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.     

Selegiline as the primary treatment of Parkinson's disease — a long-term double-blind study

Introduction – To assess the therapeutic efficacy of selegiline combined with levodopa in the long-term treatment of Parkinson's disease (PD). Material and methods – A randomized, prospective, double-blind study on 44 patients with PD needing levodopa therapy after the initial double-blind treatment with placebo or selegiline was carried out. The patients were followed-up for 5 years under combination therapy. Results – Selegiline induced a significant ( P < 0.001) slowing in the need to increase the daily levodopa dose in order to compensate for the progression of the disease. After 5 years of combination therapy the mean dose of levodopa was on average 320 mg lower in the selegiline group (405 ± 59 mg vs 725 ± 78 mg). The difference in the levodopa doses between the two groups increased along with follow-up time, as also the ratio of the levodopa doses (placebo/selegiline group). The number of daily levodopa doses needed to compensate for the occurrence of motor fluctuations was significantly lower in the selegiline group. The parkinsonian disability did not differ between the two groups because the clinical condition was kept as optimal as possible by adjusting the levodopa dosage. Nine patients in the placebo group needed initiation of additional dopaminergic therapy in comparison to one in the selegiline group ( P =0.004). During the 5-year follow-up period 11 patients were withdrawn from the selegiline group, 7 due to adverse events. There was no difference in mortality between the two groups. Conclusion – Selegiline therapy offers beneficial long-term effects in the treatment of PD.     

Selegiline in Parkinson''s disease

Twenty patients with Parkinson's disease were treated with the MAO-B inhibitor selegiline (l-deprenyl) and placebo without levodopa (L-dopa) in a randomized double-blind clinical cross-over study to analyze relative importances of dopamine (DA) synthesis and metabolism. The daily dose of selegiline was gradually increased to a maximum of 30 mg in all patients. The clinical neurological disability (Columbia score) was about 10% less on selegiline (30 mg/day) than on placebo. This difference was neither statistically nor clinically significant. The results are compatible with the possibility that treatment with selegiline without concomitant L-dopa does not significantly increase DA concentration which remains low and is determined mainly by tyrosine hydroxylase activity. At low DA levels the DA re-uptake mechanism recaptures most of the released DA and DA deamination is of minor significance. The pathway of DA oxidation becomes more important only at higher DA concentrations, accomplished by bypassing the rate limiting step of tyrosine hydroxylation using L-dopa.     

Ambulatory blood pressure in patients with Parkinson's disease without and with orthostatic hypotension

Non-invasive ambulatory recordings of blood pressure and heart rate were performed using a Spacelabs device during day and night periods in patients with Parkinson's disease with (n = 19) or without orthostatic hypotension (n = 19). In patients with orthostatic hypotension, the average systolic and diastolic blood pressure during the night (137 ± 5/80 ± 3 mmHg) was higher (p < 0.05) than during the day period (121 ± 3/76 ± 2 mmHg). In patients without orthostatic hypotension, a decrease in blood pressure was recorded during the nocturnal period. In patients with orthostatic hypotension, the blood pressure variability was higher (p < 0.05) during the day (systolic: 14.6 ± 1.3%; diastolic: 16.5 ± 1.0%) than during the night (systolic: 9.1 ± 0.8%; diastolic: 10.8 ± 1.1%). The blood pressure load (percentage of values above 140/90 mmHg) during the night was significantly higher than during the day for both systolic (41.2 ± 8.1 vs. 19.6 ± 4.7%) and diastolic blood pressure (24.9 ± 6.9 vs. 16.3 ± 4.9%). There was a decrease in heart rate in both groups during the night. A fall of 25 mmHg or more in systolic blood pressure after meals occurred in ten patients with orthostatic hypotension and in one patient without orthostatic hypotension. These results indicate that orthostatic hypotension in Parkinson's disease is associated with specific modifications of ambulatory blood pressure including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability and post-prandial hypotension.     

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.     

Selegiline and cognitive function in Parkinson''s disease

Eighteen patients with Parkinson's disease were treated with placebo for 4 weeks and with the MAO-B inhibitor selegiline for 8 weeks without levodopa in a randomized double-blind clinical study. The maximum dose of selegiline was 30 mg/day and the patients' cognitive functions were evaluated before treatment and at week 12 when they were either on 30 mg selegiline or placebo. A series of neuropsychological tests were used to study general cognitive reasoning, memory, visuospatial abilities, attention, cognitive flexibility, motor functions and depression. Specific cognitive effects were not observed. Slight improvement occurred mainly in learning (easy word associations) which may reflect a limited, nonspecific arousal effect.     

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

Abstract– 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 and levodopa in early or moderately advanced Parkinson's disease: a double-blind controlled short- and long-term study

Abstract– Selegiline 10 mg per day was compared to placebo as an adjunct to levodopa treatment in this double-blind study of early or moderately advanced Parkinson's disease. Thirty-eight patients completed an initial cross-over trial comprising two treatment periods, each of eight weeks, with a four weeks'wash-out period between them. Thirty of the patients continued in a long-term, double-blind parallel trial with a mean duration of 16 months (range 6–30 months). Selegiline treatment allowed a significant reduction of the necessary daily levodopa dose in both parts of the study and of the daily dosing frequency in the long-term investigation. In spite of this reduction of levodopa dose, an improvement was noted in tremor during the short-term selegiline periods. The side-effects were slight and related to dopamine effects and disappeared after reduction of levodopa-dose. The results support the use of selegiline as an early adjunctive treatment in Parkinson's disease.     

Selegiline in the treatment of daily fluctuations in disability of parkinsonian patients with long-term levodopa treatment

Abstract– In order to evaluate in a double-blind manner the therapeutic efficacy of selegiline in the treatment of late-phase Parkinson's disease, 19 patients with end-of-dose type fluctuations were randomized for a double-blind cross-over trial receiving either selegiline 10 mg or placebo. Each period lasted 12 weeks. During a two week prestudy period the dose of levodopa was titrated to optimal levels. The disability was evaluated using the Columbia University Disability Scale (CUDS). The patients kept a daily diary to monitor closely the frequency and severity of their fluctuations and the side-effects of treatment. Their parkinsonian disability and all main symptoms improved significantly during selegiline treatment. The mean duration of action of a levodopa dose was significantly longer and there was significantly less daily end-of-dose and early morning akinesia during selegiline treatment. The side-effects were similar in both treatments. This double-blind study confirms the findings of earlier open studies that selegiline potentiates and prolongs the therapeutic effects of levodopa and thus its use is particularly beneficial in patients with end-of-dose type fluctuations in disability.     

帕金森病患者心血管自主神经功能障碍的临床研究

目的研究帕金森病(PD)患者心血管自主神经功能障碍及其相关的影响因素。方法入选PD患者(PD组)51例和健康对照者(对照组)30例,分别进行24 h动态血压和动态ECG监测,对比分析两组的血压变异性(BPV)和心率变异性(HRV)的指标,同时对PD患者进行左旋多巴等效剂量(LED)换算、Hoehn-Yahr分期(H-Y分期)和统一PD评定量表Ⅲ(UPDRSⅢ)评分,探讨BPV和HRV的影响因素。结果 PD组BPV中24h SBPSD、dSBPSD、nSBPSD较对照组明显升高(均P0.05)。PD组HRV中SDNN、RMSSD、HF、LF较对照组明显下降(均P0.05)。PD患者BPV与病程具有正相关(P0.05),HRV与病程、H-Y分期、UPDRSⅢ评分具有负相关(均P0.05)。结论 PD患者存在心血管自主神经功能障碍,且与病程、疾病严重程度及运动症状严重程度有关。     

司来吉兰联合复合多巴治疗帕金森病的有效性和安全性

目的 探讨司来吉兰联合复合多巴治疗帕金森病的疗效和安全性.方法 将89例帕金森病患者随机分为对照组(45例)和治疗组(44例),对照组患者采用复合多巴等药物治疗,治疗组患者加用司来吉兰治疗,6个月为1个观察周期.于用药前及用药后1、3、6个月采用PD统一评分量表(UPDRS)对两组患者进行疗效评定,并观察其不良反应.结果 治疗组患者治疗1个月时与治疗前相比,除UPDRSⅢ评分降低外(P＜0.01),UPDRSⅠ、Ⅱ、Ⅳ评分变化均无统计学差异(均P＞0.05);治疗3、6个月时与治疗前比较,其UPDRSⅠ～Ⅳ评分均下降(P＜0.01);治疗3、6个月时与治疗1个月时比较,UPDRS Ⅰ、Ⅲ、Ⅳ评分降低均降低(P＜0.01,P＜0.05);治疗6个月时与治疗3个月时相比,其UPDRS Ⅰ～Ⅳ评分均无统计学差异(P＞0.05).治疗3、6个月时,治疗组UPDRSⅠ～Ⅳ评分均明显低于对照组(P＜0.01,P＜0.05).观察期内,两组患者未出现严重不良反应.结论 司来吉兰联用复合多巴可有效改善帕金森病症状,且耐受性好,不良反应少.     

The effects of acute loading with levodopa and levodopa with selegiline on blood pressure and plasma norepinephrine levels in chronic Parkinson's disease patients

OBJECTIVES: Contradictory possible cardiovascular side effects of selegiline have been reported. Therefore, we studied the effect of acute administration of selegiline with levodopa (LD) compared with LD alone, on blood pressure, pulse and norepinephrine (NE) plasma levels, during an orthostatic test on chronically treated Parkinson's disease patients (PDpts) and controls. MATERIALS AND METHODS: Twelve PDpts treated with LD (group D), 12 PDpts treated with selegiline and LD (group S) and eight volunteers (CTRL) underwent the orthostatic test. Patients repeated the test twice, before and after acute loading with 125 mg LD (group D) and 125 mg LD +5 mg selegiline (group S). RESULTS: Group S showed more episodes of postural hypotension (n = 10; two symptomatic) than group D (n = 4) and CTRL (n = 2), however not statistically significant. Plasma NE also rose significantly higher (P < 0.001) in group S. CONCLUSION: PD patients treated with selegiline showed more orthostatism and higher plasma NE after submission to the orthostatic test. These findings may be relevant to explain its deleterious effect.     

Selegiline in the treatment of Parkinson's disease — long term experience

Abstract– L-deprenyl (selegiline) has been reported as a safe effective adjunctive agent to levodopa in the control of Parkinson's symptoms, as well as a means of preventing the progressive nature of the disease process. In an ongoing study, now in its 12th year, L-deprenyl has been administered 1. as monotherapy or 2. in combination with levodopa, to previously untreated patients in the early phases of the disease; 3. added to an existing regimen of levodopa when optimal therapeutic results are not being obtained. This report reviews our experience in each of these three treatment categories.
Results obtained to date, indicate that L-deprenyl administered alone does not prevent the occurrence of signs of Parkinson's disease. It's administration with levodopa, as initial therapy, allows for use of lower dosage and less side effects of the latter agent. When L-deprenyl is added to sub-optimal responders to levodopa, it attenuates fluctuating responses, particularly those of the 'end-of-dose'variety.     

Autonomic dysfunction in Parkinson's disease assessed by sympathetic skin response: a prospective clinical and neurophysiological trial on 50 patients

To verify possible dysfunction of sympathetic skin activity in Parkinson's disease (PD), we studied the electrically evoked sympathetic skin responses (SSR) bilaterally at hands and feet in a group of 50 PD patients and in normal subjects. SSR was present in all patients. Nevertheless, significant differences in the latency and amplitude values were noted. In the group of patients prolongation of latency as well as the reduction of SSR amplitude correlates with age. The longer the disease the more SSR abnormalities could be found. Gender, type of clinical manifestation of PD or medication had no statistically significant effects. However, motor symptom asymmetries evaluated separately for each body side correlated well with interside asymmetries of SSR.     

High-dose therapy with ropinirole in patients with Parkinson's disease

Summary. Ropinirole is effective as mono- and combination therapy in PD. Previous studies have used a maximal dose of 24 mg/day; the present study assesses the effect of higher doses (up to 36 mg/day) on patients with motor fluctuations. Outcome measures were changes in the motor function score of the Unified Parkinson's Disease Rating Scale, the duration of dyskinesias and reductions in levodopa dose. 21/22 patients completed the study. The mean daily ropinirole dose at endpoint was 26.2 mg (SD, 4.43 mg, range 20–36 mg). Improvements in motor function (29%) and the duration of dyskinesias (45%) from baseline to endpoint were significant (p < 0.01 and p < 0.05, respectively). The mean levodopa dose fell by 32% during the study (from 599 mg to 409 mg; p = 0.007). Side effects were mild. High-dose ropinirole (20–36 mg/day) was well tolerated and conferred significant clinical benefit on patients with motor fluctuations. Received June 25, 2001; accepted July 9, 2001     

Selegiline in the treatment of Parkinson's disease

Abstract– Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B). It also inhibits the reuptake of catecholamines into the presynaptic nerve and enhances the synthesis of dopamine by blocking the presynaptic dopamine autoreceptors. Thanks to these properties it potentiates and prolongs the duration of action of levodopa. Several clinical trials have shown its efficacy as an adjuvant to levodopa therapy. Improvement in parkinsonian disability and reduction of fluctuations in disability can be achieved by adding selegiline to the prevailing levodopa therapy. End-of-dose type fluctuations, in particular, react favourably to selegiline. Side-effects of the therapy can be managed by reducing the dose of levodopa. According to preliminary studies selegiline may also have some benefit as monotherapy in de novo parkinsonian patients. High doses of selegiline have been found to have some antidepressant efficacy, especially in patients with nonendogenous depression. It may also have an effect on bradyphrenia and some symptoms of cognitive dysfunction and dementia. In animal models selegiline has been shown to prevent parkinsonism caused by MPTP and also to increase the life span of rats. Whether selegiline slows down the progression of Parkinson's disease needs further examination.     

Differential effects of various treatment combinations on cardiovascular dysfunction in patients with Parkinson's disease

OBJECTIVES: Patients with Parkinson's disease (PD) frequently suffer from cardiovascular dysfunction, which may be enhanced to various extents by different antiparkinsonian drugs. MATERIALS AND METHODS: We analysed electrocardiogram (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension (OH) in 148 patients with idiopathic PD assigned to five different combination therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP), selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy before and after a 1-week washout of the add-on drug. Patients were matched for age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular testing was performed at baseline, and following a 1-week washout period of the add-on drugs. RESULTS : We found that the incidence of cardiovascular dysfunction was generally higher in patients receiving a combination therapy compared with patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in combination therapy, but in only 20% of the patients receiving LD monotherapy. After discontinuation of BRO and SEL, there were significant improvements in ECG, OH and CVR. After washout of ACH and AMA, a significant improvement was found only in the CVR score. AMA and ROP were the add-on drugs with the least adverse cardiovascular effects. CONCLUSION: We conclude that pre-existing cardiovascular autonomic dysfunction should be investigated and taken into account when deciding which combination therapy to choose in the treatment of parkinsonian patients.     

Selegiline hydrochloride and cognition

Selegiline HCl, 10 mg per day has been reported to improve attention and episodic memory in Parkinson's disease and early Alzheimer's disease. Selegiline also improves motor reaction times in Parkinson's and subjective feelings of increased vitality, euphoria and energy. At doses of between 10 and 40 mg a day it has also been shown to improve, depression particularly when psychomotor retardation is prominent and anxiety minimal.     

The effect of deprenyl washout in patients with long-standing Parkinson's disease

Summary. Deprenyl, an irreversible MAO-B inhibitor, is known to have a symptomatic effect in de novo patients with Parkinson's disease (PD). It has, however, not been studied thoroughly in patients with advanced PD and response fluctuations. This study evaluated the effect of washout of deprenyl in patients with long-standing PD. Eleven PD patients who were on chronic treatment with deprenyl (mean age 57 ± 8 years, mean disease duration 8.4 ± 2.9 years), seven with response fluctuations, were enrolled in a double-blind study of a novel MAO-B inhibitor. A deprenyl washout period of one month was required prior to initiation of treatment with the trial drug. Patients were evaluated by Unified Parkinson's Disease Rating scale (UPDRS) before and one month after the washout period. Motor function was quantified by computerized tapping speed and movement time test. Results showed that neither total UPDRS scores (22 ± 16 vs. 18 ± 16, respectively) nor tapping speed and movement time changed significantly (4.4 ± 0.5 vs. 4.2 ± 0.3 Hz and 159 ± 45 vs. 161 ± 40 seconds; p > 0.1, respectively). However, eight patients reported various degrees of subjective deterioration, among them were the seven fluctuating patients. Two patients first began to experience response fluctuations during the washout period. It seems that deprenyl has a symptomatic effect, especially in patients with response fluctuations, and it may postpone the appearance of fluctuations in patients with PD. Attempts to discontinue treatment with deprenyl may aggravate disease symptoms. Received October 26, 2001; accepted January 30, 2002     

Application of heart rate variability during blood pressure measurement in patients with somatic symptom disorder

ObjectiveThis study wants to test whether the heart rate variability (HRV) analysis using sphygmomanometers can effectively reflect the physical and emotional distress of somatic symptom disorder (SSD) cases and assist in further health management.MethodsThis study includes 66 female SSD cases and 32 male SSD cases. All cases received a 200-second blood pressure (BP) measurement, after which the numerical figure for the heart rate was obtained from the BP signal for HRV analysis. All cases also filled out Patient Health Questionnaire-15 (PHQ-15), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI) to understand the extent of their somatic distress, depression, and anxiety. The relationship between psychological conditions and HRV indicators are examined statistically. Receiver operating characteristic (ROC) curve analysis was used to understand whether HRV indicators can assist in the determination of psychosomatic problems.ResultsConsidering all and female SSD cases, low-frequency power (LF) and PHQ-15 in the HRV index have the most significant correlations. In male SSD cases, root mean square of successive NN interval differences (RMSSD) and BDI-II have the highest correlations. The results of ROC curve analysis indicate that LF is useful to judge the severity of female SSD cases, while RMSSD has reference value in determining whether male patients of SSD cases have depression or not. In addition, physical stress index (PSI) can also help determine the degree of depression in male SSD cases.ConclusionThe use of BP in HRV analysis can help in the monitoring of somatic distress and depression issues in SSD cases. LF, RMSSD, PSI are potential physiological indicators.