Prevalence of Autoimmune Encephalitis in Herpes Simplex Encephalitis Explored

CT scan showing encephalitis
CT scan showing encephalitis
A significant risk factor for autoimmune encephalitis was antibody detection within a 3-week period of herpes simplex encephalitis.

Autoimmune encephalitis develops in approximately one-third of patients with herpes simplex encephalitis within a 3-month period of completing antiviral treatment, according to study results published in Lancet Neurology. Age appears to be associated with neurologic symptoms, immunotherapy response, and long-term outcome in these patients, with older patients experiencing worse outcomes compared with younger patients.

Researchers enrolled patients with clinically confirmed herpes simplex encephalitis who were receiving care at 19 secondary and tertiary centers in Spain (n=54). Patients were followed up to 2 months, 6 months, and 12 months from disease onset. In another cohort, investigators retrospectively enrolled patients who developed post-herpes autoimmune encephalitis (n=51). Clinical and demographic features were compared between patients who developed autoimmune encephalitis vs patients who did not. Comparisons were also stratified by age, with patients age ≤4 compared with patients age >4. Post-herpes autoimmune encephalitis risk factors were also assessed in the retrospective cohort.

In the retrospective cohort, a total of 14 patients (27%) developed autoimmune encephalitis after herpes simplex encephalitis, with 100% of these patients featuring neuronal antibodies at or prior to symptom onset. Of the remaining 37 patients who did not develop autoimmune encephalitis, a total of 11 (30%) patients had antibodies to NMDAR (n=3) or unknown antigens (n=8) (P <.001).

A significant risk factor for autoimmune encephalitis was antibody detection within a 3-week period of herpes simplex encephalitis (odds ratio [OR] 11.5; 95% CI, 2.7-48.8; P <.001). Patients age ≤4 were significantly more likely to experience a shorter median of days between herpes onset and autoimmune encephalitis onset when compared with patients age >4 (26 days [interquartile range 24-32] vs 43 days [interquartile range 25-54], respectively; P =.0073). In addition, individuals age ≤4 were more likely to have choreoathetosis (27 [100%] of 27 vs 0 of 31, respectively; P <.001), decreased level of consciousness (96% vs 23%, respectively; P <.001), NMDAR antibodies (89% vs 61%, respectively; P =.033), and significantly worse 1-year outcome (median modified Rankin Scale 4 [IQR 4-4] vs 2 [2-3], respectively; P <.0010; seizures 63% vs 13%, respectively; P =.001) compared with patients age <4.

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Limitations of the analysis include the relatively small number of patients in each cohort and the use of a clinician-based questionnaire to obtain retrospective data for one of the cohorts.

“Autoimmune encephalitis should be strongly considered in patients who, within this timeframe, develop new neurological or psychiatric symptoms, characterized in younger children by choreoathetosis,” the researchers wrote, “and in older children and adults by cognitive and behavioral impairment or psychosis.”


Armangue T, Spatola M, Vlagea A, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis [published online July 23, 2018]. Lancet Neurol. doi:10.1016/S1474-4422(18)30244-8