Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. ...However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.
Background
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon progressive or relapsing paralysing disease caused by inflammation of the peripheral nerves. If the ...hypothesis that it is due to autoimmunity is correct, removal of autoantibodies in the blood by plasma exchange should be beneficial.
Objectives
To assess the effects of plasma exchange for treating CIDP.
Search methods
On 30 June 2015, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also scrutinised the bibliographies of the trials, contacted the trial authors and other disease experts, and searched trials registries for ongoing studies.
Selection criteria
Randomised controlled trials (RCTs) or quasi‐RCTs in participants of any age comparing plasma exchange with sham treatment or no treatment.
Data collection and analysis
Two review authors independently selected the trials, extracted the data, and assessed risk of bias. Where possible the review authors combined data according to the methods of the Cochrane Neuromuscular Disease Review Group.
Main results
Primary outcome measure: one cross‐over trial including 18 participants showed after four weeks, 2 (95% confidence interval (CI) 0.9 to 3.1) points more improvement on an 11‐point disability scale with plasma exchange (10 exchanges over four weeks) than with sham exchange. Rapid deterioration after plasma exchange occurred in eight of 12 who had improved.
Secondary outcome measures: when we combined the results of this cross‐over trial and a trial with 29 participants treated in a parallel‐group design, there were 31 points (95% CI 18 to 45) more improvement on an impairment scale (maximum score 280) after plasma exchange (six exchanges over three weeks) than after sham exchange. There were significant improvements in both trials in an electrophysiological measure, the proximally evoked compound muscle action potential, after three or four weeks. Non‐randomised evidence indicates that plasma exchange induces adverse events in 3% to 17% of procedures. These events are sometimes serious. Both trials had a low risk of bias. A trial that showed no significant difference in the benefit between plasma exchange and intravenous immunoglobulin is included in the Cochrane review of intravenous immunoglobulin for this condition.
Authors' conclusions
Moderate‐ to high‐quality evidence from two small trials shows that plasma exchange provides significant short‐term improvement in disability, clinical impairment, and motor nerve conduction velocity in CIDP but rapid deterioration may occur afterwards. Adverse events related to difficulty with venous access, use of citrate, and haemodynamic changes are not uncommon. We need more research to identify agents that will prolong the beneficial action of plasma exchange.
Since its description by Guillain, Barré, and Strohl in 1916, Guillain-Barré syndrome (GBS) has attracted a large literature. The author reviews the history of research into its pathogenesis and ...treatment to highlight promising avenues for future research.
This is a nonsystematic personal review.
Since the early 1900s, the clinical picture of GBS has been illustrated in multiple series culminating in the ongoing International Guillain-Barré Syndrome study of 2000 patients. In the 1950s and 1960s, the inflammatory nature of the commonest form, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), was described. In the 1990s, two axonal forms, acute motor-sensory axonal neuropathy and acute motor axonal neuropathy, were recognized. In the 1990s and early 2000s, these forms were shown to be due to antibodies against Campylobacter jejuni glycans cross-reacting with glycolipids on axonal membranes. The pathogenesis of AIDP remains unknown, but T-cell responses to the compact myelin proteins, P2 and P0, which cause experimental autoimmune neuritis, suggest that T cells are important. Randomized controlled trials in the 1970s and 1980s showed no benefit from corticosteroids. Trials in the 1980s showed benefit from plasma exchange and in the 1990s from intravenous immunoglobulin.
Future research should seek biomarkers to identify subgroups with different treatment responses, define the true natural history of the disease with population-based epidemiological studies, study the pathology in autopsies early in the disease, seek causative antibodies and confirm autoimmune T-cell responses in AIDP, and expand treatment trials to include anti-T-cell agents.
Guillain-Barré syndrome (GBS) is an acute inflammatory disorder of the peripheral nervous system thought to be due to autoimmunity for which immunotherapy is usually prescribed. To provide the best ...evidence on which to base clinical practice, we systematically reviewed the results of randomized trials of immunotherapy for GBS. We searched the Cochrane Library, MEDLINE and EMBASE in July 2006 and used the methods of the Cochrane Neuromuscular Disease Group to extract and synthesize data. Almost all trials used a 7-point disability grade scale. In four trials with altogether 585 severely affected adult participants, those treated with plasma exchange (PE) improved significantly more on this scale 4 weeks after randomization than those who did not, weighted mean difference (WMD) −0.89 (95% confidence interval (CI) −1.14 to −0.63). In five trials with altogether 582 participants, the improvement on the disability grade scale with intravenous immunoglobulin (IVIg) was very similar to that with PE, WMD −0.02 (95% CI −0.25 to 0.20). There was also no significant difference between IVIg and PE for any of the other outcome measures. In one trial with 148 participants, following PE with IVIg did not produce significant extra benefit. Limited evidence from three open trials in children suggested that IVIg hastens recovery compared with supportive care alone. Corticosteroids were compared with placebo or supportive treatment in six trials with altogether 587 participants. There was significant heterogeneity in the analysis of these trials which could be accounted for by analysing separately four small trials of oral corticosteroids with altogether 120 participants, in which there was significantly less improvement after 4 weeks with corticosteroids than without, WMD −0.82 (95% CI −0.17 to −1.47), and two large trials of intravenous methylprednisolone with altogether 467 participants, in which there was no significant difference between corticosteroids and placebo WMD −0.17 (95% CI 0.06 to −0.39). None of the treatments significantly reduced mortality. Since ∼20% of patients die or have persistent disability despite immunotherapy, more research is needed to identify better treatment regimens and new therapeutic strategies.
Guillain-Barré syndrome (GBS) is an acute paralysing disease caused by inflammation of the peripheral nerves, which corticosteroids would be expected to benefit.
To examine the ability of ...corticosteroids to hasten recovery and reduce the long-term morbidity from GBS.
We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to October 2011) and EMBASE (January 1980 to October 2011).
We included randomised controlled trials (RCTs) or quasi-RCTs of any form of corticosteroid or adrenocorticotrophic hormone in GBS. Our primary outcome was change in disability grade on a seven-point scale after four weeks. Secondary outcomes included time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), death, death or disability (inability to walk without aid) after 12 months, relapse, and adverse events.
Two authors extracted the data independently.
No new trials were discovered in the new searches in June 2009 or November 2011. Six trials with 587 participants provided data for the primary outcome. According to moderate quality evidence, the disability grade change after four weeks in the corticosteroid groups was not significantly different from that in the control groups, mean difference (MD) 0.36 less improvement (95% confidence intervals (CI) 0.16 more to 0.88 less improvement). In four trials of oral corticosteroids with 120 participants in total, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids, MD 0.82 disability grades less improvement (95% CI 0.17 to 1.47). In two trials with a combined total of 467 participants, there was no significant difference, MD 0.17 (95% CI -0.06 to 0.39) of a disability grade more improvement after four weeks with intravenous corticosteroids. According to moderate to high quality evidence, there were no significant differences between the corticosteroid-treated and the control groups in any of the secondary efficacy outcomes. Diabetes was significantly more common and hypertension significantly much less common in the corticosteroid-treated participants.
According to moderate quality evidence, corticosteroids given alone do not significantly hasten recovery from GBS or affect the long-term outcome. According to low quality evidence oral corticosteroids delay recovery. Diabetes requiring insulin was significantly more common and hypertension less common with corticosteroids.
Guillain-Barré syndrome (GBS) is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin (IVIg) is beneficial in other autoimmune diseases. This is an update of a ...review first published in 2001 and previously updated in 2003, 2005, 2007 and 2010. Other Cochrane systematic reviews have shown that plasma exchange (PE) significantly hastens recovery in GBS compared with supportive treatment alone, and that corticosteroids alone are ineffective.
To determine the efficacy of IVIg for GBS.
We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 August 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to August 2011) and EMBASE (January 1980 to August 2011). We checked the bibliographies in reports of the randomised trials and contacted the authors and other experts in the field to identify additional published or unpublished data.
Randomised and quasi-randomised trials of IVIg compared with no treatment, placebo treatment, PE, or other immunomodulatory treatments in children and adults with GBS of all degrees of severity. We also included trials in which IVIg was added to another treatment.
Two authors independently selected papers, extracted data and assessed quality. We collected data about adverse events from the included trials.
In this review, seven trials with a variable risk of bias compared IVIg with PE in 623 severely affected participants. In five trials with 536 participants for whom the outcome was available, the mean difference (MD) of change in a seven-grade disability scale after four weeks was not significantly different between the two treatments: MD of 0.02 of a grade more improvement in the intravenous immunoglobulin than the plasma exchange group; 95% confidence interval (CI) 0.25 to -0.20. There were also no statistically significant differences in the other measures considered. Three studies including a total of 75 children suggested that IVIg significantly hastens recovery compared with supportive care.In one trial involving 249 participants comparing PE followed by IVIg with PE alone, the mean grade improvement was 0.2 (95% CI -0.14 to 0.54) more in the combined treatment group than in the PE alone group; not clinically significantly different, but not excluding the possibility of significant extra benefit. Another trial with 37 participants comparing immunoabsorption followed by IVIg with immunoabsorption alone did not reveal significant extra benefit from the combined treatment.Adverse events were not significantly more frequent with either treatment, but IVIg is significantly much more likely to be completed than PE.Small trials in children showed a trend towards more improvement with high-dose compared with low-dose IVIg, and no significant difference when the standard dose was given over two days rather than five days.
A previous Cochrane review has shown that PE hastens recovery compared with supportive treatment alone. There are no adequate comparisons of IVIg with placebo in adults, but this review provides moderate quality evidence that, in severe disease, IVIg started within two weeks from onset hastens recovery as much as PE. Adverse events were not significantly more frequent with either treatment but IVIg is significantly much more likely to be completed than PE. Also, according to moderate quality evidence, giving IVIg after PE did not confer significant extra benefit. In children, according to low quality evidence, IVIg probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in patients whose treatment starts more than two weeks after onset. Dose-ranging studies are also needed.
Summary Background Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects ...have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00220740. Findings During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33·5%, 95% CI 15·4–51·7; p=0·0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10·9 kPa, 4·6–17·2; p=0·0008) and the non-dominant hand (8·6 kPa, 2·6–14·6; p=0·005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0·011). The incidence of serious adverse events per infusion was 0·8% (9/1096) with IGIV-C versus 1·9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. Interpretation This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.
Corticosteroids for Guillain‐Barré syndrome Hughes, Richard AC; Brassington, Ruth; Gunn, Angela A ...
Cochrane database of systematic reviews,
10/2016, Letnik:
2016, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Background
Guillain‐Barré syndrome (GBS) is an acute paralysing disease caused by inflammation of the peripheral nerves, which corticosteroids would be expected to benefit.
Objectives
To examine the ...ability of corticosteroids to hasten recovery and reduce the long‐term morbidity from GBS.
Search methods
On 12 January 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We also searched trials registries.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs of any form of corticosteroid or adrenocorticotrophic hormone versus placebo or supportive care alone in GBS. Our primary outcome was change in disability grade on a seven‐point scale after four weeks. Secondary outcomes included time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), death, death or disability (inability to walk without aid) after 12 months, relapse, and adverse events.
Data collection and analysis
The review authors used standard methods expected by Cochrane.
Main results
The review authors discovered no new trials in the new searches in June 2009, November 2011, or January 2016. Six trials with 587 participants provided data for the primary outcome. According to moderate quality evidence, the disability grade change after four weeks in the corticosteroid groups was not significantly different from that in the control groups, mean difference (MD) 0.36 less improvement (95% confidence intervals (CI) 0.16 more to 0.88 less improvement). In four trials of oral corticosteroids with 120 participants in total, there was very low quality evidence of less improvement after four weeks with corticosteroids than without corticosteroids, MD 0.82 disability grades less improvement (95% CI 0.17 to 1.47 grades less). In two trials with a combined total of 467 participants, there was moderate quality evidence of no significant difference of a disability grade more improvement after four weeks with intravenous corticosteroids (MD 0.17, 95% CI ‐0.06 to 0.39). According to moderate quality evidence, there was also no significant difference between the corticosteroid treated and control groups for improvement by one or more grades after four weeks (risk ratio (RR) 1.08, 95% CI 0.93 to 1.24) or for death or disability after one year (RR 1.51, 95% CI 0.91 to 2.5). We found high quality evidence that the occurrence of diabetes was more common (RR 2.21, 95% CI 1.19 to 4.12) and hypertension less common (RR 0.15, 95% CI 0.05 to 0.41) in the corticosteroid‐treated participants.
Authors' conclusions
According to moderate quality evidence, corticosteroids given alone do not significantly hasten recovery from GBS or affect the long‐term outcome. According to very low quality evidence, oral corticosteroids delay recovery. Diabetes requiring insulin was more common and hypertension less common with corticosteroids based on high quality evidence.
Background
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness, probably due to an autoimmune response, which should ...benefit from corticosteroid treatment. Non‐randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, dexamethasone, is more potent and is used in smaller doses. The review was first published in 2001 and last updated in 2015; we undertook this update to identify any new evidence.
Objectives
To assess the effects of corticosteroid treatment for CIDP compared to placebo or no treatment, and to compare the effects of different corticosteroid regimens.
Search methods
On 8 November 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomised trials of corticosteroids for CIDP. We searched clinical trials registries for ongoing trials.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition.
Data collection and analysis
Two authors extracted data from included studies and assessed the risk of bias independently. The intended primary outcome was change in disability, with change in impairment after 12 weeks and side effects as secondary outcomes. We assessed strength of evidence using the GRADE approach.
Main results
One non‐blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low‐quality evidence). The trial did not report side effects in detail, but one prednisone‐treated participant died.
A double‐blind RCT comparing daily standard‐dose oral prednisolone with monthly high‐dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate‐quality evidence), or change in disability or impairment after one year (low‐quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate‐quality to low‐quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low‐quality evidence) as was moon facies (moon‐shaped appearance of the face) (moderate‐quality evidence).
Experience from large non‐randomised studies suggests that corticosteroids are beneficial, but long‐term use causes serious side effects.
Authors' conclusions
We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low‐quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long‐term risk of serious side effects. The efficacy of high‐dose monthly oral dexamethasone is probably little different from that of daily standard‐dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high‐dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response.
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