Anti-LGI1 encephalitis is a rare neuroinflammatory brain condition. Since the disease was first reported in 2010, an increasing number of anti-LGI1 antibody-positive cases have recently been described.11-15 However, there has been few large-scale epidemiological surveys of anti-LGI1 encephalitis in China. In this study, we provide detailed clinical information of 117 Chinese patients from 5 clinical centers who had positive LGI1 antibodies and report important incidence rates and long-term outcomes.
In the analysis of age distribution, we observed that the majority of patients were 40 to 70 years old (79%). Male patients were more common and this result is consistent with reported data on other autoimmune diseases. A total of 19 (16%) patients experienced a relapse in our cohort, indicating that the overall prognosis of anti-LGI1 encephalitis is good, and this finding is consistent with previous studies.1,8,11 A report from the United States on clinical syndrome and long-term follow-up of anti-LGI1 encephalitis stated that 67% of 21 patients who were followed up for more than 2 years had a favorable outcomes.4 These data are consistent with a good prognosis for anti-LGI1 encephalitis, although some differences may be related to race, region, and number of cases. Currently, research on the relationship between anti-LGI1 antibody titer and disease is still lacking, and research conducted with a large sample size is still needed for further exploration. From our perspective, the detection of anti-LGI1 antibody seems to be higher in serum.
In the last few decades, the field of autoimmune epilepsy has received increasing attention with the discovery of different subtypes of neural autoantibodies.5,16-19 In the latest 2017 epilepsy classification, autoimmune epilepsy has been recognized as a distinct entity by the International League Against Epilepsy.20 Most patients with autoimmune epilepsy present with seizures, cognitive decline, and behavioral or psychiatric dysfunction. At present, the diagnosis of autoimmune epilepsy is based on clinical characteristics, MRI results, EEG and CSF analyses. Faciobrachial dystonic seizures is considered to be the characteristic clinical symptom of anti-LGI1 encephalitis epilepsy.4,13,21 Faciobrachial dystonic seizures usually manifest as involuntary movements involving posturing of the arm and the ipsilateral hemiface or leg, occur very briefly and frequently, and respond well to immunotherapy. The treatment for patients with autoimmune epilepsy is comprised of immunotherapy and symptomatic therapy including antiseizure medications. According to multiple previous studies, the favorable effects of immunotherapy has been demonstrated to be an early initiation on seizure frequency and cognition. Immunotherapy is classically divided into first-line and second-line therapies. First-line therapies include methylprednisolone, IVIG, or plasma exchange. Second-line therapies (rituximab, mycophenolate, cyclophosphamide, azathioprine) are used in refractory cases or as a maintenance therapy to prevent relapses. The treatment of autoimmune epilepsy should be based on the severity of the clinical course. Immunotherapy plays a key role in the treatment of autoimmune epilepsy.3,5,16,22-24 A study of 29 patients with anti-LGI1 encephalitis by Sarosh et al. found that immunotherapies showed a remarkable reduction in FBDS frequency21. Among 27 patients receiving immunotherapy, 14 patients (52%) showed a > 50% reduction in seizure frequency.4 Our current research partly confirms the above findings. In our series, after 3-5 days of immunotherapy, seizures were alleviated in all the patients. This suggests the importance of immunotherapy in LGI1-related seizures. Immunotherapy should be applied in the early stage after the diagnosis of anti-LGI1 encephalitis. However, the timing of the withdrawal of immunosuppressive drugs and antiepileptic drugs in patients with different types of autoimmune encephalitis remains controversial. In our study, except for patients with relapse, steroids were maintained for 6 months. Fifteen out of 109 patients undergoing immunotherapy experienced a relapse in long-term follow-up. The reason for a relapse in some patients was irregular medication. Our report provides detailed long-term follow-up data of patients to provide useful insights for improving understanding of the disease experience of patients with anti-LGI1 encephalitis, and to better inform clinical management.
Relapses were not common in our cohort. The definition of relapse in our study was based on observations of clinical symptoms. When monitoring and evaluating the relapses, the MRI findings were not remarkable. According to previously research, the serum or CSF antibody titer did not correlate with the clinical severity perfectly. Furthermore, AE-related antibody monitoring is not routinely performed during follow-up, and better indicators should be identified in future studies. In our cohort, the brain MRIs of only 3 (3/19) patients showed abnormal signals at the onset. This is consistent with previous reports.4,5,13,19 Interestingly, we observed that a large number of EEG slow waves or intermittent spikes were detected at onset in 12 (12/19) relapsed patients. This may suggest the importance of EEG monitoring for disease recurrence. In our research, the follow-up duration was ranged from 22 to 47 months. Although, most patients experienced a first relapse within 24 months in our research, other studies have also suggested that AE relapse could occur years after the initial episode. As a result, extended follow-up may be essential.