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.

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.

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.

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.

Selegiline as primary treatment in early phase Parkinson's disease--an interim report.

We are carrying out a double-blind parallel trial comparing the effect of selegiline monotherapy and placebo in de novo parkinsonian patients. Fifty-six patients (28 in both groups) are included in the trial. This interim analysis reports the results of the first 52 evaluable patients who have had at least one follow-up visit after entering the trial. The efficacy of treatment was assessed using the Columbia University Rating Scale, the North-Western University Disability Scale and the Webster Rating Scale and followed until the addition of levodopa therapy became necessary. The data were analysed at follow-up times of up to twelve months (34 patients evaluable at the end of the period). The overall disability scores of all the rating scales used were significantly smaller in the selegiline group than in the placebo group. Levodopa treatment had become necessary in 12 patients (46%) in the selegiline group and in 14 patients (54%) in the placebo group. The side-effects were mild and similar in both treatment groups. According to the present results selegiline monotherapy seems to have therapeutic efficacy in the early phase of Parkinson's disease. Whether selegiline is able to slow down the progression of Parkinson's disease needs further clarification.

Selegiline as a primary treatment of Parkinson's disease.

In order to investigate the efficacy of selegiline as a primary treatment in Parkinson's disease (PD), we carried out a placebo controlled, double-blind prospective trial. Fifty-four de novo patients with PD were randomized to receive either selegiline (10 mg/day) or matching placebo. We continued the monotherapy until the initiation of levodopa therapy became necessary. The disability of the patients was evaluated with three different rating scales at baseline, after 3 weeks, 2, 4, 8, and 12 months, and every 4 months thereafter. Fifty-two patients were eligible for the final analysis: 27 in the selegiline group and 25 in the placebo group. The median duration of time without levodopa was 545 +/- 90 days in the selegiline treated patients and 372 +/- 28 days in the placebo treated ones (p = 0.03). The disability of the patients was significantly milder in the selegiline than in the placebo group up to 12 months. More patients showed symptomatic improvement in the selegiline than in the placebo group. However, the symptomatic effect alone did not explain the prolongation of the time without levodopa in the selegiline treated patients. Selegiline was well tolerated and no severe side effects were encountered.

Cerebral outcome after extracorporeal circulation. Comparison between prospective and retrospective evaluations.

The cerebral outcome of 100 consecutive patients who had cardiac valvular replacement was evaluated by comparing the results of prospective neurological examination with retrospective data. The latter showed that the overall prevalence of cerebral abnormalities was 6% (4% among survivors) up to ten days postoperatively and 9% thereafter. This contrasts with the 35% (37% among survivors) obtained by careful neurological investigations that showed five patients with residual signs one year after operation. Electroencephalographic and neuropsychological studies disclosed additional patients who had subclinical involvement. The results question the reportedly ever-falling cerebral complication values claimed particularly in retrospective studies and reflect what is missed when using rough clinical criteria. There is no justification in overlooking slight clinical or even subclinical dysfunction, since the elimination of them is the only acceptable criterion of cerebral safety in cardiac operations.

Neuropsychologic outcome after open-heart surgery.

A neuropsychologic (NP) study was carried out on 49 patients who had had cardiac valvular replacement to investigate the determinants of postoperative outcome. The results were assessed together with operative data and with neurologic and quantitative EEG (QEEG) findings. Of the operative variables, perfusion time and unexpected intraoperative events were the most important factors leading to postoperative NP impairment. Clinical neurologic outcome correlated positively with NP changes. Differences between various cardiologic and age groups were found in the postoperative NP findings. Changes in frequency in QEEG reflected the NP changes more reliably than did amplitude. Significantly one of the tests, a modification of the Stroop color test, was found to be prognostically important, suggesting that it might be possible to construct test batteries of value in predicting high operative risk. The results show that multiparameter investigation using NP testing together with clinical and QEEG follow-up is useful in the assessment of cerebral disorders attributable to open-heart surgery.

Neurologic complications associated with Yersiniosis.

Despite worldwide appearance of Yersinia enterocolitica infections, very little is known about the possible neurologic manifestations associated with this disease. We describe two patients who developed neurologic complications from yersiniosis. One had brachial plexus neuropathy (neuralgic amyotrophy), and the other developed the clinical picture of myelitis. The possibility of yersiniosis behind neurologic manifestations related to infectious diseases of uncertain origin should be recognized.

Asymmetric sweating in stroke: a prospective quantitative study of patients with hemispheral brain infarction.

We performed a prospective study of sweating in 40 patients with hemispheral brain infarction and 40 healthy controls to elucidate the clinical significance and prognostic value of sweating dysfunction in conjunction with brain infarction. We measured hidrosis quantitatively at six sites on each side of the body before and after a heating stimulus in the acute phase, at 1 month, and at 6 months after infarction. Excessive evaporation on the paretic side when compared with the nonparetic side was already found at baseline, but after the heating stimulus, this asymmetry reached statistical significance on the forehead, chest, forearm, and hand during the whole 6-month follow-up. Significant asymmetry in sweating occurred in 29 of the 40 patients (73%) in the acute phase of infarction, in 18 of 32 (56%) after 1 month, and in 28 of 33 (85%) after 6 months. Hyperhidrosis correlated with the severity of paresis and the presence of pyramidal tract signs. We conclude that sweating asymmetry seems to be an essential, long-lasting consequence of autonomic failure occurring in the majority of patients with hemispheral brain infarction.

Selegiline as initial treatment in de novo parkinsonian patients.

To investigate the efficacy and safety of selegiline in the early phase of Parkinson's disease (PD), we carried out a placebo-controlled, double-blind, parallel trial. De novo PD patients were randomized to receive either selegiline (10 mg/d) or matching placebo. We continued selegiline or placebo until levodopa therapy became necessary and assessed the disability using three different rating scales at baseline, after 3 weeks, at 2, 4, 8, and 12 months, and at every 4 months thereafter. Fifty-two patients were eligible for the analysis, 27 in the selegiline group and 25 in the placebo group. The median duration of time before levodopa had to be initiated was 545 +/- 90 days with selegiline and 372 +/- 28 days with placebo (p = 0.03). Disability was significantly less in the selegiline group than in the placebo group up to 12 months. The period of time during which the mean total Columbia University Rating Scale score stayed below the baseline was used to express the initial symptomatic effect of the treatments. The difference in this initial improvement time between the two groups was about 3 months and did not alone explain the difference in the delay of the need to start levodopa therapy. Selegiline was well tolerated and there were no severe side effects. We conclude that selegiline delays the need to start levodopa in de novo PD patients, has symptomatic efficacy, and possibly retards the progression of the disease.

Effect of selegiline on mortality in patients with Parkinson's disease: a meta-analysis.

INTRODUCTION: The Parkinson's Disease Research Group of the United Kingdom (PDRG-UK) reported increased mortality in PD patients treated with levodopa plus selegiline compared with those treated with levodopa alone. METHODS: We performed a meta-analysis on five long-term, prospective, randomized trials of selegiline in patients with untreated PD. Included in the analysis were four randomized, double-blind, placebo-controlled studies and one randomized, double-blind, placebo-controlled study of 2 years' duration followed by long-term, open follow-up. RESULTS: The mean duration of follow-up was 4.1 +/- 1.8 years. There were 14 deaths in 297 selegiline-treated patients (4.7%) and 17 deaths in 292 non-selegiline-treated patients (5.8%). The hazard ratio for mortality was 1.02 (95% CI 0.44 to 2.37; p = 0.96). An analysis restricted to patients receiving only levodopa with or without selegiline noted 11 deaths in 257 levodopa/selegiline-treated patients (4.3%) and 11 deaths in 254 patients treated with levodopa alone (4.3%). The hazard ratio was 1.06 (95% CI 0.44 to 2.55; p = 0.90). Death rate per 1,000 patient years was 11.4 in the selegiline group and 14.2 in the nonselegiline group. Kaplan-Meier survival curves reflecting pooled survival data showed no significant difference in duration of survival. The hazard ratio was 0.84 (95% CI 0.41 to 1.70; p = 0.63) for selegiline- versus non-selegiline-treated patients and 1.05 (95% CI 0.46 to 2.43; p = 0.91) for selegiline/levodopa- versus levodopa-treated patients. CONCLUSION: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

Long-term neurologic outcome after cardiac operation.

Cardiac surgical patients face the threat of neurologic complications in all phases of their disease and its treatment. The incidence of preoperative transient ischemic attacks and stroke ranges from 5% to 14% and from 2% to 11%, respectively. The risk of preoperative cerebrovascular accidents is higher in patients with valvular disease than in those with coronary artery disease. The prevalence of postoperative neurologic disorders varies widely because of differences in defining the clinical criteria, heterogeneity of patient populations, timing of evaluation, follow-up times, study designs, and surgical and anesthesia-related procedures. Fatal cerebral damage is very rare (< 0.1%). Focal cerebral deficits, or definite stroke, are encountered in 1% to 3% of patients and minor clinical abnormalities, in 5% to 10%. Recent studies have shown that contrary to previous concepts, valve replacement does not carry essentially higher neurologic risks than coronary bypass grafting. The most common causes of operation-related neurologic disorders are microembolization or macroembolization and hypoperfusion. Although most disorders resolve early postoperatively, some deficits persist. From the neurologic standpoint, a main objective of a cardiac surgical intervention is to prevent stroke. Today, the incidence of cardiogenic cerebrovascular accidents is very low after reparative cardiac procedures. Despite surgical and anesthesia-related improvements, neurologic complications do occur. Multidimensional investigatory procedures have shown that cardiopulmonary bypass often causes cerebral dysfunction. Whether the harmful consequences are detected depends on the evaluation criteria and the investigatory methods and timing used. Further methods are needed to prevent or treat preoperative cerebrovascular accidents and particularly to improve cerebral protection during operative procedures.

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.

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.

Clinical and prognostic correlates of EEG in open-heart surgery patients.

Sixty-five patients undergoing cardiac valve replacement were followed for one year by electroencephalography (EEG). Occurrence of delta or sharp wave disturbances of low frequency of dominant activity before operation was found to have prognostic significance. The degree of EEG change after operation correlated with clinical signs of cerebral involvement, and predicted the later course.