Structural Neuroimaging in Adults and Adolescents With Newly Diagnosed Focal Epilepsy: The Human Epilepsy Project.

BACKGROUND AND OBJECTIVES: Identification of an epileptogenic lesion on structural neuroimaging in individuals with focal epilepsy is important for management and treatment planning. The objective of this study was to determine the frequency of MRI-identified potentially epileptogenic structural abnormalities in a large multicenter study of adolescent and adult patients with newly diagnosed focal epilepsy. METHODS: Patients with a new diagnosis of focal epilepsy enrolled in the Human Epilepsy Project observational cohort study underwent 3-Tesla (3T) brain MRI using a standardized protocol. Imaging findings were classified as normal, abnormal, or incidental. Abnormal findings were classified as focal or diffuse, and as likely epilepsy-related or of unknown relationship to epilepsy. Fisher exact tests were performed to determine whether abnormal imaging or abnormality type was associated with clinical characteristics. RESULTS: 418 participants were enrolled. 218 participants (59.3%) had no abnormalities detected, 149 (35.6%) had abnormal imaging, and 21 (5.0%) had incidental findings. 78 participants (18.7%) had abnormalities that were considered epilepsy-related and 71 (17.0%) had abnormalities of unknown relationship to epilepsy. Older participants were more likely to have imaging abnormalities, while participants with focal and epilepsy-related imaging abnormalities were younger than those without these abnormalities. 131 participants (31.3%) had a family history of epilepsy. Epilepsy-related abnormalities were not associated with participant sex, family history of epilepsy, or seizure type. DISCUSSION: We found that one in five patients with newly diagnosed focal epilepsy has an MRI finding that is likely causative and may alter treatment options. An additional one in five patients has abnormalities of unknown significance. This information is important for patient counseling, prognostication, and management.

Electrically stimulated auras as a potential biomarker of the epileptogenic zone.

Electrocortical stimulation mapping (ESM) is often performed in patients undergoing stereoelectroencephalography (SEEG) prior to epilepsy surgery, with the goal of identifying functional cortex and preserving it postoperatively. ESM may also evoke a patient's typical seizure semiology. The purpose of this study was to determine whether the sites at which typical auras are evoked during ESM are associated with other known clinical and electrophysiologic biomarkers of the epileptogenic zone: the seizure onset zone (SOZ), the early spread zone (ES), and high-frequency oscillations (HFOs). We found that the sites at which auras were provoked were not consistently associated with known biomarkers (p = 0.09). We conclude that evoked auras during ESM may reflect electrical spread rather than true epileptogenicity, and that a larger study is needed to assess their potential value as independent epileptic biomarkers.

Representation of women plenary speakers at the American Academy of Neurology Annual Meeting.

OBJECTIVE: To determine whether women have been equitably represented among plenary speakers at the American Academy of Neurology (AAN) Annual Meeting by counting and categorizing speakers and comparing outcomes to AAN membership and US neurology workforce data. METHODS: Lists of plenary speakers between 1958 and 2019 (62 years) were obtained from the AAN. The primary outcome measures were numbers and proportions of men and women in aggregate and among physicians. RESULTS: We identified 635 plenary speakers, including 148 (23.3%) women. Specifically, women made up 14.6% (19 of 130) of presidential and 25.5% (129 of 505) of nonpresidential plenary session speakers. The inclusion of women plenary speakers was meaningfully higher (h = 0.33; difference 14.9%; 95% confidence interval 4.2%-26.7%) for nonphysicians (27 of 74 [36.5%]) than physicians (121 of 561 [21.6%]). Although at zero levels for Annual Meetings held between 1958 and 1990 and at mostly low but varying levels thereafter, the representation of women and women physicians has been at or above their proportions in the AAN membership and US neurology workforce since 2017. Comparison of representation by plenary session name revealed an unequal distribution of women, with women physicians concentrated in the Sidney Carter Award in Child Neurology presidential session. CONCLUSION: Historically and recently, women and women physicians were underrepresented among AAN plenary speakers. As the AAN has taken active steps to address equity, women have been included in more representative proportions overall. However, notable gaps remain, especially in specific prestigious plenary sessions, and further research is needed to determine causality.

Spinal cord α-synuclein deposition associated with myoclonus in patients with MSA-C.

OBJECTIVE: To test the hypothesis that myoclonus in patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) is associated with a heavier burden of α-synuclein deposition in the motor regions of the spinal cord, we compared the degree of α-synuclein deposition in spinal cords of 3 patients with MSA-C with myoclonus and 3 without myoclonus. METHODS: All human tissue was obtained by the Massachusetts General Hospital Department of Pathology with support from and according to neuropathology guidelines of the Massachusetts Alzheimer's Disease Research Center. Tissue was stained with Luxol fast blue and hematoxylin & eosin for morphologic evaluation, and with a mouse monoclonal antibody to α-synuclein and Vectastain DAB kit. Images of the spinal cord sections were digitized using a 10× objective lens. Grayscale versions of these images were transferred to ImageJ software for quantitative analysis of 8 different regions of interest (ROIs) in the spinal cord: dorsal column, anterior white column, left and right dorsal horns, left and right anterior horns, and left and right lateral corticospinal tracts. A mixed-effect, multiple linear regression model was constructed to determine if patients with and without myoclonus had significantly different distributions of α-synuclein deposition across the various ROIs. RESULTS: Patients with myoclonus had more α-synuclein in the anterior horns (p < 0.001) and lateral corticospinal tracts (p = 0.02) than those without myoclonus. CONCLUSIONS: In MSA-C, myoclonus appears to be associated with a higher burden of α-synuclein deposition within spinal cord motor regions. Future studies with more patients will be needed to confirm these findings.

Antiepileptic Drug Management in Hospitalized Epilepsy Patients With Nil Per Os Diets: A Retrospective Review.

BACKGROUND AND PURPOSE: Antiepileptic drug (AED) management in patients with epilepsy who cannot take their usual oral medications is a common neurologic dilemma in the hospital setting. Strategies to maintain seizure control in patients with nil per os (NPO, nothing by mouth) diet orders include continuation of oral AEDs despite NPO nutrition orders, administration of intravenous AED(s), or temporary administration of benzodiazepines. The frequency with which these strategies are used and their effectiveness in preventing in-hospital seizures is unknown. METHODS: We conducted a retrospective cohort study to determine AED management strategies and seizure frequency in hospitalized epilepsy patients with NPO diet status admitted to an academic medical center between 2001 and 2016. Clinical documentation was reviewed. Antiepileptic drug selection (medication and route of administration) and presence or absence of seizures were recorded. RESULTS: We identified 199 admissions during which epilepsy patients had NPO diet orders. Antiepileptic drug management strategies included continuation of oral medications (50.3% of admissions), intravenous AED monotherapy (22.1%), intravenous AED polytherapy (12.6%), benzodiazepines (1.0%), holding AEDs (4.5%), or a combination (9.5%). Seizures occurred during 14 admissions. Treatment with AED polytherapy prior to admission and changing the patient's AED regimen during admission were associated with increased odds of seizures during admission (P = .0028; P = .0114). CONCLUSIONS: These results suggest that patients' home oral AED regimens should be continued when possible in order to minimize the frequency of seizures during hospitalizations.

Emergency Management of Epilepsy and Seizures.

Seizure- and epilepsy-related complications are a common cause of emergency medical evaluation, accounting for 5% of 911 calls and 1% of emergency department visits. Emergency physicians and neurologists must be able to recognize and treat seizure- and epilepsy-related emergencies. This review describes the emergency evaluation and management of new onset seizures, breakthrough seizures in patients with known epilepsy, status epilepticus, acute symptomatic seizures, and acute adverse effects of antiepileptic drugs.

Women physicians underrepresented in American Academy of Neurology recognition awards.

OBJECTIVE: To investigate representation by gender among recipients of physician recognition awards presented by the American Academy of Neurology (AAN). METHODS: We analyzed lists of individual recipients over the 63-year history of the AAN recognition awards. Included were awards intended primarily for physician recipients that recognized a body of work over the course of a career. The primary outcome measures were total numbers and proportions of men and women physician award recipients. RESULTS: During the period studied, the proportion of women increased from 18% (1996) to 31.5% (2016) among AAN US neurologist members and from 18.6% (1992) to 35% (2015) in academia, and the AAN presented 323 awards to physician recipients. Of these recipients, 264 (81.7%) were men and 59 (18.3%) were women. During the most recent 10-year period studied (2008-2017), the proportion of women increased from 24.7% (2008) to 31.5% (2016) among AAN US neurologist members and from 28% (2009) to 35% (2015) in academia, and the AAN presented 187 awards to physician recipients, comprising 146 men (78.1%) and 41 women (21.9%). Although it has been more than 2 decades since the proportion of women among US neurologist members of the AAN was lower than 18%, 1 in 4 AAN award categories demonstrated 0% to 18% representation of women among physician recipients during the most recent decade. Moreover, for highly prestigious awards, underrepresentation was more pronounced. CONCLUSION: Although the reasons why are not clear, women were often underrepresented among individual physician recognition award recipient lists, particularly for highly prestigious awards.

Where Are the Women? The Underrepresentation of Women Physicians Among Recognition Award Recipients From Medical Specialty Societies.

Membership in medical societies is associated with a number of benefits to members that may include professional education, opportunities to present research, scientific and/or leadership training, networking, and others. In this perspective article, the authors address the value that medical specialty society membership and inclusion have in the development of an academic physician's career and how underrepresentation of women may pose barriers to their career advancement. Because society membership itself is not likely sufficient to support the advancement of academic physicians, this report focuses on one key component of advancement that also can be used as a measure of inclusion in society activities-the representation of women physicians among recipients of recognition awards. Previous reports demonstrated underrepresentation of women physicians among recognition award recipients from 2 physical medicine and rehabilitation specialty organizations, including examples of zero or near-zero results. This report investigated whether zero or near-zero representation of women physicians among recognition award recipients from medical specialty societies extended beyond the field of physical medicine and rehabilitation. Examples of the underrepresentation of women physicians, as compared with their presence in the respective field, was found across a range of additional specialties, including dermatology, neurology, anesthesiology, orthopedic surgery, head and neck surgery, and plastic surgery. The authors propose a call for action across the entire spectrum of medical specialty societies to: (1) examine gender diversity and inclusion data through the lens of the organization's mission, values, and culture; (2) transparently report the results to members and other stakeholders including medical schools and academic medical centers; (3) investigate potential causes of less than proportionate representation of women; (4) implement strategies designed to improve inclusion; (5) track outcomes as a means to measure progress and inform future strategies; and (6) publish the results to engage community members in conversation about the equitable representation of women.

Placental passage of antiepileptic drugs at delivery and neonatal outcomes.

Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical-to-maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical-to-maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical-to-maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical-to-maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications.

What to do when patients with epilepsy cannot take their usual oral medications.

When people with epilepsy are hospitalised for medical or surgical conditions, they may be unable to take their home antiepileptic drugs (AEDs). Such 'nil by mouth' people with epilepsy require alternative AED regimens to prevent breakthrough seizures. Here, we describe several strategies for maintaining seizure control in patients with epilepsy who have medical or surgical contraindications to their home oral regimens. These strategies include using non-pill oral formulations, using an intravenous formulation of the patient's home AED(s), using a benzodiazepine bridge and/or using alternative intravenous AED(s) when there are no intravenous formulations.

Myeloradiculopathy associated with chikungunya virus infection.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.

Characteristics and clinical impact of stimulation-evoked seizures during extraoperative cortical mapping.

Extraoperative electrocortical stimulation mapping (ESM) is used to identify functional cortex prior to epilepsy surgery, with the goal of preserving function postoperatively. Although attempts are made to avoid stimulation-evoked seizure activity, the clinical impact of these events with regard to safety, clinical utility, functional outcome, and even disruption to the procedure itself is unknown. We conducted a retrospective review of 57 patients with pharmacoresistant focal epilepsy who underwent intracranial electrode implantation and ESM. Stimulation-evoked seizures (afterdischarges associated with clinical signs or symptoms) occurred in 19 patients (33%). Mapping sessions were disrupted for 11 of these patients (i.e., 19% of the full sample and 58% of the subgroup of patients with stimulation-evoked seizures). Patients who had ESM disruption were no less likely than patients without ESM disruption to be seizure-free at one year (p=0.63) and two years (p=0.57) postoperatively. Among 23 patients who underwent language assessment pre- and postoperatively, 4 (17%) had evoked seizures that disrupted language mapping; these patients were no more likely to show postoperative language declines relative to those who had no ESM disruption (p=0.26). Results suggest that evoked seizures occur frequently during ESM and can disrupt the procedure; however, these events do not appear to adversely affect postoperative outcomes. Nevertheless, attempts should be made to limit stimulation-evoked seizures in order to reduce patient discomfort, increase efficiency, and maximize the utility of ESM.

Maternal Depression and Family Media Use: A Questionnaire and Diary Analysis.

We describe the association between postpartum depression and the quantity and content of infant media use. Households with depressed mothers viewed twice as much television as households with non-depressed mothers did, and depressed mothers appeared to derive comparatively greater pleasure from television viewing. Maternal depression was associated with an increased exposure to child-directed content by 6-9-month-old infants, although it was not associated with an increased exposure to adult-directed programming. Depressed mothers also reported being less likely to sit and talk with their children during television use or to consult outside sources of information about media. This increase in television exposure without corresponding parental involvement could negatively affect developmental outcomes.

Glioblastoma biomarkers from bench to bedside: advances and challenges.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.