Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. OBJECTIVES: To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. METHODS: Randomized, double-blinded, double-crossover trial. RESULTS: In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). CONCLUSIONS: Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). CONCLUSIONS: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.

Programming Directional Deep Brain Stimulation in Parkinson's Disease: A Randomized Prospective Trial Comparing Early versus Delayed Stimulation Steering.

INTRODUCTION: Programming directional leads poses new challenges as the optimal strategy is yet to be established. We designed a randomized control study to establish an evidence-based programming algorithm for patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation with directional leads. METHODS: Fourteen consecutive patients were randomized to programming with either early or delayed (i.e., starting with a "ring mode") steered stimulation. Motor scores, number of programming visits, calls to the clinic, battery consumption, and stimulation adjustments required were recorded and compared between groups, using the Wilcoxon signed-ranks test, after 3 months of open-label programming. RESULTS: Thirteen patients (25 electrodes) were included, of which 23 were steerable. Nine out of 14 electrodes allocated to delayed steered stimulation were changed to steered mode due to side effects during the course of the study. No patients (11 electrodes) initially allocated to early steered stimulation were converted to ring mode. The 2 study arms did not differ in any of the considered measures at 3 months. CONCLUSION: Programming with early or delayed steered stimulation is equally effective in the short term. However, delayed steering is less time consuming and is not always needed.

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients.

BackgroundWith growing numbers of patients receiving deep brain stimulation (DBS), radiologists are encountering these neuromodulation devices at an increasing rate. Current MRI safety guidelines, however, limit MRI access in these patients.PurposeTo describe an MRI (1.5 T and 3 T) experience and safety profile in a large cohort of participants with active DBS systems and characterize the hardware-related artifacts on images from functional MRI.Materials and MethodsIn this prospective study, study participants receiving active DBS underwent 1.5- or 3-T MRI (T1-weighted imaging and gradient-recalled echo [GRE]-echo-planar imaging [EPI]) between June 2017 and October 2018. Short- and long-term adverse events were tracked. The authors quantified DBS hardware-related artifacts on images from GRE-EPI (functional MRI) at the cranial coil wire and electrode contacts. Segmented artifacts were then transformed into standard space to define the brain areas affected by signal loss. Two-sample t tests were used to assess the difference in artifact size between 1.5- and 3-T MRI.ResultsA total of 102 participants (mean age ± standard deviation, 60 years ± 11; 65 men) were evaluated. No MRI-related short- and long-term adverse events or acute changes were observed. DBS artifacts were most prominent near the electrode contacts and over the frontoparietal cortical area where the redundancy of the extension wire is placed subcutaneously. The mean electrode contact artifact diameter was 9.3 mm ± 1.6, and 1.9% ± 0.8 of the brain was obscured by the coil artifact. The coil artifacts were larger at 3 T than at 1.5 T, obscuring 2.1% ± 0.7 and 1.4% ± 0.7 of intracranial volume, respectively (P < .001). The superficial frontoparietal cortex and deep structures neighboring the electrode contacts were most commonly obscured.ConclusionWith a priori local safety testing, patients receiving deep brain stimulation may safely undergo 1.5- and 3-T MRI. Deep brain stimulation hardware-related artifacts only affect a small proportion of the brain.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Martin in this issue.

IncobotulinumtoxinA and Deep Brain Stimulation.

Guidelines recommend Botulinum toxin-A (BoNT-A) after deep brain stimulation (DBS), although the effectiveness of their combined use is uncertain. A chart review of Parkinson's disease (17) and dystonia (7) patients undergoing 302 injections with IncobotulinumtoxinA before or after DBS was performed. Patients with cervical dystonia received less IncobotulinumtoxinA after DBS (290.7 ± 124.0 vs. 192.4 ± 131.4, p = 0.005) and experienced an increased benefit (4.0 ± 3.4 vs. 8.4 ± 3.6 weeks, p = 0.003). No significant differences were found when comparing the treatment outcomes of 14 patients who received both IncobotulinumtoxinA and OnabotulinumtoxinA after DBS. The use of BoNT-A after DBS is a useful strategy although prospective studies are needed.

L'incobotulinumtoxine A et la stimulation cérébrale profonde. Il est des lignes directrices qui recommandent l'incobotulinumtoxine A à la suite de la thérapie de stimulation cérébrale profonde (SCP), et ce, même si l'efficacité de leur utilisation combinée demeure incertaine. Nous avons passé en revue les dossiers de 17 patients atteints de la maladie de Parkinson (MP) et de 7 patients atteints de dystonie ayant reçu 302 injections d'incobotulinumtoxine A avant ou après que des séances de SCP ont été effectuées. Fait à noter, les patients atteints de dystonie cervicale se sont vu injecter moins d'incobotulinumtoxine A après une séance de SCP (290,7 ± 124,0 contre 192,4 ± 131,4 ; p = 0,005). Ils ont aussi soutenu avoir ressenti un bien-être accru (4,0 ± 3,4 contre 8,4 ± 3,6 semaines ; p = 0,003). Chez 14 patients ayant bénéficié à la fois d'incobotulinumtoxine A et d'onabotulinumtoxine A, aucune différence notable n'a été observée au moment de comparer l'efficacité de ces deux traitements une fois des séances de SCP complétées. Bref, l'utilisation d'incobotulinumtoxine A après des séances de SCP apparaît comme une stratégie adéquate bien que des études prospectives s'imposent encore.

Therapeutic Window of Deep Brain Stimulation Using Cathodic Monopolar, Bipolar, Semi-Bipolar, and Anodic Stimulation.

OBJECTIVES: To compare the therapeutic window (TW) of cathodic monopolar, bipolar, anodic monopolar, and a novel "semi-bipolar" stimulation in ten Parkinson's disease patients who underwent deep brain stimulation of the subthalamic nucleus. MATERIALS AND METHODS: Patients were assessed in the "OFF" L-dopa condition. Each upper limb was tested separately for therapeutic threshold, TW and side-effect threshold (SET). Battery consumption index (BCI) also was documented. RESULTS: Compared to cathodic stimulation, therapeutic threshold was significantly higher for anodic, bipolar, and semi-bipolar stimulation (3.8 ± 1.6 vs. 4.9 ± 2.1, 5.0 ± 1.9, and 5.2 ± 1.9 mA, p = 0.0006, 0.0002, and 0.008, respectively). SET was significantly higher for bipolar stimulation (10.9 ± 2.5 mA) vs. cathodic (6.8 ± 2.2 mA, p < 0.0001) and anodic stimulation (9.2 ± 2.6 mA, p = 0.005). The SET of anodic and semi-bipolar stimulation was significantly higher vs. cathodic stimulation (p < 0.0001). TW of cathodic stimulation (2.5 ± 1.5 mA) was significantly narrower vs. bipolar (5.4 ± 2.0 mA, p < 0.0001), semi-bipolar (4.6 ± 2.6 mA, p = 0.001) and anodic stimulation (4.3 ± 2.3 mA, p < 0.0001). Bipolar (p = 0.005) and semi-bipolar (p = 0.0005) stimulation had a significantly wider TW vs. anodic stimulation. BCI of cathodic stimulation (5.9 ± 1.3) was significantly lower compared to bipolar (13.7 ± 6.8, p < 0.0001), semi-bipolar (11.0 ± 4.3, p = 0.0005), and anodic stimulation (8.1 ± 3.0, p < 0.0001). Anodic BCI was significantly lower than bipolar (p = 0.005) and semi-bipolar (p = 0.0002) stimulation while semi-bipolar BCI was lower than bipolar stimulation (p = 0.0005). CONCLUSIONS: While awaiting further studies, our findings suggest that cathodic stimulation should be preferred in light of its reduced battery consumption, possibly followed by semi-bipolar in case of stimulation-induced side-effects.

Can head trauma trigger adult-onset Rasmussen's encephalitis?

Rasmussen's encephalitis (RE) is a rare unilateral inflammatory brain disorder that causes progressive neurocognitive deterioration and refractory epilepsy including epilepsia partialis continua (EPC). We describe a patient with a unique presentation, where right upper limb EPC due to RE began within 2weeks of a concussive left frontal head injury, in a 36-year-old female without other identifiable etiology, no prior neurological deficit nor suggestion of intracranial pathology or infection, and no preceding seizures. The diagnosis of RE followed extensive investigation, excluding confounding diagnoses, with supportive histopathology, and her EPC has proven refractory to treatment. In the absence of a satisfactory alternative etiology and exclusion of differential diagnoses, the most likely cause or precipitant of this patient's RE was head trauma.

Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.

Flexible vs. standard subthalamic stimulation in Parkinson disease: A double-blind proof-of-concept cross-over trial.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamus (STN) is effective for the treatment of cardinal motor signs of Parkinson disease (PD). Structures around the STN can suppress dyskinesia and tremor (zona incerta) and improve gait and balance (substantia nigra pars reticulata). OBJECTIVE: Is the newer 8-contact linear lead connected to a 'flexible' DBS system superior to standard 4-contact stimulation in PD patients receiving STN DBS? METHODS: After 3 months of open label programming, 10 patients were randomized to standard or flexible stimulation before crossing over to the other arm (3 months each period). Patients and assessors were blinded. RESULTS: A trend to improvement in Patient Global Impression of Change scores was seen with standard to flexible stimulation and worsening from flexible to standard stimulation (mean ± SD: 0.7 ± 1.2 and -0.4 ± 1.5 respectively, p = 0.152). There was a significant reduction in the number of troublesome symptoms reported prior to DBS (2.6 ± 3.3 per patient), more so with flexible stimulation (0.4 ± 0.6 vs. 1.5 ± 1.6 with standard stimulation, p = 0.001 and p = 0.034). There was no significant difference between the flexible and standard stimulation groups. CONCLUSION: Further studies confirming that flexible stimulation is superior to standard DBS are warranted.

Functional outcomes of an integrated Parkinson's Disease Wellbeing Program.

INTRODUCTION: There is growing evidence that exercise provides benefit in treating motor and non-motor symptoms in Parkinson's disease (PD). OBJECTIVES: The aims of this study were to determine (a) whether a 5-week PD-specific program resulted in sustained physical and psychosocial benefits, and (b) the relationship between patient characteristics, exercise, falls and physical and psychosocial parameters. DESIGN: Single-centre prospective observational study. METHODS: A total of 135 consecutive patients with mild-to-moderate PD underwent a 5-week PD-specific education and exercise program from August 2013 to March 2015. Gait, mobility and psychosocial measures were compared at baseline, 6 weeks and 12 months. RESULTS: Significant improvements in physical (walking distance in 2 minutes, number of "Sit To Stands" in 30 seconds, time in seconds taken to "Timed Up and Go," fast gait velocity over 10 m, Berg Balance Scale [BBS]) and psychosocial (quality of life (QoL) [PDQ-39], depression and anxiety [DASS-21], and fatigue [PSF-16]) measures were seen at 6 weeks (all P < .01) with physical improvements sustained at 12 months (all P < .001). The number of patients at 12 months with ≥1 fall reduced from 66% to 33%, and the number not exercising reduced from 42% to 21%. A lack of exercise correlated with ≥1 fall at 12 months (OR 3.39, 95% CI 1.36-8.39, P = .009). It was also associated with poorer balance and psychosocial parameters at 12 months (all P < .05). CONCLUSIONS: Patients recruited into a 5-week Parkinson's disease education and exercise program achieved significant 12-month benefits in physical but not psychosocial measures. Patients with ≥1 fall post-treatment were less likely to have been exercising at 12-month follow-up.

Unusual gait disorders: a phenomenological approach and classification.

INTRODUCTION: Gait impairment is a very common problem in clinical practice. Multiple classifications of gait disorders are available based on anatomy, etiology, pathology and phenomenology. These classifications provide a diagnostic guide but do not clearly explain the pathophysiology of some gait disorders, which can sometimes hinder the diagnostic process. In this context, unusual gait disorders become an even more difficult clinical challenge. Areas covered: The scientific and non-scientific literature contains illustrative descriptions of unusual gait disorders based on their predominant signs and/or comparisons with normal and abnormal zoological and folkloric patterns. Unusual gait disorder phenomenology can be carefully deconstructed in order to achieve an integral approach. We present a pragmatic, phenomenological approach to various unusual gait disorders and highlight key features underlying their phenotypes. We also propose unifying terminology to facilitate diagnosis and academic communication. Expert commentary: Advanced gait analysis, neurophysiological and neuroimaging techniques have allowed for us to recognize that locomotion is a complex motor behavior that requires simultaneous integration of multiple neurological and non-neurological systems. A phenomenological approach such as the one proposed in this review could be useful while those objective techniques become more widely available in clinical practice.

Impact of small vessel disease on severity of motor and cognitive impairment in Parkinson's disease.

BACKGROUND: Subcortical small vessel disease and vascular risk factors are associated with motor and cognitive impairment. In this study we examined the relationship between these factors and the severity of motor impairment and dementia in pathologically-confirmed Parkinson's disease (PD). METHODS: The extent and severity of small vessel disease (SVD) was assessed pathologically in 77 patients with PD. The severity of motor impairment was determined using a cumulative index derived from longitudinal measures of Hoehn and Yahr score. The presence of dementia was scored using the Clinical Dementia Rating. The presence or absence of vascular risk factors and stroke were also recorded. Interactions were assessed using stepwise multiple regression analyses. RESULTS: Significant correlations were demonstrated between perivascular pallor in the globus pallidus interna and the Hoehn and Yahr stage and between increasing Braak PD stage, the number of vascular risk factors and dementia. Among the vascular risk factors, hypertension was the only variable to independently correlate with dementia. SVD pathology did not correlate with dementia in our cohort. CONCLUSIONS: This study demonstrates an association between SVD and motor impairment, and between vascular risk factors, particularly hypertension, and dementia in PD and highlights the need to manage vascular co-morbidities in PD patients.