Tarja H. Haapaniemi

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 Parkinsons 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.

Heart rate variability in patients with untreated Parkinson’s disease

The aim of this study was to evaluate cardiovascular responses as a marker of autonomic nervous system (ANS) disturbances in patients with untreated Parkinson’s disease (PD) and to assess the relationship between them and the clinical characteristics of PD. The ANS functions were investigated in 50 patients with PD and 55 healthy subjects by measuring standard cardiovascular autonomic reflexes and heart rate variability (HRV) at rest using spectral analysis (the autoregressive model and the fast Fourier transformation), the percentage of the counts of beat‐to‐beat variation greater than 50 ms and the fractal dimension. Significantly attenuated HRV and deficient blood pressure reaction to tilting were found in the PD patient group. The patients with hypokinesia/rigidity as the initial symptom of PD had a more pronounced HRV deficit than those with tremor onset. Untreated PD patients suffer significant failure in cardiovascular nervous system regulation, and in patients with hypokinesia/rigidity as their initial disease manifestation the risk of this ANS dysfunction is high. However, in the early stages of PD these changes did not reach significance at individual level.

[123I]β-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 Parkinsons disease (PD) and controls using single‐photon emission computed tomography (SPECT) with 2β‐carboxymethoxy‐3β‐(4‐iodophenyl)tropane ([123I]β‐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 Parkinsons 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]β‐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. Mov. Disord. 16:124–130, 2001.

Circadian heart rate variability in Parkinson's disease.

Abstract. Parkinsons disease is known to affect the reflex cardiovascular control systems, resulting in a suppressed heart rate variability, but present knowledge concerning the long-term characteristics of heart rate and heart rate variability, e. g. circadian regulation, is limited.We investigated the circadian fluctuation of the time domain, frequency domain and some non-linear measures of heart rate variability in 44 untreated patients with Parkinsons disease and 43 age- and sex-matched control subjects.In the parkinsonian patients, the measured power spectral components of heart rate variability (low-frequency power and high-frequency power) and the SD1 value of the Poincaré two dimensional vector analysis, that quantifies the short term beat-to-beat variability, were suppressed at night. During the daytime only the SD1 of the Poincaré was suppressed. The night-to-day-ratios of the heart rate variability measures did not differ significantly between the patients and the controls.The results indicate that the long-term parasympathetic cardiovascular regulation is impaired in untreated patients with Parkinsons disease. The dysfunction is more pronounced at night.

Sweating in Parkinsonian patients with wearing-off.

Disorders of the autonomic nervous system are common in Parkinsons disease (PD). Earlier studies suggest that some nonmotor symptoms may fluctuate with the motor symptoms, but the possible interrelationship between motor phenomena and sweating has not been studied. The authors measured sweating by using an evaporimeter on three different areas of the body (right hand, left hand, chest) immediately before the morning PD medication (baseline), and thereafter hourly up to 4 hour, in 16 PD patients with wearing‐off type of motor fluctuations and in 15 patients without clinical motor fluctuations. The clinical state of the patients was evaluated using the Unified Parkinsons Disease Rating Scale motor score every hour. Sweating increased during the 4‐hour follow‐up, and reached its maximum level at the time of the highest Unified Parkinsons Disease Rating Scale motor score phase (off‐stage) in patients with wearing‐off (initially affected hand, P = 0.007; left hand, P = 0.004; right hand, P = 0.034), but in the patients without wearing‐off no changes in sweating were observed during the follow‐up. Sweating of the left hand (P < 0.001), right hand (P < 0.001), and initially affected hand (P = 0.008) during the whole observation period was significantly higher in patients with motor fluctuations than in those without. The present study shows that sweating fluctuates in conjunction with wearing‐off phenomenon.

Efficacy of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease.

SummaryBackground. Deep brain stimulation (DBS) has, for the most part, replaced irreversible stereotactic coagulations in the surgical treatment of advanced Parkinson’s disease. This study was undertaken to evaluate the benefits of bilateral STN stimulation related to its potential risks and side effects. Method. Twenty-nine consecutive Parkinsonian patients treated with STN-DBS were prospectively followed-up. Effects on Parkinsonian symptoms were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS). The evaluation was performed preoperatively and included postoperative follow-up evaluations at one and twelve months. All evaluations were made during the patient’s best on-medication phase and postoperative follow-ups were conducted under both stimulator-on and stimulator-off conditions by a blinded neurologist. A neuropsychologist also evaluated the patients at every visit. Findings. Two patients were excluded from the analysis because of severe surgical complications and three for an infection demanding the removal of the stimulator material. Other complications and side effects were clearly milder and temporary. At twelve months after surgery dyskinesia scores in the UPDRS were 53% lower than preoperative values. The results of the UPDRS motor scores improved 31.4% and activities of daily living (ADL) scores increased 19% compared with the preoperative situation. Also, the daily levodopa dose was 22% lower. Neuropsychological changes were minor, except for some deterioration in verbal fluency. Conclusion. The majority of Parkinsonian patients experienced significant and long lasting relief from their motor symptoms and an improvement in ADL functions due to DBS-STN therapy when evaluated at the best on-medication phase.

Suppressed sympathetic skin response in Parkinson disease

The sympathetic skin response (SSR) was used to evaluate sympathetic sudomotor activity in Parkinson disease (PD) and the effects of antiparkinsonian medication on the disease. We recorded SSRs to electric and auditory stimulation in 58 untreated patients with PD and in 20 healthy controls. In addition to amplitude and latency measurements, we examined the number of SSRs evoked by a single stimulus and the response adaptation after repetitive stimuli. The patients with PD subsequently were randomized for administration of levodopa/carbidopa (n=19), bromocriptine (n=20), or selegiline (n=19) as their initial treatment. The measurement were repeated after 6 months of medication and after a washout period. SSR amplitudes were significantly lower in patients with PD than in the control subjects at baseline. The amplitude reduction was more pronounced in patients with high Unified Parkinsons Disease Rating Scale scores, in those with high tremor scores, and in those with PD symptoms that had lasted more than 1 year. The levodopa/carbidopa and bromocriptine treatments did not influence SSRs, although selegiline slightly decreased the amplitude. The synchronous responses after a single stimulus were often repetitive in the patients with PD than in the controls, although the response adaptation tendencies were similar. In conclusion, the degenerative process in PD involves the sudomotor system as reflected by the progressive suppression of SSR amplitudes with a correlation to PD symptom duration and clinical disability, whereas PD medications seems to have only minor effects. The changes in amplitude and the repetitiveness of SSRs with normal adaptation may be caused by deficits at several levels of the SSR reflex arch.

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 Parkinsons 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 frequencyand time-domain analysis techniques of stationary short-term HRV recordings revealed significant differences in cardiovascular regulation between untreated patients with Parkinsons disease and the controls. This confirms cardiovascular regulation failure before treatment in the early stages of Parkinsons 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 Parkinsons disease.

Nocturnal cardiac autonomic regulation in Parkinson's disease.

Abstract.Diminished heart rate (HR) variability has been reported in patients with early phase Parkinson’s disease (PD) using standardized cardiovascular reflex tests. However, limited data exist on HR variability during sleep; thus the present study was performed to investigate the characteristics of HR variability during different sleep stages. The HR variability of 21 newly diagnosed and untreated PD patients and of 22 control subjects was evaluated by using time domain, frequency domain and non-linear methods and by analyzing HR reactions to body movements during the different sleep stages (non-REM stages S1–4 and the REM stage). The nocturnal cardiac autonomic control was disturbed in PD patients compared to controls both during sleep and waking. HR reactions to body movements were decreased especially during REM sleep referring to defective sympathetic cardiovascular control. High frequency spectral power of HR variability was attenuated in the patients in waking and during non-REM sleep but not during REM sleep suggesting that parasympathetic cardiovascular control is also affected in early PD. However, the variance of R-R intervals during non-REM sleep was significantly increased in PD patients. Especially during this sleep stage the patients also moved more than the controls. HR variability is decreased not only in waking but also during sleep in PD patients. However, the increased variance of HR during non-REM sleep refers that in early phase of PD cardiovascular system is still able to react to changing body circumstances. Furthermore, our findings suggest that the indicators measuring the dominant sympathetic or parasympathetic activity of each given sleep stage are the most sensitive measures in revealing disturbed nocturnal ANS function.

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 Parkinsons 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.