Faculty Bibliography

OBJECTIVE:This study examines the American Headache Society First Contact-Headache in Primary Care program metrics to date in order to assess the program's reach and provide direction for future initiatives. BACKGROUND:Approximately 4 million primary care office visits annually are headache-specific encounters. Therefore, it is important that primary care providers are knowledgeable about headache management. Recognizing the need, the American Headache Society First Contact designed the comprehensive First Contact-Headache in Primary Care program with input from an advisory board comprised of a diverse group of physicians and advanced practice providers with backgrounds in family and internal medicine, pediatrics, obstetrics and gynecology, and neurology. This is the first study to assess the reach of the program and critically examine how to best meet the needs of clinicians and patients going forward. METHODS:We report descriptive statistics for the First Contact website metrics from October 2020 to June 2023 and grand rounds program data from May 2020 to December 2023. We also conducted a cross-sectional analysis of survey data from presentations conducted at two large national family medicine symposia, as well as a thematic analysis of the question: "Please indicate what areas of your practice could be enhanced or improved with additional education?" RESULTS:The First Contact program homepage was the second most visited page on the American Headache Society website (>100,000 views). A total of 20 podcast episodes were created for the program (>3500 plays). The First Contact program held 99 events (72 institutional grand rounds, 22 State-level meetings, and five national meetings), reaching >7000 clinicians. The institutional grand rounds and state-level meetings were held across 27 States and Washington D.C. Only 31.9% (30/94) of First Contact program events (excluding national meetings) occurred in the West census region, which has the fewest headache subspecialists and lowest headache subspecialist density in the United States. When examining survey data of participants who attended the two virtual national family medicine symposia (39.3% response rate, N = 636/1620), 85.7% (544/635) reported being "completely confident" or "very confident" in their ability to recognize and accurately diagnose patients presenting with a primary complaint of headache and 81.5% (517/634) reported being "completely confident" or "very confident" in their ability to develop evidence-based treatment plans that are tailored to the needs of individual patients. The use of diagnostic tools to recognize patients with migraine (60.4%, 384/636) and translating standards of care to the practice setting (42.5%, 270/636) were the most reported intended changes by participants. Most participants reported that program content was of clinical relevance and would improve their patients' outcomes (90.5% [571/631] and 90.6% [572/631], respectively). Over three-quarters (77.8%, 495/636) of participants reported areas of their practice that can be improved by additional education specifically regarding workflow, diagnosis, and management. CONCLUSION/CONCLUSIONS:This study evaluates one of the first national initiatives for primary care education. Data from the two First Contact Family Medicine national symposia indicate the program is generally well received with most participants reporting improved confidence and intention to implement key changes in practice to improve care for patients with headache; however, there remain areas of exploration for education that could further enhance participant experience and expand the reach of the initiatives. Areas for future programming include continued education on multifactorial approaches to headache treatment and suggestions for addressing cost, insurance, and time constraints. Also, future work may examine where the First Contact program might focus initiatives based on specific areas of need in headache care, such as geographic "desert" areas, racial and ethnic disparities, and uninsured/underinsured populations.

OBJECTIVE:Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate. METHODS:Using individual-level data from 20 focal-onset seizure trials provided by seven pharmaceutical companies, we evaluated associations with change in seizure frequency in participants randomized to placebo. We used multivariable logistic regression to evaluate participant and study factors associated with differing rates of 50% reduction in seizure frequency during blinded placebo treatment, as compared to pre-randomization baseline seizure frequency. In addition, we focused on the association of placebo responder rate with pre-randomization baseline seizure frequency and country of recruitment. RESULTS:). In addition, there was a significantly higher 50RR in participants with a baseline seizure frequency of six or fewer seizures per 28 days (29% vs 21%, p = .00018). SIGNIFICANCE/CONCLUSIONS:These results can assist future RCTs in estimating the expected placebo responder rate, which may lead to more reliable power estimates. Higher placebo responder rate was associated with markers of less-refractory epilepsy. There were concerning significant differences in placebo responder rate by country and geographic region as well as an elevated placebo responder rate in participants with baseline seizure frequency close to the minimum eligibility criteria.

OBJECTIVE:To examine the efficacy and safety of sodium oxybate versus placebo in a phase IIb randomized double-blind placebo-controlled 2-period cross-over clinical trial in patients with isolated laryngeal dystonia (LD). METHODS:The study was conducted from January 2018 to December 2021, pausing during the COVID-19 pandemic, at Massachusetts Eye and Ear in 106 patients with alcohol-responsive (EtOH+) and alcohol-non-responsive (EtOH-) LD (53 to receive 1.5g of sodium oxybate first, 53 to receive matching placebo first). The primary outcome was a change from baseline in LD symptom severity 40 minutes after drug intake. Safety was based on vital signs, cognitive function, suicidality, daytime sleepiness, and adverse events. Patients, investigators, and outcome assessors were masked to study procedures. RESULTS:Compared to baseline, EtOH+ but not EtOH- patients had a statistically significant improvement in LD symptoms following sodium oxybate versus placebo (EtOH+: 98.75% confidence interval [CI] = 0.6-26.9; p = 0.008; EtOH-: 98.75% CI = -6.2 to 18.7; p = 0.42). Statistically significant minimum drug efficacy in EtOH+ patients was found at ≥16% symptom improvement (OR = 2.09; 98.75% CI = 0.75-5.80; p = 0.036), with an average of 40.81% benefits (98.75% CI = 34.7-48.6). Drug efficacy waned by 300 minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Common adverse events included mild dizziness, nausea, and daytime sleepiness. INTERPRETATION/CONCLUSIONS:Sodium oxybate showed clinically meaningful improvement of symptoms in EtOH+ LD patients, with acceptable tolerability. Sodium oxybate offers the first pathophysiologically relevant oral treatment for laryngeal dystonia. ANN NEUROL 2024.

Paired vagus nerve stimulation (VNS) has emerged as a promising strategy to potentiate recovery after neurological injury. This approach, which combines short bursts of electrical stimulation of the vagus nerve with rehabilitation exercises, received approval from the US Food and Drug Aministration in 2021 as the first neuromodulation-based therapy for chronic stroke. Because this treatment is increasingly implemented in clinical practice, there is a need to take stock of what we know about this approach and what we have yet to learn. Here, we provide a survey on the foundational basis of VNS therapy for stroke and offer insight into the mechanisms that underlie potentiated recovery, focusing on the principles of neuromodulatory reinforcement. We discuss the current state of observations regarding synaptic reorganization in motor networks that are enhanced by VNS, and we propose other prospective loci of neuromodulation that should be evaluated in the future. Finally, we highlight the future opportunities and challenges to be faced as this approach is increasingly translated to clinical use. Collectively, a clearer understanding of the mechanistic basis of VNS therapy may reveal ways to maximize its benefits.

BACKGROUND:There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH). METHODS:We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation methodology to generate recommendations. RESULTS:The initial literature search yielded 1,988 articles, and 15 formed the basis of the recommendations. PICO 1: although there was no significant impact of ASM on the outcomes of early or late seizure or mortality, meta-analyses demonstrated increased adverse events and higher relative risk of poor functional outcomes at 90 days with prophylactic ASM use. PICO 2: we did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or adverse events, although point estimates tended to favor LEV. PICO 3: based on one decision analysis, quality-adjusted life-years were increased with a shorter duration of ASM prophylaxis. CONCLUSIONS:We suggest avoidance of prophylactic ASM in hospitalized adult patients with acute nontraumatic ICH (weak recommendation, very low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days; weak recommendation, very low quality of evidence).

BACKGROUND:Underlying intracranial stenosis is the most common cause of failed mechanical thrombectomy in acute ischemic stroke patients with large vessel occlusion. Adjunct emergent stenting is sometimes performed to improve or maintain reperfusion, despite limited data regarding its safety or efficacy. METHODS:We conducted a prospective multicenter observational international cohort study. Patients were enrolled between January 2022 and December 2023 at 25 thrombectomy capable centers in North America, Europe, and Asia. Consecutive patients treated with mechanical thrombectomy were included if they were identified as having underlying intracranial stenosis, defined as 50-99% residual stenosis of the target vessel or intra-procedural re-occlusion. The primary outcome was functional independence, defined as modified Rankin Scale of 0-2 at 90 days. After applying inverse probability of treatment weighting (IPTW) based on propensity scores, we compared outcomes among patients who underwent adjunct emergent intracranial stenting (stenting) versus those who received mechanical thrombectomy alone. RESULTS:A total of 417 patients were included; 218 patients treated with mechanical thrombectomy alone (168 anterior circulation) and 199 with mechanical thrombectomy plus stenting (144 anterior circulation). Patients in the stenting group were less likely to be non-Hispanic White (51.8% vs 62.4%, p=0.03), and less likely to have diabetes (33.2% vs 43.1%, p=0.037) or hyperlipidemia (43.2% vs 56%, p= 0.009). In addition, there was a lower rate of IV thrombolysis use in the stenting group (18.6% vs 27.5%, p=0.03). There was a higher rate of successful reperfusion (modified Treatment In Cerebral Infarction score ≥ 2B) in the stenting versus mechanical thrombectomy alone group (90.9% vs 77.9%, p<0.001) and a higher rate of a 24-hour infarct volume of <30 mL (n=260, 67.9% vs 50.3%, p=0.005). The overall complication rate was higher in the stenting group (12.6% vs 5%, p=0.006), but there was not a significant difference in the rate of symptomatic hemorrhage (9% vs 5.5%, p=0.162). Functional independence at 90 days was significantly higher in the stenting group (42.2% vs. 28.4%, adjusted odds ratio 2.67; 95% CI, 1.66-4.32). CONCLUSIONS:In patients with underlying stenosis who achieved reperfusion with mechanical thrombectomy, adjunct emergent stenting was associated with better functional outcome without a significantly increased risk of symptomatic hemorrhage. REGISTRATION/BACKGROUND:https://clinicaltrials.gov/study/NCT05403593.