The Clinical Value of 18 F-FDG-PET in Autoimmune Encephalitis Associated With LGI1 Antibody

Abstract

Purpose: The metabolic patterns of ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) in autoimmune encephalitis associated with leucine-rich glioma-inactivated 1 antibody (LGI1 AE) are still unclear. We performed a cohort study to investigate the clinical metabolic characteristics and diagnostic value based on ¹⁸F-FDG-PET in patients with LGI1 AE. Materials and Methods: A total of 34 patients including 18 patients (53%) in the acute phase and 16 patients (47%) in the chronic phase who were diagnosed with LGI1 AE were retrospectively analyzed from October 2014 to June 2018 at the Department of Neurology in Beijing Tiantan Hospital, the Capital Medical University. The clinical data were collected by searching through electronic medical records. Results: The initial ¹⁸F-FDG-PET scan indicated a significant abnormal metabolic pattern in 31 LGI1 AE patients (91%), whereas only 20 patients (59%) showed an abnormal MRI signal (P < 0.05). The ¹⁸F-FDG-PET metabolic pattern was reversible after treatment; most of the patients showed an almost normal uptake of ¹⁸F-FDG-PET after discharge. Regarding the spatial distribution, the abnormal metabolic pattern in LGI1 AE subjects exhibiting hypermetabolism was specifically located in the basal ganglia (BG) and medial temporal lobe (MTL). BG hypermetabolism was observed in 28 subjects (82%), and 68% of patients showed MTL hypermetabolism. A total of 17 patients (50%) exhibited faciobrachial dystonic seizures (FBDS), and the remaining subjects showed non-FBDS symptoms (50 and 50%). BG-only hypermetabolism was detected in seven subjects in the FBDS subgroup (7/16) but in only one subject in the non-FBDS subgroup (1/15) (44 vs. 7%, P < 0.05). Conclusion: ¹⁸F-FDG-PET imaging was more sensitive than MRI in the diagnosis of LGI1 AE. Isolated BG hypermetabolism was more frequently observed in subjects with FBDS, suggesting the potential involvement of the BG.

Keywords: 18F-FDG-PET; FBDS; LGI1; basal ganglia; medial temporal lobe.

Figure 1

Neuroimaging testing in the diagnostic tracking of LGI1 AE. Neuroimaging testing plays an essential role in the diagnosis of LGI1 AE. The sensitivity of ¹⁸F-FDG-PET was higher than that of MRI; the ¹⁸F-FDG-PET scan was always positive when the MRI was positive, but when the MRI scan was negative for the diagnosis of LGI1 AE, 79% of the patients were still positive on the ¹⁸F-FDG-PET scan. LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; EEG, electroencephalogram; MRI, magnetic resonance imaging; PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; +, positive; –, negative.

Figure 2

¹⁸F-FDG-PET metabolic pattern in patients with LGI1 AE. (A) Typical BG and MTL hypermetabolism based on ¹⁸F-FDG-PET in patients with LGI1 AE. Age-matched control patients with colorectal cancer in the absence of central nervous system lesions indicating healthy metabolism in the BG (a) and MTL (b). Representative increased metabolism in the BG (c) and MTL (d) in a patient with LGI1 AE. (B) MRI-negative and PET-positive metabolic patterns in LGI1 AE subjects. The axial fluid-attenuated inversion recovery image indicates a normal signal in the BG (a) and MTL (b), whereas ¹⁸F-FDG-PET reveals hypermetabolism in the identical location from the same patient with LGI1 AE (c,d). (C) The brain sequences in ¹⁸F-FDG-PET with LGI1 AE patients. Total brain ¹⁸F-FDG-PET mapping indicates the BG and MTL as two distinctive targets in LGI1 AE patients (d–h). (D) The reversible metabolic pattern in LGI1 AE. ¹⁸F-FDG-PET indicates increased ¹⁸F-FDG uptake in the BG and MTL. Furthermore, the ¹⁸F-FDG PET scan shows markedly decreased ¹⁸F-FDG uptake in the BG and MTL during the 3-month follow-up period. LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; MRI, magnetic resonance imaging; PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; MTL, medial temporal lobe; BG, basal ganglia.

Figure 3

¹⁸F-FDG-PET hypermetabolism in LGI1 AE patients with FBDS. (A) Neuroimaging comparison of the subgroups of LGI1 AE. (B) Representative ¹⁸F-FDG-PET hypermetabolism among different subgroups after SPM (P < 0.01) analysis. (C) The comparison of the ¹⁸F-FDG-PET hypermetabolic pattern between FBDS and non-FBDS. In the FBDS group, the abnormal PET signal more often appeared in the BG-only group and the BG + MTL group. However, in the non-FBDS group, the abnormal PET signal significantly appeared in the BG + MTL group. (D) A comparison of the ¹⁸F-FDG-PET hypermetabolic pattern in FBDS and non-FBDS. In the BG-only group, the frequency of FBDS was higher than that of non-FBDS (P < 0.001). LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; FBDS, faciobrachial dystonic seizures; MRI, magnetic resonance imaging; PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; MTL, medial temporal lobe; BG, basal ganglia. +, positive; –, negative.

Figure 4

¹⁸F-FDG-PET hypermetabolism in eight patients with LGI1 AE recurrence. (A) Representations of the distribution of metabolic patterns without SPM analysis. (B) Normalized SUVmax value in different brain regions and the threshold of BG and MTL based on ROC. (C) The rate of relapse of the subgroups based on the metabolic pattern. The findings showed that patients presenting with BG-only or BG + MTL hypermetabolism had a lower rate of relapse (P < 0.05). LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; ¹⁸F-FDG-PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; BG, basal ganglia; MTL, medial temporal lobe.

Figure 5

¹⁸F-FDG-PET characteristics of LGI1 AE patients in different clinical phases. FDG-PET hypermetabolism was specifically located in the BG and MTL, whether it was in the acute phase or chronic phase, and there is no statistical metabolic change between acute and chronic phases for BG and MTL. LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; ¹⁸F-FDG-PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; BG, basal ganglia; MTL, medial temporal lobe.

Figure 6

Ictal EEG pattern in an LGI1 AE patient with FBDS. (A) The ictal EEG of a 50-year-old woman with FBDS. No significant rhythm changes were noted except for artifacts of movements that were observed at the onset of the dystonic seizures. However, the EEG indicated low voltage in the right central and parietal areas before 5 s from onset (square frame). (B) The postictal EEG of the patient with FBDS. The EEG demonstrated rhythmic slow wave activity in the left temporal region (square frame) after the termination of FBDS, which was accompanied by hand automatism. LGI1, leucine-rich glioma-inactivated 1; AE, autoimmune encephalitis; FBDS, faciobrachial dystonic seizures; EEG, electroencephalogram.