Encephalitis, Tick-Borne

Essentials of Diagnosis

• Flaviviral encephalitis found in Eastern, Central, and occasionally Northern Europe and Asia

• Transmitted via ticks or ingestion of unpasteurized milk

• Long-term neurologic sequelae occur in 2–25% of cases

General Considerations

• Occurs predominantly in the late spring through fall

• Usually a consequence of exposure to infected ticks

• Unpasteurized milk from viremic livestock is also a recognized form of transmission

• Transmission by transplantation of solid organs is reported leading to fatal outcomes

• The principal reservoirs for tick-borne encephalitis (TBE) virus are ticks with small rodents as amplifying host; humans are an accidental host

• Incubation period for tick-borne exposures is 7–14 days but only 3–4 days for milk ingestion

• There are three subtypes

  • European subtype, transmitted by I ricinus

  • Siberian subtypes, transmitted by I persulcatus

  • Far Eastern subtypes, transmitted by I persulcatus

• Powassan virus

  • Only North American member of the tick-borne encephalitis

  • Vector is several Ixodes species ticks

  • Incubation period can range from 1 to 5 weeks

  • Most reported cases are neuroinvasive

• Alkhurma hemorrhagic fever

  • A flavivirus first uncovered in Jeddah, Saudi Arabia in 1995

  • Reemerging in the Middle East with occurrences in tourists to Egypt, Djibouti, and possibly India

  • Its extent of geographic distribution is currently unknown

Demographics

• Virus is endemic in certain parts of Europe and Asia

• The number of cases reported annually fluctuates significantly depending on surveillance, human activities, socioeconomic factors, ecology, and climate

Symptoms and Signs

• Most cases are subclinical

• Many cases resemble a flu-like syndrome with 2–10 days of fever (usually with malaise, headache, and myalgias)

• In some cases, the disease is biphasic where the initial flu-like period is followed by a 1- to 21-day symptom-free interval followed by a second phase with fevers and neurologic symptoms

• Neurologic manifestations range from febrile headache to aseptic meningitis and encephalitis with or without myelitis (preferentially of the cervical anterior horn) and spinal paralysis (usually flaccid)

• A myeloradiculitic form can also develop but is less common

• Peripheral facial palsies, sometimes bilateral, tend to occur infrequently late in the course of infection, usually after encephalitis and usually are associated with a favorable outcome within 30–90 days

• Mortality in TBE is usually a consequence of brain edema or bulbar involvement

• European subtype is usually milder with up to 2% mortality and 30% neuroinvasive disease

• Siberian subtype is associated with 3% mortality and chronic, progressive disease

• Far Eastern subtype is usually more severe with up to 40% mortality and higher likelihood of neurologic involvement

• All three subtypes are more severe among the elderly and usually less severe among children

• Coinfection with Borrelia burgdorferi (the agent of Lyme disease; transmitted by the same tick vector) may result in more severe disease

Differential Diagnosis

• Other causes of aseptic meningitis such as enteroviral infections, poliomyelitis (no longer reported from Eastern Europe), herpes simplex encephalitis

• Tularemia, the rickettsial diseases, babesiosis, Lyme disease, and other flaviviral infections

• Coinfections are documented with Anaplasma, Babesia, and Borrelia

Laboratory Findings

• No laboratory test can distinguish between the subtypes, although an enzyme immunoassay shows promise

• Leukocytosis and neutrophilia are common

• Hyponatremia is more commonly seen than with other viral encephalitides

• Abnormal cerebrospinal fluid findings include a pleocytosis that may persist for up to 4 months

• When neurologic symptoms develop, the TBE virus is typically no longer detectable in blood and CSF samples

• Virus detection by reverse transcriptase-polymerase chain reaction (RT-PCR) in ticks from TBE patients, if available, can help with the diagnosis

• TBE virus IgM and IgG are detected by enzyme-linked immunosorbent assay (ELISA) when neurologic symptoms occur

• Cross-reactivity with other flaviviruses or a vaccinated state may require confirmation by detection of TBE virus–specific antibodies by plaque-reduction neutralization tests

Imaging Studies

• Neuroimaging shows hyperintense lesions in the thalamus, brainstem, basal ganglia, and cerebral atrophy

• Therapy is largely supportive

• No specific antiviral treatment

Complications

• The main sequela is paresis

• Other causes of long-term morbidity include

  • Protracted cognitive dysfunction

  • Persistent spinal nerve paralysis

• The postencephalitic syndrome occurs with both subtypes and is characterized by

  • Headache

  • Difficulties concentrating

  • Balance disorders

  • Dysphasia

  • Hearing defects

  • Chronic fatigue

• A progressive motor neuron disease and partial continuous epilepsy are complications seen with the Eastern subtype

• Long-standing psychiatric complications include

  • Attention deficits

  • Slowness of thought and learning impairment

  • Depression

  • Lability

  • Mutism

Prevention

• There is no available TBE vaccine in the United States

• There are four inactivated TBE virus vaccines for adults and children licensed in Europe and 1 available in China

  • Vaccine is safe, effective, and should provide cross-protection against all three TBE virus subtypes

  • The initial vaccination schedule requires two to three doses given over 6 or more months with boosters every 1–5 years

  • Recent data support adding an extra booster vaccine dose for individuals aged 50 years and older

  • Complications of vaccine include

    • Neuritis

    • Neuropathies of peripheral nerves (plexus neuropathy—paresis of lower limb muscles, polyradiculopathy)

Prognosis

• The three subtypes of TPE have different prognoses

  • European subtype is usually milder with up to 2% mortality and 30% neuroinvasive disease

  • Siberian subtype is associated with 3% mortality and chronic, progressive disease

  • Far Eastern subtype is usually more severe with up to 40% mortality and higher likelihood of neurologic involvement

• All three subtypes are more severe among elderly adults compared with children

• Coinfection with Borrelia burgdorferi (the agent of Lyme disease; transmitted by the same tick vector) may result in more severe disease

• Mortality is usually a consequence of brain edema or bulbar involvement