We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite Relapsing/Remitting (RR) MS and Brain MRI confirmed.

Patients were randomly assigned to receive a loading dose of ImmunoGlobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years.

The primary outcome measures were change in the Yearly Exacerbation Rate (YER), proportion of exacerbation-free patients, and time until first exacerbation.

Neurologic disability, exacerbation severity, and changes in Brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion.

Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate.

Six patients in the IVIG group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group.

The median time to first exacerbation was 233 days in the IVIG group versus 82 days in the placebo group (p = 0.003).

Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIG group and increased by 0.15 in the placebo group.

Total lesion score evaluated by Brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups.

Our results suggest that IVIG may be safe and effective in reducing the frequency of exacerbations in RR/MS.

High-dose IntraVenous ImmunoGlobulin (IVIG) has emerged as an important therapy for various Neurologic Diseases.

Different interpretations of clinical trial results; the expected benefit of IVIG compared with that of alternate therapies; and issues about IVIG's safety, cost, and mechanisms of action have raised concern and uncertainty among practitioners.

To clarify these areas, this paper examines the clinical, serologic, and Immunologic data on more than 110 patients with various AutoImmune Neurologic Diseases.

Who received IVIG during the past 6 years at the National Institute of Neurological Disorders and Stroke.

It also reviews work by other investigators on the efficacy, risks, benefits, and mechanisms of the action of IVIG in these diseases.

In controlled clinical trials, IVIG has been effective in treating the Guillain-Barre Syndrome, Multifocal Motor Neuropathy, Chronic Inflammatory DeMyelinating Polyneuropathy, and Dermatomyositis.

In other controlled or open-label trials and case reports, IVIG produced improvement in several patients with the Lambert-Eaton Myasthenic Syndrome and Myasthenia Gravis.

But, had a variable, mild, or unsubstantiated benefit in some patients with Inclusion-Body Myositis, Paraproteinemic IgM DeMyelinating Polyneuropathy, certain intractable childhood Epilepsies, Polymyositis, Multiple Sclerosis, Optic Neuritis, and the Stiff-Man Syndrome.

The primary adverse reactions were: Headache; Aseptic Meningitis, Skin Reactions, Thromboembolic Events, and Renal Tubular Necrosis occurred rarely.

The most relevant ImmunoModulatory actions of IVIG, operating alone or in combination, are inhibition of Complement deposition, neutralization of Cytokines, modulation of Fc-receptor-mediated Phagocytosis, and down-regulation of AutoAntibody production.

Therapy with IVIG is effective for certain AutoImmune Neurologic Diseases, but its spectrum of efficacy has not been fully established. Additional controlled clinical trials are needed.

Intravenous ImmunoGlobulin (IVIG) is advocated as a safe treatment for Immune-mediated Neurologic Disease. We reviewed the medical records of 88 patients who were given IVIG for a Neurologic illness.

Major complications in four patients (4.5%) included Congestive Heart failure in a patient with Polymyositis, Hypotension after a recent Myocardial Infarction, deep venous thrombosis in a bed-bound patient, and acute renal failure with Diabetic Nephropathy.

Other adverse effects included Vasomotor Symptoms 26, Headache 23, Rash 5, Leukopenia 4, Fever 3, Neutropenia 1, Proteinuria (1.9 g/day) 1, Viral Syndrome 1, Dyspnea 1, and Pruritis 1.

Fifty-two patients (59%) had some adverse effect of IVIg infusion, most commonly Vasomotor Symptoms, Headaches, Fever, or Shortness Of Breath in 40 (45%), which improved with reduced infusion rate or symptomatic medications.

Five (6%) had asymptomatic laboratory abnormalities and seven (8%) had other minor adverse effects.

Adverse effects led to discontinuation of therapy in 16% and permanent termination of therapy in 10% of patients. There was no mortality or long-term morbidity.