Resolving 'vascular parkinsonism' -COL22A1 as a genetic adult-onset leukoencephalopathy.

We describe an elderly woman meeting criteria for vascular parkinsonism/dementia associated with a likely pathogenic variant in the COL22A1 gene, supported by functional experiments in a zebrafish model. We suggest that white matter hyperintensities may not represent small-vessel ischemic disease and that, if confirmed by further observations, COL22A1 may be included among the adult-onset leukoencephalopathies mislabeled as "vascular parkinsonism."

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

Background: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.

Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al.

Spectrum of Pediatric to Early Adulthood -Associated Movement Disorders.

Background: pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders.

Cases: We describe the range of movement disorders seen in six patients (four female, two male) with variants [three novel (c.2214del, c.

Disentangling the Association Between Neurologic Deficits, Patient-Reported Impairments, and Quality of Life After Ischemic Stroke.

Background And Objectives: The EuroQol Group 5-Dimension Self-Reported Questionnaire (EQ-5D) is a well-established instrument to assess quality of life and generates generic utility values for health states reported by patients, derived from assessments by the general public. We hypothesized that language problems and other nonmotor deficits are not captured as well as motor deficits by this system. We aimed to quantify the association between disabling neurologic deficits and the EQ-5D dimension scores and the utility score in patients with ischemic stroke.

Recruitment in Acute Stroke Trials: Challenges and Potential Solutions.

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke.

Why do 'OFF' periods still occur during continuous drug delivery in Parkinson's disease?

Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson's disease (PD) to control motor and non-motor fluctuations ('OFF' periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.

Blinding of outcome assessors and its association with outcome in a randomized open-label stroke trial.

Background: It is challenging for outcome assessors to remain blinded during outcome assessment in trials with prospective randomized open blinded endpoint (PROBE) design. If assessors are able to guess the correct treatment allocation more often than expected based on chance, the assessors may have been not properly blinded.

Aims: We aimed to assess blinding of outcome assessors in a stroke trial with PROBE design and its association with outcome.

Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series.

The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to 4-factor prothrombin complex concentrate (4F-PCC), institutional formulary restrictions, and navigation of clinical scenarios involving patients clinically worsen despite initial reversal efforts. The combination use of 4F-PCC and AA has not been evaluated in clinical trials and the outcomes of such patients with FXA-inhibitor associated intracranial hemorrhage (ICH) are unknown. A total of five patients, including four outside hospital transfers, received 4F-PCC prior to AA for FXa-inhibitor associated ICH (n = 3 apixaban, n = 2 rivaroxaban; n = 4 ICH, n = 1 TBI).

Improving self-efficacy in seizure first aid: Developing a seizure first aid certification program in the United States.

Objectives: Seizures and epilepsy are very common neurologic disorders, yet knowledge of how to help a person having a seizure is sorely lacking, increasing the potential for injury and early death for people with seizures. We developed a standardized seizure first aid (SFA) training certification for the general public and evaluated its impact on knowledge and self-efficacy about SFA and program satisfaction.

Methods: The Epilepsy Foundation's SFA certification was developed by a multidisciplinary group of experts, with extensive review, feasibility testing, and analysis of pilot tests from 10 sessions with 177 participants.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018.

Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States.

Lessons Learned from Phase II and Phase III Trials Investigating Therapeutic Agents for Cerebral Ischemia Associated with Aneurysmal Subarachnoid Hemorrhage.

One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH.

Indirect treatment comparison of cenobamate to other ASMs for the treatment of uncontrolled focal seizures.

Objective: The efficacy and safety of cenobamate relative to other antiseizure medications (ASMs) has not been evaluated. An indirect treatment comparison (network meta-analysis) was performed to determine if adjunctive cenobamate increases the odds ratio (OR) for ≥50% responder rate or for withdrawals due to treatment-emergent adverse events (TEAEs) leading to ASM discontinuation versus adjunctive therapy with other ASMs.

Methods: A systematic literature review was conducted to identify randomized, double-blind, placebo-controlled trials (maintenance phase ≥ 12 weeks) assessing adjunctive ASMs in adults with uncontrolled focal seizures.

Inebilizumab for treatment of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by recurrent optic neuritis and transverse myelitis often resulting in severe disability. Anti-AQP4-immunoglobulin G (IgG) is a pathogenic product of CD19-positive plasma cells found in most, but not all, individuals with NMOSD and is associated with immune-mediated neurologic injury. Inebilizumab, an afucosylated humanized IgG1κ, anti-CD19 monoclonal antibody, may target pathogenic CD19-expressing B cells.

Seizures and Cognitive Outcome After Traumatic Brain Injury: A Post Hoc Analysis.

Introduction: Seizures and abnormal periodic or rhythmic patterns are observed on continuous electroencephalography monitoring (cEEG) in up to half of patients hospitalized with moderate to severe traumatic brain injury (TBI). We aimed to determine the impact of seizures and abnormal periodic or rhythmic patterns on cognitive outcome 3 months following moderate to severe TBI.

Methods: This was a post hoc analysis of the multicenter randomized controlled phase 2 INTREPID clinical trial conducted from 2010 to 2016 across 20 United States Level I trauma centers.

Fresh Cadaver Simulation Model with Continuous Extracorporeal Circulation as a Training Platform for Intracranial High-Flow Bypass: Technical Note and Rheologic Feasibility Evaluation.

 As endovascular techniques evolve toward replacing open surgery, several clinical scenarios still require surgical revascularization. Characterizing this era are decreasing surgical volumes and lack of realistic training models. In an effort to develop lifelike simulation models, we developed a platform for surgical training on high-flow bypass in a fresh cadaver model.