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Background and purpose  Tick‐borne encephalitis (TBE) is a common viral disease in central Europe and Asia. Severe or even lethal neurological symptoms may ensue. With limited therapeutic options, active vaccination against the TBE virus (TBEV) is strongly recommended in endemic areas. A systematic analysis of the clinical picture and cerebral imaging findings associated with TBE was conducted with particular focus on patients who acquired TBE despite previous vaccination.    Methods  A cohort of 52 patients with serologically proven TBE treated at our centre in a 10‐year period who received at least one cerebral magnetic resonance imaging (MRI) was retrospectively described. Extension of MRI changes was systematically assessed by an experienced neuroradiologist. Standard statistical procedures were performed.    Results  Fifty‐two patients with a definite serological diagnosis of TBE were included. The most common presentation was encephalitis (67%). MRI showed TBE‐associated parenchymal lesions in 33% of all patients. Sites of predilection included the periaqueductal grey, the thalamus and the brainstem. Ten patients had received at least one prior active or passive TBEV immunization. All of these had a maximal Rankin Scale score of at least 4. The median number of affected anatomical regions on MRI was significantly higher than in the non‐vaccinated cohort.    Conclusions  To our knowledge, this is the first study systematically describing the peculiarities of MRI in patients vaccinated against TBE. In addition to a severe clinical course, they exhibit more extensive MRI lesions than a non‐vaccinated cohort. Possible reasons for these findings include incomplete seroconversion, more virulent TBEV strains or antibody‐dependent enhancement.

Patients with breakthrough tick‐borne encephalitis suffer a more severe clinical course and display extensive magnetic resonance imaging changes