No treatment has been found which predictably prevents further attacks and progression of disease activity in multiple sclerosis (MS). Similarly, no treatment will reverse long standing neurological dysfunction in this disease. Observations in the experimental allergic encephalomyelitis animal model of MS and in the Theiler's model of demyelination suggests that immunoglobulins directed against CNS components promote oligodendroglial proliferation and new myelin synthesis. Preliminary studies in inflammatory-demyelinating diseases of the human peripheral and central nervous system suggest that the repeated intravenous administration of purified human immunoglobulin (IVIG) is followed by clinical improvement. The objective of this proposed study is to determine if high dose IVIG is more effective than placebo in promoting clinical recovery in multiple sclerosis patients. In this randomized, placebo-controlled, double-blinded clinical trial, we test the hypothesis that the repeated administration of IVIG will result in a meaningful degree of recovery of apparently irreversibly lost neurological function (weakness) in MS. Seventy-six MS patients who have developed a fixed, apparently permanent weakness (upper or lower limbs; """"""""targeted neurological deficit"""""""") which has not improved within the preceding 4-30 months will be randomized to receive either IVIG or placebo (O.1% human serum albumin in 10$ maltose) daily for five days and then every two weeks for three months (total 11 fusions). The primary outcome will be an assessment of whether there has been an improvement in muscle strength (targeted neurological deficit) at six months as measured by isometric muscle strength measurements in the Biomechanics Laboratory. Secondary analyses will include whether treatment (placebo) has improved dexterity in the limb(s) with the targeted neurological deficit (also, gait if relevant) as judged by two blinded, nontreating neurologists reviewing serial videotaped neurological examinations. Other secondary analyses will include the degree of improvement and the reduction of impairment as judged by the blinded, treating neurologist based on the patient's disability rating scales in MS and performance on functional tests. If shown to be effective, IVIG administration could possibly benefit the large proportion of MS patients who have active disease by presumably enhancing the potential for myelin repair in the evolution of the inflammatory-demyelinating lesion.
