CIDP in Childhood — A Clinical Review
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical Center. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Childhood chronic inflammatory demyelinating polyradiuculoneuropathy follows a similar course as the adult counterpart and responds well to treatment with intravenous immunoglobulin.
Source: McMillan HJ, et al. Childhood chronic inflammatory demyelinating polyradiculoneuropathy: Combined analysis of a large cohort and eleven published series. Neuromuscul Disord 2013;23:103-111.
How does childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) compare to the adult form with respect to disease onset, clinical features, long-term outcome, and response to treatment? To address this question, records of all CIDP patients seen at Boston Children’s Hospital from 1989-2009 were reviewed and pooled with data from 11 previous case series spanning 1980-2009 to provide a complete review of childhood CIDP.
Inclusion criteria required a history of progressive or relapsing sensorimotor polyneuropathy in patients ≤ 19 years of age, with areflexia or hyporeflexia, fewer than 10 white cells/mm3 in cerebrospinal fluid (CSF), and a pattern consistent with acquired demyelination in at least two nerves on nerve conduction studies (NCS), comprising slowed nerve conduction velocities, abnormal temporal dispersion or conduction block, prolonged distal latencies, and prolonged or absent F-waves. Patients were excluded if they had a family history of hereditary neuropathy, had exposure to drugs or toxins, were suspected of having a metabolic disorder, or demonstrated a sensory level or sphincteric abnormality. Clinical deficits were quantified using the modified Rankin scale, graded 0 (asymptomatic) to 6 (death). Response to treatment was defined as “good” when minimal-to-no functional impairment was reported by the treating physician, “partial” where some degree of clinical improvement was reported, and “no response” where either no clinical improvement was seen or the patient deteriorated.
At Boston Children’s Hospital, 30/32 CIDP patients met all entry criteria, with two excluded due to either elevated CSF white count (13 white cells/mm3) or equivocal NCS. Males and females were equally affected, with 60% of children demonstrating disease progression spanning more than 8 weeks, and 20% each presenting over 4-8 weeks, or < 4 weeks, mimicking Guillain-Barré syndrome. Only 30% demonstrated a monophasic course, with 70% having relapsing CIDP. Intravenous immunoglobulin (IVIG) was initially given to most, with 80% showing a good response, and long-term follow-up (mean 3.8 years) revealed that 45% were off all immunosuppressive agents with no (55%) or minimal (43%) clinical deficits. Among 143 previously published CIDP patients, the combined initial response rate for IVIG or prednisone was 79% and 84%, respectively, with only 14% responding to plasma exchange as a first-line therapy. Rankin scale improved from 3.7 to 0.7 overall. As in adults, IVIG is the treatment of choice for childhood CIDP.
For most patients with CIDP, maintenance therapy will be required. Cochrane Database System Reviews indicate that only class IV (insufficient) evidence supports the use of conventional immunosuppressive agents for those failing IVIG, prednisone, or plasma exchange. Neither azathioprine, cyclosporine, methotrexate, cyclophosphamide, nor mycophenolate mofetil are of proven efficacy in such patients. Various biologic agents may be useful, but hard data are not yet available.
Natalizumab, a monoclonal antibody directed against integrin subunits on the surface of activated T cells, is under consideration for therapeutic trial in CIDP. In a single case report, it proved ineffective. Rituximab, a monoclonal antibody directed against the B-cell surface antigen CD20, has had conflicting results but may be an option in otherwise refractory CIDP. Alemtuzumab, a recombinant DNA-derived humanized monoclonal antibody directed against the cell surface glycoprotein CD52 on the surface of most B and T lymphocytes, has had variable success, but secondary autoimmunity developed in several patients. Eculizumab, a monoclonal antibody that inhibits the production of terminal complement component C5a and membrane attack complex C5b-9 by binding to complement protein C5, has not yet been offered in CIDP but was deemed safe in 13 patients with multifocal motor neuropathy.1
1. Stubgen J-P. A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci 2013;326:1-9.