Clinical and Electroencephalographic Features of the Seizures in Neuronal Surface Antibody-Associated Autoimmune Encephalitis

Abstract

Objectives: To investigate clinical and electroencephalographic features of the seizures in different types of neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE). Methods: The clinical data of the seizures were analyzed in 18 patients with NSAb-associated AEs diagnosed in the First Affiliated Hospital of Dalian Medical University. Results: From May 2013 to April 2019, a total of 18 cases of NSAb-associated AE were diagnosed, including 9 cases of leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis, 7 cases of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and 2 cases of anti-γ-aminobutyric acid B receptor (GABA_BR) encephalitis. All nine cases (100%) with LGI1 AE had seizures manifesting in three types: faciobranchial dystonia seizure (FBDS) (44.4%), mesial temporal lobe epilepsy (MTLE)-like seizure (66.7%), and focal to bilateral tonic-clonic seizure (FBTCS) (77.8%). Six of nine (66.7%) showed abnormal signal on hippocampus or basal ganglia in brain MRI. Five of seven cases (71%) with anti-NMDAR encephalitis had seizures manifesting in three types: focal aware seizure (40%), focal-impaired awareness seizure (20%), generalized tonic-clonic seizure (GTCS) (100%), and status epilepticus (SE) (40%). Three of seven (42.8%) showed abnormalities in brain MRI. Both patients with anti-GABA_BR encephalitis had seizures manifesting in two types: GTCS and MTLE-like seizure, one with SE. One showed abnormal signal on left hippocampus in brain MRI. All patients (100%) with three types of AE had abnormalities in electroencephalogram (EEG), showing diffuse (4/18) or focal slow waves (14/18) in background, interictal (10/18), or ictal (6/18) epileptic discharges in the temporal or other regions; two patients with anti-NMDAR encephalitis showed delta activity or rhythm in frontotemporal region. All patients with seizures showed good response to immunotherapy except one with LGI1 AE. Conclusions: Most patients with NSAb-associated AE had seizures; seizure types varied between different types of AE. In LGI1 AE, the hippocampus and basal ganglia were two main targets; the corresponding seizure type was MTLE-like seizure and FBDS, respectively. Anti-NMDAR encephalitis had more generalized than focal seizures. Delta activity or rhythm in the frontotemporal region in EEG was helpful for diagnosis. Anti-GABA_BR encephalitis was characterized by refractory seizures as initial symptom, mainly GTCS or MTLE-like seizure. Most seizures in NSAb-associated AE showed good response to immunotherapy, and antiepileptic drugs should be considered as an add-on symptomatic treatment.

Keywords: GABABR antibody; LGI1 antibody; NMDAR antibody; autoimmune encephalitis; neuronal surface antibody; seizure.

Figure 1

Case 4, male, 62 years old, who was diagnosed with leucine-rich glioma-inactivated 1 protein (LGI1) antibody associated autoimmune encephalitis (AE). (A) Ictal electroencephalogram (EEG) of a subclinical seizure showed rhythmic sharp wave discharges in bilateral temporal regions, with amplitude and frequency modulated gradually. (B,C) Twenty-three days after onset and before immunotherapy, brain MRI showed high T2/fluid-attenuated inversion recovery (FLAIR) signal on bilateral hippocampus. (D,E) About 3 months after onset and after immunotherapy, brain MRI showed significant improvement in the high T2/FLAIR signal on bilateral hippocampus.

Figure 2

Case 9, female, 63 years old, who was diagnosed with leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated autoimmune encephalitis (AE). (A) Ictal electroencephalogram (EEG) of faciobranchial dystonia seizure (FBDS) showed that 1 s before the clinical onset, the amplitude of all the leads suppressed, followed by artifact of movements, which continued for 5 s, and then recovered to background. (B,C) Nineteen days after onset and before immunotherapy, brain MRI showed high T1/T2 signal on the left basal ganglia (caudal nucleus and lenticular nucleus). (D,E) Thirty-three days after onset (10 days after immunotherapy), brain MRI showed significant improvement in the high T1/T2 signal on the left basal ganglia.

Figure 3

Case 10, male, 25 years old, who was diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Electroencephalogram (EEG) showed delta activity or rhythm in bilateral frontotemporal region.

Figure 4

Case 17, male, 64 years old, who was diagnosed with anti-γ-aminobutyric acid B receptor (GABA_BR) encephalitis. (A–D) Twenty-one days after onset and before immunotherapy, brain MRI showed high T2/fluid-attenuated inversion recovery (FLAIR) signal in the left hippocampus.

Figure 5

Case 17, male, 64 years old, who was diagnosed with anti-γ-aminobutyric acid B receptor (GABA_BR) encephalitis. (A,B) Twenty-one days after onset and before immunotherapy, electroencephalogram (EEG) showed slow waves in the left temporal region (A), and a subclinical electrographic seizure originating from the left temporal region (B). (C,D) Ten days after immunotherapy, EEG showed significant improvement in background activities (C), with scatted slow waves in the left posterior region (D).