Role of 18F-FDG PET scan in diagnosis of autoimmune encephalitis

Introduction: Autoimmune encephalitis (AE) involves a group of non-infectious central nervous system (CNS) inflammation in response to paraneoplastic or autoimmune antibodies against neuronal antigens such as NMDAR, MOG, GABA, and GAD65. As the result of several published case studies, clinicians’ awareness and knowledge regarding AE have rapidly grown in the past decade. Currently cerebrospinal fluid (CSF) autoantibodies level is the gold standard for clinical diagnosis of AE. However, our knowledge regarding antibodies responsible for AE are still growing and current antibody panels and limited accuracy of detection techniques may miss the diagnosis, and results in a misleading treatment. As a result of this clinical judgment challenge, recent studies have suggested the use of CNS imaging for AE diagnosis. In this review we aim to summarize the role of ¹⁸F-FDG PET in AE diagnosis.

Methods: A comprehensive literature review was performed in the MEDLINE, Embase, Cochrane library databases, and Web of Science. Search result was screened for English studies including case reports/series, cohort studies, and clinical trials regarding AE diagnosis using ¹⁸F-FDG PET scan without any publication date limitation. Included studies were reviewed regarding the study design, patient population, and outcomes.

Results: Previous studies showed that patients with AE may have magnetic resonance imaging (MRI) changes (including T2-FLAIR hyperintensities in the temporal lobe). However, several studies indicated normal or nonspecific changes in brain MRI of patients with AE especially in the acute phase. On the other hand, ¹⁸F-FDG PET studies showed abnormal findings in AE patients with normal MRI. With the rate of up to 50% missing AE diagnosis with MRI while the 18F-FDG PET showed pathological changes. Additionally, in some AE cases, ¹⁸F-FDG PET was the only diagnostic modality showing pathological patterns while initial MRI, CSF, and Electroencephalography (EEG) were all normal.

Different pathological patterns have been reported for ¹⁸F-FDG PET scan of patients with AE, including hyper- or hypometabolism of medial temporal lobe in limbic encephalitis. Overall, regional brain hypometabolism is the most frequently observed pathological change. However, hypermetabolism changes were more reported than hypometabolism in cases with more severe symptoms or shorter time interval between symptoms start and scanning. The hypometabolism pattern can be explained by the receptor internalization, suppression of synaptic plasticity and currents, and reducing normal neuronal activities by autoantibodies. Moreover, specific metabolic FDG PET patterns often correspond to the encephalitis autoantibody subtypes. ¹⁸F-FDG-PET was reported abnormal in medial occipital region in patients with anti-NMDA receptor AE. Additionally, ¹⁸F-FDG PET scan was strongly corelated with clinicals symptoms severity compared to MRI findings.

Conclusions: ¹⁸F-FDG PET has a high diagnostic sensitivity for autoimmune encephalitis and strongly correlates with clinical symptoms compared to other diagnostic modalities. Therefore ¹⁸F-FDG PET provides a helpful opportunity to overcome the challenges of diagnosing and treatment response assessment of AE. Local hypometabolism is the most common pathological finding in ¹⁸F-FDG PET of patients with AE and future studies are needed to focus on the specificity of ¹⁸F-FDG PET in AE diagnosis.