Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy affecting 1–2 subjects per 100,000 every year worldwide. It causes, in its classic form, symmetric weakness in the proximal ...and distal limb muscles with common involvement of the cranial nerves, particularly facial weakness. Respiratory function is compromised in a case in four. Randomised controlled trials have demonstrated the benefit of therapeutic plasma exchange in hastening time to recovery. Intravenous immunoglobulin was subsequently shown to be as efficacious as plasma exchange in adult subjects. In children, few trials have shown the benefit of intravenous immunoglobulin versus supportive care. Pharmacokinetic studies suggested a relationship between increase in immunoglobulin G level post-infusion and outcome, implying administration of larger doses may be beneficial in subjects with poor prognosis. However, a subsequent trial of a second dose of immunoglobulin in such subjects failed to show improved outcome, while demonstrating a higher risk of thromboembolic side-effects. Monoclonal antibody therapy has more recently been investigated for GBS, after multiple studies in animal models, with different agents and variable postulated mechanisms of action. Eculizumab, a humanised monoclonal antibody against the complement protein C5, was tested in in two randomised, double-blind, placebo-controlled phase 2 trials. Neither showed benefit versus immunoglobulins alone on disability level at 4 weeks, although one study importantly suggested possible, clinically highly relevant, late effects on normalising function. A phase 3 trial is in progress. Preliminary results of a placebo-controlled ongoing study of ANX005, a humanised recombinant antibody against C1q inhibiting the complement cascade, have been promising.
Despite the use of plasma exchanges and intravenous immunoglobulins, Guillain-Barré syndrome (GBS) still carries non-negligible morbidity and mortality. Furthermore, the psychosocial consequences of ...GBS may persist longer than expected. Various aetiological, clinical, electrophysiological and immunological factors may carry prognostic predictive value. The objective of this article was to perform a summary of the current knowledge-base on outcome and its determinants in adequately-treated adult-onset GBS. Relevant prospective literature was reviewed through a Medline search of English-language articles published between 1966 and March 2012. GBS causes severe persistent disability in 14% of patients at 1 year. Loss of full strength, persistent pain and need for professional change occurs in about 40%. Mortality is of about 4% within the first year. Analysis of prognostic predictors consistently demonstrates the negative impact of higher age, preceding diarrhoea, greater disability/weaker muscles at admission, short interval between symptom-onset and admission, mechanical ventilation and absent/low amplitude compound muscle action potentials. Further outcome studies will soon be underway and may in future contribute to adequately integrate all potential factors in more reliable predictive models.
Chronic inflammatory demyelinating polyneuropathy with anti‐myelin associated glycoprotein antibodies represents a small subgroup of patients for whom management may not be straightforward. A recent ...study offers insight into this issue, with results suggesting priority should be given to the clinical phenotype.
ABSTRACT
Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional ...scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first‐line, high‐dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long‐term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy. Muscle Nerve 51:657–661, 2015
Introduction/Aim
The use of outcome measures is recommended for chronic inflammatory demyelinating polyneuropathy (CIDP). Implications of minimal important differences (MID) to ascertain responder ...status are unknown. The reliability of patient‐reported treatment‐response in relation to clinically relevant change is also unknown.
Methods
We retrospectively studied 72 subjects with “definite” or “probable” CIDP evaluated at pre‐specified time‐intervals pre‐ and post‐treatment. We derived MID and the minimum detectable change with 95% confidence intervals (MDC95) for four scales. Scale sensitivities were determined with applicable MID‐defined cutoffs (aMIDc), to detect subjects with self‐identifying treatment response through a single question.
Results
The use of MID was not valid for the Medical Research Council Sum Score, as MDC95 > MID. The aMIDc for the Overall Neuropathy Limitation Score (ONLS) was 1 (sensitivity: 84.7%). The aMIDc for the centile Inflammatory Rasch‐built Overall Disability Scale (cI‐RODS) was 8 (sensitivity: 62.3%). The aMIDc for grip strength was 4 kg (sensitivity: 79.1%). MID‐defined amelioration of any one scale among ONLS, cI‐RODS, or grip strength, significantly improved sensitivity to detect treatment‐responders compared with the ONLS alone (McNemar test: P = .008, odds ratio: 3.36 95% confidence interval: 1.44–7.86). Patient‐reported improvement was highly reliable in relation to MID‐defined amelioration on any one scale.
Discussion
In subjects with CIDP, MID‐defined amelioration of any one of three commonly used outcome measures offers optimum relevance and sensitivity to detect self‐identifying treatment‐responders. Patient reliability to single‐question ascertainment of response is high in relation to MID‐defined clinical relevance. These findings support use of multiple outcome measures in CIDP monitoring and justify enhanced patient involvement in the process.
See Editorial on pages 1–3 in this issue.
Serial electrophysiology has been suggested as essential for accurate diagnosis in Guillain-Barré syndrome (GBS). However, whether more adapted electrophysiological criteria may allow a single study ...to be sufficient is unknown.
We retrospectively reviewed records of 365 consecutive patients with GBS from Birmingham, U.K., and Garches, France, admitted between 1998 and 2013. Electrophysiology was analysed using existing criteria as well as a set of modified criteria, developed using sensitive and specific cut-off values for demyelination and incorporating new knowledge on electrophysiology of axonal GBS. We compared diagnostic rates and classification changes using modified criteria with published literature relating to serial studies.
With existing criteria, we found similar proportions of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (71.5% vs. 72%; p=1), axonal GBS (17.5% vs. 14.7%; p=0.62) and equivocal forms (9.9% vs. 13.3%; p=0.41) to the previous studies considered. With modified criteria, we identified comparable rates of AIDP (56.2% vs. 58.7%; p=0.70), axonal GBS (35.1% vs. 36%; p=0.89) and equivocal forms (7.7% vs. 5.3%; p=0.63) with a single nerve conduction study as compared with when serial electrophysiology was used in previous analyses. We observed an identical diagnostic shift from AIDP to axonal GBS with modified criteria as that described with serial studies (21.5% vs. 18.5%; p=0.72). Classification changes with modified criteria correlated significantly with performing of electrophysiology ≤7 days after symptom onset (p=0.045), indicating their greater usefulness in earlier disease stages.
A single electrophysiological study may suffice to establish the ultimate electrodiagnosis of GBS subtype if the proposed modified electrodiagnostic criteria are used.
PDF
