By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
In a retrospective chart review of 281 treatment-naïve patients with chronic inflammatory demyelinating polyradiculoneuropathy, lack of response to intravenous immunoglobulin was predicted by 1) presence of painful neuropathy and
2) strength differences between arm and leg muscles.
Kuitwaard K, et al. Intravenous immunoglobulin response in treatment-naive chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 2014;0:1-6. doi:10.1136/jnnp-2014-309042
Glucocorticoids, intravenous immune globulin (IVIG), and plasma exchange are equally efficacious for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), each having its own advantages and disadvantages. Although expensive and sometimes limited in availability, depending on manufacturer supply and accessibility to specialized centers, IVIG and plasma exchange offer more rapid improvement for CIDP than do steroids, but are less likely to induce remission. As an alternative, steroids are inexpensive, yet associated with multiple clinically significant side effects. Can neurologists predict which CIDP patient is less likely to respond to IVIG, thereby avoiding its cost and inconvenience?
Medical records of treatment-naive CIDP patients seen between 1980 and 2011 at Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and London Health Sciences Center, London, Ontario, Canada, were retrospectively reviewed. Clinical diagnostic criteria for typical or atypical CIDP, as determined by the European Federation of Neurological Societies/Peripheral Nerve Society, were fulfilled in all. Exclusionary criteria included patients with chronic acquired or hereditary neuropathy, multifocal motor neuropathy, recurrent Guillain-Barré syndrome, and those with an IgM monoclonal gammopathy of undetermined significance (MGUS) if they also demonstrated antibodies against myelin-associated glycoprotein. IVIG 2 g/kg was the initial therapy in all patients, with fresh frozen plasma used prior to IVIG availability. Improvement of at least 1 grade on the modified Rankin scale was considered clinically significant. Statistical analysis comprised the ?2 test, Fisher’s exact test, and the Mann-Whitney U test, with a two-sided P value < 0.05 considered significant.
Among 281 treatment-naive CIDP patients given one course of IVIG, encompassing 179 males and 102 females, with 13 patients under age 18 years, 76% (n = 214) improved, with no significant difference appreciated between adults and children and no correlation between response and patient age. Among IVIG non-responders, plasma exchange and steroids resulted in subsequent improvement in 66% and 58%, respectively, with a total of 79% improving after either or both. Remission was achieved after a single IVIG course in 16% (n = 14). Response to IVIG was positively associated with the absence of pain, equivalent arm and leg weakness, absence of MGUS, and absence of other autoimmune disease in univariate analysis, and positively associated with the absence of pain and the presence of equivalent arm and leg weakness in multivariate analysis. Pain or a difference in weakness between arms and legs were not associated with response to steroids. Pain or a difference in weakness in arms and legs may be signs of an IVIG non-responder.
Commentary
What is/are the antibody target(s) in CIDP? Contactin-2, a neuronal membrane protein that functions as a cell adhesion molecule, and connexin 32, one of a family of transmembrane proteins that forms paranodal gap junctions and mutation of which results in X-linked Charcot-Marie-Tooth disease, have been suggested as potential target antigens in peripheral nervous system demyelination. Antibodies to contactin-2 have been reported in patients with multiple sclerosis. Nevertheless, sera from 45 CIDP patients, five multifocal motor neuropathy patients and four with combined central demyelination and CIDP failed to show binding for
either antigen using an anti-human fluorescent antibody.1 But the search for the immune target in CIDP will continue.
Reference
- Stathopoulos P, et al. Search for autoantibodies targeting the nodes of Ranvier in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Neurology 2014;82(Suppl)P1.028.
