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Background and Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown., Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019. Our study included hospitalized adults at least 18 years of age diagnosed with MG without an associated thymoma. We used joinpoint regression to analyze annual trends in thymectomy volume and surgical approach (minimally invasive vs trans-sternal) from 2012 to 2019. Using logistic regression models, we examined patient and hospital-level factors that may have influenced whether thymectomy was performed, such as age, sex, race, insurance payor, hospital size and teaching status, and Elixhauser Comorbidity Index. Sampling weights were applied to account for the complex survey design of NIS., Results: The total number of thymectomy procedures increased by 69.8% per year (95% CI 40.1-105.8) between 2012 and 2019. Trans-sternal thymectomies increased by 62.8% per year (95% CI 35.8-95.2) and minimally invasive thymectomies by 83.7% per year (95% CI 38.1-144.3). Thymectomies were significantly more likely to occur in 2017-2019 compared with 2012-2016 (OR 1.93, 95% CI 1.62-2.31). In a multivariable regression model, several factors decreased the odds of patients with MG having a thymectomy: older age, Black race (OR 0.62, 95% CI 0.49-0.77), female (OR 0.73, 95% CI 0.63-0.86), and higher Elixhauser Comorbidity Index. Patients in medium (OR 1.82, 95% CI 1.30-2.55) or large (OR 2.81, 95% CI 2.07-3.82) size and urban teaching hospitals (OR 6.09, 95% CI 2.65-13.97) were more likely to undergo thymectomy., Discussion: Thymectomy is being performed more frequently for non-thymomatous MG, especially after 2016 after publication of a positive phase III clinical trial. There are several disparities in thymectomy utilization that warrant further attention., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Immune checkpoint inhibitors have revolutionized cancer therapy and are increasingly used to treat a wide range of oncological conditions, with dramatic benefits for many patients. Unfortunately, the resulting increase in T cell effector function often results in immune-related adverse events (irAEs), which can involve any organ system, including the central nervous system (CNS) and peripheral nervous system (PNS). Neurological irAEs involve the PNS in two-thirds of affected patients. Muscle involvement (immune-related myopathy) is the most common PNS irAE and can be associated with neuromuscular junction involvement. Immune-related peripheral neuropathy most commonly takes the form of polyradiculoneuropathy or cranial neuropathies. Immune-related myopathy (with or without neuromuscular junction involvement) often occurs along with immune-related myocarditis, and this overlap syndrome is associated with substantially increased mortality. This Review focuses on PNS adverse events associated with immune checkpoint inhibition. Underlying pathophysiological mechanisms are discussed, including antigen homology between self and tumour, epitope spreading and activation of pre-existing autoreactive T cells. An overview of current approaches to clinical management is provided, including cytokine-directed therapies that aim to decouple anticancer immunity from autoimmunity and emerging treatments for patients with severe (life-threatening) presentations., (© 2024. Springer Nature Limited.)

Background: Advances in video image analysis and artificial intelligence provide the opportunity to transform the approach to patient evaluation through objective digital evaluation., Objectives: We assessed ability to quantitate Zoom video recordings of a standardized neurological examination the myasthenia gravis core examination (MG-CE), which had been designed for telemedicine evaluations., Methods: We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis undergoing the MG-CE. Computer vision in combination with artificial intelligence methods were used to build algorithms to analyze videos with a focus on eye or body motions. For the assessment of examinations involving vocalization, signal processing methods were developed, including natural language processing. A series of algorithms were built that could automatically compute the metrics of the MG-CE., Results: Fifty-one patients with MG with videos recorded twice on separate days and 15 control subjects were assessed once. We were successful in quantitating lid, eye, and arm positions and as well as well as develop respiratory metrics using breath counts. Cheek puff exercise was found to be of limited value for quantitation. Technical limitations included variations in illumination, bandwidth, and recording being done on the examiner side, not the patient., Conclusions: Several aspects of the MG-CE can be quantitated to produce continuous measures via standard Zoom video recordings. Further development of the technology offer the ability for trained, non-physician, health care providers to perform precise examination of patients with MG outside the clinic, including for clinical trials., Plain Language Summary: Advances in video image analysis and artificial intelligence provide the opportunity to transform the approach to patient evaluation. Here, we asked whether video recordings of the typical telemedicine examination for the patient with myasthenia gravis be used to quantitate examination findings? Despite recordings not made for purpose, we were able to develop and apply computer vision and artificial intelligence to Zoom recorded videos to successfully quantitate eye muscle, facial muscle, and limb fatigue. The analysis also pointed out limitations of human assessments of bulbar and respiratory assessments. The neuromuscular examination can be enhanced by advance technologies, which have the promise to improve clinical trial outcome measures as well as standard care.

Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets., Competing Interests: Declaration of interests AF, MVG, BJ, and JH are supported by the Fondation pour la recherche médicale (DQ20170336751) BETPSY project as part of the second Investissements d’Avenir programme (18-RHUS-0012), supported by a public grant overseen by the Agence Nationale de la Recherche. AF received a grant to perform research abroad by the European Academy of Neurology. ACG received grants or contracts from Project Data Sphere (neurologic immune related adverse events research funding), Biosensics (wearable sensor and digital technologies for quantitative assessment and remote monitoring of symptoms in myasthenia gravis grant), and National Institutes of Health (1R44NS122672–01A1, 5U54NS115054–03 MGFA) high impact pilot grant. AG received honoria and support to travel for itox retreat MD Anderson in 2022, Houston Methodist MGFA conference, and Grand Rounds (Umass, Cornell, Duke). AG participated on Data Safety Advisory Boards with Alexion, Argenx, and UCB pharma and Data Safety and Monitoring Board for Remote Monitoring and Management of Chemotherapy Induced Peripheral Neuropathy (REMOTE CIPN; NCT04763356). AG is chair of the Medical and Scientific Advisory Board (MGFA of New England). AV received a grant to perform research abroad by the European Academy of Neurology. AZ received grant for research by Roche and Genentech. AZ has a patent submitted on anti-DACH1 and anti-PDE10A as biomarkers of paraneoplastic autoimmunity. AZ received consulting fees (no personal remuneration) from Alexion Pharmaceuticals. JH receives royalties from licensing fees to Athena Diagnostics, Euroimmun, and ravo Diagnostika for a patent for the use of anti-CV2/CRMP5 as diagnostic tests. MVG is supported by the Fundación Martín Escudero to perform research abroad. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Prior to 2021, the neuromuscular medicine fellowship application process suffered from non-standardized timelines and substantial variability. To rectify this, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) established a standardized application timeline and an online application portal in 2020-2021, followed by the introduction of a partial match process. In 2021-2022, AANEM launched a traditional, binding, two-way match system for fellowship positions allocation based on the Gale-Shapley stable matching algorithm. Surveys assessing perceptions of fairness in the application portal and match process were dispatched to applicants and program directors following the 2021 and 2022 recruitment cycles. In the 2020-21 cycle, 90% of program directors and 95% of applicants affirmed the standardized timeline benefited applicants. However, 57% of applicants deemed the process as unfair. All programs and most applicants (58%) favored a transition to a two-way match. The implementation of the two-way match in 2021-22 attracted participation from 97% of programs, with 80% of applicants and 95% of programs viewing the process as fair to applicants. A significant majority of both applicants (86%) and programs (94%) supported maintaining the standardized timeline and two-way match. We advocate for the universal adoption of the AANEM Match for neuromuscular fellowship recruitment and a standardized fellowship application timeline across all neurologic specialties to promote transparency, fairness, and equity for applicants., Competing Interests: The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Introduction/aims: High-risk medication exposure is a modifiable risk factor for myasthenic exacerbation and crisis. We evaluated whether real-time electronic clinical decision support (CDS) was effective in reducing the rate of prescribing potentially high-risk medications to avoid or use with caution in patients with myasthenia gravis., Methods: An expert panel reviewed the available drug-disease pairings and associated severity levels to activate the alerts for CDS. All unique alerts activated in both inpatient and outpatient contexts were analyzed over a two-year period. Clinical context, alert severity, medication class, and alert action were collected. The primary outcome was alert override rate. Secondary outcomes included the percentage of unique medication exposures avoided and predictors of alert override., Results: During the analysis period, 2817 unique alerts fired, representing 830 distinct patient-medication exposures for 577 unique patients. The overall alert override rate was 85% (80.3% for inpatient alerts and 95.8% for outpatient alerts). Of unique medication-patient exposures, 19% were avoided because of the alert. Assigned alert severity of "contraindicated" were less likely to be overridden (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.32-0.56), as well as alerts activated during evening staffing (OR 0.69, 95% CI 0.55-0.87)., Discussion: Implementation of a myasthenia gravis drug-disease interaction alert reduced overall patient exposure to potentially harmful medications by approximately 19%. Future optimization includes enhanced provider and pharmacist education. Further refinement of alert logic criteria to optimize medication risk reduction and reduce alert fatigue is warranted to support clinicians in prescribing and reduce electronic health record time burden., (© 2023 Wiley Periodicals LLC.)

Introduction/aims: Safety and outcomes data on eculizumab for generalized myasthenia gravis (gMG) in clinical practice remain limited. Outcomes and concomitant medication use may differ in practice compared with clinical trials. We analyzed the clinical and safety outcomes of patients who received eculizumab at our institutions., Methods: Patients with acetylcholine receptor antibody positive (AChR+) gMG, who received ≥1 dose of eculizumab and had ≥1 follow-up before December 10, 2021, were identified. Data were abstracted by chart review. Outcomes included MG Foundation of America Post Intervention Status (MGFA-PIS), Clinical Classification (MGFA-CC), MG-Activities of Daily Living (MG-ADL), concurrent immunomodulatory therapy use, and adverse events., Results: Twelve patients were included. Mean age at eculizumab initiation was 57.4 y (range, 21-77). Eight had refractory MG. Four had history of thymoma and thymectomy. A mean of 3.2 (range, 2-5) immunomodulatory therapies were previously tried. Mean follow-up duration was 18 mo (range, 2-21.6). Clinical improvement occurred rapidly; MGFA-PIS was improved in 80%, and MGFA-CC improved in 83% at 1 mo. Mean MG-ADL decreased from 8.7 to 2.8 at 1 mo, and remained ≤ 3 .5 over 1.5 y. Mean daily prednisone dose decreased from 22.5 mg to 7.2 mg at 1.5 y. Five of 7 patients discontinued maintenance IVIG or PLEX. No patients had meningococcal infections and adverse events were mild., Discussion: Clinical improvement occurred in most patients after eculizumab initiation, beginning as quickly as 1 mo. Steroids were tapered and maintenance IVIG and PLEX were discontinued in most. Eculizumab had a favorable safety profile even when combined with other immunosuppressants., (© 2022 Wiley Periodicals LLC.)

For many years, Neuromuscular Medicine programs lacked a standardized means of handling fellowship applications and offering positions. Programs interviewed applicants and made offers as early as the first half of Post Graduate Year 3 (PGY3), a suboptimal timeline for applicants who may have had little prior exposure to neuromuscular or electrodiagnostic medicine. In 2021, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed the Neuromuscular Fellowship Portal to standardize a later timeline and establish a process for fellowship applications and offers. In its first year, the Neuromuscular Fellowship Portal used a unique one-way match, in which the portal released serial offers to applicants based on rank order lists submitted by programs. Fifty-two Neuromuscular Medicine programs and seven electromyography (EMG)-focused Clinical Neurophysiology programs participated. Sixty-eight positions were filled, a similar number to previous years. A survey of fellowship directors and applicants following this process showed overwhelming support for the standardized timeline and application portal, but all program directors and most applicants favored moving to a traditional match. To maintain the existing application timeline and minimize costs for all parties, the AANEM Neuromuscular Fellowship Portal will host a two-way match, based on existing commercial match algorithms, in 2022. A match will afford a fair and efficient process for all involved. Both Neuromuscular Medicine and EMG-focused Clinical Neurophysiology programs will be encouraged to participate. The process undertaken by the AANEM can stand as an example for other neurologic subspecialties who are interested in standardizing their application timeline., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG., (© The Author(s) 2022. Published by Oxford University Press.)

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., (© 2021 Wiley Periodicals LLC.)

Immuno-oncology agents, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapies, are increasing in use for a growing list of oncologic indications. While harnessing the immune system against cancer cells has a potent anti-tumor effect, it can also cause widespread autoimmune toxicities that limit therapeutic potential. Neurologic toxicities have unique presentations and can progress rapidly, necessitating prompt recognition. In this article, we review the spectrum of central and peripheral neurologic immune-related adverse events (irAEs) associated with ICI therapies, emphasizing a diagnostic framework that includes consideration of the therapy regimen, timing of symptom onset, presence of non-neurologic irAEs, pre-existing neurologic disease, and syndrome specific features. In addition, we review the immune effector cell-associated neurotoxicity syndrome (ICANS) associated with CAR-T cell therapy and address diagnostic challenges specific to patients with brain metastases. As immunotherapy use grows, so too will the number of patients affected by neurotoxicity. There is an urgent need to understand pathogenic mechanisms, predictors, and optimal treatments of these toxicities, so that we can manage them without sacrificing anti-tumor efficacy., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study's objectives were to evaluate the intervention's (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs., Methods: A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016-October 3, 2017) and after (October 3, 2017-October 24, 2018) SIC Service initiation. The primary outcome was readmission rate after index hospitalization. Secondary outcomes included length of stay (LOS) for admissions, corticosteroid and non-steroidal second-line immunosuppression use, ICI discontinuation, and inpatient mortality., Results: In the pre-SIC period, 127 of 1169 patients treated with ICIs were hospitalized for irAEs; in the post-SIC period, 122 of 1159. After SIC service initiation, reductions were observed in irAE readmission rate (14.8% post-SIC vs 25.9% pre-SIC; OR 0.46; 95% CI 0.22 to 0.95; p=0.036) and readmission LOS (median 6 days post-SIC vs 7 days pre-SIC; 95% CI -16.03 to -0.14; p=0.046). No significant pre-initiation and post-initiation differences were detected in corticosteroid use, second-line immunosuppression, ICI discontinuation, or inpatient mortality rates. The SIC Service collected 789 blood and tissue samples from 234 patients with suspected irAEs., Conclusions: This is the first study to report that establishing a highly subspecialized care team focused on irAEs is associated with improved patient outcomes and reduced healthcare utilization. Furthermore, the SIC Service successfully integrated blood and tissue collection safety into routine care., Competing Interests: Competing interests: LZ—Merck consultant. JC—consultant for BMS and Sanofi-Genzyme. DJ—scientific advisory board fee from Eisai, EMD Serono, Genentech, Ipsen, Novartis, Guardant, Petra Pharma, Mapkure, Vibliome Therapeutics, and Relay Therapeutics; institutional research funds from Novartis, Genentech, EMD Serono, Eisai, Takeda, Placon Therapeutics, Syros, Ribon Therapeutics, Infinity Pharmaceuticals, InventisBio and Amgen. GMB—sponsored research agreements with Palleon Therapeutics and Olink Proteomics; scientific advisory board for Novartis and Nektar Therapeutics; consulting for Merck. MD—consultant for Moderna, Tillotts Pharma, ORIC Pharmaceuticals, and Partner Therapeutics; research funding from Novartis and Eli Lilly; scientific advisory board for Neoleukin Therapeutics. ACG—consultant for Momenta, Alexion, UCB/Ra pharma; royalties from Oakstone Publishing; research funding from Myasthenia Gravis Foundation of America, MGNET and Project Datasphere. BDM—consultant for Sanofi, AbbVie, and Celestial Pharmaceuticals. He has also received sponsored research agreements from Boehringer-Ingelheim, Bayer, and Bristol-Myers Squib. MK—consultant for Novartis and Mymee; speaker fees for Lilly. TGN—advisory fees from Parexel, BMS, H3 Biomedicine, AbbVie, and Intrinsic Imaging; grant support from AstraZeneca. JRF—research grants from Bristol Myers Squibb and X4 Pharmaceuticals. MJM—received honarium/acted as a consultant for AstraZeneca, Nektar Therapeutics, Catalyst Pharmaceuticals, Immunai Aditya Bardia; consulting or advisory role for bioTheranostics, Genentech, Genentech/Roche (Inst), Immunomedics, Immunomedics (Inst), Innocrin Pharma (Inst), Merck, Merck (Inst), Novartis, Novartis (Inst), Pfizer, Pfizer (Inst), Radius Health (Inst), Radius Pharma, Sanofi, Spectrum Pharmaceuticals; research funding from bioTheranostics. RS—consultant/scientific advisory board member for AstraZeneca, Bristol-Myers Squibb, Eisai, Iovance, Merck, Novartis, OncoSec, Pfizer, Replimune; research funding from Merck and Amgen. SB—consultant for Third Rock Consulting and Two River Consulting; equity holdings in Kronos Bio and Allogene Therapeutics. YRS—consultant for Castle Biosciences., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction/aims: Telemedicine may be particularly well-suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness, and the potential for increased risk of virus exposure among patients with MG during the coronavirus disease 2019 (COVID-19) pandemic during in-person clinical visits. A disease-specific telemedicine physical examination to reflect myasthenic weakness does not currently exist., Methods: This paper outlines step-by-step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG-CE) is introduced as a MG-specific, telemedicine, physical examination, which contains eight components (ptosis, diplopia, facial strength, bulbar strength, dysarthria, single breath count, arm strength, and sit to stand) and takes approximately 10 minutes to complete., Results: Pre-visit preparation, remote ascertainment of patient-reported outcome scales and visit documentation are also addressed., Discussion: Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation., (© 2021 Wiley Periodicals LLC.)

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, improving outcomes in patients with advanced malignancies. The use of ICIs in clinical practice, and the number of ICI clinical trials, are rapidly increasing. The use of ICIs in combination with other forms of cancer therapy, such as chemotherapy, radiotherapy, or targeted therapy, is also expanding. However, immune-related adverse events (irAEs) can be serious in up to a third of patients. Critical questions remain surrounding the characteristics and outcomes of irAEs, and how they may affect the overall risk-benefit relationship for combination therapies. This article proposes a framework for irAE classification and reporting, and identifies limitations in the capture and sharing of data on irAEs from current clinical trial and real-world data. We outline key gaps and suggestions for clinicians, clinical investigators, drug sponsors, patients, and other stakeholders to make these critical data more available to researchers for pooled analysis, to advance contemporary understanding of irAEs, and ultimately improve the efficacy of ICIs., Competing Interests: Competing interests: KLR receives support from Teladoc and Project Data Sphere. MR owns shares of Pfizer Inc. ACG has served on advisory boards/consulted with Alexion, RA Pharma (UCB), and Momenta (Jansen). She also receives support from Project Data Sphere. MD has received support from Novartis, Eli Lilly, Moderna, Tillotts Pharma, ORIC Pharmaceuticals, and Partner Therapeutics. He is engaged with Moderna and Neoleukin Therapeutics. LZ has received support from Merck US. DBJ has received support from BMS and Incyte and serves on advisory boards for Array Biopharma, BMS, Catalyst, Iovance, Jansen, Merck, Novartis, and Oncosec. OR has received support from Merck, Celgene, Five Prime, GSK, Bayer, Roche, Puretech, Imvacx, and Sobi, has an immunotherapy patent pending, and serves as CMO of Outcomes4me., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: ACG has served on an advisory board and/or consulted with Alexion, Ra Pharma/UCB and Momenta pharmaceuticals/Janssen. She has received royalties from Oakstone Publishing and research support from the Myasthenia Gravis Foundation of America, the MG Rare Disease Network and Project Data Sphere® for an irAE-N registry. She has received clinical trial support to the institution from Ra Pharma and Momenta. LBB receives salary support from Biogen, royalties from Oakstone Publishing, and research support from Project Data Sphere for an irAE-N registry. BKC reports research support from Project Data Sphere for an irAE-N registry. JH receives research support from Project Data Sphere for an irAE-N registry and from GE Healthcare. THS is an employee at the not-for-profit corporation Project DS, with a trade name of Project Data Sphere. AAA served on medical advisory boards for Alexion, Sarepta, CSL Behring, Strongbridge Pharma, Argenx, Ra Pharmaceuticals, and as a neurology consultant for Johnson & Johnson COVID-19 vaccine trials. ABW served on a medical advisory board or as a consultant with Iovance, Novartis, Shanghai Jo’Ann Medical Technology. PKB has consulted for Angiochem, Genentech-Roche, Lilly, Tesaro, Voyager Therapeutics, ElevateBio, Pfizer (Array), Pfizer, SK Life Sciences and Dantari, received grant/research support (to Massachusetts General Hospital) from Merck, BMS and Lilly and honoraria from Merck, Pfizer, Genentech-Roche and Lilly. TAC has received royalties from Wolters Kluwer. SLC serves as the Editor of the Neurology®Podcast and Neurology Minute™. She has received research and/or clinical fellowship support from the Western Institute for Veterans Research, the Siegel Rare Neuroimmune Association, the Immune Deficiency Foundation, Alexion, the Barbara Gural Steinmetz Foundation, and the Sumaira Foundation for NMO. She has served on an advisory board and/or consulted with Alexion, Genentech, VielaBio, Guidepoint, Clarion Healthcare Consulting, ExpertConnect (majority fees paid to University of Utah). JC has received consulting fees from Sanofi-Genzyme and BMS. JD is a consultant for Blue Earth Diagnostics, Magnolia, Gamaka Bio, and Unum Therapeutics. JD has received research support from Beacon Biosignals, Boehringer Ingelheim, Brystol-Myers Squibb, Eli Lilly, Medimmune, Acerta Pharma, Orbus Therapeutics, and Novartis Pharmaceuticals. JD has received royalties from Wolters Kluwer for serving as an author for UpToDate. MD has research funding from Novartis and Eli Lilly, has served as a consultant for Roche-Genentech, Tillotts Pharma, ORIC Pharmaceuticals, Partner Therapeutics, and Moderna, and is a member of the Scientific Advisory Board for Neoleukin Therapeutics. CTD has served on advisory boards for Argenx and Dysimmune Diseases Foundation. He has received royalties from Oakstone Publishing. He has received grant support from NINDS/NeuroNext. DD has served on an advisory board and/or consulted for UCB, Astellas and Immunovant pharmaceuticals. All compensation for the consulting activities is paid to Mayo Clinic. He has patents pending for KLHL11 and LUZP4 as markers of neurological autoimmunity and germ cell tumors. JG has received research to UCSF support from Genentech/Roche for a clinical trial, performed consulting for Biogen, and received personal compensation for medical-legal consulting. JTG has served as a consultant in past 12 months for Immunovant, Alexion, Momenta, Ra Pharma, Grifols, Jacobus, Cabaletta, Regeneron, Argenx, Signant, UCB, Toleranzia and Piedmont Pharmaceuticals. He receives industry grant support from UCB pharma for a fellowship training grant. Full disclosure statement available at: https://dcri.org/about-us/conflict-of-interest/. DBJ has served on advisory boards for Array Biopharma, BMS, Catalyst Biopharma, Iovance, Jansen, Merck, Novartis, and Oncosec, and has received research funding from BMS and Incyte. VCJ is a site investigator in myasthenia gravis research trials sponsored by PCORI and by Alexion Pharmaceuticals. RK receives research funding from Alexion Pharmaceuticals. NK reports no relevant disclosures. NRL is a consultant and has received honoraria from Bayer, Seattle Genetics, Sanofi, Fortress Biotech, Silverback Therapeutics and SYNOX Therapeutics. JL reports no disclosures. AM reports no disclosures. MM-L reports no relevant disclosures. MJM has served on an advisory board and/or consulted with AstraZeneca Pharmaceuticals, Nektar Therapeutics, Catalyst Pharmaceuticals and Immunai. JN has received research funding from Merck and AstraZeneca; served as a consultant/advisory board member with Merck, AstraZeneca, BMS, Pfizer, Takeda, Roche/Genentech, Daiichi/Sankyo and has received honoraria from Merck, AstraZeneca, BMS, Pfizer, Takeda, Roche/Genentech. TGN reports acting as a consultant for Parexel, Bristol Myers-Squibb, H3 Biomedicine, AbbVie, and Intrinsic Imaging unrelated to the current research. TGN reports grant funding from AstraZeneca unrelated to current research. DR has been an advisor or consultant with AbbVie; Advantagene; Agenus; Agios; Amgen; Bayer; Boston Biomedical; Boehringer Ingelheim; Bristol-Myers Squibb; Celldex; Deciphera; DelMar; EMD Serono; Genenta; Genentech/Roche; Imvax; Inovio; Kintara; Kiyatec; Medicenna Biopharma; Merck; Merck KGaA; Monteris; Neuvogen; Novartis; Novocure; Oncorus; Oxigene; Regeneron; Stemline; Sumitono Dainippon Pharma; Taiho Oncology. Research support to his institution has been provided by Acerta Phamaceuticals; Agenus; Celldex; EMD Serono; Incyte; Inovio; Omniox; Tragara. KMR has served on an advisory board and/or consulted with Merck, BMS, and Eisai. BDS has served on an advisory board and/or consulted with Janssen, Kite/Gilead, and Celgene/BMS. RS has served on an advisory board and/or consulted with AstraZeneca, Bristol-Myers Squib, Eisai, Iovance, Merck, Novartis, Oncosec, Pfizer, and Replimune. He has received research funding from Merck. NW has served on an advisory board with Seattle Genetics, received royalties from Wolters Kluwer and research support from Merck. KW reports no disclosures. LZ has been a consultant for Merck. WCL is an employee of the not-for-profit corporation Project DS, with a trade name of Project Data Sphere. KLR has received personal compensation from Teladoc research support from Project Data Sphere for a irAE-N registry., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies., Methods: This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal)., Results: Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65-410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07-4.50; P = 0.033)., Conclusion: In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology.)

Background: The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death., Methods: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected., Results: In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution, the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (30.7%; n = 138), pulmonary (15.8%; n = 71), hepatic (14.2%; n = 64), endocrine (12.2%; n = 55), neurologic (8.4%; n = 38), cardiac (6.7%; n = 30), and dermatologic (4.4%; n = 20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; p < .001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; p < .001), relative to PD-1/PD-L1 monotherapy recipients, and patients with multiple toxicity had a 5-fold increase in inpatient mortality., Conclusion: This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions, and earlier. In addition, admissions for patients with multi-organ involvement is common and those patients are at highest risk of inpatient mortality., Implications for Practice: The number of patients admitted to Massachusetts General Hospital for immune-related adverse events (irAEs) has gradually increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death., (© 2021 AlphaMed Press.)

Introduction: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG)., Methods: We studied the clinical course of COVID-19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle-specific tyrosine kinase antibodies) between April 1, 2020-April 30-2020., Results: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID-19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications., Discussion: Our findings suggest that the clinical course and outcomes in patients with MG and COVID-19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population., (© 2020 Wiley Periodicals, Inc.)

The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance regarding neuromuscular care delivery, telemedicine, and education, and (5) effect on neuromuscular research. We outline key unanswered clinical questions and highlight the need for team-based and interspecialty collaboration. Primary goals of clinical research during this time are to develop evidence-based best practices and to minimize morbidity and mortality related to COVID-19 for patients with neuromuscular disorders., (© 2020 American Academy of Neurology.)

Expanding use of immune-checkpoint inhibitors (ICIs) underscores the importance of accurate diagnosis and timely management of neurological immune-related adverse events (irAE-N). We evaluate the real-world frequency, phenotypes, co-occurring immune-related adverse events (irAEs), and long-term outcomes of severe, grade III to V irAE-N at a tertiary care center over 6 years. We analyze how our experience supports published literature and professional society guidelines. We also discuss these data with regard to common clinical scenarios, such as combination therapy, ICI rechallenge and risk of relapse of irAE-N, and corticosteroid taper, which are not specifically addressed by current guidelines and/or have limited data. Recommendations for management and future irAE-N reporting are outlined. ANN NEUROL 2020;87:659-669., (© 2020 American Neurological Association.)

Purpose of Review: This article reviews the pathophysiology, epidemiology, clinical presentation, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and of botulism, and immune-related myasthenia gravis (MG) occurring in the context of immune checkpoint inhibitor therapy for cancer., Recent Findings: The suspicion that LEMS is rare but also likely underdiagnosed is supported by recent epidemiologic data. A validated, LEMS-specific scale now exists to assess and monitor disease, and symptomatic and immunomodulatory treatments are available. As presynaptic disorders of neuromuscular transmission, LEMS and botulism share electrodiagnostic abnormalities but have important distinguishing features. Knowledge of the clinical features of botulism is needed, particularly with continued cases of infant botulism, the opioid epidemic increasing the incidence of wound botulism, and medical use of botulinum toxin, which may cause iatrogenic botulism. Foodborne botulism remains rare. Prompt recognition of botulism and administration of antitoxin can improve outcomes. MG may be exacerbated or may present de novo in the context of immune activation from immune checkpoint inhibitor therapies for cancer. Immune-related MG commonly overlaps with myositis and myocarditis. Corticosteroids typically result in improvement. However, immune-related MG can be more fulminant than its idiopathic counterpart and may cause permanent disability or death., Summary: The diagnosis of LEMS, botulism, or immune-related MG can generally be made from the patient's history, supplemented with directed questions, a physical examination designed to demonstrate abnormalities, and laboratory and electrodiagnostic testing. Early diagnosis and carefully selected treatment not only improve outcomes of the neuromuscular disease but can affect the prognosis of underlying malignancy, when present.

Objective: To describe the spectrum, clinical course, and management of neuropathies associated with immune checkpoint inhibitors (ICIs)., Methods: Patients with ICI-related neuropathy (irNeuropathy) were identified and their clinical characteristics compared to neuropathy attributed to cytotoxic agents., Results: We identified 19 patients with irNeuropathies. ICIs included anti-programmed death-1 (PD1), 9; anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), 2; and combination of anti-CTLA4 and anti-PD1, 8. Median number of ICI doses prior to neuropathy onset was 4. Rate of neuropathies following ICI therapy was 0.7%. Underlying malignancies included melanoma (n = 15), lung adenocarcinoma (n = 3), and cholangiocarcinoma (n = 1). Neuropathy phenotypes were cranial neuropathies with or without meningitis (n = 7), nonlength-dependent polyradiculoneuropathies with and without cranial nerve involvement (n = 6), small-fiber/autonomic neuropathy (n = 2), ANCA-associated mononeuritis multiplex (n = 1), sensory neuronopathy (n = 1), length-dependent sensorimotor axonal polyneuropathy (n = 1), and neuralgic amyotrophy (n = 1). Immune-related adverse events involving other organ systems were common (58%). Corticosteroid use for management of neuropathy was associated with improvement in median modified Rankin Scale score (1 vs 0, p = 0.001) and Inflammatory Neuropathy Cause and Treatment Disability score (2 vs 0.5, p = 0.012) (Class IV). Significantly higher proportion of irNeuropathies had acute or subacute and nonlength-dependent presentations ( p < 0.001) and rate of hospitalization for irNeuropathy was also higher ( p = 0.002) compared to toxic neuropathy from chemotherapy., Conclusion: Neuropathy is a rare complication of ICIs that often responds to immunosuppression. Recognition of its wide phenotypic spectrum and distinct clinical characteristics and prompt management with corticosteroids may lead to favorable outcomes., (© 2019 American Academy of Neurology.)

Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood. Here, we report a fatal case of encephalitis arising during anti-programmed cell death receptor 1 therapy in a patient with metastatic melanoma. Histologic analyses revealed robust T cell infiltration and prominent programmed death ligand 1 expression. We identified 209 reported cases in global pharmacovigilance databases (across multiple cancer types) of encephalitis associated with checkpoint inhibitor regimens, with a 19% fatality rate. We performed further analyses from the index case and two additional cases to shed light on this recurrent and fulminant irAE. Spatial and multi-omic analyses pinpointed activated memory CD4 + T cells as highly enriched in the inflamed, affected region. We identified a highly oligoclonal T cell receptor repertoire, which we localized to activated memory cytotoxic (CD45RO + GZMB + Ki67 + ) CD4 cells. We also identified Epstein-Barr virus-specific T cell receptors and EBV + lymphocytes in the affected region, which we speculate contributed to neural inflammation in the index case. Collectively, the three cases studied here identify CD4 + and CD8 + T cells as culprits of checkpoint inhibitor-associated immune encephalitis.

Immune checkpoint inhibitors (ICIs) initiate antitumor immunity by blocking the action of immune inhibitor-signaled cytotoxic proteins, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, and programmed cell death ligand 1. However, in rare cases (∼1%-12% of patients), ICI treatment causes neurologic immune-related adverse events (irAEs). These include, but are not limited to, headache, encephalitis, neuropathies, myasthenia gravis, and myositis. The symptoms associated with irAEs can range from mild (grade 1-2) to severe (grade 3-4); however, they are often challenging to diagnose because they may present as generalized symptoms, such as fatigue and weakness, that can also be caused by the cancer itself. Here, we present an illustrative case of a 67-year-old woman who presented with signs of a neurologic irAE, including progressive dysphagia and weakness leading to falls, which started during treatment with pembrolizumab and worsened following initiation of ipilimumab. Following neurological and pathological evaluation, she was diagnosed with myositis. She was treated with steroids and improved rapidly. In this article, we review previous literature to provide guidance to frequently asked questions concerning the diagnosis and management of neurologic irAEs in patients with advanced cancer. With prompt and effective treatment, most patients will achieve a complete recovery. KEY POINTS: Neurologic immune-related adverse events (irAEs) affect approximately 1% of patients treated with immune checkpoint inhibitor (ICI) monotherapy and 2%-3% treated with combination therapy. These irAEs can affect any portion of the nervous system, although peripheral nerve system manifestations are most common. Overlap syndromes with multiple neurologic irAEs or other affected organ systems frequently exist.Diagnosis of neurologic irAEs can be challenging. Routine testing may be unremarkable and symptoms frequently mimic those from cancer or side effects of other therapies. Optimal management is currently unknown. A systematic, highly coordinated, and multidisciplinary approach is critical.Outcomes from neurologic irAEs are typically favorable with the current practice of holding the ICI and starting corticosteroids. Some patients are even successfully retreated with an ICI. A subset of patients, however, have a fulminant and potentially fatal course.Improved risk assessments and targeted therapies are needed., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Neuromuscular disorders may present and progress differently in women than in men. During pregnancy, medication adjustment, hormonal effects, and other alterations in physiology may influence the manifestation of a variety of neuromuscular disorders. The expression of existing conditions may change; previously asymptomatic conditions may be unmasked, or entirely new conditions may develop. Additionally, neuromuscular disorders and their treatments may have implications for the fetus. Such factors must be carefully considered when counseling and treating pregnant women and those considering pregnancy. This article reviews considerations specific to women and issues surrounding pregnancy in disorders of the neuromuscular junction, focal neuropathies, and acquired and inherited disorders of the nerve and muscle., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG)., Methods: In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures., Results: As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages of B10 cells. In addition, we observed an increase in MuSK antibody levels with more severe disease., Conclusions: We found prominent B-cell pathology in the distinct form of MG with MuSK autoantibodies. Increased BAFF levels have been described in other autoimmune diseases, including acetylcholine receptor antibody-positive MG. This finding suggests a role for BAFF in the survival of B cells in MuSK MG, which has important therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential mechanism for the breakdown in immune tolerance in patients with MuSK MG.

Purpose of Review: This article provides an overview of the most common peripheral neuropathic disorders in pregnancy with a focus on clinical recognition, diagnosis, and treatment., Recent Findings: The literature on this topic consists primarily of case reports, case series, and retrospective reviews. Recent work, particularly in carpal tunnel syndrome, brachial neuritis, and inherited neuropathies in pregnancy, has added to our knowledge of this field. Awareness of diabetic polyneuropathy with associated autonomic dysfunction in pregnancy has grown as the incidence of diabetes mellitus increases in women of childbearing age., Summary: Women may develop mononeuropathy, plexopathy, radiculopathy, or polyneuropathy during pregnancy or postpartum. Pregnancy often influences consideration of etiology, treatment, and prognosis. In women of childbearing age with known acquired or genetic neuromuscular disorders, pregnancy should be anticipated and appropriate counseling provided. An interdisciplinary approach with other medical specialties is often necessary.

Introduction: Venous access for therapeutic plasma exchange (TPE) in myasthenia gravis (MG) can be achieved by central venous catheters (CVC) or peripheral veins (PV), and the preferred method varies among providers. We evaluated our institutional experience with TPE venous access method and complications., Methods: We reviewed all TPE-treated MG patients (2005-2010) through blinded chart review. TPE complications were categorized as serious or minor. Serious complications ended the procedure and/or were potentially life-threatening., Results: A total of 134 MG patients received 230 TPE courses; 56% were outpatient procedures. Whenever feasible, TPE was performed by PV access, which was successful in 75% of courses. Over 90% in both groups improved after TPE. Compared with PV access, CVCs were associated with more total (68% vs. 35%) and serious complications (41% vs. 4%), including 2 deaths., Conclusions: PV access for TPE can be used successfully in most MG patients and may reduce morbidity of the procedure., (Copyright © 2012 Wiley Periodicals, Inc.)

Preexisting and coincident neuromuscular disorders in pregnancy are challenging for clinicians because of the heterogeneity of disease and the limited data in the literature. Many questions arise regarding the effect of disease on the pregnancy, delivery, and newborn in addition to the effect of pregnancy on the course of disease. Each disorder has particular considerations and possible complications. An interdisciplinary team of physicians is essential. This article discusses the most recent literature on neuromuscular disorders in pregnancy including acquired root, plexus, and peripheral nerve lesions; acquired and inherited neuropathies and myopathies; disorders of the neuromuscular junction; and motor neuron diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)