BACKGROUND: Approximately 60% of patients with autoimmune encephalitis (AE) exhibit secondary acute symptomatic seizures and showed highly sensitive to immunotherapy. However, it is difficult for many patients to receive early immunotherapy since the early identification of the cause in AE is more complex. This study aimed to investigate the early predictors of initial immune-related seizures and to guide the evaluation of treatment and prognosis.
METHODS: One hundred and fifty-four patients with new-onset \"unknown etiology\" seizures with a course of disease less than 6 months were included. Serum and/or cerebrospinal fluid neuron-specific autoantibodies (NSAbs), including N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5- Methyl-4-isoxazole propionic acid receptor 1 (AMPAR1), AMPAR2, anti-leucine rich glioma inactivated 1 antibody (LGI1), anti-gamma-aminobutyric acid type B receptor (GABABR), anti-contact protein-related protein-2 (CASPR2) were used to screen for immune etiology of the seizures. In addition, patients with epilepsy and encephalopathy were also examined via brain MRI, long-term video EEG, antibody prevalence in epilepsy and encephalopathy (APE2) score, and modified Rankin Scale (mRS). A logistic regression model was used to analyze the early predictors of immune etiology.
RESULTS: Thirty-four cases (22.1%) were positive for NSAbs. Among all 154 patients, 23 cases of autoimmune encephalitis (AE) (21 cases of NSAbs positive), 1 case of ganglionic glioma (NSAbs positive), 130 cases of epilepsy or seizures (12 cases of NSAbs positive) were recorded. Also, there were 17 patients (11.0%) with APE2 ≥ 4 points, and all of them met the clinical diagnosis of AE. The sensitivity and specificity of APE2 ≥ 4 points for predicting AE were 73.9% and 100%. The results of multivariate analysis showed that the NSAbs and APE2 scores independently influenced the early prediction of initial immune-related seizures (P < 0.05).
CONCLUSIONS: NSAbs and APE2 scores could act as early predictors of initial immune-related seizures.

Seizures are a very common manifestation of autoimmune encephalitis (AE), ranging from 33% to 100% depending on the antigen, most often accompanied by other clinical features such as behavioral changes, movement disorders, memory deficits, autoimmune disturbances, and altered levels of consciousness. Unusual seizure frequency, resistance to antiepileptic treatment, and often, definitive response to immunotherapy emphasize the importance for neurologists to consider the probable etiology of immune disorders. Studies on pathogenic mechanisms of autoantibodies have improved the understanding of different pathophysiologies and clinical characteristics of different AE groups. In encephalitis with antibodies to neuronal extracellular antigens, autoantibodies play a direct role in disease pathogenesis. They have access to target antigens and can potentially alter the structure and function of antigens but induce relatively little neuronal death. Prompt immunotherapy is usually very effective, and long-term antiepileptic treatment may not be needed. In contrast, in encephalitis with antibodies against intracellular antigens, autoantibodies may not be directly pathogenic but serve as tumor markers. These autoantibodies cannot reach intracellular target antigens and are considered to result from a T-cell-mediated immune response against antigens released by apoptotic tumor cells, which contain nerve tissue or express neuronal proteins. Neuronal loss is frequently described and predominantly induced through cytotoxic T-cell mechanisms. They often exhibit an inadequate response to immunotherapy and require early tumor treatment. Long-term antiepileptic treatment is usually needed. In conclusion, each neural autoantibody can specifically precipitate seizures. Early proper management of these cases may help prevent neurological deterioration and manage the occurrence of seizures. Consequently, confirmation of the presence of neuronal autoantibodies is strongly recommended even in patients with confirmed AE, as they are not only essential in achieving a good outcome but also may provide evidence for underlying neoplasia.

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In recent years, as an increasing number of neuronal autoantibodies have been detected and used for clinical diagnosis, clinicians have become more aware of autoimmune encephalitis, causing its reported incidence to trend upward over several years. To date, however, there has been no large-scale epidemiological survey of autoimmune encephalitis in adults and children, and its epidemiological characteristics remain unclear. Six main types of antibodies are detected and used to diagnose autoimmune encephalitis in Chongqing, Southwestern China: anti-NMDA receptor antibody, anti-GABAB receptor antibody, anti-LGI1 antibody, anti-CASPR2 antibody, anti-AMPA1 receptor antibody, and anti-AMPA2 receptor antibody. From January 2012 to February 2018, 189 patients at six general hospitals in Chongqing were diagnosed with autoimmune encephalitis and were positive for neuronal autoantibodies. In this report, the epidemic situation and the antibody distribution among these patients are analyzed and described in detail. The differences in disease severity among different ages and between the sexes are evaluated, and the correlation between antibody titer and disease severity is also assessed.