Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

A short course of high-dose intravenous methylprednisolone did not reduce disability or enhance recovery in patients with the Guillain-Barré syndrome

ACP J Club. 1993 Sept-Oct;119:35. doi:10.7326/ACPJC-1993-119-2-035


Source Citation

Guillain-Barré Syndrome Steroid Trial Group. Double-blind trial of intravenous methylprednisolone in Guillain-Barré syndrome. Lancet. 1993 Mar 6;341:586-90.


Abstract

Objective

To evaluate the effectiveness of high-dose intravenous methylprednisolone (IVMP) in reducing disability in patients with the Guillain-Barré syndrome.

Design

Randomized, double-blind, placebo-controlled trial with 48-week follow-up.

Setting

International multicenter trial.

Patients

242 patients (mean age 50 y, 57% men) hospitalized for the Guillain-Barré syndrome who were randomized within 15 days of the onset of neurologic symptoms and who were too weak to run. Exclusion criteria were atypical Guillain-Barré syndrome, central nervous system involvement, previous episodes of the Guillain-Barré syndrome, contraindication to steroids, preexisting disease that prevented assessment of disability, age < 16 years, or circumstances likely to prevent follow-up for 1 year. 2 patients withdrew from the study.

Intervention

124 patients were allocated to IVMP, 500 mg daily for 5 days, and 118 were assigned to placebo (normal saline). Patients received plasma exchange (plasmapheresis) according to the practice of the institution; 66 patients received plasma exchange in the IVMP group compared with 77 in the placebo group.

Main outcome measures

Change in disability graded on a mobility and ventilation requirement scale from 0 (healthy) to 6 (dead) and an upper-limb impairment scale from 0 (normal) to 4 (no movement), after 4 weeks and further intervals up to 48 weeks; median time to discontinuation of ventilation and median time to unaided walking.

Main results

Intention-to-treat analysis was used. 1 patient in each group did not receive any trial infusions. The recovery rate for the groups was similar with respect to disability and arm impairment. After 4 weeks, the IVMP group had a mean disability grade improvement of 0.80 compared with 0.73 in the placebo group {mean difference 0.07, 95% CI -0.23 to 0.37}*. This result did not change after adjusting for the effects of initial disability grade, age, gender, or plasma exchange. Median time to discontinuation of ventilation was 18 days in the IVMP group compared with 27 days in the placebo group (median difference 9 d, CI -9.6 to 27.6 d). The median time to unaided walking was 38 days in the IVMP group compared with 50 days in the placebo group (median difference 12 d, CI -21.3 to 45.3 d).

Conclusion

A short 5-day course of high-dose (500 mg) intravenous methylprednisolone did not reduce disability or enhance recovery in patients with the Guillain-Barré syndrome.

Source of funding: Medical Research Council.

For article reprint: Professor RAC Hughes, Professor of Neurology, GUY's and St. Thomas's Medical and Dental School, Medical School Building, Guy's Hospital, London Bridge, London SE1 9RT. FAX 44-171-955-4864.

*Mean difference and 95% CI calculated from data in article.


Commentary

With supportive intensive care, mortality in the Guillain-Barré syndrome is less than 10%, and good recovery occurs in about 75% of patients. Morbidity, however, is high because many patients require several weeks of assisted ventilation and most have 6 to 12 months of generalized weakness. Although plasmapheresis is a safe and specific treatment that accelerates recovery, about 30% of patients do not respond. Even among the responders, recovery may take several weeks, and rarely, autonomic instability precludes plasmapheresis altogether. Thus, we need cheaper, more effective, and easier-to-administer treatments. An open, controlled trial (1) found no benefit in 21 patients treated with oral prednisolone; in a later study (2), prednisone combined with plasmapheresis did not improve the outcome in 12 patients compared with controls receiving plasmapheresis alone. On the other hand, a small uncontrolled study of 11 patients given high doses of IVMP reported marked improvement (3).

The current trial of high doses of IVMP is large and well designed, and the assessment of disability outcomes was blinded. Thus, this study is comparable to the landmark plasmapheresis studies. In the current trial, the patients who also received plasmapheresis provided an opportunity to study the synergism between steroids and plasmapheresis. The present investigation definitively shows the lack of substantial benefit from steroid treatment, regardless of plasmapheresis.

Thus, high-dose IVMP is not recommended as an adjunct or substitute for plasmapheresis in patients with the Guillain-Barré syndrome. This role is now achieved by intravenous immunoglobulin. In a multicenter randomized trial involving 379 adults with severe Guillain-Barré syndrome, intravenous immunoglobulin was as effective as plasmapheresis (4). Considering the ease of administration and few adverse effects, intravenous immunoglobulin is currently the treatment of first choice.

Nagagopal Venna, MD
Boston City HospitalBoston, Massachusetts, USA


References

1. Hughes RA, Newsom-Davis JM, Perkins GD, Peirce JM. Controlled trial prednisolone in acute polyneuropathy. Lancet. 1978;2:750-3.

2. Mendell JR, Kissell JT, Kennedy MS, et al. Plasma exchange and prednisone in Guillain-Barré syndrome: a controlled randomized trial. Neurology. 1985;35:1551-5.

3. Hass A, Trabert W, Grebrich N, Schimrigk K. High-dose steroid therapy in Gulillain-Barré syndrome. J Neuroimmunol. 1988;20:305-8.

4. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of plasma exhange, intravenous immunoglobulin, and combined treatment in Guillain-Barré syndrome. Lancet. 1997;349:225-30.