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.

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.

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.

No abstract

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.