Chronic Immune-mediated Neuropathies Research Articles

Dose-exposure-efficacy response of intravenous immunoglobulin G 10% in multifocal motor neuropathy.

Multifocal motor neuropathy is a rare chronic immune-mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose-exposure-response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure. Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double-blind, placebo-controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic-pharmacodynamic model. The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter-patient variabilities in multifocal motor neuropathy. Model-based simulations for various dosing regimens (0.4-2.0 g/kg every 2-4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength. These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose-splitting provided similar outcomes while offering flexibility and convenience.

Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN), an acquired chronic progressive immune-mediated motor neuropathy, is characterized by asymmetrical distal upper limb muscle weakness and muscle atrophy without sensory impairment. Differentiation from amyotrophic lateral sclerosis is usually challenging, and electrophysiological studies show multifocal conduction blocks. Immunoglobulin (Ig)M GM1 antibodies are detected in approximately 50% of patients. In contrast to chronic inflammatory demyelinating polyneuropathy, corticosteroids are ineffective for management of MMN, and IVIg is the sole established treatment.

Semiquantitative assessment of preganglionic nerves for chronic immune-mediated neuropathies using brachial plexus magnetic resonance imaging.

Brachial plexus magnetic resonance imaging (MRI) is an important noninvasive supplementary diagnostic method of chronic immune peripheral neuropathies, but few MRI studies on the preganglionic nerves have been conducted. This retrospective cross-sectional study aimed to establish a reliable assessment for brachial plexus preganglionic nerve thickness and to use this method to assess and compare nerve characteristics in various types of peripheral neuropathies. Hospitalized patients diagnosed as positive for anti-neurofascin-155 (NF155)-positive autoimmune nodopathy (AN) (NF155+), chronic inflammatory demyelinating polyneuropathy (CIDP), or multifocal motor neuropathy (MMN) at Huashan Hospital of Fudan University in Shanghai, China, who underwent brachial plexus MRI between October 2011 and August 2023 were consecutively recruited for this study. We also recruited participants who underwent brachial plexus MRI during this period with no history of trauma, inflammation, tumors, compression, or degenerative conditions as healthy controls. According to our self-developed semiquantitative assessment of preganglionic nerves, we assessed the bilateral preganglionic C5-C8 nerves individually and scored the enlargement degree from 0 to 4 points. Furthermore, a sum score ≥20 was defined as definite enlargement. A total of 122 participants were enrolled, including 28 with NF155+, 40 with CIDP, 15 with MMN, and 39 healthy controls. In the comparison of the single-nerve scores, we found that there was a significant difference distribution among the four groups (χ2 test; P<0.001), with the patients with NF155+ exhibiting the highest scores in each of the bilateral C5-C8 nerves. In the comparison of the sum scores, a descending tendency was observed in patients NF155+, CIDP, and MMN, with median scores of 11, 4, and 0 points, respectively (Kruskal-Wallis test; P=0.003, P<0.001, and P=0.005, respectively for NF155+ vs. CIDP, NF155+ vs. MMN, and CIDP vs. MMN). The proportion of definite enlargement in those with NF155+ was greater than that in healthy controls (21% vs. 0%; χ2 test; P=0.004), and the sum score at 0 points was lower in the NF155+ group than in CIDP, MMN, and healthy control groups (7% vs. 37%, 87%, and 41%, respectively; χ2 test; P<0.001). This semiquantitative assessment can be a valuable tool for measuring preganglionic nerve enlargement, which was found to be decreased, respectively, in those with NF155+, CIDP, and MMN. Presence of definite enlargement could be a strong indicator of NF155+ in clinic.

A borderline case between multifocal motor neuropathy and motor chronic inflammatory demyelinating polyneuropathy revealed by the magnetic fatigue test

A 26-year-old woman presented with a seven-month history of weakness in her left upper limb, progressing to difficulty lifting her arms within a few weeks. Her symptoms progressed with fluctuations. For the past three months, she has been unable to stand due to weakness in her proximal lower limbs. Nerve conduction studies did not show any definite conduction block or abnormal sensory conduction, but motor conduction studies showed a slight prolongation of the terminal latency and a decrease in the frequency of the F-wave. A magnetic fatigue test indicated a proximal conduction block. Her symptoms were rapidly resolved with intravenous immunoglobulin treatment, leading to a diagnosis of chronic immune-mediated neuropathy, met both criteria for multifocal motor neuropathy (MMN) and motor chronic inflammatory demyelinating polyneuropathy (CIDP). Our case highlights the utility of the magnetic fatigue test in detecting conduction blocks and its role in differentiating between MMN and motor CIDP.

Chronic Immune-Mediated Demyelinating Neuropathies.

This article is an overview of chronic demyelinating neuropathies and highlights the phenotypic categorization, diagnosis, and treatment of chronic immune-mediated neuropathies. The clinical and diagnostic characteristics of other chronic demyelinating neuropathies that are common mimics of immune-mediated neuropathies are also discussed. The underlying pathophysiology of chronic demyelinating neuropathies is heterogeneous, and components of both humoral and cellular immune responses are thought to play a role in the immune-mediated types of chronic demyelinating neuropathy. The role of the humoral response is highlighted with a specific focus on the relatively recent discovery of antibody-mediated antinodal and paranodal demyelinating neuropathies. Additionally, new diagnostic criteria for some of the chronic demyelinating neuropathies, as well as ways to differentiate chronic inflammatory demyelinating polyradiculoneuropathy from other chronic demyelinating polyneuropathies, are discussed. Chronic demyelinating neuropathies can present with overlapping clinical characteristics with seemingly subtle variations. It is clinically important to differentiate these types of neuropathies because the treatment and management can vary and affect prognosis.

Chronic inflammatory demyelinating polyneuropathy with an acute onset. Clinical case

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous treatable dysimmune neuropathy. The variety of clinical forms and course of the disease can be challenging for proper diagnosis and early treatment. In a quarter of cases CIDP starts acutely, mimicking GuillainBarr syndrome. The early diagnosis is especially important regarding differences in treatment and prognosis of these conditions. In this article, we present a clinical case of acute onset CIDP with a detailed analysis of the differential diagnosis between acute and chronic immune-mediated neuropathies.

Rituximab in chronic immune mediated neuropathies: a systematic review

Chronic immune mediated neuropathy is a heterogenous group of peripheral nerve diseases, encompassing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), autoimmune nodopathy, multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) neuropathy. Rituximab (RTX) is a chimeric monoclonal antibody targeting the CD20 antigen, which has been used in the treatment of autoimmune neuropathies, although the efficacy of RTX remains unclear. A literature search was performed using Medline, Embase and Cochrane Register for studies between 2000 and 2021 using the search terms “Chronic inflammatory demyelinating polyneuropathy” OR “Multifocal motor neuropathy” OR “Myelin associated glycoprotein” OR “Distal acquired demyelinating neuropathy” OR “Multifocal acquired demyelinating sensory and motor neuropathy” OR “demyelinating neuropathy” AND “Rituximab”. Twenty-three studies were included, of which two were randomised controlled trials, 6 prospective studies and 15 retrospective studies. RTX was effective in 63% of CIDP patients, 48% of anti-MAG neuropathy, and 96% of patients with autoimmune nodopathy. Neurophysiological improvement was evident in 58% of CIDP and 40% of anti-MAG neuropathy patients. Low rates of serious adverse events (2.6%) were observed. These results indicate that RTX has potential as a treatment in immune mediated polyneuropathy, although the quality of evidence supporting its use it poor. Randomized controlled trials are required to reliably establish the efficacy and safety of RTX. Trial registration number: CRD42020179666.

P 46. Assessment of individualized treatment decisions for intravenous immunoglobulin therapy in patients with chronic immune-mediated neuropathies: observational study design and progress

Introduction. Chronic immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are associated with immune mediated peripheral nerve damage and neurological deficits. Randomized, controlled clinical trials have demonstrated the effectiveness of human intravenous immunoglobulin (IVIG) for these conditions. IVIG is considered a treatment of choice for both disorders. German and EFNS/PNS guidelines recommend individualization of IVIG therapy during treatment for CIDP and MMN. However, there is a lack of documentation of individualized dosing in real-world practice. Objective. This study is designed to determine the patterns of use of 10% IVIG in real-world clinical practice and identify the factors driving treatment decisions for patients with CIDP or MMN. Methods. The study is non-interventional, longitudinal, multicenter design. Primary data collected will be physicians“ practice patterns, demographics, treatment regimens and tolerability of 10% IVIG. Adult patients (n=150) diagnosed with CIDP or MMN and with current or prospective therapy with 10% IVIG will be eligible for the study. Approximately 40 sites in Germany will participate in the study. The planned recruitment period for the study is 18 months starting in first half of 2021. Results. According to the study protocol, patient demographics, medical and disease history and concomitant medication are to be assessed at baseline. Data will be collected at the baseline visit and at each infusion visit (approximately every 3 weeks as scheduled for routine care) for up to 18 months . In addition, the study will include an initial , cross-sectional, quantitative survey for participating physicians on their current practice patterns for CIDP and MMN. The survey will include assessment of initial therapy choices, IVIG dosing, outcome measures, dosing reductions and treatment schemes for relapses. The criteria used for decisions about initiation, continuation and individualization of IVIG treatment (dosing, intervals, co-medication) will be recorded at each visit. Physicians are also requested to provide the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score at baseline and other study visits, if these scores are routinely determined. The physician-assessed Clinical Global Impression of Improvement (CGI-I) is to be performed at all visits. The potential impact of the COVID-19 pandemic on an individual subject“s treatment algorithm will also be captured in the electronic data capture system . To assess safety, serious adverse events and adverse drug reactions will be evaluated at each visit. Conclusions. Results from this clinical trial will allow identification of the factors driving treatment decisions by physicians utilizing 10% IVIG to treat patients with CIDP or MMN as part of their clinical routine and allow assessment of the influence of patient-reported outcomes and objective clinical measures.

Early onset familial relapsing polyneuropathy, mimicking CIDP; A lesson from clinical genetics

Background: In children, chronic immune-mediated neuropathies present with slowly progressive or relapsing episodes of gait difficulty, symmetric weakness and sometimes paraesthesia. Infancy and early childhood age of presentation and familial recurrence are believed to be atypical features.&#x0D; Case presentation: Herein, we describe two brothers from a non- consanguineous Iraqi family, who presented with episodes of acute immune-mediated demyelinating peripheral neuropathy in early infancy that relapsed recurrently. Mild haemolytic anaemia was also reported. Inherited metabolic disorders were suspected and Whole Exome Sequencing of the youngest brother revealed homozygous frame shift mutation in CD59 gene, confirming the diagnosis of autosomal recessive hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy (HACD59).&#x0D; Conclusion: The report highlights the advantage of genetic testing in such rare and inherited conditions. In the lack of necessary non-traditional diagnostic methods, it is substantial to maintain the accustomed medical practice and strategies, based on available clinical data.

Update on therapy of chronic immune-mediated neuropathies.

Chronic immune-mediated neuropathies, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), neuropathies associated with monoclonal gammopathy, and multifocal motor neuropathy (MMN), are a group of disorders deemed to be caused by an immune response against peripheral nerve antigens. Several immune therapies have been reported to be variably effective in these neuropathies including steroids, plasma exchange, and high-dose intravenous (IVIg) or subcutaneous (SCIg) immunoglobulins. These therapies are however far from being invariably effective and may be associated with a number of side effects leading to the use of immunosuppressive agents whose efficacy has not been so far confirmed in randomized trials. More recently, new biological agents, such as rituximab, have proved to be effective in patients with neuropathy associated with IgM monoclonal gammopathy and are currently tested in CIDP.

Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study.

Background:Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce.Methods:We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS).Results:A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p = 0.04, χ2-test, n = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p = 0.02, t-test, n = 48). Patients with Lewis-Sumner syndrome (n = 9) and autoantibody mediated neuropathies (n = 13) had excellent response rates after treatment with RTX (90–100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ.Conclusion:Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.

A Pilot Study on Serial Nerve Ultrasound in Miller Fisher Syndrome.

Objective: Miller Fisher syndrome (MFS) is predominantly a clinical diagnosis, with classic triad of ophthalmoplegia, ataxia, and generalized reduced reflexes. Previous studies in chronic and acute immune-mediated neuropathies indicated that ultrasound, may help to detect changes that could correspond with disease activity. We studied the feasibility of serial nerve ultrasound in MFS, using a healthy controls.Methods: All MFS patients (n = 5) and healthy controls (n = 18), underwent a standardized sonographic protocol that evaluated nerve sizes of facial, large arm and leg nerves, and spinal nerve roots. All MFS patients underwent routine ancillary investigations, including electrodiagnostic testing and for presence of anti-GQ1b antibodies. In addition, four MFS patients had 2nd, and 3rd clinical and sonographic evaluation at 14 and 90 days from onset.Results: The width of the facial nerve was significantly larger in the MFS group than in the control group (MFS: 1.19 ± 0.31 mm vs. normal: 0.67 ± 0.13 mm, P = 0.01). The size of the cervical roots and the nerves in the limbs were similar between the two groups. Two patients' facial nerve size subsided with time, but the decrease in other nerves' sizes were not obvious.Conclusion: Our study showed that serial nerve ultrasound studies are feasible in MFS, and can capture changes in facial nerve size that could complement routine diagnostic tests. Further studies are warranted to determine and compare its test characteristics in MFS.

Immune-Mediated Neuropathies.

The purpose of this review article is to discuss the pathogenesis of acute and chronic immune-mediated neuropathies along with the recent advances in their treatment. Since the first description of Guillain-Barre syndrome (GBS) more than a century ago, there have been numerous forms of immune-mediated neuropathies described expanding the spectrum. Understanding the role of the immune system in the pathogenesis of immune-mediated neuropathies has been an advancement towards the diagnosis and treatment. It is postulated that immune-mediated neuropathies are a group of diseases resulting from autoimmunity towards multiple components of peripheral nervous system. These have a wide range of pathologic mechanisms, defined clinical presentations, electro-diagnostic and laboratory findings which help in diagnosis and management. Although immunosuppression is the common modality of treatment for these disorders, uncovering distinct pathogenic mechanisms can allow for targeted immunomodulation.

Autoimmune Peripheral Neuropathies and Contribution of Antiganglioside/Sulphatide Autoantibody Testing.

Peripheral immune-mediated polyneuropathies (IMPN) are a diverse group of rare neurological illnesses characterized by nerve damage. Leading morphological features are mostly nerve fibre demyelination or combination of axonal damage and demyelination. There has been remarkable progress in the clinical and electrophysiological categorization of acute (fulminant, life-threatening) and chronic (progressive/remitting-relapsing) immune-mediated neuropathies recently. Besides electrophysiological and morphological makers, autoantibodies against glycolipids or paranodal/nodal molecules have been recommended as candidate markers for IMPN. The progress in testing for autoantibodies (autoAbs) to glycolipids such as gangliosides and sulfatide may have significant implications on the stratification of patients and their treatment response. Thus, this topic was reviewed in a presentation held during the 1st Panhellenic Congress of Autoimmune Diseases, Rheumatology and Clinical Immunology in Portaria, Pelion, Greece. For acute IMPN, often referred to as Guillain-Barré syndrome and its variants, several serological markers including autoAbs to gangliosides and sulphatide have been employed successfully in clinical routine. However, the evolution of serological diagnosis of chronic variants, such as chronic inflammatory demyelinating polyneuropathy or multifocal motor neuropathy, is less satisfactory. Serological diagnostic markers could, therefore, help in the differential diagnosis due to their assumed pathogenic role. Additionally, stratification of patients to improve their response to treatment may be possible. In general, a majority of patients respond well to causal therapy that includes intravenous immunoglobulins and plasmapheresis. As second line therapy options, biologicals (e.g., rituximab) and immunosuppressant or immunomodulatory drugs may be considered when patients do not respond adequately.

Intravenous immunoglobulins in patients with clinically suspected chronic immune-mediated neuropathy

Intravenous immunoglobulins (IVIg) are an efficacious treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). IVIg is considered in patients who have a high suspicion of an inflammatory neuropathy, but do not meet diagnostic criteria. The objective of this retrospective study was to assess which diagnostic results led to the decision to administer IVIg and to determine the rate of improvement.We included consecutive patients suspected of CIDP or MMN who did not meet the electrophysiological EFNS/PNS criteria and received IVIg treatment. Patients were included in a tertiary referral center for inflammatory neuropathies and motor neuron diseases.Thirty-five patients were included; 19 patients suspected of CIDP and 16 suspected of MMN. Nerve hypertrophy on ultrasound (80% of patients suspected of CIDP and 67% of patients suspected of MMN) and/or elevated cerebrospinal fluid (CSF) protein (53% of patients suspected of CIDP and 45% of patients suspected of MMN) were the most frequent findings that supported the diagnosis. Thirteen patients suspected of CIDP (68%) and five patients suspected of MMN (31%) responded to treatment. There was no association between the presence of the EFNS/PNS supportive criteria, including nerve hypertrophy on ultrasound, and treatment response.In conclusion, enlarged nerves on ultrasound and elevated CSF protein were the main reasons to start IVIg treatment in our study, although findings did not correlate with treatment response. In tertiary referral clinics, IVIg treatment could be considered in selected patients with a high suspicion of an inflammatory neuropathy, especially in those suspected of CIDP.

Clinical relevance of serum antibodies to GD1b in immune-mediated neuropathies.

Antibodies to the ganglioside GD1b have been reported in various forms of immune-mediated neuropathy, but their clinical relevance for diagnosis and prognosis is unknown. We investigated the prevalence of anti-GD1b antibodies in acute and chronic immune-mediated neuropathies, and the clinical presentation and outcome in Guillain-Barré syndrome (GBS) and Miller Fisher-GBS overlap syndrome (MF-GBS). Anti-GD1b, anti-GM1 and anti-GQ1b antibodies were tested in serum of patients with GBS (N = 165), Miller Fisher syndrome (N = 10), MF-GBS (N = 28), monoclonal gammopathy of unknown significance neuropathy (MGUS; N = 101), chronic inflammatory demyelinating polyneuropathy (N = 29), paraneoplastic syndrome with anti-Hu-associated neuropathy (PNS; N = 11), other auto-immune diseases (AID; N = 60), and healthy controls (HC; N = 60). All samples were tested by enzyme-linked immunosorbent assay according to the Inflammatory Neuropathy Cause and Treatment protocol. IgM anti-GD1b antibodies were found in GBS (N = 4; 2.4%), MGUS (N = 3; 3.0%), and PNS patients (N = 1; 9.1%). IgG anti-GD1b antibodies were found in GBS (N = 20; 12.1%) and MF-GBS (N = 4; 14.3%) patients, but not in the AID and HC group. In the combined group of MF-GBS and GBS patients ((MF-)GBS), 14/36 (38.9%) patients with IgG anti-GD1b antibodies also had IgG anti-GM1 antibodies, and IgG anti-GD1b and IgG anti-GQ1b antibodies were found in 3/29 (10.3%) patients. Patients with (MF-)GBS and anti-GD1b without anti-GM1 antibodies did not differ regarding sensory disturbances or disease severity but recovered faster regarding the ability to walk independently compared with patients without anti-GD1b antibodies (P = 0.031) and with patients with both anti-GD1b and anti-GM1 antibodies (P = 0.034). In conclusion, testing for anti-GD1b antibodies may identify a specific group of immune-mediated neuropathies and (MF-)GBS patients with only anti-GD1b antibodies tend to recover faster.

Anti-ganglioside complex antibodies in chronic immune-mediated neuropathies

Background: Recently, IgG anti-ganglioside complex (GSCs) antibodies have been reported in patients with Guillain-Barré and Miller Fisher syndrome. Some researchers in Europe reported IgM anti-GSCs antibodies in multifocal motor neuropathy (MMN) and other chronic immune-mediated neuropathies.

Editorial introductions

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Jean-Marc LégerJean-Marc LégerDr Léger started his career in neurology at the University Hospital Pitié-Salpêtrière and University Pierre et Marie Curie (Paris VI), France, in 1980, where he trained in general neurology and clinical neurophysiology. He was then nominated as full-time senior neurologist in 1987 in the Department of Neurology, then Institut Hospitalo-Universitaire (IHU) de Neurosciences, University Hospital Pitié-Salpêtrière, and received his post-graduate degree (Habilitation à diriger des Recherches) from University Paris VI in 1991. He is currently coordinator, together with Dr Eymard, of the National Referral Center for rare Neuromuscular Diseases, that was built up in the IHU de Neurosciences/Institut du Cerveau et de la Moelle Epinière (IHU/ICM), at University Hospital Pitié-Salpêtrière, in 2004. Dr Léger's clinical and research interests are in the field of peripheral neuropathy and in particular chronic immune-mediated neuropathy. He has authored and co-authored more than 200 articles in peer-reviewed journals, and contributed more than 30 chapters to books on neurology, mainly in the field of diagnostic features and therapeutic trials in vasculitic neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy and paraproteinaemic neuropathies. He served as Editor-in-Chief of the Revue Neurologique for 8 years and as member of the Editorial Board of Brain for 5 years, and is currently member of the Board of the European Journal of Neurology and Associate Editor of the Journal of the Peripheral Nervous System. Dr Léger is past President of the Société Française de Neurologie, in which he served as Secretary General for 8 years. He served as officer of the Management Committee of the European Federation of Neurological Societies (EFNS) and as chairman of the Training and Education Committee of the EFNS. He is also past member of the Board and member of the Education Committee of the Peripheral Nerve Society, and has organized its biennial meeting in Saint-Malo, France, in July 2013. He is Fellow of the American Academy of Neurology (FAAN), and Corresponding Fellow of the American Neurological Association. He was elected as Full Member of the Académie Nationale de Médecine, France, in 2016. Benedikt SchoserBenedikt SchoserBenedikt Schoser started his career with training in muscle pathology by Hans Goebel and finishing his medical thesis at the institute of neuropathology in Mainz, Germany in 1993. He started his career in neurology at the University Hospitals Mainz, Frankfurt, and Hamburg, Germany, in 1993, where he was trained in general neurology, intensive care neurology, psychiatry, and clinical neurophysiology. After spending a year in Thomas Jentsch's laboratory at the institute of neuropathophysiology in Hamburg, he was nominated as full-time senior neurologist in 2001 at the Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich. He received his post-graduate degree (Habilitation) from Ludwig-Maximilians-University Munich in 2004. He is currently senior consultant neurologist and co-chair of the Friedrich-Baur-Institute, the major national referral centre for rare neuromuscular diseases in Germany. Dr Schoser's clinical and research interests are in the field of multisystemic neuromuscular diseases and in particular metabolic and myotonic myopathies. He has authored and co-authored more than 180 articles in peer-reviewed journals, and contributed more than 20 chapters to books on neurology and muscle pathology, mainly in the field of diagnostic features and therapeutic trials in myotonic dystrophies, myasthenic syndromes, metabolic myopathies, and inflammatory myopathies. He serves as member of the Editorial Board of Neuromuscular disorders, Journal of Neuromuscular diseases, and Zeitschrift für Rheumatologie. Dr Schoser is co-founder and chair of the European Pompe consortium (EPOC). He served as co-chair of the Scientific muscle and neuromuscular junction panel of the European Academy of Neurology (EAN).

Pharmacokinetics and Pharmacodynamics of Intravenous Immunoglobulin G Maintenance Therapy in Chronic Immune-mediated Neuropathies.

The regimen for IVIg maintenance treatment varies considerably between patients with chronic immune-mediated neuropathies. Although it is widely recognized that treatment regimens should be improved, detailed pharmacokinetics (PK) of IVIg have not yet been established. We aimed to determine the PK of IVIg maintenance treatment in patients with clinically stable, treatment-dependent, chronic immune-mediated neuropathy. Patients received a median IVIg dose of 30 g (range, 15-70 g) every 14 days (range, 7-28 days) resulting in high IgG peak levels (median, 25.9 g/L; range, 16.7-41.0 g/L) and trough levels (median, 16.1 g/L; range, 9.7-23.6 g/L). IgG PK parameters, including half-life (median, 23.1 days; range, 11-60 days), were constant during subsequent courses in the same patients, but varied considerably between patients. The IgG levels at 1 week after infusion correlated with grip strength. These results provide insight into the PK of IVIg maintenance treatment in patients with chronic immune-mediated neuropathies.

Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies.

In this study we evaluated a new neuropathy ultrasound protocol (NUP) for differentiating chronic immune-mediated neuropathies. The NUP was evaluated in 110 patients with clinical presentations of chronic immune-mediated neuropathy. All patients were first evaluated clinically and electrophysiologically and divided into 4 polyneuropathy groups: (a) symmetric demyelinating; (b) symmetric axonal; (c) asymmetric demyelinating; and (d) asymmetric axonal. During step 2, the NUP was evaluated prospectively for all 4 study groups. Overall, the NUP led to correct classification in 42 of 49 (85.7%) patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 of 15 (86.9%) with multifocal motor neuropathy (MMN), and 5 of 5 (100%) with multifocal-acquired demyelinating sensory and motor neuropathy (MADSAM). The NUP had >80% sensitivity and specificity in distinguishing CIDP, MMN, and MADSAM in all 4 study groups. The NUP is a useful addition in the differential diagnosis of chronic immune-mediated neuropathies in everyday practice. Muscle Nerve 54: 864-871, 2016.