Faculty Bibliography

Consumer wearable devices are commonly used by patients and consumers for several reasons with increasing application as new technologies are developed. Use of these devices is an emerging issue in Neurology because of increased adoption and the additional data reported to providers by patients. Understanding of possible functions, limitations, and effect on patients of non-US Food and Drug Administration (FDA)-cleared wearable technology to inform neurologic care is needed. A common theme in people with neurologic conditions regarding consumer wearables and associated tracking applications is that there is significant promise in these tools, but adherence (days per use/per week), continued engagement (attrition), and unintended consequences such as heightened anxiety remain important issues. Further understanding and validation of these devices is needed within the field of Neurology before full use and confidence can be achieved. Below, we provide examples of non-FDA-cleared wearable devices used in Neurology in the areas of epilepsy, headache, cardiac monitoring, and sleep.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS. METHODS:nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome. RESULTS:= 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated. DISCUSSION/CONCLUSIONS:Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

PURPOSE OF REVIEW/UNASSIGNED:Alzheimer disease (AD) and epilepsy are major causes of neurologic disability and are reciprocally related: epileptiform discharges, subclinical seizures, and epilepsy are more prevalent in patients with AD compared with controls; progressive cognitive impairment commonly afflicts epilepsy patients; and late-onset epilepsy patients have higher rates of new-onset dementia. RECENT FINDINGS/UNASSIGNED:Epidemiologic studies support shared risk factors (e.g., genetic variants, vascular disease, sleep disorders, microbiome) with notable divergences. AD and epilepsy have some overlapping anatomic (e.g., hippocampus, entorhinal, and association cortex), clinical (e.g., memory, attentional, and executive) impairments, and neuropathologic (e.g., amyloid, tau, neurofibrillary tangles) features. Shared clinical and translational challenges include underlying mechanisms (e.g., genetic variants, neuroinflammation, metabolic and mitochondrial dysfunction, excitatory/inhibitory imbalance, microbiome, and sociodemographic factors) and identifying valid and reliable biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, Aβ42/Aβ40 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. SUMMARY/UNASSIGNED:Identifying convergences and divergences between epilepsy and AD may inform our understanding. The clinical, neurophysiologic, neuropathologic, and molecular pathologic changes in AD and epilepsy may reveal pathophysiologic insights and therapeutic opportunities.

Health equity research in neurology and neuroscience faces a unique challenge in the current United States climate of funding scarcity and prioritization of other research topics. The low funding contrasts with rising interest and scholarship in the field. Neuroscientists in the early phases of their career are particularly vulnerable to the detrimental effects of reduced funding due to their relatively lower publication history and established sources of support for projects. Here, we introduce the Early Career Network within the Society of Equity Neuroscience (SEQUINS). The group is dedicated to the support of early-career neurologists and neuroscientists who pursue health equity neuroscience research. We will accomplish this via a combination of virtual and in-person events as well as the establishment of a robust community of scientists. Together, we will foster camaraderie, solidarity, and shared interests to propel the field of health equity neuroscience forward.

OBJECTIVE:Cenobamate has been shown to be an effective antiseizure medication for some patients with drug-resistant focal epilepsy being considered for epilepsy surgery. This retrospective single-center study evaluated whether surgery was obtained within 12 months for patients who received cenobamate as a treatment during the presurgical evaluation and those who did not, comparing across years before and after cenobamate approval. METHODS:Patients undergoing surgical evaluation for drug-resistant focal epilepsy at the University of Colorado during 2018 and 2023 who had 12 months of follow-up data were analyzed. Comparison years were also chosen to avoid the confounding effect of the COVID-19 pandemic on surgical volume (2020-2021). This allowed for comparison times before and after cenobamate's US Food and Drug Administration approval. The primary outcome (surgery within 12 months) was modeled with potential explanatory variables using multiple logistic regression. A p-value of <.05 was considered significant. RESULTS:After controlling for potentially confounding clinical and demographic variables, cenobamate use during the presurgical evaluation period was associated with .13 lower odds of surgery within 12 months compared to not being prescribed this medication (95% confidence interval [CI] = .04-.42, p < .001). Being Hispanic or Latino was significantly associated with .23 lower odds of surgery within 12 months compared to patients who did not report being Hispanic or Latino (95% CI = .09-.61, p = .003). Year of evaluation (2023 vs. 2018), education level, age, and sex did not have significant associations with undergoing surgery within 12 months. SIGNIFICANCE/CONCLUSIONS:Patients with drug-resistant focal epilepsy undergoing evaluation for epilepsy surgery may benefit from cenobamate. In this study, patients who received cenobamate during the presurgical evaluation were less likely to undergo surgery within 12 months. The delay to surgery identified among Hispanic and Latino patients suggests potential barriers to care in this patient population warranting further investigation.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Carotid webs are an underrecognized cause of ischemic stroke in young adults and are associated with a high risk of recurrence when managed with medical therapy alone. Although carotid endarterectomy (CEA) is increasingly performed, histopathological confirmation remains infrequently reported, and the underlying pathological substrate of symptomatic carotid webs is not well defined. In this study, we present the largest pathologically confirmed series of symptomatic carotid webs treated with CEA, providing a comprehensive clinicopathological characterization and evaluation of long-term surgical outcomes. METHODS:Patients with symptomatic carotid webs were retrospectively identified from institutional databases encompassing both inpatient and outpatient encounters. Clinical features, imaging characteristics, surgical findings, and histopathological results from CEA specimens are presented. RESULTS:Among 39 patients with symptomatic carotid web, 34 underwent CEA with histopathological confirmation of the diagnosis, characterized by focal eccentric intimal fibromyxoid tissue, fibromuscular dysplasia, hyperplasia, or thickening. Notably, concurrent atheromatous changes were noted in 6 patients. All webs were located within 3 cm of the carotid bifurcation, and most (76%) were localized on the posterior wall. Competing stroke mechanisms were identified in 15% of patients. Two-thirds of patients presented with a large or medium vessel occlusion and over half received acute reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy). Two patients experienced transient, minor cranial nerves injuries (hypoglossal nerve and marginal mandibular branch) after CEA. At a median follow-up of 29 months, no patients experienced recurrent stroke (95% CI: 0%-10%), and the median modified Rankin Scale score was 1 (0-1). CONCLUSION/CONCLUSIONS:This study supports CEA as a safe and effective therapeutic option for patients with symptomatic carotid webs and demonstrates its diagnostic value through direct histopathological confirmation. By presenting the largest pathologically validated series to date, our findings further define the vascular pathology underlying carotid webs and underscore the diagnostic value of surgical resection for definitive diagnosis.

Over 50% of persons living with dementia (PLWD) and their care partners (dyads) visit the emergency department (ED) every year. In the ED, healthcare professionals face complex challenges managing acute issues and symptoms of Alzheimer's disease and Alzheimer's disease-related dementias without provider training or in-ED structures to ensure a successful discharge. While many of these visits are for conditions more suitable for ambulatory care, as many as 50% of PLWD discharged from the ED return within 30 days, suggesting opportunities to improve ED care, and discharge processes. Emergency Care Redesign (ECR) includes intentional workflows where physicians, nurses, and social workers engage in a team-based approach with structured assessments to manage a myriad of potential psychosocial and behavioral issues contributing to the need for ED care. Three core components comprise this evidence-based, efficient pragmatic intervention for PLWD and their care partners: (1) problem identification, (2) problem prioritization, and (3) provision of non-pharmacologic solutions supported by community resources. Although these components are essential to provide optimal ED care and reduce revisits and other adverse outcomes, they require an embedded clinical decision support structure, focused training, and clear workflows. In this paper, we describe the ECR intervention as one of three being implemented in the cluster-randomized multifactorial pragmatic trial, Emergency Departments LEading Transformation of Alzheimer's and Dementia Care (ED-LEAD), designed to improve care for PLWD and their outcomes after discharge home within 15 health systems and 79 EDs across the United States.

OBJECTIVES/OBJECTIVE:Temporal lobe epilepsy (TLE) impacts multiple brain networks. Aberrant functional connectivity has been demonstrated in resting-state networks (RSNs) that mediate higher brain functions in TLE. This study aimed to identify the reproducible patterns of altered functional connectivity in TLE in a large, international cohort through ENIGMA-Epilepsy. METHODS:Resting-state functional MRI datasets from nine centers across North America, South America, Europe and South Africa, including 442 people with TLE and 387 healthy adults, were analyzed. We examined group differences in whole-brain connectivity in patients compared to controls in seven major RSNs. We also investigated whole-brain connectivity maps for key nodes within the default mode network (DMN). Furthermore, the associations between connectivity patterns and clinical variables were assessed. RESULTS:We found lower within-network connectivity scores (13.6% on average) and higher between-network connectivity scores (129% on average) in non-limbic RSN in TLE. This pattern was reproducible across all seven sites and most robust for DMN and visual networks. Patterns of connectivity were not associated with age of seizure onset or disease duration and were mostly similar in patients with left and right TLE with a few exceptions; isolated regions of high connectivity in left TLE and lower connectivity in right TLE compared to controls. SIGNIFICANCE/CONCLUSIONS:We show strong evidence of lower connectivity within most RSNs and higher connectivity outside of these networks that was highly consistent across geographically diverse sites, demonstrating the robustness and generalizability of our findings. The findings demonstrate a consistent disruption of network organization in TLE that may underlie cognitive co-morbidities and seizure propagation patterns observed in this patient population. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:In this international ENIGMA-Epilepsy study, resting-state fMRI data from 442 individuals with TLE showed reduced connectivity within major resting-state networks (about 14% lower) and markedly increased connectivity between networks (about 129% higher), compared to 387 healthy controls. These patterns were highly reproducible across sites. Connectivity alterations were not related to age of onset or disease duration and were largely similar across left and right TLE, aside from small, region-specific differences. Overall, the study demonstrates a robust, widespread reorganization of brain network connectivity in TLE, which may help explain associated cognitive difficulties and seizure spread.

OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN/METHODS:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING/METHODS:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS/METHODS:A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS/RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.