Anna M. Bank

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 tumours 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.

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 physicians 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 organizations 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.

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.

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.

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 patients home AED(s), using a benzodiazepine bridge and/or using alternative intravenous AED(s) when there are no intravenous formulations.

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.

Sudden unexpected death in epilepsy in a patient with a cardiac pacemaker

PURPOSE Epilepsy is a common neurologic disorder requiring continued treatment during pregnancy. Treatment with antiepileptic drugs (AEDs) is needed for seizure control, but the risk of adverse events has to be minimized for both mother and foetus. Available data on pregnancy and foetal/postnatal outcomes following eslicarbazepine acetate (ESL) exposure via parent is herein presented for the first time. METHODS ESLs global safety database was reviewed to identify pregnancy cases with exposure to ESL reported up to October 21st, 2017. The EMBASE™ and MEDLINE® databases were searched to identify literature reports of such cases published between May 1st, 2009 and October 21st, 2017. RESULTS Overall, 91 notifications of pregnancy were identified, of which 79 involved ESL exposure: 28 during clinical trials and 51 from 8-years of post-marketing surveillance. Thirty pregnancies resulted in live birth without congenital anomalies; in 25 pregnancies the outcome was ongoing and 3 was unknown; 18 cases resulted in abortion (10 spontaneous and 8 induced) and congenital anomalies were identified in 5 cases (no clear relationship with ESL was established). ESL was used concomitantly to other AEDs in 11 of the 15 pregnancies for which the outcome was spontaneous abortion and congenital anomaly. Literature review did not yield additional information. CONCLUSIONS Available data are insufficient to draw conclusions regarding ESL use during pregnancy. Although no particular safety problem was identified, ESL exposure during pregnancy will continue to be monitored and evaluated.

Winged Scapula Secondary to Neuroborreliosis

A 76-year-old woman presented to the hospital with 10 days of back pain, right deltoid weakness, and a circular rash. Examination showed a right pronator drift and weakness of right shoulder abduction and elbow extension. Diffuse leptomeningeal and lumbar root enhancement was seen on magnetic resonance imaging of the spine (Figure 1). Cerebrospinal fluid (CSF) studies showed 440 white blood cells (87% lymphocytes) and 137 mg/dL protein. Borrelia burgdorferi testing showed positive serum immunoglobulin G (IgG) and negative CSF polymerase chain reaction (PCR). Testing for herpes simplex virus, eastern equine encephalomyelitis, West Nile virus (WNV), enterovirus, varicella zoster virus, and cytology was negative. She was presumptively treated for neuroborreliosis with intravenous ceftriaxone for 4 weeks. Magnetic resonance imaging 1 month later showed near resolution of enhancement (Figure 1). Frozen pretreatment CSF samples were reanalyzed for antibodies to Borrelia burgdorferi using antibody capture enzyme immunoassay (EIA), demonstrating CSF:serum ratio of IgM 1⁄4 2.2, IgG > 42, and IgA 1⁄4 19.4 (normal range < 1). Examination showed medial winging of the right scapula on arm flexion (Figure 2), most likely due to unilateral long thoracic nerve palsy from Borrelia burgdorferi. Only 3 such cases have been reported in Europe. To our knowledge, this is the first case of Borrelia burgdorferi long thoracic nerve palsy to be reported in North America, illustrating that neuroborreliosis is an important diagnostic consideration in patients with peripheral nerve palsies in endemic areas and the superior sensitivity of EIA over PCR in its diagnosis. Informed consent was obtained from the patient for this publication.

Opinion and Special Articles: Creation of a diversity and inclusion certificate program for neurology residents

Neurologists must provide excellent care to an increasingly diverse patient population. According to census projections, the United States will become a majority–minority nation by 2060, with no single ethnic or racial group making up a majority of the population.1 Diversity of gender, sex, sexual orientation, race, ethnicity, socioeconomic status, age, ability, and religion must be acknowledged and understood in order to provide equitable patient care.

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.