Clinical characteristics, long-term functional outcomes and relapse of anti-LGI1/Caspr2 encephalitis: a prospective cohort study in Western China

Abstract

Objective: To study the clinical characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and anti-contactin-associated protein-like 2 (Caspr2) encephalitis and to investigate factors associated with poor long-term neurological functional outcomes and relapse among patients in western China.

Methods: In this single-center prospective cohort study, we consecutively enrolled patients with anti-LGI1 encephalitis and anti-Caspr2 encephalitis from April 2014 to February 2021. Patient outcomes were assessed using the modified Rankin scale. Predictors of long-term functional outcomes and relapse were analyzed.

Results: Forty-four anti-LGI1 encephalitis patients [median age: 44 years, range: 18-82 years; females: 25 (56.8%)], 35 anti-Caspr2 encephalitis patients [median age: 43 years, range: 14-80 years; females: 19 (54.3%)], and 5 dual-positive patients [median age: 44 years, range: 36-58 years; females: 5 (100%)] were enrolled. Overall, 86.4% anti-LGI1 encephalitis patients and 80% anti-Caspr2 encephalitis had a favorable neurological functional outcome (mRS 0-2). Tumor occurrence and weight loss were associated with poor long-term functional outcomes in anti-LGI1 encephalitis, whereas in anti-Caspr2 encephalitis, predictors included behavioral disorder at acute phase, abnormalities in brain magnetic resonance imaging, higher modified Rankin scale scores at onset, poor response to the initial immunotherapy at 4 weeks, age at onset<30 years, and relapse (p<0.05). Overall, 13.6% of anti-LGI1 encephalitis patients and 20% of anti-Caspr2 encephalitis patients had at least one relapse. Sleep disorder at the acute phase was the risk factor of relapse in anti-LGI1 encephalitis, while female, age at onset <30 years, and behavioral disorder at acute phase were the risk factors of relapse in anti-Caspr2 encephalitis (log rank p<0.05).

Conclusion: The clinical characteristics such as age, gender, and tumor occurrence rates of anti-LGI1 encephalitis and anti-Caspr2 encephalitis in western China are different from those in the Western countries. Most patients in our study had favorable long-term functional outcomes. The relapse rates are still high in both types of encephalitis, which warrants caution.

Keywords: Autoimmune encephalitis; Caspr2; Cohort studies; LGI1; Prospective.

Figure 1.

Demographic, clinical manifestations, and functional outcomes evaluated at different follow-up points (3, 6, 9, 12, 18, 24 months after disease onset) of patients with anti-LGI1 encephalitis and anti-Caspr2 encephalitis. The distributions of patients by age and sex in anti-LGI1 encephalitis (a) and anti-Caspr2 encephalitis (b). The proportions of anti-LGI1 encephalitis patients (c) and anti-Caspr2 encephalitis patients (d) with cumulative clinical symptoms stratified by different ages at onset. The modified Rankin scale scores at different follow-up points in patients with anti-LGI1 encephalitis (e) and anti-Caspr2 encephalitis (f).

Figure 2.

Disease and treatment courses in 13 patients with relapses. Each line shows the disease course and the treatment of the patient with relapse. The triangles represent disease events, which included the disease initial onset and relapse episode. The numbers in the triangles and squares represent the modified Rankin scale scores during the event and at the last follow-up, respectively. AZA, oral prednisone; Caspr2, contactin-associated protein-like 2; CTX, cyclophosphamide; IVIG, IV immunoglobulin; IVMP, IV methylprednisolone; LGI1, leucine-rich glioma-inactivated 1; MMF, mycophenolate mofetil.

Figure 3.

Kaplan–Meier curves showing the relapse rate over time in patients with anti-LGI1 encephalitis and anti-Caspr2 encephalitis. Kaplan–Meier curve shows that anti-LGI1 encephalitis patients with sleep disorder (log rank p = 0.041) had an increased risk of relapse (a). Kaplan–Meier curves show that anti-Caspr2 encephalitis patients with behavioral disorder (log rank p = 0.041), age at onset<30 years (log rank p = 0.013), and female patients (log rank p = 0.035) had an increased risk of relapse (b–d).