To report clinical characteristics and fluorodeoxyglucose positron emission tomography(FDG-PET) findings in brain and musculoskeletal systems of anti-glutamic acid decarboxylase 65(anti-GAD65) associated neurologic disorders.

Anti-GAD65 associated neurologic disorders are difficult to diagnose due to their rarity and limited awareness of the expanding spectrum of presentations. There is a lack of paraclinical markers available that aid in their diagnosis. Hence, there is a great unmet need to identify additional markers that may help support a clinical suspicion.   

Retrospective medical record review from 1997 to 2018 at Johns Hopkins Hospital(JHH) revealed 170 patients with anti-GAD65 associated neurologic disorders, of which forty-three underwent whole body FDG-PET, including  brain. Only individuals with FDG-PET scans completed and/or reviewed by a JHH radiologist were included.

Average age of cohort was 49 years(range:18-77). The majority were female(61%) and Caucasian(57%). Thirty-one(72%) had Stiff-person Syndrome phenotype. Fourteen had coexisting autoimmune conditions. Two had paraneoplastic etiology. Forty-two patients had elevated serum anti-GAD65 antibodies and one elevated anti-glycine antibody only. Twenty-five had CSF studies; twelve showed elevated anti-GAD65 antibodies. Brain MRI was performed in forty-two patients; four had cerebellar atrophy. Eighteen(42%) had abnormal brain FDG-PET activity; most commonly cerebral cortex hypometabolism. Four showed FDG-PET changes in cerebellum, with three corresponding to MRI changes and all corresponding to clinical phenotype. Neither presence nor titer of CSF anti-GAD65 antibody correlated with brain PET. Eight(19%) had abnormal  activity in musculature: two diffuse hypermetabolism and six focal hypermetabolism that corresponded to symptomatic regions.

FDG-PET abnormalities in anti-GAD65 associated neurological disorders have not been characterized previously and may be under-recognized. Though FDG-PET is often initially obtained for workup of underlying malignancy, abnormalities in brain and musculature may be noted. Further studies are needed to evaluate the association of FDG-PET changes to clinical phenotype and utility in serving as an imaging biomarker.