A report of the Quality Standards Subcommittee (QSS) of the American Academy of Neurology
RAC Hughes, MD; EFM Wijdicks, MD; R Barohn, MD; E Benson, DR Cornblath, MD; AF Hahn, MD; JM Meythaler, MD; RG Miller, MD; JT Sladky; JC Stevens, MD Published in Neurology 2003;61:736-740.
Class IV.
Level Possibly effective, ineffective or harmful, or as C useful/predictive or not useful/predictive Level Data inadequate or conflicting; Treatment, test, U or predictor unproven
Introduction:
Prevalence: GBS affects between one and four per 100,000 of the worlds population annually.
Economic Impact: The costs in the US have been estimated as $110,000 for direct health care and $360,000 in lost productivity per patient.
Introduction:
Health Outcomes: Respiratory failure requiring ventilation in about 25% of patients with GBS Death in 4% to 15% of GBS patients Persistent disability in about 20% patients with GBS Persistent fatigue in 67% of patients with GBS
Question #1: Does initial immunotherapy hasten recovery from GBS symptoms?
Diagnostic criteria
In most studies, the primary outcome measure used disability scale, where: 0 = normal 1 = symptoms but able to run 2 = unable to run 3 = unable to walk unaided 4 = bed-bound 5 = needing ventilation 6 = dead Most studies included patients with severe disease, at least grade 3 on that scale.
Class Results II RCT Improved by one or more disability grades after four weeks
PE group 50%; Control group 40%
Osterman, 1984
Compare PE with supportive treatment
II RCT
Ventilated patients improvement by one or more disability grades at one month (p<0.01)
PE group 50%; Control group 35%
Handgrip strength was significantly greater in the PE group (p<0.001) The mean ( SD) time on ventilator was slightly shortened
PE group (n=4) 11.7 12.2 days; Control group (n=3) 15.3 6.1 days
The mean recovery time in days was almost identical between the two groups
PE 76.6 88.4 vs. Supportive Treatment 79.1 55.8
Class Results II RCT PE patients recovered walking with assistance faster than the control patients (p<0.01) Recovered 1 or more disability grades after 4 weeks
PE group 67/109; Control group 41/111
For ventilated patients, time to onset of recover walking assistance was shorter in the PE than the control group (p<0.05)
Class
Results
II RCT In the PE group, time to onset of motor recovery was significantly shortened compared to the control group (p=0.0002).
The number of patients with one or more grades of improvement at one month was significantly more
PE group 56.5%; Control group 28.3%
Conclusions
Plasma exchange hastens recovery in non-ambulant patients with GBS who present within four weeks from the onset of neuropathic symptoms (Class II evidence). Plasma exchange also hastens recovery in ambulant patients who present within two weeks but the evidence is limited to one trial (Class II evidence).
The effects of plasma exchange and IVIg are equivalent in patients requiring aid to walk(Class I evidence).
Treatment with CSF filtration has not been adequately tested (Limited Class II evidence).
Recommendations
PE is recommended in non-ambulant patients within four weeks from onset (Level A, Class II evidence). PE is recommended for ambulant patients within two weeks from onset (Level B, limited Class II evidence).
II Nonblinded RCT
Grses, 1995
Compare IVIG with supportive treatment
II RCT
Conclusions
Intravenous immunoglobulin has not been adequately compared with placebo (limited Class II evidence). Such comparison is not now needed because, when started within two weeks from the onset, IVIg has equivalent efficacy to PE in hastening recovery from patients with GBS who require aid to walk (Class I evidence). Multiple complications were significantly less frequent with IVIg than with PE (Class I evidence). There is no evidence concerning the relative efficacy of PE and IVIg in patients with axonal forms of GBS.
Recommendations
IVIg is recommended for patients with GBS who require aid to walk within two (Level A recommendation) or four weeks from the onset of neuropathic symptoms (Level B recommendation derived from Class II evidence concerning PE started within the first four weeks). The effects of IVIg and plasma exchange are equivalent. (Level B recommendation Class I evidence concerning the comparisons between PE and IVIg started within the first two weeks).
Analysis of evidence
Author/Year Class Results
PSGBS II Group, 1997 Single To compare IVIg blind with PE and with PE followed by IVIg RCT
No significant difference in any outcome measure between any of the three regimens The difference between the change in disability grade between PE and IVIg was so small as to fulfill previously declared criteria for equivalence
Analysis of evidence
Author / Class Results Year Nomura et al., 2001
To compare IVIg with PE and with PE followed by IVIg
II RCT
Conclusions
Sequential treatment with PE followed by IVIg does not have a superior effect to either treatment given alone (Class I evidence). Sequential treatment with immunoabsorption followed by IVIg has not been adequately tested (Limited Class IV evidence).
Recommendations
Sequential treatment with PE followed by IVIg is not recommended (Level A recommendation, Class I evidence). Immunoabsorption followed by IVIg is not recommended (Level U recommendation, Class IV evidence).
Conclusion
There is only limited Class IV evidence from a single small non-randomized, unblinded study.
Recommendation
The evidence is insufficient to recommend the use of immunoabsorption (Level U recommendation, Class IV evidence).
Analysis of evidence
Author/Year Swick and McQuillen, 1976
Effect of ACTH
Class II RCT
Results Average disease duration, excluding one ACTH patient who died ACTH group 4.4 months; Placebo patients 9.0 months.
Less improvement in disability grade after one, three and 12 months in the prednisolone than the untreated patients, which was significant (p<0.05) for those randomized within seven days from onset
Analysis of evidence
Author/Year Class Results
Analysis of evidence
Author/Year GBS Steroid Trial Group, 1993
Effect of iv methylprednisolone
Class I RCT
Results The mean difference in disability grade after four weeks was 0.06 (-0.23 0.36) grade more improvement in the steroid than the placebo group Neither this nor any other outcome variable showed a significant difference No significant difference in any outcome
II Alternate allocation CT
Analysis of evidence
Author/Year The Dutch GBS Group, 1994
Effect of iv methylPrednisolone added to IVIg
Results
76% improved one grade; Control group 53% (p=0.04)
Conclusion
The combined evidence from all trials shows no benefit from corticosteroids (Class I evidence). The results of a trial of the combination of intravenous methylprednisolone and IVIg are awaited.
Recommendation
Corticosteroids are not recommended in the treatment of GBS (Level A, Class I evidence).
Question #2: Are there special issues in the management of children with GBS?
Conclusion
There are no adequate randomized controlled trials of treatment in children.
Recommendation
Plasma exchange or IVIg are treatment options for treating children with severe GBS (Level B recommendation derived from class II evidence in adults).
Future research
More research is needed to evaluate immunotherapy in GBS, particularly the use of combination treatments and further treatment after the initial course. There is a need to identify patients who are at greater risk of an adverse outcome and to discover whether subgroups have differential responses to treatment (including children, people with axonal forms of GBS, and Fishers syndrome). Research should also investigate the best methods of supportive care for monitoring autonomic and pulmonary function, weaning from ventilation, treating pain, managing fatigue, and rehabilitation.