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© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., 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., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation.

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.

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.

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

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.Lignes directrices sur la prise en charge de l’amylose héréditaire à transthyrétine, accompagnée de polyneuropathie, au Canada.L’amylose héréditaire à transthyrétine (ATTRh) est une maladie évolutive, causée par des mutations du gène de la transthyrétine (TTR), qui entraînent un dysfonctionnement plurisystémique. L’agrégation, le mauvais repliement et la fibrillisation pathogènes de la TTR aboutissent au dépôt de protéines amyloïdes dans plusieurs organes, et affectent souvent le système nerveux périphérique et le cœur. Les troubles neurologiques fréquents comprennent une polyneuropathie sensorimotrice (PN), une neuropathie autonome, une polyneuropathie des petites fibres et le syndrome du canal carpien. Chez bon nombre de patients, la maladie a connu une évolution importante en raison de la pose tardive du diagnostic, la PN-ATTRh ne faisant pas l’objet d’un diagnostic différentiel. Santé Canada a approuvé, depuis peu, deux nouveaux médicaments modificateurs de la PN-ATTRh et efficaces contre l’affection, soit l’inotersen et le patisiran. La pose précoce du diagnostic revêt une importance cruciale dans l’instauration, en temps opportun, de ces tout nouveaux traitements qui atténuent les troubles, améliorent la qualité de vie et prolongent la survie. Les auteurs, par l’élaboration de la nouvelle ligne directrice, espèrent sensibiliser la communauté médicale à la PN-ATTRh, et améliorer les résultats cliniques qui y sont associés, en formulant des recommandations sur le diagnostic et le traitement de la maladie au Canada ainsi que sur la surveillance de son évolution.

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.

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.

ObjectivesTo estimate patient-acceptable symptom state (PASS) cut points for myasthenia gravis (MG) health scales.MethodsWe 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).ResultsOne 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.ConclusionsWe 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.

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.

Electrophysiological studies are essential for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), but the utility of nerve conduction studies in monitoring outcomes in individual CIDP patients is controversial. Electrophysiological improvements after short-term treatment have been described in large cohorts of CIDP patients, but the magnitude of the changes is small and might be obscured in individual patients due to the variation inherent in nerve conduction testing. We present the case of a CIDP patient treated successfully with immunosuppression and followed for 31 years with serial standardized clinical and electrophysiological evaluations. Improvement in electrophysiological parameters lagged clinical changes for up to 2 years, but all motor parameters improved (distal motor and F wave latencies, conduction velocities, and compound muscle action potential amplitudes) even with evidence of initial axonal damage. Worsening of electrophysiological parameters, specifically increasing F wave latencies, heralded clinical relapse by as much as a year. Electrophysiological parameters do improve with treatment in CIDP patients, although the changes can take up to 2 years, and also worsening electrophysiological parameters can herald clinical relapse and might help guide therapeutic decisions.

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.

Background: In January 2020, the first case of Guillain Barre syndrome (GBS) due to COVID-19 was documented in China. GBS is known to be postinfectious following several types of infections. Although causality can only be proven through large epidemiological studies, we intended to study this association by a thorough review of the literature. Methods: We searched PubMed, EMBASE, and Google scholar and included all papers with English or Spanish full text and original data of patients with GBS and recent COVID infection. Variables of interest were demographics, diagnostic investigations, and the latency between arboviral and neurological symptoms. Further variables were pooled to identify GBS clinical and electrophysiological variants, used treatments, and outcomes. The certainty of GBS diagnosis was verified using Brighton criteria. Results: We identified a total of 109 GBS cases. Ninety-nine cases had confirmed COVID-19 infection with an average age of 56.07 years. The average latency period between the arboviral symptoms and neurologic manifestations for confirmed COVID-19 cases was 12.2 d. The predominant GBS clinical and electromyography variants were the classical sensorimotor GBS and acute demyelinating polyneuropathy respectively. Forty cases required intensive care, 33 cases required mechanical ventilation, and 6 cases were complicated by death. Conclusions: Studies on COVID-19-related GBS commonly reported sensorimotor demyelinating GBS with frequent facial palsy. The time between the onset of infectious and neurological symptoms suggests a postinfectious mechanism. Early diagnosis of GBS in COVID-19 patients is important as it might be associated with a severe disease course requiring intensive care and mechanical ventilation.

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.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.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.Our results demonstrate that an EOG-based signal analysis is a potentially viable non-invasive alternative for MG screening.The proposed approach could lead to early detection of MG and thereby improve clinical outcomes in this population.

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.

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.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.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.This framework will be used to develop a patient-reported outcome of cramp severity and impact.Évaluer qualitativement l’impact et la gravité des crampes musculaires tout en étant axé sur les patients qui en souffrent. Contexte : Il existe un besoin urgent de mettre en œuvre de nouvelles options thérapeutiquespour le soulagementdes crampes musculaires. Cela dit, aucun patient qui en souffre ne semble avoir fait état d’optionstenant compte de la totalité de leurexpérience. À cet égard, nous avons effectué une étude qualitative afin justement de mieux cerner l’expérience de ces patients et de comprendreles facteurs qui déterminentl’impact que les crampes peuvent avoir dans leur vie. Nous voulons du coup orienter l’élaboration d’indicateursaxés sur les patients eux-mêmes, indicateurs visant à mesurer l’impact et la gravité de leurs crampes musculaires. Méthodes : Nous avons recruté des patients atteints de crampes musculaires en raison de plusieurs étiologies, par exemple des pathologies du motoneurone, des crampes liées à une grossesse, des cas de cirrhosenécessitant une hémodialyse, des crampes idiopathiquesou déclenchées par l’exercice, etc. Les patients recrutés ont participé à des entrevues semi-structurées portant sur leur expérience en lien avec des crampes musculaires, leurs réponses étant enregistrées et par la suite transcrites. En plus déterminer la taille de notre échantillon à l’aide de la saturation de données, nous avons ensuite analysé ces dernières au moyen de la méthode d’analyse de contenu. Enfin, nous avons élaboré un cadre conceptuel de la gravité des crampes musculaires et de leur impact général. Résultats : Une fois nos données saturées, dix patients ont été interviewés. Les expériences liées à leurs crampes se sont révélées comparables peu importe les maladies et les états physiologiques. Parmi les principaux aspects caractérisant l’impact général des crampes, mentionnons les suivants : les caractéristiques des crampes, les perturbations du sommeil qu’elles entraînent, leur interférence dans des activités de jour et leurs effets sur la santé mentale. Conclusions : Ce cadre de référence sera utilisé pour élaborer un outil mesurant la gravité et l’impact des crampes musculaires, et ce, en fonction de l’apport des patients eux-mêmes.

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.

Background: High levels of uric acid (UA) are associated with various peripheral neuropathies. Furthermore, uric acid levels have been found to correlate with both the clinical and electrophysiological severity of diabetic sensorimotor polyneuropathy, mainly with sensory functions. Objectives: To determine whether higher UA levels are associated negatively with nerve function in healthy subjects. Methods: A total of 126 healthy subjects recruited prospectively for another study were included. We extracted demographic data, body mass index (BMI), blood pressure, Toronto Clinical Neuropathy Score (TCNS), electrophysiological findings, vibration perception thresholds (VPT), and laboratory test results including UA, hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and lipid levels. Results: The mean age of the cohort was 56 ± 17 years with 56% females. Males had higher UA values compared with females. Univariate beta regression coefficient analysis between UA levels and demographic, clinical, electrophysiological, and laboratory findings showed significant positive correlations with male gender, components of the metabolic syndrome, and with VPT, while an inverse correlation was found with electrophysiological sensory parameters. A multivariate regression model showed positive correlations only with BMI, finger VPT, and triglycerides. Conclusion: Higher UA levels correlate with lower sensory nerve function in healthy subjects, expanding the evidence of possible negative influence of UA on peripheral nerves, although a causative role has not yet established.

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.

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.

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.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) 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.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Background: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis. Methods: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403). Findings: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21–11·53, p

BACKGROUND AND PURPOSE Long-term treatment of myasthenia gravis (MG) includes symptomatic and course-modifying therapies that target the immune system. Recently, both intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) have emerged as viable options for chronic therapy, considering the favourable safety-efficacy profile and possible immunosuppressant sparing properties. The aim was to investigate the outcomes of the long-term care of generalized MG with immunoglobulin (Ig). METHODS This is a retrospective, repeated-measures design study. Charts of generalized MG patients, treated with IVIG/SCIG for at least 6 months, from January 2015 to January 2020, were analysed. The primary outcome was the mean change in Myasthenia Gravis Impairment Index (MGII) after treatment with Ig, comparing baseline to IVIG and SCIG treatment periods. Secondary outcomes included the changes in pyridostigmine, immunosuppressive medications and patient-reported outcome 'percentage of normal' (0%-100%). RESULTS Thirty-four patients were treated with chronic Ig therapy (30 IVIG/SCIG, three SCIG, one IVIG). The mean durations of IVIG and SCIG periods were 21.8 ± 19.4 (range 3-64) months and 19.5 ± 11.3 (range 5-45) months respectively. There was a significant reduction in MGII scores (27.7 ± 15.7 baseline; 22.0 ± 17.4 IVIG period; 19.5 ± 18.1 SCIG period; F = 17.9; d.f. = 1.7; P

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.

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.

Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) show varying degrees of response to intravenous immunoglobulin (IVIg) therapy. This randomised phase III study in patients with CIDP (ProCID trial) will compare the efficacy and safety of 3 different doses (0.5, 1.0, and 2.0 g/kg) of IVIg 10% (panzyga) administered every 3 weeks for 24 weeks. The primary efficacy endpoint is the rate of treatment response, defined as a decrease in adjusted inflammatory neuropathy cause and treatment disability score of ≥1 point, in the IVIg 1.0 g/kg arm at week 24. Patients with definite or probable CIDP according to European Federation of Neurological Sciences/Peripheral Nerve Society criteria with IVIg or corticosteroid dependency and active disease are eligible. All potentially eligible patients will undergo IVIg or corticosteroid dose reduction (washout phase) over ≤12 weeks or until deterioration of CIDP (active disease). Patients with deterioration during the washout phase will be randomised to receive study treatment during a dose-evaluation phase starting with a loading dose of IVIg 2.0 g/kg followed by maintenance treatment with IVIg 0.5, 1.0, or 2.0 g/kg every 3 weeks. Rescue medication (2 doses of IVIg 2.0 g/kg given 3 weeks apart) will be administered to patients in the IVIg 0.5 and 1.0 g/kg groups who deteriorate after week 3 and before week 18 or who do not improve at week 6. Safety, tolerability and quality of life will be assessed. The ProCID study will provide new information on the best maintenance dose of IVIg for patients with CIDP.

To determine the cross-sectional threshold at which hemoglobin A1c (HbA1c) is associated with polyneuropathy in healthy controls, and the values associated with the most pronounced decline in nerve function in patients with diabetes.We used data from a cross-sectional cohort study of healthy controls and type 2 diabetes patients assessed between November 2010 and May 2013. Healthy controls and patients with diabetes were compared at different HbA1c ranges:5.5%, 5.5-5.9%, and 6-6.4% for controls, and 6.5-7.4% and7.5% for patients with diabetes.The total cohort included 53 controls and 164 patients with diabetes. Subclinical small nerve fiber impairments were observed in controls at HbA1c levels of 5.5-6%, compared with HbA1c5.5%, for example: lower Laser Doppler flare imaging area of 2.8 ± 1.4 versus 3.9 ± 2 mmThese findings underscore the importance of early treatment at the prediabetes and early diabetes stages to prevent nerve fiber decline that is likely irreversible.

INTRODUCTION Patients with myasthenia gravis often experience fatigue, but its effect on quality of life (QoL) is underestimated, and fatigue is rarely measured in clinical trials. METHODS Two hundred fifty-seven myasthenic patients completed the Neuro-QoL-Fatigue and measures of disease severity and QoL. We studied the relationship between fatigue and clinical and demographic variables. Finally, we studied the responsiveness of the Neuro-QoL-Fatigue in 95 patients receiving treatments for myasthenia and estimated the minimal important difference (MID). RESULTS Fatigue correlated with greater disease severity (r = 0.52-0.69, P

Introduction Monoclonal gammopathy has been reported in several polyneuropathies. In this study, we sought to explore the frequency and characteristics of monoclonal gammopathy in patients with diabetic sensorimotor polyneuropathy (DSP). Methods Patients with type 1 and type 2 diabetes mellitus (DM 1, DM 2) and controls without diabetes were evaluated between November 2008 and December 2013. Results Fifty controls, 66 patients with DM 1, and 106 patients with DM 2 were included, with average ages of 43 ± 18, 45 ± 17, and 65 ± 10 years, respectively; the frequency of monoclonal gammopathy was 0%, 8%, and 15%, respectively. In patients with DSP, the frequency of monoclonal gammopathy increased to 14% in DM 1 and 21% in DM 2; the most common monoclonal proteins were immunoglobulin (Ig) M and IgG, respectively. Discussion DSP might be associated with a high frequency of monoclonal gammopathy, with different characteristics in DM 1 and in DM 2. Muscle Nerve 57: 1018-1021, 2018.

Objectives To explore the correlations between different muscle cramp characteristics including cramp frequency and severity and clinical and large and small nerve fiber measures in patients with diabetes type 1 (DM 1) and 2 (DM 2). Methods Prospective cross sectional study of healthy controls and patients with DM 1 and DM 2 recruited between April 2009 and November 2012. Participants underwent clinical evaluation and large and small nerve fiber studies, and the frequency and correlations of muscle cramps were explored. Results 37 controls, 51 patients with DM 1, and 69 patients with DM 2 were studied. Muscle cramps were the most frequent symptom captured by the Toronto Clinical Neuropathy Score (TCNS) in all groups, up to 78% in patients with DM 2. In patients with DM 1, but not DM 2, muscle cramp frequency and severity were correlated with clinical (TCNS) and both large (electrophysiology and vibration perception thresholds) and small nerve fiber measures. Conclusions Muscle cramps are frequent in diabetes and are correlated with clinical and both small and large nerve fiber measures in DM 1, suggesting that their origin and propagation might extend beyond the motor nerve. Significance Muscle cramps correlate with nerve fiber measures in DM 1.

BACKGROUND AND PURPOSE The Toronto Clinical Neuropathy Score (TCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy. In this study, we aimed to explore the performance of the TCNS in non-diabetic polyneuropathies. METHODS We performed a prospective study from November 2016 to May 2017 of patients with non-diabetic polyneuropathy. Patients had clinical, electrophysiological and functional assessments of their polyneuropathy, and the findings were correlated with the TCNS. RESULTS The TCNS correlated with all clinical, electrophysiological and disability measures of polyneuropathy, mostly at a moderate level (e.g. r = -0.58 for sural nerve action potential amplitude). Higher TCNS severity grades were associated with worse polyneuropathy on all measures in the lower limbs, and with worse electrophysiological parameters and vibration perception thresholds in the upper limbs. The scale also showed excellent reliability and accuracy (kappa, 0.92-0.93 for inter- and intra-observer reliability; area under the receiver operating characteristics curve, 0.93). CONCLUSION The TCNS is a valid and reliable scale for a wide spectrum of polyneuropathies, and might be useful in clinical practise and research for the diagnosis and staging of polyneuropathy.

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Introduction Diabetic sensorimotor polyneuropathy (DSP) is the most frequent complication in patients with diabetes mellitus (DM), and is associated with age, DM duration, and HbA1c levels. In addition, higher uric acid (UA) levels are reported in patients with DSP. Objectives To explore whether UA levels correlate with DSP severity. Methods We extracted the demographic data, clinical history, neurological and electrophysiological examinations and laboratory findings of 115 patients diagnosed with DSP from January 2012 to December 2015. Results The mean age of the total cohort was 62 ± 13 years, with 61% men. A positive correlation was demonstrated between uric acid levels and increasing sensory symptoms, and more abnormal electrophysiological findings and vibration perception thresholds. In addition, correlations with gait abnormality, the presence of paraproteinemia and creatine kinase levels were found. Discussion Our study results show that uric acid levels correlate with clinical and electrophysiological severity of DSP, providing additional evidence for the relationship between the two, and a potential therapeutic target for DSP.

Myasthenia gravis (MG) can lead to weakness in different patterns of muscle groups. Limb muscle weakness is most typically seen in a limb girdle pattern, although variants exist. In the current study, we aimed to describe a unique MG phenotype consisting of selective or predominant triceps muscle weakness. We performed a retrospective review of MG patients who developed focal or predominant triceps muscle weakness between 2006 and 2016. The clinical, electrophysiological and serological characteristics of these patients were examined. 8 MG patients were identified, including 7 males, all of whom were African-American. Two patients underwent muscle biopsy, and one patient underwent cervical spine decompression surgery. All showed significant improvement following immunosuppressive treatment, although one patient experienced a relapse of muscle weakness. This case series highlights a relatively uncommon MG clinical phenotype of selective triceps muscle weakness, mainly in African-American males, in line with previous literature. Familiarity with this phenotype is important in order to facilitate diagnosis and appropriate treatment for this group, and avoid unnecessary investigations or treatments.

Introduction: Assessing myasthenia gravis (MG) can be challenging, and multiple scales are available to evaluate disease severity. We evaluated the utility of a single simple question, namely “what percentage of normal do you feel regarding your MG, 0-100% normal”, as part of the MG evaluation. Methods: A retrospective chart review of patients attending the neuromuscular clinic from 01/2014 to 12/2015 was performed. Responses were correlated with symptoms and signs, QMGS (quantitative myasthenia gravis score), MGII (myasthenia gravis impairment index), and MG-QOL15 (myasthenia gravis quality of life). Results: The total cohort included 169 patients. The percentage of normal correlated strongly with limb muscle weakness and MG scales, moderately with bulbar and respiratory symptoms, and weakly with ocular manifestations. Discussion: The question “what percentage of normal do you feel regarding your MG”, is a feasible and valid question, and can be incorporated easily into routine clinical evaluation. This article is protected by copyright. All rights reserved.

Some patients with chronic inflammatory demyelinating polyradiculoneuropathy who respond to initial intravenous immunoglobulin require repeated courses over prolonged periods of time; however, evidence to guide dosage and interval of intravenous immunoglobulin during maintenance therapy is limited. Optimizing treatment requires assessment of underlying disease activity and clinical outcome. Electrophysiological measures of demyelination, and clinical measures using handgrip strength and walking velocity promise to be particularly informative. Major advances in resolution and image processing have expanded clinical applications for ultrasound to include the study of peripheral nerves. Ultrasonography shows promise in diagnosing chronic inflammatory demyelinating polyradiculoneuropathy and distinguishing it from other conditions, providing first ever insight into gross pathology of peripheral nerves. Ultrasonography may also have a role in monitoring disease activity and treatment response.

Introduction Electrophysiological studies play an important role in the diagnosis of myasthenia gravis (MG). The objectives of this study was to explore the correlation of jitter and decrement with various clinical symptoms and signs and disease severity. Methods We performed a retrospective chart review of 75 MG patients who attended the neuromuscular clinic from April 2013 to May 2014. We compared clinical characteristics between patients with high jitter (>100 µs) and decrement (>10%), and patients with lower values to explore the correlations and optimal thresholds of jitter and decrement for different clinical features. Results High jitter and decrement values were associated with more severe disease, manifested by more frequent symptomatic bulbar and limb muscle weakness, more frequent ocular and limb muscle weakness on examination, higher quantitative MG score, and generalized disease. Conclusions The yield of the electrophysiological assessment in MG extends beyond disease diagnosis and correlates with disease severity and the presence of generalized disease. Muscle Nerve 56: 445–448, 2017

ObjectiveTo determine whether IV immunoglobulin (IVIg) is more effective than placebo at reducing disability in patients with diabetes and demyelinating polyneuropathy features.MethodsThis 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.ResultsTwenty-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.ConclusionsIVIg 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 evidenceThis study provides Class I evidence that for patients with diabetes and demyelinating polyneuropathy features, IVIg did not significantly reduce disability.

INTRODUCTION:Although focal motor seizures may resemble one or more movement disorders their phenomenology and prevalence remain uncertain. METHODS:To examine the extent to which focal motor seizures can present with a phenomenology fulfilling diagnostic criteria for movement disorders, 100 consecutive patients with focal motor seizures were rated by movement disorders experts, epileptologists, and general neurologists. RESULTS:A focal motor seizure phenomenologically manifested as a defined movement disorder in 29% of the patients from a consecutive video-EEG documented cohort as per consensus among experts: myoclonus and dystonia (10 and 9 cases, respectively) were the most common movement disorders, followed by chorea (4), stereotypies (3) myoclonus-dystonia (2), and tremor (1). CONCLUSIONS:Movement disorders and focal motor epilepsy share overlapping movement phenomenology. © This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.