Surgical Complications in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease: Experience in 800 Patients.

INTRODUCTION: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD). METHODS: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared. RESULTS: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation. CONCLUSION: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.

Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

Long-Term Follow-Up of the LEAP Study: Early Versus Delayed Levodopa in Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. METHODS: The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start). Follow-up visits were performed 3 and 5 years after baseline. We assessed the between-group differences in terms of square root transformed total Unified Parkinson's Disease Rating Scale score at 3 and 5 years with linear regression. We compared the prevalence of dyskinesia, prevalence of wearing off, and the levodopa equivalent daily dose. RESULTS: A total of 321 patients completed the 5-year visit. The adjusted square root transformed total Unified Parkinson's Disease Rating Scale did not differ between treatment groups at 3 (estimated difference, 0.17; standard error, 0.13; P = 0.18) and 5 years (estimated difference, 0.24; standard error, 0.13; P = 0.07). At 5 years, 46 of 160 patients in the early-start group and 62 of 161 patients in the delayed-start group experienced dyskinesia (P = 0.06). The prevalence of wearing off and the levodopa equivalent daily dose were not significantly different between groups. CONCLUSIONS: We did not find a difference in disease progression or in prevalence of motor complications between patients with early PD starting treatment with a low dose of levodopa 40 weeks earlier versus 40 weeks later over the subsequent 5 years. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep Brain Stimulation for Orthostatic Tremor: An Observational Study.

BACKGROUND: Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. OBJECTIVE: To evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects. METHODS: Nine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. RESULTS: Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS. CONCLUSION: Vim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

Bidirectional Interplay between Deep Brain Stimulation and Cognition in Parkinson's Disease: A Systematic Review.

BACKGROUND: Deep brain stimulation (DBS) is efficacious for treating motor symptoms in Parkinson's disease (PD). OBJECTIVES: The aim is to evaluate the evidence regarding DBS effectiveness after postoperative cognitive deterioration, the impact of preoperative cognition on DBS effectiveness, and the impact of DBS on cognition. METHODS: Literature searches were performed on MEDLINE, EMBASE, and CENTRAL (Cochrane library). Primary outcomes were OFF-drug Unified Parkinson Disease Rating Scale Part III score and cognitive test scores. RESULTS: DBS effectiveness did not differ in patients with postoperative declining compared to stable cognition (n = 5 studies). Preoperative cognition did not influence DBS effectiveness (n = 1 study). DBS moderately decreased verbal fluency compared to the best medical treatment (n = 24 studies), which may be transient. CONCLUSION: DBS motor effectiveness in PD does not appear to be influenced by cognition. DBS in PD seems cognitively safe, except for a moderate decline in verbal fluency. Further research is warranted. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predicting Delayed In-Hospital Recovery of Physical Function After Total Knee Arthroplasty.

Objective: To identify patients at high risk of delayed in-hospital functional recovery after knee replacement surgery by developing and validating a prediction model, including a combination of preoperative physical fitness parameters and patient characteristics. Design: Retrospective cohort study using binary logistic regression. Setting: University hospital, orthopedic department. Participants: 260 adults (N=260) (≥18y) with knee osteoarthritis awaiting primary unilateral total knee arthroplasty and assessed during usual care between 2016 and 2020. Intervention: Not applicable. Main Outcome Measures: Time to reach in-hospital functional independence (in days), measured by the modified Iowa Level of Assistance Scale. A score of 0 means completely independent. Potential predictor variables are a combination of preoperative physical fitness parameters and patient characteristics. Results: Binary logistic regression modeling was applied to develop the initial model. A low de Morton Mobility Index (DEMMI), walking aid use indoors, and a low handgrip strength (HGS) were the most important predictors of delayed in-hospital recovery. This model was internally validated and had an optimism-corrected R2 of 0.07 and an area under curve of 61.2%. The probability of a high risk of delayed in-hospital recovery is expressed by the following equation:Phighrisk=(1/(1+e(-(2.638-0.193×DEMMI+0.879×indoorwalkingaid-0.007×HGS))))×100%. Conclusions: The model has a low predictive value and a poor discriminative ability. However, there is a positive association between preoperative physical fitness and postoperative recovery of physical function. The validity of our model to distinguish between high and low risk, based on preoperative fitness values and patient characteristics, is limited.

7-Tesla Magnetic Resonance Imaging Scanning in Deep Brain Stimulation for Parkinson's Disease: Improving Visualization of the Dorsolateral Subthalamic Nucleus.

BACKGROUND: Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. METHODS: By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. RESULTS: From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. CONCLUSION: Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

Measurement properties of the childhood bladder and bowel dysfunction questionnaire.

OBJECTIVES: The childhood bladder and bowel dysfunction questionnaire (CBBDQ) was previously found feasible, structurally valid, with good internal consistency. The purpose of this study was to evaluate the remaining measurement properties according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). METHODS: A prospective cohort study among parents of children aged 5-12 years was conducted. Calculated were the area under the curve (AUC) (criterion validity, responsiveness, interpretability) and intra-class correlation coefficients (ICCagreement ) (construct validity and test-retest reliability). RESULTS: One hundred and seventy-two parents were included from March 2019 to April 2021. Correlating the bladder subscales of the CBBDQ with the Vancouver symptom score for dysfunctional elimination (VSSDES) and proxy-reported pediatric incontinence quality of life (p-PinQ) showed convergent validity (ICCsagreement : 0.76 and 0.74). Divergent validity was found when correlating the bowel subscales of the CBBDQ with the VSSDES (ICCagreement : 0.52). Excellent criterion validity (AUC: 0.98); excellent test-retest reliability (ICCagreement : 0.94) and, at 6 months, fair responsiveness (AUC: 0.74) were found. The minimal important change was 4.5, with cut-off value of 11. CONCLUSION: The CBBDQ has been developed according to COSMIN standards. The items were defined using the consensus-based ICCS standards and Rome-III criteria. The measurement properties were identified using enough participants. Although interpretability is not considered a measurement property, interpretability aspects are reported here as they refer to what instrument scores mean. The 18-item-CBBDQ met the measurement properties of validity, reliability, and responsiveness, as defined by COSMIN. The CBBDQ is suitable for self-administration by parents, and completion takes little time.

Efficacy and safety of adjunctive oral therapy in Parkinson's disease with motor complications: a systematic review and network meta-analysis.

Background: The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications. Methods: In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia. Results: 74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile. Conclusions: COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.

Changes in neurologists' treatment preferences for Parkinson's disease in the Netherlands.

•Data about treatment preferences for Parkinson's disease (PD) are scarce.•A survey was sent to neurologists in the Netherlands in 2010 and 2021.•In 2021, levodopa was increasingly prescribed for PD.•In 2021, levodopa was increasingly prescribed for younger PD patients.•In 2021, Deep Brain Stimulation became the treatment choice for advanced PD.

Reliability of patient-specific gait profiles with inertial measurement units during the 2-min walk test in incomplete spinal cord injury.

Most established clinical walking tests assess specific aspects of movement function (velocity, endurance, etc.) but are generally unable to determine specific biomechanical or neurological deficits that limit an individual's ability to walk. Recently, inertial measurement units (IMU) have been used to collect objective kinematic data for gait analysis and could be a valuable extension for clinical assessments (e.g., functional walking measures). This study assesses the reliability of an IMU-based overground gait analysis during the 2-min walk test (2mWT) in individuals with spinal cord injury (SCI). Furthermore, the study elaborates on the capability of IMUs to distinguish between different gait characteristics in individuals with SCI. Twenty-six individuals (aged 22-79) with acute or chronic SCI (AIS: C and D) completed the 2mWT with IMUs attached above each ankle on 2 test days, separated by 1 to 7 days. The IMU-based gait analysis showed good to excellent test-retest reliability (ICC: 0.77-0.99) for all gait parameters. Gait profiles remained stable between two measurements. Sensor-based gait profiling was able to reveal patient-specific gait impairments even in individuals with the same walking performance in the 2mWT. IMUs are a valuable add-on to clinical gait assessments and deliver reliable information on detailed gait pathologies in individuals with SCI.Trial registration: NCT04555759.

Exercise- and education-based prehabilitation before total knee arthroplasty: a pilot study.

OBJECTIVE: To determine the feasibility and estimates of effects of a supervised exercise- and education-based prehabilitation programme aiming to improve knee functioning compared with usual care in patients awaiting total knee arthroplasty. DESIGN: A randomized controlled pilot study. SUBJECTS: Patients receiving primary, unilateral total knee arthroplasty. METHODS: Patients randomized to the intervention group participated in a personalized 4-8-week prehabilitation programme before surgery. Feasibility of the intervention and self-reported knee functioning, pain, physical performance and hospital stay were assessed at baseline, immediately preoperatively, 6 and 12 weeks after surgery. RESULTS: Twenty patients (mean age 72.7±5.95 years) were enrolled in this study. The personalized prehabilitation programme was found to be feasible and safe, with an exercise adherence of 90%. Significant medium interaction effects between groups and over time favouring prehabilitation were reported for the sport subscale of the Knee Osteoarthritis Outcome Score (F(3/54) = 2.895, p = 0.043, η² = 0.139) and Tegner Activity Scale (F(2.2/39.1) = 3.20, p = 0.048, η² = 0.151). CONCLUSION: The absence of adverse events and high adherence to the programme, coupled with beneficial changes shown in the intervention group, support the conduct of a full-scale trial investigating the effectiveness of prehabilitation.

Programming Algorithm for the Management of Speech Impairment in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) has an ambiguous relation to speech. Speech impairment can be a stimulation-induced side effect, and parkinsonian dysarthria can improve with STN-DBS. Owing to the lack of an up-to-date and evidence-based approach, DBS reprogramming for speech impairment is largely blind and greatly relies on the physician's experience. In this study, we aimed to establish an evidence- and experience-based algorithm for managing speech impairment in patients with PD treated with STN-DBS. MATERIALS AND METHODS: We performed a single-center retrospective study to identify patients with STN-DBS and speech impairment. Onset of speech impairment, lead localization, and assessment of DBS-induced nature of speech impairment were collected. When DBS settings were adjusted for improving speech, the magnitude and duration of effect were collected. We also performed a systematic literature review to identify studies describing the effects of parameter adjustments aimed at improving speech impairment in patients with PD receiving STN-DBS. RESULTS: In the retrospective study, 245 of 631 patients (38.8%) with STN-DBS had significant speech impairment. The probability of sustained marked improvement upon reprogramming was generally low (27.9%). In the systematic review, 23 of 662 identified studies were included. Only two randomized controlled trials have been performed, providing evidence for interleaving-interlink stimulation only. Considerable methodologic heterogeneity precluded the conduction of a meta-analysis. CONCLUSIONS: Speech impairment in STN-DBS for PD is frequent, but high-quality evidence regarding DBS parameter adjustments is scarce, and the probability of sustained improvement is low. To improve this outcome, we propose an evidence- and experience-based approach to address speech impairment in STN-DBS that can be used in clinical practice.

Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation.

BACKGROUND: This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline. METHODS: 110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life. RESULTS: There were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson's Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02). CONCLUSIONS: This study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms. TRIAL REGISTRATION NUMBER: NTR5809.

Methodology and application of three-dimensional technology for brace design and production for treatment in patients with adolescent idiopathic scoliosis: a scoping review protocol.

INTRODUCTION: Conservative treatment for adolescent idiopathic scoliosis (AIS) using bracing has proven to be effective at reducing curve progression. However, variation in brace design and lack of brace specificity hamper clinical treatment outcomes as well as the predictability and comparison hereof. To overcome this, recent technological developments aim to generate transparent and objective criteria for brace manufacturing by applying computer-aided design software and additive manufacturing to produce braces for scoliosis treatment. Yet, the extent of its applicability and clinical implementation are to be determined. This study will identify and map the available evidence for the methodology and application of three-dimensional technology for the design and production of clinical braces used for treatment in patients with AIS. METHODS AND ANALYSIS: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. This scoping review will consider studies on methodology of three-dimensional technological methodology and applications that have been or are currently being applied in brace treatment of AIS. The following databases will be searched: MEDLINE, Web of Science, Cochrane Database of Systematic Reviews and Embase (OVID). Search limits will be applied; for example, only articles written in the English language published after 2000 will be included. The retrieved articles will be screened independently by two researchers. A third researcher will be consulted in case of disagreement. Data from relevant articles will be independently extracted by two researchers and presented in a tabular manner accompanied by a descriptive narration. ETHICS AND DISSEMINATION: Considering the nature of the study, no ethical approval needed to be requested. The study result will be submitted to a peer-reviewed journal.

Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.

Evaluation of Primary Allied Health Care in Patients Recovering From COVID-19 at 6-Month Follow-up: Dutch Nationwide Prospective Cohort Study.

BACKGROUND: Patients recovering from COVID-19 often experience persistent problems in their daily activities related to limitations in physical, nutritional, cognitive, and mental functioning. To date, it is unknown what treatment is needed to support patients in their recovery from COVID-19. OBJECTIVE: This study aimed to evaluate the primary allied health care of patients recovering from COVID-19 at 6-month follow-up and to explore which baseline characteristics are associated with changes in the scores of outcomes between baseline and 6-month follow-up. METHODS: This Dutch nationwide prospective cohort study evaluated the recovery of patients receiving primary allied health care (ie, dietitians, exercise therapists, occupational therapists, physical therapists, and speech and language therapists) after COVID-19. All treatments offered by primary allied health professionals in daily practice were part of usual care. Patient-reported outcome measures on participation, health-related quality of life, fatigue, physical functioning, and psychological well-being were assessed at baseline and at 3- and 6-month follow-up. Linear mixed model analyses were used to evaluate recovery over time, and uni- and multivariable linear regression analyses were used to examine the association between baseline characteristics and recovery. RESULTS: A total of 1451 adult patients recovering from COVID-19 and receiving treatment from 1 or more primary allied health professionals were included. For participation (Utrecht Scale for Evaluation of Rehabilitation-Participation range 0-100), estimated mean differences of at least 2.3 points were observed at all time points. For the health-related quality of life (EuroQol Visual Analog Scale, range 0-100), the mean increase was 12.3 (95% CI 11.1-13.6) points at 6 months. Significant improvements were found for fatigue (Fatigue Severity Scale, range 1-7): the mean decrease was -0.7 (95% CI -0.8 to -0.6) points at 6 months. However, severe fatigue was reported by 742/929 (79.9%) patients after 6 months. For physical functioning (Patient-Reported Outcomes Measurement Information System-Physical Function Short Form 10b, range 13.8-61.3), the mean increase was 5.9 (95% CI 5.9-6.4) points at 6 months. Mean differences of -0.8 (95% CI -1.0 to -0.5) points for anxiety (Hospital Anxiety and Depression Scale range 0-21) and -1.6 (95% CI -1.8 to -1.3) points for depression were found after 6 months. A worse baseline score, hospital admission, and male sex were associated with greater improvement between baseline and 6-month follow-up, whereas age, the BMI, comorbidities, and smoking status were not associated with mean changes in any outcome measures. CONCLUSIONS: Patients recovering from COVID-19 who receive primary allied health care make progress in recovery but still experience many limitations in their daily activities after 6 months. Our findings provide reference values to health care providers and health care policy makers regarding what to expect from the recovery of patients who receive health care from 1 or more primary allied health professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735744; https://tinyurl.com/3vf337pn. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2340/jrm.v54.2506.

Dopamine pathway and Parkinson's risk variants are associated with levodopa-induced dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. Objectives: To investigate the effects of genetic variants on risk and time to LID. Methods: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1,612 PD patients with and 3,175 without LID. Results: We found that GBA1 variants were associated with LID risk (OR=1.65, 95% CI=1.21-2.26, p=0.0017) and LRRK2 variants with reduced time to LID onset (HR=1.42, 95% CI=1.09-1.84, p=0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile=1.27, 95% CI=1.03-1.56, p=0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile=1.38, 95% CI=1.07-1.79, p=0.0128; HRfourth_quartile=1.38, 95% CI=1.06-1.78, p=0.0147). Conclusions: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care.

Directional versus ring-mode deep brain stimulation for Parkinson's disease: protocol of a multi-centre double-blind randomised crossover trial.

BACKGROUND: The effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson's disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson's disease (STEERING) study is to investigate if directional DBS for Parkinson's disease results in a better clinical outcome when compared to ring-mode DBS. METHODS: The STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson's disease, subthalamic nucleus DBS in a 'classic' ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as 'responders' (i.e., patient with a satisfactory effect of ring-mode DBS) or 'non-responder' (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28-66) followed by directional DBS for 56 days (28-66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson's Disease Rating Scale - Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications-Dyskinesia, disease related quality of life measured with the Parkinson's Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants' therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together. DISCUSSION: The STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson's disease DBS patients or if directional DBS should only be used in a case-based approach. TRIAL REGISTRATION: This trial was registered on the Netherlands Trial Register, as trial NL6508 ( NTR6696 ) on June 23, 2017.

Variability of Active Cervical Range of Motion Within and Between Days in Healthy Participants: A Prospective Observational Study.

OBJECTIVE: The purpose of this study was to determine the intraday and interday variability and systematic change over the day of active cervical range of motion (aCROM) measurements in asymptomatic persons using a clinically applicable measurement device. METHODS: A prospective observational study was performed. Sixteen adults (8 men and 8 women, median age 51 years) without neck pain in the last 3 months were recruited in 2 physiotherapy practices. Active cervical range of motion was estimated using the Apple iPhone application "3D Range of Motion." Measurements were performed 3 times a day for 7 days and spread over a period of 3 weeks. Mean values of aCROM were calculated. Intraday and interday variability was estimated by calculating limits of agreement. RESULTS: The limits of agreement for intraday variability ranged from ±12.1° for left rotation to ±15.5° for total rotation. For interday variability, the limits of agreement ranged from ±14.2° for right rotation to ±20.1° for total rotation. No systematic change over the day was found. CONCLUSION: This study showed substantial intraday and interday variability of aCROM measurements in asymptomatic people. No trend toward an increased or decreased aCROM was observed during the course of the day. When interpreting aCROM values, clinicians should consider the degree of variation in aCROM measurements over time.