Can Qigong improve non-motor symptoms in people with Parkinson's disease - A pilot randomized controlled trial?

Non-motor symptoms (NMS) including sleep disorders, anxiety, depression, fatigue, and cognitive decline can significantly impact quality of life in people with PD. Qigong exercise is a mind-body exercise that shows a wide range of benefits in various medical conditions. The purpose of this study was to investigate the effect of Qigong exercise on NMS with a focus on sleep quality. Seventeen participants completed a 12-week intervention of Qigong (n = 8) or sham Qigong (n = 9). Disease severity, anxiety and depression levels, fatigue, cognition, quality of life, and other NMS of the participants were evaluated prior to the intervention and at the end of the 12-week intervention. After the intervention, both Qigong and sham-Qigong group showed significant improvement in sleep quality (p < 0.05) and overall NMS (p < 0.05). No significant difference was found between groups. Qigong exercise has the potential as a rehabilitation method for people with PD, specifically alleviating NMS in PD. However, this finding needs to be carefully considered due to the small sample size and potentially low intervention fidelity of this study.

Changing the treatment paradigm for Parkinson's disease psychosis with pimavanserin.

Introduction: Parkinson's disease psychosis (PDP) may affect up to 60% of patients with Parkinson's disease over the course of their disease, and is associated with poor prognosis, including increased risks of mortality and nursing home placement. PDP treatments have been limited to off-label use of atypical antipsychotics, most of which pose risks of worsened motor symptoms and other potential adverse events (AEs) due to their dopamine receptor blockade and additional off-target receptor affinities. Pimavanserin is a highly selective 5-HT2A inverse agonist and poses no known risks for worsening of parkinsonism or other off-target receptor AEs. Pimavanserin is the first and only medication approved for PDP treatment. Areas covered: This review covers estimated prevalence, clinical characteristics, diagnostic criteria, and risk factors for PDP; the hypothetical progression of PDP; management of PDP including use of antipsychotics; pharmacology and clinical trial data on pimavanserin; and expert opinion on PDP treatment. The NLM/PubMed database was searched for papers using the search terms of "PDP" AND "treatment" AND "pimavanserin" for the last 10 years. Expert opinion: The recent insights into PDP pathophysiology and approval of the only medication specifically to treat PDP are key advances that should improve the recognition, diagnosis, and management of PDP.

MDS evidence-based review of treatments for essential tremor.

BACKGROUND: Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor. OBJECTIVES: To conduct an evidence-based review of current pharmacological and surgical treatments for essential tremor, using standardized criteria defined a priori by the International Parkinson and Movement Disorder Society. METHODS: We followed the recommendations of the International Parkinson and Movement Disorder Society Evidence Based Medicine Committee. RESULTS: Sixty-four studies of pharmacological and surgical interventions were included in the review. Propranolol and primidone were classified as clinically useful, similar to Topiramate, but only for doses higher than 200 mg/day. Alprazolam and botulinum toxin type A were classified as possibly useful. Unilateral Ventralis intermedius thalamic DBS, radiofrequency thalamotomy, and MRI-guided focused ultrasound thalamotomy were considered possibly useful. All the above recommendations were made for limb tremor in essential tremor. There was insufficient evidence for voice and head tremor as well as for the remaining interventions. CONCLUSION: Propranolol, primidone, and topiramate (>200 mg/day) are the pharmacological interventions in which the data reviewed robustly supported efficacy. Their safety profile and patient preference may guide the prioritization of these interventions in clinical practice. MRI-guided focused ultrasound thalamotomy was, for the first time, assessed and was considered to be possibly useful. There is a need to improve study design in essential tremor and overcome the limitation of small sample sizes, cross-over studies, short-term follow-up studies, and use of nonvalidated clinical scales. © 2019 International Parkinson and Movement Disorder Society.

Effects of Qigong Exercise on Non-Motor Symptoms and Inflammatory Status in Parkinson's Disease: A Protocol for a Randomized Controlled Trial.

Background: Non-motor symptoms such as sleep disturbance, cognitive decline, fatigue, anxiety, and depression in Parkinson's disease (PD) impact quality of life. Increased levels of pro-inflammatory cytokines in individuals with PD have been reported, which may contribute to non-motor symptoms. A mind-body exercise, Qigong, has demonstrated benefits across different medical conditions. However, a lack of evidence causes clinicians and patients to be uncertain about the effects of Qigong in individuals with PD. This study will examine the effects of Qigong on non-motor symptoms and inflammatory status in individuals with PD. Methods: Sixty individuals with PD will be recruited. Qigong and sham Qigong group (n = 30 for each) will receive a 12-week intervention. Participants will practice their assigned exercise at home (2×/day) and attend routinely group exercise meetings. Results: Clinical questionnaires and neuropsychological tests will measure non-motor symptoms including sleep quality (primary outcome). Biomarker assays will measure inflammatory status. A two-way mixed-design analysis of variance (ANOVA) will be utilized. Conclusions: This study may generate evidence for the benefits of Qigong on non-motor symptoms of PD and the effect on inflammatory status. Findings may lead to the development of a novel, safe, and cost-effective rehabilitation approach for individuals with PD.

Qigong exercise may improve sleep quality and gait performance in Parkinson's disease: a pilot study.

PURPOSE: Parkinson's disease (PD) involves a variety of motor and non-motor symptoms, several of which, including gait abnormalities and sleep disorders, are generally not adequately managed with standard therapy. This study aimed to determine the impact of Qigong as a potential complementary therapy in the management of gait and sleep-related symptoms in PD. METHODS: Seven subjects (aged 66.9 ± 8.1 years) with PD participated in a six-week Qigong exercise intervention. Pre- and post-intervention testing was performed to assess sleep quality, cognitive function, fatigue, quality of life, gait performance (stride time, stride length, double support time, and velocity), and gait variability (stride time and length variability). RESULTS: Following Qigong, subjects showed improvement in some aspects of sleep quality. Fatigue remained unchanged. Gait function was improved by a significant reduction of stride time and a slight increase in stride length. Together these changes resulted in significant improvements to gait velocity. In addition, time spent in double limb support was reduced following the intervention. Overall gait variability improved significantly, particularly in the reduction of stride time variability. CONCLUSIONS: These results suggest that Qigong may provide benefit for gait performance and sleep quality in PD patients. However, larger, controlled studies are required to determine the immediate and long-term benefits of Qigong for PD sleep and gait problems as well as the impact on other aspects of the disease.

Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor.

OBJECT: The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). METHODS: Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. RESULTS: Ninety-one patients (78 at 1 year; 42 at 2-7 years [mean 4 years]; and 22 at >7-12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. CONCLUSIONS: Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.

Use of brain MRI after deep brain stimulation hardware implantation.

The objective of this study was to examine the experience with and safety of brain 1.5 Tesla (T) magnetic resonance imaging (MRI) in deep brain stimulation (DBS) patients. This was a retrospective review of brain MRI scanning performed on DBS patients at the University of Kansas Medical Center between January 1995 and December 2007. A total of 249 DBS patients underwent 445 brain 1.5 T MRI scan sessions encompassing 1,092 individual scans using a transmit-receive head coil, representing the cumulative scanning of 1,649 DBS leads. Patients with complete implanted DBS systems as well as those with externalized leads underwent brain imaging. For the majority of scans, specific absorption rates localized to the head (SAR(H)) were estimated and in all cases SAR(H) were higher than that specified in the present product labeling. There were no clinical or hardware related adverse events secondary to brain MRI scanning. Our data should not be extrapolated to encourage MRI scanning beyond the present labeling. Rather, our data may contribute to further defining safe MRI scanning parameters that might ultimately be adopted in future product labeling as more centers report in detail their experiences.

Postural tremor suppression is dependent on thalamic stimulation frequency.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) reduces tremor in people with essential tremor (ET), yet the dependence of tremor suppression on stimulation frequency remains unclear. To address this issue, we tested tremor suppression for three 15-second measurements during a variety of stimulation frequencies in 11 ET patients treated with VIM DBS. Stimulation frequencies at or above 100 Hz produced maximal benefit; higher frequencies provided no additional benefit. If this short-term measure predicts long-term response in routine activities at home, then this stimulation frequency setting will prolong battery half-life compared to higher frequency settings. These findings suggest that ET patients treated with VIM DBS may receive adequate benefit from stimulation frequencies about 100 Hz and this setting compared to commonly used higher settings will prolong battery life of surgically implanted pulse generators.

Open-label trial regarding the use of acupuncture and yin tui na in Parkinson's disease outpatients: a pilot study on efficacy, tolerability, and quality of life.

OBJECTIVES: This study evaluates the effects of sequential tui na massage, acupuncture, and instrument-delivered qigong for patients with Parkinson disease (PD) over a 6-month period. DESIGN: Patients received weekly treatments, which included tui na massage prior to acupuncture followed by instrument-delivered qigong. Each patient was assessed at baseline and at 6 months. SETTING: The setting was an outpatient research/academic clinic for patients with PD and nonacademic acupuncture clinic. SUBJECTS: Twenty-five (25) patients with idiopathic PD were the subjects. OUTCOME MEASURES: Before and after treatment patients were evaluated with the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr Staging (H&Y), Schwab and England Activities of Daily Living (S & E), Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39) quality of life assessment, and patient global assessments. RESULTS: There were no significant improvements in treatment measures; however, there was a 2.4-point worsening in UPDRS motor scores (24.0 versus 26.4, p = 0.018). There was a 16% improvement in the PDQ- 39 total score (23.2 versus 19.6, p = 0.044) and a 29% improvement in the BDI (9.6 versus 6.8, p = 0.006). Sixteen (16) patients reported moderate to marked improvement. There were no adverse effects. CONCLUSIONS: Acupuncture is safe and well tolerated in patients with PD. Most patients reported subjective improvement. The BDI and PDQ-39 total score, measuring depression and quality of life, demonstrated some improvement, but UPDRS motor scores worsened.

Deep brain stimulation in Parkinson's disease.

Throughout the past decade, there has been a marked increase in surgical therapies, primarily deep brain stimulation (DBS), for the treatment of advanced Parkinson's disease (PD). DBS of the thalamus has been shown to be effective in reducing parkinsonian tremor; however, it is not the treatment of choice for PD given the progression of other symptoms such as rigidity and bradykinesia. Stimulation of the globus pallidus or the subthalamic nucleus is safe and efficacious in the long-term treatment of all cardinal symptoms of PD, and they are currently the surgeries of choice. Serious adverse events with DBS can occur in 1% to 2% of patients, infection in 5% to 8% of patients, and hardware complications in approximately 25% of patients. Complications associated with DBS are related to the experience of the surgical center. Referring physicians and patients should be aware of the number of surgical procedures and complication rates of any prospective surgical center.

Deep brain stimulation and essential tremor.

Essential tremor (ET) is one of the most common movement disorders and can cause significant functional disability in some patients. Although medications can improve tremor in some patients, approximately 50% of patients have medication-resistant symptoms. In patients with ET who experience marked disability due to the tremor, surgical therapy, primarily deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the thalamus, is a viable treatment option. Multiple studies of DBS of the thalamus have shown that it is efficacious in the treatment of ET hand tremor, often with secondary improvement in voice and head tremor. Long-term studies have reported that a majority of patients continue to experience improvement in tremor. Adverse effects related to stimulation are usually mild and can be managed with changes in stimulation parameters. Long-term hardware complications include equipment malfunction, skin erosion, and battery replacements, which require additional surgery. Deep brain stimulation of the thalamus is a safe and efficacious procedure and should be considered in patients with ET who experience medication-resistant disabling tremor.

Essential tremor: differential diagnosis and current therapy.

Essential tremor is a common movement disorder that affects between 5 and 10 million persons in the United States. It is characterized primarily by an action and postural tremor most often affecting the arms, but it can also affect other body parts. Essential tremor is a progressive neurologic disorder and can cause substantial disability in some patients. Although there is no cure for essential tremor, pharmacologic and surgical treatments can provide some benefit. Primidone and propranolol are first-line treatments. Other medications with potential efficacy include benzodiazepines, gabapentin, topiramate, and botulinum toxin. Patients with medication-resistant tremor may benefit from thalamotomy or deep brain stimulation of the thalamus. The use of medical and surgical therapies can provide benefit in up to 80% of patients with essential tremor.

Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up.

OBJECT: Bilateral subthalamic nucleus (STN) stimulation is increasingly used in patients with advanced Parkinson disease (PD). This study was performed to evaluate the long-term efficacy and safety of bilateral STN stimulation in cases of PD. METHODS: The authors performed a prospective, open-label study in patients with PD who underwent bilateral STN stimulation. The authors compared motor scores and activities of daily living (ADL) scores based on the Unified PD Rating Scale (UPDRS) obtained before surgery while patients were in the medication-off state with scores obtained at follow-up evaluations of these patients while in the medication-off/stimulator-on state. Data contained in patient diaries were also compared. Thirty-three patients with PD were evaluated 12 months postoperatively and 19 were evaluated at a mean follow-up time of 28 months. A comparison between UPDRS scores obtained in patients in the medication-off/stimulator-on state and those obtained when patients were in the baseline medication-off state showed a 27% improvement in ADL scores and a 28% improvement in motor scores after surgery. There was a 57% reduction in the use of levodopa-equivalent medication doses. The percentage of the waking day that patients were in the medication-on state increased from 38 to 72%. Surgical complications included seizures (three patients), confusion (five patients), hemiballismus (one patient), and visual disturbance (one patient). Stimulation-related adverse effects were mild. Device-related events included nine lead replacements, seven lead revisions, six extension replacements, and 12 implantable pulse generator (IPG) replacements; one IPG was cleaned and one IPG was placed in a pocket because of the presence of a shunt. CONCLUSIONS: Bilateral STN simulation is associated with a significant improvement in the motor features of PD. Device-related events were common in the first 20 patients who underwent surgery, often requiring repeated surgeries.

Pulse width is associated with cognitive decline after thalamic stimulation for essential tremor.

The present study sought to identify predictors of cognitive decline after thalamic deep brain stimulation (DBS) for essential tremor (ET). Twenty-seven patients (55%) with ET demonstrated mild cognitive decrements relative to pre-surgical baseline (ET-D), whereas 22 patients (45%) were classified as neuropsychologically stable (ET-S). The ET-D and ET-S groups were comparable in terms of baseline demographic, disease, and neuropsychological characteristics, as well as post-surgical motor outcomes. However, the ET-D group had significantly higher pulse width (PW) stimulator settings, and a greater proportion of ET-D than ET-S patients underwent left in comparison to right thalamic stimulation. A subsequent step-wise discriminant function analysis revealed that disease onset after age 37 years and higher PW settings (>or=120 micros) were the strongest predictors of post-surgical cognitive decline in this sample. Findings indicate that although relatively higher PW settings might afford optimal tremor control in some patients, the corresponding risk of mild, probably often subclinical, cognitive morbidity must be weighed accordingly.

Benefits and risks of pharmacological treatments for essential tremor.

Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.

Effect of motor improvement on quality of life following subthalamic stimulation is mediated by changes in depressive symptomatology.

BACKGROUND/AIMS: Subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves motor symptoms and quality of life (QOL). Because depression is a potent correlate of QOL, and STN-DBS may be associated with changes in mood, this study sought to determine whether QOL improvement is a direct or indirect consequence of motor improvement. METHODS: 26 patients with PD, free of dementia and major depression, who consecutively underwent bilateral, microelectrode-guided STN-DBS, underwent preoperative and 3-month postoperative neuropsychological evaluation, including measures of QOL (PD Questionnaire -39) and depressive symptoms (Beck Depression Inventory). RESULTS: Motor score in the Unified Parkinson's Disease Rating Scale (UPDRS Part III) improved significantly with STN-DBS relative to preoperative 'on' and 'off' scores, as did QOL and depressive symptoms. Extent of QOL improvement tended to be associated with improvement in motor score from presurgical on to postsurgical on stimulation and on medication state. QOL improvement was significantly related to amelioration of depressive symptoms. Partial correlations revealed that the association between QOL improvement and depression remained significant when influence of motor improvement on QOL and depression was controlled for. The motor-QOL association was no longer significant when effects of depression were controlled for. CONCLUSIONS: Significant QOL improvements after STN-DBS are associated with improved motor 'on' state and depressive symptoms. The influence of motor improvement on QOL may be largely indirect by reducing depression.

Thalamic stimulation for midbrain tremor after partial hemangioma resection.

We describe a patient with disabling medication-resistant midbrain tremor developed after partial hemangioma resection, who responded to deep brain stimulation of the thalamus.

Long-term efficacy of globus pallidus stimulation for the treatment of Parkinson's disease.

OBJECTIVE: To determine the long-term efficacy and safety of globus pallidus internus (GPi) stimulation for Parkinson's disease (PD). BACKGROUND: We previously reported 3-month data for 5 patients who underwent GPi stimulation for PD. We now report long-term data on these 5 patients and 4 additional patients. METHODS: Nine PD patients, 5 men and 4 women, with an average age of 49 years and disease duration of 10 years, underwent GPi stimulation. Six patients had staged bilateral implants and 3 patients had unilateral implants. The mean follow-up was 48.5 months. All patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and completed 2-day diaries before and after surgery. RESULTS: There was a 21% improvement in UPDRS Part II (activities of daily living; ADL) scores and a 37% improvement in UPDRS Part III (motor) scores when the longest follow-up in the 'stimulation-on/medication-off' state was compared to the 'medication-off' state at baseline. The UPDRS Part II (ADL) scores improved by 30% and the UPDRS Part III (motor) scores improved by 39% when the longest follow-up in the 'stimulation-on/mediation-on' state was compared to the 'medication-on' state at baseline. As measured by patient diaries, 'on' time increased from 25 to 59% and 'on with dyskinesia' decreased from 42 to 15%. Surgical- and device-related complications included transient hemiparesis in the operating room, postoperative seizures, and implantable pulse generator and lead problems. There were seven device-related events requiring additional surgical procedures. CONCLUSIONS: GPi stimulation continues to be effective for the long-term treatment of the disabling symptoms of PD; however, the physician and patient should be aware that device-related problems are not uncommon and additional surgery may be necessary.