Clinical Features and Long-Term Outcomes of Anti-Leucine-Rich Glioma-Inactivated 1 Encephalitis: A Multi-Center Study

Abstract

Purpose: To describe the clinical manifestation, immunotherapy, and long-term outcomes of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.

Patients and methods: This study was a retrospective analysis of 117 patients with a diagnosis of anti-LGI1 encephalitis identified from the databases of multiple clinical centers between September 2014 and December 2019. The clinical features, ancillary test results, and details of long-term outcomes were evaluated.

Results: Among the 117 patients with anti-LGI1 encephalitis, 69.2% (81/117) were male and 30.8% (36/117) were female. The median age of all patients at the onset of the disease was 57 years (interquartile range [IQR], 52-67). The median time from symptom onset to diagnosis was 8.7 weeks (IQR, 4.2-25). The main clinical features identified were seizures, cognitive impairment, and mental and behavioral abnormalities. Of the 117 patients, 109 were treated with immunotherapy. Symptoms including memory, mental ability, and behavior improved in all 109 patients after 3-5 days of treatment. The median time of follow-up for the treated patients was 33 months (IQR, 17-42). Of the treated patients, 16.2% (19/117) experienced a relapse, with a median delay of 5 months (IQR, 2.1-17) between onset and the first relapse. There were no mortalities over the follow-up period.

Conclusion: The long-term outcome of patients with anti-LGI1 encephalitis was mostly favorable, although some patients continued to experience cognitive dysfunction. Early recognition is important for prompt initiation of immunotherapy that can improve clinical symptoms of anti-LGI1 encephalitis.

Keywords: anti-LGI1 encephalitis; autoimmune epilepsy; follow-up; immunotherapy; relapse.

Figure 1

(A) Trends in the numbers of annually diagnosed cases of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. (B) Distribution of gender and age of patients with anti-LGI1 encephalitis.

Figure 2

(A) Initial symptoms in 117 patients with anti–leucine-rich glioma-inactivated 1 (LGI1) encephalitis. (B) Assessment of cognitive function of 42 patients at the time of initial admission to the hospital. MMSE, Mini-Mental State Examination; MOCA, Montreal Cognitive Assessment Scale; FBDS, faciobrachial dystonic seizure. (C) Modified Rankin Scale (mRS) score at onset and follow-up. A, mRS score at onset; B, mRS score at 6 months after immunosuppressive therapy; C, mRS score at the last follow-up. ****P < 0.0001.

Figure 3

Brain magnetic resonance imaging and positron emission tomography (PET) scans of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. Axial fluid-attenuated inversion recovery (A, C, D) and T2-weighted (B) images. Bilateral high signal in the medial temporal lobe (A–C). Bilateral abnormal signals in the medial temporal lobe and occipital lobe (D). PET images show bilateral hypermetabolism in the basal ganglia and medial temporal cortex (more significant on the right) (E–H).

Figure 4

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis video electroencephalogram (EEG). (A) The EEG shows slow background rhythm as well as slow and sharp waves in both frontal areas (Fp1\F3\Fp2\F4). (B) Monitoring the faciobrachial dystonic seizures (FBDSs), amplitudes of the bilateral cerebral hemispheres were asymmetrical with diffuse slow waves in the left cerebral hemisphere, and no epileptiform discharges were detected.