[Treating immune-mediated diseases].
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Autoimmune Diseases↗
Biomedical subjects
Jean-Marc Léger
Publications and source records attributed to Jean-Marc Léger.
[Multifocal motor neuropathy with persistent conduction blocks. A chronic immune-mediated neuropathy].
Multifocal motor neuropathy with persistent conduction blocks was first specifically identified in 1986. Its major criterion is conduction blocks in motor nerves only. Clinically, this is a multifocal, thus asymmetric, neuropathy that begins and predominant touches upper limbs; it especially affects men after the age of 50 years and has a chronic course with relapses. Approximately 40-50% of patients also have IgM serum antibodies directed against GM1 ganglioside. There are no other laboratory criteria, although moderately high protein levels are found in cerebrospinal fluid. Its course is unpredictable, because the neuropathy may remain limited to one or two motor nerves or extend progressively to all the motor nerves of all four limbs. In general, there is no damage to sensory or cranial nerves or to the autonomic or central nervous systems. Intravenous polyvalent immunoglobulins at high doses are remarkably effective in the short term in 70 to 80% of cases. Corticosteroids and plasma exchange are generally ineffective and may aggravate the neuropathy. The long-term efficacy of intravenous immunoglobulins in delaying motor decline and axon loss in the affected motor nerves is controversial. No information is currently available about the long-term efficacy of other immunomodulatory treatment.
Adult↗
Multifocal motor neuropathy.
PURPOSE OF THIS REVIEW: To conduct a critical review of recent studies on the clinical and therapeutic aspects of multifocal motor neuropathy, and to analyse their implications for patient management. RECENT FINDINGS: Recent studies have contributed to defining the specific position of multifocal motor neuropathy within the spectrum of chronic immune-mediated polyneuropathies. One study compared features of this condition with multifocal acquired demyelinating sensory and motor neuropathy, while others have focused on pathological alterations at the site of conduction blocks. A further study described six new cases of multifocal acquired motor neuropathy, which should be considered as a variant of multifocal motor neuropathy. Several Cochrane reviews and review articles have shown evidence of the efficacy of intravenous immunoglobulins in the treatment of multifocal motor neuropathy. The issue of long-term intravenous immunoglobulins in multifocal motor neuropathy, however, has yielded controversial results. Two studies have shown progressive motor deterioration in most patients, correlated with electrophysiological signs indicative of axonal degeneration, while a third study found signs of sustained clinical and electrophysiological improvement after a mean follow up of 7.25 years. SUMMARY: Multifocal motor neuropathy is a distinct clinical entity that differs from chronic inflammatory demyelinating polyradiculoneuropathy and multifocal acquired demyelinating sensory and motor neuropathy, although they share some electrophysiological characteristics. Although the aetiology remains unsolved, frequent association with high-titer antibodies against ganglioside GM1, together with an often positive response to intravenous immunoglobulins further support an autoimmune mechanism. New therapeutic strategies are required, however, that focus on the effects and the costs of treatment over long-term follow up.
Humans↗
A review of the medical management of chronic inflammatory demyelinating polyradiculoneuropathy.
Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare condition, but merits consideration due to its disabling consequences for patients and the growing existence of efficacious therapies during the last few decades. The first step is to characterise this neuropathy among the chronic dysimmune polyneuropathies, according to clinical, electrophysiologicalal and sometimes pathologicalal and immunochemical criteria. Typical CIDP is currently defined by criteria which have progressively improved since the first attempt made by an Ad Hoc Subcommittee of the American Academy of Neurology in 1991. However, CIDP may be associated with several concurrent diseases, and other chronic demyelinating polyneuropathies may be considered as either subtypes of CIDP, such as sensory CIDP and multifocal acquired sensory and motor neuropathy, or frontiers of CIDP, such as multi-focal motor neuropathy and polyneuropathy associated with monoclonal gammopathy. These considerations are helpful in the choice of treatments, as the response to immunomodulatory agents is different according to the type of the dysimmune neuropathy. CIDP is considered to be an immune-mediated disorder and may respond dramatically to numerous short-term therapies, such as corticosteroids, plasma exchanges, or intravenous immunoglobulin. The aim of this review is both to summarise the main results of the published open and randomised controlled trials for CIDP, and to provide some information about randomised controlled trials currently in progress. The objectives of the current and future trials are firstly, to choose the best regimen for short-term treatments, and secondly, to test new immunosuppressants in long-term therapy, if the neurological condition requires it.
Clinical Trials as Topic↗
Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy.
Electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were proposed by an Ad Hoc Subcommittee of the American Academy of Neurology (AAN) in 1991. Only 60% of CIDP patients fulfilled these criteria, which therefore appear poorly sensitive. We therefore sought to revise the electrophysiological criteria. We selected 40 CIDP patients and compared them with 35 patients with axonal polyneuropathy, 116 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease, and 66 patients with immunoglobulin M (IgM) monoclonal gammopathy. The proposed electrophysiological criteria identified 90% of the CIDP patients, although 3% of patients with axonal polyneuropathy were falsely identified. For the CIDP patients, sensitivity and specificity were 90% and 97%, respectively. Of the patients with IgM monoclonal gammaglobulin of undetermined significance (MGUS) and CMT1A, 100% fulfilled these new criteria, whereas 90% and 97%, respectively, fulfilled the AAN criteria. These results suggest that the AAN criteria are more appropriate for IgM MGUS and CMT1A patients than for CIDP patients. We therefore propose new electrophysiological criteria for CIDP that appear to have better sensitivity.
Adult↗
A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy.
This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 [0.67] grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation.
Aged↗