High-dose
intravenous immune globulin (
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-Barré 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 reaction was
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.