John Libbey Eurotext

Autoimmune encephalitis and anti-GAD/GABA-A receptor antibodies Volume 17, issue 1, March 2015

To the Editor,

We refer to the publication of Kojima et al 2014: “PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis”. Neurological disorders associated with antibodies against cell surface and synaptic proteins are fascinating diseases that have changed paradigms in neurological practice, mainly because these disorders were previously unknown and/or mischaracterized (Leypoldt et al., 2014). In a recent report, Kojima et al. (2014) described a patient with limbic encephalitis and refractory status epilepticus attributed to the presence of low-titer anti-glutamic acid decarboxylase (GAD) antibodies. The authors did not perform comprehensive autoantibody studies, and therefore, the attribution of the patient's syndrome to GAD65 autoimmunity is highly questionable. Indeed, antibodies against gamma-aminobutyric acid (GABA)-A receptor should have been examined. This is important, since the patient had several findings very similar to other patients with encephalitis associated with GABA-A receptor antibodies.

The GABA-A receptor is one of the most recently identified antigens (Petit-Pedrol et al., 2014) within the category of autoimmune encephalitis associated with antibodies against synaptic receptors. High-titer serum and CSF GABA-A receptor antibodies were recently reported in six patients with autoimmune encephalitis associated with seizures or status epilepticus, four of whom required pharmacologically induced coma. Epileptic symptoms were preceded by, or associated with, a change in behaviour or level of cognition in all patients. Brain MRI showed extensive multifocal abnormalities on FLAIR and T2 imaging, with cortical and subcortical involvement without contrast enhancement, which highly resembled the findings for the patient reported by Kojima et al. (2014). Patients often had coexistent autoantibodies against less relevant or intracellular proteins, including anti-thyroid peroxidase antibodies (three patients), anti-GAD65 antibodies (one patient), and anti-GABA-B receptor antibodies (one patient). Importantly, the antibodies of the patients altered the levels of GABA-A receptors in cultured neurons, and most patients improved after treatment.

The patient reported by Kojima et al. had a history of thymoma, although no relapsing neoplasia was found. Interestingly, two cases of anti-GABA-A receptor antibody-associated encephalitis were recently reported in association with thymoma (Ohkawa et al., 2014), one of whom had concomitant anti-LGI1 antibodies, while the other had anti-Caspr2 antibodies.

Altogether, the clinical picture, MRI findings, and history of thymoma in the patient reported by Kojima and colleagues are suggestive of anti-GABA-A receptor antibody-associated encephalitis, a disorder that may occur in patients with a propensity for autoimmunity and sometimes co-existent anti-GAD65 antibodies.