Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects.
BACKGROUND
Although IVIg is highly effective in several autoimmune neuromuscular disorders (neuropathies, myopathies and neuromuscular junction disorders), its effectiveness in autoimmune or neuroinflammatory CNS diseases, with the exception of multiple sclerosis, has not been explored. Emerging data suggest that IVIg may have a role not only in certain antibody-mediated CNS diseases but also in some neurodegenerative disorders associated with "neuroinflammation" mediated by proinflammatory cytokines.


METHODS
Data from a previously reported controlled study conducted in patients with stiff person syndrome (SPS) are presented as a paradigm of a CNS disorder associated with specific autoantibodies responding to IVIg. Emerging data using IVIg in various neuroinflammatory and neurodegenerative conditions such as Alzheimers disease, postpolio syndrome (PPS), fibrotic disorders, chronic painful conditions and narcoplepsy are summarized.


RESULTS
On the basis of a double-blind placebo-controlled trial conducted in SPS patients with high anti-GAD antibodies, IVIg was shown to be effective resulting in improvement of stiffness and heightened sensitivity scores and increasing the patients' ability to carry out daily activities. In SPS, IVIg also suppressed the anti-GAD antibodies titers probably via an anti-idiotypic effect. A controlled study in patients with PPS, showed reduction in cytokines in serum and CSF with concomitant improvement in the patients' strength and ability to carry out their daily activities. The effect of IVIg in a small number of patients with Alzheimer's disease was promising by reducing the ADAS-cog scores, suggesting a reversal of disease progression. IVIg has been shown to have an effect on tissue fibrosis and in certain subacute painful conditions by suppressing cytokines that mediate fibrosis or pain. In another uncontrolled study, IVIg reduced the number of cataplectic attacks in narcolepsy patients.


CONCLUSIONS
IVIg is effective in anti-GAD-positive patients with SPS. Whether it is also effective in other GAD-positive CNS disorders such as epilepsies, cerebellar degenerations or Batten's disease need to be studied in control trials. Emerging data suggest that IVIg, by suppressing proinflammatory cytokines, may exert a beneficial effect in patients with Alzheimer's disease, postpolio syndrome, chronic pain syndromes, fibrotic disorders and narcolepsy. Controlled studies are being planned or conducted to substantiate the benefit of IVIg in neurodegenerative disorders.
Dalakas
Marinos C
MC
Neuromuscular Diseases Section, NINDS, National Institutes of Health, Building 10, Room 4N248, 10 Center Drive MSC, Bethesda, MD 20892-1382, USA. dalakasm@ninds.nih.gov
D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy*; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007249:Inflammation; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D016756:Immunoglobulins, Intravenous