Development of an Equity, Diversity, Inclusion, and Anti-racism Pledge as the Foundation for Action in an Academic Department of Neurology.

Racial inequities as illustrated by the health disparities in COVID19 infections and deaths, the recent killings of Black men and women by law enforcement, and the widening socioeconomic inequality and have brought systemic racism into a national conversation. These unprecedented times may have deleterious consequences, increasing stress, and trauma for many members of the neurology workforce. The Equity, Diversity, Inclusion and Anti-Racism Committee within our Department of Neurology provides infrastructure and guidance to foster a culture of belonging and addresses the well-being of faculty, staff, and trainees. Here, we present the creation and implementation of our Equity, Diversity, Inclusion, and Anti-Racism (EDIA) Pledge which was central to our committee's response to these unprecedented times. We outline the process of developing this unique EDIA Pledge and provide a roadmap for approaching these important topics through a CME Neurology Grand Rounds aimed at fostering a diverse, inclusive, equitable and antiracist work environment. Through the lived experiences of 4 faculty members, we identify the impact of bias and microaggressions, and encourage allyship and personal development for cultural intelligence. We hope these efforts will inspire Neurology departments and other academic institutions across the globe to make a similar pledge.

A prototype worldwide survey of diagnostic and treatment modalities for stroke.

Stroke is a global health problem. However, very little is known about stroke care in low- to middle-income countries. Obtaining country-specific information could enable us to develop targeted programs to improve stroke care. We surveyed neurologists from 12 countries (Chile, Georgia, Nigeria, Qatar, India, Lithuania, Kazakhstan, Indonesia, Denmark, Brazil, Belgium, and Bangladesh) using a web-based survey tool. Data were analyzed both for individual countries and by income classification (low income, lower middle income, upper middle income, and high income). Six percent (n = 200) of 3123 targeted physicians completed the survey. There was a significant correlation between income classification and access and affordability of head computed tomography scan (ρ = .215, P = .002), transthoracic echocardiogram (ρ = .181, P = .012), extracranial carotid Doppler ultrasound (ρ = .312, P ≤ .000), cardiac telemetry (ρ = .353, P ≤ .000), and stroke treatments such as intravenous thrombolysis (ρ = .276, P ≤ .001), and carotid endarterectomy (ρ = .214, P ≤ .004); stroke quality measures such as venous thromboembolism prophylaxis during hospital stay (ρ = .163, P ≤ .022), discharge from hospital on antithrombotic therapy (ρ = .266, P ≤ .000), consideration for acute thrombolytic therapy (ρ = .358, P ≤ .000), and antithrombotic therapy prescribed by end of hospital day 2 (ρ = .334, P ≤ .000). However, there was no significant correlation between income classification and the access and affordability of antiplatelet agents, vitamin K antagonists and statins, anticoagulation for atrial fibrillation/flutter, statin medication, stroke education, and assessment for rehabilitation. Our study shows that it is possible to get an overview of stroke treatment measures in different countries by conducting an internet-based survey. The generalizability of the findings may be limited by the low survey response rate.

Pregabalin or placebo used adjunctively with levetiracetam in refractory partial-onset epilepsy: a post hoc efficacy and safety analysis in combined clinical trials.

OBJECTIVE: Some patients with epilepsy require treatment with >1 adjunctive antiepileptic drug (AED) to achieve adequate seizure remission. The purpose of this analysis was to evaluate the efficacy and safety of adding adjunctive pregabalin to an AED regimen that included levetiracetam in patients with refractory partial-onset epilepsy. RESEARCH DESIGN AND METHODS: Data from the pregabalin and placebo arms of two placebo-controlled, double-blind, randomized studies of pregabalin in patients who received adjunctive treatment with levetiracetam in addition to ≥1 other AEDs were pooled for this post hoc analysis. Patients (aged ≥18 years) had ≥4 partial-onset seizures and no 28-day period free of seizures during baseline. Efficacy outcomes included Response Ratio (RRatio), change from baseline in seizure frequency, proportion of patients with ≥50% reduction in seizure frequency, and 28-day seizure-freedom rate. Safety was evaluated using adverse events (AEs). RESULTS: In total, 138 patients were included in the analysis (placebo, n = 47; pregabalin, n = 91). Pregabalin was significantly better than placebo for difference in least squares mean of the RRatio (-16.4; 95% confidence interval [CI]: -28.5, -4.5; p = 0.0085), median of the difference in percentage change from baseline in seizure frequency (-22.3; 95% CI: -40.1, -7.2; p = 0.0095), and proportion of 50% responders (36.3 vs. 17.0; odds ratio, 3.2; 95% CI: 1.3, 8.3; p = 0.018), but not 28-day seizure-freedom rate (7 [7.7%] vs. 2 [4.3%]; p = 0.353). The most common AEs when adding pregabalin were dizziness/vertigo, fatigue, somnolence, blurred vision, and increased weight that were not proportional to the number of concomitant AEDs. CONCLUSIONS: In this population of patients with refractory partial-onset seizures, adding pregabalin to an AED regimen with levetiracetam produced further seizure reductions. The safety profile of pregabalin in patients receiving levetiracetam and ≥1 other AEDs did not appear to be compromised by the number of concomitant AEDs.

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PURPOSE: To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. METHODS: Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. RESULTS: Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. CONCLUSIONS: Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Real-time differentiation of nonconvulsive status epilepticus from other encephalopathies using quantitative EEG analysis: a pilot study.

PURPOSE: Distinguishing nonconvulsive status epilepticus (NCSE) from some nonepileptic encephalopathies is a challenging problem. In many situations, NCSE and nonepileptic encephalopathies are indistinguishable by clinical symptoms and can produce very similar electroencephalography (EEG) patterns. Misdiagnosis or delay to diagnosis of NCSE may increase the rate of morbidity and mortality. METHODS: We developed a fast-differentiating algorithm using quantitative EEG analysis to distinguish NCSE patients from patients with toxic/metabolic encephalopathy (TME). EEG recordings were collected from 11 patients, including 6 with NCSE and 5 with TME. Three nonlinear dynamic measures were used in the proposed algorithm: the maximum short-term Lyapunov exponent (STLmax), phase of attractor (phase/angular frequency), and approximate entropy (ApEn). A further refined metric derived from STLmax and phase of attractor (the mean distance to EEG epoch samples from their centroid in the feature space) was also utilized as a criterion. Paired t tests were carried out to further clarify the separation between the EEG patterns of NCSE and TME. RESULTS: Computational results showed that the performance of the proposed algorithm was sufficient to distinguish NCSE from TME. The results were consistent in all subjects in our study. CONCLUSIONS: The study presents evidence that the maximum short-term Lyapunov exponents (STLmax) and phase of attractors (phase/angular frequency) can be useful in assisting clinical diagnosis of NCSE. Findings presented in this article provide a promising indication that the proposed algorithm may correctly distinguish NCSE from TME. Although the exact mechanism of this association remains unknown, the authors suggest that epileptic activity is highly associated with and can be modeled by dynamic systems.

A robust spike and wave algorithm for detecting seizures in a genetic absence seizure model.

Animal Models are used extensively in basic epilepsy research. In many studies, there is a need to accurately score and quantify all epileptic spike and wave discharges (SWDs) as captured by electroencephalographic (EEG) recordings. Manual scoring of long term EEG recordings is a time-consuming and tedious task that requires inordinate amount of time of laboratory personnel and an experienced electroencephalographer. In this paper, we adapt a SWD detection algorithm, originally proposed by the authors for absence (petit mal) seizure detection in humans, to detect SWDs appearing in EEG recordings of Fischer 334 rats. The algorithm is robust with respect to the threshold parameters. Results are compared to manual scoring and the effect of different threshold parameters is discussed.

Antiepileptic drug intervention decouples electroencephalogram (EEG) signals: a case study in Unverricht-Lundborg Disease.

Change in severity of myoclonus as an outcome measure of antiepileptic drug (AED) treatment in patients with Unverricht-Lundborg Disease (ULD) has been estimated by utilizing the Unified Myoclonus Rating Scale (UMRS). In this study, we measure treatment effects through EEG analysis using mutual information approach to quantify interdependence/coupling strength among different electrode sites. Mutual information is known to have the ability to capture linear and non-linear dependencies between EEG time series with superior performance over the traditional linear measures. One subject with ULD participated in this study and 1-hour EEG recordings were acquired before and after treatment of AED. Our results indicate that the mutual information is significantly lower after taking the add-on AED for four weeks at least. This finding could lead to a new insight for developing a new outcome measure for patient with ULD, when UMRS could potentially fail to detect a significant difference.

The influence of vagus nerve stimulation on memory.

BACKGROUND: Vagus nerve stimulation (VNS) has been shown to improve memory. OBJECTIVE: The purpose of this study was to learn at which stage of memory formation this influence occurs. METHODS: Ten subjects who had been implanted with vagus nerve stimulators for the treatment of intractable seizures performed tasks that assessed learning and retention (Hopkins Verbal Learning Test) during actual and sham VNS. RESULTS: We found that VNS had no effect on learning but enhanced consolidation, which led to improved retention. CONCLUSIONS: The means by which VNS improves retention is probably related to the increased activity in the nucleus of the tractus solitarius and the locus coeruleus-central adrenergic system that activates the amygdala and increases long-term potentiation in the hippocampus.

Effect of vagus nerve stimulation on creativity and cognitive flexibility.

OBJECTIVE: The purpose of this study was to determine whether vagus nerve stimulation influences cognitive flexibility and creativity. METHODS: Ten subjects, in whom vagus nerve stimulators had been implanted for the treatment of intractable seizures, performed tasks that assessed cognitive flexibility (solving anagrams), creativity (Torrance Test), and memory (Hopkins Verbal Learning Test) during actual and sham vagus nerve stimulation. RESULTS: Vagus nerve stimulation impaired cognitive flexibility and creativity, but these results could not be explained by the induction of a general encephalopathy because VNS did not impair learning and improved retention. CONCLUSIONS: The means by which vagus nerve stimulation impairs cognitive flexibility and creative thinking is probably related to increased activity of the locus coeruleus-central adrenergic system that increases the signal-to-noise ratio and improves the brain's ability to attend to sensory input, but decreases its ability to recruit large-scale networks.

Safety of 25- and 50-mg capsules in the initiation of zonisamide therapy in patients with epilepsy: an uncontrolled, open-label study.

OBJECTIVE: This study was designed to assess the safety of 25- and 50-mg dosage strengths of zonisamide for initial titration in patients with epilepsy. RESEARCH DESIGN AND METHODS: This phase 3, multicenter, open-label, uncontrolled study conducted at 26 study sites in the United States included male and female patients with epilepsy >or= 12 years of age. After a screening visit, subjects began zonisamide therapy at a dosage depending on their body weight. Zonisamide was titrated to 100 mg/day. MAIN OUTCOME MEASURES: At the study's conclusion, information regarding adverse events (AEs) and body weight was recorded. RESULTS: One hundred forty-three subjects enrolled and received at least one zonisamide dose. Of these subjects, 125 reached at least the 100-mg dosage before terminating the study. Eighty-two subjects (57.3%) experienced at least one AE. Most commonly reported AEs included headache, somnolence, asthenia, rhinitis, nausea, and rash. No significant change in patient body weight was noted during the study (95% confidence interval: -0.1, 0.6). CONCLUSIONS: Study limitations include the open-label design and the lack of direct comparison between lower (25- and 50-mg) and higher (100-mg) starting dosages. Despite these limitations, the 25- and 50-mg zonisamide dosage formulations were well tolerated in this study.

Seizure-alert dogs: a review and preliminary study.

PURPOSE: Gather data on incidence of canine alerting/responding behavior with a defined patient population. Research development and use of purported alerting dogs. METHODS: Review of the literature was performed. A qualitative questionnaire was completed by epilepsy patients. Service dog trainers were identified. RESULTS: Of 63 patients, 29 owned pet dogs. Nine reported their dog responded to seizures, three also were reported to alert to seizure onset. There was no significant evidence of correlation between alerting/responding behavior and the patients' demographics, health, or attitude/opinion of pets. Seizure-alerting/responding behavior of the dog did not appear to depend on its age, gender or breed. A literature review revealed psychological and practical benefits of service dogs are well documented. Fifteen trainers of seizure-assist dogs were identified and interviewed. CONCLUSIONS: Findings suggest some dogs have innate ability to alert and/or respond to seizures. Suggests a trend in type of seizure/auras a dog may alert to. Success of these dogs depends largely on the handler's awareness and response to the dog's alerting behavior. Warrants further research to aid in the selection of patients who may benefit from seizure-assist dogs, for identification and further training of these dogs and possibly the development of seizure-alerting devices.

Progressive Myoclonic Epilepsies.

The treatment of progressive myoclonus epilepsy (PME) remains a major therapeutic challenge in neurology. Generalized convulsive seizures are often well controlled through classic antiepileptic drugs (AEDs) like valproate and clonazepam, whereas myoclonus, the main symptom that is affecting patients most in their daily life, is usually refractory to standard AEDs. Alternative therapy concepts have been and still are investigated. Among the new drugs, zonisamide and piracetam have shown the most promising results as add-on treatments. Other therapeutic approaches, like the use of antioxidants, 5-hydroxytryptophan (5-HTP), and baclofen should also be taken into consideration for the treatment of intractable cases of PME. Nonpharmacologic treatment options such as diet and physical therapy should always be considered, because they may save costs and side effects. In some instances, the occasional use of alcohol has shown beneficial effects.