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Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder in which early effective treatment is important to minimize disability from axonal degeneration. It has been suggested that some patients with CIDP may benefit from rituximab therapy, but there is no definitive evidence for this.Methods: Baseline and post-rituximab-therapy neuromuscular Medical Research Council (MRC) sum scores, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, and functional status were assessed in 11 patients with refactory CIDP.Results: The MRC sum score, INCAT disability score, and functional status improved in all patients after rituximab therapy.Discussion: Our study provides evidence of the efficacy of rituximab therapy in at least some patients with CIDP. A placebo-controlled study to assess the effectiveness of rituximab therapy in CIDP with and without nodal antibodies is required to identify disease markers that predict responsiveness. [ABSTRACT FROM AUTHOR]

Importance Workers exposed to aerosolized brain in a swine-processing plant developed immune-mediated polyradiculoneuropathy (IP) possibly triggered by an immune response. Objective Immunohistochemistry results were correlated with electrophysiological variables to examine the immunopathogenesis of this disorder. Design/setting Laboratory studies used normal nerve tissue that was exposed to sera from 12 IP patients; 10 exposed controls; and 10 unexposed controls. Clinical and electrophysiological data from IP patients were obtained from medical record reviews. Main outcome measures Analysis included electromyography results of IP patients and nerve conduction studies examining CMAP amplitude, distal motor latency, motor conduction velocity, F-wave latency, sensory nerve action potential amplitude, and sensory nerve conduction velocity. Case and control results were compared relative to distance from exposure. Results Electrodiagnostic findings revealed prolongation of the distal and f-wave latencies suggestive of demyelination at the level of the nerve root and distal nerve terminals. Immunohistochemical results identified an antibody to the peripheral nerve, with staining at the level of the axolemma. Thus, IP may be a primary axonopathy with secondary paranodal demyelination causing the conduction changes. Staining of the distal and proximal portions of the nerve appears consistent with easier access through the blood-nerve barrier. Conclusions and relevance IP is an immune-mediated neuropathy related to antibodies to an axon-based antigen on peripheral nerves. Secondary paranodal demyelination is likely. Further studies to identify the primary axonal antigenic target would be useful. [ABSTRACT FROM AUTHOR]

Background: Lumbosacral radiculoplexus neuropathy (LRPN) originally described in diabetic patients is a distinct clinical condition characterized by debilitating pain, weakness and atrophy most commonly affecting the proximal thigh muscles asymmetrically. The syndrome is usually monophasic and preceded by significant weight loss (at least more than 10 lbs). Though a self-limited condition, recovery is gradual with some residual weakness. Recent advances and research has provided new insights in the pathogenesis and thereby management of this syndrome. In this paper, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with diabetic and non-diabetic LRPN. Materials and Methods: Literature in English published between 1953 and 2008 was searched in the MEDLINE and Pubmed database, maintained by the US National library of medicine and National institutes of health, using key words of diabetic amyotrophy, lumbosacral radiculoplexus neuropathy, diabetic proximal neuropathy, diabetic radiculopathy and diabetic lumbosacral plexopathy. In addition, literature reported in various textbooks on peripheral neuropathy was reviewed as well. Observation: The diagnosis relies mostly on clinical suspicion and characteristic electromyographic findings. The exact pathogenesis of the illness remains unknown, but there seems to be a component of immune-mediated inflammatory microvasculitis which causes secondary ischemia of the lumbosacral plexus. This has prompted a trial of immunosuppressive agents (like steroids) with an attempt to alter the course of the illness. A few reports have noted that immunosuppression when instituted early in the course of the illness (within three months of symptom onset) may hasten the recovery and improve symptoms. Conclusion: Though the exact mechanism of LRPN in diabetic and non-diabetic patients remains unknown, new evidence alludes to an underlying inflammatory vasculitic process. Early treatment with immunosuppressants may be beneficial in some cases, although the data available at this time is limited to a small cohort of patients. The decision is individualized weighing the risks and benefits in a given patient. Future research in this direction with double-blinded case-controlled studies is required to investigate this further. [ABSTRACT FROM AUTHOR]

Abstract: Degos'' disease or malignant atrophic papulosis is a rare disseminated occlusive vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and less often other organ systems. The exact etiology of this vasculopathy has not been established. Infections, autoimmune disease and coagulation defects have been proposed as underlying pathogenic mechanisms, but none have been confirmed. Here, we report the clinical, radiological and histopathologic features of Degos'' disease in a 41-year-old man following streptococcal throat infection. Prior postulated hypothesis as post-infectious immunologic mechanism may be further supported by this case. [Copyright &y& Elsevier]

A letter to the editor is presented in response to an article about a patient diagnosed with carcinoid tumor with paraneoplastic vasculitic neuropathy by Suraj Ashok Muley and colleagues in the 2007 issue.

The article presents a study which compares the diagnostic sensitivities of patients with carpal tunnel syndrome (CTS). All the patients fulfilled CTS clinical criteria and a significant portion of patients had rheumatoid arthritis, diabetes and hypothyroidism. It showed that addition of a single test, median/radial sensory latency or median/ulnar sensory latency would improve diagnostic sensitivity in all patients with CTS.

Introduction/Aims: Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody‐positive generalized myasthenia gravis (AChR+ve gMG). Methods: This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre‐ and post‐efgartigimod myasthenia gravis activities of daily living (MG‐ADL) scores. Information regarding MG history, concomitant treatment(s), MG‐ADL and other MG‐specific measures, laboratory data, and adverse events were recorded. Results: A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG‐ADL after the completion of the first cycle of efgartigimod (mean pre‐efgartigimod 8.02) (±3.09) versus post‐efgartigimod 4.33 (±3.62). Twenty‐five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG‐ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects. Discussion: Efgartigimod led to clinically meaningful improvement in MG‐ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about a patient with well-controlled type 2 diabetes who developed isolated bibrachial diabetic plexopathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic, proximal and distal, asymmetrical or symmetrical, motor and sensory demyelinating polyneuropathy with a progressive course for at least 2 months. The accurate diagnosis is crucial as CIDP is amenable to treatment. Recent advances have provided new strategies and options for management of this syndrome. In this article, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with CIDP. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Eculizumab has been shown to be efficacious in acetylcholine receptor antibody–positive (AChR+) Myasthenia Gravis Foundation of America (MGFA) class II, III, and IV generalized myasthenia gravis (gMG) patients. However, it has not been studied in MGFA class V gMG patients. Methods: We report three AChR+, refractory, MGFA class V gMG patients treated with eculizumab. MGFA class, MG‐Composite (MGC) score and MG Activities of Daily Living (MG‐ADL) score were assessed before and after eculizumab. Results: Two of three gMG patients, refractory to intravenous immunoglobulin, plasmapheresis, prednisone, and (in one case) rituximab, showed a robust response to eculizumab with marked improvement in MGFA, MG‐ADL, and MGC measures. The third patient showed a partial response to eculizumab but remained on noninvasive ventilation and gastrostomy intubation. Patients 1 and 2 achieved minimal manifestation status at week 4 and week 6, respectively, and showed continued improvement on MG‐ADL and MGC scores through weeks 55 and 43, respectively, with eculizumab. The third patient showed a partial response at week 10, followed by a slight decline in his MG‐ADL score, but noted a slow but an incomplete improvement afterward on MG‐ADL and MGC scores, possibly due to delayed eculizumab infusion. Discussion: Eculizumab may play a role in the treatment of patients with MGFA class V, refractory gMG. Larger studies are required to provide further evidence. [ABSTRACT FROM AUTHOR]

This work proposes an alternative to simulation-based receiver operating characteristic (ROC) analysis for assessment of fMRI data analysis methodologies. Specifically, we apply the rapidly developing nonparametric prediction, activation, influence, and reproducibility resampling (NPAIRS) framework to obtain cross-validation-based model performance estimates of prediction accuracy and global reproducibility for various degrees of model complexity. We rely on the concept of an analysis chain meta-model in which all parameters of the preprocessing steps along with the final statistical model are treated as estimated model parameters. Our ROC analog, then, consists of plotting prediction vs. reproducibility results as curves of model complexity for competing meta-models. Two theoretical underpinnings are crucial to utilizing this new validation technique. First, we explore the relationship between global signal-to-noise and our reproducibility estimates as derived previously. Second, we submit our model complexity curves in the prediction versus reproducibility space as reflecting classic bias-variance tradeoffs. Among the particular analysis chains considered, we found little impact in performance metrics with alignment, some benefit with temporal detrending, and greatest improvement with spatial smoothing. [Copyright &y& Elsevier]

Introduction: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG).Methods: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days.Results: We showed that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats.Discussion: We demonstrated that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. Muscle Nerve 57: 814-820, 2018. [ABSTRACT FROM AUTHOR]

Background: Lumbosacral radiculoplexus neuropathy (LRPN) originally described in diabetic patients is a distinct clinical condition characterized by debilitating pain, weakness and atrophy most commonly affecting the proximal thigh muscles asymmetrically. The syndrome is usually monophasic and preceded by significant weight loss (at least more than 10 lbs). Though a self-limited condition, recovery is gradual with some residual weakness. Recent advances and research has provided new insights in the pathogenesis and thereby management of this syndrome. In this paper, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with diabetic and non-diabetic LRPN.Materials and Methods: Literature in English published between 1953 and 2008 was searched in the MEDLINE and Pubmed database, maintained by the US National library of medicine and National institutes of health, using key words of diabetic amyotrophy, lumbosacral radiculoplexus neuropathy, diabetic proximal neuropathy, diabetic radiculopathy and diabetic lumbosacral plexopathy. In addition, literature reported in various textbooks on peripheral neuropathy was reviewed as well.Observation: The diagnosis relies mostly on clinical suspicion and characteristic electromyographic findings. The exact pathogenesis of the illness remains unknown, but there seems to be a component of immune-mediated inflammatory microvasculitis which causes secondary ischemia of the lumbosacral plexus. This has prompted a trial of immunosuppressive agents (like steroids) with an attempt to alter the course of the illness. A few reports have noted that immunosuppression when instituted early in the course of the illness (within three months of symptom onset) may hasten the recovery and improve symptoms.Conclusion: Though the exact mechanism of LRPN in diabetic and non-diabetic patients remains unknown, new evidence alludes to an underlying inflammatory vasculitic process. Early treatment with immunosuppressants may be beneficial in some cases, although the data available at this time is limited to a small cohort of patients. The decision is individualized weighing the risks and benefits in a given patient. Future research in this direction with double-blinded case-controlled studies is required to investigate this further. [ABSTRACT FROM AUTHOR]

We introduce a data-analysis framework and performance metrics for evaluating and optimizing the interaction between activation tasks, experimental designs, and the methodological choices and tools for data acquisition, preprocessing, data analysis, and extraction of statistical parametric maps (SPMs). Our NPAIRS (nonparametric prediction, activation, influence, and reproducibility resampling) framework provides an alternative to simulations and ROC curves by using real PET and fMRI data sets to examine the relationship between prediction accuracy and the signal-to-noise ratios (SNRs) associated with reproducible SPMs. Using cross-validation resampling we plot training–test set predictions of the experimental design variables (e.g., brain-state labels) versus reproducibility SNR metrics for the associated SPMs. We demonstrate the utility of this framework across the wide range of performance metrics obtained from [15O]water PET studies of 12 age- and sex-matched data sets performing different motor tasks (8 subjects/set). For the 12 data sets we apply NPAIRS with both univariate and multivariate data-analysis approaches to: (1) demonstrate that this framework may be used to obtain reproducible SPMs from any data-analysis approach on a common Z-score scale (rSPM{Z}); (2) demonstrate that the histogram of a rSPM{Z} image may be modeled as the sum of a data-analysis-dependent noise distribution and a task-dependent, Gaussian signal distribution that scales monotonically with our reproducibility performance metric; (3) explore the relation between prediction and reproducibility performance metrics with an emphasis on bias-variance tradeoffs for flexible, multivariate models; and (4) measure the broad range of reproducibility SNRs and the significant influence of individual subjects. A companion paper describes learning curves for four of these 12 data sets, which describe an alternative mutual-information prediction metric and NPAIRS reproducibility as a function of training-set sizes from 2 to 18 subjects. We propose the NPAIRS framework as a validation tool for testing and optimizing methodological choices and tools in functional neuroimaging. [Copyright &y& Elsevier]