Diagnostics
Recommended diagnostic criteria for a confirmed case of TBE are given in Box 1. In addition to clinical symptoms of infection in the central nervous system, inflammatory markers are usually present in the serum. Leucocytosis is common, while the CRP level tends to be normal or only slightly elevated (4, 5, 7, 10).
Box 1 Recommended diagnostic criteria for a confirmed case of TBE (12).
Clinical symptoms of infection in the central nervous system
Pleocytosis in spinal fluid (> 5 × 106 cells/L)
At least one microbiological criterion:
Presence of specific IgM and IgG antibodies in serum
Presence of specific IgM antibodies in spinal fluid
Significant increase in IgG antibodies in two consecutive serum samples
Detection of TBE virus RNA
A lumbar puncture is needed to make the diagnosis. Moderate pleocytosis with lymphocytic predominance is classic, but early in the course, polymorphonuclear cells can be predominant (2). Albumin and protein levels are usually within the normal range, and elevated values correlate with the presence of encephalitis (4, 5, 7).
Detection of antibodies in the serum is the cornerstone of microbiological diagnostics (12). Specific antibodies are absent in the initial phase of the illness but are present when symptoms of central nervous system infection occur. Negative serology early in the course of the disease does not therefore rule out TBE. IgM antibodies have the highest sensitivity and can be detected in the majority of patients at the time of admission (7, 9). When only IgM antibodies are initially detected, a control sample should be taken after 10–14 days to confirm the development of IgG antibodies.
Antibody testing in spinal fluid is not routinely recommended, but the detection of intrathecally produced IgM antibodies is diagnostic in cases of suspected vaccine failure (12).
The TBE virus RNA can be detected by PCR examination in blood during the initial phase of the illness, but the test has low sensitivity and is not routinely performed in spinal fluid (12).
Microbiological diagnostics are indicated in order to rule out differential diagnoses requiring treatment, such as herpes virus and varicella encephalitis, neuroborreliosis and bacterial meningitis. Coinfection with Borrelia burgdorferi can occur (4, 9).
EEG usually supports the diagnosis in cases of meningoencephalitis (8, 13). An increased amount of slow background activity is the most common pathological finding, while other focal activity in the EEG is unusual (8, 13).
Diagnostic imaging such as MRI or CT scans are most beneficial in cases of acute and severe symptoms, primarily to rule out differential diagnoses that may require urgent treatment, for example intracranial bleeding, infarction or abscess. In TBE, any findings on a head MRI tend to be localised in the thalamus and basal ganglia, but these findings have low diagnostic specificity (12, 13).
Two examples of the aforementioned diagnostics and clinical presentations are presented in the case studies in Boxes 2 and 3.
Box 2
Patient 1
A boy of lower secondary school age developed a headache and a high fever in late summer. His condition deteriorated, with symptoms of unsteadiness, nausea, light sensitivity and impaired fine motor skills. Upon admission, he was clinically stable but had a stiff neck and exhibited noticeable behaviour changes. A head MRI was normal except for increased leptomeningeal enhancement, as seen in meningitis. A lumbar puncture revealed mononuclear pleocytosis as well as elevated levels of albumin and protein. Empiric therapy for acute encephalitis and neuroborreliosis was initiated. The boy developed spasticity, hyperreflexia and inverted plantar reflex. A standard panel for microbiological diagnostics in spinal fluid did not provide evidence of an etiological agent. An EEG performed on day three showed pathological findings with episodic slow activity. On the same day, IgM and IgG antibodies against the TBE virus were detected in the serum, consistent with TBE. The boy's travel history revealed that he had spent time in a known high-risk infection area prior to admission, but without a known tick bite. He was discharged after clinical improvement on day four. A three-week EEG still showed persistent abnormalities, while the neurological examination showed normal results after five weeks and EEG after eight weeks.
Box 3
Patient 2
In early autumn, an otherwise healthy boy of preschool age, living in a high-risk infection area, was admitted after a four-day medical history of reduced general condition, vomiting, low-grade fever, lethargy and headaches. A week earlier, he had experienced transient cold-like symptoms. Upon clinical examination, he appeared unwell and feverish, but without a rash, neck stiffness, light sensitivity or obvious focal neurological deficits. Initial blood tests showed only slightly elevated infection parameters. A lumbar puncture revealed mild pleocytosis with a predominance of mononuclear cells. He was initially treated with acyclovir and ceftriaxone for a suspected central nervous system infection. Microbiological diagnostics in spinal fluid, including PCR examination for neurotropic viruses, bacterial culture and Lyme serology were negative, but IgM and IgG antibodies against the TBE virus were detected in the serum. Family members had not observed a tick bite, but clinical and laboratory findings were consistent with TBE with meningitic presentation. Antimicrobial treatment was discontinued, and the boy was discharged after clinical improvement on day three after admission. Family members reported four months later that he had fully recovered.