Case Presentation: TW is a 43-year-old woman with history of complex partial epilepsy who presented with recurrent seizures and poor memory. She has poor medication compliance and multiple emergent visits for seizures. Past workup included normal brain imaging, normal TSH and B12, and negative HIV and RPR. Electroencephalography showed left frontal interictal epileptiform discharges. Patient also had a serum paraneoplastic panel with an elevated anti-glutamate decarboxylase antibody of 730 nmol/L. On admission, vital signs were stable. Physical exam, including her neurologic exam, was unremarkable except for a Montreal Cognitive Assessment (MoCA) score of 11. Laboratory workup included a normal CBC, CMP, HIV, TSH, B12 and RPR. MRI brain revealed a focus of gray matter heterotopia adjacent to the body of the right lateral ventricle. CSF was obtained and results were positive for anti-GAD antibody. She was started on intravenous immunoglobulin (IVIG) with improvement in MoCA score to 22 after 5 days of treatment. Workup for etiology of the anti-GAD antibody revealed a small lobulated non-enhancing thin-walled cystic structure in the pancreatic head with a mildly elevated CA 19-9. Endoscopic Ultrasound with sampling of fluid was scheduled to be performed after discharge.
Discussion: Glutamate decarboxylase (GAD) is an intracellular enzyme responsible for catalyzing the reaction of L-glutamic acid into gamma-aminobutyric acid (GABA)1. GAD is expressed in pancreas and also in the brain. In rare circumstances, autoantibodies to GAD are implicated in significant neurological disorders including limbic encephalitis2. Limbic encephalitis involves the medial temporal lobe and hippocampus that can present with seizures, memory loss, hallucinations, depression, and other neuropsychiatric symptoms. Memory loss is typically short-term loss with preservation of long-term and autobiographic memories3. Magnetic resonance imaging often shows intensities in the medial temporal lobe. EEG findings can show slowing and seizure-like activity in the temporal lobes. In symptomatic patients, antibodies are often seen in the CSF2,3,4.The incidence of encephalitis of any etiology is 2-3/100,000 in northern Europe, 20% being immune-mediated5. There are no standard guidelines for treatment. Studies have shown positive results with a combination of corticosteroids, IVIG, and plasmapheresis4,6. Evidence concerning anti-GAD encephalitis with these treatments have variable results3,7,8,9. One study exploring seizure control in anti-GAD encephalitis showed corticosteroids to be most effective, but overall response to be poor10.
Conclusions: Anti-GAD is a rare cause of seizures and poor memory. It should be considered in a patient with no structural brain abnormalities and an otherwise negative workup. Unlike previous cases having poor response to IVIG, our patient had a marked improvement. One confounder is the patient’s history of non-compliance with anti-epileptic medications. It is critical to work up the underlying etiology of paraneoplastic antibodies.
To cite this abstract:Shin, Y; Smirnova, N; Molitch-Hou, E; Liu, M. NOT JUST YOUR DIABETES ANTIBODY: A CASE OF ANTI-GLUTAMATE DECARBOXYLASE ASSOCIATED LIMBIC ENCEPHALOPATHY. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract 994. https://www.shmabstracts.com/abstract/not-just-your-diabetes-antibody-a-case-of-anti-glutamate-decarboxylase-associated-limbic-encephalopathy/. Accessed December 7, 2019.