Long-term patient-reported neurocognitive and functional outcomes after tick-borne encephalitis: a prospective controlled multicenter cohort study

OBJECTIVE: To characterize cognitive symptoms the first year after tick-borne encephalitis (TBE). METHODS: We conducted a controlled, multicenter cohort study of 109 hospitalized patients ≥16 years with confirmed TBE in Norway. At 3 and 12 months after admission, patients completed BRIEF-A (Global Executive Composite (GEC) and subscales), Everyday Memory Questionnaire-Revised (EMQ-R), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessing executive functioning, memory, and post-TBE symptoms (higher scores indicate more difficulties). The primary outcomes were within-patient change in questionnaire scores from 3 to 12 months, and 12-month scores in patients compared to controls. The secondary outcomes were BRIEF-A subscale scores and proportion with clinically significant impairment. Covariates included in the analyses were age, sex, comorbidities, acute disease severity, anxiety, and depression. RESULTS: There were no significant changes from 3 to 12 months. At 12 months, scores were within the normal range, but patients had higher EMQ-R and RPQ than controls (p<0.001). BRIEF-A GECs did not differ, but patients had higher working memory subscale scores (p=0.002). These differences persisted after adjustment for anxiety and depression. Clinically significant impairment was more frequent in patients (odds ratios 2.29-8.19). Comorbidities, acute disease burden, anxiety, depression and female sex were associated with unfavorable 12 month outcome. CONCLUSION: TBE patients have an overall good one-year prognosis, but a minority-characterized by higher acute disease burden and comorbidities-have persistent cognitive difficulties that may warrant follow-up. Anxiety and depression were related to unfavorable prognosis but did not account for the cognitive differences between patients and controls. TRIAL REGISTRATION: Project #2,296,959-The NOrwegian Tick-borne Encephalitis Study-NOTES. An Observational Study on Clinical Features, Long-term Outcomes and Immune Characteristics-Cristin.