Long latency between GAD-antibody detection and development of limbic encephalitis – a case report

Susanne Fauser, Ingo Uttner, Helena Ariño, Werner A. Scherbaum, Albert Saiz, Jan Lewerenz

In the pathogenesis of limbic encephalitis other promoting factors besides the pure existence of autoantibodies are increasingly discussed to play a significant role. This is to our knowledge the first described patient in whom the presence of autoantibodies precedes the manifestation of limbic encephalitis for many years. At the age of 38 years, in the serum of a patient with polyendocrine autoimmunity high titers of cytoplasmic islet cell antibodies and of anti-glutamate decarboxylase (GAD) 65 antibodies were observed as an incidential finding, GAD67 antibodies were negative at that time. After a latency of 18 years, she manifested with refractory temporal lobe epilepsy most likely due to autoimmune limbic encephalitis. After epilepsy onset, the patient underwent magnetic resonance imaging (MRI), electroencephalography, cerebrospinal fluid (CSF), serum and neuropsychological investigations during a follow-up period of 8 years. A pharmacoresistent epilepsy with seizure onset from the right temporal lobe and declarative memory deficits were observed affecting primarily the recall of verbal informations. MRI showed a slightly increased signal in the right amygdala without progression. GAD antibodies could be detected in serum (titre 1: 1000) and CSF (titre 1:1) by immunofluorescence. Both, GAD65 and GAD67 antibodies were observed in cell-based assays. It can be assumed that in addition to a pre-existing systemic T-cell response associated with the longstanding polyendocrine autoimmunity, a delayed intrathecal autoimmunity developed leading to limbic encephalitis. This change might be reflected by the development of GAD67 antibodies in our patient. Besides the contribution of this case report to a better understandig of the pathomechanisms for the development of central nervous system (CNS) autoimmunity, it also has a clinical impact as early treatment of GAD antibody-associated CNS disorders has a better prognosis. Therefore, vigilance for symptoms indicating GAD antibody-associated CNS autoimmunity is mandatory in patients with GAD antibody-associated endocrine dysfunction.