Different FDG‐PET metabolic patterns of anti‐AMPAR and anti‐NMDAR encephalitis: Case report and literature review

Abstract

Introduction 18F‐fluorodeoxyglucose (FDG)‐PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti‐NMDAR and anti‐AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. Methods The cerebral glucose metabolism was evaluated by FDG‐PET/CT during acute‐to‐subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z‐score and visualized on three‐dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. Results The three‐dimensional stereotactic surface projection displayed frontal‐dominant hypometabolism in a 66‐year‐old female patient with anti‐AMPAR encephalitis and occipital‐dominant hypometabolism in a 29‐year‐old female patient with anti‐NMDAR encephalitis. Receptor density maps revealed opposite frontal–occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG‐PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti‐NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. Conclusions The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG‐PET of brain a valuable diagnostic tool.

Neurovascular Uncoupling in Schizophrenia: A Bimodal Meta-Analysis of Brain Perfusion and Glucose Metabolism

“…Both lower dose exposure and higher negative symptom burden related to the exaggerated effect size of the patient-control differences in middle occipital rCBF/rCMRglu. These findings are intriguing in the context of recent observations implicating occipital hypometabolism as an early biomarker of anti-NMDA receptor encephalitis, a condition with a high propensity to present with psychotic symptoms (48,49). Nevertheless, we did not find any regional associations for the PANSS positive symptom domain.…”

Metabolic scoring in autoimmune epilepsy—Should APE scores be modified?

“…They suggested that the distinct hypometabolism patterns were representative of receptor hypo-function with spatial correspondence to receptor distribution. 26 Thus, it would be interesting to see that if antigen-specific patterns, as described for NMDARE, would evolve for the other antibody subtypes also.…”

Diagnostic Value of Structural and Functional Neuroimaging in Autoimmune Epilepsy

“…The FDG-PET images of anti-NMDAR encephalitis-associated epilepsy showed a pattern of decreased metabolism from the front to the back, that is, high metabolism in the frontal lobe, temporal lobe, and basal ganglia and low metabolism in the parietal occipital lobe, and the metabolic pattern could change with disease progression, treatment, and follow-up [ 63 ]. During the acute and subacute phases, antibody levels were high in all patients, and FDG-PET indicated severe hypermetabolism in the frontal, temporal cortex, and basal ganglia and hypometabolism in bilateral occipital lobes; in the early stage of recovery, diffuse cortical metabolism was the main feature, and the antibody levels of these patients were weak and positive at the same time; during the recovery period, abnormal metabolism and antibody levels returned to normal [ 61 , 63 , 65 ]. The comparison of FDG uptake in patients and healthy probands showed the cortical anteroposterior gradient and increased uptake in the striatum [ 64 ].…”

“…AMPAR antibody-associated encephalitis is relatively rare in AE and is often associated with MTL abnormals on MRI [ 73 , 74 ]. In a 66-year-old woman with anti-AMPAR encephalitis and diabetes mellitus, MRI showed only a few high-intensity punctate lesions in the white matter, but FDG-PET revealed a wide range of low metabolism areas including the frontal, parietal, and temporal parahippocampal areas [ 65 ]. Anti-AMPAR encephalitis with generalized seizures was closely associated with sustained hypermetabolism of left hippocampal FDG in FDG-PET [ 75 ].…”

“…One patient presented with bilateral cerebellar hypermetabolism and the other with total cortical hypometabolism [ 76 ]. The metabolism of FDG in the brain is correlated with clinical manifestations, and abnormal metabolism turned to normal after antiepileptic and immune treatment [ 65 , 75 ]. Due to the low incidence of anti-AMPAR encephalitis, current functional imaging studies are limited to PET imaging, and further SPECT and fMRI studies are needed.…”