Autoimmune Limbic Encephalitis and Adult-Onset Type 1 Diabetes Caused By Anti-GAD65 Antibodies

Background: The glutamic acid decarboxylase enzyme is present in high concentrations in both the brain and pancreatic islet beta cells.  Antibodies to GAD65 have been implicated in the pathogenesis of type I diabetes and limbic encephalitis with temporal lobe epilepsy; however, these diseases rarely present concurrently.  

Objectives: We intend to present a rare case of anti-glutamic acid decarboxylase (GAD65) antibody-mediated autoimmune limbic encephalitis with temporal lobe epilepsy in which the patient later developed type I diabetes.    

Methods: We performed a thorough chart review of a 49 year-old man with hypothyroidism who presented with new-onset complex partial seizures and subsequently developed adult-onset type I diabetes.  

Results:  The patient's complex partial seizures were described as a rising “adrenaline rush” followed by a stereotyped memory of song lyrics.  Interictal neurologic examination was non-focal, whereas the ictal examination revealed acalculia despite his profession as a mathematics teacher.  Post-ictal examination revealed amnesia of ictal events.  EEG revealed interictal bitemporal slowing within the theta range and ictal rhythmic theta originating from the left anterior temporal lobe.  Brain MRI revealed gadolinium-enhancement of the left mesiotemporal lobe with corresponding hypometabolism on an interictal FDG PET.  CT with contrast of the chest, abdomen, and pelvis did not reveal an underlying malignancy.  Serologic work-up including rheumatologic markers and a paraneoplastic panel were unremarkable; however, anti-GAD65 antibody titers were elevated at level of 1:4800.  Complex partial seizures were refractory to levetiracetam, carbamazepine, phenytoin, and valproic acid.  The patient's seizure frequency improved only while receiving high-dose intravenous methylprednisolone but later increased to more than ten daily after the course was completed.  Concurrently, the patient's random blood glucose levels were noted to be greater than 500 mg/dL and he required insulin for glycemic control.  Hyperglycemic episodes occurred prior to steroid administration and was attributed to the onset of type I diabetes.

Conclusions:  In rare situations, anti-GAD65 antibodies can cause adult-onset temporal lobe epilepsy secondary to an autoimmune, non-paraneoplastic limbic encephalitis as well as adult-onset type I diabetes.  Anti-GAD65 antibody titers should be evaluated in patients presenting with adult-onset temporal lobe epilepsy or type I diabetes.