Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis

Abstract

Objective: To compare the rate of abnormal brain metabolism by FDG-PET/CT to other paraclinical findings and to describe brain metabolism patterns in autoimmune encephalitis (AE).

Methods: A retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with AE, per consensus criteria, treated at a single tertiary center over 123 months. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections with comparison to age group-matched controls. Brain region mean Z-scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made to rates of abnormal initial brain MRI, abnormal initial EEG, and presence of intrathecal inflammation.

Results: Sixty-one patients with AE (32 seropositive) underwent brain FDG-PET/CT at median 4 weeks of symptoms (interquartile range [IQR] 9 weeks) and median 4 days from MRI (IQR 8.5 days). FDG-PET/CT was abnormal in 52 (85%) patients, with 42 (69%) demonstrating only hypometabolism. Isolated hypermetabolism was demonstrated in 2 (3%) patients. Both hypermetabolic and hypometabolic brain regions were noted in 8 (13%) patients. Nine (15%) patients had normal FDG-PET/CT studies. CSF inflammation was evident in 34/55 (62%) patients, whereas initial EEG (17/56, 30%) and MRI (23/57, 40%) were abnormal in fewer. Detection of 2 or more of these paraclinical findings was in weak agreement with abnormal brain FDG-PET/CT (κ = 0.16, p = 0.02).

Conclusions: FDG-PET/CT was more often abnormal than initial EEG, MRI, and CSF studies in neurology inpatients with AE, with brain region hypometabolism the most frequently observed.

Figure 1. Antibody status of patients with AE

Antibody status of patients with AE who underwent dedicated brain FDG-PET/CT (N = 61). AE = autoimmune encephalitis; ANNA-1 = anti–neuronal nuclear antibody 1; CRMP5 = collapsin response mediator protein 5; GAD65 = 65 kDa glutamic acid decarboxylase enzyme; VGKCc = voltage-gated potassium channel-complex antibodies different from leucine-rich inactivated 1 protein (LGI1) and contactin-associated protein-2 (CASPR2); AChR = acetylcholine receptor antibody.

Figure 2. Metabolism across brain regions in AE

Boxplots of Z-scores for FDG-avidity for brain areas on dedicated FDG-PET/CT for (A) patients meeting consensus criteria for AE, (B) seronegative and seropositive patients meeting the consensus criteria for AE. Z-scores varied across brain regions for patients with AE (p < 0.005), with values for the caudate being greater than those for frontal (p < 0.005), temporal (p = 0.002), parietal (p < 0.005), and occipital (p < 0.005) lobes. No difference was noted between seronegative and seropositive patient groups (p = 0.08). AE = autoimmune encephalitis.

Figure 3. Brain MRI, brain FDG-PET/CT and hypometabolic 3D-SSP maps for 3 patients with AE

Brain MRI, brain FDG-PET/CT, and hypometabolic 3D-SSP maps, respectively, for patients with anti-NMDAR encephalitis (A–C), anti-LGI1 encephalitis (D–F), and seronegative AE (G–I). For the anti-NMDAR encephalitis patient, note normal T2/FLAIR MRI (A) with right basal ganglia, right frontotemporoparietal, left frontal, and bilateral posterior cortical hypometabolism centered on the middle occipital lobe on FDG-PET/CT and 3D-SSP maps (B and C). For the anti-LGI1 patient, note normal T2/FLAIR MRI (D) with relatively normal basal ganglia metabolism (E) in setting of diffuse frontotemporoparietal hypometabolism on FDG-PET/CT and 3D-SSP maps (E and F). For the seronegative AE patient, again note normal T2/FLAIR MRI (G) with diffuse frontotemporoparietal hypometabolism on FDG-PET/CT and 3D-SSP maps (H and I). A = anterior; AE = autoimmune encephalitis; L = left; LGI1 = leucine-rich inactivated 1 protein; NMDAR = NMDA receptor; P = posterior; R = right; and 3D-SSP, 3-dimensional stereotactic surface projection.