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.

Patient satisfaction with switching to Stalevo: an open-label evaluation in PD patients experiencing wearing-off (Simcom Study).

OBJECTIVES AND METHODS: This study investigated the ease with which 52 Parkinson's disease patients already receiving adjunct entacapone to traditional levodopa were switched to Stalevo (levodopa/carbidopa/entacapone). RESULTS: The switch to Stalevo was straightforward for most patients taking standard-release levodopa with 86% of these patients being able to replace their entire regimen without having to change the amount of levodopa taken. The majority of patients (54%, P = 0.162) preferred Stalevo; 31% preferred their prior treatment regimen; 15% had no preference. Patients found Stalevo more simple to dose (94%), more convenient to use (84%), easier to handle (84%), easier to remember (67%) and easier to swallow (59%), compared with their previous medication. CONCLUSIONS: Stalevo was well tolerated, with a low incidence of adverse events. The study shows that Stalevo is an effective, preferred and well-tolerated means of delivering levodopa/carbidopa/entacapone in one easy-to-use tablet.

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

BACKGROUND: 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.

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.

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.

Hyperbaric oxygen treatment has different effects on nerve regeneration in acellular nerve and muscle grafts.

Effects of hyperbaric oxygen treatment (HBO) on nerve regeneration in acellular nerve and muscle grafts were investigated in rats. Nerve and muscle grafts were made acellular by freeze-thawing and the obtained grafts were used to bridge a 10-mm gap in the sciatic nerve on the left and right sides, respectively. Rats were treated with HBO (100% oxygen for 90 minutes at 2.5 atmospheres absolute pressure ATA) twice a day for 7 days. Axonal outgrowth, Schwann cell migration and invasion of macrophages were examined 10 days after the graft procedure by staining neurofilaments, S-100 proteins and the macrophage antibodies ED1 and ED2, respectively. Axonal outgrowth and Schwann cell migration in acellular nerve grafts were superior to that found in the acellular muscle grafts. However, there was no difference between HBO-treated and nontreated rats in acellular nerve grafts. Such a difference was found in acellular muscle grafts concerning both axonal outgrowth and Schwann cell migration from the proximal nerve end. No differences in the content of macrophages or neovascularization (alkaline phosphatase staining) in either of the grafts and treatments were seen. It is concluded that there is a differential effect of HBO-treatment in acellular nerve and muscle grafts and that HBO-treatment has no effect on the regeneration process in acellular nerve grafts, in contrast to fresh cellular nerve grafts where a beneficial effect has previously been reported.

Effects of hyperbaric oxygen treatment on axonal outgrowth in sciatic nerve grafts in rats.

We studied the effect of hyperbaric oxygen treatment on axonal outgrowth in grafts of sciatic nerves in 40 rats. The sciatic nerve was transsected and a 10 mm long segment from the opposite side was immediately sutured in as a nerve graft. Postoperatively 17 animals were treated with 100% oxygen at 3.2 atmospheres absolute pressure for 45 minutes and the treatment was repeated at four and eight hours postoperatively and then every eight hours until evaluation. At seven days the axonal outgrowth was evaluated by immunohistochemical staining of neurofilaments in the nerve grafts. The axonal outgrowth was significantly longer in animals treated with hyperbaric oxygen. We conclude that hyperbaric oxygen can improve nerve regeneration in sciatic nerve grafts in rats.

[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.

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.

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.

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 measurements 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 Parkinson's 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 more 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.

Complete transection of the median and radial nerves during arthroscopic release of post-traumatic elbow contracture.

Arthroscopic debridement and capsular release was performed in a 57-year-old woman because of post-traumatic stiffness in the dominant right elbow joint. During this procedure, the median and radial nerves were completely transected. A few recent reports of small series have described encouraging results after arthroscopic capsular release of post-traumatic elbow contracture, but the present case demonstrates the inherent risk of damage to neurovascular structures.

Hyperbaric oxygen treatment enhances regeneration of the rat sciatic nerve.

The effect of hyperbaric oxygen (HBO) treatment on regeneration of the rat sciatic nerve was studied. The sciatic nerve was crushed with a pair of pliers and the animals were either left untreated or subjected to a series of 45-min exposures to 100% O2 at 3.3 atm absolute pressure at 0, 4, and 8 h postoperatively and then every 8 h. Regeneration was evaluated using the pinch-reflex test at 3, 4, or 5 days following surgery and with neurofilament staining at 4 days. The regeneration distances at all time points were significantly longer in animals exposed to hyperbaric oxygen treatment independent of the evaluation procedure. A short initial period of the same HBO treatment schedule, with no more treatments after 25 h, appeared as effective as when treatments were maintained being given every 8 h until evaluation. We conclude that HBO treatment stimulates axonal outgrowth following a nerve crush lesion.

Cardiac arrhythmia caused by a Kirschner wire inside the heart. An unusual complication of finger osteosynthesis.

A 45-year-old woman with no previous history of cardiac disease woke up one morning with an irregular heartbeat and fatigue. An electrocardiogram showed atrial fibrillation and plain chest radiographs revealed the presence of a metallic pin at the position of the heart. A 24 mm-long metallic pin was removed by open thoracic surgery from within the right ventricle of the heart. Postoperative examination of the pin showed it to be one of the 0.8 mm Kirschner wires that had been used for finger osteosynthesis in her left hand 31 months previously.

Proximal osteotomy in hallux valgus, long-term results of 167 operated feet. A retrospective study.

A total of 167 feet in 125 patients were treated with a proximal osteotomy of the first metatarsal for hallux valgus. In addition, in 115 feet a resection of the base of the proximal phalanx was conducted, and in 25 feet the head of some lesser metatarsal bone was resected. Eight years (range 5-10 years) postoperatively the patients were sent a questionnaire concerning the present state of their feet. In all, 105 patients (142 feet) replied, and 63% stated that they felt no pain in their feet at all. Indeed, 86% of the patients indicated that, everything considered, the operation was worthwhile. The most common complaint was the difficulty of finding shoes to fit; 22.5% of the patients stated that they had a hard time with this. The average preoperative metatarsophalangeal angle was 38 degrees, reduced by 22 degrees postoperatively. The average preoperative first intermetatarsal angle was 15 degrees, reduced by 5 degrees after the operation. In the statistical analysis, no correlation between the preoperative body mass index, the hallux angle, the first intermetatarsal angle, the reduction achieved in the above mentioned angles by the operation, and patient satisfaction was found.

Hyperbaric oxygen reduces ischemia-induced skeletal muscle injury.

The effect of hyperbaric oxygen treatment on skeletal muscle submitted to 3 or 4 hours of ischemia was studied in a rat hindlimb model after 48 hours of reperfusion. Forty-eight male Sprague-Dawley rats were allocated to four groups. In the two treatment groups, hyperbaric oxygen was given for 45 minutes at 2.2 atm immediately and 4,8,16,24,32, and 40 hours after release of the ischemia-inducing tourniquet. The injury to skeletal muscle was quantified from the uptake of 99mtechnetium-pyrophosphate (injected intravenously after 45 hours of reperfusion) in anterior tibial muscle harvested 3 hours later. The uptake was significantly lower in hyperbaric oxygen-treated rats than in untreated rats with 3 or 4 hours of ischemia (p < 0.01 and P < 0.05). After 4 hours of ischemia, the changes in levels of the intracellular muscle compounds adenosine triphosphate, phosphocreatine, and lactate were less in the hyperbaric oxygen-treated rats than in the untreated animals.

Hyperbaric oxygen treatment attenuates glutathione depletion and improves metabolic restitution in postischemic skeletal muscle.

Glutathione serves as an important intracellular defence against reactive oxygen metabolites and has been shown to be depleted from a number of tissues upon oxidative stress. In the present study we have investigated the levels of total glutathione (reduced + oxidized) in skeletal muscle of the rat after prolonged ischemia and reperfusion with and without treatment with hyperbaric oxygen (HBO) for the initial 45 minutes immediately following reperfusion. A tourniquet model for temporary, total ischemia was used, in which one hind leg was made ischemic for 3 or 4 hours. Muscle biopsies were taken after 5 hours of reperfusion. In postischemic muscle there was a significant decrease of total glutathione compared to control muscle, but in the 3-hour-ischemia-groups the loss of total glutathione was less in HBO treated animals than in untreated. HBO treatment also preserved ATP and PCr and decreased edema formation in the postischemic muscle following 3 hours of ischemia and reperfusion when compared to untreated animals. However, after 4 hours of ischemia, HBO treatment failed to improve any of these parameters in the postischemic muscle. Thus, our results demonstrate that HBO treatment lessens the metabolic, ischemic derangements and improves recovery in postischemic muscle after 3 hours of ischemia followed by reperfusion.

Hyperbaric oxygen improves wound healing in normal and ischemic skin tissue.

The influence of hyperbaric oxygen on reepithelialization and on microvascular perfusion of wounds in normal and ischemic skin tissue was investigated by using a standardized model, in ears of hairless mice. Animals were treated within 2 hours of wound creation and then twice daily with 100% oxygen at 2 atmospheres of absolute pressure. Ischemia was induced by ligating two of the three major vessels of the ear 2.5 days before wound creation. Wound surface area was measured every third day after wound creation. In addition, microvascular blood flow before and during the wound healing process was measured by scanning the ear with a new laser Doppler perfusion imager. In normal tissue (n = 13), hyperbaric oxygen therapy significantly accelerated wound healing by 2 days (p < 0.01) as compared with controls (n = 16). In ischemic tissue (n = 16), treatment with hyperbaric oxygen reduced time for reepithelialization in control animals (n = 16) from 14.3 to 9.9 days (p < 0.001). Laser Doppler data showed no difference in tissue blood flow between treated and untreated animals. In comparison with normal tissue, wound healing in ischemic tissue was characterized by a reduced and less intense hyperemic response. These data suggest that hyperbaric oxygen therapy improves reepithelialization in normal and ischemic skin tissue. The beneficial effect is not associated with changes in microvascular perfusion and therefore is probably due to high arteriolar oxygen content and oxygen diffusion.