Dafpus SGB 20

Corticosteroids for Guillain-Barr syndrome (Review)
Hughes RAC, Swan AV, van Koningsveld R, van Doorn PA
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2006, Issue 2
http://www.thecochranelibrary.com
Corticosteroids for Guillain-Barr syndrome (Review)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Analysis 1.1. Comparison 1 Corticosteroid versus control, Outcome 1 Disability grade change after four weeks. . . 19
Analysis 1.2. Comparison 1 Corticosteroid versus control, Outcome 2 Improvement by one or more grades after four
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Analysis 1.3. Comparison 1 Corticosteroid versus control, Outcome 3 Death. . . . . . . . . . . . . . . 21
Analysis 1.4. Comparison 1 Corticosteroid versus control, Outcome 4 Death or disability after one year. . . . . . 22
Analysis 1.5. Comparison 1 Corticosteroid versus control, Outcome 5 Disability grade change after 12 months. . . 23
Analysis 1.6. Comparison 1 Corticosteroid versus control, Outcome 6 Proportion of patients who relapsed. . . . 24
Analysis 1.7. Comparison 1 Corticosteroid versus control, Outcome 7 Disability grade change after six months. . . 25
Analysis 1.8. Comparison 1 Corticosteroid versus control, Outcome 8 Tx v Control OR for improvement by one or more
grades by 4 wks adj for age and initial DG. . . . . . . . . . . . . . . . . . . . . . . . . 25
Analysis 1.9. Comparison 1 Corticosteroid versus control, Outcome 9 Adverse events. . . . . . . . . . . . 26
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Corticosteroids for Guillain-Barr syndrome (Review) i

[Intervention Review]
Corticosteroids for Guillain-Barr syndrome
Richard AC Hughes1 , Anthony V Swan2 , Rinske van Koningsveld3 , Pieter A van Doorn3
1 MRC Centre for Neuromuscular Disease, PO Box 114, London, UK. 2 Cochrane Neuromuscular Disease Group, MRC Centre
for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, UK. 3 Department of Neurology, Erasmus
Medical Centre Rotterdam, Rotterdam, Netherlands
Contact address: Richard AC Hughes, MRC Centre for Neuromuscular Disease, PO Box 114, National Hospital for Neurology and
Neurosurgery, Queen Square, London, WC1N 1BG, UK. richard.a.hughes@kcl.ac.uk. r.hughes@ion.ucl.ac.uk.
Editorial group: Cochrane Neuromuscular Disease Group.

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 27 February 2007.
Citation: Hughes RAC, Swan AV, van Koningsveld R, van Doorn PA. Corticosteroids for Guillain-Barr syndrome. Cochrane Database
of Systematic Reviews 2006, Issue 2. Art. No.: CD001446. DOI: 10.1002/14651858.CD001446.pub2.
ABSTRACT
Background
The cause of Guillain-Barr syndrome is 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 Guillain-Barr syndrome.
Search strategy
We searched the Cochrane Neuromuscular Disease Group Register (February 2007), MEDLINE (January 2000 to February 2007)
and EMBASE (January 1980 to February 2007) and contacted trial authors and other experts.
Selection criteria
We included quasi-randomised or randomised controlled trials of people of all ages and all degrees of severity of Guillain-Barr syndrome
who were treated with any form of corticosteroid or adrenocorticotrophic hormone. Our primary outcome measure was change in
disability grade on a commonly used, validated seven-point scale at four weeks after randomisation. Secondary outcome measures
were: time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for
those ventilated), mortality, proportion of participants dead or disabled (unable to walk without aid) after 12 months, improvement
in disability grade after six and 12 months, relapse, and adverse events related to corticosteroid treatment.
Data collection and analysis
Two authors extracted the data.
Main results
Six trials with 587 participants provided data for our primary outcome measure .The overall evidence showed no significant difference
between the corticosteroid and non-corticosteroid treated patients in disability grade. In four trials of oral corticosteroids with 120
participants in total, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids (weighted
mean difference of 0.82 of a disability grade less improvement, 95% confidence intervals 0.17 to 1.47). In two trials with a combined
total of 467 participants, there was a trend towards more benefit from intravenous corticosteroids which was not quite significant,
weighted mean difference 0.17 (95% confidence intervals -0.06 to 0.39) of a disability grade more improvement after four weeks than
Corticosteroids for Guillain-Barr syndrome (Review) 1
with placebo. There were no important significant differences between the corticosteroid-treated participants and the control group
in any of the secondary outcome measures. Diabetes was significantly more common and hypertension much less common in the
corticosteroid-treated participants.
Authors conclusions
Limited evidence shows that oral corticosteroids significantly slow recovery from Guillain-Barr syndrome. Substantial evidence shows
that intravenous methylprednisolone alone does not produce significant benefit or harm. In combination with intravenous immunoglob-
ulin, intravenous methylprednisolone may hasten recovery but does not significantly affect the long-term outcome. More research is
needed and more effective treatments for Guillain-Barr syndrome should be sought.
PLAIN LANGUAGE SUMMARY
Oral corticosteroids may delay recovery from Guillain-Barr syndrome whereas intravenous corticosteroids may hasten recovery
when given with intravenous immunoglobulin but do not affect the long-term outcome
Guillain-Barr syndrome is an uncommon paralysing illness, usually caused by autoimmune inflammation of nerves. In 25% of
patients it leads to a requirement for artificial ventilation. About 5% of patients die and about 10% are left with persistent disability.
Corticosteroid drugs (such as prednisolone) reduce inflammation and so could theoretically lessen nerve damage. We found eight trials
with 653 participants but only six trials with 587 participants gave information about the primary outcome measure for this review,
change in a seven-point disability scale. When the results of these six trials were pooled there was no significant difference in this or
any other outcome. This result was considered unreliable because of marked variations between the trials. In four small trials of oral
corticosteroids, with 120 participants, in total there was significantly less improvement after four weeks with corticosteroids than without
corticosteroids (weighted mean difference of 0.82 of a disability grade less improvement, 95% confidence intervals 0.17 to 1.47). In
two large trials with a combined total of 467 participants, there was a trend towards more benefit from intravenous corticosteroids
which was not quite significant, weighted mean difference 0.17 (95% confidence intervals -0.06 to 0.39) of a disability grade more
improvement after four weeks than with placebo. Corticosteroids were not associated with a significant increase in harm except that
in the two trials of intravenous corticosteroids diabetes was significantly more common and hypertension much less common in the
corticosteroid treated patients. The lack of more obvious benefit from corticosteroids might be because the drugs have an effect on
muscles which counteracts the benefits of reduced inflammation in nerves.
BACKGROUND response do work in GBS. One Cochrane review concluded from

randomised controlled trials that replacing the blood plasma by
Guillain-Barr syndrome (GBS) is an acute paralysing illness usu- plasma exchange is beneficial (Raphael 2004). Another review con-
ally due to inflammation of the peripheral nerves and nerve roots. cluded that intravenous immunoglobulin is just as helpful (Hughes
It causes tingling and numbness in the limbs and rapidly progres- 2006). Theoretically, corticosteroids would be expected to reduce
sive weakness so that patients are often so weak that they cannot inflammation and so lessen nerve damage in inflammatory neu-
walk. It may affect the face and swallowing muscles and 25% of ropathy. Corticosteroids have been shown to hasten recovery in a
patients become so weak that they require artificial ventilation. rat model of GBS, experimental autoimmune neuritis, but only
About 5% of patients die in the acute stages and 10% are left when used in large doses (Hughes 1981; King 1985; Watts 1989).
with permanent severe disability. It affects 1 to 2 per 100,000 of On the other hand, corticosteroids introduce risks, including that
the population throughout the world and is more common in the of increased susceptibility to infection (Bromberg 2004). Conse-
elderly than the young. The cause of GBS is not definitely known. quently the risk-benefit ratio of corticosteroid administration in
It is probably an autoimmune disease in which the autoimmune GBS requires careful study.
response, often triggered by an infection, is directed against anti-
gens in the nerve. This leads to inflammation and nerve damage. Corticosteroid treatment has been used in GBS in individual case
Two treatments designed to reduce the presumptive autoimmune reports from the early 1950s onwards. Some authors reported ap-
parently favourable responses from small series or comparative but Types of participants
not controlled studies. No consensus about the efficacy of steroid We included children and adults with GBS of all degrees of severity.
treatment emerged from this work (see Hughes 1990 and Ropper Guillain-Barr syndrome was defined according to internationally
1991 for reviews). A retrospective cohort study compared 50 pa- accepted diagnostic criteria (Asbury 1990) as acute polyradicu-
tients treated with prednisolone 1 mg/kg daily, or equivalent doses loneuropathy causing progressive weakness of two or more limbs,
of dexamethasone, with 47 patients treated without corticosteroids an onset phase not more than four weeks, reduced or absent tendon
(Peter 1996). The baseline characteristics of the two groups ap- reflexes, and lacking alternative causes. We included studies which
peared similar. There was no significant difference between the did not conform exactly to these criteria provided that the authors
groups in mortality, intensive care unit stay, or improvement in regarded GBS or one of its synonyms, such as acute idiopathic neu-
disability by the time of hospital discharge. Complications were ropathy or acute inflammatory demyelinating polyradiculoneu-
more common in the steroid group. However a comparison of ropathy, as the preferred diagnosis. We noted any departure from
one series of corticosteroid treated patients with historical controls the internationally accepted diagnostic criteria.
suggested a beneficial effect from corticosteroids when given in
combination with intravenous immunoglobulin. In that study, 25
patients were treated with intravenous methylprednisolone 500 Types of interventions
mg daily for five days in addition to intravenous immunoglobulin We included treatment with any form of corticosteroid or adreno-
0.4 g/kg daily for five days. They were compared with a historical corticotrophic hormone.
comparative group of 74 patients treated without steroids but also
without intravenous immunoglobulin (Dutch GBS Group 1994).
After four weeks, 19 of the 25 methylprednisolone treated patients Types of outcome measures
(76%) improved by one or more disability grades on a seven-point
scale compared with only 39 of 74 (53%) patients treated in a
previously controlled trial with intravenous immunoglobulin but Primary outcomes
not corticosteroids (P value = 0.04).
Improvement in disability grade four weeks after randomisation.
The first version of this review that was published in 1999 in- We accepted the disability scale used by the authors of each trial
cluded six randomised trials and a total of 382 participants. We provided that it was closely similar to that described in one of the
have updated the review to include a new trial with 225 partici- first trials (Hughes 1978) as follows:
pants (van Koningsveld 2004) and a newly discovered trial with 0. Healthy
20 participants (Garcia 1985). 1. Minor symptoms or signs of neuropathy but capable of manual
work
2. Able to walk without support of a stick but incapable of manual
work
OBJECTIVES 3. Able to walk with a stick, appliance or support
4. Confined to bed or chair bound
The objective was to examine the ability of corticosteroids to has- 5. Requiring assisted ventilation
ten recovery and reduce the long-term morbidity from GBS. 6. Dead
In the calculation of grade changes the convention was followed
that patients who died were assigned a disability score of 6 and
retained in the analysis with this score at subsequent follow-up
METHODS intervals.
Secondary outcomes
Criteria for considering studies for this review 1. Improvement by one or more disability grades on the scale
described above, four weeks after randomisation. This measure had
not been included in the first version of this review but was used in
reviews of plasma exchange and intravenous immunoglobulin and
Types of studies
has been added to this review for consistency and comparison.
We included all randomised or quasi-randomised (e.g. alter- 2. Time from randomisation until recovery of unaided walking.
nate allocation) controlled trials of corticosteroid or adrenocor- 3. Time from randomisation until discontinuation of ventilation
ticotrophic hormone treatment for GBS. The type of additional (for those ventilated).
therapy given, if any, did not affect inclusion in this review. 4. Death.

5. Death or disability (inability to walk without aid after 12 Assessment of risk of bias in included studies
months). The assessment of methodological quality of the trials included al-
6. Improvement in disability grade after six months. location concealment, patient blinding, observer blinding, explicit
7. Improvement in disability grade after 12 months. diagnostic criteria, explicit outcome criteria, how studies dealt with
8. Relapse (defined as a period of worsening lasting at least seven baseline differences of the experimental groups, completeness of
days that followed a period of improvement lasting at least seven follow-up and adherence to treatment. We graded these items as
days) during the first year after randomisation.
A: adequate, B: moderate risk of bias, C: inadequate, and D: not
9. Occurrence of the following adverse events that are attributable done. If the information was not available the item was graded
to corticosteroids during or within one week after stopping treat- C. When agreement between authors was poor, we reassessed the
ment: studies and reached agreement by consensus.
(a) development of new infection treated with antibiotics;
(b) gastrointestinal haemorrhage;
(c) development of diabetes mellitus requiring insulin;
(d) development of hypertension requiring drug treatment. Measures of treatment effect
We calculated a weighted treatment effect across trials using the
Cochrane statistical package, Review Manager (RevMan) 4.2. Re-
sults were expressed as relative risks (RR) with 95% confidence
Search methods for identification of studies intervals (CIs) and risk differences (RDs) with 95% CIs for di-
We searched the Cochrane Neuromuscular Disease Group Trials chotomous outcomes and weighted mean differences (WMDs)
Register (February 2007), MEDLINE (January 2000 to Febru- and 95% CIs for continuous outcomes.
ary 2007) and EMBASE (January 1980 to February 2007) for
randomised and quasi-randomised controlled trials with Guil-
lain-Barr syndrome and its synonym acute polyradiculoneuri- Data synthesis
tis as the search terms; we used the search strategy described in
We used a fixed-effect model and tested for heterogeneity. Where
the Cochrane Neuromuscular Disease Review Group module. We
genuine heterogeneity not due to a few extreme studies was found
checked the bibliographies in reports of the randomised trials and
we substituted a random-effects model. We analysed all the pri-
contacted the trial authors and other experts in the field to identify
mary and secondary outcomes under consideration whenever the
additional published or unpublished data.
data allowed.
Electronic searches
Subgroup analysis and investigation of heterogeneity
For the OVID MEDLINE search strategy see Appendix 1.
We planned to examine subgroups which had been defined in ad-
vance because of their prognostic importance as identified in pre-
vious prospective studies and trials. The subgroups were defined
Data collection and analysis according to the status of the patients at randomisation as follows:
1. younger and older (children and adults up to 49 years of
age; adults aged 50 years or more);
2. more severely (requiring ventilation) or less severely affected
Selection of studies (not requiring ventilation);
Two authors checked titles and abstracts identified from the reg- 3. having or not having documented relevant sensory deficit
ister. Two authors obtained the full text of all potentially rele- on routine neurological examination (symptoms alone were to be
vant studies for independent assessment. The authors decided in- ignored);
dependently which trials fitted the inclusion criteria and graded 4. having or not having a history of diarrhoea (gastroenteritis)
their methodological quality. Disagreements about inclusion cri- within the six weeks before the onset of neuropathic symptoms;
teria were resolved by discussion between the authors. and
5. time from onset of neuropathy to start of treatment (seven
days or less after onset; more than seven up to 14 days after
onset; and more than 14 days after onset).
Data extraction and management Before the outcome of the van Koningsveld 2004 trial was known
Two authors performed data extraction independently. We ob- we decided to examine separately the effects of intravenous and
tained some missing data from trial authors. oral regimens.

Sensitivity analysis care (Garcia 1985). A trial with 242 participants compared intra-
We undertook sensitivity analyses taking into account the quality venous methylprednisolone, 500 mg daily for five days with an
of the studies. identical placebo saline solution (GBS Steroid 1993). This trial did
not show a significant difference in any outcome between the cor-
ticosteroid and placebo-treated groups. The most recent trial with
225 participants differed from the others in that all participants
RESULTS received intravenous immunoglobulin, 0.4 g/kg daily for five days
in accordance with current practice and were randomly allocated
to receive intravenous methylprednisolone, 500 mg daily for five
days, or an identical saline placebo (van Koningsveld 2004). In this
Description of studies
trial the authors reported a one disability grade improvement after
See: Characteristics of included studies; Characteristics of excluded four weeks in 63 of 113 (56%) of control and 76 of 112 (68%)
studies. methylprednisolone-treated participants (RR 1.2, 95% CI 1.0 to
1.5, P value = 0.06), a difference which was not quite significant.
After adjustment for age and severity of disability at randomisa-
Results of the search
tion the treatment effect just achieved significance, (RR 1.3, 95%
A search of the Cochrane Neuromuscular Disease Group Regis- CI 1.0 to 1.5, P value = 0.03). When the authors also adjusted
ter revealed eight references which might have been randomised for other prognostic factors not defined in the protocol (number
controlled trials. We excluded three studies: Levchenko 1989 was of days between onset of weakness and randomisation, preceding
not a randomised study, Mendell 1985 provided both plasma ex- infection with cytomegalovirus and the amplitude of compound
change and corticosteroids to the experimental group but neither muscle action potential) that were unbalanced between the treat-
to the control group and Zagar 1995 was a review. Advertising ment groups there was a significant odds ratio 2.96 (1.26 to 6.94,
for more trials among colleagues identified a further possible trial (P value = 0.01) for the primary outcome criterion. Other out-
(Haass 1988) but this was an observational study with no con- comes, including the proportion of participants requiring ventila-
trol group (see table Characteristics of excluded studies). Our tion, becoming able to walk unaided and improving one or more
search of EMBASE revealed six references which might have rep- disability grades during the first year, did not differ significantly
resented trials, including three which had not been detected by the between the groups.
other searches. We included one which was a quasi-randomised
trial (Bansal 1986) and excluded two others which were observa-
tional studies (El Zunni 1997; Naylor 1986). We identified an-
Risk of bias in included studies
other randomised controlled trial by personal contact with the au-
thor (Foyaca 2003). We excluded this trial because it did not meet Table 1 gives the quality scores for each trial. Allocation con-
criteria for adequate diagnostic criteria, as patients were included cealment was adequate in four trials in which participants were
who had pure sensory deficit, facial diplegia with paraesthesiae or randomly assigned to receive corticosteroids or ACTH or an
hyperreflexia. In addition, the trial did not meet our criteria for identical-appearing placebo (GBS Steroid 1993; Swick 1976; van
adequate definition of a single primary outcome measure and al- Koningsveld 2004). In one trial (Hughes 1978), participants were
location concealment was unclear. assigned to oral prednisolone or no corticosteroid treatment ac-
cording to a central register of random numbers which was only
revealed at the time of randomisation. In this trial the treatment al-
Included studies location concealment was also considered adequate. In the Shukla
Eight trials remained that fulfilled the selection criteria (see table 1988 trial, patients were randomly allocated to corticosteroids or
Characteristics of included studies) including 653 participants. placebo but it was not clear whether allocation was concealed. In
Only six trials with altogether 587 participants provided data for three trials (Garcia 1985; Bansal 1986; Singh 1996) participants
our primary outcome measure. The first trial compared intramus- were alternately assigned to corticosteroid or supportive care and
cular adrenocorticotrophic hormone daily for 10 days with placebo we considered the randomisation concealment inadequate.
(Swick 1976). Four trials with between 14 and 46 participants Patient blinding was intended in five trials but not in three (Bansal
compared oral prednisolone with placebo (Shukla 1988; Singh 1986; Garcia 1985; Hughes 1978). None of the trials recorded ef-
1996) or supportive treatment without steroids and no placebo fectiveness of blinding. In one trial (Hughes 1978) the participants
(Bansal 1986; Hughes 1978).The oral regimens varied but all con- were not blinded but the observers were. All the trials used in-
sisted of the equivalent of prednisolone 40 mg daily for at least two ternationally accepted diagnostic criteria (Asbury 1990) or closely
weeks (see table Characteristics of included studies). A trial with similar explicit criteria. All trials considered baseline clinical fea-
alternate allocation included 10 participants treated with methyl- tures. In three trials the baseline clinical features were similar. In
prednisolone 1500 mg daily for five days and 10 with supportive three trials, baseline differences were present: in the trial of (Swick

1976) the time to nadir was shorter in the corticosteroid group, 0.06 of a grade less improvement to 0.39 of a grade more improve-
in the trial of Bansal 1986 the corticosteroid-treated patients were ment (see Analysis 01.01)..
10 years older and in the trial of Singh 1996 corticosteroid-treated
patients were older and more disabled than the control groups.
Doubt also arose concerning this question in the GBS Steroid Secondary outcome measures
1993 trial in which there was an imbalance not at baseline but in
the subsequent treatment of the two groups, since more of the pa-
tients in the placebo group received plasma exchange than did in (1) Improvement by one or more disability grades after four
the corticosteroid group (see Discussion). In one trial there was an weeks
imbalance at randomisation in the number of days between onset Information for this outcome was available for five trials with 567
and randomisation (four days or less versus more than four days), participants. The information for this outcome was not available
amplitude of the compound muscle action potential (CMAP), for the Bansal 1986 trial. The relative rate of improving by one
and presence or absence of preceding cytomegalovirus infection, or more grades from baseline was 1.08 (95% CI 0.93 to 1.24)
all factors reported to affect prognosis (van Koningsveld 2004). more in the corticosteroid-treated than the control participants,
Follow-up was continued for a year in three trials (GBS Steroid a non-significant difference (see Analysis 01.02). In other words
1993; Hughes 1978; van Koningsveld 2004). The scores of each the absolute rate of patients improving one grade was 8% more
trial for quality measures are included in Table 1. The commonest with corticosteroids with 95% confidence intervals ranging from
problem was that the primary outcome criterion was not stated in 7% less to 24% more.
the methods section of the paper in any of the small trials. It was There was no significant heterogeneity in this analysis. In the three
stated in the two large trials (GBS Steroid 1993; van Koningsveld small oral corticosteroid trials there were 100 participants and the
2004). relative rate of improvement was less in the corticosteroid-treated
participants but the difference was not significant, WMD 0.80
(95% CI 0.55 to 1.16). When this analysis was confined to the
two large trials which used intravenous methylprednisolone the
Effects of interventions
relative rate of improvement did not quite achieve significance, be-
ing 1.14 (95% CI 0.97 to 1.34) greater in the intravenous methyl-
prednisolone-treated participants (see Analysis 01.02) than the
Primary outcome measure: change in disability grade control group. In other words the absolute rate of patients im-
four weeks after randomisation proving one grade was 14% more with corticosteroids with 95%
Information for this outcome was available for six trials with 587 confidence intervals ranging from 3% less to 34% more.
participants of whom 297 received corticosteroids and 290 did A check was made that there were no interactions between treat-
not. In the analysis of all these trials there was no significant differ- ment, age or initial disability for this outcome in the two large
ence between the groups: the weighted mean difference (WMD) trials for which data were available. The effect of age (less than
was 0.36 of a grade less improvement in the corticosteroid-treated 50 years and 50 years or more) and initial disability were tested
participants (see analyses). The 95% confidence intervals (CI) with an inverse variance meta-analysis combining the results of
ranged from 0.88 of a grade less improvement to 0.16 of a grade the GBS Steroid 1993 and van Koningsveld 2004 trials. The result
more improvement (see Analysis 01.01).There was significant gave an adjusted log odds ratio of 0.34 (95% CI -0.05 to 0.72)
heterogeneity in this analysis so that a random-effects model was (see Analysis 01.08). This is equivalent to an adjusted odds ratio
used for this computation. Inspection of the forest plot suggested of 1.41 (95% CI 0.95 to 2.07, P value = 0.08) which was in favour
more benefit from the intravenous regimens so that we undertook of corticosteroids but not quite significant (see Analysis 01.08).
separate analyses of the trials which used oral and intravenous Assuming that in the controls the probability of recovering one
regimens. In the four small trials which used oral corticosteroids or more grades is the average of those observed in the two stud-
(Bansal 1986; Hughes 1978; Shukla 1988; Singh 1996) there were ies, that is 53.2%, then these adjusted log odds ratio results are
120 participants and there was significantly less improvement in equivalent to a RR of improvement 1.16 (95% CI 0.98 to 1.32, P
corticosteroid-treated participants than in controls, WMD 0.82 value = 0.08) more with corticosteroids than with placebo, again
(95% CI 0.17 to 1.47). In the two large trials with 467 partici- not quite significant at the 5% level. This is very little different
pants which used intravenous methylprednisolone (GBS Steroid to the unadjusted pooled RR of 1.14 (95% CI 0.97 to 1.34) (see
1993; van Koningsveld 2004) there was a strong but not signif- Analysis 01.02).
icant trend towards a small amount more improvement with in-
travenous corticosteroids. The weighted mean difference was 0.17
(2) Time from randomisation until recovery of unaided
of a grade more improvement in those treated with intravenous
walking
methylprednisolone. The 95% confidence intervals ranged from

This outcome was derived for this review from the original data of included all recorded deaths regardless of the length of follow-up,
the trial of Hughes 1978 in which the median time to walk unaided and, even if the authors had excluded the case because they con-
was 29 days (95% CI 16.4 to 73.8) in the group treated with oral sidered that the death was due to an unrelated cause. We included
prednisolone and 34 days (95% CI 18.8 to 181.4) in the control a participant who was randomised to adrenocorticotrophic hor-
group. The difference between the groups, 5 days (95% CI -95 to mone in the trial of Swick (Swick 1976), left hospital against ad-
105) less in the corticosteroid group, was not significant (P value = vice and died at home. We also included a participant randomised
0.37). This outcome was also published for the largest study (GBS to no steroid treatment in another trial (Hughes 1978) who died
Steroid 1993) in which the median time to walk unaided was 38 of suicide during convalescence.
days in the group treated with steroids compared to 50 days in
the placebo group. The difference between the groups, 12 days
(95% CI -21.3 to 45.3) less in the corticosteroid group, was not (5) Proportion of patients dead or disabled (unable to walk
significant. The median time to walk unaided in the most recent without aid) after 12 months
trial (van Koningsveld 2004) was 28 days (interquartile ratio (IQR)
In the three trials in which this outcome was available (GBS
of the individual values 14 to 154 days), approximately equivalent
Steroid 1993; Hughes 1978; van Koningsveld 2004), 35 out of 252
to 95% CI of the median of 4 to 52 days) in the steroid treated
(13.9%) treated with oral prednisolone or intravenous methyl-
and 56 days (IQR 14 to 154 days, approximately equivalent to prednisolone were dead or disabled (needing aid to walk) after a
95% CI of 32 to 80 days) in the placebo-treated participants. The year compared with 22 out of 239 (9.2%) control patients. The
difference between the groups of 28 days (95% CI -6.0 to 62.0) RR of this combined outcome was not significantly different being
was not significant.
1.51 (95% CI 0.91 to 2.50) more in the corticosteroid than the
Similar outcome measures were reported in only one other trial.
placebo-treated participants (see Analysis 01.04).
The study of adrenocorticotrophic hormone (Swick 1976) in-
cluded, as an outcome measure, median time to complete recov-
ery which was 4 months (95% CI 2 to 6) in the participants
(6) Change in disability grade after six months
treated with adrenocorticotrophic hormone and 10 months (95%
CI 4.5 to 12) in the participants treated with placebo. It is difficult This outcome was obtained for the two largest trials with al-
to compute the significance of this observation since there were together 455 participants (GBS Steroid 1993; van Koningsveld
only nine participants in the corticosteroid group and seven in the 2004). There was no significant difference between the corticos-
placebo group; one participant in the treatment group died and teroid treated and the placebo treated patients, WMD 0.10 (95%
was omitted from the data. CI -0.16 to 0.36) of a grade more improvement in the corticos-
teroid treated patients, (see Analysis 01.07). The mean disability
grades of the corticosteroid and control groups were not signifi-
(3) Time from randomisation until discontinuation of cantly different after six months in one other trial (Singh 1996)
ventilation (for those ventilated) but the standard deviation was not provided so that this study was
In the GBS Steroid 1993 trial, the median time from randomi- not included in the meta-analysis.
sation to discontinuation of ventilation was 18 days in the group
treated with intravenous methylprednisolone and 27 days in the
placebo group (difference 12 days shorter with corticosteroids, (7) Change in disability grade after 12 months
95% CI 21.3 to 45.3). In contradiction to this, in the van
This outcome was available for three trials (GBS Steroid 1993;
Koningsveld 2004 trial, the median time from randomisation
Hughes 1978; van Koningsveld 2004) with 471 participants in
to discontinuation of ventilation was longer, 30 days (95% CI
total and showed almost no difference, a weighted mean differ-
16.6 to 43.4) in the 24 intravenous methylprednisolone and im-
ence of -0.03 (95% CI -0.29 to 0.23) less improvement in the
munoglobulin treated participants, compared with 26 days (95% corticosteroid group (See Analysis 01.05).
CI 15.3 to 36.7) in the 26 placebo and immunoglobulin control
participants.
(8) Relapse (defined as a period of worsening lasting at least
(4) Death seven days that followed a period of improvement lasting at
Mortality data were available from seven trials with 605 partic- least seven days) during the first year after randomisation
ipants in total. Twenty of 308 (6.5%) participants treated with Relapses during the first year after treatment were reported in three
corticosteroids died during the trial follow-up compared with 14 trials (GBS Steroid 1993; Hughes 1978; van Koningsveld 2004).
of 297 (4.7%) patients treated without, an insignificant difference Eighteen of 251 participants treated with corticosteroids relapsed
with a RR of 1.28 (95% CI 0.67 to 2.47) more deaths in the corti- compared with 15 of 239 control participants, an insignificant
costeroid-treated participants (see Analysis 01.03). This analysis difference, with a RR 1.14 (95% CI 0.59 to 2.18).

(9) Proportion of patients with specific adverse events value = 0.01). When these results were combined the relative risk
potentially attributable to corticosteroids during, or within of diabetes was significantly greater with corticosteroid treatment,
one week after stopping, treatment RR 2.21 (1.19 to 4.12, P value = 0.01) (see Analysis 01.09).
Shukla (Shukla 1988) reported one participant out of eight treated
with prednisolone who developed a perforated peptic ulcer and
another who developed psychosis but did not mention any such (d) development of hypertension requiring drug treatment
complications in eight placebo-treated participants. Side effects or In both the large trials hypertension was significantly less fre-
adverse events were not specifically reported in five trials (Hughes quent in the steroid-treated than the control group. When the
1978; Singh 1996; Swick 1976; van Koningsveld 2004). Informa- results were combined, there were highly significantly fewer par-
tion concerning the adverse events which had been preselected for ticipants who developed hypertension in the intravenous methyl-
review was available for the two intravenous methylprednisolone prednisolone group, 4/236 (1.7%), than in the placebo group, 27/
trials and has been illustrated in the analyses and summarised as 231 (7.4%), RR 0.15 (95% CI 0.05 to 0.41, P value = 0.0003)
follows. (see Analysis 01.09).
(a) development of new infection treated with antibiotics Subgroup analysis

In the first large trial (GBS Steroid 1993), 25/124 (20.2%) partic- In the absence of a significant main effect of corticosteroids on
ipants treated with intravenous methylprednisolone were reported the primary outcome measure, it is questionable whether meta-
to have had infection or septicaemia during the first four weeks of analysis of the effect on subgroups is appropriate. In one small
treatment; the proportion in the placebo group was similar, 25/ trial of oral prednisolone (Hughes 1978), the improvement of six
118 (21.2%). In the second large trial (van Koningsveld 2004), patients randomised to corticosteroids within the first week after
fewer patients treated with intravenous methylprednisolone (20/ onset was non-significantly worse four weeks after randomisation
112, 18%) had urinary tract infections than in the placebo group and significantly worse three months after randomisation com-
(35/113, 31%, P value 0.01), the opposite of the result which pared with 10 control patients randomised within the same period.
might have been expected. It is doubtful whether these two data Other information for the analyses of the subgroups selected by
sets should be analysed together but when this was done the rela- us was not available in the published reports. However, published
tive risk of infection was not significantly different, RR 0.74 (95% analyses in two of the large trials addressed this problem. In the
CI 0.52 to 1.04) (see Analysis 01.09). published report of the GBS Steroid 1993 trial, a regression anal-
ysis did not identify any interaction between age, severity at onset
(b) gastrointestinal haemorrhage or delay from onset until randomisation (within the maximum
permitted period which was 14 days) and the effect of treatment.
In the first large trial (GBS Steroid 1993), haemorrhage was
Similarly in the trial of van Koningsveld et al. (van Koningsveld
reported in 3/124 (2.4%) of corticosteroid-treated and 3/118
2004), there were no treatment interactions with age (less than 50
(2.5%) of placebo-treated participants but the site of haemor-
years or 50 years and more), disability score, duration of weakness
rhage was not recorded. In the second large trial (van Koningsveld
(<= 4 days), compound muscle action potential amplitude (=<4
2004), gastrointestinal haemorrhage occurred in 3/112 (2.6%)
mV or > 4 mV), or preceding cytomegalovirus infection. Conse-
corticosteroid treated and 2/113 (1.8%) placebo treated partici-
quently, neither trial identified subgroups in which intravenous
pants. Again it is doubtful whether these two data sets should be
methylprednisolone was more likely to be beneficial.
analysed together but when this was done the relative risk of in-
fection was not significant, RR 1.17 (95% CI 0.36 to 3.78) (see
Analysis 01.09).
Methodological quality
Because of the heterogeneity in the results from the primary out-
(c) development of diabetes mellitus come measure, the mean improvement in disability grade after
Our protocol included comparison of the proportions of patients four weeks, we repeated the analysis following omission of the
who developed diabetes mellitus requiring the use of insulin. This trials which did not have adequate allocation concealment. This
precise outcome was not stipulated for either trial but related out- reduced but did not remove the heterogeneity and made little dif-
comes were. In the first large trial (GBS Steroid 1993), diabetes ference to the result which showed almost no difference between
mellitus was reported in 5/124 (4.0%) of corticosteroid-treated the treatment groups, with a weighted mean difference of 0.01
and 5/118 (4.2%) of placebo-treated participants. The definition (95%CI -0.37 to 0.39) more improvement in the corticosteroid-
of diabetes was not stated. In the van Koningsveld 2004 trial a treated participants. The results of the separate analyses of the in-
plasma glucose >10 mmol/l occurred in 24/112 (21%) of corticos- travenous and oral regimens have been described above. There was
teroid-treated and 8/113 (7%) of placebo-treated participants (P no evidence of heterogeneity in the other analyses.

DISCUSSION possible, only 8/45 (17.8%) randomised to intravenous methyl-
prednisolone eventually received plasma exchange compared with
Eight studies examining the effects of corticosteroids in a total of 15/32 (46.9%) of placebo-treated participants (P value = 0.0125).
653 participants were included. This is a relatively small number in Since plasma exchange has been shown to be more effective than
relation to the known variability of outcome of GBS. Our primary supportive treatment (GBS Group 1985; Raphael 2004), this im-
outcome measure, mean disability grade improvement after four balance could have biased the results against detection of a benefi-
weeks, was available for six trials with 587 participants and showed cial effect from corticosteroids. However, an analysis after exclud-
no significant difference, a WMD of 0.36 of a disability grade less ing the participants in whom the use of plasma exchange had been
improvement, in the steroid group, with 95% confidence intervals declared possible showed no beneficial effect from corticosteroids.
from 0.88 of a grade less improvement to 0.16 of a grade more
improvement. There was significant heterogeneity in the results, Since analyses of the van Koningsveld 2004 trial taking into ac-
which could be explained by considering separately the results of count some prognostic factors showed significant differences in
the trials that tested oral and intravenous corticosteroids. In the favour of corticosteroids for the primary outcome measure, the
four trials of oral corticosteroids with a total of 120 participants, number of patients improving one disability grade after four weeks,
there was less improvement in the corticosteroid groups than in we undertook a similar analysis of the GBS Steroid 1993 trial
the control groups which was highly significant, WMD 0.82 of a taking into account age and disability, which were the factors for
grade less improvement (95% confidence intervals 0.16 to 1.47 of which we had information. We then used the inverse variance
a grade less improvement). In the two trials of intravenous methyl- method to combine the results of these two trials taking into ac-
prednisolone, there was a non-significant trend towards benefit count these two factors; the log odds ratio was in favour of corti-
from corticosteroids, WMD 0.17 of a grade more improvement costeroid group but the result was still not significant.
(95% confidence intervals 0.06 of a grade less improvement to The difference between the effects of oral and intravenous cor-
0.39 of a grade more improvement). No significant differences ticosteroids was unexpected. Multiple factors may play a role in
emerged from our analyses of the secondary outcome measures this finding. The first question is whether the effect is real. The
selected for this review. These were the number improving after trials of oral corticosteroids which contributed the available ev-
four weeks, the time to walk unaided, the duration of ventilation idence were of lower quality: in only one of the four trials was
(for those ventilated), the number of deaths and the number left allocation concealment adequate. Second, the numbers in each
dead or disabled (unable to walk unaided) after one year. trial were small; the total number of participants was only 120.
Third, the unfavourable effect of oral corticosteroids was only de-
There were differences between the two trials of intravenous
tected for our primary outcome measure and not for the propor-
methylprednisolone which provided the bulk of the evidence. Both
tion of patients improving one grade or for death, the only other
tested intravenous methylprednisolone 500 mg daily for five days
outcome measures for which data were available and where there
against placebo. One reported no difference in any outcome be-
was no difference. Fourth, corticosteroids are readily absorbed and
tween the corticosteroid and placebo-treated groups (GBS Steroid
the route of administration itself is unlikely to be responsible.
1993). The other differed in that both treatment groups also re-
Fifth, the oral corticosteroid courses lasted more than two weeks
ceived intravenous immunoglobulin which has now become a
in all four trials since the treatment could be continued longer at
standard treatment for GBS (van Koningsveld 2004). Their raw
the discretion of the treating physician. The intravenous courses
results were not significant for any of the outcome measures, but
only lasted five days. It is possible that early corticosteroid treat-
further analyses taking into account age and disability at ran-
ment helps by reducing inflammation and later treatment harms
domisation showed a borderline significant result for their pri-
by inhibiting macrophage clearance of myelin debris or other re-
mary outcome measure (proportion of participants improving by
pair mechanisms. Sixth, the intravenous trials tested higher initial
one or more disability grade after four weeks). The review au-
doses, approximately eight-fold higher for the five days that they
thors judged the methodological quality of both trials adequate,
were given, and rapid intravenous infusion might have a different
but there was one caveat about the GBS Steroid 1993 trial. Be-
effect on the immune system compared with oral absorption from
cause of the variation in practice and ethical issues at the time of
tablets.
the trial, there was an imbalance in the numbers of participants
who received plasma exchange in the two groups. Only 66/124 The question now arises as to the data that provide the best ev-
(53%) of the participants treated with intravenous methylpred- idence on which to base practice. Our analysis of the oral corti-
nisolone received plasma exchange compared with 77/118 (65%) costeroid trials indicates a significant negative effect which physi-
placebo-treated participants (P value = 0.08). Furthermore, the cians caring for these patients will want to take into account. Our
physicians caring for the participants in that trial had been asked at combined analysis of the intravenous methylprednisolone trials
the time of randomisation to declare whether each patient would showed no significant difference in any outcome but one of the
definitely, definitely not, or possibly receive plasma exchange. For included trials did not use intravenous immunoglobulin, which
those participants for whom plasma exchange had been declared is now part of standard care. The van Koningsveld 2004 trial is

the only trial that has tested the effect of adding corticosteroids deciding upon their use in GBS.
to intravenous immunoglobulin; physicians may place more re-
The absence of an easily demonstrable beneficial effect of corti-
liance on the data from this trial which reflects current practice
costeroids in GBS is difficult to explain. Guillain-Barr syndrome
more accurately than the earlier studies. This argument assumes
resembles the animal model experimental autoimmune neuritis
that corticosteroids given with intravenous immunoglobulin are
in which early treatment with high-dose corticosteroids does sup-
more efficacious than either given on their own. However, there
press the clinical deficit and hasten recovery (Hughes 1981; King
is a lack of other evidence to support this hypothesis. Whatever
1985; Watts 1989). In addition, the related condition, chronic
view is taken, the analyses presented in this review indicate that
inflammatory demyelinating polyradiculoneuropathy, showed a
the true effect of intravenous corticosteroids is at best small and
significant response to oral prednisone in the only randomised
was absent for long-term outcomes.
controlled trial ever performed (Dyck 1982; Mehndiratta 2004).
Serious adverse events were infrequent with the short courses of It is possible that the anticipated beneficial effects of suppressing
corticosteroids used in these trials. This was not surprising since the inflammatory response which underlies the pathology of most
observational studies and clinical experience suggest that short cases of GBS in North America and Europe is counteracted by
courses of corticosteroids rarely cause serious side-effects. The only some other unexpected and unwanted effect of corticosteroids on
differences in adverse events between groups in the two intra- the repair process. Following nerve transection in the rat, adminis-
venous methylprednisolone trials were in diabetes, which was, as tration of corticosteroids causes prolonged loss of muscle electrical
expected, significantly more common; and in hypertension, which excitability due to loss of sodium channels or activation of calcium
was, surprisingly, significantly less common in the intravenous release channels (Rich 1998; Riggs 1998). The same phenomenon,
methylprednisolone group than in the placebo group. This lat- if it occurs in man, would explain why the use of corticosteroids
ter result is difficult to explain. An association between glomeru- in severe cases of GBS, in which denervation is anticipated, does
lonephritis and GBS has been reported (Bettinelli 1989; Olbricht not have the beneficial effect predicted from its known anti-in-
1993). It is possible that intravenous methylprednisolone had a flammatory properties. If this hypothesis is correct then corticos-
favourable effect on renal function so as to prevent hypertension. teroids might be beneficial in a subgroup of patients with conduc-
Future trials of immunomodulatory treatment in GBS should tion block but not denervation. In practice it would be difficult to
monitor blood pressure and renal function. Few studies formally identify patients in whom denervation is not already occurring or
recorded the absence of the adverse events selected for consider- is about to occur. It would be helpful to develop indicators which
ation in this review. Particular adverse events that were recorded would reliably identify patients destined to have a poor prognosis.
have been included but this list may be incomplete. Consequently
the absence of evidence cannot be construed as the absence of oc-
currence of these events. We encourage organisers of future trials AUTHORS CONCLUSIONS
to collect systematically information about adverse events and dis-
ease complications which are known to occur with GBS, such as Implications for practice
infections requiring antibiotics, cardiac arrhythmia requiring in- Limited evidence from four randomised controlled trials shows
stallation of a pacemaker or use of anti-arrhythmic drugs, postu- that oral corticosteroids slow recovery from GBS. Evidence from
ral hypotension, systemic hypertension requiring treatment, deep two large trials shows that intravenous methylprednisolone admin-
vein thrombosis, and pulmonary embolism. istered for five days shows a non-significant trend towards more
rapid recovery than placebo treatment but has no significant ef-
This review prompts recommendations about the design of future
fect on long-term outcomes. In one of these trials, intravenous
GBS trials. In the trials reviewed, the principal outcome measures
methylprednisolone combined with intravenous immunoglobulin
have involved crude clinical endpoints, or a simple disability scale
showed possible benefit, which was not quite significant at four
that seem rather coarsely graded to consumers and may be insuf-
weeks but became significant when allowance was made for an
ficiently responsive to detect meaningful clinical effects. Electro-
imbalance in baseline prognostic variables. No significant bene-
physiological outcome measures have not been used and might
fit was detected at any later timepoint. There was no evidence of
provide objective surrogate endpoints, having continuous scales
harm from intravenous methylprednisolone.
that would allow the use of parametric statistics. However, such
measures may not reflect disability or handicap and are affected by
difficulties in standardisation between laboratories, which would
Implications for research
make it difficult to draw useful conclusions. Future trials should More research into the efficacy of corticosteroids is needed and
consider measuring fatigue, which is a persistent problem in many more effective treatments for Guillain-Barr syndrome should be
patients. No trial has included Health Related Quality of Life mea- sought. More responsive outcome measures should be designed
sures or incorporated cost-effectiveness calculations. Since corti- and validated. Future trials should report serious complications
costeroids are inexpensive, cost would not be a significant issue in of GBS as well as possible side effects of drugs. They should also

report separately results in subgroups of patients having clinical
features at randomisation that are known to affect prognosis. This
would require large groups of patients. An explanation should be
sought for the absence of more obvious benefit from corticos-
teroids in GBS.
ACKNOWLEDGEMENTS
We thank Professor Frans van der Mech, co-author of the first
version of this review.
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Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Bansal 1986
Methods Open parallel-group controlled trial with alternate allocation
Participants 20 patients with GBS defined according to criteria similar to those of (Asbury 1990)
Interventions Prednisolone 15 mg 4 times daily for 4 days, 10 mg 4 times daily for 3 days, 10 mg 3 times daily for 10
days and then tapered or no treatment
Outcomes Multiple including changes in the disability grade of (Hughes 1978) after 1, 2, 3, and 4 weeks and 3
months; disease duration; residual disability; death; relapse
Notes Single centre

Conducted in India
Mean (SD) age 54.5 (15.1) years in steroid and 39.6 (14.4) in the control group. Unusually large im-
provements after 4 weeks in both groups, mean 2.4 grades in steroids and 4.0 grades in control
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear D - Not used
Garcia 1985
Methods Open parallel-group controlled trial with alternate allocation
Participants 20 mostly adult patients with GBS defined according to criteria of (Asbury 1990)
Interventions Intravenous methylprednisolone 1500 mg daily for 5 days versus supportive care
Outcomes Time to recovery: not significantly different between the two groups. After 6 months 7 of 10 corticosteroid-
treated patients had returned to work or resumed domestic duties at 95% of normal. No side effects
attributable to corticosteroids reported
Notes Single centre

Conducted in Mexico.
Risk of bias
Allocation concealment? Unclear D - Not used

GBS Steroid 1993
Methods Double-blind parallel-group randomised controlled trial.
Participants 242 adult patients with GBS diagnosed according to the criteria of (Asbury 1990). Unable to run. Disease
onset <15 days
Interventions Intravenous methylprednisolone 500 mg daily for 5 days or placebo infusions
Outcomes Primary: 0.5 disability grade (Hughes 1978) difference after 4 weeks. Secondary: 0.5 disability grade
difference after 12 weeks, reduction of times to cease artificial ventilation and to recover ability to walk
unaided. After 4 weeks mean (SD) disability grade improvement in corticosteroid group was 0.73 (1.21)
grade compared with 0.8 (1.14) grade in the placebo group, difference 0.06 grade (95% CI -0.23 to 0.
36)
Notes International multicentre

Plasma exchange permitted at the discretion of the participating neurologist
Risk of bias
Allocation concealment? Yes A - Adequate
Hughes 1978
Methods Observer blind parallel-group randomised controlled trial.
Participants 40 patients of any age with acute polyneuropathy of undetermined aetiology fulfilling criteria similar to
those of (Asbury 1990)
Interventions Prednisolone 15 mg three times daily for one week, 10 mg three times daily for four days, 5 mg four times
daily for three days followed by continued treatment at discretion or no steroid treatment
Outcomes Changes in a 7 point disability grade scale after one, three and 12 months, time to onset of improvement,
time to recover ability for manual work, and proportion with residual disability were all measured. A
primary outcome measure was not predefined. There were no significant differences at any of these times
except for the subgroup of patients who were randomised within a week from the onset. In this subgroup,
the 6 control patients improved by a mean (SD) of 2.5 (0.43) grades whereas the 10 corticosteroid patients
only improved by 0.9 (0.46) grade (P value < 0.05)
Notes International multicentre.

It was decided during the trial that patients who had begun to improve before trial entry should be excluded
and so one patient was removed from each group. The 4 week grade change SD is not in the paper and has
been derived from the original data. One suicide in the control group was excluded by the authors from
their analysis but has been included in the death table in this review. There were no significant differences
at any of these times except for the subgroup of patients who were randomized within a week from the
onset. In this subgroup, the 6 control patients improved by a mean (SD) of 2.5 (0.43) grades whereas the
10 corticosteroid patients only improved 0.9 (0.46) grade (P<0.05)

Hughes 1978 (Continued)
Risk of bias
Shukla 1988
Methods Double-blind randomised parallel-group controlled trial.
Participants 16 patients with GBS fulfilling diagnostic criteria of (Asbury 1990)
Interventions Prednisolone 60 mg daily in divided doses for one week, 40 mg daily for one week, 30 mg daily for two
weeks and thereafter at the discretion of the physician or identical appearing placebo tablets
Outcomes Changes in the disability grade of Hughes (1978) after 1, 4 and 6 weeks. After 4 weeks 5 of 8 corticosteroid
and 3 of 6 placebo patients had improved 1 or more grades. 2 placebo patients dropped out
Notes Single centre.

Conducted in India.
Risk of bias
Singh 1996
Methods Double-blind controlled parallel-group trial with patients allocated alternately to one blinded treatment
or the other
Participants 52 patients with GBS fulfilling the diagnostic criteria of (Asbury 1990)
Interventions Prednisolone 40 mg twice daily for 2 weeks and thereafter gradually tapered or identical appearing placebo
tablets
Outcomes Disability grade of Hughes (1978) after 2, 4 and 24 weeks. After 4 weeks 14 of 22 placebo and 12 of 24
corticosteroid patients had improved 1 or more grades. 6 dropped out

Conducted in India.
Risk of bias

Singh 1996 (Continued)
Allocation concealment? No C - Inadequate
Swick 1976
Participants 38 patients with idiopathic polyneuritis diagnosed according to criteria of (Osler 1960). Patients requiring
artificial ventilation or with contraindications to steroids were excluded
Interventions Active treatment for adults 100 units and children 2 units/kg aqueous ACTH intramuscularly daily for
10 days or equal volumes of diluent as placebo
Outcomes Duration of hospitalisation, time to complete recovery. Excluding a patient who died in the ACTH group,
the median time to recovery was 9.00 days in the placebo and 4.4 days in the ACTH group (P value = 0.
05)

Conducted in USA.
Risk of bias
van Koningsveld 2004
Participants 225 patients with GBS fulfilling the diagnostic criteria of (Asbury 1990)
Interventions All patients received IVIg 0.4 g/kg daily for 5 days and also either intravenous methylprednisolone 500
mg daily for 5 days or placebo infusions
Outcomes Primary: improvement of one disability grade modified after (Hughes 1978) after 4 weeks. Secondary:
ability to walk unaided after 8 weeks, number of days to walk independently. After 4 weeks 63 of 113
(56%) placebo participants improved one or more grades compared with 76 of 112 (68%) corticosteroid
participants (P value = 0.06). See text for more details
Notes Multicentre centre study in the Netherlands, Belgium and Germany
Risk of bias

Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
El Zunni 1997 Not a RCT. Observational study in which 5 patients with disability grade 1 or 2 were given placebo, 5 with
disability grade 2 who were already on steroids were continued on them and 6 with disability grade 3 to 5 were
given IVIg. One of the last six died. There was no significant difference in the amount of improvement in disability
grade between the groups
Foyaca 2003 The participants were 29 HIV positive participants in a single South African centre randomly allocated to
prednisone 1 mg/kg daily or placebo. After 36 days the mean (SD) improvement on the disability scale used in
this review was significantly greater, 0.8 (0.676) in the 15 prednisone-treated and 0.07 (0.27) in the 14 placebo-
treated participants, mean difference 0.73 (95% CI 0.33 to 1.13). Ten of 15 prednisone-treated and 1 of 14
placebo-treated participants had improved one or more grades and the relative rate of improving by this amount
was significant, 9.3 (95% CI 1.4 to 63.8). Follow-up data were not available for one placebo participant for
unstated reasons.
The participants were 29 HIV positive participants in a single South African centre randomly allocated to
prednisone 1 mg/kg daily or placebo. After 36 days the mean (SD) improvement on the disability scale used in
this review was significantly greater, 0.8 (0.676) in the 15 prednisone-treated and 0.07 (0.27) in the 14 placebo-
treated participants, mean difference 0.73 (95% CI 0.33 to 1.13). Ten of 15 prednisone-treated and 1 of 14
placebo-treated participants had improved one or more grades and the relative rate of improving by this amount
was significant, 9.3 (95% CI 1.4 to 63.8). Follow-up data were not available for one placebo participant for
unstated reasons.
Allocation concealment unclear, diagnostic criteria inadequate (criteria in methods contradicted by inclusion of
non-eligible participants described in discussion)
Haass 1988 Non-randomised open study.
Levchenko 1989 Not a trial of corticosteroid treatment but a personal series of patients with severe GBS all treated with prednisolone
or methylprednisolone, 8 with and 11 without plasma exchange as well
Mendell 1985 Compared corticosteroids and plasma exchange against no treatment
Naylor 1986 Not a RCT.
Zagar 1995 Review, not a RCT.
Zhang 2000 Controlled trial comparing 22 patients treated with the Chinese herbal medicine tripterygium with 21 treated
with dexamethasone 15 to 20 mg intravenously for 15 days and then 5 to 10 mg daily for 7 days followed by oral
prednisone 30 to 60 mg daily reduced by 5 to 10 mg every two weeks. Method of randomisation unclear. None
of the outcomes selected for this review available. After 8 weeks, 20 of 22 improved in the tripterygium group
and 13 of 21 in the dexamethasone group. Tripterygium lowered serum IL-6 significantly

DATA AND ANALYSES
Comparison 1. Corticosteroid versus control
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Disability grade change after 6 587 Mean Difference (IV, Random, 95% CI) 0.36 [-0.16, 0.88]
four weeks
1.1 Oral regimens 4 120 Mean Difference (IV, Random, 95% CI) 0.82 [0.17, 1.47]
1.2 Intravenous regimens 2 467 Mean Difference (IV, Random, 95% CI) -0.17 [-0.39, 0.06]
2 Improvement by one or more 5 567 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.93, 1.24]
grades after four weeks
2.1 Oral regimens 3 100 Risk Ratio (M-H, Fixed, 95% CI) 0.80 [0.55, 1.16]
2.2 Intravenous regimens 2 467 Risk Ratio (M-H, Fixed, 95% CI) 1.14 [0.97, 1.34]
3 Death 7 605 Risk Ratio (M-H, Fixed, 95% CI) 1.28 [0.67, 2.47]
4 Death or disability after one year 3 491 Risk Ratio (M-H, Fixed, 95% CI) 1.51 [0.91, 2.50]
5 Disability grade change after 12 3 471 Mean Difference (IV, Fixed, 95% CI) 0.03 [-0.23, 0.29]
months
6 Proportion of patients who 3 490 Risk Ratio (M-H, Fixed, 95% CI) 1.14 [0.59, 2.18]
relapsed
7 Disability grade change after six 2 455 Mean Difference (IV, Fixed, 95% CI) -0.10 [-0.36, 0.16]
months
8 Tx v Control OR for 2 log(OR) (Fixed, 95% CI) 0.34 [-0.05, 0.73]
improvement by one or more
grades by 4 wks adj for age and
initial DG
9 Adverse events 2 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
9.1 New infection treated 2 467 Risk Ratio (M-H, Fixed, 95% CI) 0.74 [0.52, 1.04]
with antibiotics
9.2 Gastro-intestinal 2 467 Risk Ratio (M-H, Fixed, 95% CI) 1.17 [0.36, 3.78]
haemorrhage
9.3 Diabetes mellitus 2 467 Risk Ratio (M-H, Fixed, 95% CI) 2.21 [1.19, 4.12]
requiring insulin
9.4 Hypertension 2 467 Risk Ratio (M-H, Fixed, 95% CI) 0.15 [0.05, 0.41]

Analysis 1.1. Comparison 1 Corticosteroid versus control, Outcome 1 Disability grade change after four
weeks.
Review: Corticosteroids for Guillain-Barr syndrome
Comparison: 1 Corticosteroid versus control
Outcome: 1 Disability grade change after four weeks
Mean Mean
Study or subgroup Corticosteroids Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
1 Oral regimens
Hughes 1978 21 -0.24 (0.94) 19 -0.74 (0.81) 19.6 % 0.50 [ -0.04, 1.04 ]
Bansal 1986 10 -2.38 (0.97) 10 -3.97 (0.7) 16.6 % 1.59 [ 0.85, 2.33 ]
Shukla 1988 6 -0.67 (1.75) 8 -0.88 (1.13) 7.5 % 0.21 [ -1.39, 1.81 ]
Singh 1996 24 -0.2 (2) 22 -0.8 (2.1) 10.9 % 0.60 [ -0.59, 1.79 ]
Subtotal (95% CI) 61 59 54.6 % 0.82 [ 0.17, 1.47 ]

Heterogeneity: Tau2 = 0.21; Chi2 = 6.16, df = 3 (P = 0.10); I2 =51%
Test for overall effect: Z = 2.47 (P = 0.013)
2 Intravenous regimens
GBS Steroid 1993 124 -0.8 (1.14) 118 -0.73 (1.21) 23.0 % -0.07 [ -0.37, 0.23 ]
van Koningsveld 2004 112 -1.13 (1.3) 113 -0.83 (1.35) 22.4 % -0.30 [ -0.65, 0.05 ]
Subtotal (95% CI) 236 231 45.4 % -0.17 [ -0.39, 0.06 ]

Heterogeneity: Tau2 = 0.0; Chi2 = 0.98, df = 1 (P = 0.32); I2 =0.0%
Total (95% CI) 297 290 100.0 % 0.36 [ -0.16, 0.88 ]
Heterogeneity: Tau2 = 0.29; Chi2 = 24.60, df = 5 (P = 0.00017); I2 =80%
-4 -2 0 2 4
Favours Steroid Favours Control

Analysis 1.2. Comparison 1 Corticosteroid versus control, Outcome 2 Improvement by one or more grades
after four weeks.
Outcome: 2 Improvement by one or more grades after four weeks
Study or subgroup Corticosteroids Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Oral regimens
Hughes 1978 9/21 10/19 6.8 % 0.81 [ 0.42, 1.56 ]
Shukla 1988 3/6 5/8 2.8 % 0.80 [ 0.31, 2.10 ]
Singh 1996 12/24 14/22 9.5 % 0.79 [ 0.47, 1.31 ]
Subtotal (95% CI) 51 49 19.1 % 0.80 [ 0.55, 1.16 ]

Total events: 24 (Corticosteroids), 29 (Control)
Heterogeneity: Chi2 = 0.01, df = 2 (P = 1.00); I2 =0.0%
GBS Steroid 1993 67/124 60/118 40.0 % 1.06 [ 0.84, 1.35 ]
van Koningsveld 2004 76/112 63/113 40.8 % 1.22 [ 0.99, 1.50 ]
Subtotal (95% CI) 236 231 80.9 % 1.14 [ 0.97, 1.34 ]

Total (95% CI) 287 280 100.0 % 1.08 [ 0.93, 1.24 ]
0.2 0.5 1 2 5
Favours Control Favours Steroid

Analysis 1.3. Comparison 1 Corticosteroid versus control, Outcome 3 Death.
Outcome: 3 Death

1 Oral regimens
Bansal 1986 1/10 1/10 6.8 % 1.00 [ 0.07, 13.87 ]
Hughes 1978 1/21 2/19 14.2 % 0.45 [ 0.04, 4.60 ]
Shukla 1988 1/8 1/8 6.8 % 1.00 [ 0.07, 13.37 ]
Singh 1996 4/24 3/22 21.1 % 1.22 [ 0.31, 4.86 ]
Swick 1976 1/9 0/7 3.8 % 2.40 [ 0.11, 51.32 ]
Subtotal (95% CI) 72 66 52.6 % 1.04 [ 0.41, 2.63 ]

GBS Steroid 1993 5/124 2/118 13.8 % 2.38 [ 0.47, 12.03 ]
van Koningsveld 2004 6/112 5/113 33.6 % 1.21 [ 0.38, 3.85 ]
Subtotal (95% CI) 236 231 47.4 % 1.55 [ 0.61, 3.94 ]

Total (95% CI) 308 297 100.0 % 1.28 [ 0.67, 2.47 ]
0.01 0.1 1 10 100


Analysis 1.4. Comparison 1 Corticosteroid versus control, Outcome 4 Death or disability after one year.
Outcome: 4 Death or disability after one year

1 Oral regimens
Hughes 1978 2/21 2/19 9.3 % 0.90 [ 0.14, 5.81 ]
Subtotal (95% CI) 21 19 9.3 % 0.90 [ 0.14, 5.81 ]

Heterogeneity: not applicable
GBS Steroid 1993 21/124 9/118 40.8 % 2.22 [ 1.06, 4.65 ]
van Koningsveld 2004 12/107 11/102 49.9 % 1.04 [ 0.48, 2.25 ]
Subtotal (95% CI) 231 220 90.7 % 1.57 [ 0.93, 2.66 ]

Heterogeneity: Chi2 = 1.94, df = 1 (P = 0.16); I2 =48%
Total (95% CI) 252 239 100.0 % 1.51 [ 0.91, 2.50 ]
0.1 0.2 0.5 1 2 5 10


Analysis 1.5. Comparison 1 Corticosteroid versus control, Outcome 5 Disability grade change after 12
months.
Outcome: 5 Disability grade change after 12 months
Mean Mean
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Hughes 1978 21 -1.91 (1.14) 19 -2.32 (1.83) 7.4 % 0.41 [ -0.55, 1.37 ]
GBS Steroid 1993 124 -2.57 (1.53) 118 -2.66 (1.21) 56.3 % 0.09 [ -0.26, 0.44 ]
van Koningsveld 2004 97 -2.64 (1.54) 92 -2.5 (1.49) 36.3 % -0.14 [ -0.57, 0.29 ]
Total (95% CI) 242 229 100.0 % 0.03 [ -0.23, 0.29 ]

Test for subgroup differences: Not applicable
-1 -0.5 0 0.5 1

Analysis 1.6. Comparison 1 Corticosteroid versus control, Outcome 6 Proportion of patients who relapsed.
Outcome: 6 Proportion of patients who relapsed

1 Oral regimens
Hughes 1978 3/21 0/19 3.3 % 6.36 [ 0.35, 115.73 ]
Subtotal (95% CI) 21 19 3.3 % 6.36 [ 0.35, 115.73 ]

Heterogeneity: not applicable
GBS Steroid 1993 7/124 4/118 25.9 % 1.67 [ 0.50, 5.54 ]
van Koningsveld 2004 8/106 11/102 70.8 % 0.70 [ 0.29, 1.67 ]
Subtotal (95% CI) 230 220 96.7 % 0.96 [ 0.48, 1.91 ]

Total (95% CI) 251 239 100.0 % 1.14 [ 0.59, 2.18 ]
0.01 0.1 1 10 100


Analysis 1.7. Comparison 1 Corticosteroid versus control, Outcome 7 Disability grade change after six
months.
Outcome: 7 Disability grade change after six months
Mean Mean
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
GBS Steroid 1993 124 -2.4 (1.52) 118 -2.32 (1.25) 55.3 % -0.08 [ -0.43, 0.27 ]
van Koningsveld 2004 108 -2.41 (1.47) 105 -2.29 (1.43) 44.7 % -0.12 [ -0.51, 0.27 ]
Total (95% CI) 232 223 100.0 % -0.10 [ -0.36, 0.16 ]

-1 -0.5 0 0.5 1
Analysis 1.8. Comparison 1 Corticosteroid versus control, Outcome 8 Tx v Control OR for improvement by
one or more grades by 4 wks adj for age and initial DG.
Outcome: 8 Tx v Control OR for improvement by one or more grades by 4 wks adj for age and initial DG
Study or subgroup log(OR) (SE) log(OR) Weight log(OR)

IV,Fixed,95% CI IV,Fixed,95% CI
GBS Steroid 1993 0.0839 (0.27) 53.6 % 0.08 [ -0.45, 0.61 ]
van Koningsveld 2004 0.6365 (0.29) 46.4 % 0.64 [ 0.07, 1.20 ]
Total (95% CI) 100.0 % 0.34 [ -0.05, 0.73 ]

-4 -2 0 2 4
Favours Control Favours Steroid

Analysis 1.9. Comparison 1 Corticosteroid versus control, Outcome 9 Adverse events.
Outcome: 9 Adverse events

1 New infection treated with antibiotics

GBS Steroid 1993 25/124 25/118 42.4 % 0.95 [ 0.58, 1.56 ]
van Koningsveld 2004 20/112 35/113 57.6 % 0.58 [ 0.36, 0.93 ]
Subtotal (95% CI) 236 231 100.0 % 0.74 [ 0.52, 1.04 ]

2 Gastro-intestinal haemorrhage
GBS Steroid 1993 3/124 3/118 60.7 % 0.95 [ 0.20, 4.62 ]
van Koningsveld 2004 3/112 2/113 39.3 % 1.51 [ 0.26, 8.88 ]
Subtotal (95% CI) 236 231 100.0 % 1.17 [ 0.36, 3.78 ]

3 Diabetes mellitus requiring insulin
GBS Steroid 1993 5/124 5/118 39.1 % 0.95 [ 0.28, 3.20 ]
van Koningsveld 2004 24/112 8/113 60.9 % 3.03 [ 1.42, 6.45 ]
Subtotal (95% CI) 236 231 100.0 % 2.21 [ 1.19, 4.12 ]

4 Hypertension
GBS Steroid 1993 2/124 12/118 45.2 % 0.16 [ 0.04, 0.69 ]
van Koningsveld 2004 2/112 15/113 54.8 % 0.13 [ 0.03, 0.57 ]
Subtotal (95% CI) 236 231 100.0 % 0.15 [ 0.05, 0.41 ]

0.01 0.1 1 10 100


ADDITIONAL TABLES
Table 1. Methodological quality scores
Study ID Allocatn Observer Patient Diagnostic Primary Baseline Follow-up Adherence

concealmt blinding blinding criteria outcome differences complete to regime
Swick 1976 A A A A C A A C
Hughes A A C A C A A C
1978
Bansal 1986 D D D A C B A C
Singh 1986 C C A A C A B C
Shukla 1988 C A A A C A B C
GBS Steroid A A A A A A A A
1993
van A A A A A A A A
Koningsveld
2004
Garcia 1985 C C C A C C C C
APPENDICES
Appendix 1. Search strategy for OVID MEDLINE

1. randomized controlled trial.pt.
2. randomized controlled trials/
3. controlled clinical trial.pt.
4. controlled clinical trials/
5. random allocation/
6. double-blind method/
7. single-blind method/
8. clinical trial.pt.
9. exp clinical trials/
10. (clin$ adj25 trial$).tw.
11. ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or mask$ or dummy)).tw.
12. placebos/
13. placebo$.tw.
14. random$.tw.
15. research design/
16. (clinical trial phase i or clinical trial phase ii or clinical trial phase iii or clinical trial phase iv).pt.
17. multicenter study.pt.
18. meta analysis.pt.
19. Prospective Studies/
20. Intervention Studies/
21. Cross-Over Studies/
22. Meta-Analysis/
23. (meta?analys$ or systematic review$).tw.
24. control.tw.
25. or/1-24
26. Animal/
27. Human/
28. 26 and 27
29. 26 not 28
30. 25 not 29
31. guillain barre syndrome.mp. or Guillain-Barre Syndrome/
32. POLYRADICULONEUROPATHY/ or POLYNEUROPATHIES/
33. (acute polyradiculoneuritis or acute polyneuritis).mp. [mp=title, original title, abstract, name of substance, mesh subject heading]
34. (inflammatory adj5 neuropath$3).tw.
35. (inflammatory adj5 polyneuropath$3).tw.
36. or/31-35
37. 30 and 36
WHATS NEW
Last assessed as up-to-date: 27 February 2007.
Date Event Description
22 July 2008 Amended Converted to new review format.
HISTORY
Protocol first published: Issue 4, 1998
Review first published: Issue 1, 1999
Date Event Description
28 February 2007 New search has been performed The searches were updated in February 2007, but no
new studies were identified

(Continued)
31 January 2006 New citation required and conclusions have changed A large trial has been added almost doubling the amount
of evidence. This trial showed a trend towards more im-
provement on short-term benefit which became signif-
icant after taking into account prognostic factors that
were imbalanced between the groups at randomisation.
This did not alter the conclusion of the meta-analysis
from all trials that corticosteroids do not produce sig-
nificant benefit
21 October 1999 Amended An error in entering the standard deviations for change
in disability grade after one year for the trial of Hughes
1978, has been corrected in the table of comparisons.
This has resulted in the difference between the groups
becoming not significant for that outcome, in agreement
with the other outcome measures
CONTRIBUTIONS OF AUTHORS
Richard Hughes prepared the first draft of the initial review and extracted the data from the studies. Pieter van Doorn checked the data
for the update of the review in January 2004. Richard Hughes and Rinske van Koningsveld undertook data extraction for the update
in 2005. All authors contributed to and agreed the final text of the review.
DECLARATIONS OF INTEREST
RACH co-ordinated two randomised controlled trials which did not report a significant beneficial effect from corticosteroids. AVS
helped with the second of these. PvD and RvK undertook a trial which reported possible significant benefit.
SOURCES OF SUPPORT
Internal sources
Guys, Kings and St Thomas School of Medicine, Kings College, London, UK.
External sources
Guillain-Barr Syndrome Foundation International, USA.

INDEX TERMS
Medical Subject Headings (MeSH)

Adrenocorticotropic Hormone [therapeutic use]; Anti-Inflammatory Agents [ therapeutic use]; Glucocorticoids [ therapeutic use];
Guillain-Barre Syndrome [ drug therapy]; Randomized Controlled Trials as Topic
MeSH check words

Adult; Child; Humans


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Corticosteroids for Guillain-Barr syndrome (Review)

Hughes RAC, Swan AV, van Koningsveld R, van Doorn PA

Corticosteroids for Guillain-Barr syndrome (Review)

Corticosteroids for Guillain-Barr syndrome (Review) i

Corticosteroids for Guillain-Barr syndrome

Editorial group: Cochrane Neuromuscular Disease Group.

PLAIN LANGUAGE SUMMARY

BACKGROUND response do work in GBS. One Cochrane review concluded from

Corticosteroids for Guillain-Barr syndrome (Review) 3

Corticosteroids for Guillain-Barr syndrome (Review) 4

Corticosteroids for Guillain-Barr syndrome (Review) 5

Corticosteroids for Guillain-Barr syndrome (Review) 6

Corticosteroids for Guillain-Barr syndrome (Review) 7

(a) development of new infection treated with antibiotics Subgroup analysis

Corticosteroids for Guillain-Barr syndrome (Review) 8

Corticosteroids for Guillain-Barr syndrome (Review) 9

Corticosteroids for Guillain-Barr syndrome (Review) 10

Corticosteroids for Guillain-Barr syndrome (Review) 12

Characteristics of included studies [ordered by study ID]

Methods Open parallel-group controlled trial with alternate allocation

Notes Single centre

Item Authors judgement Description

Allocation concealment? Unclear D - Not used

Methods Open parallel-group controlled trial with alternate allocation

Notes Single centre

Item Authors judgement Description

Allocation concealment? Unclear D - Not used

Corticosteroids for Guillain-Barr syndrome (Review) 13

Methods Double-blind parallel-group randomised controlled trial.

Interventions Intravenous methylprednisolone 500 mg daily for 5 days or placebo infusions

Notes International multicentre

Item Authors judgement Description

Allocation concealment? Yes A - Adequate

Methods Observer blind parallel-group randomised controlled trial.

Notes International multicentre.

Corticosteroids for Guillain-Barr syndrome (Review) 14

Item Authors judgement Description

Allocation concealment? Yes A - Adequate

Methods Double-blind randomised parallel-group controlled trial.

Participants 16 patients with GBS fulfilling diagnostic criteria of (Asbury 1990)

Notes Single centre.

Item Authors judgement Description

Allocation concealment? Yes A - Adequate

Notes Single centre.

Item Authors judgement Description

Corticosteroids for Guillain-Barr syndrome (Review) 15

Allocation concealment? No C - Inadequate

Methods Double-blind parallel-group randomised controlled trial.

Notes Single centre.

Item Authors judgement Description

Allocation concealment? Yes A - Adequate

van Koningsveld 2004

Methods Double-blind parallel-group randomised controlled trial.

Notes Multicentre centre study in the Netherlands, Belgium and Germany

Item Authors judgement Description

Allocation concealment? Yes A - Adequate

Corticosteroids for Guillain-Barr syndrome (Review) 16

Study Reason for exclusion

Haass 1988 Non-randomised open study.

Mendell 1985 Compared corticosteroids and plasma exchange against no treatment

Naylor 1986 Not a RCT.

Zagar 1995 Review, not a RCT.

Corticosteroids for Guillain-Barr syndrome (Review) 17