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.
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.
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information ...processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for
studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, H
O
) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method requires a rather cumbersome process with prereactors and relies on externally applied reagents. Here, we report the design and implementation of a GABA microarray probe that operates on a newly conceived principle. It consists of two microbiosensors, one for glutamate (Glu) and one for GABA detection, modified with glutamate oxidase and GABASE enzymes, respectively. By simultaneously measuring and subtracting the H
O
oxidation currents generated from these microbiosensors, GABA and Glu can be detected continuously in real-time
and
and without the addition of any externally applied reagents. The detection of GABA by this probe is based upon the
generation of α-ketoglutarate from the Glu oxidation that takes place at the Glu microbiosensor. A GABA sensitivity of 36 ± 2.5 pA μM
cm
, which is 26-fold higher than reported in the literature, and a limit of detection of 2 ± 0.12 μM were achieved in an
setting. The GABA probe was successfully tested in an adult rat brain slice preparation. These results demonstrate that the developed GABA probe constitutes a novel and powerful neuroscientific tool that could be employed in the future for
longitudinal studies of the combined role of GABA and Glu (a major excitatory neurotransmitter) signaling in brain disorders, such as epilepsy and traumatic brain injury, as well as in preclinical trials of potential therapeutic agents for the treatment of these disorders.
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. Plain Language Summary: This paper reviews how the COVID-19 pandemic has made it necessary for medical educators to switch to virtual learning for neurology courses. Even though it presents challenges, virtual learning is important because students want it, it's easy to disseminate, and it can improve the quality of education. Educators can learn how to use virtual tools and methods effectively by being innovative and making sustained improvements in neurology education. This paper offers practical tips based on evidence to help educators balance in-person and virtual learning, select appropriate tools and methods, and create a supportive virtual learning environment. By taking a systematic approach, educators can set achievable goals, decide what to teach, pick the best ways to teach it, and create a schedule and materials for the course. Keywords: virtual learning, Learning Enviornment, Synchronous Learning, Asynchronous Learning, Curriculum
Background Onsite standard care and remote telecare supports were provided to adults with intellectual disabilities living in integrated community settings and evaluated in terms of effectiveness as ...consumers completed a series of novel household activities.
Methods Using an alternating treatment design with baseline and follow‐up conditions in this single‐case study, investigators compared the prompting effectiveness provided by onsite standard care staff and a remote telecare provider.
Results While both types of supports resulted in consumers completing tasks, results indicated consumers achieved slightly more independence when prompted by the telecare support provider. Additionally, telecare supports resulted in greater duration for task completion per consumer.
Conclusions Although consumers completed tasks with greater independence using telecare supports, caution should be used when interpreting results due to the small number of participants. The potential for this technology certainly exists in supporting consumers in their own homes thus, suggestions for future investigations are provided.
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.
A 30-year-old woman was evaluated because of back pain, leg stiffness, and falling. Tone was increased in the legs. Exaggeration of the normal lumbar lordosis was seen on MRI.
A diagnosis was made.
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.
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.
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