Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension.

BACKGROUND: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction. OBJECTIVES: To explore open-label tolerability and associations between trial outcomes and asymmetry data. METHODS: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months. We explored associations between trial outcomes, location of stimulation and motor asymmetry. RESULTS: 14/17 participants tolerated unilateral amplitude reduction (left-sided = 10, right-sided = 4). Two hundred eighty-four left-sided and 1113 right-sided stimulated voxels were associated with faster gait velocity, 81 left-sided and 22 right-sided stimulated voxels were associated with slower gait velocity. Amplitude reduction contralateral to shorter step length was associated with 2.4-point reduction in axial MDS-UPDRS. Reduction contralateral to longer step length was associated with 10-point increase in MDS-UPDRS. CONCLUSIONS: Left-sided amplitude reduction is potentially more tolerable than right-sided amplitude reduction. Right-sided more than left-sided stimulation could be associated with faster gait velocity. Shortened step length might reflect contralateral overstimulation.

Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

Spatiotemporal Gait Analysis of Patients with Spinocerebellar Ataxia Types 3 and 10 Using Inertial Measurement Units: A Comparative Study.

Given the high morbidity related to the progression of gait deficits in spinocerebellar ataxias (SCA), there is a growing interest in identifying biomarkers that can guide early diagnosis and rehabilitation. Spatiotemporal parameter (STP) gait analysis using inertial measurement units (IMUs) has been increasingly studied in this context. This study evaluated STP profiles in SCA types 3 and 10, compared them to controls, and correlated them with clinical scales. IMU portable sensors were used to measure STPs under four gait conditions: self-selected pace (SSP), fast pace (FP), fast pace checking-boxes (FPCB), and fast pace with serial seven subtractions (FPS7). Compared to healthy subjects, both SCA groups had higher values for step time, variability, and swing time, with lower values for gait speed, cadence, and step length. We also found a reduction in speed gain capacity in both SCA groups compared to controls and an increase in speed dual-task cost in the SCA10 group. However, there were no significant differences between the SCA groups. Swing time, mean speed, and step length were correlated with disease severity, risk of falling and functionality in both clinical groups. In the SCA3 group, fear of falling was correlated with cadence. In the SCA10 group, results of the Montreal cognitive assessment test were correlated with step time, mean speed, and step length. These results show that individuals with SCA3 and SCA10 present a highly variable, short-stepped, slow gait pattern compared to healthy subjects, and their gait quality worsened with a fast pace and dual-task involvement.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 2.

The field of neuromodulation has evolved significantly over the past decade. Developments include novel indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapeutic interventions. In this review, which is the second part of an effort to document and integrate the basic fundamentals and recent successful developments in the field, we will focus on classic paradigms for electrode placement as well as new exploratory targets, mechanisms of neuromodulation using this technique and new developments, including focused ultrasound driven ablative procedures.

O campo da neuromodulação evoluiu significativamente na última década. Esse progresso inclui novas indicações e inovações de hardware, software e técnicas de estimulação, levando a uma expansão das áreas clínicas cobertas e no papel dessas técnicas como intervenções terapêuticas eficazes. Nesta revisão, que é a segunda parte de um esforço para documentar e integrar os fundamentos básicos e os desenvolvimentos recentes e bem-sucedidos no campo, vamos nos concentrar em paradigmas clássicos para colocação de eletrodos, bem como em novos alvos exploratórios, mecanismos de neuromodulação usados por esta técnica e novos desenvolvimentos, incluindo procedimentos ablativos orientados por ultrassom focalizado.

The clinical diagnosis of Parkinson's disease.

After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

The clinical diagnosis of Parkinson's disease / O diagnóstico clínico da doença de Parkinson

Abstract After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Resumo Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1 / Princípios da estimulação cerebral profunda na doença de Parkinson na prática clínica: parte 1

Abstract Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Resumo Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Trends and disparities in deep brain stimulation utilization in the United States: a Nationwide Inpatient Sample analysis from 1993 to 2017.

Background: Deep brain stimulation (DBS) is an approved treatment option for Parkinson's Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at understanding these factors have been limited by single indications or small cohort sizes. The aim of this study is to provide an updated and comprehensive analysis of DBS utilization for multiple indications to better understand the factors driving disparities in access. Methods: The United States based National Inpatient Sample (NIS) database was utilized to analyze the surgical volume and trends of procedures based on indication, using relevant ICD codes. Predictors of DBS use were analyzed using a logistic regression model. DBS-implanted patients in each indication were compared based on the patient-, hospital-, and outcome-related variables. Findings: Our analysis of 104,356 DBS discharges from 1993 to 2017 revealed that the most frequent indications for DBS were PD (67%), ET (24%), and dystonia (4%). Although the number of DBS procedures has consistently increased over the years, radiofrequency ablation utilization has significantly decreased to only a few patients per year since 2003. Negative predictors for DBS utilization in PD and ET cohorts included age increase and female sex, while African American status was a negative predictor across all cohorts. Significant differences in patient-, hospital-, and outcome-related variables between DBS indications were also determined. Interpretation: Demographic and socioeconomic-based disparities in DBS use are evident. Although racial disparities are present across all indications, other disparities such as age, sex, wealth, and insurance status are only relevant in certain indications. Funding: This work was supported by Alan & Susan Hudson Cornerstone Chair in Neurosurgery at University Health Network.

Deep brain stimulation: new programming algorithms and teleprogramming.

INTRODUCTION: Thanks to a variety of factors, the field of neuromodulation has evolved significantly over the past decade. Developments include new indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapies. They also imply the realization that practical application involves new nuances that make patient selection, surgical technique, and the programming process even more complex, requiring continuous education and an organized structured approach. AREAS COVERED: In this review, the authors explore the developments in deep brain stimulation (DBS) technology, including electrodes, implantable pulse generators, contact configurations (i.e. directional leads and independent current control), remote programming, and sensing using local field potentials. EXPERT OPINION: The innovations in the field of DBS discussed in this review potentially provide increased effectiveness and flexibility not only to improve therapeutic response but also to address troubleshooting challenges seen in clinical practice. Directional leads and shorter pulse widths may broaden the therapeutic window of stimulation, avoiding current spread to structures that might trigger stimulation-related side effects. Similarly, independent control of current to individual contacts allows for the shaping of the electric field. Finally, sensing and remote programming represent important developments for more effective and individualized patient care.

Demographics and Clinical Characteristics of Autosomal Dominant Spinocerebellar Ataxia in Canada.

Background: Autosomal dominant (AD) spinocerebellar ataxias (SCAs) encompass a large group of rare disorders, which occurs in individuals of different ethnic backgrounds. To date, demographics, and clinical descriptions of AD SCA in Canada are lacking. Methods: A retrospective chart review of patients with a genetically confirmed diagnosis of AD SCAs was performed at five tertiary centers across Canada in the provinces of Quebec, Alberta, and Ontario. Demographic, genetic, and clinical information were collected and analyzed. Results: A total of 203 patients with AD SCA were identified. Weighted estimated prevalence of AD SCA in three large Canadian provinces was calculated (2.25 cases per 100.000) which is in keeping with the figures documented worldwide. We found that the distribution of the most common SCA differed when comparing provinces. The most prevalent SCA diagnosis in Ontario was SCA3 (49%), while the most prevalent SCA diagnosis in Alberta and Quebec was SCA2 in 26% and 47%, respectively. SCA6 was the third most prevalent SCA subtype in Quebec (14%), which was not seen as commonly in other provinces. SCA1 was uncommonly seen in both Alberta and Quebec, despite being common in Ontario. Conclusions: In this largest Canadian study, we describe the prevalence, distribution, and clinical characteristics of AD SCA. We found that the distribution of the most common SCA differed in the three provinces studied. This finding reflects the heterogenous nature of the Canadian population.