Eduardo Nobile-Orazio

Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy

This multicenter, randomized, double‐blind, crossover trial compared a 6 week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over 1 to 2 days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty‐four of the thirty‐two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11‐point disability scale 2 weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = –0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after 2 weeks and improvement in disability grade after 6 weeks. Results may have been biased against IVIg by the 8 patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in 1 patient while on prednisolone and in none with IVIg.

European federation of neurological societies/peripheral nerve society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background:  Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been published (J Peripher Nerv Syst 2005; 10: 220–228, Eur J Neurol 2006; 13: 326–332). Objectives: To revise these guidelines. Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Multifocal motor neuropathy: current concepts and controversies.

Multifocal motor neuropathy (MMN) is now a well‐defined purely motor multineuropathy characterized by the presence of multifocal partial motor conduction blocks (CB), frequent association with anti‐GM1 IgM antibodies, and usually a good response to high‐dose intravenous immunoglobulin (IVIg) therapy. However, several issues remain to be clarified in the diagnosis, pathogenesis, and therapy of this condition including its nosological position and its relation to other chronic dysimmune neuropathies; the degree of CB necessary for the diagnosis of MMN; the existence of an axonal form of MMN; the pathophysiological basis of CB; the pathogenetic role of antiganglioside antibodies; the mechanism of action of IVIg treatments in MMN and the most effective regimen; and the treatment to be used in unresponsive patients. These issues are addressed in this review of the main clinical, electrophysiological, immunological, and therapeutic features of this neuropathy. Muscle Nerve, 2005

Specificity of mouse and human monoclonal antibodies to myelin-associated glycoprotein

Some patients with neuropathy have IgM M-proteins that bind to myelin and to myelin-associated glycoprotein (MAG). We compared the binding properties of a human anti-MAG M-protein with three mouse monoclonal anti-MAG antibodies (GEN-S1, GEN-S3, GEN-S8) and with a mouse monoclonal antibody (HNK-1) that binds to both MAG and to human natural killer cells. The antibodies GEN-S1, GEN-S3, and GEN-S8 bound to different epitopes in the polypeptide portion of MAG as shown by peptide mapping, deglycosylation and competitive binding studies. The M protein and HNK-1 bound to both CNS and PNS MAG and to several additional protein bands of 70K, 30K, 26K, and 23K daltons in peripheral, but not in central myelin; they did not bind to deglycosylated MAG. The M-protein and HNK-1 immunostained myelin diffusely, whereas GEN-S8 immunostained only the periaxonal and outer regions of myelin sheath, and there was no staining with GEN-S1 or GEN-S3. The human M-proteins probably bind to a carbohydrate moiety in MAG that is also present in other PNS myelin proteins. This may explain the observed differences in immunostaining and the sparing of the CNS in patients with anti-MAG M-proteins.

High‐dose intravenous immunoglobulin therapy in multifocal motor neuropathy

We treated five consecutive patients with multifocal motor neuropathy (MMN) with high-dose intravenous immunoglobulin (IVIg). Four patients had increased levels of anti-asialo-GM1 IgM and two of anti-GM1 IgM as well; one patient had no reactivity. We treated them twice with 0.4 g/kg IVIg for 5 consecutive days at a 2-month interval, followed by maintenance infusions up to 6 to 12 months. All patients with high anti-asialo-GM1 had a consistent clinical improvement starting 3 to 10 days after the first IVIg course; in one patient, recovery was complete and persistent for 12 months without additional treatment, while in three patients, improvement only lasted 20 to 30 days. There was a similar improvement in these patients after the second course of IVIg which was maintained by periodic 2-day IVIg infusions. Clinical improvement in these patients was associated with a reduction of conduction block in most, but not all, motor nerves, while antibody titers were not consistently modified by treatment. There was no clinical or electrophysiologic improvement in the patient without antiglycolipid activity after 6 months of IVIg. IVIg may be a safe and effective therapy for MMN.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline* on management of chronic inflammatory demyelinating polyradiculoneuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Abstract  Background: Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and randomized trials and systematic reviews of treatment have been published. Objectives: The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of CIDP. Methods: Disease experts and a representative of patients considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements that were agreed in an iterative fashion. Recommendations: The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were as follows: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (good practice point); (3) if IVIg and corticosteroids are ineffective, plasma exchange should be considered (level A recommendation); (4) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (good practice point); and (5) symptomatic treatment and multidisciplinary management should be considered (good practice point).

Complement-Mediated Demyelination in Patients with IgM Monoclonal Gammopathy and Polyneuropathy

We investigated the role of complement in the pathogenesis of the demyelinating polyneuropathy that occurs in some patients with IgM monoclonal gammopathy. Seven patients with chronic sensorimotor polyneuropathy and IgM monoclonal gammopathy were examined. In six patients, the monoclonal protein recognized an epitope shared by myelin-associated glycoprotein and two peripheral-nerve glycolipids, whereas in one patient, IgM bound to an unidentified myelin antigen. Direct and indirect immunofluorescence and immunoperoxidase assays showed colocalization along the myelin sheaths of peripheral-nerve fibers of monoclonal protein with complement components C1q, C3d, and C5. In addition, terminal-complement complex that was not associated with S protein was detected in myelin sheaths. It appeared that alterations in myelin geometry caused by the separation of myelin lamellae corresponded to sites at which terminal-complement complex was deposited. We conclude that demyelination in polyneuropathy associated with IgM monoclonal gammopathy may be mediated by complement.