Search

Background and Purpose: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria., Methods: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally., Results: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%., Conclusions and Discussion: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Backgrounds and Objectives: Early use of immunosuppression has been suggested to prevent generalization of ocular myasthenia gravis (OMG), but high-quality evidence is limited in this regard. We examined whether treatment with prednisone and other immunosuppressants reduce the risk of generalization in OMG., Methods: This is a retrospective study of consecutive adults with pure OMG who had a minimum 6 months of follow-up. The main outcome was the time to developing generalized symptoms. We used propensity scores to create matched data sets of patients treated with prednisone or any immunosuppressant vs controls. We also used unmatched models with inverse probability of treatment weights (IPTW) and variable exposure times. We used Cox proportional hazards model to estimate hazard ratio (HR) for generalization, comparing treated patients vs controls., Results: A total of 154 patients were included, with a mean follow-up of 87.4 ± 73 months since onset. Forty-three (28%) were generalized, and mean time to generalization from diagnosis was 24.2 ± 24.1 months. Patients who received prednisone had lower risk of generalization than controls, with pooled HR 0.43 (95% CI 0.19-1.06) for the matched model, HR 0.46 (95% CI 0.21-0.89) for the IPTW model, and for HR 0.44 (95% CI 0.23-0.81) for the time-dependent exposure model. Patients who received any immunosuppressant had lower risk of generalization, with HR 0.30 (95% CI 0.11-0.77), 0.32 (95% CI 0.14-0.70), and 0.35 (95% CI 0.15-0.80) for the matched, IPTW, and IPTW-varying exposure models, respectively., Discussion: Our study provides evidence that steroidal and nonsteroidal immunosuppression in patients with OMG is associated with a reduced risk of developing generalized symptoms over time. This supports the early use of immunosuppression in this population., Classification of Evidence: This study provides Class III evidence that treatment of OMG with corticosteroids or nonsteroidal immunosuppressants reduces the risk of generalization.

Objective: This study assesses the utility of jitter analysis with concentric needles to evaluate disease severity in myasthenia gravis (MG), correlate changes in jitter with clinical status as well as identify reasons for any discordance., Methods: We performed a retrospective chart review of 82 MG patients and extracted data on demographics, MG subtype, antibody status, clinical scales, electrophysiology, and interventions at baseline and follow-up., Results: Baseline MGII scores correlated with jitter (r = 0.25, p = 0.024) and abnormal pairs (r = 0.24, p = 0.03). After 28 months, MGII scores correlated with jitter (r = 0.31, p = 0.006), abnormal pairs (r = 0.29, p = 0.009), and pairs with blocks (r = 0.35, p = 0.001). Changes in MGII scores correlated with changes in jitter (r = 0.35, p = 0.002), abnormal pairs (r = 0.27, p = 0.014), and pairs with blocks (r = 0.36, p = 0.001)., Conclusions: Concentric needle jitter analysis may have the potential to evaluate baseline and sequential disease severity in MG., Significance: This study highlights the potential for improved MG patient care through precise assessment and management using concentric needle jitter analysis to improve the accuracy of MG diagnosis and monitoring of disease activity., (© 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or sleep-disordered breathing. To investigate the value of multiple respiratory tests in MG, we performed clinical and respiratory assessments in patients with mild to moderate generalized disease. One-hundred and thirty-six patients completed the myasthenia gravis quality-of-life score(MG-QOL-15), myasthenia gravis impairment index(MGII), Epworth sleepiness scale(ESS), University of California-San Diego Shortness of Breath Questionnaire(UCSD-SOB), Modified Medical Research Council Dyspnea Scales(MRC-DS), supine and upright forced vital capacity(FVC), maximal inspiratory pressures(MIPs) and sniff nasal inspiratory pressures(SNIP). Seventy-three (54 %) had respiratory and/or bulbar symptoms and 45 (33 %) had baseline abnormal FVC, with no significant postural changes (p = 0.89); 55 (40.4 %) had abnormal MIPs and 50 (37 %) had abnormal SNIPs. Overall, there were low scores on respiratory and disability scales. Females had increased odds of presenting with abnormal FVC (OR 2.89, p = 0.01) and MIPs (OR 2.48, p = 0.022). There were significant correlations between MIPs, FVC and SNIPs; between MGII/MG-QOL15 and UCSD-SOB/MRC-DS and between ESS and respiratory scales in the whole group. Our data suggests that office-based respiratory measurements are a useful screening method for stable MG patients, even when presenting with minimal respiratory symptoms and no significant disability., Competing Interests: Declaration of competing interest On behalf of all authors, I confirm that there are no conflict or competing interests related to this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction/aims: Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients., Methods: Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment., Results: We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy., Discussion: Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction: Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies., Methods: An extensive literature search was performed to identify relevant studies. We prioritized meta-analysis, systematic reviews, and position statements where possible to inform any recommendations., Summary: The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain-Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders., Conclusions: Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Introduction: Current guidelines for defining good outcomes in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) are predominately defined by experts. At present, we do not have a patient-anchored definition of what constitutes a "good" outcome. Our study aimed to assess the symptom burden of people living with CIDP, as well as satisfaction with treatments and clinical outcomes., Methods: We conducted an online-survey in CIDP patients registered with the US and Canadian GBS/CIDP foundations. Respondents answered general demographic and clinical questions, as well as satisfaction with current symptom burden and treatments, plus validated outcome measures., Results: A total of 318 individuals with self-reported CIDP completed the online survey, of whom 128 (40%) considered their current disease burden as satisfactory while 190 (60%) did not. Of 305 patients who answered the treatment satisfaction question, 222(74%) were satisfied with their treatments. Patients who were satisfied with their current symptoms had, on average, better scores in quality of life and disease severity scales, although regression modeling showed that only ability to walk, stable symptoms, and health utility scores were associated with symptom satisfaction. Treatment satisfaction was associated with stable symptoms, use of IVIG, and use of one versus no medication., Conclusions: A high proportion of members of the US and Canadian GBS/CIDP Foundations reporting a diagnosis of CIDP were unsatisfied with current symptoms, despite a high level of overall satisfaction with treatments. There is an unmet need for improving long-term outcomes in people with a diagnosis of CIDP, and for studying patient-centered long-term treatment goals., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

In this brief communication, we discuss the current landscape and unmet needs of pediatric to adult transition care in neurology. Optimizing transition care is a priority for patients, families, and providers with growing discussion in neurology. We also introduce the activities of the University of Toronto Pediatric-Adult Transition Working Group - a collaborative interdivisional and inter-subspeciality group of faculty, advanced-practice providers, trainees, and patient-family advisors pursuing collaboration with patients, families, and universities from across Canada. We envision that these efforts will result in a national neurology transition strategy that will inform designation of health authority attention and funding.

Background and Aims: The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga ® ) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings., Methods: Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks., Results: All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64-90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication., Interpretation: Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP., Clinical Trial Numbers: EudraCT 2015-005443-14, NCT02638207., (© 2023. The Author(s).)

Background and Purpose: Measuring health-related quality of life (QOL) is vital for understanding the disease impact, but the complex relationship between clinical parameters and QOL remains unclear. The objective was to determine the demographic and clinical factors that influence the QOL in adults with inherited and acquired myopathies., Methods: The study was of cross-sectional design. Detailed demographic and clinical details were collected. Patients answered Neuro-QOL and Patient-Reported Outcomes Measurement Information System short-form questionnaires., Results: Data was collected from 100 consecutive in-person patient visits. Mean age of the cohort was 49.5 ± 20.1 (18-85) years, and the majority were male (53, 53%). Bivariate analysis between the various demographic and clinical features with the QOL scales revealed single simple question (SSQ), handgrip strength, Medical Research Council (MRC) sum score, female gender, and age to be nonuniformly associated with the QOL scales. There was no difference between inherited and acquired myopathies for any of the QOL scores, except for the poorer lower limb function domain in inherited myopathies (36.7 ± 7.3 vs. 40.9 ± 11.2, p = 0.049). Linear regression models revealed lower SSQ, lower handgrip strength, and lower MRC sum score to independently predict poor QOL., Conclusions: Handgrip strength and SSQ serve as novel predictors of QOL in myopathies. Handgrip strength has a significant impact on physical, mental, and social domains and deserves special attention with respect to rehabilitation. SSQ correlates well with QOL and can be employed as a quick and global assessment of a patient's well-being. Differences in QOL scores between patients with inherited and acquired myopathies were minimal., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study., Methods: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/μL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%)., Results: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/μL in 1,005 patients (83%), 5-49 cells/μL in 200 patients (16%), and ≥50 cells/μL in 13 patients (1%)., Discussion: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/μL, is compatible with GBS after a thorough exclusion of alternative diagnoses., Classification of Evidence: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS., (© 2023 American Academy of Neurology.)

Background and Purpose: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2., Methods: This multicenter North American open-label prospective investigator-initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks -10 to -1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction., Results: We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72-1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP., Conclusions: MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg., (© 2023 European Academy of Neurology.)

Background and Purpose: There have been over 500 million confirmed cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), across the globe. To date, a broad spectrum of neurological manifestations following acute infections as well as COVID-19 vaccines have been reported. The aim of this study was to describe the spectrum of neurological manifestations seen in the 'COVID-19 clinic' established in a tertiary Movement Disorders clinic., Methods: In this consecutive case-series study over the period March 2020-January 2022, clinical information regarding demographic data, clinical history and examination findings, investigation results and video recordings of outpatients with motor manifestations associated with COVID-19 infection or vaccination were reviewed., Results: Twenty-one adult patients were reviewed in this ad hoc clinic at Toronto Western Hospital. The majority of the patients were female (76%) and the mean (range) age was 50.7 ± 17.2 (21-80) years. Nine patients (43%) presented with motor manifestations following COVID-19 infection. Twelve patients (57%) developed neurological symptoms following at least one dose of the mRNA or viral vector-based COVID-19 vaccine. The most common manifestation observed was a functional movement disorder (43%). The vaccine group demonstrated a higher number of functional disorders compared to the infection group (58% vs. 22%; p = 0.08)., Conclusion: Functional motor manifestations can be associated with COVID-19 and are likely to be under-reported. In view of the co-existence of functional symptoms, movement disorders and mental health conditions observed in this study, we would advocate the use of dedicated COVID-19 Neurology clinics with full access to an experienced multidisciplinary team., (© 2022 European Academy of Neurology.)

Introduction/aim: Given the lack of information on safety of coronavirus disease 2019 (COVID-19) vaccination in myasthenia gravis (MG) patients, we aimed to review our experience after surveying patients, as part of routine clinical practice, to ensure that advice on safety is accurate., Methods: We performed a retrospective chart review of MG patients from the Prosserman Family Neuromuscular Clinic at the Toronto General Hospital who received two injections of any COVID-19 vaccine from February to August 2021. Demographic data were abstracted from the patient medical records. We assessed changes in the severity of MG using the virtual Myasthenia Gravis Impairment Index (vMGII), the simple single question (SSQ), and Patient Acceptable Symptom State (PASS). We also assessed adverse effects after vaccination., Results: We included 200 patients with a mean age of 64.3 ± 13.9 y, 51.5% were men, and 82% had generalized MG. The vMGII, SSQ, and PASS scores remained stable after each vaccine dose, and at last follow-up. Of the patients, 60% reported an adverse reaction after the first injection, and 56% after the second. The most common adverse reactions reported were local pain at the injection site, fatigue, headache, and fever., Discussion: COVID-19 vaccinations were well tolerated in MG patients and were not associated with worsening severity of their MG. The prevalence of vaccine-related adverse reactions was the same as in the general population., (© 2022 Wiley Periodicals LLC.)

Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization., Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization)., Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed)., Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality., Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis., Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54)., Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale., Methods: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni , hepatitis E virus, Mycoplasma pneumoniae , cytomegalovirus, and Epstein-Barr virus., Results: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni -positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir ( p = 0.004) and a longer time to regain the ability to walk independently ( p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni -positive patients ( p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients ( p = 0.004)., Discussion: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models., (© 2022 American Academy of Neurology.)

Introduction: Myasthenia gravis (MG) is an antibody mediated disease where pathogenic antibodies interact with the acetylcholine receptor or other proteins at the post-synaptic neuromuscular junction. There is growing evidence that immunoglobulin infusions are beneficial for clinical exacerbations and chronic refractory disease and may be an option for patients unresponsive to conventional immunosuppressive therapies., Areas Covered: We performed an extensive literature review, looking for evidence on the use of immunoglobulins for the treatment of MG, by conducting a search in MEDLINE (1946 to present), EMBASE (1947 to present) and Clinicaltrials.gov. We have included studies on the use of intravenous immunoglobulins (IVIG) and subcutaneous immunoglobulins (SCIG) for acute deterioration and chronic disease., Expert Opinion: The use of IVIG in MG provides an option for rapid improvement in critical deterioration, being preferred over more invasive and less available therapies such as plasmapheresis. For refractory MG, the addition of IVIG can improve a patient's status and reduce the dosage of immunosuppressive medications. The alternative of SCIG is also effective and has advantages of infusion time flexibility, fewer side-effects, and patient independence. The safety and efficacy of both interventions, patient preferences and quality of life may direct therapeutic choices in the future.

Intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy usually starts with a 2.0 g/kg induction dose followed by 1.0 g/kg maintenance doses every 3 weeks. No dose-ranging studies with intravenous immunoglobulin maintenance therapy have been published. The Progress in Chronic Inflammatory Demyelinating polyneuropathy (ProCID) study was a prospective, double-blind, randomized, parallel-group, multicentre, phase III study investigating the efficacy and safety of 10% liquid intravenous immunoglobulin (Panzyga®) in patients with active chronic inflammatory demyelinating polyneuropathy. Patients were randomized 1:2:1 to receive the standard intravenous immunoglobulin induction dose and then either 0.5, 1.0 or 2.0 g/kg maintenance doses every 3 weeks. The primary end point was the response rate in the 1.0 g/kg group, defined as an improvement ≥1 point in adjusted Inflammatory Neuropathy Cause and Treatment score at Week 6 versus baseline and maintained at Week 24. Secondary end points included dose response and safety. This trial was registered with EudraCT (Number 2015-005443-14) and clinicaltrials.gov (NCT02638207). Between August 2017 and September 2019, the study enrolled 142 patients. All 142 were included in the safety analyses. As no post-infusion data were available for three patients, 139 were included in the efficacy analyses, of whom 121 were previously on corticosteroids. The response rate was 80% (55/69 patients) [95% confidence interval (CI): 69-88%] in the 1.0 g/kg group, 65% (22/34; CI: 48-79%) in the 0.5 g/kg group, and 92% (33/36; CI: 78-97%) in the 2.0 g/kg group. While the proportion of responders was higher with higher maintenance doses, logistic regression analysis showed that the effect on response rate was driven by a significant difference between the 0.5 and 2.0 g/kg groups, whereas the response rates in the 0.5 and 2.0 g/kg groups did not differ significantly from the 1.0 g/kg group. Fifty-six per cent of all patients had an adjusted Inflammatory Neuropathy Cause and Treatment score improvement 3 weeks after the induction dose alone. Treatment-related adverse events were reported in 16 (45.7%), 32 (46.4%) and 20 (52.6%) patients in the 0.5, 1.0 and 2.0 g/kg dose groups, respectively. The most common adverse reaction was headache. There were no treatment-related deaths. Intravenous immunoglobulin (1.0 g/kg) was efficacious and well tolerated as maintenance treatment for patients with chronic inflammatory demyelinating polyneuropathy. Further studies of different maintenance doses of intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy are warranted., (© The Author(s) (2022). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: To investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP., Methods: We performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline., Results: We included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP., Conclusion: Measures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation., Significance: There are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alcantara, Ngo, de la Cruz, Menon, Barnett-Tapia, Katzberg and Bril.)

Transition in paediatric health care refers to the planned process of shifting to an adult model of care and is highly individualised, patient focussed and requires a coordinated effort from different health care professionals. Through this retrospective study, we describe the spectrum of neuromuscular diseases evaluated through a paediatric to adult neuromuscular transition program in a tertiary academic centre in Canada, and also the speciality supports needed for these patients. 126 patients were transitioned during the study period. The most common clinical diagnosis was muscle disease (44.4%), followed by neuropathy (27.8%), neuromuscular junction disorders (15.9%) and motor neuron disease (MND) (10.3%). The majority of cases were inherited neuromuscular disorders (66.6%); 58.3% had a genetically confirmed diagnosis. Cardiac and respiratory abnormalities were encountered in 8.7% and 27.7% and transitioning was required for 39.8% and 35.7% respectively. Scoliosis was seen in 30.2% of patients; 9.5% underwent spine surgery. Patients with MND had maximum requirements for self-care (46.2% of MND) and a mobility device for ambulation was required in 69.2% of MND. We observed a wide range of systemic issues requiring the services of endocrinology, gastroenterology, speech and language pathology and psychiatry. A multidisciplinary clinical care model may provide optimal care for patients transitioning from paediatric to adult care health systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity., Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors., Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort., Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America., Classification of Evidence: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS., Trial Registration Information: NCT01582763., (© 2021 American Academy of Neurology.)

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

Background: Myasthenia gravis (MG) is an autoimmune disorder that frequently affects young women of reproductive age. The multidirectional interplay between MG, pregnancy, and fetal health poses a complex scenario for pregnant women with MG and the healthcare team. Here, we reviewed our local experience with MG, pregnancy, and outcomes., Methods: We performed a retrospective chart review of patients with MG attending the Prosserman Family Neuromuscular Clinic from 2001 to 2019 and who were referred to a high-risk pregnancy clinic. MG status was defined as stable, better, or worse. Information was collected on the delivery route, pregnancy, and neonatal complications., Results: We identified 20 women with MG for a total of 28 pregnancies. Worsening was observed in 50% of pregnancies: 18% during pregnancy, 25% following delivery, and 7% during both. 66.7% of patients with MG duration of 2 years or less had worsening during pregnancy. Three patients who stopped immunosuppressive treatment during pregnancy worsened and one had a crisis. C-section was done in 29% of pregnancies. The rate of delivery complications was 7% and of neonatal MG was 7%., Conclusion: A high proportion of MG patients worsened during pregnancy, particularly those with disease duration less than 2 years, and those who discontinued immunosuppression during pregnancy. However, pregnancy was largely unaffected, rate of neonatal MG was low, frequencies of C-section, delivery complications, and premature births were similar to the general population. While the study has limitations due to the retrospective nature, these insights provide some guidance when counseling young myasthenic women about family planning.

Please verify edits, "These techniques", or specify. This article reviews advanced electrodiagnostic techniques used to assess for neuromuscular junction disorders, including repetitive nerve stimulation, conventional or concentric-needle single-fiber electromyography (SFEMG), and stimulated SFEMG. These techniques have high sensitivity but limited specificity. Novel methods currently under investigation are discussed, including vestibular ocular myogenic potential and oculography analysis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson)., Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS., Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination., Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria., Main Outcomes and Measures: Clinical characteristics and mortality rate., Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later., Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Introduction/aims: The purpose of this study was to evaluate the clinical profile of myasthenia gravis (MG) in older patients and determine the impact of medical comorbidities on their MG status and outcome., Methods: This was a retrospective chart review of patients with a symptom onset of MG at or after 65 years of age. Correlations were made between demographics, clinical characteristics, the Myasthenia Gravis Foundation of America (MGFA) severity scale scores, and Myasthenia Gravis Impairment Index (MGII) scores with two outcome measures: MGFA Post-Intervention Status (MGFA-PIS) and Simple Single Question (SSQ)., Results: The study population included 109 patients, with 90 of them having more than one follow-up visit. Their mean age was 75.3 ± 6.9 years and sex distribution was even. Of these patients, 67.7% had generalized MG. Nine-one percent of patients had one comorbidity. None of the demographic factors or comorbidities showed an association with MGFA-PIS, SSQ, or MGII after correction for multiple comparisons. Seventy-one percent of the patients improved with treatment, 12.4% remained unchanged, and 16.6% showed worsening at their last follow-up visit., Discussion: Our study shows that patients with very-late-onset MG had a good prognosis and treatment response. None of the comorbidities had an impact on the severity of myasthenic symptoms or on outcome in these patients., (© 2021 Wiley Periodicals LLC.)

Introduction/aims: The aim of the study was to determine the association between the virtual Myasthenia Gravis Impairment Index (vMGII) with other patient-reported outcomes (PROs) of myasthenia gravis (MG) and its usefulness in telephone consultations with MG patients., Methods: This was a retrospective case series in which vMGII score along with virtual Single Simple Question (vSSQ), virtual Patient-Acceptable Symptom State PASS (vPASS) response, and patient disease status based on Myathenia Gravis Foundation of America postintervention status were collected during telephone consultation along with the MGII, SSQ, and PASS responses during the preceding in-person clinic visits., Results: In 214 patients, the mean difference of vMGII between the vPASS "Yes" and "No" groups was -14.2 ± 1.4 (95% confidence interval, -16.9 to -11.3; P < .001) with mean vMGII for vPASS "Yes" group being 6.4 ± 7.7 and vPASS "No" being 20.5 ± 11.5. A vMGII of 11.5 or higher predicted vPASS "yes" response with a sensitivity of 78.7% and specificity of 81.4%. A strong negative correlation was found between the vMGII and vSSQ (r = -.667; P < .001). The mean vMGII was 0.48 ± 1.42 for patients in remission, and 9.31 ± 10.93 for improved, 9.32 ± 8.79 for stable, and 22.58 ± 14.04 for worsened groups (P < .001). These associations were the same as those obtained during the preceding in-person clinic visit and the direction of change in MGII scores also indicated change in disease status., Discussion: vMGII is an effective measure to assess an MG patient's disease status in telephone consultations and relates well with other PRO measures. The vMGII remains reliable for assessing MG disease status even with removal of the physical examination component., (© 2021 Wiley Periodicals LLC.)

Introduction: There is limited evidence regarding the impact of World Health Organization (WHO) subtype of thymoma on post-thymectomy outcome of thymoma-associated myasthenia gravis (TAMG). The objective was to determine if the pathological subtypes of thymoma were associated with post-thymectomy outcomes of myasthenia gravis (MG), in patients with TAMG., Methods: We performed a retrospective study of consecutive patients with TAMG who attended the neuromuscular clinic between January 2018 and December 2019 with a minimum follow-up of 1 y after thymectomy. Outcome measures were MG Impairment Index (MGII), single-simple question (SSQ), Myasthenia Gravis Foundation of America post-intervention status (MGFA PIS) and non-responder MG status at last assessment., Results: Ninety-five patients were included; mean age at onset was 48.1 ± 12.1 y; 54(56.8%) were females. Thirteen patients developed MG post-thymectomy. The most common thymoma was WHO type B2 in 39 (41.1%). Most patients (40, 42.1%) had Masaoka stage II thymoma. There was no association of thymoma subtypes or Masaoka stage of disease with age, gender, MG phenotype, serology, post-thymectomy onset, interval from onset to thymectomy, MGII, SSQ, MGFA PIS, or non-responder status. Associations were found between positive serology and lower MGII (11.1 ± 14.2 vs 23 ± 12.9, P = .050), thymic follicular hyperplasia (TFH) and higher SSQ (89.3 ± 11.7 vs 80.1 ± 20.2, P-.043), and lack of recurrence and higher SSQ (84.1 ± 18 vs 72.5 ± 20, P = .037)., Discussion: The WHO pathological subtype of thymoma did not correlate with MG outcomes. However, positive acetylcholine antibody serology, presence of TFH, and non-recurrence of thymoma predict a favorable outcome., (© 2021 Wiley Periodicals LLC.)

Background: Lower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are available for lower limb cramps; some are controversial or could cause harm, and often, people experience no benefit from the interventions used. This is an update of a Cochrane Review first published in 2012. We updated the review to incorporate new evidence., Objectives: To assess the effects of non-drug, non-invasive therapies for lower limb muscle cramps., Search Methods: In August 2018 and May 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of included studies. We imposed no restrictions by language or publication date., Selection Criteria: We included all randomised controlled trials (RCTs) of non-drug, non-invasive interventions tested over at least four weeks, for lower limb muscle cramps in any group of people, except pregnant women. The primary outcome was cramp frequency. Secondary outcomes were cramp pain severity, cramp duration, health-related quality of life, quality of sleep, participation in activities of daily living, proportion of participants reporting lower limb muscle cramps, and adverse events., Data Collection and Analysis: Two review authors independently selected trials, assessed risk of bias, and cross-checked data extraction and analyses according to standard Cochrane procedures., Main Results: We included three trials, with 201 participants, all 50 years of age and older; none had neurological disease. All trials evaluated a form of stretching for lower limb muscle cramps. A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps (measured on a 10 cm visual analogue scale (VAS) where 0 = no pain and 10 cm = worst pain imaginable) in people aged 55 years and older, compared to no intervention (mean difference (MD) -1.30, 95% confidence interval (CI) -1.74 to -0.86; 1 RCT, 80 participants; low-certainty evidence). The certainty of evidence was very low for cramp frequency (change in number of cramps per night from week zero to week six) comparing the stretching group and the no intervention group (MD -1.2, 95% CI -1.8 to -0.6; 80 participants; very low-certainty evidence). Calf stretching alone for 12 weeks may make little to no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older (stretching group median number of cramps in the last four weeks (Md) 4, interquartile range (IQR) 8; N = 48; sham stretching group Md 3, IQR 7.63; N = 46) (U = 973.5, z = -0.995, P = 0.32, r = 0.10; 1 RCT, 94 participants; low-certainty evidence). This trial did not report cramp severity. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome (N = 24). It was not possible to fully analyse the frequency data and the scale used to measure cramp severity is not validated. No study reported health-related quality of life, quality of sleep, or participation in activities of daily living. No participant in these three studies reported adverse events. The evidence for adverse events was of moderate certainty as the studies were too small to detect uncommon events. In two of the three studies, outcomes were at risk of recall bias, and tools used to measure outcomes were not validated. Due to limitations in study designs that led to risks of bias, and imprecise findings with wide CIs, we cannot be certain that findings of future studies will be similar to those presented in this review., Authors' Conclusions: A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain. Calf stretching alone compared to sham stretching for 12 weeks may make little or no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome. Overall, use of unvalidated outcome measures and inconsistent diagnostic criteria make it difficult to compare the studies and apply findings to clinical practice. Given the prevalence and impact of lower limb muscle cramps, there is a pressing need to carefully evaluate many of the commonly recommended and emerging non-drug therapies in well-designed RCTs across all types of lower limb muscle cramps. A specific cramp outcome tool should be developed and validated for use in future research., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Purpose: Defining refractory myasthenia gravis is important, as this can drive clinical decision making, for example, by escalating treatments in refractory individuals. There are several definitions of refractory myasthenia, and their performances have not been compared. Having valid and reliable criteria can help select patients in whom more aggressive treatments may be needed., Methods: We applied five different refractory myasthenia criteria (Drachman, Mantegazza, Suh, the International Consensus Guideline (ICG), and the randomised controlled trial of eculizumab in refractory, anti-acetylcholine receptor positive, generalised myasthenia gravis (REGAIN), to a cohort of 237 patients. We compared the proportion of refractory patients among different criteria and their scores on disease severity, fatigue, and quality-of-life (QoL) scales. We also assessed the agreement for each criterion between two trained assessors., Results: The Drachman, Mantegazza, and Suh criteria resulted in high proportions of refractory individuals (40.1%, 39.2%, and 38.8%, respectively), compared with the ICG and REGAIN criteria (9.7% and 3.0%, respectively). Refractory patients by the ICG and REGAIN criteria had worse disease severity, QoL, and fatigue scores, compared with patients classified as refractory by other criteria. All criteria had high agreement between raters (between 70% and 100%)., Conclusions: There is high variability in the proportion of refractory myasthenia gravis patients depending on the criteria used, with ICG and REGAIN criteria capturing patients with worse disease severity. This reflects conceptual differences as to what refractory means. Further multicenter studies are needed to determine appropriate criteria for refractory myasthenia gravis., (© 2020 European Academy of Neurology.)

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Menon, Katzberg and Bril.)

Background: We aimed to determine the safety and tolerance of higher rates of infusion of intravenous immunoglobulin (IVIG) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)., Methods: Patients began infusions with 10% IVIG at the standard rate of 0.08 mL/kg/min. If tolerated, infusion rates were incrementally increased to 0.14 mL/kg/min. We considered the frequency of infusions with adverse events (AEs) as the primary outcome., Results: Nineteen of 25 patients safely tolerated the maximum rate of 0.14 mL/kg/min. We observed 25 treatment-related AEs (TAEs) over 13 infusions at standard or transitional rates, across seven patients. We observed no TAEs associated with the maximum infusion rate., Conclusions: We found that 10% IVIG can be safely administered at a high infusion rate (0.14 ml/kg/min) in most CIDP patients, reducing the treatment time and burden on healthcare resources., (© 2020 Wiley Periodicals LLC.)

Objectives: To estimate patient-acceptable symptom state (PASS) cut points for myasthenia gravis (MG) health scales., Methods: We conducted an electronic survey that included the Myasthenia Gravis Impairment Index (MGII), EuroQol 5-Dimension (EQ5D), and a simple PASS question. PASS-anchored thresholds were estimated for the MGII questionnaire through receiver operating characteristic curves. We used the MGII PASS cut point in a validation cohort of 257 patients to estimate PASS thresholds for other clinically relevant health scales such as the Quantitative Myasthenia Gravis Scale (QMGS), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC), and Myasthenia Quality of Life (MG-QoL15)., Results: One hundred twenty-four of ≈250 invited patients answered the electronic survey (49% response rate), and 80 considered their current symptom state acceptable (PASS-positive). They had lower MGII scores than PASS-negative patients (7.76 ± 9.37 vs 25.0 ± 13.7, p < 0.0001) and better EQ5D scores (0.86 ± 0.17 vs 0.69 ± 0.18, p < 0.0001). The MGII questionnaire threshold for PASS was ≤10 points. With the use of this threshold in an independent dataset of 257 patients, all patients in remission or minimal manifestation status were PASS-positive. In addition, some patients in Classes I, II, and IIIA also achieved PASS status. PASS thresholds for the QMGS, MG-ADL, MGC, and MG-QoL15 were ≤7, 2, 3, and 8 points, respectively., Conclusions: We have estimated thresholds for commonly used myasthenia health scales reflecting patient-acceptable states in patients with MG. These thresholds indicate a global state of well being, rather than a change in scores, or being better. Therefore, PASS thresholds can be used as secondary endpoints for myasthenia research., (© 2020 American Academy of Neurology.)

Objectives: The purpose of this study was to prospectively evaluate sleep patterns and the presence of sleep-disordered breathing in children with myasthenia gravis. We further aimed to examine the relationship between sleep and daytime respiratory function using spirometry tests including upright and supine forced vital capacity, sniff nasal inspiratory pressure, and maximal inspiratory pressure., Methods: Eleven children between 3 and 18 years old with confirmed myasthenia gravis were recruited from The Hospital for Sick Children Neuromuscular Clinic in this prospective observational study. After informed consent was obtained, patients underwent a comprehensive clinical assessment with collection of anthropometric data. Following this, all subjects performed pulmonary function tests, overnight polysomnography and completed the Epworth Sleepiness Scale questionnaire., Results: Two of eleven children who reported no symptoms of sleep disordered breathing were diagnosed with mild to moderate obstructive sleep apnea. Pulmonary function tests showed abnormal maximal inspiratory pressure in 6 of 11 patients, whereas seated forced vital capacity as well as seated to supine forced vital capacity ratios were normal in the entire group., Conclusions: In our small group of pediatric myasthenia gravis subjects, there was an unexpected finding of obstructive sleep apnea in 2 of the 11 patients studied. Maximal inspiratory pressure appears to be a more sensitive method of detecting abnormalities compared to upright or seated forced vital capacity. A larger multicenter study is needed to validate our findings and to determine the impact of obstructive sleep apnea in the pediatric myasthenia gravis population as well as risk factors associated with sleep disordered breathing.

Muscle cramps, defined as a painful contraction of a muscle or muscle group, are a common symptom most people have experienced throughout their lifespan. In some cases cramps can be frequent, severe, and disabling, thus requiring medical assessment and intervention. Physiologic states such as pregnancy and exercise are associated with excessive muscle cramps, as are numerous medical and neurologic conditions, medications such as diuretics and statins, and peripheral nerve hyperexcitability syndromes. Treatment options for muscle cramps are limited, although recent studies have shown that mexiletine could be a safe and efficient alternative for patients with amyotrophic lateral sclerosis., Competing Interests: Disclosure The author disclose that some of this work was supported by a New Initiatives grant from the Division of Neurology at the University of Toronto., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Nerve injury from peripheral nerve block (PNB) is an uncommon but potentially serious complication. We present a retrospective cohort study to evaluate the incidence and etiology of new postoperative neurological symptoms after surgery and regional anesthesia., Methods: We performed a retrospective cohort study of all PNBs performed on elective orthopedic and plastic surgical patients over 6 years (2011-2017). We collected patient and surgical data, results of neurophysiological and imaging tests, neurology and chronic pain consultations, etiology and outcome for patients with prolonged neurological symptoms (lasting ≥10 days)., Results: A total of 26 251 PNBs were performed in 19 219 patients during the study period. Transient postoperative neurological symptoms (<10 days) were reported by 14.4% (95% CI 13.1% to 15.7%) of patients who were reached by telephone follow-up. Prolonged postoperative neurological symptoms (≥10 days) were identified and investigated in 20 cases (1:1000, 95% CI 0.6 to 1.6). Of these 20 cases, three (0.2:1000, 95% CI 0.04 to 0.5) were deemed to be block related, seven related to surgical causes, three due to musculoskeletal causes or pain syndromes, one was suspected of having an inflammatory etiology and six remained of undetermined etiology. Of those who completed follow-up, 56% had full recovery of their symptoms with the remaining having partial recovery., Conclusion: This retrospective review of 19 219 patients receiving PNBs for anesthesia or analgesia suggests that determining the etiology and causative factors of postoperative neurological symptoms is a complex, often challenging process that requires a multidisciplinary approach. We suggest a classification of cases based on the etiology. A most likely cause was identified in 70% of cases. This type of classification system can help broaden the differential diagnosis, help consider non-regional anesthesia and non-surgical causes and may be useful for clinical and research purposes., Competing Interests: Competing interests: AP has a research grant from Fisher and Paykel for an unrelated study. VC has received honoraria from Philips Healthcare., (© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the past two decades, there has been a fundamental shift away from traditional cytotoxic chemotherapy towards the identification, and subsequent suppression of specific oncogenes. Immunotherapy and targeted therapy prime the immune system, potentially leading to deleterious side effects. The following case of Guillain-Barré Syndrome (GBS) emphasizes the importance of considering every agent when iatrogenic toxicity is suspected. We underline the possibility of immune priming by checkpoint inhibitors. An optimal understanding of the pathogenesis and toxicity of targeted therapy is key in an era where the prognosis of melanoma is revolutionized by the use of novel agents. Our case emphasizes the importance of considering every agent in the context of toxicity induced by combined novel therapies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Elevated creatine kinase (CK) level was redefined by the European Federation of Neurological Societies)EFNS(as 1.5 times the upper limit of normal. In the current study we sought to determine the sensitivity and specificity of CK testing for the diagnosis of neuromuscular disorders., Methods: Demographics and CK levels were retrospectively extracted from an electronic database for 234 patients with neuromuscular disorders. Sensitivity, specificity, and likelihood ratios and the area under curve were determined for each diagnosis and different cutoff CK values., Results: Using the EFNS cutoff values significantly reduced CK test sensitivity. Creatine kinase values >1000 IU/L showed a high likelihood (11.04) for myopathies and a low likelihood for polyneuropathies (0)., Discussion: European Federation of Neurological Societies cutoff values significantly reduce CK sensitivity for diagnosing neuromuscular disorders. While low CK values cannot exclude a neuromuscular disease, values >1000 IU/L are associated with a high likelihood of myopathy., (© 2019 Wiley Periodicals, Inc.)

Background: There is an urgent need for new therapeutic options to treat muscle cramps; however, no patient-reported measures exist that capture the entire cramp experience. We conducted a qualitative study to assess the experience of patients suffering muscle cramps, aiming to understand what factors determine the impact cramps have in patients' lives to guide the development of a patient-centered outcome measure of cramp severity and impact., Methods: We enrolled patients with cramps due to several etiologies, including motor neuron disease, pregnancy-induced cramps, cirrhosis and hemodialysis, and idiopathic and exercise-induced cramps. Patients participated in semistructured interviews about their experiences with muscle cramps and their responses were recorded and transcribed. Data were analyzed with content analysis using data saturation to determine the sample size. We subsequently developed a conceptual framework of cramp severity and overall cramp impact., Results: Ten patients were interviewed when data saturation was reached. The cramp experience was similar across disease and physiological states known to cause muscle cramps. The main themes that compose the overall cramp impact are cramp characteristics, sleep interference, daytime activities interference, and the effect on mental health., Conclusions: This framework will be used to develop a patient-reported outcome of cramp severity and impact.

Objective: A precursor to more severe forms of Myasthenia Gravis (MG) is ocular MG (OMG) in which the MG symptoms are localized to the eyes. Current MG diagnostic methods are often invasive, painful, and not always specific. The objective of the proposed work was to extract quantifiable features from electrooculography (EOG) signals recorded around the eyes and develop an alternative non-invasive screening method for detecting MG., Methods: EOG signals acquired from MG and Control subjects were analyzed for eye movement characteristics and quantified using time and wavelet domain signal processing techniques. The ability of the proposed approaches to classify MG vs. control subjects was evaluated using a linear discriminant analysis (LDA) based classifier., Results: The range of overall classification accuracies achieved by the proposed time and wavelet domain approaches for different groupings were between 82.1-83.3% (Rise Rate feature: P < 0.01, AUC ≥ 0.87) and 82.1-87.2% (Mean Scale Band Energy feature: P < 0.01, AUC ≥ 0.89), respectively., Conclusion: Our results demonstrate that an EOG-based signal analysis is a potentially viable non-invasive alternative for MG screening., Significance: The proposed approach could lead to early detection of MG and thereby improve clinical outcomes in this population., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine whether IV immunoglobulin (IVIg) is more effective than placebo at reducing disability in patients with diabetes and demyelinating polyneuropathy features., Methods: This is a double-blinded, single-center, randomized, controlled crossover trial of IVIg treatment vs placebo. The primary outcome measure was the mean change in Overall Neuropathy Limitation Scale (ONLS) scores during the IVIg phasecompared with the placebo phase. Secondary outcomes include changes in the Rasch-built Overall Disability Scale, Medical Research Council sum scores, grip strength, electrophysiologic measurements, quality of life, and adverse effects., Results: Twenty-five subjects were recruited between March 2015 and April 2017. The mean change in ONLS scores was -0.2 points during the IVIg phase and 0.0 points during the placebo phase ( p = 0.23). Secondary outcomes did not show significant differences between IVIg and placebo., Conclusions: IVIg did not reduce disability, improve strength, or quality of life in patients with demyelinating polyneuropathy features and diabetes after 3 months of treatment in comparison with placebo. Therefore, careful consideration of the primary diagnosis is required before immunomodulatory therapy., Classification of Evidence: This study provides Class I evidence that for patients with diabetes and demyelinating polyneuropathy features, IVIg did not significantly reduce disability., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: Multifocal motor neuropathy (MMN) is a treatable autoimmune polyneuropathy, which may prove challenging diagnostically in the setting of absent conduction blocks or advanced axonal loss. Relatively few studies have examined the role of ultrasound (US) in MMN., Methods: Retrospective, cross-sectional study of patients with MMN who underwent peripheral nerve US. Charts were reviewed to extract clinical, sonographic, and electrophysiological data., Results: Eleven patients with MMN underwent US between 2013 and 2015; of these 11 patients, 7 had ≥3 abnormal nerve segments, and 6 had ≥5 sites of increased cross-sectional area (CSA). There was moderate correlation between the degree of amplitude drop observed in the median and ulnar motor nerves, and CSA. Significant correlation between CSA and limb strength was only observed for the median nerve., Conclusions: Peripheral nerve US shows promise as a diagnostic tool in MMN and may be helpful to distinguish MMN from motor neuron disease.