Intravenous amantadine on freezing of gait in Parkinson’s disease: a randomized controlled trial

To compare the effects of intravenous amantadine and placebo therapy on freezing of gait in patients with Parkinson’s disease, this randomized, double-blind, placebo-controlled, multicenter trial compared the efficacy of 5 days intravenous amantadine and placebo treatments on freezing of gait in 42 subjects randomly allocated 2:1 to amantadine or placebo groups. Changes in freezing of gait questionnaire (FOG-Q) scores and in unified Parkinson’s disease rating scale (UPDRS) scores, from baseline to immediately (V1) and 1 month (V2) after treatments, were assessed. Among the 42 patients (amantadine n = 29, placebo n = 13, a mean age 65.5 ± 9.4 years and a mean FOG-Q score 17.4 ± 3.2), 40 subjects completed treatment. There was no significant group difference on the primary outcome measure as total FOG-Q score changes at V1. However a significant beneficial effect of amantadine on freezing was seen at V2 in the UPDRS Part II freezing and FOG-Q item 3 scores, and there was significant improvement in the UPDRS Part IV total score and in the UPDRS Part II getting out of bed score in the amantadine group at both V1 and V2. There was no serious adverse event reported during the study. The intravenous amantadine therapy did not show a significant improvement on overall FOG-Q scores in patients with moderate-to-severe freezing; however, it might be beneficial by attenuating freezing severity and improving patients’ mobility. To prove this finding further studies with larger sample sizes are warranted in the future.     

Non-invasive brain stimulation for speech in Parkinson’s disease: A randomized controlled trial

BackgroundHypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson’s disease (PD).ObjectivesWe evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI.MethodsA randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses.ResultsAltogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area.ConclusionsThis is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.     

Effectiveness of a dance-physiotherapy combined intervention in Parkinson’s disease: a randomized controlled pilot trial

Neurological Sciences - Physical therapies have been recommended as crucial components in Parkinson’s disease (PD) rehabilitation. The study aims to examine the effectiveness of a new...     

Effects of bilateral subthalamic stimulation on sleep in Parkinson’s disease

Abstract.Objective: Sleep disturbances are frequently observed in Parkinsons disease (PD). Bilateral chronic subthalamic nucleus (STN) stimulation is an alternative treatment for advanced PD. Improvements in motor disturbances after STN stimulation are well documented and seem to be associated with better sleep quality, even though the objective effect on sleep structure remains unclear. We have therefore studied the sleep/wakefulness cycle before and after surgical treatment in 10 consecutive parkinsonian patients.Methods: Subjective sleep quality and sleep recordings were evaluated one month before and three months after initiation of STN stimulation. After surgery, the recordings were performed under two conditions: with stimulation (the on condition) and—if patients had given their consent—in the absence of stimulation (the off condition).Results: With STN stimulation, subjective and objective sleep qualities were improved. Total sleep time, sleep efficiency and the durations of deep slow wave sleep and paradoxical sleep increased significantly. When stimulation was absent, sleep disturbances were similar to those observed before surgery.Conclusion: Chronic STN stimulation is associated with a sleep improvement, which can be explained in part by the concomitant decrease in motor disturbances but also by the reduction in dosages of antiparkinsonian medication. However, we can not exclude a direct effect of STN stimulation on sleep regulatory centres.     

Relevance of sleep quality on caregiver burden in Parkinson’s disease

Neurological Sciences - Parkinson’s disease (PD) is a neurodegenerative disorder which affects the quality of life of patient and their family. Sleep disorders appear in 80–90% of PD...     

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson’s disease

Journal of Neurology - Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term...     

Patient-centered integrated healthcare improves quality of life in Parkinson’s disease patients: a randomized controlled trial

Introduction

Improving quality of life (QoL) is a key issue when dealing with Parkinson’s disease (PD). Integrative care shows potential to achieve improvements in QoL. Here, we analyzed whether a community-based, open-label, integrated approach improves QoL in PD patients.

Methods

PD patients were screened for eligibility and evaluated by a university-based PD specialist, a PD nurse, and a general neurologist at a local practice. Patients were randomly assigned to a control group (CG), receiving standard German neurological treatment including a baseline assessment and follow-up visit at 6 months, or an interventional group (IG) who received an individually tailored therapy plan and additional home visits. Patients and investigators were not blinded for either intervention. Primary outcome analysis compared the differential change of PDQ-39 from baseline to 6-month follow-up between CG and IG. Between-group changes in mood, motor/non-motor functioning, and cognition were secondary outcomes.

Results

300 patients were included and randomized equally to IG and CG. 132 IG and 125 CG patients had a valid PDQ-39 at follow-up and qualified for the modified ITT analysis. PDQ-39 improved more in IG compared to CG [2.2 points (95% CI ? 4.4 to 0.1); p = 0.044]. Likewise, change scores between IG and CG favored IG for UPDRS III (p < 0.001, mean change 3.3, 95% CI ? 4.9 to ? 1.7) and PD-NMS (p < 0.001, mean change 11.3, 95% CI ? 17.1 to ? 5.5).

Conclusions

Data show that an integrated approach, compared to regular PD care, improves QoL as well as motor and nonmotor PD symptoms over 6 months. Future studies need to address the cost–benefit ratio and whether positive effects can be maintained beyond intervention.

     

Parkinson’s disease sleep scale, sleep logs, and actigraphy in the evaluation of sleep in parkinsonian patients

The aim of this study was to compare the results of the day-to-day self-evaluation of sleep quality by sleep logs with Parkinson’s disease sleep scale (PDSS) in Parkinson’s disease (PD) patients. Actigraphy was used as an independent analysis of nighttime activity interfering with sleep. A total of 71 idiopathic PD patients and 21 age- and sex-matched normal individuals lacking any type of sleep disturbance were recruited. Sleep was evaluated by PDSS, 7-d sleep log and actigraphy. Sleep logs and PDSS showed reduced sleep quality and daytime somnolence scores in moderate/severe PD patients as compared to healthy controls. Significant correlations were found between sleep quality in sleep logs and all domains of PDSS sleep quality, except for the presence of nocturia, which correlated with nocturnal activity. PD severity and depression were the only predictors of reduced sleep quality. The retrospective and day-to-day sleep self-evaluations were coincident. Reduced sleep quality was related to increased PD severity and depression scores.     

Does the clinical practice guideline on Parkinson’s disease change health outcomes? A cluster randomized controlled trial

The successful transfer of clinical practice guidelines (CPGs) into patient care depends on the appropriateness of the implementation method. This study strived for a better understanding of which intervention strategy is effective in implementing the CPG on Parkinson’s disease (CPG-PD). In a cluster randomized controlled trial, we compared the impact of two different implementation strategies of the CPG-PD on health outcomes of PD patients. The primary outcome of health-related quality of life was measured by PDQ-39. The neurologists of the intervention group (IG) versus a control group (CG) received the CPG-PD with special instructions, a 4-h training and were offered personal feedback. Patients were followed over three assessment times: baseline, post-test (6 months) and follow-up (9 months). Lack of time and remuneration resulted in low study participation (32 out of 619 contacted neurologists). Multilevel modelling revealed that primary (PDQ-39) and secondary efficacy variables (EQ-5D, CGI, HADS-D, ZUF-8) of 386 patients were not affected significantly by the intervention and failed to show any significant difference between the two groups. The EQ-5D VAS scale (p = 0.0288) and the CGI-P severity scale (p = 0.0072) showed a significant worsening over time. A significant decrease of hours of dyskinesias in the IG (p = 0.007) was observed, whereas Parkinson symptoms did not change significantly between the groups. Lacking awareness of the CPG-PD seems to be no longer a barrier for its use, but it is still a major challenge to find effective implementation methods to optimise clinical outcome. Further studies are needed for a more comprehensive understanding of successful implementation strategies.     

Deep brain stimulation in Parkinson’s disease: meta-analysis of randomized controlled trials

Until recent years there has been no evidence from randomized controlled trials (RCTs) on the efficacy of deep brain stimulation (DBS) for Parkinson’s disease (PD). This review and meta-analysis of RCTs describes the efficacy of DBS in improving motor signs, functionality and quality of life of PD patients. Several electronic databases were consulted up to April 2013. RCTs that compared DBS plus medication versus medication (alone or plus sham DBS) in PD patients were included. Outcome measures were motor function, waking time on good functioning without troublesome dyskinesias, levodopa-equivalent dose reduction, medication-induced complications, activities of daily living, health-related quality of life, and neurocognitive and psychiatric effects. Six RCTs (n = 1,184) that compared DBS plus medication versus medication alone were included. The results show that DBS significantly improves patients’ symptoms, functionality and quality of life. Effects sizes are intense for the reduction of motor signs and improvement of functionality in the off-medication phase, in addition to the reduction of the required medication dose and its associated complications. Moderate effects were observed in the case of motor signs and time in good functionality in the on-medication phase, in addition to the quality of life. Although the number of RCTs obtained is small, the total sample size is relatively large, confirming the efficacy of DBS in the control of motor signs and improvement of patients’ functionality and quality of life. More controlled research is required on the neurocognitive and psychiatric effects of DBS.     

Drooling in Parkinson’s disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins

IntroductionBotulinum toxins are a therapeutic option for drooling in Parkinson’s Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD.Methods1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models.Results1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: −0.194 ± 0.61, range: −1.28 to 0.97, 95% CI −0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen’s d: −1.32, CI −1.86 to −0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands.ConclusionsThis study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful.     

Update on the clinical application of deep brain stimulation in sleep dysfunction of Parkinson’s disease

Sleep dysfunctions, including rapid eye movement sleep behavior disorder, sleep fragmentation, excessive daytime sleepiness and various other dysfunctions, can seriously affect quality of life in patients with Parkinson’s disease (PD). Emerging evidence suggests that deep brain stimulation (DBS) exerts a substantial effect when used to treat sleep dysfunctions, which are common nonmotor symptoms experienced by patients with PD. However, far less is known about the specific mechanisms underlying the effects of DBS on sleep processes and the factors that potentially influence these effects. These issues therefore need to be further clarified. Intriguingly, a number of recent studies have evaluated the effects of applying DBS to various brain targets on sleep in patients with PD. Deeper research into the efficacy of applying DBS to each brain target may help determine which region should be targeted during surgery in PD patients. Furthermore, compared with pharmacological therapy, DBS had more beneficial effects on sleep symptoms, and appropriate management involving the joint application of dopamine replacement therapy and DBS might accelerate the effects of treatment. Here, we review the potential roles DBS may play and provide clinical guidance for the use of DBS in treating sleep dysfunctions in PD patients.     

Transdermal rotigotine in advanced Parkinson’s disease: a randomized,double-blind,placebo-controlled trial

Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson’s disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on–off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were ?10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and ?4.4 ± 7.4 in the placebo group (p < 0.001). There was a significantly greater reduction in the off-time (p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD.     

Recognition and diagnosis of sleep disorders in Parkinson’s disease

Sleep disturbances are among the most frequent and incapacitating non-motor symptoms of Parkinson’s disease (PD), and are increasingly recognized as an important determinant of impaired quality of life. Here we review several recent developments regarding the recognition and diagnosis of sleep disorders in PD. In addition, we provide a practical and easily applicable approach to the diagnostic process as a basis for tailored therapeutic interventions. This includes a stepwise scheme that guides the clinical interview and subsequent ancillary investigations. In this scheme, the various possible sleep disorders are arranged not in order of prevalence, but in a ‘differential diagnostic’ order. We also provide recommendations for the use of sleep registrations such as polysomnography. Furthermore, we point out when a sleep specialist could be consulted to provide additional diagnostic and therapeutic input. This structured approach facilitates early detection of sleep disturbances in PD, so treatment can be initiated promptly.     

Increased brain connectivity and activation after cognitive rehabilitation in Parkinson’s disease: a randomized controlled trial

Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson’s disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.     

Pergolide effect on cognitive functions in early-mild Parkinson’s disease

Summary. In the present study, we evaluated the effect of pergolide, a mixed D1/D2 agonist, on cognitive function in mild Parkinsons disease (PD). After a two-week wash-out phase, twenty patients with a Hoehn and Yahr score 2.5 entered a 16-week, cross-over study in which the order of administration of pergolide or 1-dopa was randomly assigned. Cognitive assessment was performed after the wash-out phase and repeated after eight weeks (before patients were switched to the other drug) and at the end of the study. There were no significant differences in test scores among the three experimental modalities (off-treatment vs. l-dopa, off-treatment vs. pergolide, pergolide vs. l-dopa).In another cohort of comparably mild PD patients we had previously demonstrated that pramipexole, a mixed D2/D3 agonist, slightly but significantly worsened verbal fluency in comparison to l-dopa; moreover, pramipexole impaired short term verbal memory and attentional-executive functions in comparison to both l-dopa and the off-treatment condition. Taken together, these findings suggest that dopamine agonists may influence cognition in PD according to their pharmacological characteristics. Unlike the D2/D3 agonist pramipexole, pergolide and l-dopa, both of which stimulate D1- and D2-receptor subtypes, do not appear to impair cognitive function.     

The efficacy and safety of coenzyme Q10 in Parkinson’s disease: a meta-analysis of randomized controlled trials

The objective of this meta-analysis was to evaluate the effects of coenzyme Q10 (CoQ10) for the treatment of Parkinson’s disease (PD) patients in order to arrive at qualitative and quantitative conclusions about the efficacy of CoQ10. Databases searched included PubMed, Google scholar, CNKI, Wan-Fang, and the Cochrane Library from inception to March 2016. We only included sham-controlled, randomized clinical trials of CoQ10 intervention for motor dysfunction in patients with PD. Relevant measures were extracted independently by two investigators. Weighted mean differences (WMD) were calculated with random-effects models. Eight studies with a total of 899 patients were included. Random-effects analysis revealed a pooled WMD of 1.02, indicating no significant difference when CoQ10 treatment compared with placebo in terms of UPDRS part 3 (p = 0.54). Meanwhile, the effect size of UPDRS part 1, UPDRS part 2, and total UPDRS scores were similar in CoQ10 group with in placebo group (p > 0.05). Moreover, we found CoQ10 was well tolerated compared with placebo group. Subgroup analysis showed that the effect size of CoQ10 in monocentric studies was larger than in multicenter studies. Using the GRADE criteria, we characterized the quality of evidence presented in this meta-analysis as moderate to high level. The current meta-analysis provided evidence that CoQ10 was safe and well tolerated in participants with PD and no superior to placebo in terms of motor symptoms. According to these results, we cannot recommend CoQ10 for the routine treatment of PD right now.     

Age,drugs, or disease: What alters the macrostructure of sleep in Parkinson’s disease?

ObjectiveTo describe the alterations in the macrostructure of sleep in a large cohort of sleep-disturbed patients with Parkinson’s disease (PD) and investigate influencing factors.MethodsA cohort of sleep-disturbed but otherwise unselected PD patients (n = 351) was investigated with video-supported polysomnography. We analyzed the influence of age, disease duration, disease severity, and dopaminergic medication on subjective sleep perception, sleep efficiency, the amount of slow wave sleep, awakenings, periodic leg movements in sleep (PLMS), and REM sleep behavior disorder (RBD).ResultsSleep efficiency and slow wave sleep decreased with age (p = 0.003 and p = 0.041, respectively). The number of awakenings and the frequency of RBD increased with age (p = 0.028 and p = 0.006, respectively). Higher Hoehn & Yahr stages were associated with more PLMS (p = 0.017). A higher daily dose of levodopa corresponded to more RBD (p < 0.001). Neither disease duration nor levodopa dosage had any influence on sleep efficiency, slow wave sleep, awakenings, or PLMS. Dopamine agonists increased awakenings (p < 0.001) and lowered PLMS (p < 0.001). Subjective sleep perception was not influenced by any of the factors analyzed. The only path model that could be replicated identified disease severity and dopamine agonists as interdependent factors influencing awakenings and PLMS.ConclusionAge leads to less sleep and a higher risk for RBD, and disease severity increases motor phenomena such as PLMS; dopamine agonists reduce PLMS but increase awakenings. No single factor analyzed influenced subjective sleep perception in this cohort of sleep disturbed PD patients.