Predicting a positive response to intravenous immunoglobulin in isolated lower motor neuron syndromes.

James R Burrell,Dominic Rowe,Con Yiannikas,Matthew C Kiernan,Huaibin Cai

doi:10.1371/journal.pone.0027041

Abstract

ObjectiveTo determine clinically related characteristics in patients with pure lower motor neuron (LMN) syndromes, not fulfilling accepted diagnostic criteria, who were likely to respond to intravenous immunoglobulin (IVIg) treatment.MethodsDemographic, clinical, laboratory and neurophysiological characteristics were prospectively collected from patients with undifferentiated isolated LMN syndromes who were then treated with IVIg. Patients were classified as either responders or non-responders to therapy with IVIg based on clinical data and the two groups were compared.ResultsFrom a total cohort of 42 patients (30 males, 12 females, aged 18-83 years), 31 patients responded to IVIg and 11 did not. Compared to patients that developed progressive neurological decline, responders were typically younger (45.8 compared to 56.0 years, P<0.05) and had upper limb (83.9% compared to 63.6%, NS), unilateral (80.6% compared to 45.5%, P<0.05), and isolated distal (54.1% compared to 9.1%, P<0.05) weakness. Patients with predominantly upper limb, asymmetrical, and distal weakness were more likely to respond to IVIg therapy. Of the patients who responded to treatment, only 12.9% had detectable GM1 antibodies and conduction block (not fulfilling diagnostic criteria) was only identified in 22.6%.ConclusionsMore than 70% of patients with pure LMN syndromes from the present series responded to treatment with IVIg therapy, despite a low prevalence of detectable GM1 antibodies and conduction block. Patients with isolated LMN presentations, not fulfilling accepted diagnostic criteria, may respond to IVIg therapy, irrespective of the presence of conduction block or GM1 antibodies, and should be given an empirical trial of IVIg to determine treatment responsiveness.

Highlights

From a clinical perspective, it is often difficult to distinguish amyotrophic lateral sclerosis (ALS) from more treatable motor neuropathies early in the course of the illness, in patients with pure lower motor neuron (LMN) involvement. [1] For instance, patients with multifocal motor neuropathy (MMN) present with lower motor neuron (LMN) syndromes, typically with asymmetrical weakness of the distal upper limbs
MMN is rare, up to 78% of patients will improve with intravenous immunoglobulin (IVIg) therapy, whereas patients with ALS will continue to deteriorate. [3,4] IVIg therapy is expensive and prescription is often restricted by regulatory authorities
In addition to common and mild side effects such as headache, fever, and malaise, therapy with IVIg may occasionally be complicated by nephrotoxicity, [5] anaphylaxis, myocardial infarction, stroke or even death [6] further supporting the general view that IVIg therapy should be reserved for patients likely to benefit

Summary

Introduction

It is often difficult to distinguish amyotrophic lateral sclerosis (ALS) from more treatable motor neuropathies early in the course of the illness, in patients with pure lower motor neuron (LMN) involvement. [1] For instance, patients with multifocal motor neuropathy (MMN) present with lower motor neuron (LMN) syndromes, typically with asymmetrical weakness of the distal upper limbs. It is often difficult to distinguish amyotrophic lateral sclerosis (ALS) from more treatable motor neuropathies early in the course of the illness, in patients with pure lower motor neuron (LMN) involvement. [1] For instance, patients with multifocal motor neuropathy (MMN) present with lower motor neuron (LMN) syndromes, typically with asymmetrical weakness of the distal upper limbs. Often difficult in clinical practice, the distinction of ALS and other degenerative lower motor neuron diseases from MMN remains crucial as therapy with IVIg is likely to benefit patients with MMN. Patients with an MMN-like presentation, but without CB, may be initially diagnosed as ALS, a therapeutic treatment trial may show benefit from IVIg. Patients with an MMN-like presentation, but without CB, may be initially diagnosed as ALS, a therapeutic treatment trial may show benefit from IVIg. [7]

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Results

Conclusion