The use of immunoglobulins in the treatment of human epilepsy

The use of immunoglobulin (IVIg) in intractable epilepsy is one of its oldest applications in medicine, starting from the empirical observation of its beneficial effect on seizures. Immune system dysfunction may play a role in epilepsy by triggering, maintaining or, unexpectedly, improving intractable seizures. Several laboratory and clinical investigations are in favor of an immunological basis for different forms of experimental and human epilepsies. A wide range of immune abnormalities have been reported, suggesting the existence of different subtypes of epileptic syndromes with different abnormalities of the immune system. In this view, IVIg with its broad immunomodulatory mechanism of action could be effective in different forms of immune-dysregulated intractable epilepsies. Non-immunological mechanisms of action have been also suggested, based either on human epilepsy data or on animal experimental data. The possible anticonvulsant properties and the ability of IVIg to interfere with the final common pathway of seizures at a cellular level, with a significant increase in seizure threshold, have been demonstrated in different experimental epilepsy model. Although IVIg may represent a valuable resource in some drug-refractory epilepsies and its effectiveness has important pathogenetic implications, controlled studies with the systematic monitoring of immunological markers are needed to define more precise indications and to optimize the administration protocols.