Three-dimensional gait analysis of the effect of directional steering on gait in patients with Parkinson's disease.

INTRODUCTION: Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system. METHODS: Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control. RESULTS: Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°. CONCLUSION: Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.

Impaired virtual space-tilting perception in Parkinson's disease with Pisa syndrome.

INTRODUCTION: The mechanism of Pisa syndrome in Parkinson's disease (PD) is unclear. We aimed to analyze the spatial perception of patients with PD with Pisa syndrome using virtual reality. METHODS: In total, 16 patients with Pisa syndrome, 16 age-matched patients without Pisa syndrome, and 16 age-matched controls were included. They viewed the virtual room gradually tilting to different 8 directions randomized across trials. The 75% discrimination threshold angle and the mean tilting discrimination angle for each direction were evaluated. Participants' lateral trunk deviation was measured using Kinect. Neuropsychological status was evaluated, using the Mini-Mental Status Examination (MMSE), the Japanese version of the Montreal-Cognitive Assessment, Frontal Assessment Battery, and the color-word interference task of the Stroop test. Visuospatial abilities were assessed using Benton Judgement of Line Orientation, and vestibular function was evaluated using Subjective Visual Vertical (SVV). RESULTS: The 75% discrimination threshold in the tilting discrimination angle was larger in all directions for those in the Pisa syndrome group compared to patients in the without Pisa syndrome group and those in the control group. There were significant differences between the three groups for Front-Right, Right, and Back. Patients with Pisa syndrome showed a significantly worse performance in these tests compared with controls and tended to have worse SVV performance compared with patients without Pisa syndrome. CONCLUSION: The present findings support the hypothesis of visuo-spatial disability and/or attentional impairment in patients with Pisa syndrome.

Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury.

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.

Current Status of Telemedicine for Parkinson's Disease in Japan: A Single-Center Cross-Sectional Questionnaire Survey.

OBJECTIVE: Using telemedicine is a way to improve the accessibility of specialists for patients with Parkinson's disease (PD); however, it is not widely used in Japan. We investigated the efficacy of telemedicine in PD by using a single-center cross-sectional questionnaire survey. METHODS: We sent a questionnaire to patients who agreed to participate from among 52 patients with PD who had used telemedicine services at Juntendo University Hospital from October 2017 to November 2018. Caregivers were asked to respond to one question separately. RESULTS: A total of 38 patients responded to the questionnaire. Most patients were satisfied with the telemedicine consultation (7.8 ± 1.9), reporting that it was effective in reducing their travel burden. Twenty-one patients attended a telemedicine consultation with their caregivers, and their satisfaction was high (8.4 ± 1.8). CONCLUSION: In a specific cohort in Japan, patients with PD and their caregivers were mostly satisfied with the telemedicine service.

Closed-loop programming using external responses for deep brain stimulation in Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD). Clinicians face various challenges in adjusting stimulation parameters and configurations in clinical DBS settings owing to inexperience, time constraints, and recent advances in DBS technology that have expanded the number of possible contact configurations. We aimed to assess the efficacy of a closed-loop algorithm (CLA) for the DBS-programming method using external motion sensor-based motor assessments in patients with PD. METHODS: In this randomized, double-blind, crossover study, we enrolled 12 patients who underwent eight-ring-contact DBS lead implantations bilaterally in the subthalamic nucleus. The DBS settings of the participants were programmed using a standard of care (SOC) and CLA method. The clinical effects of both programming methods were assessed in a randomized crossover fashion. The outcomes were evaluated using the Unified Parkinson's Disease Scale part III (UPDRS-III) and sensor-based scores for baseline (medication-off/stimulation-off) and both programming methods. The number of programming steps required for each programming method was also recorded. RESULTS: The UPDRS-III scores and sensor-based scores were significantly improved by SOC and CLA settings compared to the baseline. No statistical difference was observed between SOC and CLA. The programming steps were significantly reduced in the CLA settings compared to those in the SOC. No serious adverse events were observed. CONCLUSION: CLA can optimize DBS settings prospectively with similar therapeutic benefits as that of the SOC and reduce the number of programming steps. Automated optimization of DBS settings would reduce the burden of programming for both clinicians and patients.

Rescue Levodopa/Carbidopa Intestinal Gel for Secondary Deep Brain Stimulation Failure.

OBJECTIVE: The long-term efficacy of deep brain stimulation (DBS) for motor fluctuations in advanced Parkinson's disease (PD) has been well established; however, motor fluctuations may recur over time despite multiple adjustments of DBS settings and medications. METHODS: We conducted a retrospective chart review of three patients for whom levodopa-carbidopa intestinal gel (LCIG) was additionally administered as a rescue therapy for secondary DBS failure due to the recurrence of motor fluctuations. RESULTS: The three patients had advanced PD with a disease duration of 14-19 years, and had undergone DBS for motor fluctuations refractory to standard medical management. LCIG was administered to the patients because of symptom recurrence years after DBS and provided complementary effects in all patients. CONCLUSION: The cases presented here show that rescue LCIG therapy may be a complementary treatment option for patients with post-DBS advanced PD who have a recurrence of troublesome motor complications.

Balance and Gait Improvements of Postoperative Rehabilitation in Patients with Parkinson's Disease Treated with Subthalamic Nucleus Deep Brain Stimulation (STN-DBS).

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a surgical treatment to reduce the "off" state motor symptoms of Parkinson's disease (PD). Postural instability is one of the major impairments, which induces disabilities of activities of daily living (ADLs). The effectiveness of STN-DBS for postural instability is unclear, and the effect of rehabilitation following STN-DBS has remained uncertain. OBJECTIVE: The purpose of this study was to examine changes in balance ability, gait function, motor performance, and ADLs following 2 weeks of postoperative rehabilitation in PD patients treated with STN-DBS. METHODS: Sixteen patients were reviewed retrospectively from February 2016 to March 2017. All patients were tested in their "on" medication state for balance and gait performance using the Mini-Balance Evaluation Systems Test (Mini-BESTest) and the Timed "Up and Go" (TUG) test before the operation, after the operation, and during the discharge period. The UPDRS motor score (UPDRS-III) and Barthel Index (BI) were assessed before the operation and during the discharge period. Rehabilitation focused on muscle strengthening with stretching and proactive balance training. Friedman's test and the post hoc Wilcoxon's signed-rank test were used to analyze the balance assessments, and ANOVA and the post hoc Tukey's test were used to analyze gait performance. The significance level was p < 0.05. RESULTS: During the discharge period, the Mini-BESTest and TUG were significantly improved compared with the preoperative and postoperative periods (p < 0.05). There were no differences between preoperative and postoperative periods in the Mini-BESTest (p=0.12) and TUG (p=0.91). The BI and motor sections of the UPDRS did not differ significantly between the preoperative and postoperative periods (p=0.45, p=0.22). CONCLUSION: The results of this study suggest that postoperative rehabilitation improves balance and gait ability in patients with PD treated with STN-DBS.

Pilot feasibility study of a semi-automated three-dimensional scoring system for cervical dystonia.

The objective of this study is to test the feasibility of a semi-automated scoring system for the Toronto Western Spasmodic Torticollis Scale (TWSTRS) severity scale in patients with cervical dystonia. The TWSTRS requires training and experience. We previously developed a system to measure neck angle by analyzing three-dimensional position, obtained using Kinect, a marker-less three-dimensional depth sensor. The system can track patients' faces and bodies, automatically analyze neck angles, and semi-automatically calculate the TWSTRS severity scale score. We compared the TWSTRS severity scale scores calculated by the system with the video-based scores calculated by a neurologist trained in movement disorders. A correlation coefficient analysis was then conducted. Absolute accuracy was measured using intra-class correlation (ICC) (3,1), with 95% limits of agreement. To analyze the subscales, Cohen's kappa coefficient (κ) was calculated. A p-value of < .05 was considered statistically significant. Thirty patients were enrolled. Their average age was 52.3±16.0 years, and the male to female ratio was 3:2. The average disease duration was 11.3±12.7 years. Total score measurements by the system were significantly correlated with those rated by the movement disorder-trained neurologist (r = .596, p < .05). There was a significant correlation (r = .655, p < .05) with regard to the automated part of the scale. An adequate ICC (3,1) of .562 was obtained for total severity score (p < .001, 95% confidence interval [CI]: .259-.765), while the equivalent score was .617 for the total automated part (p < .001, 95% CI .336-.798). Our three-dimensional motion capture system, which can measure head angles and semi-automatically calculate the TWSTRS severity scale score utilizing a single-depth camera, demonstrated adequate validity and reliability. This low-cost and portable system could be applied by general practitioners treating cervical dystonia to obtain objective measurements.

Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone.

Mutations in lysosomal genes increase the risk of neurodegenerative diseases, as is the case for Parkinson's disease. Here, we found that pathogenic and protective mutations in arylsulfatase A (ARSA), a gene responsible for metachromatic leukodystrophy, a lysosomal storage disorder, are linked to Parkinson's disease. Plasma ARSA protein levels were changed in Parkinson's disease patients. ARSA deficiency caused increases in α-synuclein aggregation and secretion, and increases in α-synuclein propagation in cells and nematodes. Despite being a lysosomal protein, ARSA directly interacts with α-synuclein in the cytosol. The interaction was more extensive with protective ARSA variant and less with pathogenic ARSA variant than wild-type. ARSA inhibited the in vitro fibrillation of α-synuclein in a dose-dependent manner. Ectopic expression of ARSA reversed the α-synuclein phenotypes in both cell and fly models of synucleinopathy, the effects correlating with the extent of the physical interaction between these molecules. Collectively, these results suggest that ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein.

A Randomized Crossover Pilot Study of Telemedicine Delivered via iPads in Parkinson's Disease.

BACKGROUND: We investigated the feasibility and safety of a video-based telemedicine system, delivered via a tablet, in Parkinson's disease (PD). METHODS: In a randomized, crossover, open-label pilot trial, we compared a telemedicine period (regular visits every two months with intermediate video calls via an iPad mini) with a control period (regular visits every two months), both lasting 6 months. We included 10 patients diagnosed with PD according to the British Brain Bank criteria, aged 20-75 years. The primary outcome was the PD questionnaire summary index (PDQ-39 SI). Secondary outcomes included the Hoehn and Yahr Stage and scores on the Unified PD Rating Scale (UPDRS) part I-IV, Beck Depression Inventory (BDI), and visual analog scale for satisfaction. RESULTS: Both study periods were completed by 10 patients with PD. Friedman's test revealed that there were no significant differences between the two periods in primary and secondary outcomes (p > 0.05). With respect to visual analog scale scores for satisfaction, participants indicated high satisfaction with the telemedicine system. The number of extra hospital visits and phone calls did not differ between the periods. There were no adverse events or side effects. CONCLUSIONS: We observed that a telemedicine system delivered via a tablet could successfully be used by patients as a part of their care. Further studies investigating the use of telemedicine to replace in-person visits are warranted. This trial is registered with UMIN000015536.

Dopamine transporter imaging predicts motor responsiveness to levodopa challenge in patients with Parkinson's disease: A pilot study of DATSCAN for subthalamic deep brain stimulation.

Imaging studies are necessary prior to subthalamic deep brain stimulation (STN-DBS). Dopamine transporter (DAT) imaging is a powerful tool for visualizing dopamine terminals in the striatum, but its usefulness in STN-DBS is unclear. Here, we retrospectively investigated the relationship between motor symptoms and the specific binding ratio (SBR) on DAT imaging in patients with Parkinson's disease (PD). We included 23 consecutive patients (9 female; 14 male) who were evaluated for DBS eligibility between October 2013 and October 2014 and subsequently received bilateral STN-DBS. Correlation and simple regression analyses were performed on SBR values and clinical parameters before and after surgery. SBR value was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the "ON" state before surgery (rs=-0.637, p=0.001) and positively correlated with the reduction of the levodopa equivalent daily dose by surgery (r=0.422, p=0.045). A simple regression analysis revealed that SBR value was positively correlated with UPDRS motor score improvement after levodopa challenge before surgery (p=0.001, R2=0.423). DAT imaging may be useful in STN-DBS candidate selection and the identification of the therapeutic mechanism of STN-DBS in patients with advanced PD and motor symptom fluctuations.

Current Topics in Deep Brain Stimulation for Parkinson Disease.

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology.