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Background: According to Braak staging of Parkinson's disease (PD), detection of autonomic dysfunction would help with early diagnosis of PD. Objective: To determine whether the autonomic nervous system is involved in the early stage of PD, we evaluated cardiovascular and sudomotor function in early untreated PD patients. Methods: Orthostatic blood pressure regulation, heart rate variability, skin vasomotor function, and palmar sympathetic sweat responses were examined in 50 early untreated PD patients and 20 healthy control subjects. Results: The mean decrease in systolic blood pressure during head-up tilt in PD patients was mildly but significantly larger than in controls (p = 0.0001). There were no differences between the 2 groups in heart rate variability, with analysis of low frequency (LF; mediated by baroreflex feedback), and high frequency (HF; mainly reflecting parasympathetic vagal) modulation. However, LF/HF, an index of sympatho-parasympathetic balance, was lower in the PD group than in controls (p = 0.02). Amplitudes of palmar sweat responses to deep inspiration (p = 0.004), mental arithmetic (p = 0.01), and exercise (p = 0.01) in PD patients were lower than in controls, with negative correlations with motor severity. Amplitudes of palmar skin vasomotor reflexes in PD patients did not differ from controls. Conclusions: Our study indicates impairment of sympathetic cardiovascular and sudomotor function with orthostatic dysregulation of blood pressure control, reduced LF/HF and reduction in palm sweat responses even in early untreated PD patients. [ABSTRACT FROM AUTHOR]

Non-motor symptoms are now commonly recognized in Parkinson's disease (PD) and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-Parkinsonian) drugs and can result in atypical blood pressure (BP) readings and related symptoms such as orthostatic hypotension (OH) and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT) or an (active) standing test (also known as Schellong test) in the laboratory, but 24 h ambulatory blood pressure monitoring (ABPM) in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary) is followed which will be discussed in this review. A 24-h ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR) can be obtained and establish whether or not a patient has a fall of BP at night (i.e., "dipper" vs. non-"dipper"). The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders, and obstructive sleep apnea, which are common in PD. Additionally, a 24-h ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 h ABPM in PD, summarize findings of such studies in PD, and briefly consider common daily stimuli that might affect 24 h ABPM. [ABSTRACT FROM AUTHOR]

Abstract: Aim: A previous study on a small number of patients showed that low skin temperature of the hands, the so called “cold hands sign”, may be useful for distinguishing multiple system atrophy (MSA) from Parkinson''s disease (PD). We have further investigated skin temperature of the hand in a larger number of patients. Methods: Skin temperature on the palm was measured in 50 MSA (11 MSA-P and 39 MSA-C patients) and 50 PD patients, and 25 normal healthy subjects. Results: Palm skin temperature was significantly lower in MSA patients (32.0 ± 2.7 °C) than in controls (34.1 ± 0.9 °C, p = 0.0002), but was not different compared with the PD group (32.9 ± 1.8 °C, p = 0.06). Temperatures of <28 °C were observed in 3 MSA patients (6%) and none of the PD patients and controls. There was no significant difference in palm skin temperature between patients with and without orthostatic hypotension for each patient group, or between MSA-P and MSA-C patients. Conclusion: The cold hand (<28 °C) is a useful marker for distinguishing MSA from PD, but it is not common in MSA patients, and its sensitivity may be low for differentiating between MSA and PD. [Copyright &y& Elsevier]

Aim: To clarify the characteristics of hemodynamic responses to exercise and orthostasis in Parkinson's disease patients, especially those with autonomic failure. Methods: Clinical audit of supine cycling exercise test data (with active standing tests pre- and post-exercise) of Parkinson's patients with autonomic dysfunction. 23 patients (71 ± 7 yr, 7 females) with a confirmed diagnosis of Parkinson's were identified. Results: Group mean systolic blood pressure (SBP) fell during pre-exercise standing (−39 ± 29 mmHg, P < 0.001, 17 patients had orthostatic hypotension (OH)), while heart rate (HR) increased (+13 ± 7 beats min−1, P < 0.001). SBP (P < 0.001) increased during exercise with a wide variation in responses. SBP increased in 13 patients (INC; +30 ± 14 mmHg) and either did not change or decreased in 10 patients (DEC −12 ± 11 mmHg, P < 0.001 vs INC). The increase in HR was not different between sub-groups (30 ± 12 vs 25 ± 10 beats min−1, INC vs. DEC, P = 0.29). The size of the pre-exercise stand SBP reduction was greater in DEC vs INC (−64 ± 23 (10 out of 10 had OH) vs −19 ± 16 mmHg (7 out of 13 had OH), respectively, P < 0.001). The HR elevation was not different between sub-groups (13 ± 8 vs 13 ± 4 beats min−1, DEC vs INC, P = 0.94). Post-exercise SBP/DBP were lower for both sub-groups compared to pre-exercise and the standing SBP reduction post-exercise was not greater relative to pre-exercise in either sub-group. Conclusion: Exercise-induced hypotension can occur in Parkinson's disease patients with autonomic failure with the magnitude of the exercise response being related to the severity of autonomic dysfunction. Exercise does not appear to worsen OH in this sample of Parkinson's patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Funding: Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund. [Copyright &y& Elsevier]

Abstract: Post-mortem studies of multiple system atrophy (MSA) patients have shown widespread subcortical neurodegeneration. In this study, we have used 18F-dopa PET, a marker of monoaminergic nerve terminal function, to explore in vivo changes in striatal and extrastriatal dopamine, noradrenaline, and serotonin transmission for a cohort of patients with MSA with predominant parkinsonism. Fourteen patients with MSA, ten patients with idiopathic Parkinson''s disease (PD) matched for disease duration, and ten healthy controls were studied with 18F-dopa PET. Regions of interest (ROIs) were placed to sample 18F-dopa uptake in thirteen structures and mean activity was compared between groups. The MSA patients showed significantly decreased 18F-dopa uptake in putamen, caudate nucleus, ventral striatum, globus pallidus externa and red nucleus compared to controls, whereas PD patients only had decreased 18F-dopa uptake in putamen, caudate nucleus, and ventral striatum. MSA cases with orthostatic hypotension had lower 18F-dopa uptake in the locus coeruleus than patients without this symptom. In conclusion, 18F-dopa PET showed more widespread basal ganglia dysfunction in MSA than in PD with similar disease duration, and extrastriatal loss of monoaminergic innervation could be detected in the red nucleus and locus coeruleus. In contrast to PD, there was no evidence of early compensatory increases in regional 18F-dopa uptake. [Copyright &y& Elsevier]

Abstract: Introduction: Our objective was to assess the usefulness of the Scales for Outcomes in Parkinson’s disease – Autonomic (SCOPA-AUT) in the differential diagnosis of Parkinsonisms and clarify its relation with 123-I-MIBG cardiac scintigraphy. Methods: A total of 112 patients with Parkinson’s disease (PD), 12 with multiple system atrophy parkinsonian variant (MSA-P) and 20 with progressive supranuclear palsy (PSP) participated in the study. The following variables were collected: age, sex, age at onset, length of illness, type and dose of anti-Parkinson medication, and score on the Unified Parkinson’s Disease Rating Scale. The Unified Multiple System Atrophy Rating Scale was administered to patients with MSA and the Progressive Supranuclear Palsy Rating Scale to those with PSP. Finally, the SCOPA-AUT was administered to all the patients. Cardiac 123I-MIBG SPECT scans were performed on a subset of patients (25 with PD and 5 with MSA-P). Results: Statistically significant differences were observed (p < 0.01) in the SCOPA-AUT scores between patients with PD (14.75+/−8.09) and those with MSA (21.07+/−5.56), the latter having higher scores on the bowel function (20.07+/−13.40 vs 34.92+/−14.91) and urinary domains (30.21+/−21.55 vs 49.26+/−21.40) (p < 0.01). No correlation was found between the SCOPA-AUT score and anti-Parkinson’s medication and heart:mediastinum (H/M) MIBG uptake ratio in the cardiac SPECT (at 4 h). Discussion: Severity of dysautonomia as measured by the SCOPA-AUT was not correlated with clinical severity, time since onset or the H/M ratio. In the patients with PD, the only variable associated with the H/M ratio was age at onset of the disease. [Copyright &y& Elsevier]

Abstract: In Parkinsons disease and multiple system atrophy (MSA), cardiovascular dysfunction may occur for a variety of reasons and may manifest itself through inappropriate changes and/or levels in blood pressure, heart rate and/or regional vascular perfusion in a range of situations. The early occurrence of orthostatic hypotension often leads to consideration of MSA, especially in the presence of other features of autonomic failure. Orthostatic hypotension, however, is increasingly recognised in PD, and especially with increasing age, severity of disease and as a result of drug therapy, sometimes for associated disorders. Investigation of cardiovascular autonomic dysfunction in Parkinsonism is therefore important for a variety of reasons, that include determining the precise diagnosis and in predicting prognosis. In Parkinsonian disorders, understanding the pathophysiological basis of the cardiovascular autonomic dysfunction aids targeting of therapy, improves management strategies and provides benefit for such patients. [Copyright &y& Elsevier]