To determine whether rituximab 375 mg/m(2) was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating ...neuropathy).
Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) ≥4 and visual analog pain scale >4 or ataxia score ≥2. The primary outcome was mean change in ISS at 12 months.
Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m(2) rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 ± 2.7 in the rituximab group, and 1.0 ± 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p = 0.027), the self-evaluation scale (p = 0.016), and 2 subscores of the Short Form-36 questionnaire.
Although primary outcome measures provide no evidence to support the use of rituximab in IgM anti-MAG demyelinating neuropathy, there were improvements in several secondary outcomes in per protocol analysis.
This study provides Class I evidence that rituximab is ineffective in improving ISS in patients with IgM anti-MAG demyelinating neuropathy.
Abstract
Infiltration of the peripheral nervous system (PNS) by lymphoma, called neurolymphomatosis, is a rare condition among the spectrum of lymphoma-associated neuropathies; its diagnosis is ...challenging. Cerebrospinal fluid (CSF) analysis is of great value, but nerve biopsy (NB) may be necessary to prove invasion by malignant cells. Clonality polymerase chain reaction (PCR)-based analysis is a validated method in the diagnosis of hematological malignancies, but there are very little data on its diagnostic yield on NB samples. We explored the contribution of NB with clonality analysis to the diagnosis of neurolymphomatosis in 15 patients with negative CSF analysis. Moreover, we assessed the performance of clonality testing in a case-control manner, using patients with inflammatory infiltrates on NB as controls. Neurolymphomatosis was the first manifestation of lymphoma in 60% and could be diagnosed on routine histology alone in 40%. Clonality testing showed monoclonal rearrangement in 86.7% and was unsuccessful in 8.1%. Performance of clonality testing was as follows: 92.9% positive predictive value, 90% negative predictive value, 86.7% sensitivity, 94.7% specificity. This study confirms the diagnostic challenge of neurolymphomatosis, the usefulness of NB in patients with negative CSF analysis, and highlights the high yield of PCR-based clonality testing to assess the malignant nature of PNS lymphoid infiltrates.
We retrospectively analyzed 146 patients fulfilling the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria for definite chronic inflammatory ...demyelinating polyradiculoneuropathy (CIDP) to (1) evaluate the relevance of these criteria, (2) assess the frequency of CIDP variants, and (3) determine the response to treatment and the prognosis. We found that 75% of these patients fulfilled the main EFNS/PNS clinical and electrophysiological criteria (type I). The remaining patients were diagnosed using laboratory tools as supportive criteria. The common form of CIDP represented 51% of patients. We observed a high frequency of the sensory variant (35% of patients) and the rapid onset form (18%). A positive response to treatment was observed in 87% of patients, with a similar efficacy of prednisone and IVIg. However, in the long term, 40% of treated patients remained dependent on treatment. The IVIg dependency rate was higher than the prednisone or plasma exchange dependency rate (55%, 18%, and 23%, respectively; p = 0.0054). Severe handicap was observed in 24% of patients.
Au cours de cet atelier, nous reviendrons rapidement sur les complications classiques des chimiothérapies anticancéreuses, mais aborderons aussi les formes trompeuses de neuropathies ...post-chimiothérapie qui peuvent en imposer pour un autre mécanisme que post-chimiothérapie. Nous discuterons également des nouvelles immunothérapies par inhibition des points de contrôle et de leurs effets secondaires potentiels sur le système neuromusculaire. L’ensemble de cet atelier sera illustré par de nombreux cas cliniques.
Objective
Myotonias are inherited disorders of the skeletal muscle excitability. Nondystrophic forms are caused by mutations in genes coding for the muscle chloride or sodium channel. Myotonia is ...either relieved or worsened by repeated exercise and can merge into flaccid weakness during exposure to cold, according to causal mutations. We designed an easy electromyography (EMG) protocol combining repeated short exercise and cold as provocative tests to discriminate groups of mutations.
Methods
Surface‐recorded compound muscle action potential was used to monitor muscle electrical activity. The protocol was applied on 31 unaffected control subjects and on a large population of 54 patients with chloride or sodium channel mutations known to cause the different forms of myotonia.
Results
In patients, repeated short exercise test at room temperature disclosed three distinct abnormal patterns of compound muscle action potential changes (I‐III), which matched the clinical symptoms. Combining repeated exercise with cold exposure clarified the EMG patterns in a way that enabled a clear correlation between the electrophysiological and genetic defects.
Interpretation
We hypothesize that segregation of mutations into the different EMG patterns depended on the underlying pathophysiological mechanisms. Results allow us to suggest EMG guidelines for the molecular diagnosis, which can be used in clinical practice. Ann Neurol 2006
The Rituximab vs. Placebo in Polyneuropathy Associated With Anti‐MAG IgM Monoclonal Gammopathy (RIMAG) study showed no improvement using the inflammatory neuropathy cause and treatment sensory score ...(ISS) as primary outcome in patients with IgM anti‐myelin‐associated glycoprotein neuropathy (IgM anti‐MAG neuropathy) treated with rituximab, when compared with placebo. However, some secondary outcomes seemed to improve in the per protocol analysis. Patients from one participating center in the RIMAG study underwent a new evaluation after a median follow‐up of 6 (interquartile range (IQR) 4.9; 6.5) years, using the same outcome measures used in the original study. Data were recorded in seven rituximab patients (group 1) and in eight placebo patients (group 2). In group 2, six of eight patients received immunotherapy during follow‐up, while only two of seven did in group 1. No significant change was observed in either the ISS or the secondary outcomes in both groups, with the exception of worsening in the 10‐m walk time in group 2 (p = 0.016). The RIMAG follow‐up study failed to find any significant change in most outcome measures in patients from the RIMAG study, some of them having received new immunotherapies. This study stresses the lack of useful clinical scales sensitive enough to capture small, even meaningful, improvement in IgM anti‐MAG neuropathy.
BackgroundTremor is an underrecognized feature in certain neuropathy subtypes. Phenomenology shownWe show a patient with a disabling neuropathic tremor and mild cerebellar syndrome associated with ...chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-neurofascin-155 (NF155) antibodies. Educational valueAnti-NF155 testing should be considered in patients with CIDP and disabling tremor because of therapeutic implications.
Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease and the diagnosis is complicated by heterogeneity of the variant forms. Underdiagnosis is undesirable as ...effective treatments exist. Conversely, overdiagnosis can lead to inappropriate and expensive treatment and delay the initiation of appropriate treatment. Summary: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria are used widely in clinical trials and clinical practice. A limitation of the criteria is the requirement for at least one demyelinating parameter as there are certain situations (e.g. proximally located demyelinating process, secondary axonal loss, predominant involvement of sensory fibers) where this criterion may be not apparent; this can lead to misclassification of the neuropathy as axonal. To prevent this situation, the French CIDP Study Group has proposed a set of clinical and electrophysiological signs that are atypical for chronic idiopathic axonal polyneuropathy and suggestive for CIDP. Greater use of supportive diagnostic tools such as magnetic resonance imaging in clinical practice is not only extending the boundaries of CIDP but also contributing to over-representation of some variants, such as those involving the plexus, and sensory or minimal forms of CIDP. Many misdiagnoses can be avoided by adapting the diagnostic strategy to the clinical phenotype of CIDP. Key Messages: Early and accurate diagnosis of CIDP facilitates the selection of appropriate therapy to improve prognosis. Understanding the limitations of diagnostic criteria and adapting the diagnostic strategy to clinical phenotype can enhance precision and avoid diagnostic pitfalls.
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