Approach

Encephalitis is one of the most challenging syndromes to diagnose and manage, particularly because a specific pathogen is identified in less than 50% of cases.[3]

Diagnostic difficulties in establishing an aetiology include the vast number of infectious and non-infectious causes, and misperceptions about molecular versus serological testing.[3]

An individualised diagnostic approach is indicated, based on consideration of:[3]

  • Immune status

  • Seasonality

  • Geography

  • Animal and arthropod exposures

  • Clinical findings, and

  • Radiographic abnormalities

History

A recent history of tick bite in disease-endemic areas, 4-28 days before the onset of symptoms is critical to diagnosis.[10] However, about one-third of patients do not notice the tick bite.[13]

Tick-borne encephalitis (TBE) occurs throughout the northern hemisphere between June and October, with a peak in July, and mirrors the geographical distribution of the usual vector, Ixodes species ticks.[10][14]​​

Most infections result from tick bites acquired in forested areas through activities such as camping, hiking, fishing, bicycling, and collecting mushrooms, berries, or flowers. Outdoor occupations such as forestry and military training increase the risk of TBE.[11]

Consumption of raw (unpasteurised) milk or dairy products in disease-endemic areas are also significant risks for exposure.[8][15]​​​​

The risk is negligible for people who live in urban or unforested areas, or who do not consume unpasteurised dairy products.[11]

Clinical presentation

TBE follows an incubation period of a median of 8 days (range 2-28 days) after a tick bite.[11] Approximately two-thirds of patients are asymptomatic.[9][11]​​​​ The incidence and severity of disease are highest in people aged ≥50 years.[11]

TBE is biphasic in 72% to 87% of patients.[13] In the fever-myalgia phase (or first phase), patients may present with:[8][13]​​​​

  • Fever (99%)

  • Fatigue (63%)

  • General malaise (62%)

  • Headache and body pains (54%)

  • Nausea

Typical duration of this phase is 5 days (range 2-10 days).[13]

Following the fever-myalgia phase, there is typically a 7-day (range 1-21 days) symptom-free interval before the second phase.[13]

In the central nervous system phase (or second phase), patients may present with:[13]

  • Mild meningitis to severe encephalitis, with or without myelitis and spinal paralysis

  • Altered consciousness (approximately 33%)

  • Cranial and spinal nerve palsies (3% to 13%); cranial nerve involvement mainly associated with ocular, facial, and pharyngeal motor function

  • Vestibular and hearing defects

  • Seizures (<5%)

  • Flaccid poliomyelitis-like paralysis that, unlike poliomyelitis, usually affects the arms, shoulders, and levator muscles of the head

  • Monoparesis, paraparesis, and tetraparesis, paralysis of respiratory muscles requiring ventilator support (5% to 10%).

Typical duration of this second phase is 7-10 days.[8] 

The European subtype is associated with milder disease, with 20% to 30% of patients experiencing the second phase. In children, the second phase is generally limited to meningitis, whereas in adults aged >40 years, there is an increased risk of encephalitis.[9]

Initial investigations

In general, initial tests should be the same as for suspected viral encephalitis. These include:[2][20]​​

  • FBC

  • ESR and CRP

  • LFTs

  • CT brain

  • Cerebrospinal fluid (CSF) analysis (if no contraindications to lumbar puncture)

  • CSF/serum serology for TBE-specific antibodies (IgM and IgG).

Leukopenia, thrombocytopenia, and slightly raised serum transaminases can be seen in this first stage, although leukocytosis is frequent in the second stage.[13] Seroconversion without prominent morbidity is common.[13]

CSF analyses reveal moderate pleocytosis, with two-thirds of patients having ≤100 leukocytes per microlitre.[13] Despite this, objective meningeal signs can be absent in about 19%.[13]

An initial predominance of polymorphonuclear cells in the CSF is later changed to an almost 100% mononuclear cell dominance.[13] Two-thirds have a moderately increased CSF albumin, peaking at a median day 9.[13]

In the UK, testing can be arranged with the Rare and Imported Pathogens Laboratory if TBE is suspected.[9]

Other investigations

These include:

  • Serum or CSF can also be tested for the presence of TBE virus by reverse-transcription polymerase chain reaction (RT-PCR).[2][20]​​​​ However, RT-PCR is only useful in the first phase of the illness. Viral RNA is usually undetectable by the time neurological symptoms are recognised.[29]​​

  • CT head is useful in the emergency setting to evaluate for brain oedema before lumbar puncture.[2]

  • MRI head shows abnormalities in approximately 20% of infected patients. The most common MRI abnormalities are thalamus lesions: these can be unilateral or bilateral, multifocal or diffuse.[2]

  • EEG monitoring for seizures may be indicated in acutely unwell patients.[2]

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