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Deep brain stimulation (DBS) is a widely used therapy for Parkinson’s disease (PD) but lacks dynamic responsiveness to changing clinical and neural states. Feedback control might improve therapeutic effectiveness, but the optimal control strategy and additional benefits of ‘adaptive’ neurostimulation are unclear. Here we present the results of a blinded randomized cross-over pilot trial aimed at determining the neural correlates of specific motor signs in individuals with PD and the feasibility of using these signals to drive adaptive DBS. Four male patients with PD were recruited from a population undergoing DBS implantation for motor fluctuations, with each patient receiving adaptive DBS and continuous DBS. We identified stimulation-entrained gamma oscillations in the subthalamic nucleus or motor cortex as optimal markers of high versus low dopaminergic states and their associated residual motor signs in all four patients. We then demonstrated improved motor symptoms and quality of life with adaptive compared to clinically optimized standard stimulation. The results of this pilot trial highlight the promise of personalized adaptive neurostimulation in PD based on data-driven selection of neural signals. Furthermore, these findings provide the foundation for further larger clinical trials to evaluate the efficacy of personalized adaptive neurostimulation in PD and other neurological disorders. ClinicalTrials.gov registration: NCT03582891 . A small clinical study shows that adaptive deep brain stimulation (DBS), based on real-time brain activity, for Parkinson’s disease significantly improved motor symptoms and quality of life compared with conventional DBS.

Iron deposition in the substantia nigra has been implicated in Parkinson’s disease. Chelation with deferiprone reduced brain iron content but led to worse scores on scales of the movement disorder at 36 weeks.

We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation. PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS). Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects. This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

In a randomized, sham-controlled trial involving 40 patients, therapeutic lesions on one side in the subthalamic nucleus were produced by focused ultrasound. At 4 months, motor performance was better in the active-treatment group. Twelve patients had neurologic deficits, many of which resolved by 12 months.

In this 2-year trial involving patients with Parkinson's disease and early motor complications, subthalamic stimulation plus medical therapy resulted in better quality of life and motor function than medical therapy alone. Parkinson's disease is a progressive neurodegenerative disease that affects dopaminergic neurotransmission, resulting in bradykinesia, rigidity, and rest tremor. After an initial honeymoon period, during which there is a sustained response to dopaminergic treatment, beneficial effects are hampered by levodopa-induced motor complications, 1 progressively compromising quality of life. 2 – 4 Because levodopa-responsive parkinsonian symptoms are improved by high-frequency stimulation of the subthalamic nucleus, 5 , 6 neurostimulation has become an established treatment for advanced Parkinson's disease with medically intractable fluctuations and dyskinesia 7 – 10 and has shown long-term efficacy. 11 – 13 It is typically used after the disease has been present for 11 to 13 years, 7 – . . .

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test–retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society–Unified Parkinson's Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

In this randomized trial, tai chi was more effective than resistance-training or stretching programs in improving the postural stability of patients with Parkinson's disease. Tai chi also was more effective than the stretching program in reducing the number of falls. Movement impairments, especially loss of the ability to maintain standing balance, adversely affect function and quality of life in patients with Parkinson's disease. 1 , 2 With progression of the disease, patients lose postural stability and have gait dysfunction, difficulty managing activities of daily living, and frequent falls. 3 , 4 Although some motor dysfunction, such as tremor, may be alleviated with drug therapy, characteristics such as postural instability are less responsive to medication and require alternative approaches. 5 , 6 Exercise is an integral part of the management of Parkinson's disease because physical activity has been shown to retard the deterioration of motor functions and . . .

Gait disorders represent a therapeutic challenge in Parkinson’s disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and “Landscape” (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI. Clinical assessment was repeated at 8-week. At 4-week, both groups showed reduced freezing of gait severity, improved walking speed and quality of life. Moreover, AOT was associated with reduced motor disability and improved balance. AOT group showed a sustained positive effect on motor disability, walking speed, balance and quality of life at 8-week, with a trend toward a persisting reduced freezing of gait severity. At 4-week vs. baseline, AOT group showed increased recruitment of fronto-parietal areas during fMRI tasks, while the Landscape group showed a reduced fMRI activity of the left postcentral and inferior parietal gyri and right rolandic operculum and supramarginal gyrus. In AOT group, functional brain changes were associated with clinical improvements at 4-week and predicted clinical evolution at 8-week. AOT has a more lasting effect in improving motor function, gait and quality of life in PD patients relative to physical therapy alone. AOT-related performance gains are associated with an increased recruitment of motor regions and fronto-parietal mirror neuron and attentional control areas.

In this randomized trial of deep-brain stimulation targeted to either the globus pallidus interna or the subthalamic nucleus in patients with advanced Parkinson's disease, the patients assigned to pallidal stimulation and those assigned to subthalamic stimulation had a similar improvement in motor function. In this trial of deep-brain stimulation targeted to either the globus pallidus interna or the subthalamic nucleus in patients with advanced Parkinson's disease, the patients assigned to pallidal stimulation and those assigned to subthalamic stimulation had a similar improvement in motor function. Randomized studies have shown that treatment with deep-brain stimulation, which involves the surgical implantation of a device that sends electrical impulses to specific parts of the brain, is superior to medical therapy for improving motor function and quality of life for patients with advanced Parkinson's disease. 1 , 2 The globus pallidus interna and the subthalamic nucleus are both accepted targets for deep-brain stimulation. The subthalamic nucleus is used more commonly as the target, despite the lack of evidence showing that neurostimulation of this target provides a better outcome. Our multicenter, randomized, blinded trial, called the Veterans Affairs Cooperative Studies Program (CSP) . . .

In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function in patients with advanced Parkinson's disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial. We did a multicentre, double-blind, sham-surgery controlled trial in patients with advanced Parkinson's disease. Patients were randomly assigned (2:1) by a central, computer generated, randomisation code to receive either AAV2-neurturin (5·4×1011 vector genomes) injected bilaterally into the putamen or sham surgery. All patients and study personnel with the exception of the neurosurgical team were masked to treatment assignment. The primary endpoint was change from baseline to 12 months in the motor subscore of the unified Parkinson's disease rating scale in the practically-defined off state. All randomly assigned patients who had at least one assessment after baseline were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT00400634. Between December, 2006, and November, 2008, 58 patients from nine sites in the USA participated in the trial. There was no significant difference in the primary endpoint in patients treated with AAV2-neurturin compared with control individuals (difference −0·31 [SE 2·63], 95% CI −5·58 to 4·97; p=0·91). Serious adverse events occurred in 13 of 38 patients treated with AAV2-neurturin and four of 20 control individuals. Three patients in the AAV2-neurturin group and two in the sham surgery group developed tumours. Intraputaminal AAV2-neurturin is not superior to sham surgery when assessed using the UPDRS motor score at 12 months. However, the possibility of a benefit with additional targeting of the substantia nigra and longer term follow-up should be investigated in further studies. Ceregene and Michael J Fox Foundation for Parkinson's Research.