The Prevalence of Parkinsonism in the Oldest Old: A 90+Study

Objective: To estimate prevalence of parkinsonism in the oldest-old and assess its association with age, gender, dementia, and falls. Background: Prevalence of parkinsonism increases with age up to age 85. However, whether it plateaus after age 90 is not clear, possibly due to the low number of these participants examined in previous studies or views that these features are attributable to the aging process. Methods: In-person clinical exams using modified UPDRS and Tinneti scales were analyzed in 966 participants from The 90+ Study, a population-based study of aging and dementia in people aged 90 and above. Parkinsonism was defined as meeting at least 2 of 4 core clinical criteria for parkinsonism (bradykinesia, resting tremor, rigidity, postural instability). One must be bradykinesia and all with at least mild severity. Dementia was diagnosed from in-person examinations by trained examiners using DSM-IV criteria. Results: The overall parkinsonism prevalence was 14.0[percnt]. People aged 90-94 had a prevalence of 12.4[percnt], significantly lower than those older than 95 (18.1[percnt]). Parkinsonism was significantly more frequent in participants with dementia (32.3[percnt]) compared to those who were cognitively-impaired-non-demented (7.9[percnt]) or normal (5.1[percnt]). Parkinsonism was more prevalent in those who reported a fall (15.6[percnt]) compared to non-fallers (11.5[percnt]) and was even higher in those with multiple falls in the last year (18.7[percnt]). Parkinsonism prevalence did not differ by gender. A multivariable logistic regression on gender, age, and dementia showed that dementia had the strongest association with parkinsonism. Conclusions: Despite analyses showing that prevalence of parkinsonism may plateau after age 90, it continued to increase in this study. Parkinsonism is associated with falls, frequent hospitalizations, and greater caregiver burden. Because higher fall rates and dementia are strongly associated with parkinsonism, early identification may lend opportunity to prevent adverse events and intervene in those with dementia. Study Supported by: The 90+ Stud

Frameless Stereotactic Robot-Assisted Subthalamic Nucleus Deep Brain Stimulation: Case Report.

BackgroundElectrode implantation for deep brain stimulation (DBS) can be performed in numerous ways, but the current "gold standard" is the use of frame-based systems for accuracy. Robotic stereotactic procedures, however, have gained increased interest because of their ease of use and reliability, but there could be concern about their safety in the United States as the result of recent lawsuits (e.g., the da Vinci Surgical System). We report the first DBS implantation performed using a robot (ROSA robotic device) approved by Food and Drug Administration for use in North America.Case descriptionA 56-year-old, right-handed woman with a 12-year history of Parkinson disease is described. She was offered bilateral subthalamic nucleus DBS placement to address motor fluctuations and dyskinesias. DBS electrode implantation was implemented successfully with ROSA robotic stereotactic assistance. Using preoperative magnetic resonance imaging scan acquisitions, we targeted the patient's subthalamic nucleus bilaterally. Bone fiducials were placed and intraoperative computed tomography (CT) imaging was obtained. The magnetic resonance imaging and CT were fused, and the patient was registered to the ROSA software. Trajectories were obtained and a microdrive device was fixed to the robotic arm to advance the electrode to the correct location. Electrodes were then placed bilaterally. Intraoperative CT showed good placement with no complications encountered.ConclusionsThe advantages of robotic assistance in stereotactic procedures are as follows: 1) improved accuracy, 2) "arc-less" approach, and 3) minor adjustments can be made in multiple planes to the entry point without adjustment of a frame. The case demonstrates robotic stereotactic assistance viability as an alternative to traditional frame-based or frameless systems in U.S. hospitals

Frameless Stereotactic Robot-Assisted Subthalamic Nucleus Deep Brain Stimulation: Case Report.

BackgroundElectrode implantation for deep brain stimulation (DBS) can be performed in numerous ways, but the current "gold standard" is the use of frame-based systems for accuracy. Robotic stereotactic procedures, however, have gained increased interest because of their ease of use and reliability, but there could be concern about their safety in the United States as the result of recent lawsuits (e.g., the da Vinci Surgical System). We report the first DBS implantation performed using a robot (ROSA robotic device) approved by Food and Drug Administration for use in North America.Case descriptionA 56-year-old, right-handed woman with a 12-year history of Parkinson disease is described. She was offered bilateral subthalamic nucleus DBS placement to address motor fluctuations and dyskinesias. DBS electrode implantation was implemented successfully with ROSA robotic stereotactic assistance. Using preoperative magnetic resonance imaging scan acquisitions, we targeted the patient's subthalamic nucleus bilaterally. Bone fiducials were placed and intraoperative computed tomography (CT) imaging was obtained. The magnetic resonance imaging and CT were fused, and the patient was registered to the ROSA software. Trajectories were obtained and a microdrive device was fixed to the robotic arm to advance the electrode to the correct location. Electrodes were then placed bilaterally. Intraoperative CT showed good placement with no complications encountered.ConclusionsThe advantages of robotic assistance in stereotactic procedures are as follows: 1) improved accuracy, 2) "arc-less" approach, and 3) minor adjustments can be made in multiple planes to the entry point without adjustment of a frame. The case demonstrates robotic stereotactic assistance viability as an alternative to traditional frame-based or frameless systems in U.S. hospitals

Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial

© 2021 American Medical Association. All rights reserved. Importance: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials. Objective: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS. Design, Setting, and Participants: This double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements. Interventions: Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks. Main Outcomes and Measures: The primary outcome was change in short-interval intracortical inhibition (SICI; SICI-1was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies. Results: A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI-1increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P =.009) in the 900-mg/d ezogabine group vs placebo group. The SICI-1did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P =.31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P =.04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, -2.64 to 6.54; P =.40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P \u3c.001). Conclusions and Relevance: Ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02450552