect not responsive to levodopa therapy found in patients with MSA.

Antiparkinson Agents↗

PubMed2005

Hyperintense putaminal rim sign is not a hallmark of multiple system atrophy at 3T.

BACKGROUND AND PURPOSE: Hyperintense putaminal rim (HPR) on the T2-weighted imaging, which has been observed in our daily practice while reading 3T brain images, has been described as a finding typical of multiple system atrophy (MSA). We hypothesized that the HPR sign is not an exclusive hallmark of MSA at a high magnetic field strength, but rather may be a normal finding. METHODS: Ten consecutive clinically healthy age-matched adults who showed recognizable HPR at 3T were subsequently examined on a 1.5T imaging system within 2 hours. MR examination included axial T2-weighted fast spin-echo (FSE), fluid attenuated inversion recovery (FLAIR) on a 3T scanner, and equivalent T2-weighted FSE at 1.5T. MR images were obtained parallel to the intercommissural plane. All the images were interpreted by 2 experienced neuroradiologists. RESULTS: All 10 subjects (3 men and 7 women; aged 52 +/- 6.1 years [range, 44-61 years], expressed as mean +/- SD) with the positive HPR sign on axial T2-weighted FSE at 3T had negative findings at 1.5T. Such hyperintense rim was also vague or absent on the 3T-FLAIR images. CONCLUSION: Our data suggest that the HPR at 3T scans is a nonspecific, normal finding. FLAIR may be helpful in discriminating between normal subjects and patients with MSA in case of isolated HPR at 3T.

Adult↗

PubMed2004

A quantitative study of the pathological changes in ten patients with multiple system atrophy (MSA).

The densities of the glial cytoplasmic inclusions (GCI), neuronal inclusions (NI), and abnormal neurons were studied in the frontal cortex, hippocampus, cerebellum, basal ganglia and areas of the pons and medulla in 10 cases of multiple system atrophy (MSA). GCI density was greater in the substantia nigra and globus pallidus compared with the frontal cortex and hippocampus. Abnormal neurons were most abundant in the frontal cortex, substantia nigra, and inferior olivary nucleus. NI and abnormal neuron densities were positively correlated in the globus pallidus but negatively correlated in the hippocampus. The NI and GCI were only positively correlated in the pons. GCI in the pons and inferior olivary nucleus, NI in the substantia nigra, and abnormal neurons in the frontal cortex varied significantly between cases. The MSA cases did not cluster according to disease subtype. The data suggest that: 1) the greatest densities of pathological changes occur in the substantia nigra and globus pallidus, 2) density of the GCI is unrelated to that of the NI, and 3) there is overlapping pathology between the various subtypes of MSA.

Age of Onset↗

PubMed1992

Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure.

To investigate whether activation of afferent and central baroreceptor pathways could differentiate between pure autonomic failure (PAF) and multiple system atrophy with autonomic failure (MSA), we determined the effect of upright tilt on circulating levels of vasopressin in patients with PAF and patients with MSA. We also studied 14 normal subjects, nine of whom developed acute hypotension due to vasovagal syncope. In patients with PAF and in normal subjects with vasovagal syncope, upright tilt induced marked hypotension and a pronounced increase in the plasma concentration of vasopressin (1.1 +/- 0.3 to 38.0 +/- 8.0 pmol/l in PAF and 1.0 +/- 0.2 to 27.4 +/- 7.2 pmol/l in vasovagal syncope, p less than 0.005 for both). In patients with MSA, upright tilt also elicited profound hypotension but circulating levels of vasopressin increased little (0.5 +/- 0.1 to 1.5 +/- 0.3 pmol/l, p less than 0.05). During upright tilt, the plasma concentration of norepinephrine significantly increased in normal subjects but did not increase in patients with autonomic failure. Our results indicate that afferent and central baroreceptor pathways involved in vasopressin release are normal in patients with PAF but are impaired in patients with MSA. Thus, measurement of baroreceptor-mediated vasopressin release appears to provide a clear marker to differentiate between patients with PAF and patients with MSA.

Adult↗

PubMed2002

Haemodynamic responses during head-up tilt and tilt reversal in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy.

Continuous haemodynamic responses to head-up tilt (HUT) and its reversal were studied in 21 subjects with sympathetic denervation due to primary chronic autonomic failure; 10 had pure autonomic failure (PAF; peripheral failure) and 11 had multiple system atrophy (MSA; central failure); 8 healthy subjects (controls) also were studied. Supine systolic, diastolic and mean arterial pressure (MAP) and total peripheral resistance (TPR) were highest in PAF. The MAP response to HUT and tilt reversal were different between groups. After HUT, MAP increased in controls (12+/-4 mmHg), but decreased in PAF and MSA (41+/-4 & 19+/-4 mmHg respectively); the fall in PAF was greater than in MSA. With tilt reversal, MAP returned promptly, but not entirely to pretilt levels in controls, with small (insignificant) overshoots in MSA and PAF. The TPR response to HUT and tilt reversal was different between groups. After HUT, TPR increased in controls (0.31+/-0.04 PRU), decreased in PAF (0.23+/-0.1 PRU) and was unchanged in MSA. With tilt reversal, TPR remained elevated (15 %) above baseline in the controls and rose in PAF (13 %) with no change in MSA. There were no differences in supine heart rate (HR), stroke volume (SV) or cardiac output (CO) between the three groups; HR, SV or CO responses to HUT or tilt reversal also did not differ between the groups. Thus, after HUT, MAP decreased, with greater hypotension induced in PAF than MSA. Since CO did not differ between groups, the decrease in TPR appears to account for the greater fall in BP in PAF than in MSA. The elevated TPR at rest pre-tilt and after tilt reversal probably contributed to supine hypertension in PAF. These haemodynamic observations may aid therapeutic strategies to reduce orthostatic hypotension and prevent supine hypertension.

Aged↗

PubMed2005

Subcortical dementia revisited: similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA).

To examine the similarities and differences in cognitive function between three predominantly subcortical dementing disorders associated with parkinsonism we compared the profiles of cognitive performance in 39 patients with Progressive Supranuclear Palsy (PSP), 26 patients with Multiple System Atrophy (MSA) and 25 with Corticobasal Degeneration (CBD) with those of 30 patients with classic cortical dementia, Alzheimer's Disease (AD), using two different cognitive screening tests: Dementia Rating Scale (DRS) and Addenbrooke's Cognitive Examination (ACE). The cognitive profile on ACE and DRS subtests distinguished subcortical diseases from each other as well as from AD. All parkinsonian syndromes were characterized by a disproportionate impairment in verbal fluency, particularly letter fluency. The three diseases differed, however, in the degree of language, memory and visuospatial impairment. We conclude that similarities, as well as differences, between PSP, MSA and CBD can be detected using a brief, clinically applicable cognitive screening test. The pattern of cognitive impairment is likely to reflect a different distribution of pathology, in particular a higher degree of cortical involvement in PSP and CBD.

Aged↗

PubMed2003

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Aged↗

PubMedDate not supplied

[A case of multiple system atrophy treated with erythropoietin].

The patient, a women aged 52, with a three-year history of treatment for arterial hypotension, was admitted to hospital because of progressing worsening of symptoms. The whole clinical syndrome made possible the recognition of multiple system atrophy as the cause of her symptoms. In view of failures in previous treatment it was decided to give her erythropoietin injections for four weeks. The treatment led to improvement of her status. The authors discuss the probable action mechanism of erythropoietin in this case.

Erythropoietin↗

PubMed2000

Constant involvement of the Betz cells and pyramidal tract in multiple system atrophy: a clinicopathological study of seven autopsy cases.

We investigated clinicopathologically the pyramidal signs, including spasticity, hyperreflexia, and Babinski's sign, and the involvement of the pyramidal tract and primary motor cortex, in seven Japanese autopsy cases of multiple system atrophy (MSA). Pyramidal signs were observed in six (86%) of the seven autopsy cases. Hyperreflexia and Babinski's sign were each evident in five patients, but spasticity was observed in only one patient. Loss of Betz cells and presence of glial cytoplasmic inclusions in the primary motor cortex were noticed in all seven cases. Astrocytosis in the fifth layer of the primary motor cortex was noticed in five cases, but its presence was not related to the duration of the disease. Involvement of the pyramidal tract in the spinal cord, particularly of the small myelinated fibers, was observed in all seven cases, but no involvement of the pyramidal tract in the midbrain was evident in any of the six cases in which this structure was examined. In MSA, pyramidal signs were shown to be present more frequently than believed before, and the clinicopathological correlation between pyramidal signs and involvement of the pyramidal tract was obvious. Constant involvement of Betz cells in MSA has not been reported. Our clinicopathological findings may also make a contribution to the understanding of the clinicopathological hallmarks of MSA.

Female↗

PubMed1999

Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy.

By using three-dimensional magnetic resonance imaging-based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinson's syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA-P, n = 12) or ataxia (MSA-C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA-C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA-P, 15 of 17 patients with MSA-C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA-P could not be separated from patients with PSP. In conclusion, total intracranial volume-normalized magnetic resonance imaging-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism.

Adult↗

PubMed2002

Cerebral metabolic changes in early multiple system atrophy: a PET study.

Previous positron emission tomography (PET) studies have shown widespread hypometabolism in the brain of advanced MSA but the time course of these metabolic abnormalities is largely unknown. In order to clarify the principal disease processes in multiple system atrophy (MSA) in the early stage, we investigated regional cerebral glucose metabolism (rCMGglc) and nigral dopaminergic function in nine patients with early stage of MSA using [(18)F]fluorodeoxyglucose (FDG) and 6-L-[(18)F]fluorodopa ((18)F-Dopa) positron emission tomography (PET) (two men and seven women; age, 59.3+/-5.4 years; disease duration, 29.7+/-14.6 months). The rCMRglc in the early MSA patients significantly decreased in the cerebellum, brainstem, and striatum compared with that in nine normal subjects. A significant correlation was found between the severity of autonomic dysfunction and rCMRglc within the brainstem. The severity of extrapyramidal signs also correlated with the decline of F-Dopa uptake but not that of rCMRglc within the striatum. The degree of atrophy on MRI has correlated with neither the clinical symptoms nor rCMRglc at the cerebellum and the brainstem. Our PET studies demonstrated widespread metabolic abnormalities except for the cerebral cortex in the brain of MSA even in the early stage. The hypometabolism in the brainstem was tightly linked to the autonomic dysfunction. Not the striatal dysfunction but the nigral damage may be responsible for the extrapyramidal symptoms in early MSA.

Aged↗

PubMed2004

Imaging of dopamine transporters and D2 receptors in patients with Parkinson's disease and multiple system atrophy.

PURPOSE: The aim of this study was to ascertain whether combined presynaptic and postsynaptic dopaminergic single-photon emission computed tomography (SPECT) scanning is useful for differentiation between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy of the striatonigral type (MSA) and healthy subjects. METHODS: SPECT measurements of the dopamine transporter (DAT) were done with 123I-beta-CIT, while for determination of the dopamine D2-like receptors (D2), 123I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight patients with MSA and 11 healthy age-matched control subjects. RESULTS: Putaminal DAT binding was reduced to 32% of control values in IPD and to 19% of control values in MSA . Significantly higher striatal asymmetry in DAT binding was found in MSA than in controls, but IPD patients had significantly higher asymmetry than MSA patients. Striatal D2 binding did not differ significantly between patients and healthy controls but the ratio between caudate DAT and D2 binding was significantly higher in patients with IPD than in those with MSA, even when disease severity was taken into account. CONCLUSION: Patients with reduced striatal 123I-beta-CIT binding and a side-to-side difference greater than 15% are likely to suffer from IPD. Patients with reduced striatal 123I-beta-CIT binding and a side-to-side difference of between 5% and 15% are more likely to have MSA. 123I-epidepride SPECT measurements may add further diagnostic information, since the ratio between DAT and D2 receptor binding is significantly higher in IPD than in MSA.

Adult↗

PubMed2001

Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration.

The atypical parkinsonian or Parkinson Plus syndromes are often difficult to differentiate from Parkinson's disease and each other. In this article, the clinicopathological characteristics of dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration are discussed. These disorders, although clinically distinct, may have more similarities than previously thought, based on modern immunocytochemical techniques and new genetic findings. These intriguing interconnections at a basic molecular level have provided the scientific rationale for lumping these diseases into two groups, the synucleinopathies and the tauopathies.

Basal Ganglia Diseases↗

PubMed1999

Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy.

The symptoms caused by or relating to orthostatic hypotension (over 20 mmHg systolic blood pressure) were evaluated using a questionnaire in 72 patients with primary chronic autonomic failure, 32 of whom had pure autonomic failure (PAF, and 40 multiple system atrophy (MSA). The most common posturally related symptoms were dizziness (84% PAF, 83% MSA), syncope (91% PAF, 45% MSA), visual disturbances (75% PAF, 53% MSA) and suboccipital/paracervical 'coat-hanger' neck pain (8 l% PAF, 53% MSA). Chest pain occurred mainly in patients with PAF (44% PAF, 13% MSA). Improvement occurred with sitting or lying flat. Non-specific symptoms (weakness, lethargy and fatigue) were common in both groups (91% PAF, 85% MSA); six patients (one PAF, five MSA) had these symptoms only. Postural symptoms (mainly dizziness and neck pain) were worse in the morning and with warm temperature, straining, exertion, arm movements and food ingestion; they were more common in PAF. Compensatory autonomic symptoms, such as palpitations and sweating, did not occur in either group. In conclusion, orthostatic hypotension caused symptoms of cerebral hypoperfusion (syncope, dizziness and visual disturbances); neck pain, presumably due to muscle hypoperfusion, also occurred frequently. These symptoms were exacerbated by various factors in daily life and were relieved by returning to the horizontal. Non-specific symptoms (such as fatigue) also were common. In MSA, despite substantial orthostatic hypotension, fewer patients had syncope, visual disturbance and neck pain; the reasons for this are unclear. Lack of these features does not exclude the need to assess and investigate orthostatic hypotension and possible autonomic failure.

Adaptation, Physiological↗

PubMed1991

Antibody in the CSF of patients with multiple system atrophy reacts specifically with rat locus ceruleus.

Idiopathic chronic autonomic dysfunction may occur as pure autonomic failure (PAF) or in association with multiple system atrophy (MSA). CSF immunoreactivity to rat locus ceruleus occurred in a significantly greater number of samples from MSA patients compared to control subjects or patients with PAF. Other brain regions infrequently showed immunoreactivity. These findings suggest that degeneration in MSA may release antigen(s) that induce antibodies against locus ceruleus neurons. Further studies are required to determine whether immune abnormalities play a pathogenetic role in MSA. Lack of CSF immunoreactivity in PAF is consistent with primarily peripheral involvement.

Adult↗