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Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN., (© 2024 Peripheral Nerve Society.)

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission., (© 2023 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point)., (© 2021 European Academy of Neurology and Peripheral Nerve Society.)

Background and Aims: To develop recommendations for vaccination for coronavirus-19 (COVID-19) in patients with inflammatory neuropathies., Methods: Key questions were formulated in order to perform a literature review on the safety and efficacy of vaccines in patients with inflammatory neuropathies. Based on the best evidence and expert opinion, a list of recommendations was formulated to inform decision on vaccination for COVID-19 in patients with inflammatory neuropathies and increase adherence to vaccination programmes., Results: Recommendations addressing safety and efficacy of vaccination in patients with inflammatory neuropathies were formulated. No data are currently available on the safety and efficacy of COVID-19 vaccines in patients with inflammatory neuropathies or other immune-mediated conditions. There is only sparse data on the safety of previous available vaccines in patients with inflammatory neuropathies, but studies on other autoimmune disorders indicate that these are safe and mostly efficacious. Patients with inflammatory neuropathies might be at increased risk for severe illness from COVID-19., Interpretation: Patients with inflammatory neuropathies should be encouraged to adhere to the vaccination campaign for COVID-19. These recommendations provide guidance on the management of vaccinations for COVID-19 in patients with inflammatory neuropathies. More research is needed regarding the safety and efficacy of vaccination in patients with inflammatory neuropathies and other immune conditions., (© 2021 Peripheral Nerve Society.)

This prospective, multicenter, single-arm, open-label phase 3 study aimed to evaluate the efficacy and safety of IqYmune in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients received one induction dose of 2 g/kg and then seven maintenance doses of 1 g/kg at 3-week intervals. The primary endpoint was the responder rate at the end of study (EOS), defined as an improvement of ≥1 point on the adjusted inflammatory neuropathy cause and treatment (INCAT) disability scale. The responder rate was compared with the responder rate of a historical placebo group (33.3%). Secondary endpoints included changes from baseline to EOS of adjusted INCAT disability score, grip strength, Medical Research Council (MRC) sum score, Rasch-modified MRC sum score, Rasch-built overall disability scale score and the clinical global impression. Forty-two patients, including 23 Ig-naïve and 19 Ig-pre-treated, were included in the efficacy set. The overall response rate at EOS was 76.2% (95% confidence interval [60.5%-87.9%]). The superiority of IqYmune compared to the historical placebo control was demonstrated (P < .0001). The responder rate was numerically higher in Ig-pre-treated than in Ig-naïve patients but confidence intervals were overlapping (84.2% [60.4%-96.6%] vs 69.6% [47.1%-86.8%]). All secondary endpoints confirmed this conclusion. The median time to response was 15 weeks [8.9-19.1 weeks]. A total of 156 adverse events including five serious were considered related to IqYmune, 87.2% were mild. Neither hemolysis nor signs of renal or hepatic impairment were observed. These results demonstrate that IqYmune is an effective and well-tolerated treatment in patients with CIDP., (© 2020 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

To evaluate the utility of different outcome measures to monitor dose adjustment of intravenous immunoglobulin (IVIg) therapy in patients with chronic inflammatory neuropathy (CIN). We assessed the adjustment of IVIg maintenance therapy in 20 patients (10 CIDP and 10 MMN) by regularly monitoring grip strength (GS) using a Martin Vigorimeter, RODS, and quality of life using the SF-36 questionnaire. These measures were regularly performed by the patient at home. We also assessed the extended MRC sumscore (eMRC sumscore) at each outpatient visit for IVIg infusion. We also enrolled 30 healthy controls to measure any possible training effect of GS with time and to analyze random fluctuation of GS. Clinically relevant change was detected by eMRC sumscore in 14 (93%) patients, by RODS in 11 (73%) patients, and by GS in 8 (53%) patients. Early sensitivity was greatest for RODS (73%), followed by GS (53%), and eMRC sumscore (27%). This differed from CIDP, with an early change in RODS in 100% of patients, and MMN with an early change in GS in 75%. None of the outcome measures alone was sufficient to detect clinically significant changes in all patients. Home monitoring of outcome measures objectively assisted clinical decision during individualization of IVIg treatment. We recommend a multimodal approach using different outcome measures to monitor the individual patient with CIN., (© 2020 Peripheral Nerve Society.)

Background and aims to report the clinical features and the relevance of diagnostic investigations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We retrospectively reviewed data from patients with a clinical diagnosis of CIDP included in a national database. Among the 500 included patients with a clinical diagnosis of CIDP, 437 patients (87%) fulfilled the EFNS/PNS criteria for CIDP (definite in 407, probable in 26, possible in four). In 352 patients (86%) motor nerve conduction abnormalities consistent with demyelination were sufficient for the diagnosis of definite CIDP. In 55 patients this diagnosis required the addition of one or two (from probable or from possible CIDP, respectively) supportive tests, while in 20 cases they improved the diagnosis from possible to probable CIDP, seven patients did not change diagnosis. Considering these 85 patients, CSF studies were performed in 79 cases (93%) upgrading the certainty of diagnosis in 59% of examined patients. Sensory nerve conduction studies were performed in 85% of patients with an improvement of diagnosis in 32% of cases. Nerve biopsy and US/MRI exams resulted positive in about 40% of examined patients, but they were performed in few patients (7 patients and 16 patients, respectively). A response to therapy was present in 84% of treated patients (n = 77), contributing to support the diagnosis in 40 patients in whom the other supportive criteria were not sufficient. In most patients with CIDP the diagnosis is possible solely with motor nerve conduction studies while other investigations may help improving the diagnosis in a minority of patients. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

In this study, we assessed the modifications over time of daily activities and quality of life (QoL) in 32 subjects with anti-myelin-glycoprotein (MAG) antibody neuropathy. A widespread panel including clinical scores and patient-reported questionnaires, in compliance of the terms by the International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization (WHO), was employed at enrollment (T0) and at follow-up evaluation (T1) after a mean interval of 15.4 ± 5.7 months. The Sensory Modality Sum score (SMS) at four limbs showed a significant worsening over time (mean score 27.2 ± 3.9 at T0 vs 25.7 ± 3 at T1 at upper limbs, P = .03; 20.5 ± 4.8 at T0 vs 18.6 ± 5.9 at T1 at lower limbs, P = .04). The Visual Analogue Scale (VAS) for pain significantly worsened at upper limbs at T1 (mean values 0.84 ± 1.95 at T0 vs 1.78 ± 2.6 at T1, P = .03). All the other tests did not show significant differences between T0 and T1. In the subgroup who underwent rituximab (15/32 treated before T0, 3/32 patients treated between T0 and T1 with median interval of 1 year), no significant differences were observed between T0 and T1. Despite the quite long follow-up, statistical significance was not achieved either for the limited number of patients or for the lack of sensitive outcome measures. In our cohort, the significant worsening of the SMS and VAS after a median of 14 months can be considered as a reliable expression of the natural history of the disease, and suggest that these scales might represent possible outcome measures in anti-MAG antibody neuropathy., (© 2019 Peripheral Nerve Society.)

Intravenous immunoglobulin (IVIg) is the gold-standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double-blind, multi-centre, active-control, crossover study, aimed to evaluate the non-inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty-two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®. Each product was administered for 24 weeks. The primary endpoint was the difference between IqYmune® and Kiovig® in mean assessments of modified Medical Research Council (MMRC) 10 sum score (strength of 5 upper-limb and 5 lower-limb muscle groups, on both sides, giving a score from 0 to 100) during the evaluation period (non-inferiority margin of Δ = 2). A linear mixed model analysis demonstrated the non-inferiority of IqYmune® relative to Kiovig®, independently of the covariates (value at baseline, treatment period, and treatment sequence). The estimated "IqYmune® - Kiovig®" difference was -0.01, with a 95% confidence interval (CI) -0.51 to 0.48. The number of adverse reactions (ARs) and the percentage of patients affected were similar for the two products: 39 ARs in 10 patients with IqYmune® vs 32 ARs in 11 patients with Kiovig®. No thromboembolic events nor haemolysis nor renal impairment were observed. In this first clinical trial comparing two IVIg brands for maintenance treatment of MMN, efficacy and tolerability of both brands were similar., (© 2018 LFB. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.)

High-dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25-60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg., (© 2016 Peripheral Nerve Society.)

We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients., (© 2015 Peripheral Nerve Society.)

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), gammopathy-related polyneuropathy (MGUSP), and multifocal motor neuropathy (MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference (MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p < 0.0001) and showed good intra-class correlation coefficients (Jamar [Right/Left hands]: ICC 0.997/0.96; Vigori: ICC 0.95/0.98). Meaningful changes were comparable between the two instruments, being higher in GBS compared to CIDP patients. In MGUSP/MMN poor responsiveness was seen. Significant more patients preferred the Vigorimeter. In conclusion, validity, reliability, and responsiveness aspects were comparable between the Jamar dynamometer and Vigorimeter. However, based on patients' preference, the Vigorimeter is recommended in future studies in immune-mediated neuropathies., (© 2015 Peripheral Nerve Society.)

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12 months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor-subset, a self-evaluation scale, grip strength, and MMN-RODS© (Rasch-built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor- (SF-36 question-2) and distribution-based (½ × SD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut-offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID-SE ≥ 1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN., (© 2015 Peripheral Nerve Society.)

This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP., (© 2015 Peripheral Nerve Society.)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and often disabling sensory motor neuropathy postulated as caused by an immune attack against peripheral nerve myelin. In addition to a classic sensory–motor polyneuropathy, other phenotypes of CIDP have been described including the Lewis- Sumner syndrome, distal acquired demyelinating symmetric (DADS) neuropathy, pure motor CIDP, pure sensory CIDP including chronic immune sensory polyradiculopathy (CISP), and focal CIDP. These phenotypes are currently considered to be variants of CIDP, even if the possibility that they represent different demyelinating neuropathies cannot be fully excluded considering differences in their response to therapy. Several data support the role of the immune system in the pathogenesis of CIDP even if the precise targets and actors (antibodies and lymphocytes) of this immune response remain uncertain. Recent studies have shown that the therapeutic response may differ in patients with peculiar clinical presentations supporting the hypothesis that different pathogenetic mechanisms may underlie the heterogeneity of CIDP. The majority of patients with CIDP show improvement after immune therapies including corticosteroids, plasma exchange, and high-dose intravenous immunoglobulin (IVIg). It remains unclear why none of the other immune therapies that were reported to be variably effective in other immune disorders proved to be effective also in CIDP.

The identification of a distinct subgroup of patients within the spectrum of lower motor neuron syndromes (LMNS) is crucial as some are potentially treatable. We describe the clinical and neuropathological characteristics of a patient presenting with a rapidly progressive LMNS associated with high titers of anti-GM1 antibodies, leading to respiratory failure within 10 months. Histopathological study of a biopsy of a obturator nerve motor branch demonstrated a predominantly axonal motor neuropathy, while electron microscopy analysis localized macrophages located within the periaxonal space. Immunohistochemistry demonstrated deposits of complement activation products (C3i) and immunoglobulins (IgM) on nerve fibers. The patient's clinical, immunological and pathological findings are consistent with a diagnosis of a chronic motor axonal neuropathy (CMAN), likely of immune-mediated origin., (© 2011 Peripheral Nerve Society.)

Antibodies to several nerve antigens have been reported in patients with chronic immune-mediated demyelinating neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and IgM paraproteinemic demyelinating polyneuropathy. The association of some reactivities with specific neuropathies, such as IgM antibodies to the myelin-associated glycoprotein in neuropathy associated with IgM monoclonal gammopathy, permitted to cast some light in their pathogenetic mechanisms and introduced new useful tools in their diagnosis. Other antibodies have been variably associated with other forms of neuropathy or with neuropathy itself, casting some doubts on their diagnostic relevance in the workout of these neuropathies. This is particularly true for IgM antibodies to glycolipids, including ganglioside and sulfatides, whose possible role in immune-mediated neuropathies is still debated and will be here reviewed., (© 2011 Peripheral Nerve Society.)

Several articles on multifocal motor neuropathy (MMN) have appeared in 2007 and 2008, broadening the boundaries of this neuropathy and improving its diagnosis. A number of retrospective studies confirmed the prolonged efficacy of high-dose intravenous immunoglobulins (IVIg) in this neuropathy. The efficacy of other immune therapies was not however, confirmed in other studies in MMN including a randomized controlled trial on mycophenolate mofetil as adjunctive therapy to IVIg. These negative results and the lack of new other studies on the cause of MMN should lead to some reconsideration on its pathogenesis.

We evaluated the efficacy and safety of rituximab in an open-label, uncontrolled study of 13 patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (MAG) and correlated the response to therapy with clinical and laboratory features. One year after rituximab therapy, anti-MAG immunoglobulin M (IgM) titers were significantly reduced. At that time, eight patients (62%) had improved in both the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore and the Medical Research Council sumscore for muscle strength and seven of them also in the INCAT disability score. The improvement in the mean INCAT sensory sumscore was significant at 12 months and correlated with lower anti-MAG antibody at entry and at follow-up. This study suggests that rituximab may be efficacious in patients with anti-MAG associated neuropathy and particularly on sensory impairment and in those with moderately elevated antibody titers. These findings suggest that antibody reduction below a critical level may be necessary to achieve clinical improvement.

We found comparable levels of tumor necrosis factor (TNF)-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10, and IL-12 in the sera of 22 patients with multifocal motor neuropathy (MMN), 12 with amyotrophic lateral sclerosis (ALS), 12 multiple sclerosis, seven chronic inflammatory demyelinating polyneuropathy, five myasthenia gravis, and 13 healthy controls (NS). TNF-alpha levels, however, were higher in 15 (68%) MMN patients than in any NS. In all but one MMN patient tested, TNF-alpha levels repeatedly, albeit slightly, increased after each intravenous immunoglobulin infusion in parallel with clinical improvement and decreased 3-4 weeks after therapy, while in both ALS patients tested, they decreased or remained unchanged. The possible pathogenetic relevance of serum TNF-alpha modification in MMN remains to be clarified.

We present the case of a 58-year-old man, who has suffered from type 1 diabetes mellitus since he was young. He had monoclonal IgM kappa gammopathy of undetermined significance and high anti-MAG antibody titer. He developed a polyneuropathic picture with the clinical and laboratory features of chronic inflammatory demyelinating polyneuropathy within the span of approximately 2 years. He benefited from IV administration of high doses of immunoglobulins. Investigation of all parameters, but particularly of the clinical phenotype, can lead to a better definition of the polyneuropathic picture, especially for therapeutic and prognostic purposes.