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Results for “Multiple System Atrophy”

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At least 433 records · Page 24Linked to original sources
PubMed2006

MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease.

PURPOSE: To prospectively assess if middle cerebellar peduncle (MCP) atrophy, evaluated at magnetic resonance (MR) imaging, can help differentiate multiple system atrophy (MSA) from Parkinson disease (PD). MATERIALS AND METHODS: All participants provided informed consent for participation in the study, which was approved by the institutional review board. Sixteen consecutive patients with MSA, 26 consecutive patients with PD, and 14 healthy control subjects were examined with MR imaging. Images were interpreted independently by two experienced neuroradiologists blinded to clinical information, who visually inspected the images for the presence or absence of putaminal atrophy, putaminal hypointensity, slitlike hyperintensity in the posterolateral margin of the putamen, brainstem atrophy, hyperintensity of the MCP, and cruciform hyperintensity of the pons. Measurements of MCP width on T1-weighted volumetric spoiled gradient-echo images were performed in all subjects. Differences in MCP width among the groups were evaluated by using the Kruskall-Wallis test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni correction. RESULTS: All patients (mean age, 63.88 years; range, 55-72 years) with MSA had at least one of the features commonly observed in this disease on MR images, whereas control subjects (mean age, 66.93 years; range, 61-77 years) and all but one patient with PD (mean age, 65.31 years; range, 51-79 years) had normal MR images. The average MCP width was significantly smaller in patients with MSA (6.10 mm+/-1.18 [standard deviation]) than in those with PD (9.32 mm+/-0.77, P<.001) or control subjects (9.80 mm+/-0.66, P<.001). CONCLUSION: Measurement of MCP width on MR images may be useful for distinguishing patients with MSA from those with PD.

Aged↗
PubMedDate not supplied

Hemiballism in a patient with probable multiple system atrophy.

We report a patient with long-standing asymmetrical parkinsonism, cerebellar ataxia and dysautonomia, suggestive of multiple system atrophy (MSA). However, the patient also developed involuntary repetitive movements similar to ballic dyskinesias and mental deterioration. MRI revealed major involvement of both posterior fossa structures and basal ganglia. The case would be accommodated within a rubric of MSA widened to include involvement of the subthalamic nucleus and the medial part of the pallidum, pathology which may account for the ballic movements. Additionally the patient's cognitive and behavioural disturbances suggest an impairment of striato-prefrontal cortex loop.

Autonomic Nervous System Diseases↗
PubMed2001

Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration.

Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain alpha-synuclein as a major component, are characteristic cytopathological features of multiple system atrophy (MSA). We report MSA of 19 years' duration in a 73-year-old woman. Her initial symptom was parkinsonism, with dementia appearing about 8 years later. Postmortem examination showed marked atrophy of the frontal and temporal white matter and limbic system, in addition to the pathology typical of MSA. In the limbic system, severe neuronal loss and astrocytosis were observed, and the remaining neurons often had lightly eosinophilic, spherical cytoplasmic inclusions. Interestingly, a double-labeling immunofluorescence study revealed that the NCIs in the dentate gyrus and amygdaloid nucleus, and the GCIs in the frontal and temporal white matter often expressed both alpha-synuclein NACP-5 and phosphorylated tau AT8 epitopes. Double-immunolabeling electron microscopy of the NCIs in the dentate gyrus and the GCIs in the temporal white matter clearly revealed labeling of their constituent granule-associated filaments with NACP-5, and some of them were also labeled with AT8. These findings strongly suggested that some alpha-synuclein filaments were decorated with phosphorylated tau without formation of fibrils such as paired helical filaments. Immunoblotting of sarkosyl-insoluble tau indicated that the accumulated tau consisted mainly of four-repeat tau isoforms of 383 amino acids and 412 amino acids. We consider that the limbic system can be a major site of neurodegeneration in MSA of long duration. The mechanisms of such abnormal tau accumulation in the NCIs and GCIs are unknown.

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PubMed2005

Alpha-1-antichymotrypsin gene polymorphism and susceptibility to multiple system atrophy (MSA).

We investigated three genotypes (AA, AT, and TT) produced by signal peptide polymorphism of the alpha-1-antichymotrypsin (ACT) gene in 105 patients with multiple system atrophy (MSA) and age-matched controls. The frequency of ACT-AA genotype was significantly higher in patients with MSA (20.0%) than in controls (10.5%). The onset of MSA was significantly earlier and the disease progressed significantly faster in patients with ACT-AA genotype than in those with non-ACT-AA genotypes. The ACT concentration in cerebrospinal fluid was increased in patients with ACT-AA. To our knowledge, this is the first study to show that the ACT-AA genotype is a risk factor and modulating factor for MSA. Our findings suggest the involvement of ACT-relating inflammatory process in the pathogenesis of MSA.

Age of Onset↗
PubMed2005

Continuous positive airway pressure for sleep-related breathing disorders in multiple system atrophy: long-term acceptance.

BACKGROUND AND PURPOSE: To assess the long-term acceptance of non-invasive nasal continuous positive air pressure (CPAP) in multiple system atrophy (MSA) patients with polysomnographic (PSG)-confirmed sleep apneas and/or nocturnal stridor. PATIENTS AND METHODS: Sleep-related breathing disorders were investigated by PSG in 22 MSA patients in whom stridor and sleep-related respiratory disturbances were clinically suspected. Patients in whom the first PSG disclosed either a sleep apnea/hypopnea index (AHI)> or =10 or stridor with or without apneas underwent a second PSG for CPAP titration. RESULTS: Three patients presented with an obstructive sleep apnea syndrome without stridor, whereas 15 patients presented stridor occurring alone or accompanied by apneas. Twelve patients pursued CPAP. Two severely disabled patients died a few days after CPAP initiation, and five discontinued CPAP because of discomfort. One patient died after 17 months of follow-up. Since the onset of CPAP, the four remaining patients reported more efficacious sleep and improved daytime alertness. These patients had significantly less severe disease at the time of CPAP initiation. Age, disease duration, the presence of sleep complaints, excessive daytime somnolence (EDS) and AHI did not account for CPAP compliance. CONCLUSION: The severity of motor impairment at the initiation of treatment appears to be the most significant limiting factor for CPAP long-term acceptance.

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PubMed2005

Pyramidal tract imaging in multiple-system atrophy.

A new radiological finding of T2 FLAIR hyperintensities in the pyramidal tracts is described in a patient clinically thought to have idiopathic Parkinson's disease but histologically proven to have multiple-system atrophy.

Adult↗
PubMed2003

[A patient with multiple system atrophy presenting prolonged levodopa-responsive parkinsonism and off-dystonia of the trunk].

A 46-year-old man had a 7-year history of dopa-responsive parkinsonism. Four years after starting levodopa, he had typical motor complications such as wearing-off and peak dose as well as off-period dystonia of his trunk. Brain MRI showed marked atrophy of the brainstem and cerebellum, and the cross sign was present in the pontine base. There was neither abnormal signal intensity nor atrophy in the basal ganglia. Then, he was suspected as having multiple system atrophy (MSA). It is not easy to differentiate MSA from Parkinson diseases, particularly when the patient shows good response to levodopa and motor complications like those seen in Parkinson's disease. If the striatal pathology was not severe and nigral degeneration was prominent, presynaptic parkinsonism might occur in MSA, and putaminal preservation might account for good response to levodopa therapy. In patients with MSA, disproportionate antecollis is common before levodopa treatment, and levodopa induced off-dystonia of his trunk is very rare.

Brain↗
PubMed2000

Immunohistochemical and biochemical studies demonstrate a distinct profile of alpha-synuclein permutations in multiple system atrophy.

Although alpha-synuclein (alpha-syn) has been implicated as a major component of the abnormal filaments that form glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA), it is uncertain if GCIs are homogenous and contain full-length alpha-syn. Since this has implications for hypotheses about the pathogenesis of GCIs, we used a novel panel of antibodies to defined regions throughout alpha-syn in immunohistochemical epitope mapping studies of GCIs in MSA brains. Although the immunostaining profile of GCIs with these antibodies was similar for all MSA brains, there were significant differences in the immunoreactivity of the alpha-syn epitopes detected in GCIs. Notably, carboxy-terminal alpha-syn epitopes were immunodominant in GCIs, but the entire panel of antibodies immunostained cortical Lewy bodies (LBs) in dementia with LBs brain with similar intensity. While the distribution of alpha-syn labeled GCIs paralleled that previously reported using silver stains, antibodies to carboxy-terminal alpha-syn epitopes revealed a previously undescribed burden of GCIs in the MSA hippocampal formation. Finally, Western blots demonstrated detergent insoluble monomeric and high-molecular weight alpha-syn species in GCI rich MSA cerebellar white matter. Collectively, these data indicate that alpha-syn is a prominent component of GCIs in MSA, and that GCIs and LBs may result from cell type specific conformational or post-translational permutations in alpha-syn.

Aged↗
PubMed2006

Involvement of hypocretin neurons in multiple system atrophy.

Hypocretin/Orexin (Hcrt/Orx) neurons of the posterolateral hypothalamus have been implicated in control of sleep and autonomic function. Sleep disorders and autonomic failure are important manifestations of multiple system atrophy (MSA). We sought to determine whether Hcrt/Orx neurons were involved in this disorder. Hypothalamus was obtained from seven subjects with neuropathologically confirmed MSA, and seven age-matched controls. 50 mum sections obtained throughout the posterior hypothalamus were immunostained for Hcrt-1 and alpha-synuclein. In MSA, there was a marked reduction of the total numbers of Hcrt/Orx neurons compared to controls (1,009 +/- 190 cells in MSA vs. 3,206 +/- 185 in controls, P < 0.0001). There were abundant glial cytoplasmic inclusions in the area of distribution of Hcrt/Orx neurons in MSA. This is the first demonstration of loss of Hcrt/Orx neurons in MSA, which is consistent with a system degeneration of neurons involved in homeostatic function, including sleep and autonomic regulation, in this disorder.

Adult↗
PubMed2026

Plasma cfDNA hypermethylation at SNCA intron 1 as a potential blood-based epigenetic signal in Parkinson's disease and multiple system atrophy.

BACKGROUND: The accumulation of &#x3b1;-synuclein (SNCA) in the central nervous system is a hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). SNCA intron 1 methylation is implicated in SNCA transcriptional regulation and may serve as a peripheral epigenetic signal in synucleinopathies. However, studies of SNCA methylation in leukocyte-derived DNA have yielded inconsistent results. We aimed to evaluate whether cell-free DNA (cfDNA)-based SNCA intron 1 methylation differs in PD or MSA compared with normal controls (NC). METHODS: Plasma cfDNA was collected from 105 patients with PD, 50 with MSA, and 114 NC. DNA methylation at CpG sites 10-17 was quantified by bisulfite pyrosequencing. Multivariable linear and logistic regression models, adjusted for age, sex, and education, were used to compare methylation levels and estimate odds ratios (ORs). RESULTS: Patients with PD exhibited hypermethylation at CpG site 14 and higher mean methylation across CpG sites 10-17 compared with NC. Patients with MSA showed hypermethylation at CpG sites 10, 12, 13, and 17 and elevated mean methylation. Elevated mean methylation was also observed in drug-na&#xef;ve de novo PD and early-stage PD patients. Compared with the lowest tertile, the highest mean methylation tertile was associated with increased odds of PD (OR, 2.49; 95% CI, 1.08-5.92) and MSA (OR, 5.02; 95% CI, 1.58-18.00). CONCLUSION: Plasma cfDNA SNCA intron 1 hypermethylation is associated with PD and MSA and detectable in drug-na&#xef;ve and early-stage PD. It may represent a peripheral epigenetic alteration and warrants evaluation as an adjunctive signal for early screening.

Humans↗
PubMed2006

Camptocormia associated with focal myositis in multiple-system atrophy.

Camptocormia (CC) or pronounced forward flexion of the trunk is a common symptom of Parkinson's disease. We describe 2 patients with probable, respectively possible multiple-system atrophy and CC. Magnetic resonance imaging of the erector trunci showed focal patchy hyperintensities with gadolinium enhancement and muscle biopsy was indicative of variably pronounced focal myositis. CC was progressive and the major handicap for both patients after 1 and 1.5 years of follow-up, respectively. The therapeutic response was poor. Similarities with the dropped-head syndrome suggest that the muscle pathology may be either the primary cause of CC, a focal reaction to the CC posture, or a coincident syndrome of old age.

Aged↗
PubMed1993

[Multiple system atrophy (MSA)].

Sporadic olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome (SDS), striatonigral degeneration (SND) are classified as multiple system atrophy (MSA), based on their clinicopathological findings. These clinical features, neuroimaging including CT, MRI, PET and SPECT findings, autonomic function test, pathological findings and treatments are reviewed. Several advances such as noradrenaline loading test, low signal intensity on T2 weighted image on super-conductive MRI and glial cytoplasmic inclusions in the central nervous system on pathological finding are notable. However, unsatisfactory medical treatment for MSA must be resolved in a near future.

Autonomic Nervous System↗
PubMed1976

[Multiple systemic atrophies, mental retardation, neurogenic amyotrophy and congenital bone fragility. A new neuro-generative disorder].

Five cases of a congenital neurological disorder are reported. Four patients, born after a breech delivery, belong to one sibship while the fifth patient is the only child in another family. The clinical features include quadriplegia, amyotrophy, a peripheral neuropathy, severe mental retardation and a subluxation of the hips. X-rays reveal diffuse osteoporosis and multiple spontaneous fractures. Autopsies in 3 patients showed multiple system atrophies involving the spinal cord and the cerebellum, coarse cerebral gyri and a marked reduction in volume of the white matter. These various pathological features are compared with the lesions found in a few other cases reported in the literature, none of which can be considered to be identical to the ones described. It is therefore felt that the condition under discussion represents a new syndrome to be classified, at least temporarily, within the group of multiple system atrophies.

Atrophy↗
PubMed2002

Effects of a startle on heart rate in patients with multiple system atrophy.

The patient cooperation usually required for neurophysiological assessment of autonomic cardioregulatory function is difficult to obtain from patients with bradykinesia. A particularly interesting condition occurs in multiple system atrophy (MSA), which features both bradykinesia and autonomic dysfunction. Another characteristic of patients with MSA is their normal motor reaction to a startling stimulus. We used startle as a stimulus for testing autonomic cardioregulatory function in patients with MSA, thus avoiding the need for patient cooperation. In 10 healthy volunteers and 8 MSA patients, we recorded the electrocardiographic QRS complex with surface electrodes attached over the chest and delivered an acoustic startle stimulus after 8 seconds of baseline recording. We calculated the ratio between the pre-stimulus and the post-stimulus heart beat intervals (R-R ratio) by dividing the mean prestimulus R-R interval by the shortest R-R interval obtained within 10 seconds poststimulus. Healthy volunteers had a significant shortening of the R-R interval. The peak of the effect occurred after 2 to 5 seconds, with a mean R-R ratio of 1.14 (S.D. = 0.09). In contrast, R-R shortening was markedly reduced in patients, even though they had a normal motor response. The mean R-R ratio in patients was 1.03 (S.D. = 0.03), significantly lower than in healthy volunteers (P < 0.01). Our results demonstrate an abnormally reduced modulation of the heart beat frequency in patients with MSA, compatible with a dysfunction on pathways responsible for autonomic regulation. The method described here may be useful in the assessment of cardioregulatory function in poorly cooperative patients with normal startle responses.

Acoustic Stimulation↗
PubMed2007

Abnormal responses to repetitive transcranial magnetic stimulation in multiple system atrophy.

We studied the response of the motor cortex to brief trains of suprathreshold repetitive transcranial magnetic stimulations (rTMS) in patients with the Parkinson-variant of multiple system atrophy (MSA-P) and compared it to patients with idiopathic Parkinson's disease (PD) and healthy controls. Eight subjects were studied in each group, and patients were matched for disease severity as assessed by Hoehn & Yahr stages. rTMS was delivered at rest and during low-level contractions in trains of 10 stimulations at 5 Hz, and stimulation intensity was set to result in an motor evoked potential (MEP) in the first dorsal interosseus muscle of 0.5 to 1.0 mV. In MSA-P, MEP amplitude at rest was already reduced after the second stimulus and remained so, while it did not change in PD and controls. During contraction, MEP size did not change during the train in any group. The silent period that followed the last stimulus was of similar duration as the first stimulus in MSA-P, but was increased in PD and controls. These findings indicate that abnormal inhibition occurs within the motor cortex in MSA-P, despite dopaminergic treatment and indicate differences in cortical dysfunction between MSA-P and PD. We suggest that these abnormalities reflect the motor cortex pathology found in MSA-P.

Electromyography↗
PubMed2000

Sleep and periodic leg movement patterns in drug-free patients with Parkinson's disease and multiple system atrophy.

STUDY OBJECTIVE: To assess and compare polygraphic sleep measures and periodic leg movement (PLM) patterns in untreated patients with mild to moderate Parkinson's disease (PD), multiple system atrophy (MSA) and healthy age-matched controls. DESIGN: Polysomnographic recordings of 2 consecutive nights were performed in 10 patients with PD (mean age 65 years, mean Hoehn and Yahr stage 2.2), 10 patients with MSA (mean age 61 years) and in a control group of 10 healthy subjects (mean age 64 years). All patients and controls were free of antiparkinsonian medication and other centrally active drugs for 2 weeks prior to polysomnography. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. RESULTS: Sleep measures for the second night showed a significantly lower total sleep time, sleep efficiency and sleep period time in PD and MSA patients compared to healthy controls. PLM-indices during sleep and wakefulness were significantly higher in PD, but not in MSA patients compared to controls. Five patients with PD and 7 patients with MSA, but no control subject, showed abnormal rapid eye movement (REM) sleep features (i.e., REM sleep without atonia or behavioral manifestations typical for REM sleep behavior disorder). CONCLUSIONS: Sleep disruption and increased motor activity during REM and non REM sleep are a frequent finding in PD and MSA. An increased PLM index in untreated PD patients may be due to a dopaminergic deficit and is probably not associated with dopaminergic treatment.

Aged↗
PubMed2005

Gastric emptying after semi-solid food in multiple system atrophy and Parkinson disease.

BACKGROUND: Gastrointestinal symptoms such as nausea, abdominal pain, and bloating are frequent complaints in patients with Parkinson disease (PD) and in patients with multiple system atrophy (MSA), and may be associated with delayed gastric emptying (GE). Although several GE studies in patients with PD have been performed, scant data exist in patients with MSA. METHODS: We assessed GE half-times (T50) in 12 patients with MSA and compared them with those of 12 patients with PD and 12 age-matched healthy controls.GE was estimated scintigraphically using the left anterior oblique method after ingestion of a (99m)Tc colloid-labeled balanced semi-solid meal (yogurt). GE data were obtained every 15 minutes until there was complete emptying of the stomach. Blood pressure, heart rate, plasma glucose and glucosylated hemoglobin were regularly determined. RESULTS: Reproducibility of the GE technique was excellent (Bland-Altman analysis, limits of agreement: -2.3 to 2.8). T50 was longer in MSA (82+/-3.4 min) and in PD (90.6+/-3.9 min) patients compared with controls (46.2+/-0.7) (two-way ANOVA, p<0.0001). T50 did not differ between patients with MSA and those with PD. No correlation existed between T50 and age, duration of the disease, magnitude of postprandial hypotension, levels of plasma glucose and glucosylated hemoglobin (Kendall's tau, p>0.05). CONCLUSIONS: Our results suggest that patients with MSA have GE rates similar to those of patients with PD, but slower than healthy age matched individuals. It remains to be investigated whether gastrointestinal dysfunction in MSA is related to both brain and peripheral pathology, as is presumed for PD.

Aged↗