ASSOCIATION BETWEEN AUTOIMMUNE ENCEPHALITIS AND EPILEPTIC CRISIS FROM THE PERSPECTIVE OF ANTIBODY HEADED TO SURFACE NEUROMEMBRANE
hippocampus, amygdala, frontobasal and insular regions of the brain parenchyma1. It is a rare condition
with an etiology first associated with paraneoplastic phenomena but recently associated with antibodies
that act on the neuromembrane-surface. Clinical manifestations can precede in 6 years the neoplastic
diagnosis allowing faster diagnosis, better prognosis and treatment1. The LE could be classified in two
categories2: a) paraneoplastic LE: related to antibodies directed against intracellular antigens (GAD65,
ANNA-1), associated with cytotoxic T Cell; b) non-paraneoplastic LE (NPLE): related to antibodies directed
to cell membrane antigens (VGKC, NMDAR, GABA, AMPA), with better clinical and neuroimaging response
to immunotherapy than patients with paraneoplastic LE, except when the antibodies are directed against
intra neuronal antigens, as is the anti-GAD antibodies. Initial manifestations are depression or anxiety
symptoms, characterized for apathy followed by subacute involvement of the short term memory,
psychotic symptoms, psychomotor agitation and epileptic crisis. There was an increase of studies relating
neuroantigens found in autoimmune encephalitis to epileptic episodes. Objective: Investigate the
association between epilepsy nonrespondent to conventional treatment and autoimmune encephalitis,
discussing the particularities of different antibodies directed to the neuromembrane and their clinical
implications. Material and Methods: Review study using articles classified as case reports and original
researches published in English on Pubmed and Scielo databases between January 2012 and July 2015.
Discussion: 1. Antibody mediated limbic encephalitis is an increasingly recognized cause of seizures in
cryptogenic epilepsy2; 2. Anti-Hu antibodies are those most frequently described with seizures, epilepsia
partialis continua, and status epilepticus2,3,4; 3. Anti-GAD antibodies and LE is a rare condition and few
cases have been reported in the literature. It has been proposed that anti-GAD antibodies could impair
GABAergic synaptic transmission by reducing GABA synthesis and interfering with exocytosis of GABA,
leading to increase excitability and lower seizure threshold3,4,9; 4. Anti-NMDAR encephalitis was first
described in patients with paraneoplastic encephalitis resulting from ovarian teratomas. Some years later
it was shown that the antibodies reacted with the NR1 subunit of the NMDAR. Other publications also
showed that NMDAR encephalitis also could be found in the absence of a tumor. Clinically, patients
present with seizures, memory loss, and psychiatric symptoms, such as fear, insomnia, anxiety, mania,
and paranoia1,5,4,7 ; 5. The VGKC antibodies were later recognized as a common cause of LE and seizures.
More recently, it was discovered that the actual antigen target of these antibodies are proteins associated
with the VGKC complex, specifically leucine-rich gliomainactivated 1 protein (Lgi1) and contactinassociated protein 2(CASPR2)4,5,8,10. Conclusion: Cryptogenic epilepsy can be caused by autoimmune
mechanisms as in the case of LE. Common antibodies present in both pathologies were identified and
served as justification to the clinical manifestations of the disease. The treatment consists in immunotherapy, which justifies the fact that this form of epilepsy does not respond to conventional
treatment. Due to the different response to treatment health care professionals must consider the
autoimmune cause in refractary epilepsy cases or new installed epileptic disorder.
MACHADO, S; et al. What should you know about limbic encephalitis? Arq Neuropsiquiatr, 70(10):817-
, July 2012.
CORRELL, C. M. Antibodies in Epilepsy. CurrNeurolNeurosci Rep, March, 2013.
DAVIS, R; DALMAU, J. Autoimmunity, Seizures, and Status Epilepticus. Epilepsia, p. 46-49, September,
GARCÍA, M. E; et al. Acute amnesia and seizures in a young female. Epileptic Disord, 455-60, 2013.
BIEN, C.G; BAUER, J. Autoimmune Epilepsies. The American Society for Experimental
NeuroTherapeutics, v.11, p. 311–318, February, 2014.
MYIA, K; TAKAHASHI, Y; MORI,H. Anti-NMDAR autoimmune encephalitis. Official Journal of the
Japanese Society of Child Neurology, v. 36, p. 645-652, 2014.
PETIT-PEDROL, M. et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the
GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies.
Lancet Neurol, v. 13, p. 276–86, March, 2014.
RAMANATHAN, S. et al. Characterisation of a syndrome of autoimmune adult onset focal epilepsy and
encephalitis. Journal of Clinical Neuroscience, v. 21, p. 1169-1175, 2014.
SHEN, C. Immune- Mediated Limbic Encephalitis - Tip of the Iceberg in Chilhood Autoimmune Epilepsy.
Pediatrics and Neonatology, v.54 , p. 217-218, 2013.
VALENCIA, M. D. I. Epilepsy in Systemic Autoimmune Disorders. Seminars in Pediatric Neurology, v.21,
- Não há apontamentos.
This work is licensed under a Creative Commons Attribution 3.0 License.