The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure.
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BACKGROUND: Oral ingestion of water increases seated blood pressure in patients with chronic autonomic failure by mechanisms that remain unclear. As orthostatic hypotension is common in chronic autonomic failure, and is not always adequately controlled by medication, the potential benefits of water ingestion on standing blood pressure were studied in two types of autonomic failure: multiple system atrophy (MSA), in which the lesion is central and pre-ganglionic, and pure autonomic failure (PAF), in which the lesion is post-ganglionic. METHODS: In 14 patients with autonomic failure (seven PAF and seven MSA) standing blood pressure and heart rate were measured before, and 15 and 35 minutes after ingestion of 480 ml distilled water. Patients remained seated for 15 minutes after water ingestion, with beat to beat cardiovascular indices measured with the Portapres II device with subsequent Modelflow analysis. RESULTS: Standing prior to water ingestion caused a significant fall in blood pressure in all patients. After water ingestion there was a rise in seated blood pressure. Seated and standing blood pressure at 15 and 35 minutes after water ingestion was significantly higher than before water, with an improvement in orthostatic symptoms. The time to first significant rise in seated blood pressure occurred at 5 minutes post water ingestion in PAF and at 13 minutes in MSA. These increases were accompanied by increases in total peripheral resistance, reaching significance by 5 minutes in PAF and 13 minutes in MSA. There were no significant changes in cardiac output, stroke volume, or ejection fraction. CONCLUSIONS: Water is thus beneficial in improving standing BP in AF, acting within 15 minutes in both MSA and PAF. The earlier onset of the pressor effect in PAF may reflect the differing lesion site and underlying pathophysiology between these conditions. (+info)
Involvement of medullary regions controlling sympathetic output in Lewy body disease.
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We sought to determine the involvement of medullary regions controlling sympathetic output in pathologically confirmed diffuse Lewy body disease (LBD). We studied eight limbic or neocortical stage LBD and eight multiple system atrophy (MSA) cases, confirmed neuropathologically, and eight age-matched controls. Five of the LBD cases and all MSA cases had orthostatic hypotension. Serial 50-mum sections obtained from the medulla rostral to the obex were immunostained for tyrosine hydroxylase, tryptophan hydroxylase and alpha-synuclein. Analysis was focused on the ventrolateral medulla and medullary raphe nuclei. In LBD cases, there were Lewy bodies and neurites, as well as dystrophic neurons in the ventrolateral medulla, but the number of catecholaminergic and serotonergic neurons was not significantly reduced. All these groups were depleted in MSA. There were Lewy body pathology and dystrophic neurons in the raphe in all LBD cases. Cell numbers were reduced in both the raphe obscurus and raphe pallidus. Our findings suggest that, although LBD affects medullary autonomic areas, it does so less severely than MSA, particularly in the case of the VLM, which controls sympathetic outputs maintaining arterial pressure. In LBD, orthostatic hypotension may be due primarily to involvement of sympathetic ganglion neurons rather than ventrolateral medulla neurons. (+info)
Post-micturitional hypotension in patients with multiple system atrophy.
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BACKGROUND: Patients with multiple system atrophy (MSA) occasionally have episodes of syncope or pre-syncope after micturition. OBJECTIVE: To clarify the mechanism of these episodes by investigating the haemodynamic changes associated with micturition. METHODS: 25 patients with probable MSA and 16 age matched normal controls were studied. Continuous records of blood pressure and heart rate were made during water cystometry, along with the Valsalva manoeuvre, head up tilt testing, measurement of plasma noradrenaline, and calculation of coefficient of variance of RR intervals. RESULTS: Compared with normal controls, MSA patients had a lower baseline blood pressure, smaller blood pressure and heart rate increases during bladder filling, and an abnormal fall in blood pressure for a longer duration after voiding, resulting in significantly lower blood pressure than at baseline (mean systolic blood pressure reduction -15.2 mm Hg), and hypotension compared with control blood pressure (-29.0 mm Hg). The blood pressure fall was greater in patients with micturition syncope/pre-syncope than in those without. It was also greater in patients with abdominal straining resulting from difficulty in voiding. Other cardiovascular indices did not correlate with the fall in blood pressure. CONCLUSIONS: Hypotension after voiding in MSA patients may result from generalised autonomic dysfunction and abnormal abdominal straining, resulting in micturition syncope. (+info)
Differentiation of Parkinson's disease and atypical parkinsonian syndromes by transcranial ultrasound.
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Neuroimaging is known to complement clinical findings in the diagnostic work up of parkinsonian syndromes. Recently, transcranial ultrasound was reported to have a high diagnostic yield in differentiating idiopathic Parkinson's disease (IPD) from atypical parkinsonian syndromes. This report summarises the sonographic findings of 102 patients with IPD, 34 patients with multiple system atrophy, and 21 patients with progressive supranuclear palsy. Increased echogenicity of the substantia nigra is predictive for IPD whereas a low echogenic substantia nigra, particularly when combined with a hyperechogenic lentiform nucleus, strongly suggests an atypical Parkinsonian syndrome. The underlying causes for the differential echo pattern of the substantia nigra remain unknown. (+info)
Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy.
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Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial alpha-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies. (+info)
Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration.
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Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse alpha-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that alpha-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA. (+info)
Voxel-wise analysis of [123I]beta-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease.
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To investigate the cerebral dopamine transporter status in the early stages of the parkinson-variant of multiple system atrophy (MSA-P), 15 patients with MSA-P and a disease duration up to 3 years were studied with [123I]beta-CIT single photon emission computed tomography (SPECT). Data were compared with 13 age-matched healthy control subjects and 15 patients with idiopathic Parkinson's disease (IPD), matched for age and disease duration. Parametric SPECT images of the specific-to-nondisplaceable equilibrium partition coefficient (V3''), which is proportional to the receptor density (Bmax) have been generated. To objectively localize focal changes in dopaminergic function throughout the entire brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to our [123I]beta-CIT SPECT study. Both MSA-P and IPD patients showed significant decreases in striatal [123I]beta-CIT SPECT uptake. However, in MSA-P patients an additional reduction in midbrain [123I]beta-CIT signal was localized with SPM compared with control subjects (MSA-P, V3'': 0.89 +/- 0.37 versus controls V3'': 1.81 +/- 0.38; P < 0.001) and patients with IPD (V3'': 1.84 +/- 0.26; P < 0.001). Stepwise linear discriminant analysis of mean [123I]beta-CIT uptake in the putamen, caudate and midbrain identified the caudate and midbrain as indices to classify correctly 95.2% of subjects as either normal, patients with MSA-P or IPD. Voxel-wise analysis of [123I]beta-CIT SPECT revealed more widespread decline of monoaminergic transporter availability in MSA-P compared with IPD, matching the underlying pathological features. We suggest that the quantification of midbrain DAT signal should be included in the routine clinical analysis of [123I]beta-CIT SPECT in patients with uncertain parkinsonism. (+info)
The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group.
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The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients. (+info)