Epilepsy: an autoimmune disease?

Association of severe myoclonic epilepsy of infancy (SMEI) with probable autoimmune lymphoproliferative syndrome-variant

“…29,42,47 The genetically induced FAS pathway deficiency may have predisposed our DALD patient to the development of organ-specific autoimmune autoantibody production and thyroideal disease with possible involvement of cytotoxic mechanisms mediated by FAS-FASL pathway. The presence of antimicrosomal antibodies, associated with hypothyroidism, slowing of EEG background activity, diffuse mild brain atrophy, neuropsychological sign, 48 improved epileptic activity after cortisone, could suggest a direct effect of IgG-mediated antimicrosomal antibodies, possibly due to a common brain-thyroid antigen 49,50 involving neurons and glia (Hashimoto encephalopathy). 32 However, the low titre of anti-microsomal antibodies may also demonstrate a unique predisposition to develop multiple antibodies.…”

“…In normal conditions, the neurons in CNS are protected from brain-reactive antibodies by the blood-brain barrier, but possible breaches in the barrier may permit antibody activity. 51 It was observed that patients producing one autoantibody have a predisposition to form also other autoantibodies 50 and that undiscovered antibodies in epilepsy may coexist with not yet identified or irrelevant antibodies. 48,50 Therefore, some Authors advise to investigate the same target protein for genetic and autoimmune diseases, because similar symptoms may be due to mutation and to autoantibodies targeting the same protein.…”

“…51 It was observed that patients producing one autoantibody have a predisposition to form also other autoantibodies 50 and that undiscovered antibodies in epilepsy may coexist with not yet identified or irrelevant antibodies. 48,50 Therefore, some Authors advise to investigate the same target protein for genetic and autoimmune diseases, because similar symptoms may be due to mutation and to autoantibodies targeting the same protein. 50 In our case, the association of epilepsy with non-organ specific ANA and antimicrosomal organspecific autoantibodies, dysphagia, abnormalities of peripheral sensory-motor nerve conduction, bilateral leg pain and hyperreflexia, atonia, and EMG abnormalities suggest a role of autoantibodies against the Na + ion channels 50,52,53 acting on the surface of neurons, with consequent slow inactivation 15,54 which results in epileptiform activity in mammalian brain 52,53 and conduction block in peripheral nerve.…”

“…48,50 Therefore, some Authors advise to investigate the same target protein for genetic and autoimmune diseases, because similar symptoms may be due to mutation and to autoantibodies targeting the same protein. 50 In our case, the association of epilepsy with non-organ specific ANA and antimicrosomal organspecific autoantibodies, dysphagia, abnormalities of peripheral sensory-motor nerve conduction, bilateral leg pain and hyperreflexia, atonia, and EMG abnormalities suggest a role of autoantibodies against the Na + ion channels 50,52,53 acting on the surface of neurons, with consequent slow inactivation 15,54 which results in epileptiform activity in mammalian brain 52,53 and conduction block in peripheral nerve. 56 The identification of SCN1A mutation involving Na + channels in SMEI and GEFS + suggests that an autoimmune attack to the mutated Na + channels, recognized as non-self by the organism, may be present in some cases of SMEI, as reported in other epilepsies.…”

“…56 The identification of SCN1A mutation involving Na + channels in SMEI and GEFS + suggests that an autoimmune attack to the mutated Na + channels, recognized as non-self by the organism, may be present in some cases of SMEI, as reported in other epilepsies. 50 In this context, CNS should be the target of an immune block of Na + channels 53 or of an immuno-inflammatory reaction involving the neuronal Na + channels (with cytokine, mainly 1L-1β, production) which started in the peripheral lymphoid system. This condition could also be present in prolonged seizures associated with fever, in status epilepticus 16 or after systemic infections.…”