By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
In this controversial report comparing patients with Guillain-Barré syndrome treated with intravenous immunoglobulin vs. no treatment the group that appears to have fared the best were patients who had an acute demyelinating syndrome, and not an axonal variant. This was an observational study and not a randomized treatment trial.
Kalita J, Misra UK, Chaudhary SK, et al. Outcome of Guillain-Barré syndrome following intravenous immunoglobulin compared to natural course. Eur J Neurol 2022;29:3071-3080.
Efficacy of intravenous immunoglobulin (IVIG) in Guillain-Barré syndrome (GBS) is comparable to plasma exchange (PLEX), with IVIG preferred because of its rapid implementation, ease of administration, and safety. Yet, in a recent international observational study, one course of IVIG did not improve the overall disease course in patients with mild GBS, nor do IVIG-treated children fare better at six months compared to the natural course.1
Furthermore, given the inability to pass scrutiny of a medical ethics review board, trials comparing IVIG with placebo for the treatment of GBS are unlikely to be forthcoming. Will we ever know the outcomes of patients with various forms of GBS following IVIG treatment compared to the natural course of untreated disease? Given that antiganglioside antibodies differ in different neurophysiological subtypes of GBS, and that IVIG or PLEX may not be equally effective in all subtypes, can we learn which subtype of GBS is more likely to respond to IVIG?
A retrospective review of 528 registry-based GBS patients seen at Sanjay Gandhi Post Graduate Institute of Medical Sciences in Lucknow, India, disclosed 189 IVIG-treated patients who were compared to 199 age-matched and peak disability-matched GBS controls untreated because of the inability to afford treatment. Laboratory investigations included routine blood work, human immunodeficiency virus (HIV) serology, chest radiograph, electrocardiogram, and cerebrospinal fluid analysis. All patients underwent nerve conduction studies (NCS) on admission, which, if normal or equivocal, were repeated after three to four weeks.
GBS clinical subtypes were classified as motor-sensory, pure motor, or Miller-Fisher syndrome (MFS), and electrophysiological subtypes were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy, or equivocal, if NCS did not fall into any of the previous categories. Disability was graded using the 0-6 Guillain-Barré Syndrome Disability Score, with the primary outcome measure being functional disability at six months and secondary outcomes encompassing duration of hospitalization, mechanical ventilation, and in-hospital death. Statistical analysis included the Wilk-Shapiro test, the independent t-test or Mann-Whitney U test, and the chi-squared test, with P-value < 0.05 considered significant.
In-hospital deaths were comparable in treated and untreated patients, with five and four deaths, respectively, as were three-month recovery rates, whereas at six months, significantly fewer IVIG-treated patients had poor recovery. Benefit, however, was appreciated only in the AIDP group, but not for those with AMAN. Deaths were higher in the MFS subtype compared to the pure motor or motor-sensory subtypes, with significantly more patients in the IVIG group requiring mechanical ventilation and having a significantly longer hospital stay (20 days vs. 15 days).
Predictors of six-month outcome were early admission, peak disability, electrophysiologic subtype, and duration of hospital stay, with age, gender, clinical subtype, bulbar palsy, facial weakness, and autonomic dysfunction playing no role. IVIG benefits AIDP variants of GBS, but not AMAN, where further controlled trials will be needed to determine its best therapy.
COMMENTARY
Which clinical factors that can be evaluated in an emergency department (ED) predict outcome in GBS? A retrospective review of ED records, dating from Jan. 1, 2014, to Dec. 31, 2018, from the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, which evaluates about 75,000 patients annually, disclosed 69 patients with GBS and nine with MFS.2 Early need for mechanical ventilation significantly correlated with the modified Erasmus GBS outcome score (mEGOS), which is calculated based on age, diarrhea before symptom onset, and severity of muscle weakness, as measured by the Medical Research Council sum score, suggesting that mEGOS may be an early and useful tool to predict GBS outcome.
REFERENCES
- Verboon C, Harbo T, Cornblath DR, et al. Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: An international observational study.
J Neurol Neurosurg Psychiatry 2021;92:1080-1088.
- Covino M, Romozzi M, Simeoni B, et al. Guillain-Barré syndrome from an emergency department view: How to better predict the outcome? Neurol Res 2022; May 17:1-5. doi: 10.1080/01616412.2022.2075661. [Online ahead of print].
