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International audience; BackgroundGrowing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact.MethodsAll patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and myasthenia gravis from October 2017 to October 2018 were included.ResultsOut of 142 patients, 111 (78%) had a modification of their IVIg treatment. We noted that 75 (68%) patients had a delay in IVIg treatment, 41 (37%) patients had a decrease in IVIg doses and 31 (28%) experienced IVIg treatment interruption. Thirty percent of patients for whom IVIg treatment was discontinued were switched to other treatments mainly plasma exchange (16%) or corticosteroids (13%). Switches to plasma exchange or corticosteroids were carried out in order to save immunoglobulins for patients who had no other alternatives. Fifty-eight (52%) patients presented a deterioration of their clinical score after IVIg treatment changes including 31 (28%) patients who had a moderate or a clinically significant deterioration. Concerning practice modifications, we noted a substantial though not significant decrease in median IVIg dose for myasthenia gravis and a significant increase in the delay between IVIg courses for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (P = 0.011 and P = 0.018 respectively).ConclusionOur study showed a rather important number of changes in IVIg treatment related to IVIg shortage during the period considered. These changes had a negative impact on the clinical status of some patients.

Objective To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. Methods Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. Results TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. Conclusions TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. Significance This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Although they are common symptoms of ALS, there is little information on the prevalence of spasticity and spasticity-related pain. Consecutive patients were prospectively recruited from an ALS referral center. Clinical assessment, functional scores, features of spasticity-related pains has been recorded. In a cohort of 150 patients, 36% presented with spasticity. Spastic patients were younger, with a longer duration of disease. Spasticity accelerates the functional decline of patients. Spasticity-related pain was reported in 42.5% of spastic patients with mild pain. However, 16.7% of spastic patients presented significant pain with numeric rating scale≥4. More clinical trials are needed to treat spasticity more effectively and to relieve ALS patients.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Objective Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics. Methods The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies. Results All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve 7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%. Conclusions Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier. Significance Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a “demyelinating” neuropathy.

Background Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. Results Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. Conclusion During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.

Objective This study was undertaken to establish by a multicentric approach the reliability of a new technique evaluating motor axon excitability. Methods The minimal threshold, the lowest stimulus intensity allowing a maximal response by 1 mA increments (iUP) and then by 0.1 mA adjustments (iMAX) were prospectively derived from three nerves (median, ulnar, fibular) in four university centers (Liege, Marseille, Fraiture, Nice). iMAX procedure was applied in 28 healthy volunteers (twice) and 32 patients with Charcot-Marie-Tooth (CMT1a), chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barre syndrome (SGB) or axonal neuropathy. Results Healthy volunteers results were not significantly different between centers. Correlation coefficients between test and retest were moderate (> 0.5). Upper limits of normal were established using the 95th percentile. Comparison of volunteers and patient groups indicated significant increases in iMAX parameters especially for the CMT1a and CIDP groups. In CMT1a, iMAX abnormalities were homogeneous at the three stimulation sites, which was not the case for CIDP. Conclusions The iMAX procedure is reliable and allows the monitoring of motor axon excitability disorders. Significance The iMAX technique should prove useful to monitor motor axonal excitability in routine clinical practice as it is a fast, non-invasive procedure, easily applicable without specific software or devices.

ObjectiveMutations in superoxide dismutase 1 gene (SOD1), encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the production of these aberrant and deleterious SOD1 species, antisense oligonucleotide approaches have recently emerged and showed promising effects in clinical trials. To offer the possibility to any patient with SOD1-ALS to benefit of such a gene therapy, it is necessary to ascertain whether any variant of unknown significance (VUS), detected for example in SOD1 non-coding sequences, is pathogenic.MethodsWe analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.ResultsWe identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358–10T>G nearsplice SOD1 variant was corroborated based on its high frequency (as the second most frequent SOD1 variant) in French fALS, the segregation analysis confirmed in eight affected members of a large pedigree, the typical SOD1-related phenotype observed (with lower limb onset and prominent lower motor neuron involvement), and findings on postmortem tissues showing SOD1 misaccumulation.ConclusionsOur results highlighted nearsplice/intronic mutations in SOD1 are responsible for a significant portion of French fALS and suggested the systematic analysis of the SOD1 mRNA sequence could become the method of choice for SOD1 screening, not to miss these specific cases.

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium (23Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions. Purpose To use 23Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects. Materials and Methods Twenty-seven participants with ALS (mean age, 54 years ± 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years ± 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1H MRI also was investigated. Results Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P < .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue ± 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue ± 2.7; P < .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm3. Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman ρ = -0.57; 95% confidence interval: -0.78, -0.16; P = .005; n = 23). Conclusion Quantitative 23Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials. © RSNA, 2019 Online supplemental material is available for this article.

In peripheral neuropathies with antibodies against Myelin Associated Glycoprotein (MAG), an IgM monoclonal gammopathy recognizes a specific epitope called Human Natural Killer 1 (HNK1) shared by NK lymphocytes and several components of the peripheral nerve myelin. Recently an ELISA test has been developed to detect antibodies against HNK1 epitope. Objectives were to determine the usefulness of this assay in the management of anti-MAG neuropathy. Anti-HNK1 antibodies were assessed with the GanglioCombi™ MAG ELISA test (Buhlmann) in 41 anti-MAG neuropathies and in 118 controls: 34 chronic inflammatory demyelinating polyradiculoneuropathies, 3 Miller Fisher syndromes, 12 sensory neuronopathies, 63 length-dependent axonal sensory polyneuropathies, 6 healthy controls. Anti-HNK1 antibody was tested before and 1 year after rituximab therapy in seven patients with anti-MAG neuropathy. Anti-HNK1 antibodies were positive in 40/41 anti-MAG neuropathies, and in 1/118 controls (sensitivity 98%, specificity 99%). Only considering controls with IgM paraprotein, specificity was 96% (23/24). In anti-MAG neuropathies, anti-HNK1 titre was correlated with sensory deficiency evaluated with the INCAT sensory sum score (r = 0.4, p = 0.01) and with disability evaluated with the Rasch-built Overall Disability Scale (r = $$-$$ 0.4, p = 0.01) and Overall Neuropathy Limitation Scale (r = 0.4, p = 0.02). Anti-HNK1 titres were not related to age, disease duration, atypical clinical features and anti-MAG antibodies titres. Anti-MAG titres were not associated with disease severity. Anti-HNK1 titres were decreased by 18% 1 year after rituximab treatment. Anti-HNK1 antibodies have good sensitivity and specificity for the diagnosis of anti-MAG neuropathy. Interestingly, anti-HNK1 titres are related to the disease severity and decrease after rituximab infusions.

Vitamin B12 (B12) has a fundamental role in both central and peripheral nervous system function at all ages. Neurologic manifestations may be the earliest and often the only manifestation of B12 deficiency. Mostly because of the poor sensitivity of methods of determination for B12 levels, peripheral neuropathy remains a classical but underdiagnosed complication of B12 deficiency. So the clinical and electrophysiological characteristics of B12-responsive neuropathy are not well known.A retrospective study of patients with B12-responsive neuropathy was conducted at our hospital on a 3-year period. The criteria for inclusion were: (a) neuropathy confirmed by the electrophysiological study (nerve conduction study); and (b) improvement of at least 1 point of the total Overall Neuropathy Limitations Scale score after vitamin B12 treatment.Nine patients were identified. Serum B12 level was low in only four. Four patients had sensorimotor (predominantly sensory) axonal polyneuropathy while five had only sensory neuronopathy. Six improved in less than 1 month after B12 supplementation.B12-responsive neuropathy is a more heterogeneous group of neuropathy than previously described. B12 deficiency is a cause of peripheral neuropathy and should systematically be ruled out in the clinical setting of idiopathic neuropathy or sensory neuronopathy because of potential reversibility.B12: vitamin B12; CMAP: compound muscle action potentials; DRG: dorsal root ganglia; ENMG: electroneuromyography; MCCT: motor central conduction time; MEP: motor evoked potentials; MMA: methylmalonic acid; MMCoAM: L-methylmalonyl-CoenzymeA mutase; ONLS: overall neuropathy limitations scale; SCV: sensory conduction velocities; SNAP: sensory nerve action potentials; SNN: sensory neuronopathy; SSS: SNAP sum score.

Background and importance An enlargement of the number of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to shortages of IVIg.1 Aim and objectives The objective of this work was to evaluate the impact of this situation on patient management in one French university centre, considering practice modifications and clinical outcomes. Material and methods All patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, Guillain–Barre syndrome and myasthenia gravis were included, from October 2017 to October 2018. The analysis of practices was carried out between 2016 and 2019. Results Of 155 patients, 72% had a modification of IVIg treatment, including 51% who had a delay in treatment, 28% a decrease in dose and 21% experienced an interruption in IVIg treatment. About 29% of patients for whom IVIg treatment was stopped were switched to other treatments, mainly plasma exchange. 58 patients presented one deterioration of their clinical score after prescription changes, including 31 patients who had a moderate or a clinically significant deterioration. For 17 patients, clinical deterioration was directly related to the IVIg shortage. Concerning practice modifications, we noted a substantial but not significant decrease in the median dose for myasthenia gravis and a significant increase in the delay between treatments for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (p=0.011 and p=0.018). Conclusion and relevance Our study showed a rather important number of IVIg prescription changes related to IVIG shortages during the study period. These changes had a negative impact on the clinical status of some patients. The interest of this study is essential because of the fragility of the post coronavirus disease period related to a lack of plasma from which blood products derive. References and/or acknowledgements Sewell WAC, Kerr J, Behr-Gross M-E, et al. European consensus proposal for immunoglobulin therapies. Eur J Immunol 2014;44:2207–14. The authors thank the department of neuromuscular diseases and the pharmacy team for their help in collecting the data. Conflict of interest No conflict of interest

This monocentric prospective study of patient suffering from Amyotrophic lateral sclerosis (ALS) aims to evaluate the prognosis and diagnostic potential of both Neurofilament-Light (Nf-L) and neuroinflammatory biomarkers in serum and CSF. Candidate markers levels were measured using multiplex method in serum of 60 ALS patients, 94 healthy controls of 43 patients suffering from Inflammatory Peripheral Neuropathies (IPN). A comparative CSF analysis was performed for 20 ALS and 17 IPN patients. Among the altered biomarkers, CSF Nf-L level remains the best marker of ALS severity, while serum levels correlate strongly with disease progression. The combination of Nf-L and ICAM-1 concentrations in the CSF and IFN-γ concentration in the serum differentiate ALS patients from IPN patients with improved sensibility and specificity relative to individual biomarkers. A cutoff value of 0.49 for the fitted values of these 3 biomarkers discriminate ALS from IPN patients with a specificity of 100% (78.20–100%) and a sensibility of 85.71% (57.19–98.22%) with an AUC of 0.99 ± 0.01. The measure of Nf-L and neuroinflammatory biomarkers in CSF and serum can be useful biomarkers panel in the differential diagnosis of ALS.

Mutations in superoxide dismutase 1 gene (We analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.We identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358-10TG nearspliceOur results highlighted nearsplice/intronic mutations in

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

Objective Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX. Methods In 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90–360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles. Results The repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators. Conclusions The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability. Significance A variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation.

Background Fat infiltration in individual muscles of sporadic inclusion body myositis (sIBM) patients has rarely been assessed. Methods Sixteen sIBM patients were assessed using MRI of the thighs and lower legs (LL). The severity of fat infiltration, proximal-to-distal and side asymmetries, and the correlations with clinical and functional parameters were investigated. Results All the patients had fat-infiltrated muscles, and thighs were more severely affected than LL. A proximal-to-distal gradient of fat infiltration was mainly observed for adductors, quadriceps, sartorius, and medial gastrocnemius muscles. A strong negative correlation was observed between the whole muscle fat fraction in the thighs and LL and the Inclusion Body Myositis Functional Rating Scale and Medical Research Council scores for the lower limbs. Conclusions Fat infiltration in individual muscles of sIBM patients is heterogeneous in terms of proximal-to-distal gradient and severity was correlated with clinical scores. These results should be considered for both natural history investigation and clinical trials.

In Amyotrophic lateral sclerosis (ALS), disease severity, ineffective treatment, and increasing dependence on caregivers may give rise to hopelessness and suicidal ideation among patients. In clinical practice, the desire for death among patients with ALS often accompanies the desire to live and fear of death. Thus, we decided to study suicidal ideation among patients with ALS and examine protective factors and reasons for living.We conducted a prospective, observational cohort study that recruited patients during routine visits to the outpatient multidisciplinary reference center for ALS. Depression was measured using the Beck Depression Inventory, suicidal ideation was assessed using the Columbia Suicide Severity Rating Scale, and reasons for living were assessed using the Reasons for Living inventory for adults.Among the 71 patients included, 39% expressed either passive (wish to die) or active suicidal ideation. Patients who expressed suicidal ideation were more likely to report depressive symptoms and have worse disability scores. A significant difference in the survival and coping beliefs subscore of the RFL inventory, which was negatively associated with suicidal ideation, had been found between those who did and did not have suicidal ideation.These findings have stressed the need for caregivers to recognize depression and other distressing expressions as well as provide adequate treatment. Therefore, close attention should be given to those suffering from depression while providing optimal care in terms of not only drug treatment but also psychological support.

The need for a valid biomarker for assessing disease progression and for use in clinical trials on amyotrophic lateral sclerosis (ALS) has stimulated the study of methods that could measure the number of motor units. Motor unit number index (MUNIX) is a newly developed neurophysiological technique that was demonstrated to have a good correlation with the number of motor units in a given muscle, even though it does not necessarily accurately express the actual number of viable motor neurons. Several studies demonstrated the technique is reproducible and capable of following motor neuron loss in patients with ALS and peripheral polyneuropathies. The main goal of this review was to conduct an extensive review of the literature using MUNIX. We conducted a systematic search in English medical literature published in two databases (PubMed and SCOPUS). In this review, we aimed to answer the following queries: Comparison of MUNIX with other MUNE techniques; the reproducibility of MUNIX; the utility of MUNIX in ALS and preclinical muscles, peripheral neuropathies, and other neurological disorders.

Introduction There is uncertainty as to whether the Guillain-Barre syndrome (GBS) subtypes, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), can be diagnosed electrophysiologically. Methods We prospectively included 58 GBS patients. Electrodiagnostic testing (EDX) was performed at means of 5 and 33 days after disease onset. Two traditional and one recent criteria sets were used to classify studies as demyelinating or axonal. Results were correlated with anti-ganglioside antibodies and reversible conduction failure (RCF). Results No classification shifts were observed, but more patients were classified as axonal with recent criteria. RCF and anti-ganglioside antibodies were present in both subtypes, more frequently in the axonal subtype. Discussion Serial EDX has no effect on GBS subtype proportions. The absence of exclusive correlation with RCF and anti-ganglioside antibodies may challenge the concept of demyelinating and axonal GBS subtypes based upon electrophysiological criteria. Frequent RCF indicates that nodal/paranodal alterations may represent the main pathophysiology. Muscle Nerve, 2018.

Objective: Current diagnostic electrophysiological criteria can miss the early stages of Guillain-Barre syndrome (GBS). We evaluated the diagnostic efficiency of the triple stimulation technique (TST) in highlighting proximal conduction blocks (CBs) in patients who do not meet the electrophysiological criteria for GBS. Methods: All patients with a diagnosis of clinical GBS referred to our center between September 2014 and January 2016 were included in the study. For patients who did not fulfill the electrophysiological criteria of GBS, we performed the TST examination. Results: Among the 44 included patients, 86% fulfilled the electrophysiological criteria of GBS during the initial nerve conduction study (NCS). The six remaining patients had proximal CBs revealed by TST examination. Therefore, a combination of a conventional NCS and the TST allowed 100% of the patients to be electrophysiologically diagnosed. Conclusions: TST is useful for the diagnosis of GBS in association with NCS, particularly in the early stages of the disease. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective To investigate the relationship between Motor Unit Number Index (MUNIX) and functional scales in patients with anti-Myelin Associated Glycoprotein (MAG) neuropathy and to know if MUNIX is modify after rituximab (RTX) therapy. Methods 17 patients were enrolled, of whom 6 were prospectively evaluated during one year after RTX treatment. MUNIX technique was assessed in abductor digiti mini (ADM), abductor pollicis brevi (APB) and tibialis anterior (TA) muscles. MUNIX sum score was calculated by adding the results of ADM, APB and TA muscles. Results MUNIX sum score was correlated with overall neuropathy limitation scale (ONLS) ( r =−0.55, p =0.02), grip strength in dominant hand ( r =0.63, p =0.01) MRC testing ( r =0.71, p r =0.71, p =0.001). Twelve months after RTX, four patients improved their disability measured on the ONLS score, five patients had improved MUNIX sum score with a median increase of 37% compared to initial evaluation. Conclusions MUNIX is related to motor impairment and disability in anti-MAG neuropathy and MUNIX is modified after immunosuppressive treatment. Significance Considering its advantages, MUNIX may be a suitable test to evaluate anti-MAG neuropathy in clinical trials.

Introduction We propose a motor unit number index (MUNIX) global sum score in amyotrophic lateral sclerosis (ALS) to estimate the loss of functional motor units. Methods MUNIX was assessed for 18 ALS patients and 17 healthy controls in 7 muscles: the abductor pollicis brevis (APB), abductor digiti minimi (ADM), tibialis anterior (TA), deltoid, trapezius, submental complex, and orbicularis oris. Results MUNIX was significantly lower in ALS patients than in healthy controls for the APB, ADM, TA, and trapezius muscles. The MUNIX sum score of 4 muscles (ADM + APB + trapezius + TA) was lower in ALS patients (P = 0.01) and was correlated with clinical scores. Discussion The global MUNIX sum score proposed in this study estimates the loss of lower motor neurons in several body regions, including the trapezius, and is correlated with clinical impairment in ALS patients. Muscle Nerve 56: 202–206, 2017

International audience; Background: Conduction blocks (CB) are the diagnostic hallmark of multifocal motor neuropathy (MMN). Conventional nerve conduction studies cannot detect CB above Erb's point. Our purpose was to compare the performance of the motor evoked potential with triple stimulation technique (MEP-TST) and MRI in the detection of abnormalities of the brachial plexus.Methods: Examinations were performed on 26 patients with MMN (11 definite, 6 probable, 9 possible), of whom 7 had no CB. Results: MEP-TST detected proximal CB in 19/26 patients. Plexus MRI showed T2 hyperintensity in 18/26 patients, with nerve enlargement in 14/18. A combination of both techniques increased the detection rate of brachial plexus abnormalities to 96% of patients (25/26).Conclusions: MEP-TST and MRI have high sensitivities for detecting brachial plexus abnormalities. A combination of the two techniques increases the detection rate of supportive criteria for the diagnosis of MMN

Intravenous immunoglobulins (IVIg) are commonly used for treatment of dysimmune diseases, but they are known to promote thrombotic events. The medical records of patients who received IVIg infusions to treat neuromuscular disorders were retrospectively studied during two periods: the on-demand period (May 2013-January 2015), when patients received anticoagulant prophylaxis based on personal thrombotic risk factors, and the systematic period (May 2015-January 2017), when patients received systematic anticoagulant prophylaxis. Of the 334 total patients included, 19/153 received anticoagulant prophylaxis in the on-demand period, and 181 were treated in the systematic period. In the on-demand period, thrombosis occurred in three patients (1.96%) as one central retinal artery occlusion, one pulmonary embolism, and one brachiocephalic vein thrombosis. In the systematic period, thrombosis occurred in two patients (1.1%), both as pulmonary embolisms. There was no statistical difference in thrombosis incidence between the periods (P=0.66). The only factor associated with thrombosis was splenectomy (20% versus 0.3% in patients without thrombosis, P=0.03). There were no adverse events due to thromboprophylaxis by low-molecular-weight heparin in either period. Systematic thromboprophylaxis did not significantly reduce the incidence of thrombosis versus thromboprophylaxis based on personal thrombotic risk.

Objectives To evaluate the sensitivity and specificity of the latency difference (DLat) between ulnar and median nerves of the arm after stimulation at the wrist; one of the easiest techniques proposed for recognizing ulnar neuropathy at the elbow (UNE). As latency difference is not a standardized technique, we set up a multicenter study to recruit large numbers of normal subjects and patients with UNE or generalized neuropathy. Methods Six centers participated in the study with data obtained from three groups of participants, controls (CTRLs), patients with UNE and patients with generalized neuropathy (GNP). We first verified the anatomical superposition of the ulnar and median nerves in cadaver examination. The optimal recording site for these two nerves was found to be 10 cm above the medial epicondyle. We then standardized the position of the arm with full extension of the elbow and stimulated first the median and then the ulnar nerves at the wrist. CTRLs were examined on both arms at two consecutive visits. Results We recorded 32 idiopathic UNE cases, 44 GNP patients and 62 controls. We demonstrated that a DLat cut-off value of 0.69 ms brings a sensitivity of 0.86 and specificity of 0.89 to discriminate CTRLs from UNE. We also validated that intra-examiner reproducibility was good. Conclusion We report a lower normal value for DLat than reported in several non-standardized studies and CTRL and UNE groups have clearly separated DLat values. Significance Due to its high sensitivity, our standardized technique could be used as a first-line diagnostic tool when UNE is suspected.

Introduction: The diagnostic sensitivity of repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) varies as a function of the number of muscles or the choice of muscles studied. Methods: By exploring 12 muscles bilaterally, we evaluated the global sensitivity of RNS at rest, the sensitivity in different clinical forms, and the sensitivity of different combinations of muscles studied. Results: The global sensitivity of RNS was 82%, and specificity was 100%. The sensitivity in the MG subgroups was as follows: ocular (O) = 67%, oculo-bulbar (OB) = 86%, and generalized (G) = 89%. The most sensitive muscles were the anconeus in group O, orbicularis oculi (OO) or nasalis in group OB, and the trapezius in group G. Maximum sensitivity was obtained by exploring OO, trapezius, and anconeus bilaterally. Conclusions: We recommend bilateral exploration of at least 3 muscles: a facial muscle, trapezius, and anconeus. This article is protected by copyright. All rights reserved.

To determine whether motor unit number index (MUNIX) is pertinent to monitor the effect of intravenous immunoglobulins (IVIg) in multifocal motor neuropathy (MMN).MUNIX was assessed longitudinally in 7 MMN patients and 17 healthy controls in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. A MUNIX sum-score and a compound muscle action potential (CMAP) sum-score were calculated by summing up the scores of APB and ADM. MMN patients were evaluated on the first day of IVIg infusion, 5 MMN patients were evaluated 22days after IVIg infusion, and 3 MMN patients were evaluated 1month after two IVIg infusions.Intraclass correlation coefficient of the MUNIX sum-score in healthy controls was 0.85, showing good test-retest reproducibility. MUNIX and CMAP sum-scores were lower in MMN patients than in healthy controls (p0.01 and 0.02, respectively). MUNIX sum-score improved in three of the five patients 22days after IVIg infusion and in two of the three patients 1month after 2 IVIg infusions, whereas CMAP sum-score improved in only one patient in both evaluations.In this preliminary study, MUNIX seems to be a reliable and sensitive tool to monitor the short-term efficiency of IVIg in MMN.MUNIX can help monitor IVIg treatment in MMN.

Introduction Les inhibiteurs de check point (ICP) ont revolutionne la prise en charge therapeutique de nombreux cancers. Leur mode d’action novateur consiste a reprimer l’inhibition de l’immunite lymphocytaire anti-tumorale induite par le cancer. Le prix a payer est souvent l’induction d’une auto-immunite qui peut toucher jusqu’a 90 % des patients. Nous presentons ici le cas d’un patient ayant presente plusieurs complications auto-immunes neurologiques suite a un traitement par nivolumab + ipilimumab. Observation Il s’agit d’un patient de 68 ans sans antecedent particulier en dehors d’un melanome metastatique (pulmonaire et osseux) diagnostique en juin 2019 et pris en charge par double immunotherapie nivolumab et ipilimumab. Le patient beneficiait de 2 cures a 3 semaines d’intervalle au mois de juillet 2019. La cure prevue en aout etait decalee en raison d’une alteration de l’etat general et d’une cytolyse hepatique a 3N predominant sur les ASAT, avec un bilan etiologique d’hepatite aigue negatif. Le 14 aout, le patient etait hospitalise en service de neurologie pour confusion, dyspnee, troubles de la deglutition et faiblesse motrice compliquee d’une perte de la marche. L’examen clinique objectivait une desorientation spatiotemporelle, des crepitants bi-pulmonaires, un reflux hepato-jugulaire, un deficit moteur des 4 membres predominant sur les ceintures evalue a 4/5, un ptosis et une dysphonie a predominance vesperale. Le bilan biologique retrouvait des CPK a 5000 UI/L, des proBNP a 24 000 UI/L, et une troponine superieure a 10N. L’ECG est normal. L’electromyogramme montre un trace myogene en detection et la recherche de decrement a la stimulation nerveuse repetitive a basse est positive sur les 2 trapezes et un ancone. L’analyse du LCR est sterile, tout comme les PCRmycobacterie, HSV, CMV, listeria mais retrouve une pleiocytose a 25 lymphocytes par mm3. L’IRM musculaire retrouve un infiltrat inflammatoire des 2 deltoides et du myocarde. L’IRM cerebrale retrouve des hypersignaux FLAIR sous corticaux en faveur d’une encephalite. Le bilan immunologique retrouve un DOT myosite negatif, des anticorps anti-recepteur de l’acetylcholine positifs a 2 nmol/L pour une normale N Discussion Les inhibiteurs de check point ont permis une amelioration nette de la survie dans certains cancers, en particulier le melanome metastatique, et leur balance benefice–risque est clairement favorable. Les complications auto-immunes qui leur sont associees sont plus frequentes en cas de bitherapie comme dans notre cas, et peuvent parfois etre d’evolution dramatique. La toxicite neurologique des ICP est relativement rare, estimee a 5 % des complications immunologiques de ces traitements. La particularite de notre patient est d’avoir presente simultanement une myosite auto-immune avec myocardite, une myasthenie auto-immune et une encephalite limbique. Des associations synchrones de differentes maladies auto-immunes sont decrites dans le cadre des effets indesirables des ICP, et ne doivent pas egarer le clinicien. Les complications immunologiques des ICP sont le plus souvent benignes, puisque moins de 10 % necessitent un arret du traitement, mais les atteintes neurologiques semblent relativement plus severes, et en particulier, 25 % des myosites rapportees ont ete fatales. Conclusion Ce patient a presente simultanement une myosite auto-immune avec myocardite, une myasthenie auto-immune et une encephalite limbique induites par les ICP dans un contexte de melanome metastatique. La toxicite immunologique des ICP peut etre complexe, associant plusieurs entites syndromiques differentes susceptibles retarder le diagnostic, et gravissime, comme dans notre cas.

International audience; Introduction. - A retrospective analysis was performed to document the clinical and electrophysiological features of Guillain-Barre syndrome (GBS) subtypes using different diagnostic criteria. Methods. - One hundred GBS patients were included. Clinical and laboratory features were analyzed, and patients were classified according to four sets of diagnostic criteria. Electrodiagnostic criteria were also analyzed. Results. - A total of 69 patients met Asbury and Cornblath's criteria, 96 met Van der Meche's criteria, 99 met Wakerley's diagnostic classification and 86 met level 1 or 2 of the Brighton criteria. Rates of GBS subtypes were: 69% classic GBS; 8% Miller-Fisher syndrome; 12% paraparetic GBS; 2% pharyngeal-cervical-brachial GBS; and 9% unclassified. Those for electrodiagnostic subtypes were 52% demyelinating and 9% axonal according to Hadden's criteria us 41% demyelinating and 41% axonal as per Rajabally's criteria. Conclusion. - In this study of case distribution within the GBS spectrum of a retrospective cohort of French patients, the application of new diagnostic criteria enabled accurate diagnoses and classifications of the different subtypes, and also increased the recognition of axonal GBS. (C) 2018 Elsevier Masson SAS. All rights reserved.

Introduction Depuis une dizaine d’annees, les immunotherapies inhibitrices des check-point blockers anti-PD1, anti-PDL1 et anti-CTLA4 completent de maniere efficace l’arsenal therapeutique contre les cancers. Elles agissent en supprimant le blocage des cellules de l’immunite par les cellules cancereuses et donc en stimulant l’immunite anti-tumorale. L’effet secondaire le plus frequent est donc l’auto immunite qui peut affecter jusqu’a 90 % des patients. Nous presentons ici le cas d’un patient ayant presente plusieurs complications auto-immunes suite a un traitement par nivolumab. Observation Il s’agit d’un patient de 72 ans ayant pour antecedent une thyroidite de Quervain et une thyroidectomie compliquee d’une hypothyroidie substituee. Il presente en janvier 2018 un adenocarcinome pulmonaire avec metastases osseuses, traite par 4 cures de carboplatine-taxol avec un entretien par 3 cycles de pemetrexed. Malgre ce traitement, en septembre 2018 la maladie marque une progression osseuse, ganglionnaire et surrenalienne motivant un traitement par nivolumab, une premiere cure composee de j1 et j15 en octobre. Debut novembre, la deuxieme cure est decalee devant une cytolyse a 5 N predominant sur les ASAT. Le bilan d’hepatite aigue est negatif, la cytolyse d’aggrave. En parallele, apparition de troubles de deglutition, d’une dysphonie et d’un ptosis. Le 17 novembre, il est hospitalise en unite de soins intensifs pour un choc cardiogenique. Un diagnostic de myocardite est pose sur le rehaussement myocardique des ventricules a l’IRM. L’etat du patient necessite un soutien aminergique par dobutamine et une corticotherapie a 2 mg/kg/jour est debutee pour le traitement d’une myocardite auto-immune secondaire au nivolumab. La myocardite s’ameliore avec une FEVG a 52 % et la disparition des troubles du rythme. Cependant les symptomes neurologiques s’aggravent avec[AMG1] une diplegie faciale, une aphagie, une diplopie, un deficit moteur axial avec tete tombante, le patient estaphone [AMG2] et anarthrique. Il n’y a pas de fluctuation des symptomes. Les CK sont tres augmentees a 4000 UI/L, malgre la normalisation des enzymes cardiaques et du bilan hepatique. L’electroneuromyogramme montre un trace myogene en detection et la recherche de decrement a la stimulation nerveuse repetitive a basse frequence sur 13 couples nerf/muscle est negative. Nous evoquons une myosite auto-immune secondaire au nivolumab. Le DOT myosite est negatif. Les anticorps anti-recepteurs de l’acethylcholine sont faiblement positifs a 0,95 nmol/L (N Discussion Ces nouveaux traitements sont tres prometteurs en termes de survie, la tolerance est globalement bonne, leurs indications augmentent (melanome, cancer colo-rectal, adenocarcinome pulmonaire, carcinome urothelial, lymphome Hodgkinien…). Il faut neanmoins garder a l’esprit leurs complications auto-immunes qui peuvent etre gravissimes. Les complications neurologiques representent 5 % des complications des inhibiteurs des check-points ; parmi elles, le systeme nerveux peripherique est atteint dans 60 a 75 % des cas. Les cas de myosites associees aux inhibiteurs des check-point presentent parfois une dysphonie, une dysphagie ou une fatigabilite, evocateurs de myasthenie ce qui peut etre trompeur. L’association de ces deux atteintes auto-immunes, rare habituellement est plus frequente. Les complications auto-immunes sont le plus souvent benignes, moins de 10 % d’entre elles necessitent un arret de l’immunotherapie. Cependant certaines atteintes peuvent etre severes, comme celles presentees par notre patient. En effet, 25 % des myosites secondaires aux immunotherapies anticancereuses ont ete fatales. Conclusion Ce patient a presente une myosite auto-immune avec myocardite et une myasthenie auto-immune secondaires a un traitement par anti-PD1 en deuxieme ligne de traitement d’un adenocarcinome pulmonaire metastatique. Alors que l’evolution des complications est favorable dans 70 % des cas apres traitement, notre patient a presente un effet indesirable de grade 5.

Introduction: Conduction block (CB) has been included in the Rajabally criteria for axonal Guillain–Barre syndrome (GBS). Because the nerve roots may be affected early in GBS, detection of proximal CB by the triple stimulation technique (TST) can be useful. Methods: We describe TST findings in 2 patients who presented with the pharyngeal–cervical–brachial (PCB) variant of axonal GBS. Results: In the first patient, although conventional nerve conduction studies (NCS) did not fit electrodiagnostic criteria for axonal GBS, the TST detected proximal CB in the median and ulnar nerves. In the second patient, NCS fulfilled criteria for axonal GBS, and the TST detected proximal CB in the median nerve. After plasmapheresis, NCS and TST findings were normalized, suggesting reversible conduction failure rather than demyelinating CB. Conclusion: The TST may be useful for diagnosis of PCB when NCS remain inconclusive. The technique provides additional clues for classifying PCB into the acute nodo-paranodopathies. Muscle Nerve, 2015

Resume Si un deficit moteur distal evoque classiquement une atteinte de la corne anterieure ou du nerf peripherique, il peut etre plus rarement l’expression d’une maladie musculaire. Une myopathie doit etre evoquee devant un deficit distal moteur pur, selectif, ne correspondant pas une systematisation tronculaire ou radiculaire. L’interrogatoire et l’examen clinique minutieux doivent rechercher des signes en faveur d’une atteinte musculaire plus diffuse ou d’autres atteintes systemiques. Les examens complementaires tels que le dosage des CPK, l’ENMG, l’imagerie musculaire apportent des arguments au diagnostic topographique mais peuvent etre d’interpretation difficile. La biopsie musculaire est un element cle du diagnostic : en confirmant le caractere myopathique du deficit et en mettant en evidence des anomalies (vacuoles bordees, deficit proteique) permettant d’orienter l’enquete moleculaire. La clinique, l’ENMG et l’imagerie musculaire doivent guider le siege de la biopsie pour ameliorer sa rentabilite. Les maladies musculaires se presentant par un deficit distal sont essentiellement des maladies musculaires genetiques. Le diagnostic moleculaire repose sur une strategie de sequencage cible « gene par gene » par methode Sanger tenant compte de l’âge de debut, du mode de transmission, de la topographie de l’atteinte et de la presence ou non de vacuoles bordees en histopathologie. Cependant, l’avenement du sequencage a haut debit ouvre de nouvelles perspectives dans le diagnostic de ces pathologies.

Objectives: To assess the usefulness of serial electrophysiology in Guillain-Barre syndrome (GBS) in a multicenter setting and the reasons for change in electrodiagnostic subtypes with serial studies. Methods: We retrospectively analysed serial electrophysiology of 51 patients with GBS from 4 European centres. Proportions of subtypes were determined at each timing. Individual case analyses were also performed where diagnostic changes occurred with either criteria, to ascertain if changes were due to disease progression or criteria inadequacy. Results: At first study, comparing old vs new criteria, acute inflammatory demyelinating polyneuropathy (AIDP) was diagnosed in 70.6% vs 51%, axonal GBS in 15.7% vs 39.2%, equivocal forms in 11.8% vs 7.8%. At second study, AIDP was diagnosed in 72.5% vs 52.9%, axonal GBS in 9.8% vs 33.3%, equivocal forms in 15.7% vs 11.7%. Subtype proportions were unchanged, indicating serial studies did not, in the cohort, alter diagnostic rates for each subtype irrespective of criteria used. Individual review of cases where subtype electrodiagnosis changed indicated suboptimal specificity for AIDP/sensitivity for axonal GBS as main cause of diagnostic shifts with old criteria, whereas disease progression explained most changes with new criteria (55.6% vs 81.8%; P = .039). Conclusions: Serial electrophysiology is unhelpful in GBS. Repeat studies cannot represent the gold standard as electrodiagnosis may alter due to disease progression. Changes in electrodiagnosis relate more often to disease progression with new criteria but are more frequently due to suboptimal sensitivity/specificity with old criteria. A single electrophysiological study using the most accurate available criteria appears sufficient in GBS.

International audience; BACKGROUND AND PURPOSE: The frequency of pain and cramps is uncertain in anti-myelin associated glycoprotein antibody (anti-MAG) neuropathy. Whether these symptoms may affect function/quality of life is unknown.METHODS: A cross-sectional study of the prevalence, correlates and impact of pain, pain subtypes and cramps, their severity, frequency and anatomical distribution was performed for 55 clinically stable patients with anti-MAG neuropathy.RESULTS: Pain of any type was reported by 80% of subjects. The most common subtype was paraesthesiae and dysaesthesiae (70%). Cramps were reported by >60% of patients, with lower limb cramps in all and upper limb cramps in about 20%. Cramps affected daily activities in >30% of these subjects, sleep in 60%, ability to exercise in >30%. Total pain score correlated with several Short Form 36 health-related quality of life (SF-36 HR-QoL) measures (PCONCLUSIONS: Neuropathic pain and cramps may affect function and quality of life in anti-MAG neuropathy. Optimizing treatments of these symptoms, including by adequate levels of physiotherapy, may be beneficial in affected patients and requires further research.

Objective: The aim of this study was to assess the usefulness of motor unit number index (MUNIX) tech-nique in Charcot-Marie-Tooth disease and test the correlation between MUNIX and clinical impairment. Methods: MUNIX technique was performed in the abductor pollicis brevis (APB), the abductor digiti min-imi (ADM) and the tibialis anterior (TA) muscles in the nondominant side. A MUNIX sum score was cal-culated by adding the MUNIX of these 3 muscles. Muscle strength was measured using the MRC (medical research council) scale. Disability was evaluated using several functional scales, including CMT neuropa-thy score version 2 (CMTNSv2) and overall neuropathy limitation scale (ONLS). Results: A total of 56 CMT patients were enrolled. The MUNIX scores of the ADM, APB and TA muscles correlated with the MRC score of the corresponding muscle (p < 0.01). The MUNIX sum score correlated with the clinical scales CMTNSv2 (r = -0.65, p < 0.01) and ONLS (r = -0.57, p < 0.01). Conclusion: MUNIX correlates with muscle strength and clinical measurements of disability in patients with CMT disease. Significance: The MUNIX technique evaluates motor axonal loss and correlates with disability. The MUNIX sum score may be a useful outcome measure of disease progression in CMT. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Our objective was to assess determinants of quality of life (QoL) in anti-myelin associated glycoprotein antibody (MAG) neuropathy. The SF-36 questionnaire was assessed in 55 patients, from Marseille, Angers (France) and Birmingham (UK). Routine clinical evaluations included Medical Research Council (MRC) sum score, inflammatory neuropathy cause and treatment (INCAT) sensory score, inflammatory Rasch-built overall disability score (I-RODS), ataxia score, Jamar grip dynamometry, timed 10-m walk, neuropathic pain symptom inventory (NPSI) score, and fatigue severity score (FSS). Physical component summary (PCS) and mental component summary (MCS) of the SF36 questionnaire were significantly lower than in reported normal subjects of both countries (p0.001). All SF-36 domains correlated with I-RODS, except MCS for which significance was, however, approached (p = 0.056). PCS correlated with MRC sum score, ataxia score, timed 10-m walk, tremor, Jamar grip dynamometry, NPSI pain score, FSS and level of social support. MCS correlated exclusively with FSS and level of social support. In multivariate regression, PCS was associated independently with I-RODS (p0.001) and NPSI pain score (p = 0.011), whereas MCS was associated independently with FSS (p = 0.022). QoL is accurately predicted in anti-MAG neuropathy by the I-RODS and FSS, lending support to their use in clinical and research settings. Effective measures to improve QoL should include tremor and neuropathic pain treatment, fatigue management, and improved social support.

International audience; h i g h l i g h t s Motor-evoked potential (MEP) gain is decreased in patients with amyotrophic lateral sclerosis (ALS). MEP gain may allow the early detection of upper motor neuron dysfunction in patients and improve the diagnosis of ALS. The diagnostic utility of MEP gain is equivalent to the triple stimulation technique (TST) and better than diffusion tensor imaging (DTI). a b s t r a c t Objective: The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amy-otrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background elec-tromyographic activity) represents an efficient alternative to assess UMN dysfunction. Methods: MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). Results: MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. Conclusion: MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. Significance: MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction.

We propose a motor unit number index (MUNIX) global sum score in amyotrophic lateral sclerosis (ALS) to estimate the loss of functional motor units.MUNIX was assessed for 18 ALS patients and 17 healthy controls in 7 muscles: the abductor pollicis brevis (APB), abductor digiti minimi (ADM), tibialis anterior (TA), deltoid, trapezius, submental complex, and orbicularis oris.MUNIX was significantly lower in ALS patients than in healthy controls for the APB, ADM, TA, and trapezius muscles. The MUNIX sum score of 4 muscles (ADM + APB + trapezius + TA) was lower in ALS patients (P = 0.01) and was correlated with clinical scores.The global MUNIX sum score proposed in this study estimates the loss of lower motor neurons in several body regions, including the trapezius, and is correlated with clinical impairment in ALS patients. Muscle Nerve 56: 202-206, 2017.

Les examens electrophysiologiques sont un element important de l’evaluation des patients atteints de SLA car ils permettent de quantifier de facon non invasive la dysfonction des neurones moteurs. En particulier, la determination du nombre d’unites motrices (UM) innervant un muscle est d’un interet considerable parce qu’elle a l’avantage de ne pas etre influencee par la reinnervation compensatrice, contrairement aux evaluations cliniques et aux autres mesures electrophysiologiques. Plusieurs techniques ont ete developpees pour estimer le nombre d’UM in vivo. Ces methodes necessitent du temps et une maitrise technique importante. La technique Motor Unit Number Index (MUNIX), developpee par l’equipe de Stalberg en 2004, fournit un index directement correle au nombre d’UM fonctionnelles. Elle utilise un modele mathematique base sur l’aire et la puissance du potentiel global d’action musculaire (PGAM) apres une stimulation nerveuse electrique supramaximale et de l’electromyogramme de surface a differents niveaux de contraction volontaire concentrique. Sa realisation est rapide (environ 5 min par muscle), ainsi que son apprentissage, et elle est bien supportee par les patients. La mesure de MUNIX peut donc etre realisee facilement sur plusieurs muscles, permettant une evaluation des differents territoires affectes par la maladie. Plusieurs etudes ont montre une bonne reproductibilite intra- et inter-examinateur chez les sujets sains et les patients SLA. MUNIX est diminue chez les patients SLA compares aux sujets sains, et sa diminution est correlee aux mesures cliniques telles que l’ALSFRS-R ou le testing musculaire. Les etudes longitudinales montrent de facon interessante une diminution significative de MUNIX dans le temps, qui pourrait etre plus rapide que la diminution de l’amplitude du PGAM voire meme que l’alteration des scores cliniques. La diminution de MUNIX pourrait etre mesuree dans des muscles encore asymptomatiques. MUNIX pourrait ainsi etre un marqueur sensible pour quantifier la progression de la SLA sur une periode courte et donc un outil pertinent dans les essais therapeutiques.

To determine the test-retest reliability of motor unit number index (MUNIX) technique and to explore if the MUNIX sumscore could be related with disability in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).The MUNIX technique was unilaterally assessed in the abductor digiti mini (ADM), the abductor pollicis brevi (APB) and the tibialis anterior (TA) muscles two different times by two blinded examiners. The MUNIX sumscore was calculated by adding the results of the ADM, APB and TA muscles.14 CIDP patients were enrolled. The intraclass correlation coefficient (ICC) was great for inter and intra variability for ADM muscles (0.8 and 0.81), TA muscles (0.86 and 0.89) and MUNIX sumscore (0.76 and 0.83). The MUNIX sumscores from the first and second evaluations were strongly correlated (r=0.83, p0.001). The MUNIX sumscore was significantly correlated with MRC testing (r=0.71, p0.01), overall neuropathy limitation scale (ONLS) (r=-0.70, p0.001), rasch-built overall disability scale (R-ODS) (r=0.71, p0.001).The MUNIX technique has a good reproducibility and the MUNIX sumscore is related to the disability.The MUNIX technique estimates the axonal loss and the number of functional motor units. The MUNIX sumscore may be a good instrument to evaluate the CIDP patients during their follow-up.

Conduction block (CB) has been included in the Rajabally criteria for axonal Guillain-Barré syndrome (GBS). Because the nerve roots may be affected early in GBS, detection of proximal CB by the triple stimulation technique (TST) can be useful.We describe TST findings in 2 patients who presented with the pharyngeal-cervical-brachial (PCB) variant of axonal GBS.In the first patient, although conventional nerve conduction studies (NCS) did not fit electrodiagnostic criteria for axonal GBS, the TST detected proximal CB in the median and ulnar nerves. In the second patient, NCS fulfilled criteria for axonal GBS, and the TST detected proximal CB in the median nerve. After plasmapheresis, NCS and TST findings were normalized, suggesting reversible conduction failure rather than demyelinating CB.The TST may be useful for diagnosis of PCB when NCS remain inconclusive. The technique provides additional clues for classifying PCB into the acute nodo-paranodopathies.

International audience; In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2 *-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R = -0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p \textless 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p \textless 0.005), and λ// (axial diffusivity) decreased significantly in CST (p = 0.0004) and PST (p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 \textless \textbarR\textbar \textless 0.87, p \textless 0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.

Introduction Les dissections carotidiennes ont souvent des consequences ischemiques en aval, mais peuvent egalement etre responsables de complications locales, de nature compressive. Observation Nous presentons le cas d’un patient de 57 ans, sans antecedent connu, qui a presente une hemicrânie droite, suivie d’une dysphagie et d’une dysphonie s’installant rapidement en une douzaine d’heures. A l’examen, le patient presentait une atteinte des nerfs crâniens XII, X et IX droits, sans atteinte sensitivo-motrice des voies longues. Par ailleurs, le patient presentait un syndrome dysmorphique jamais explore (hypoplasie claviculaire, persistance de la fontanelle anterieure, dents surnumeraires, scoliose severe), correspondant a une dysplasie cleido-crânienne. La premiere IRM cerebrale realisee a son admission aux urgences etait normale. L’IRM cerebrale centree sur la base du crâne realisee quelques jours apres montra une lesion en regard du foramen jugulaire interne et du canal de l’hypoglosse droits, lesion dont la nature a finalement ete determinee apres un angioscanner des troncs supra-aortiques, montrant un aspect de dissection de l’artere carotide interne droite, dont l’hematome de paroi comprimait les nerfs crâniens IX, X, et XII droits et responsable de ce syndrome du carrefour condylo-dechire posterieur (SCDP) droit aigu. Discussion Le SCDP ou syndrome de Collet-Sicard releve de causes variees, notamment la dissection de la carotide interne, dont la presentation peut etre trompeuse. La dysplasie cleido-crânienne est chez notre patient responsable d’une tortuosite importante de l’artere carotide interne, mais aucune donnee n’atteste que cette rare dysmorphie congenitale soit associee a un sur-risque de dissection vasculaire. Conclusion La dissection de l’artere carotide interne est une cause de SCDP, responsable d’un tableau clinique severe (aphagie, dysarthrie notamment), ayant pu chez ce patient etre favorisee par une dysplasie cleido-crânienne non connue.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculopathy frequently triggered by infection. It has also been reported in some cases after surgical procedures. We describe the first case of GBS occurring 9 days after lung lobectomy for localized lung cancer and efficiently treated with intravenous immunoglobulins. The exact physiopathology of GBS after surgical procedures is unknown. An immune-mediated process and perioperative infection are the most accepted etiologic hypotheses.