Recurrent falls and mortality in Parkinson's disease: a prospective two-year follow-up study.

OBJECTIVES: To evaluate the risk factors for recurrent falling and mortality in Parkinson's disease (PD) in a prospective study design. MATERIALS AND METHODS: One hundred and twenty-five PD patients were included in the study. Baseline medical data were collected, and patients were clinically tested for mobility and balance. Falls were prospectively recorded for 2 years. Mortality was documented 4 years after the baseline. RESULTS: Seventy-nine patients reported altogether 3125 falls during the follow-up, and 59 patients were classified as recurrent fallers. Altogether 126 fall injuries including six fractures were reported. Eighteen patients had died by the time of the hospital chart review. History of falling (OR 3.02, 95% CI 1.23-7.44) and the Unified Parkinson's Disease Rating Scale activities of daily living score (OR 1.13, 95% CI 1.04-1.22) were independent risk factors for recurrent falling in PD, whereas slow walking speed (OR 16.28, 95% CI 1.85-142.97) was an independent risk factor for mortality in PD. CONCLUSIONS: History of falling and disease severity indicate increased risk of recurrent falls in PD, while patients with slow walking speed may have an increased risk of mortality. Recurrent falling was not associated with increased risk of mortality in PD in this study.

Sweating impairment in patients with multiple sclerosis.

OBJECTIVES: To measure sweating in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sweating was measured by an evaporimeter after a heating stimulus in 29 MS patients and in 15 healthy control subjects. RESULTS: The MS patients sweated markedly less than the controls. After 10 min of heating the sweating was significantly lower in the forehead (P = 0.034), feet (right, P = 0.033; left, P = 0.037) and legs (right, P = 0.043; left, P = 0.029) of the MS patients than in those of the controls. After 15 min of heating the difference was statistically significant only in the feet (right, P = 0.043; left, P = 0.029). The Expanded Disability Status Scale score correlated inversely with sweating at 15 min of heating in the left hand (r = 0.42, P < 0.05), and in the left (r = 0.36, P < 0.05) and right foot (r = 0.37, P < 0.05). CONCLUSIONS: MS is associated with an impairment in thermoregulatory sweating which seems to be related to the disease severity.

Mobility and balance in Parkinson's disease: a population-based study.

BACKGROUND AND PURPOSE: To assess the clinical correlates of mobility and balance, and to identify the risk factors for falls in Parkinson's disease (PD). METHODS: One-hundred and nineteen PD patients underwent clinical examination and tests for mobility and balance using the Timed Up & Go (TUG) test, walking speed, and the measurement of postural sway. RESULTS: The fallers (35% of the subjects) performed significantly worse in the TUG test than the non-fallers, and they also had a slower walking speed (P = 0.037 and P = 0.006, respectively). The total Unified Parkinson's Disease Rating Scale (UPDRS) score and age were positively associated with the TUG-test score. The severity of the disease and the use of walking aids correlated negatively with the walking speed, whereas the use of dopamine agonists was positively associated with the walking speed. The UPDRS total score [odds ratio (OR) 1.04, 95% confidence intervals (CI) 1.01-1.07] and increased postural sway (OR 1.25, 95% CI 1.02-1.54) were independent risk factors for falling in PD. CONCLUSION: Advanced age and severity of the disease are related to impaired mobility and balance in PD patients. The severity of the disease and increased postural sway seem to be the most important independent risk factors for falling in PD.

Sympathetic skin responses in multiple sclerosis.

OBJECTIVES: This study assessed the sympathetic skin responses (SSRs) and their correlation with brain lesion volumes in patients with multiple sclerosis (MS). MATERIALS AND METHODS: The SSRs were measured in 27 patients with MS and 27 healthy controls. The volumes of the proton density-weighted MS lesions in the brain were measured using MRI. RESULTS: The SSRs were abnormal in 52% of the patients with MS, but absent only in clinically severe MS. The total lesion volume in the whole brain correlated significantly with both the severity of MS expressed by the EDSS score (P < 0.001) and the decreased SSR amplitudes in the feet (P < 0.01). Focal lesion volumes in the temporal lobe (P < 0.01), in the pons (P < 0.01) and in the cerebellum (P < 0.01) were also separately associated with abnormal SSR reflexes. CONCLUSIONS: Sudomotor regulation failure in MS is associated with certain focal MS lesions.

Blood pressure and heart rate in parkinsonian patients with and without wearing-off.

Our study aimed to investigate the cardiovascular autonomic regulation related to the wearing-off phenomenon in Parkinson's disease (PD). We measured blood pressure (BP) and heart rate (HR) at rest and during orthostatic test in 16 patients with PD with wearing-off and in 15 patients with PD without wearing-off both before (baseline) and repetitively at 1-h intervals for up to 4 h after the morning PD medication dose. The patients with wearing-off had fluctuation of BP during the observation period, BP increasing when the motor performance worsened and vice versa. The mean supine BP was at its highest at the baseline measurement (patients with wearing-off, 145 +/- 18 mmHg; patients without wearing-off, 138 +/- 17 mmHg), fell during the first hour (patients with wearing-off, 119 +/- 17 mmHg; patients without wearing-off, 126 +/- 18 mmHg), and then rose again toward the end of the observation period (patients with wearing-off, 136 +/- 15 mmHg; patients without wearing-off, 138 +/- 18 mmHg). This BP change was statistically significant only in PD patients with wearing-off (P < 0.001). In conclusion, BP seems to fluctuate with motor impairment in PD patients with wearing-off. This fluctuation may represent autonomic dysfunction caused by the PD process itself, the effect of PD medication, or both.

Natriuretic peptides and mortality after stroke.

BACKGROUND AND PURPOSE: Measurement of natriuretic peptides provides prognostic information in various patient populations. The prognostic value of natriuretic peptides among patients with acute stroke is not known, although elevated peptide levels have been observed. METHODS: A series of 51 patients (mean age, 68+/-11 years) with first-ever ischemic stroke underwent a comprehensive clinical examination and measurements of plasma atrial natriuretic peptides (N-ANP) and brain natriuretic peptides (N-BNP) in the acute phase of stroke. The patients were followed-up for 44+/-21 months. Risk factors for all-cause mortality were assessed. Control populations, matched for gender and age, consisted of 51 patients with acute myocardial infarction (AMI) and 25 healthy subjects. RESULTS: Plasma concentrations of N-ANP (mean+/-SD, 988+/-993 pmol/L) and N-BNP (751+/-1608 pmol/L) in the stroke patients were at the same level as those in the AMI patients (NS for both), but significantly higher than those of the healthy subjects (358+/-103 pmol/L, P<0.001 and 54+/-26 pmol/L, P<0.01, respectively). Elevated levels of N-ANP and N-BNP predicted mortality after stroke (risk ratio [RR] 4.3, P<0.01 and RR 3.9, P<0.01, respectively) and after AMI (P<0.05), and remained independent predictors of death after stroke even after adjustment for age, diabetes, coronary artery disease, and medication (RR 3.9, P<0.05 and RR 3.7, P<0.05, respectively). CONCLUSIONS: Plasma levels of natriuretic peptides are elevated in the acute phase of stroke and predict poststroke mortality.

Cerebral CT and MRI findings in cervicocephalic artery dissection.

PURPOSE: To explore the frequency and patterns of brain infarction and other brain manifestations in cervicocephalic artery dissection (CCAD) and to evaluate the correlation between vessel wall findings and infarctions. MATERIAL AND METHODS: The medical records and films of 136 consecutive CCAD patients diagnosed in Oulu University Hospital during the 20-year period since 1982 were reviewed. Five patients with no brain imaging were excluded. RESULTS: One-hundred-and-twenty-seven patients underwent cerebral CT and four patients MRI. Brain infarction was detected in 73 patients (56%), 43 of whom had cerebral infarction associated with anterior circulation dissection and 30 cerebellar infarction associated with posterior circulation dissection. Occlusion of the dissected vessel was accompanied by infarction in 76%, irregular stenosis in 40%, and other findings in 12%. Of the anterior circulation infarctions, territorial and subcortical infarctions and territorial infarctions with fragmentation, which are considered embolic, accounted for 95%, while only 5% were in the watershed area and considered hemodynamic. Intracranial posterior circulation dissection rarely caused infarction (in 1/11 of the dissected vessels), whereas intracranial anterior circulation dissection resulted in infarction more commonly (9/12). Altogether 23% of patients with intracranial CCAD had subarachnoid hemorrhage. Hemorrhagic transformation was present in five patients. CONCLUSIONS: More than half of CCAD patients have cerebral or cerebellar infarction at CT or conventional MR imaging. Occlusion of the dissected vessel is accompanied by infarction more often than other vessel wall abnormalities. Most cerebral infarctions caused by arterial dissections are of embolic origin. Intracranial dissections cause subarachnoid hemorrhage in more than 20% of patients.

The generic 15D instrument is valid and feasible for measuring health related quality of life in Parkinson's disease.

OBJECTIVES: To test the validity and feasibility of the generic 15D health related quality of life (HRQoL) instrument in Parkinson's disease (PD) and compare parkinsonian patients with the general population. Much effort has gone into developing disease specific HRQoL measures for PD, but only generic measures allow comparisons with the general population. New HRQoL tools are needed for PD because earlier ones have low feasibility in elderly patients. METHODS: The study comprised 260 patients with idiopathic PD and age and sex matched controls. HRQoL was evaluated using the disease specific questionnaire PDQ-39 and the 15D generic instrument. PD severity was assessed by Hoehn and Yahr staging, and the activities of daily living (ADL) and motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The mean 15D score (scale 0-1; overall HRQoL) was lower in PD (0.77) than in controls (0.86). Patients with PD had significantly lower scores than controls in 13 of the 15 dimensions of 15D. Scores of the corresponding dimensions of PDQ-39 and 15D correlated significantly, confirming the convergent validity of 15D. In multiple stepwise regression analysis, the UPDRS ADL score explained 55% of the variation in the 15D score. CONCLUSIONS: 15D is a valid, feasible, and sensitive tool to assess quality of life in PD. PD has a major impact on HRQoL, which is related to disease progression. Mobility, eating, speech, and sexual functions are most affected. The ADL measure of the UPDRS and the 15D provide an easily assessable view of HRQoL in PD.

Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS.

OBJECTIVE: The aim of the present study was to investigate the cardiovascular autonomic control in clinically definite multiple sclerosis (MS) patients with a standardised battery of cardiovascular tests and to correlate these findings with the brain magnetic resonance imaging (MRI) lesion load. METHODS: Fifty-one patients with MS and 50 healthy controls were studied. Brain MRI was performed in all patients showing typical MS lesions. The cardiovascular tests were carried out using a standardised battery. RESULTS: Heart rate (HR) responses to deep breathing (P < 0.05) and tilt table testing (P < 0.001) were significantly decreased in MS patients when compared to those of the controls. Blood pressure (BP) responses in the tilt table test were also impaired in MS patients (diastolic P < 0.001, systolic P < 0.05). Of the different brain areas investigated the total volume of the midbrain MRI lesions (P < 0.05) was the one most clearly associated with the impaired BP responses. CONCLUSIONS: MS results in both reduced HR variation and decreased BP reactions indicating disturbed cardiovascular regulation. In particular, the midbrain lesions found in MS are associated with cardiovascular dysfunction.

Heart rate dynamics predict poststroke mortality.

BACKGROUND: Impaired cardiovascular autonomic regulation assessed by heart rate (HR) variability provides prognostic information in patients with heart disease as well as among elderly. Reduced HR variability has been described in stroke patients, but the prognostic significance of HR variability measures after stroke has not been studied. METHODS: A series of 84 patients (mean age 59 +/- 12 years) with an acute first-ever ischemic stroke underwent a comprehensive clinical investigation, laboratory tests, and 24-hour EKG recordings and were followed up for 7 years (mean 83 +/- 54 months). Various conventional and newer qualitative measures of HR variability were analyzed from the baseline 24-hour EKG. Risk factors for all-cause mortality were assessed. RESULTS: During the follow-up, 33 (39%) patients died and 51 survived. Among all the variables analyzed, abnormal long-term HR variability measure power-law slope beta (beta < -1.5), reflecting an altered distribution of spectral characteristics over ultra and very low frequency bands, was the best univariate predictor of death (hazard ratio 4.5, 95% CI 2.2 to 9.5, p < 0.001). High age, poor Scandinavian Stroke Scale score, and abnormal short-term HR variability scaling measure (alpha) also predicted mortality in univariate analysis. In multivariate analysis, after adjustment for age, the only independent predictor of the risk of death was abnormal long-term power-law slope beta (hazard ratio 3.8, CI 1.8 to 8.2, p < 0.001). Conventional HR variability measures showed no prognostic power. CONCLUSION: Abnormal long-term HR dynamics predict poststroke mortality. This measure may have value in the risk stratification of stroke patients.

Extracranial internal carotid and vertebral artery dissections: angiographic spectrum, course and prognosis.

We reviewed the clinical and radiological findings of 93 consecutive patients with 111 extracranial internal carotid (ICAD) and vertebral artery (VAD) dissections and one concomitant intracranial VAD; 83% of the patients had unilateral and 17% multiple vessel dissections. The diagnosis was made by intra-arterial digital subtraction angiography in 92 patients and MR angiography in one. Follow-up angiography was performed in 77 cases (83%): of 49 initially stenotic arteries, 40 became completely or almost completely normal, while three showed slight improvement. Of 30 initially occluded arteries, nine had completely or partly recanalised. Of 12 pseudoaneurysms eight were unchanged at follow-up. The proximal vertebral artery was involved as often as the C1-C2 level. Recurrences were rare: a new dissection in another vessel was found in three patients. Kinking or coiling was found in 23% of the dissected internal carotid arteries.

Economic burden and quality of life impairment increase with severity of PD.

PURPOSE: To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson's disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. CONCLUSIONS: There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.

Comparison of heart rate variability analysis methods in patients with Parkinson's disease.

The aim of the present study was to evaluate different analysis methods for revealing heart rate variability (HRV) differences between untreated patients with Parkinson's disease and healthy controls. HRV in standard cardiovascular reflex tests and during a 10 min rest period were measured by time- and frequency-domain and geometrical and non-linear analysis methods. Both frequency- and time-domain measures revealed abnormal HRV in the patients, whereas non-linear and geometrical measures did not. The absolute high-frequency spectral power of HRV was the strongest independent predictor to separate the patients from the controls (p = 0.001), when the main time-domain and absolute frequency-domain measures were compared with each other. When the corresponding normalised spectral units, instead of the absolute units, were used in the comparison, the two best single measures for separating the groups were the 30/15 ratio of the tilting test (p = 0.003) and the max/min ratio during deep breathing (p = 0.024). When the correlations between the different measures were estimated, the time-domain measures, fractal dimension and absolute spectral powers correlated with each other. The frequency- and time-domain analysis techniques of stationary short-term HRV recordings revealed significant differences in cardiovascular regulation between untreated patients with Parkinson's disease and the controls. This confirms cardiovascular regulation failure before treatment in the early stages of Parkinson's disease. The HRV spectral powers, in absolute units, were the most effective single parameters in segregating the two groups, emphasising the role of spectral analysis in the evaluation of HRV in Parkinson's disease.

Enoxaparin vs heparin for prevention of deep-vein thrombosis in acute ischaemic stroke: a randomized, double-blind study.

OBJECTIVES: To compare the efficacy, safety, and overall risk-benefit profile of enoxaparin and unfractionated heparin (UFH) prophylaxis of venous thromboembolic complications in patients with acute ischaemic stroke. METHODS: Patients with ischaemic stroke resulting in lower-limb paralysis lasting for at least 24 h and necessitating bedrest, were randomized within 48 h of the onset of stroke, and treated with enoxaparin (40 mg subcutaneously once daily) or UFH (5000 IU subcutaneously thrice daily) for 10 +/- 2 days. Main outcome measures were deep-vein thrombosis, pulmonary embolism (PE), death from any cause, intracranial haemorrhage including haemorrhagic infarction, or any other major bleeding. RESULTS: Outcome events occurred within 3 months of stroke in 40/106 patients treated with enoxaparin (37.7%) and 52/106 patients treated with UFH (49.1%, P=0.127). Fewer patients treated with enoxaparin (14, 13.2%) than with UFH (20, 18.9%) had evidence of haemorrhagic transformation of ischaemic stroke. CONCLUSIONS: Enoxaparin administered subcutaneously once daily was as safe and effective as subcutaneous UFH given thrice daily in the prevention of thromboembolic events in patients with lower limb paralysis caused by acute ischaemic stroke.

[123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients.

Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinson's disease (PD) and controls using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The striatal DAT specific to non-displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]beta-CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas.

Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

OBJECTIVES: Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. METHODS: 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. RESULTS: All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. CONCLUSIONS: Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

Domains and determinants of quality of life after stroke caused by brain infarction.

OBJECTIVE: To evaluate the domain-specific quality of life (QOL), including physical, social and role functioning, mental health, vitality, bodily pain, and general health domains, and to assess QOL's clinical and sociodemographic correlates in patients who were disabled by ischemic stroke. DESIGN: One-year prospective study of an inception cohort of patients with first-ever brain infarction. SETTING: Stroke unit of a neurologic department of a university hospital. PATIENTS: Eighty-five consecutive patients (36 women, 49 men; mean age +/- SD, 65+/-12.5 yr) with first-ever stroke of a mild to moderate nature caused by brain infarction. MAIN OUTCOME MEASURES: Patients were examined at 3 and 12 months poststroke. QOL was measured using the RAND 36-Item Health Survey. The variables studied were lateralization of cerebral lesion, neurologic and functional status, depression, age, gender, marital status, and living conditions. Depression was evaluated according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Neurologic impairment was assessed by Scandinavian Stroke Scale, performance in activities of daily living by the Barthel index, and the intellectual deterioration by the Mini-Mental State Examination. RESULTS: QOL was poorer for the patients with mild to moderate stroke impairments at 3 months poststroke. The test domains most prone to being affected were physical functioning, physical role limitations, vitality, and general health. Only the domains of physical functioning and physical role limitations improved during the follow-up at 1 year. Depression, although mostly minor, was the most important reason for impaired QOL. Depression, being married, and age emerged as significant independent contributors to the low score value of vitality. Depression and being married were related to the low score value of physical role limitations. CONCLUSIONS: Stroke affects QOL, impairing its physical and psychosocial domains. The most important determinants of low QOL seem to be depression and being married. These findings provide new challenges for stroke rehabilitation, calling for identification of patients and spouses in need of supportive services.

Aphasia, depression, and non-verbal cognitive impairment in ischaemic stroke.

Aphasia, depression, and cognitive dysfunction are common consequences of stroke, but knowledge of their interrelationship is limited. This 1-year prospective study was designed to evaluate prevalence and course of post-stroke aphasia and to study its psychiatric, neurological, and cognitive correlates. We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65. 8 years) with first-ever ischaemic brain infarction. The patients were clinically examined, and presence and type of aphasia were evaluated during the 1st week after stroke and 3 and 12 months later. Psychiatric and neuropsychological evaluations were performed 3 and 12 months after stroke. Aphasia was diagnosed in 34% of the patients during the acute phase, and two thirds of them remained so 12 months later. Seventy percent of the aphasic patients fulfilled the DSM-III-R criteria of depression 3 months and 62% 12 months after stroke. The prevalence of major depression increased from 11 to 33% during the 12-month follow-up period. The non-verbal neuropsychological test performance in the aphasic patients was significantly inferior to that of the patients with dominant hemisphere lesion without aphasia. One third of the patients with ischaemic stroke suffer from communicative disorders which seem to increase the risk of depression and non-verbal cognitive deficits. Although the prevalence of depression in aphasic patients decreases in the long term, the proportion of patients suffering from major depression seems to increase. We emphasize the importance of the multidimensional evaluation of aphasic stroke patients.

Auditory P300 event related potential in minor ischemic stroke.

OBJECTIVE: Various degenerative cerebral diseases and even depression may cause abnormalities of the cognitive event related potentials (ERPs). We conducted the present study to elucidate the effects of ischemic stroke on the P300 ERP component. MATERIAL AND METHODS: We recorded the P300 wave using an auditory oddball paradigm in 38 consecutive brain infarct patients with mild neurological deficits at 3 and 12 months post-stroke, and in 29 healthy control subjects. RESULTS: Brain infarction slightly prolonged the P300 latency, and the observed delay was related to the presence and degree of post-stroke depression evaluated with the Zung Depression Scale and the DSM-III criteria. Infarction did not affect the P300 amplitude or its distribution on the scalp. The results of the patients with hemispheric brain infarction and those of the patients with brainstem infarction were similar, and also the values of the patients with the left- and right-sided lesions. The normal physiological correlation between subject age and the P300 latency was absent at 3 months post-stroke, but was present at 12 months post-stroke. CONCLUSION: Brain infarction delays the P300 ERP and temporarily distorts its age-related physiology. The increase of the P300 latency seems to be associated with the post-stroke depression.

Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease.

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n = 20), bromocriptine (n = 20) or selegiline (n = 20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and suppress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation.