Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Development and Evaluation of Maze-Like Puzzle Games to Assess Cognitive and Motor Function in Aging and Neurodegenerative Diseases.

There is currently a need for engaging, user-friendly, and repeatable tasks for assessment of cognitive and motor function in aging and neurodegenerative diseases. This study evaluated the feasibility of a maze-like Numberlink puzzle game in assessing differences in game-based measures of cognition and motor function due to age and neurodegenerative diseases. Fifty-five participants, including young (18-31 years, n = 18), older (64-79 years, n = 14), and oldest adults (86-98 years, n = 14), and patients with Parkinson's (59-76 years, n = 4) and Huntington's disease (HD; 35-66 years, n = 5) played different difficulty levels of the Numberlink puzzle game and completed usability questionnaires and tests for psychomotor, attentional, visuospatial, and constructional and executive function. Analyses of Numberlink game-based cognitive (solving time and errors) and motor [mean velocity and movement direction changes (MDC)] performance metrics revealed statistically significant differences between age groups and between patients with HD and older adults. However, patients with Parkinson's disease (PD) did not differ from older adults. Correlational analyses showed significant associations between game-based performance and movement metrics and performance on neuropsychological tests for psychomotor, attentional, visuospatial, and constructional and executive function. Furthermore, varying characteristics of the Numberlink puzzle game succeeded in creating graded difficulty levels. Findings from this study support recent suggestions that data from a maze-like puzzle game provide potential "digital biomarkers" to assess changes in psychomotor, visuoconstructional, and executive function related to aging and neurodegeneration. In particular, game-based movement measures from the maze-like puzzle Numberlink games are promising as a tool to monitor the progression of motor impairment in neurodegenerative diseases. Further studies are needed to more comprehensively establish the cognitive validity and test-retest reliability of using Numberlink puzzles as a valid cognitive assessment tool.

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 µg) compared to placebo 11 months after initiation of therapy on United Parkinson's Disease Rating Scale (UPDRS) III scores in the « off ¼ condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off ¼ condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01341431.