Prognosis in CIDP

Abstract & Commentary

By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.

Synopsis: Mode of onset, distribution of symptoms, and electrophysiological characteristics may be prognostic factors for predicting a favourable outcome.

Source: Kuwabara S, et al. Long Term Prognosis of Chronic Inflammatory Demyelinating Polyneuropathy: A Five Year Follow Up of 38 Cases. J Neurol Neurosurg Psychiatry. 2006:77;66-70.

To determine the long term outcome and prognosis of chronic inflammatory demyelinating polyneuropathy (CIDP), 38 patients with CIDP were followed for 5 years with bimonthly clinical examinations and annual electrodiagnostic studies. Patients were excluded if they demonstrated the presence of monoclonal gammopathy, anti-myelin-associated glycoprotein (anti-MAG) antibody, or multifocal motor neuropathy with conduction block. Clinical assessments encompassed Hughes functional grade (0 = normal, 1 = minimal symptoms, 2 = walks 5 meters independently, 3 = walks 5 meters with assistance, 4 = chair/bed bound, 5 = requires assisted ventilation, 6 = dead), grip strength, deltoid/wrist flexor/iliopsoas/tibialis anterior muscle strength, deep tendon reflexes, and sensory (pinprick, touch, and vibratory) examination.

Electrodiagnostic studies included median, ulnar, tibial, and peroneal motor, and antidromic median and sural sensory nerve conduction studies. All patients received immunomodulatory therapy including high-dose corticosteroids (89%, n = 34), intravenous immunoglobulin (45%, n = 17), or plasma exchange (34%, n = 13). Combined therapy was given in 58% (n = 22), and azathioprine or cyclophosphamide in 2 patients each. Treatment was considered efficacious if Hughes grade improved by one or more. Statistical analysis was provided by chi-square or Fisher's exact test and Mann-Whitney U test, with logistic regression used to analyze categorized outcome variables.

By study end (5 years), 26% of patients (n = 10) were in complete remission for at least 2 years, with normal nerve conduction studies and a Hughes functional grade of 0. Nine of these had received steroid therapy, and one patient intravenous immunoglobulin infusion. Relapse on steroid taper in 2 patients mandated plasma exchange and increased steroid dosage, with resultant complete remission. Minimal symptoms or independent ambulation was achieved in an additional 61% (n = 23), with 10 (26%) requiring ongoing immunomodulatory treatment and 13 (34%) free of medication. Two patients each (10%) were able to walk with assistance or were chair/bed bound, and one tetraplegic patient (3%) died of pneumonia. None were ventilator dependent. Continued post-study follow-up for up to 15 years (mean, 10.5 years) continued to show similar results.

Subacute onset, symmetrical symptoms, lack of muscle atrophy, good response to initial steroid therapy, and predominantly distal motor nerve conduction abnormalities were all significantly associated with complete remission at 5 years, whereas, insidious onset, asymmetrical symptoms, presence of muscle atrophy, lack of response to initial steroid therapy, and diffuse motor nerve conduction abnormalities were associated with treatment failure or relapse. Prognosis in CIDP is favorable, but a significant proportion (39%) requires continued medical treatment, and 13% remain severely disabled.

Commentary

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a form of chronic immune-mediated demyelinating neuropathy (CI-MDP), of which several variants exist (Lewis RA. Sem Neurol. 2005;25;217-228). Usually, motor symptoms dominate in CIDP. Sensory symptoms are preponderate in 10-15%, but nerve conduction studies will reveal demyelinating motor abnormalities even in these. IgM paraproteinemia, less so IgG or IgA, is associated with demyelinating polyneuropathy, of which 33%, if followed for 20 years, will develop myeloma, amyloidosis, or other hematologic malignancy. Distal, slowly progressive, painless sensorimotor demyelinating polyneuropathy, with or without anti-myelin-associated glycoprotein (anti-MAG) antibodies and with or without IgM antibodies, may all be a single entity (Katz JS et al. Neurology. 2000;54;615-620). IgM neuropathy is poorly responsive to immunosuppression in most, but monoclonal antibody therapy (Rituxan) may hold promise. Sensory ataxic demyelinating neuropathy with IgM antibodies to GM2, GalNAc-GD1A, and CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraproteinemia, cold agglutinins, and disialosyl antibodies) are rare syndromes of demyelinating neuropathy that may respond to intravenous immunoglobulin.