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.