Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: 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, 2010 and 2012. 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. OBJECTIVES: We had the following four objectives.1. To examine the efficacy of intravenous immunoglobulin (IVIg) in hastening recovery and reducing the long-term morbidity from Guillain-Barré syndrome (GBS).2. To determine the most efficacious dose of IVIg in hastening recovery and reducing the long-term morbidity from GBS.3. To compare the efficacy of IVIg and plasma exchange (PE) or immunoabsorption in hastening recovery and reducing the long-term morbidity from GBS.4. To compare the efficacy of IVIg added to PE with PE alone in hastening recovery and reducing the long-term morbidity from GBS. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (2 December 2013), CENTRAL (2013, Issue 12 in The Cochrane Library), MEDLINE (January 1966 to November 2013) and EMBASE (January 1980 to November 2013). 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of the randomised trials and contacted the authors and other experts in the field to identify additional published or unpublished data. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed quality. We collected data about adverse events from the included trials. MAIN RESULTS: Twelve trials were found to be eligible for inclusion 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. The primary outcome for this review, available for only one trial with 21 mildly affected children, showed significantly more improvement in disability grade after four weeks with IVIg than supportive treatment alone, MD 1.42, 95% CI 2.57 to 0.27.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 34 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. AUTHORS' CONCLUSIONS: 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 and one is in progress.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: 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. OBJECTIVES: To determine the efficacy of IVIg for GBS. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed quality. We collected data about adverse events from the included trials. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin is beneficial in other autoimmune diseases. OBJECTIVES: We aimed to determine the efficacy of intravenous immunoglobulin for Guillain-Barré syndrome. SEARCH STRATEGY: We updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register, MEDLINE and EMBASE in June 2009 using the terms 'Guillain-Barré syndrome' and 'acute polyradiculoneuritis' combined with 'intravenous immunoglobulin'. SELECTION CRITERIA: We included randomised and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed quality. MAIN RESULTS: Another Cochrane systematic review has shown that plasma exchange significantly hastens recovery. In this review, five trials compared intravenous immunoglobulin with plasma exchange in 536 severely affected, mostly adult participants. The mean difference of change in a seven-grade disability scale after four weeks was not significantly different between the two treatments: 0.02 (95% CI 0.25 to -0.20) of a grade more improvement in the intravenous immunoglobulin than the plasma exchange group. There were also no statistically significant differences in the other measures considered. Three studies including a total of 75 children suggested that intravenous immunoglobulin significantly hastens recovery compared with supportive care.In one trial involving 249 participants comparing plasma exchange followed by intravenous immunoglobulin with plasma exchange alone, the mean grade improvement was 0.2 (95% CI -0.14 to 0.54) more in the combined treatment group than in the plasma exchange alone group, not significantly different but not excluding the possibility of significant extra benefit. Another trial with 37 participants comparing immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone did not reveal significant extra benefit from the combined treatment.Small trials in children showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin and no significant difference when the standard dose was given over two days rather than five days. AUTHORS' CONCLUSIONS: A previous Cochrane review has shown that plasma exchange hastens recovery compared with supportive treatment alone. There are no adequate comparisons of intravenous immunoglobulin with placebo in adults but this review provides moderate quality evidence that, in severe disease, intravenous immunoglobulin started within two weeks from onset hastens recovery as much as plasma exchange. Adverse events were not significantly more frequent with either treatment but intravenous immunoglobulin is significantly much more likely to be completed than plasma exchange. Also according to moderate quality evidence, giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit. In children, according to low quality evidence, intravenous immunoglobulin 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.

Corticosteroids for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is caused by inflammation of the peripheral nerves, which corticosteroids should benefit. OBJECTIVES: To examine the efficacy of corticosteroids. SEARCH STRATEGY: We searched The Cochrane Neuromuscular Disease Group Trials Specialized Register (June 2009), MEDLINE (January 1966 to June 2009) and EMBASE from (January 1980 to June 2009). SELECTION CRITERIA: We included quasi-randomised or randomised controlled trials of any form of corticosteroid or adrenocorticotrophic hormone. 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: Two authors extracted the data. MAIN RESULTS: No new trials were discovered in the new search in June 2009. 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, weighted mean difference (WMD) 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, WMD 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, WMD 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. 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 low quality evidence oral corticosteroids delay recovery. Diabetes requiring insulin was significantly more and hypertension less common with corticosteroids.

Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is a disease causing progressive or relapsing and remitting weakness and numbness. It is probably due to an autoimmune process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. OBJECTIVES: We aimed to review systematically the evidence from randomised trials of cytotoxic drugs and interferons other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Specialised Register (May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2), MEDLINE (January 1977 to May 2010), EMBASE (January 1980 to May 2010), CINAHL (January 1982 to May 2010) and LILACS (January 1982 to May 2010). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials. SELECTION CRITERIA: We sought randomised and quasi-randomised trials of all immunosuppressive agents such as azathioprine, cyclophosphamide, methotrexate, ciclosporin A, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as interferon alfa and interferon beta in participants fulfilling standard diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, judged their methodological quality and extracted data. We wanted to measure the change in disability after one year as our primary outcome. Our secondary outcomes were change in disability after four or more weeks (from randomisation), change in impairment after at least one year, change in maximum motor nerve conduction velocity and compound muscle action potential amplitude after one year and for those participants who were receiving corticosteroids or intravenous immunoglobulin, the amount of this medication given during at least one year after randomisation. Participants with one or more serious adverse events during the first year was also a secondary outcome. MAIN RESULTS: Four trials fulfilled the selection criteria, one of azathioprine (27 participants), two of interferon beta-1a (77 participants in total) and one of methotrexate (60 participants). None of these trials showed significant benefit in the primary outcome or secondary outcomes selected for this review. AUTHORS' CONCLUSIONS: The evidence from randomised trials does not show significant benefit from azathioprine, interferon beta-1a or methotrexate but none of the trials was large enough to rule out small or moderate benefit. The evidence from observational studies is insufficient to avoid the need for randomised controlled trials to discover whether these drugs are beneficial. Future trials should have improved designs, more sensitive outcome measures and longer durations.

Immunotherapy for Guillain-Barré syndrome: a systematic review.

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 approximately 20% of patients die or have persistent disability despite immunotherapy, more research is needed to identify better treatment regimens and new therapeutic strategies.

A clinical prognostic scoring system for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute post-infectious immune-mediated peripheral neuropathy with a highly variable clinical course and outcome. We aimed to develop and validate a scoring system based on clinical characteristics in the acute phase of GBS to predict outcome at 6 months. METHODS: We studied patients with GBS who were unable to walk independently. A derivation set included 388 patients from two randomised controlled trials and one pilot study. Potential predictors were assessed for their association with the inability to walk independently at 6 months. A simple clinical scoring system was developed on the basis of regression coefficients of predictors in a multivariable logistic regression model. Model performance was quantified with respect to discrimination (area under receiver operating characteristics curve, AUC) and calibration (graphically). We validated our scoring system in a set of 374 patients from another randomised trial. FINDINGS: We included three variables that were predictive of poor outcome at 6 months in our model: age, preceding diarrhoea, and GBS disability score at 2 weeks after entry. Scores ranged from 1 to 7, with three categories for age, two for diarrhoea, and five for GBS disability score at 2 weeks. Predictions corresponding to these prognostic scores ranged from 1% to 83% for the inability to walk independently at 6 months. Predictions agreed well with observed outcome frequencies (adequate calibration) and showed a very good discriminative ability (AUC 0.85) in both data sets. INTERPRETATION: A simple scoring system for patients with GBS, based on three clinical characteristics, accurately predicts outcome at 6 months. The system could be used to counsel individual patients and identify high-risk groups to guide future trials.

Effects of knee joint angle and tilt table incline on force distribution at the feet and supporting straps.

OBJECTIVE: To investigate the effects of tilt table incline and knee flexion angle on the degree of weight bearing and forces exerted across the supporting straps. DESIGN: A quantitative and exploratory study to investigate the effects of a mechanical procedure. SETTING: Physiotherapy gymnasium. SUBJECTS: Twelve healthy subjects (9 female, 3 male) aged 22-45 years. INTERVENTIONS: Subjects stood on a tilt table, on two occasions, with simulated contractures of 10 degrees and 40 degrees knee flexion. Nine tilt angles, between 10 degrees and 90 degrees, were maintained for 1 minute each in random order. MAIN OUTCOME MEASURES: Force was recorded from single-point load cells placed under the feet, and at knee and chest straps. RESULTS: The degree of simulated knee contracture (10 degrees or 40 degrees) influenced the distribution of forces at different recording sites. Weight bearing increased with table incline and was significantly less with the 40 degrees than the 10 degrees knee angle (p < 0.001). Conversely, forces across the knee straps were systemically higher with the 40 degrees knee angle (p < 0.0001). The effects were accentuated by greater body weight. Forces across the chest strap also increased with tilt and were significantly larger with the 40 degrees knee angle (p < 0.05). CONCLUSIONS: The relationships between table incline, angle of knee flexion and distribution of forces generated during tilt table standing have been quantified and described. Standing with flexed knees involved less weight bearing under the feet and greater force exerted across the supporting straps. These effects were more pronounced at the higher knee angle and with greater body weight, and could be modified by reducing table incline.

Effects of multisensory stimulation in people with Huntington's disease: a randomized controlled pilot study.

OBJECTIVE: To investigate whether behavioural, motor and physiological responses of individuals with Huntington's disease (HD) to a controlled multisensory environment (MSE) are effective as a therapeutic (sustained effects) or leisure (immediate effects) activity. DESIGN: Pilot study--a randomized, controlled, two-group design. SETTING: Specialist residential unit for people with mid-late stage HD. SUBJECTS: Twelve patients with HD (one subject from each group dropped out during the study after week 8 due to medical complications). INTERVENTIONS: Patients attended eight, 30-minute sessions over a four-week period, of multisensory stimulation (MSE, treatment group) or relaxation activities (control group). MAIN OUTCOME MEASURES: Between-group comparisons for changes between assessment sessions for two behavioural assessments: Rehabilitation Evaluation--Hall and Baker (REHAB), Behaviour and Mood Disturbance Scale (BMD); a motor assessment: the dyskinesia section of the St Hans Rating Scale (SHRS); physiological measures: blood pressure, heart rate and respiratory rate. Secondary measures during intervention sessions included behavioural assessment using the Interact. RESULTS: There were no significant differences found between the groups for any main outcome measures made between sessions. The MSE group showed some positive effects within-sessions, with the Interact showing significant between-group differences in immediate effects on mood (p = 0.028). There was also a significantly different change over time for within-session changes in stimulation levels (p = 0.0002) and mood (p = 0.0001) between the groups. No physiological effects were observed in relation to sessions in either group. Two MSE subjects underwent changes in medication during the study period. CONCLUSIONS: There was no therapeutic effect of MSEs over the four-week study period. MSEs appear to be more effective thanconventional relaxation techniques as a leisure activity.

A case-case comparison of Campylobacter coli and Campylobacter jejuni infection: a tool for generating hypotheses.

Preventing campylobacteriosis depends on a thorough understanding of its epidemiology. We used case-case analysis to compare cases of Campylobacter coli infection with cases of C. jejuni infection, to generate hypotheses for infection from standardized, population-based sentinel surveillance information in England and Wales. Persons with C. coli infection were more likely to have drunk bottled water than were those with C. jejuni infection and, in general, were more likely to have eaten pâté. Important differences in exposures were identified for these two Campylobacter species. Exposures that are a risk for infection for both comparison groups might not be identified or might be underestimated by case-case analysis. Similarly, the magnitude or direction of population risk cannot be assessed accurately. Nevertheless, our findings suggest that case-control studies should be conducted at the species level.