What initiates epilepsy? Viral or bacterial infections of RE patients before the presence of symptoms may contribute to the disease. A direct causal link between viral infection and the production of excitotoxic antibodies to GluR3 was demonstrated by the immunization of mice with LP-BM5 murine leukemia virus, which evoked (by partial molecular mimicry) antibodies to GluR3 that were able to activate and kill neurons via excitotoxicity (A. Basile). Immunogenetic factors may contribute to susceptibility. Preliminary evidence was presented concerning a group of eight adult RE patients that showed a significantly increased frequency of HLA-A2 (100% of patients; 24% of controls), HLA-B44 (67% of patients; 5% of controls) and HLA-DR4 (83% of patients; 36% of controls) (I. Hart, UK) and from some pediatric RE patients with either HLA-A2 or HLA-B44 (Y. Ganor & M. Levite). In mice, the amount of antibodies to GluR3B also depends on their major histocompatibility background (M. Levite).
surgical intervention that disconnects
the epileptic areas by removing certain
cortical structures—is so far the only
recommended therapy for RE patients that
are unresponsive to anticonvulsants.
Novel and striking support for
beneficial immunotherapy of RE was
presented such as IVIg , steroids and
After long-term treatments with monthly hIVIg (intravenous human immunoglobulin, 2 g/kg) and an H2 antagonist (histamine receptor 2 antagonist), all eight treated adult RE patients showed significant improvements in function, decreased seizures, SPECT (single photon emission computed tomography), MRI (magnetic resonance imaging) and less inflammation in the CSF. These improvements were maintained for up to 5 years (I. Hart). In addition, selective removal of IgG by protein A immunoadsorption was effective in one RE patient who had detectable antibodies to GluR3; removal caused interruption of status epilepticus on different occasions, reduced seizure frequency and improvement of cognitive functions (C. Antozzi). Finally, plasma exchange or IVIg evoked good responses of patients with epilepsy-associated Hashimoto's or viral encephalitis (B. Lang), in which antibodies to voltage-gated potassium channels were found.
Together, the above findings suggest that epileptic patients should be tested for antibodies, primarily to GluR3. If positive, long-term immunotherapy should be considered before severe brain surgery. Although neurologists may now be required to accept the tantalizing concept that some human epilepsies have an autoimmune basis and treat their patients accordingly, immunologists and neurobiologists will have to continue to expand their studies of autoimmune epilepsy, as probably only the tip of the iceberg has been discovered so far.