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Results for “Multiple System Atrophy”

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PubMed1985

Vasopressin secretion in progressive autonomic failure: evidence for defective afferent cardiovascular pathways.

Patients with progressive autonomic failure with multiple system atrophy show a severely blunted response of plasma arginine vasopressin to the stimulus of head-up tilt. Whether this could be due to lesions either at one or more sites within ascending neural pathways from cardiovascular stretch receptors in the thorax or, alternatively, to lesions affecting vasopressin secreting cells within the hypothalamus was investigated. The arginine vasopressin response to an intravenous infusion of hypertonic saline was determined in six patients with progressive autonomic failure. The mean plasma concentration of arginine vasopressin rose from 1.0 to 3.7 pmol/l, a change comparable to that observed in normal controls. This demonstrates normal functioning of the efferent connections from the osmoreceptors within the hypothalamus and suggests that the loss of vasopressin response to head-up tilt is due to lesions in ascending pathways from cardiovascular receptors. There was a significant rise in mean blood pressure during the infusions on patients with progressive autonomic failure, a change which was not observed with the controls. This may have been at least partly caused by the rise in circulating arginine vasopressin concentrations, since these patients have been reported to be extremely sensitive to the pressor effects of arginine vasopressin.

Afferent Pathways↗

PubMed1987

MRI in autonomic failure.

A significant rank correlation between rigidity and putaminal signal dropout on magnetic resonance imaging (MRI) in patients with multiple system atrophy suggests that putaminal degeneration may cause this clinical finding. Absence of putaminal abnormalities on MRI in patients with pure autonomic failure may prove useful in differentiating these two autonomic disorders.

Aged↗

PubMed1988

Gastrin responses in patients with adrenergic insufficiency.

High basal gastrin levels in pure autonomic failure could result from peripheral vagus nerve involvement, whereas the increased response during hypoglycaemia may reflect adrenergic supersensitivity. A reduced gastrin increment in multiple system atrophy was found following insulin-hypoglycaemia and is consistent with decreased gastrin release secondary to diminished central sympathetic nervous system activation in the absence of peripheral denervation supersensitivity.

Adult↗

PubMed1989

The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine.

Cerebral blood flow (CBF) and middle cerebral artery velocity (MCAv) have been measured using 133xenon washout and transcranial Doppler in ten patients with autonomic failure. Four pure autonomic failure and four multiple system atrophy patients behaved similarly: tilting them sufficiently to induce significant orthostatic hypotension without causing syncopal symptoms led to a significant fall in their mean MCAv, but no change in their mean CBF. These findings suggest that cerebral autoregulation is preserved in autonomic failure, orthostatic hypotension resulting in a reactive vasodilatation which lowers MCAv, reduces vascular resistance, and maintains CBF. Ephedrine helped to correct the orthostatic hypotension, but had no direct effect on CBF. Two siblings with orthostatic hypotension secondary to dopamine-beta-hydroxylase deficiency also had preserved cerebral autoregulation, but ephedrine led to paradoxical hypotension in these patients.

Adult↗

PubMed1991

Square wave jerks in parkinsonian syndromes.

The frequency of square wave jerks (SWJ) was compared in eight patients with progressive supranuclear palsy (PSP), 25 patients with multiple system atrophy or Parkinson's disease plus (MSA/PP), 85 patients with idiopathic Parkinson's disease (PD) and 20 age-matched normal volunteers. In the control group, the mean (SD) SWJ frequency (SWJ larger than 1 degree amplitude) was 2.3 (2.4)/min. Abnormal ocular fixation (SWJ frequency greater than 10/min) was observed in a large proportion of PSP patients (7/8) and of MSA/PP patients (16/25) but in few PD patients (13/85). In the group of PD patients with abnormal ocular fixation, freezing of gait, falls and instability were more severe than in the group of PD patients with normal fixation. The study of ocular fixation may help to differentiate PD clinically from other Parkinsonian syndromes. SWJ are probably not related to the central degeneration of the dopaminergic nigrostriatal pathway observed in PD.

Aged↗

PubMed1991

The influence of food on postural hypotension in three groups with chronic autonomic failure--clinical and therapeutic implications.

The effect of a balanced liquid meal on supine and postural blood pressure (BP) responses was investigated in three groups of patients with chronic autonomic failure; 10 with associated neurological impairment (multiple system atrophy (MSA), Shy-Drager syndrome) and seven without (of which five had pure autonomic failure (PAF); and two had a deficiency of the enzyme dopamine beta hydroxylase, DBH-deficiency). All had marked postural hypotension. Subjects with normal autonomic function were also studied. In MSA and PAF food lowered supine BP substantially, with a more rapid and greater fall in PAF. After food, the levels of BP reached were considerably lower because of the reduced supine BP and many had to be returned to the horizontal position earlier than before. Ingestion of a similar volume of water alone had no effect in MSA or PAF. In DBH deficiency, food had variable but minimal effects on BP while supine and during head-up tilt. In subjects with normal autonomic function food did not affect BP. The BP responses to food thus varied in the three groups with chronic autonomic failure. The influence of food on both supine and postural BP therefore should be considered in the clinical and laboratory assessment of autonomic dysfunction and in relation to therapeutic approaches, designed to alleviate postural hypotension.

Adult↗

PubMed1991

Central and peripheral effects of arecoline in patients with autonomic failure.

Increased plasma adrenalin (A) levels following arecoline in normal subjects and patients with multiple system atrophy (MSA) may result from nicotinic adrenal stimulation. Lack of this response in patients with pure autonomic failure (PAF) is consistent with peripheral sympathetic dysfunction. The mechanisms underlying diminished plasma corticotropin (ACTH) responses to arecoline may differ in patients with autonomic failure. Hypothalamic, cholinergic degeneration could prevent the response in MSA whereas patients with PAF do not manifest the normal increase in A which may be required to elicit an ACTH response. The appearance and exacerbation of tremor, vertigo, and pathological affect in the MSA group suggest that some central cholinergic receptors remain functional.

Adrenocorticotropic Hormone↗

PubMed1992

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.

Adult↗

PubMed1994

Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson's syndrome.

Movement disorders presenting with parkinsonism may share histopathological features with Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by the accumulation of pathological prion protein in brain. To investigate a possible aetiological link between these conditions and Creutzfeldt-Jakob disease, histoblot immunostaining for pathological prion protein was carried out in 90 cases including idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, Steele-Richardson-Olszewski syndrome, corticobasal degeneration, and Pick's disease. Pathological prion protein was identified in four controls with Creutzfeldt-Jakob disease but not in any of the other diseases examined. The findings suggest that an aetiological role for prions in these movement disorders is unlikely. Histoblotting provides a useful method for screening large areas of tissue for the presence of pathological prion protein and may be helpful in the differential diagnosis of difficult cases.

Brain↗

PubMed1994

Pure autonomic failure: a new case with clinical, biochemical, and necropsy data.

Postmortem examination of a patient with pure autonomic failure showed loss of intermediolateral column cells and of sympathetic ganglionic neurons; there were Lewy bodies in sympathetic neurons. No neuronal loss or Lewy bodies were seen in pigmented brainstem nuclei. This case indicates that pure autonomic failure can occur in the absence of presymptomatic Parkinson's disease. Furthermore, it supports the view that in pure autonomic failure the lesion is more distal than in autonomic failure associated with multiple system atrophy.

Autonomic Nervous System Diseases↗

PubMed1999

Bilateral Horner's syndrome: detection and occurrence.

OBJECTIVE: To develop a method for the detection of bilateral Horner's syndrome in patients with bilateral interruption of the cervical sympathetic pathway or widespread autonomic neuropathy. METHODS: Darkness pupil diameters and redilatation times during light reflexes have been recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with bilateral Horner's syndrome. The aetiologies of the last group were diabetic autonomic neuropathy (three cases), amyloidosis (four), pure autonomic failure (PAF) (four), dopamine-beta-hydroxylase deficiency (two), and one case each of hereditary sensory and autonomic neuropathy (HSAN) type III, carcinomatous sympathetic neuropathy, familial dysautonomia, multiple system atrophy, Anderson-Fabry disease, and anterior spinal artery thrombosis at C5,6 and one had had bilateral cervical sympathectomies. RESULTS: Darkness diameters on the affected side were below normal in 12 patients with unilateral Horner's syndrome, the measurement yielding only 26% sensitivity for detection of the condition. By contrast, the time taken to reach three quarter recovery in the light reflex (T3/4) was abnormally prolonged (redilatation lag) in 33 of the same eyes. The measurement yielded 70% sensitivity and 95% specificity for detection of the condition. In 20 cases, diagnosed on clinical grounds as having bilateral Horner's syndrome of various aetiologies, pupil diameters were abnormally small on both sides in five and on one side in three patients. Fourteen of these patients had significant redilatation lag in both eyes, five patients in one eye, and one patient had it in neither eye. Measurement of redilatation lag was therefore a more sensitive diagnostic test than pupil diameter in both unilateral and bilateral Horner's syndrome. CONCLUSIONS: Provided that the pupils are not tonic, bilateral Horner's syndrome can be diagnosed on the basis of redilatation lag. It occurs clinically in some generalised autonomic neuropathies and with interruption of the local sympathetic nerve supplies to the two eyes.

Adult↗

PubMed1999

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study.

OBJECTIVE: Although both orthostatic hypotension and urinary incontinence have been reported in a number of parkinsonian syndromes, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of these features have not been studied systematically in pathologically confirmed cases. METHODS: 77 cases with pathologically confirmed parkinsonian syndromes (PD, n=11; MSA, n=15; DLB, n=14; CBD, n=13; PSP, n=24), collected up to 1994, formed the basis for a multicentre clinicopathological study organised by the NINDS to improve the differential diagnosis of parkinsonian disorders. The present study determined the time course-that is, latency to onset and duration from onset to death, of symptomatic orthostatic hypotension, and urinary incontinence in the NINDS series. Furthermore, the diagnostic validity of a predefined latency to onset within 1 year of disease onset of symptomatic orthostatic hypotension or urinary incontinence was analysed. RESULTS: Significant group differences for latency, but not duration, of symptomatic orthostatic hypotension and urinary incontinence were found. Latencies to onset of either feature were short in patients with MSA, intermediate in patients with DLB, CBD, and PSP, and long in those with PD. Symptomatic orthostatic hypotension occurring within the first year after disease onset predicted MSA in 75% of cases; early urinary incontinence was less predictive for MSA (56%). CONCLUSION: Latency to onset, but not duration, of symptomatic orthostatic hypotension or urinary incontinence differentiates PD from other parkinsonian syndromes, particularly MSA.

Age of Onset↗

PubMed2000

Late onset levodopa responsive Huntington's disease with minimal chorea masquerading as Parkinson plus syndrome.

Huntington's disease is characterised by hyperkinetic movements, mainly chorea, cognitive dysfunction, and psychiatric abnormalities. Non-dopa responsive parkinsonism occurs in the later stages of choreic disease or as the predominant feature of juvenile patients (Westphal variant). Late onset Huntington's disease presenting as levodopa responsive parkinsonism is rare. A series of four patients with late onset Huntington's disease presenting as levodopa responsive parkinsonism and cardiovascular dysautonomia, initially misdiagnosed as multiple system atrophy (MSA) in three patients, is reported. Levodopa treatment did not unmask significant chorea. These cases suggest the presence of a distinct phenotypic variant of Huntington's disease to be added to the differential diagnosis of other akinetic rigid syndromes.

Aged↗

PubMed2003

Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension.

BACKGROUND: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension. OBJECTIVE: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs. DESIGN: Prospective open label single dose trial. MATERIAL: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3). METHODS: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine. RESULTS: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms. CONCLUSIONS: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.

Acetylcholinesterase↗

PubMed2000

Single photon emission tomography imaging in parkinsonian disorders: a review.

Parkinsonian symptoms are associated with a number of neurodegenerative disorders, such as Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. Pathological evidence has shown clearly that these disorders are associated with a loss of neurons, particularly in the nigrostriatal dopaminergic pathway. Positron emission tomography (PET) and single photon emission tomography (SPECT) now are able to visualise and quantify changes in cerebral blood flow, glucose metabolism, and dopaminergic function produced by parkinsonian disorders. Both PET and SPECT have become important tools in the differential diagnosis of these diseases, and may have sufficient sensitivity to detect neuronal changes before the onset of clinical symptoms. Imaging is now being utilised to elucidate the genetic contribution to Parkinson's disease, and in longitudinal studies to assess the efficacy and mode of action of neuroprotective drug and surgical treatments. This review summarises recent applications of SPECT imaging in the study of parkinsonian disorders, with particular reference to the increasing role it is playing in the understanding, diagnosis and management of these diseases.

Journal Article↗

PubMed2006

Mechanisms of neuronal death in synucleinopathy.

alpha-synuclein is a key molecule in the pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy. In this mini-review, we mainly focus on recent data obtained from cellular models of synucleinopathy and discuss the possible mechanisms of neurodegeneration. Recent progress suggests that the aggregate formation of alpha-synuclein is cytoprotective and that its precursor oligomer (protofibril) may be cytotoxic. The catechol-derived quinones are the candidate molecules that facilitate the oligomer formation of alpha-synuclein. Furthermore, the cellular membranes are shown to be the primary targets injured by mutant alpha-synucleins, and the mitochondrial dysfunction seems to be an initial step in the neuronal death.

Journal Article↗

PubMed2000

Acute challenge with apomorphine and levodopa in Parkinsonism.

BACKGROUND: The diagnosis of different parkinsonian syndromes and the ability to predict long-term drug efficacy constitute important clinical issues. DESIGN: Motor responses to the acute administration of levodopa and apomorphine were analyzed in a series of 134 parkinsonian patients, including 83 patients with a clinical diagnosis of idiopathic Parkinson's disease (PD), 28 patients with multiple-system atrophy (MSA), 6 with progressive supranuclear palsy, and 17 with an unclassified parkinsonian syndrome. METHODS: The patients received oral levodopa/carbidopa (250/25 mg) and subcutaneous apomorphine (1.5, 3 and 4.5 mg). Clinical variations of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score were evaluated 1 h following levodopa administration or 20 min following apomorphine. The motor improvement produced by each acute challenge was matched with the clinical diagnosis and with the response to chronic levodopa treatment. The diagnosis was verified by repeated clinical assessments or by autopsy in 2 cases. A receiver operating characteristics curve was plotted comparing PD vs. non-PD, PD vs. MSA and chronic responders vs. nonresponders. Cutoff threshold improvement was defined as the value closest to the crossing point for 80% sensitivity and 80% specificity, corresponding to the best trade-off for a predictive evaluation. RESULTS: UPDRS motor score improvement was on average higher in PD than in non-PD patients (levodopa: 29.8 vs. 12.2%; apomorphine 1.5 mg: 27.1 vs. 10.5%; apomorphine 3 mg: 27.7 vs. 9.7%; apomorphine 4.5 mg: 28.8 vs. 11.8%; p < 0.01 with Student's t test). When PD patients were compared to non-PD patients, levodopa challenge had the best diagnostic accuracy with a threshold improvement of 16%. Apomorphine had the best diagnostic accuracy with a threshold improvement of 13.5% for 1.5 mg, 13% for 3 mg, and 16% for 4.5 mg. This meant that patients improving at least 16% in all tests had the highest probability of having PD. When PD patients were compared to MSA patients, levodopa acute challenge had the best diagnostic accuracy with a threshold improvement of 17%. Apomorphine had the best diagnostic accuracy with an improvement of 13% for 1.5 mg, 15% for 3 mg, and 18% for 4.5 mg. This meant that patients improving at least 18% in all tests had the highest probability of having PD rather than MSA. When patients who responded to chronic levodopa treatment were compared to those who did not, acute challenge with levodopa had the best predictive accuracy with a threshold improvement of 14.5%. Apomorphine had the best predictive accuracy with an improvement of 13% for 1.5 mg, and 14% for 3 and 4.5 mg. This meant that patients improving at least 14.5% in all tests had the highest probability of responding to chronic treatment. CONCLUSION: A good agreement was found between acute challenges with levodopa/carbidopa and apomorphine, and the use of both improved the reliability of the test. Different threshold improvements after acute challenges would support a diagnosis of PD or the exclusion of MSA, and would have a predictive value for subsequent response to chronic levodopa therapy.

Age of Onset↗

PubMed1998

Investigational techniques.

There are various clinical neurophysiological techniques which have been applied to the investigation of the pelvic floor and neurogenic bladder. Sphincter electromyography (EMG) has proved to be particularly valuable in identifying patients with parkinsonism who have multiple system atrophy. EMG of the striated muscle of the urethral sphincter is essential in recognizing the abnormal spontaneous activity which causes urinary retention in young women. Tests which examine aspects of nerve conduction velocity have proved to be of lesser value both because such investigations test conduction of nerve fibres rather than levels of innervation, and furthermore examine large myelinated fibre conduction rather than that of the unmyelinated fibres which comprise the autonomic innervation.

Adult↗