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Results for “Multiple System Atrophy”

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PubMed1991

Circulatory autonomic failure 50 years after acute poliomyelitis.

A 59-year old woman who presented with postural dizziness 50 years after an acute episode of poliomyelitis is described. There were no new neurological signs and no evidence of motor neuron disease. She had postural hypotension with an abnormal Valsalva. Investigations led to a diagnosis of hypo-adrenergic orthostatic hypotension, with a predominantly preganglionic sympathetic lesion and intact vagal baroreflex pathways. Although pure autonomic failure and multiple system atrophy are possible causes of circulatory autonomic failure, no other new neurological or autonomic features have developed during a 2 year follow-up. We propose that hypo-adrenergic orthostatic hypotension may be a late complication of poliomyelitis. Deterioration in ambulatory ability in a patient with previous poliomyelitis should additionally include assessment of cardiovascular autonomic function.

Autonomic Nervous System Diseases↗

PubMed1993

The influence of the type, duration, severity and levodopa treatment of Parkinson's disease on cardiovascular autonomic responses.

The influence of the type, duration, severity and levodopa treatment of Parkinson's disease on autonomic involvement has been assessed. The Valsalva manoeuvre, deep breathing, handgrip and orthostatic tests were performed in 50 patients with Parkinson's disease and in a control group of 30 healthy subjects. No attempt was made to classify further patients with parkinsonian features into groups such as the Shy-Drager syndrome or multiple system atrophy. All test results were significantly smaller in patients than in healthy subjects. The diastolic pressure increase during handgrip was significantly smaller in akinetic-rigid than in tremor-akinetic-rigid type patients. The Valsalva ratio and orthostatic test results were significantly smaller in patients with longer duration than in those with shorter duration of disease. All test results except those of the orthostatic test were significantly smaller in patients with the more severe form than in those with the less severe form of disease. Comparing test results of levodopa-treated and -untreated patients no significant differences were found. Our studies in parkinsonian patients suggest that (1) sympathetic impairment is more pronounced in akinetic-rigid than in tremor-akinetic-rigid type patients; (2) sympathetic impairment occurs early, whereas parasympathetic impairment develops later; (3) sympathetic and parasympathetic impairment parallels the severity of disease; (4) orthostatic parameters are more duration-sensitive than severity-sensitive; (5) chronic levodopa treatment does not markedly influence cardiovascular autonomic responses.

Adult↗

PubMed1993

Olfactory dysfunction in the Shy-Drager syndrome.

The aetiology of the Shy-Drager syndrome (multiple system atrophy) is unknown. We reported previously a preliminary association between environmental-occupational risk factors and Shy-Drager syndrome. To further investigate this relationship, we evaluated olfactory function in eight patients in different stages of disease. When the eight patients' olfactory function was compared with 203 age- and sex-matched controls using a self-administered olfactory test, seven scored below the 39th percentile of this population. Five of the eight patients had total anosmia or microsmia. Additional studies will be required to elucidate the significance of this abnormal clinical observation.

Aged↗

PubMed1993

Serum alpha 1-antichymotrypsin is not a useful marker for Alzheimer's disease or dementia in Parkinson's disease.

We measured serum alpha 1-antichymotrypsin (ACT) levels in patients with Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy (MSA) and age-matched controls to evaluate whether serum ACT levels in AD patients were elevated and whether ACT levels in PD patients with dementia differed from those in PD or AD. None of the patient groups displayed an increase in ACT levels. We conclude that serum ACT is not useful as a marker, nor in AD nor in dementia in PD.

Aged↗

PubMed1997

Neuropeptide Y innervation of nitric oxide-synthesizing sympathetic preganglionic neurons in humans.

We sought to determine whether neuropeptide Y (NPY) terminals are concentrated in the intermediolateral (IML) cell column and innervate human NADPH-diaphorase (NADPH-d)-reactive sympathetic preganglionic neurons (SPNs). Spinal cords were obtained at autopsy from one man and two women, cut into segments, and immersion fixed in 2% paraformaldehyde for 24 h. The T1, T3, T6 and T8 spinal cord segments were cut serially at 50 microns in the coronal, sagittal and horizontal planes. Alternating consecutive sections were double stained for NADPH-d and NPY or NPY alone. NPY-immunoreactive fibers were identified at all levels analyzed and varicosities appeared to run and cover the NADPH-d processes for long distances. NPY-immunoreactive varicosities were heavily concentrated around the soma and proximal dendrites of NADPH-d SPNs. NPY may exert many possible actions at the level of the IML cell column. Depletion of NPY-containing bulbospinal neurons may contribute to sympathetic failure in disorders such as multiple system atrophy.

Adrenergic Fibers↗

PubMed1997

Efficacy of compression of different capacitance beds in the amelioration of orthostatic hypotension.

Orthostatic hypotension (OH) is the most disabling and serious manifestation of adrenergic failure, occurring in the autonomic neuropathies, pure autonomic failure (PAF) and multiple system atrophy (MSA). No specific treatment is currently available for most etiologies of OH. A reduction in venous capacity, secondary to some physical counter maneuvers (e.g., squatting or leg crossing), or the use of compressive garments, can ameliorate OH. However, there is little information on the differential efficacy, or the mechanisms of improvement, engendered by compression of specific capacitance beds. We therefore evaluated the efficacy of compression of specific compartments (calves, thighs, low abdomen, calves and thighs, and all compartments combined), using a modified antigravity suit, on the end-points of orthostatic blood pressure, and symptoms of orthostatic intolerance. Fourteen patients (PAF, n = 9; MSA, n = 3; diabetic autonomic neuropathy, n = 2; five males and nine females) with clinical OH were studied. The mean age was 62 years (range 31-78). The mean +/- SEM orthostatic systolic blood pressure when all compartments were compressed was 115.9 +/- 7.4 mmHg, significantly improved (p < 0.001) over the head-up tilt value without compression of 89.6 +/- 7.0 mmHg. The abdomen was the only single compartment whose compression significantly reduced OH (p < 0.005). There was a significant increase of peripheral resistance index (PRI) with compression of abdomen (p < 0.001) or all compartments (p < 0.001); end-diastolic index and cardiac index did not change. We conclude that denervation increases vascular capacity, and that venous compression improves OH by reducing this capacity and increasing PRI. Compression of all compartments is the most efficacious, followed by abdominal compression, whereas leg compression alone was less effective, presumably reflecting the large capacity of the abdomen relative to the legs.

Adult↗

PubMed1997

Stimulation of sympathetic activity by carbon dioxide in patients with autonomic failure compared to normal subjects.

In vivo studies selectively assessing preganglionic and central autonomic nervous system activity in patients with autonomic failure have so far been limited to testing pituitary function. In animal experiments carbon dioxide (CO2) selectively stimulates central sympathetic nuclei in the ventrolateral medulla and preganglionic sympathetic neurons in the cervical trunk. This central stimulation seems to overrule less pronounced peripheral vasodilatatory effects. This study addressed the question of whether hypercapnea is a suitable challenge procedure to test preganglionic and central autonomic activity in healthy subjects and in patients with autonomic failure of preganglionic and central origin. Seven patients with multiple system atrophy (MSA) and 30 age-matched healthy volunteers underwent a protocol including a Valsalva manoeuvre (VM) under normo- and hypercapnic conditions and exposure to hypercapnea under supine resting conditions. Blood pressure (BP), heart rate (HR) and end-tidal CO2 partial pressure were measured continuously and non-invasively. In normal controls hypercapnea induced significantly higher BP values in phases II, IIe, III and IV of the VM compared to the normocapnic VM and a significant increase in BP during steady-state supine exposure compared to normocapnic baseline. HR increased significantly only after 40 s of steady-state hypercapnea during the latter challenge. In patients with MSA and autonomic failure, in whom a predominantly preganglionic lesion of the autonomic nervous system is established, no significant effects of hypercapnea on the cardiovascular parameters were found. Although this non-invasive challenge procedure cannot differentiate between pre- and postganglionic autonomic failure, exposure to hypercapnea enables the investigation of efferent autonomic activity to vasoconstrictors generated from autonomic centres in the brainstem and cervical trunk.

Aged↗

PubMed1998

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue.

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders. The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%. It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.

Adult↗

PubMed2001

The metabolic, catecholamine and cardiovascular effects of exercise in human sympathetic denervation.

The cardiovascular and metabolic responses to supine leg exercise were measured in 9 healthy subjects (controls) and in 19 subjects with two primary forms of autonomic failure (11 with peripheral sympathetic denervation [pure autonomic failure; PAF], 8 with central sympathetic failure [multiple system atrophy; MSA]). With exercise, blood pressure increased in controls and fell markedly in subjects with PAF and MSA. Blood pressure returned to baseline in controls, but remained low in the PAF and MSA groups. With exercise, heart rate increased more in controls than the PAF and MSA groups. Resting plasma noradrenaline concentrations in controls and in subjects with MSA were similar, but were lower in subjects with PAF. With exercise, plasma noradrenaline concentrations increased in controls and were unchanged in subjects with PAF; there was no significant increase in the MSA group. Resting plasma lactate, pyruvate and lactate/pyruvate ratios were similar in all three groups. With exercise, lactate concentrations increased until 2 minutes post exercise in all groups. Pyruvate concentrations after 9 minutes' exercise were higher in controls than in the PAF group but were similar to the MSA group; thereafter, concentrations increased similarly in all groups. The lactate/pyruvate ratio increased until 2 minutes post exercise in all groups. Resting plasma free fatty acids, and beta-hydroxybutyrate were similar in all groups. Plasma glycerol concentrations in control and MSA subjects were similar; concentrations were lower in PAF subjects. With exercise, plasma free fatty acids and glycerol concentrations remained unchanged in all groups; beta-hydroxybutyrate concentrations decreased less in control subjects than in PAF and MSA subjects. In conclusion, there were similar concentrations of plasma free fatty acids, glycerol and beta-hydroxybutyrate in control, PAF and MSA subjects; this could indicate up-regulation of beta-receptors in AF, or that sympathetic activity plays a smaller role in lipolysis. Plasma lactate and pyruvate concentrations increased similarly in all groups, despite marked differences in BP; this suggested an impairment of production or clearance of lactate in AF. A role for lactate-induced vasodilatation, not compensated for by sympathetic vasoconstriction, remains speculative.

3-Hydroxybutyric Acid↗

PubMed2004

Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson's disease and related disorders: it can be a specific marker for Lewy body disease.

Recently, reliable and clear evidence for the usefulness of 123I-MIBG scintigraphy in the diagnosis of Parkinson's disease (PD) has been accumulated and it has become increasingly popular as one of the most accurate means of diagnosing the disease. PD, one of the most common neurodegenerative disorders, is characterized by resting tremor, rigidity, bradykinesia or akinesia, and postural instability. The disease is characterized pathologically by distinctive neuronal inclusions called Lewy bodies in many surviving cells of dopaminergic neurons of the substantia nigra pars compacta and other specific brain regions. Furthermore Lewy body type degeneration in the cardiac plexus has been observed in PD. In PD, cardiac MIBG uptake is reduced markedly even in the early disease stages; therefore, MIBG imaging can be used as an indicator of the presence of PD rather than disease severity. Other parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration demonstrate normal cardiac MIBG uptake or only mild reduction of MIBG uptake, indicating that MIBG imaging is a powerful method to differentiate PD from other parkinsonian syndromes. Dementia with Lewy bodies (DLB) also shows severe reduction of MIBG uptake, whereas Alzheimer's disease (AD) demonstrates normal MIBG uptake, permitting differentiation of DLB from AD using MIBG scintigraphy. In pure autonomic failure, which shares similar pathological findings with PD and is thought to be associated with diffuse loss of sympathetic terminal innervation, cardiac MIBG uptake also decreases markedly. Considering all the data together, marked reduction of cardiac MIBG uptake seems to be a specific marker of Lewy body disease and thus extremely useful in the differentiation from other diseases with similar symptoms without Lewy bodies.

3-Iodobenzylguanidine↗

PubMed2005

PET evaluation of the relationship between D2 receptor binding and glucose metabolism in patients with parkinsonism.

OBJECTIVE: To clarify the relationship between D2 receptor binding and the cerebral metabolic rate for glucose (CMRGlu) in patients with parkinsonism, we simultaneously measured both of these factors, and then compared the results. METHODS: The subjects consisted of 24 patients: 9 with Parkinson's disease (PD), 3 with Juvenile Parkinson's disease (JPD), 9 with multiple system atrophy (MSA), and 3 with progressive supranuclear palsy (PSP). The striatal D2 receptor binding was measured by the C-11 raclopride transient equilibrium method. CMRGlu was investigated by the F-18 fluorodeoxyglucose autoradiographic method. RESULTS: The D2 receptor binding in both the caudate nucleus and putamen showed a positive correlation with the CMRGlu in the PD-JPD group, but the two parameters demonstrated no correlation in the MSA-PSP group. The left/right (L/R) ratio of D2 receptor binding in the putamen showed a positive correlation with that of CMRGlu in the MSA-PSP group, while the two demonsrated no correlation in the PD-JPD group. CONCLUSION: Our PET study showed striatal D2 receptor binding and the CMRGlu to be closely related in patients with parkinsonism, even though the results obtained using the L/R ratios tended to differ substantially from those obtained using absolute values. The reason for this difference is not clear, but this finding may reflect the pathophysiology of these disease entities.

Adult↗

PubMed2005

Annular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Hypothesis.

Recently, we demonstrated that soluble 30-50 nm-sized annular alpha-synuclein oligomers are released by mild detergent treatment from glial cytoplasmic inclusions (GCIs) purified from multiple system atrophy brain tissue (Pountney et al., J. Neurochem. 90:502, 2004). Dynamic antibody recognition imaging using a specific anti-alpha-synuclein antibody confirmed that the annular structures were positive for alpha-synuclein. This showed that pathological alpha-synucleinopathy aggregates can be a source of annular alpha-synuclein species. In contrast to pathological alpha-synuclein, recombinant alpha-synuclein yielded only spherical oligomers after detergent treatment, indicating a greater propensity of the pathological protein to form stable annular oligomers. In vitro, we found that Ca2+ binding to monomeric alpha-synuclein, specifically amongst a range of different metal ions, induced the rapid formation of annular oligomers (Lowe et al., Protein Sci.,13:3245, 2004). Hence, alpha-synuclein speciation may also be influenced by the intracytoplasmic Ca2+ concentration. We also showed that annular alpha-synuclein oligomers can nucleate filament formation. We hypothesize that soluble alpha-synuclein annular oligomers may be cytotoxic species, either by interacting with cell membranes or components of the ubiquitin proteasome system. The equilibrium between alpha-synuclein species may be influenced by intracellular Ca2+ status, interaction with lipid vesicles or other factors.

Animals↗

PubMed2000

NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson's disease brains.

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP), also called alpha-synuclein, is a major component of Lewy bodies in Parkinson's disease (PD) as well as of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. We previously reported argyrophilic, tau-negative glial inclusions in the midbrains of patients with PD and have now conducted immunocytochemical and ultrastructural examinations. The PD glial inclusions also are immunoreactive for NACP/alpha-synuclein, but not for beta-synuclein, and ultrastructurally are composed of filamentous structures about 25-40 nm in diameter. Double immunolabeling showed that the inclusions were present in both astrocytic and oligodendroglial cells. They were located within the substantia nigra in 13 of 30 patients with PD and outside the nigra in 24. The number of inclusions was correlated with the severity of nigral neuronal loss. These findings indicate that abnormal accumulation of NACP/alpha-synuclein in glial cells is a pathological feature of PD related to its progression.

Aged↗

PubMed2000

C-terminal alpha-synuclein immunoreactivity in structures other than Lewy bodies in neurodegenerative disorders.

alpha-Synuclein is a presynaptic terminal protein that accumulates abnormally in plaques in Alzheimer's disease (AD), in Lewy bodies in Lewy body disease (LBD) and in filamentous inclusions in multiple system atrophy. Since it has been previously shown that proteinase K or formic acid pretreatment enhances alpha-synuclein immunoreactivity in Lewy bodies and plaques, we hypothesized that the immunoreactivity in tangles, glial cells and Pick bodies might be revealed by such pretreatment. Brain sections from patients with AD, LBD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease were pretreated with proteinase K or formic acid and immunostained with antibodies against the N-terminal, C-terminal or non-amyloid beta component of AD amyloid (NAC) regions of alpha-synuclein. This study showed that after proteinase K (but not formic acid) pretreatment the anti-C terminus antibody immunostained neurofibrillary tangles of AD, PSP and CBD, and glial inclusions of PSP and CBD, as well as Pick bodies. Western blot analysis confirmed that in cases other than LBD, the anti-C terminus antibodies also recognized the native alpha-synuclein band and no cross-reactive bands were observed. In contrast, in LBD, after formic acid pretreatment with the anti-NAC antibody astroglial cells and granular neurons were immunostained. The N-terminal region antibody only recognized the lesions in LBD cases and not those of other neurodegenerative disorders. These results support the view that different fragments of alpha-synuclein might play an important role in the pathogenesis of several neurodegenerative disorders.

Aged↗

PubMed2000

SPECT and PET imaging of the dopaminergic system in Parkinson's disease.

This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta-CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease.

Dopamine↗

PubMed2000

Cognition and emotion in different stages and subtypes of Parkinson's disease.

This paper reviews the main neuropsychological features of movement disorders such as Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Huntington's disease (HD), corticobasal degeneration (CBD), and diffuse Lewy body disease (DLBD). These neurodegenerative disorders all share a prominent frontal lobe-like syndrome which can be explained by damage to connections between the basal ganglia and the cortical areas involved in movement, and in behavioural and mood control. In this paper different types of cognitive and mood alteration are described in an attempt to identify additional reasons for the differential diagnosis of parkinsonism-like syndromes.

Cognition↗

PubMed2005

[Ataxias. Diagnostic procedure and treatment].

Ataxia disorders (or ataxias) include both hereditary and nonhereditary diseases of the cerebellum and spinal cord, all of which are clinically characterized by progressive ataxia. A distinction is made between ataxia disorders and focal diseases of the cerebellum (tumor, abscess, infarction, hemorrhage, demyelinating disease). Ataxias are classified according to the molecular causes, being divided into hereditary ataxias, sporadic degenerative ataxias, and acquired ataxias. The diagnostic tests to be applied should be selected to suit the individual clinical situation in each case. When a patient experiences disease onset before the age of 25 years and the disease affects only one generation autosomal recessive ataxias must be considered. If one of the patient's parents had a similar disease spinocerebellar ataxia (SCA) with a dominant autosomal mode of inheritance is probable. Patients with sporadic disease starting in adulthood may have an acquired ataxia, such as alcoholic cerebellar degeneration (ACD) or paraneoplastic cerebellar degeneration (PCD), or a sporadic degenerative ataxia, such as multiple system atrophy (MSA) or sporadic adult-onset ataxia (SAOA). Therapies based on the underlying molecular pathogenesis are available for a number of ataxia disorders.

Ataxia↗

PubMed1997

[Atypical Parkinson syndrome].

Various clinico-pathological studies have shown that appr. 20% of patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD) may have neuropathological evidence of alternative causes of parkinsonism. Most of these misdiagnosed "IPD" patients meet clinical criteria for either multiple system atrophy (MSA), or progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD). A careful history and physical examination, as well as follow-ups and selected investigations are essential for an accurate clinical diagnosis of these atypical parkinsonian syndromes. The following paper therefore provides a review of clinical features and diagnostic findings in MSA, PSP and CBD, in order to facilitate recognition of these patients.

Brain↗