Retrospective analysis of safety and outcomes of rituximab for myasthenia gravis in patients ≥65 years old.

INTRODUCTION/AIMS: Optimal management of myasthenia gravis (MG) in individuals ≥65 y old is unknown and patient factors may limit therapeutic choices. Safety and efficacy of rituximab in older patients with MG has not been well-studied. METHODS: This retrospective study examined 40 patients (14 patients ≥65 y old) treated with rituximab for MG. The primary efficacy outcome was the proportion of patients reaching "Improved" or better on Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) at 12 mo, compared between younger and older patients. RESULTS: Ninety-two percent of patients ≥65 y old achieved MGFA PIS Improved or better at 12 mo compared to 69% of those <65 y old (P = .11). Median prednisone dose for the cohort decreased in the year following rituximab initiation (20 mg [interquartile range, 10-35] to 10 mg [0-13], P = .01). Non-refractory MG was predictive of favorable outcome, whereas age was not. Serious adverse events (SAEs) were similar between older and younger patients (21.4% vs. 30.8%, P = .715). No patients ≥65 y old required discontinuation of rituximab due to SAE. One death occurred in a patient <65 y old due to systemic inflammatory response syndrome. DISCUSSION: At 12 mo following initiation of rituximab for MG, patients ≥65 y old experienced similarly high rates of improvement in their myasthenic symptoms as younger patients, without an increased risk of experiencing SAEs. Rituximab should be considered in the treatment paradigm in older patients and in non-refractory MG patients of any age.

Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses.

Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

Integrating Virtual Teaching in a New Era of Medical Education: Lessons from a Neurology Course.

The COVID-19 pandemic has led to a sudden shift toward virtual learning in neurology education, which presents challenges for educators. However, virtual learning is here to stay for three key reasons: demand among students, ease of dissemination, and potential to improve educational quality. Despite challenges, educators can teach effectively using appropriate virtual tools and methods, with innovative approaches that will ultimately lead to sustained improvements in neurology education. Here, we aim to help educators effectively incorporate virtual instruction into their "new normal" by offering practical, evidence-based tips for balancing in-person and virtual learning, selecting the appropriate tools and methods for virtual teaching, and creating a supportive virtual learning environment. Using a systematic approach, educators can identify specific, achievable goals, determine the content's scope, appropriate assessments, select appropriate teaching methods, and create the session schedule and materials. Here we described evidence-based strategies for best practices, developing virtual material, and creating the appropriate virtual learning environment.

Curriculum Innovations: Improving Residents' Knowledge and Interest in Outpatient Neurology Through an Interactive Patient-Centered Didactic Series.

Introduction and Problem Statement: Neurology residency training is inpatient focused, underemphasizing outpatient disorders. We implemented a novel didactic series of facilitated discussions between a patient and their outpatient neurologist to expose residents to outpatient topics and management skills. Objectives: (1) Improve residents' understanding of the roles and responsibilities of the neurologist in the outpatient setting; (2) share with residents the patient's perspective of living with chronic neurologic disease; and (3) improve residents' understanding of what effective shared decision making entails. Methods and Curriculum Description: Residents in an academic neurology program participated. Six bimonthly, 1-hour sessions were piloted in person in 2016; participants were surveyed after each session to refine the format. The formal program (6 sessions) was held virtually in 2020-2021. Each session focused on 1 disorder. The format was conversational and moderated by a course director. Discussion points were preplanned and focused on patients' experiences living with chronic neurologic disease and shared decision making. Residents, participating faculty, and patients were surveyed at the conclusion of the 2020-2021 series to evaluate its effectiveness. Results and Assessment Data: Fifty-five survey responses were completed by residents during the pilot. Only 12 residents (22%) indicated that they longitudinally followed more than 1 patient with the condition represented in the session. Qualitative comments from residents and faculty (n = 5) identified that hearing the patient perspective was the most valuable component of the series. Twenty-one of 54 residents evaluated the final program. A majority of residents, 100% of faculty (n = 6), and 100% of patients (n = 6) felt that the program's 3 learning objectives were met. Forty-eight percent of residents reported increased interest in outpatient careers. Faculty agreed that the session format was as effective as traditional lecture, without added preparation burden. Patients felt that sharing their experiences would help physicians better understand their illness and improve care for future patients; all would participate again. Discussion and Lessons Learned: Our series effectively educated residents about underrepresented outpatient topics. Hearing patients' perspectives was instrumental in achieving our learning objectives. Key factors for successful implementation included a faculty moderator, preplanned questions, and teaching slides to emphasize key learning points. Future work should evaluate whether residents' increased knowledge and interest translates into sustained behavior change and more residents selecting outpatient careers.

Integrating Advanced Practice Providers in an Academic Department of Neurology.

BACKGROUND AND OBJECTIVES: Integrating advanced practice providers (APPs) into neurologic practice can improve access, promote patient education, and reduce health care costs. APPs receive limited formal education in neurology, so on-the-job training is essential. We set out to identify common challenges and best practices for onboarding, training, and integrating APPs into neurologic practice. METHODS: We conducted a survey and focus group with 8 APPs currently practicing within an academic neurology department as part of a clinical quality improvement initiative. We explored their roles in multidisciplinary teams, challenges faced during onboarding and training, and strategies for success. Qualitative thematic analysis was performed. RESULTS: Neurology APPs serve diverse roles including caring for hospitalized and ambulatory patients, performing procedures, assisting trainees, and performing research. Participants reported limited formal neurologic education before their job and a need for educational sessions and resources tailored to APPs. Neuroanatomy, neuroimaging, and generating a neurologic differential diagnosis were key knowledge gaps identified. We identified 7 informal strategies for on-the-job training, 7 challenges to on-the-job training, and factors promoting or threatening job satisfaction. Graded responsibility and clinical mentorship were essential for successful onboarding. APPs desired peer-to-peer mentorship and structured educational opportunities. DISCUSSION: Common challenges and success strategies identified can inform the design of a formal curriculum for onboarding neurology APPs. Our findings suggest that an optimal APP training process involves graded responsibility and support for self-directed learning, employs peer mentors, and targets education of the multidisciplinary team including physicians and patients. Our results may inform other institutions recruiting, hiring, and training APPs.

Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors.

Expanding the US Food and Drug Administration-approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%-12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.

Entrapment Neuropathies of the Upper Extremity.

Upper extremity entrapment neuropathies are common and can cause pain, sensory loss, and muscle weakness that lead to functional disability. In this article, the authors review common entrapment neuropathies of the upper extremities, including median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, and radial neuropathy. The authors discuss the pathophysiology of nerve compression and typical etiologies, as well as strategies for differentiating between common mimics such as cervical radiculopathy and for selecting between various treatment modalities.

Entrapment Neuropathies of the Lower Extremity.

Entrapment neuropathies in the lower limbs are a common neurologic problem and may present in any medical setting. Accurate identification and management of these nerve palsies can prevent pain, sensory loss, incoordination, and muscle weakness that may significantly affect a patient's functional mobility. In this article, the authors focus on the cause, signs and symptoms, diagnosis, and treatment of select entrapment neuropathies of the lower extremity, including palsies of the common peroneal, lateral femoral cutaneous, femoral, and posterior tibial nerves.

Toxic Myopathies.

PURPOSE OF REVIEW: This article reviews the pathogenesis, clinical features, and management of toxic myopathy related to common medications, critical illness, and illicit substances. RECENT FINDINGS: Muscle symptoms are common among statin users and are usually reversible after discontinuation of the statin; rarely, however, statins trigger an immune-mediated necrotizing myopathy that persists and requires immunomodulatory therapy. Autoantibodies targeting 3-hydroxy-3-methylglutaryl coenzyme A reductase can distinguish the toxic and immune-mediated forms. Immune checkpoint inhibitors, increasingly used in the treatment of advanced cancer, have recently been associated with the development of inflammatory myositis. A reversible mitochondrial myopathy has long been associated with zidovudine, but recent reports elucidate the risk of myopathy with newer antivirals, such as telbivudine and raltegravir. SUMMARY: The medications most commonly associated with myopathy include statins, amiodarone, chloroquine, hydroxychloroquine, colchicine, certain antivirals, and corticosteroids, and myopathy can occur with chronic alcoholism. Certain clinical, electrodiagnostic, and histologic features can aid in early recognition. Stopping the use of the offending agent reverses symptoms in most cases, but specific and timely treatment may be required in cases related to agents that trigger immune-mediated muscle injury.

Approach to Peripheral Neuropathy for the Primary Care Clinician.

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy.

Autoimmune Myopathies: Updates on Evaluation and Treatment.

The major forms of autoimmune myopathies include dermatomyositis (DM), polymyositis (PM), myositis associated with antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). While each of these conditions has unique clinical and histopathological features, they all share an immune-mediated component. These conditions can occur in isolation or can be associated with systemic malignancies or connective tissue disorders (overlap syndromes). As more has been learned about these conditions, it has become clear that traditional classification schemes do not adequately group patients according to shared clinical features and prognosis. Newer classifications are now utilizing myositis-specific autoantibodies which correlate with clinical and histopathological phenotypes and risk of malignancy, and help in offering prognostic information with regard to treatment response. Based on observational data and expert opinion, corticosteroids are considered first-line therapy for DM, PM, ASS, and IMNM, although intravenous immunoglobulin (IVIG) is increasingly being used as initial therapy in IMNM related to statin use. Second-line agents are often required, but further prospective investigation is required regarding the optimal choice and timing of these agents.

Screening for major depression in post-myocardial infarction patients: operating characteristics of the Beck Depression Inventory-II.

OBJECTIVE: To assess the operating characteristics of the Beck-Depression Inventory-II (BDI-II) and the BDI-II cognitive subscale (BDI-II-cog) in screening for major depression (MDD) in post-myocardial infarction (MI) patients. METHODS: Between October 2003 and July 2005, 131 post-MI patients admitted to an urban academic medical center completed the BDI-II and a semi-structured interview for depression within 72 hours of symptom onset. Sensitivity, specificity, positive and negative predictive values, overall correct classification, and likelihood ratios for various cutoff values on both scales were evaluated by comparing scores to interview diagnosis of MDD. Receiver-operator curves (ROC) were also calculated and area under the curve (AUC) measured. RESULTS: The optimal cutoff value for the BDI-II was > or = 16, with a sensitivity of 88.2% and a specificity of 92.1%. Cutoff values of > or = 3 or > or = 4 were both acceptable for the BDI-II-cog (sensitivity = 88.2% and 82.4%, respectively; specificity = 81.6% and 88.6 %, respectively). AUC was 0.96 for the BDI-II and 0.89 for the cognitive subscale. CONCLUSIONS: Effective depression screening is important in post-MI patients because of depression's independent association with morbidity and mortality following MI. Our results suggest that the BDI-II and its cognitive subscale are effective tools for screening for MDD in post-MI patients.