Epidemiology

• The estimated annual incidence of encephalitis in the UK is 4 per 100,000.¹
• Infections are most frequent and severe in children and the elderly.
• Herpes simplex can cause a benign lymphocytic meningitis in adults, but usually produces a severe encephalitis in neonates. Infection in adults can also be very severe.
• Post-infectious encephalitis is the most common demyelinating condition and is most often seen in children, as it may complicate the common childhood exanthemas.

Aetiology

• HIV infection is of increasing importance; toxoplasmic meningoencephalitis was one of the first opportunistic infections to be described in HIV-infected patients.²
• Viral:
  • Viral encephalitis may be due either to:
    • Acute viral encephalitis (caused by a direct viral infection of the brain).
    • Post-infectious encephalitis (also called acute disseminated encephalomyelitis) which is an autoimmune process, following a viral infection elsewhere in the body.
  • Most viral infections in childhood are able to cause encephalitis.
  • The most common cause in the UK is herpes simplex.
  • Other common viral causes are herpes zoster, Epstein-Barr virus, mumps, measles and enteroviruses.
  • Other viral causes include cytomegalovirus, adenovirus, influenza virus, polio virus, rubella, rabies, arbovirus (e.g. California virus, Japanese B encephalitis, St Louis, West Nile encephalitis, eastern and western equine encephalitis), reovirus (Colorado tick fever virus), parvovirus B19.³
• Bacterial causes: tuberculosis, mycoplasma, listeria, Lyme disease, Bartonella henselae (cat scratch fever), leptospira, brucella, legionella, neurosyphilis, all causes of bacterial meningitis.
• Rickettsial: Rocky Mountain spotted fever, endemic typhus, epidemic typhus, Q fever, human monocytic ehrlichiosis.
• Fungal: cryptococcosis, coccidiomycosis, histoplasmosis, North American blastomycosis, candidiasis.
• Parasitic: African trypanosomiasis, toxoplasmosis, echinococcus, schistosomiasis, primary amoebic meningoencephalitis (see box below).

Presentation

Most patients with viral encephalitis present with the symptoms of meningitis (fever, headache, neck stiffness, vomiting) followed by altered consciousness, convulsions, and sometimes focal neurological signs, signs of raised intracranial pressure, or psychiatric symptoms. There may be an association with a history of infection elsewhere in the body.

• Encephalitis may begin with a flu-like illness or with a headache, followed by a rapid development of altered consciousness, with confusion, drowsiness, seizures and coma.
• Symptoms may also include symptoms of increased intracranial pressure such as severe headache, vertigo, nausea, convulsions and mental confusion. Other possible symptoms include photophobia, sensory changes and neck stiffness.
• Epilepsy, focal neurological signs and cognitive impairment may develop.
• Subacute sclerosing panencephalitis is a late complication of measles and presents four to ten years after the initial infection. Progression may be slow or rapid with personality change, dementia, seizures, ataxia and death. Progressive rubella panencephalitis is similar.

Differential diagnosis

• Meningitis
• Behcet's syndrome
• Systemic lupus erythematosus
• Post-vaccine encephalomyelitis
• Stroke
• Multiple sclerosis
• Syphilis
• Intracerebral tumour
• Leukaemia
• Lymphoma

In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy.⁵ Clues to the origin of the encephalitis may be ascertained from the presentation, e.g.:

• A history of recent foreign travel, contact with animals, insect bites, immune status and occupation may all give a clue to the infecting organism.
• Chickenpox encephalitis often has cerebellar involvement.
• Herpes simplex encephalitis is often associated with temporal lobe epilepsy.

Investigations

• Cerebrospinal fluid:
  • Viral encephalomyelitis leads to a variable pleocytosis (10-2000 cells/mm3). Mononuclear cells predominate.
  • CSF protein level is generally increased in encephalomyelitis and the proportion of IgG is increased.
  • Elevated CSF specific antibody levels relative to serum indicates CNS infection with the respective organism.
  • Polymerase chain reaction analysis of the CSF can be useful to diagnose several viral infections, including herpes simplex, Epstein-Barr, varicella zoster, cytomegalovirus, HIV, rabies and tuberculosis.⁶
• Full blood count and film: leucocytosis. May indicate atypical lymphocytes in Epstein-Barr viral infections, morulae of Ehrlichia, trypanosomes in trypanosomiasis, borreliae in relapsing fever, or the gametes of Plasmodium falciparum in malaria.
• Other blood tests should include blood cultures, renal function and electrolytes, liver function, glucose, ESR and CRP.
• Other cultures, e.g. throat swabs and stool cultures, may be indicated.
• CT scan:
  • Can help rule out space-occupying lesions, strokes, basilar fractures of the skull, and detect CSF leaks to localise fracture sites.
  • CT scan is also used to identify raised intracranial pressure, which will then need to delay a lumbar puncture.
• MRI scan:
  • Provides a sensitive detection of demyelination and can provide evidence of oedematous changes that occur in the early stage of encephalitis.
• Electroencephalogram (EEG):
  • Frequently abnormal (diffuse slowing with periodic discharges) in chronic and acute herpes simplex encephalitis and can sometimes help determine the localisation in the early stages.
  • Is more useful than a CT scan in the first week.

Management

• Urgent hospital admission.
• Immediate parenteral antibiotics for possible diagnosis of meningitis. Intravenous or intramuscular benzylpenicillin should be given as long as not allergic to penicillins.
• In any case of possible encephalitis, prompt treatment with aciclovir by intravenous infusion, to cover herpes simplex. Aciclovir can be life saving but must be started immediately the diagnosis is suspected. Aciclovir has been shown to greatly improve the prognosis if given before coma develops but any delay in starting treatment leads to a much worse prognosis.
• Pyrimethamine plus sulfadiazine, pyrimethamine plus clindamycin, and trimethoprim-sulfamethoxazole regimes are effective in treating some HIV-infected patients with toxoplasmic meningoencephalitis.²
• There is no specific treatment for other viral causes and the emphasis of treatment is supportive .
• Intravenous mannitol and dexamethasone to reduce cerebral oedema.
• Intravenous fluids need to be given very carefully in order not to aggravate cerebral oedema.
• Other treatments may include anti-convulsants and sedatives (to reduce agitation).
• Intensive care, including ventilation may also be necessary in severe cases to reduce brain swelling.
• Intravenous broad spectrum antibiotics to treat secondary bacterial infections.
• Acute disseminated encephalomyelitis is treated with high dose steroids, which may improve the outcome if started early enough.

Complications

• Inappropriate antidiuretic hormone secretion
• Disseminated intravascular coagulation
• Cardiac and respiratory arrest
• Epilepsy
• There are a broad range of potential neuropsychiatric impairments. Significant changes may occur in personality and in the ability to function even if there is a complete physical recovery. Residual impairment may be cognitive, behavioural or emotional and vary greatly in severity. Severe amnesic syndrome caused by profound damage to the temporal lobes may occur.
• Physical problems include mild balance, co-ordination and dexterity problems or major neurological problems with speech and swallowing problems and total dependency.

Prognosis

• The prognosis depends on the age of the patient and the underlying aetiology.
• The poorest prognosis for viral encephalitis occurs in patients with herpes simplex encephalitis and subacute sclerosing panencephalitis.

Prevention

• Some encephalitides can be reliably prevented by vaccination, e.g. Japanese encephalitis and rabies.⁶
• Vector control is the main method of prevention for some pathogens, e.g. arboviruses.

Document references

1. Encephalitis, Health Protection Agency
2. Dedicoat M, Livesley N; Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings).; Cochrane Database Syst Rev. 2006 Jul 19;3:CD005420. [abstract]
3. Barah F, Vallely PJ, Chiswick ML, et al; Association of human parvovirus B19 infection with acute meningoencephalitis.; Lancet. 2001 Sep 1;358(9283):729-30. [abstract]
4. Vargas-Zepeda J, Gomez-Alcala AV, Vasquez-Morales JA, et al; Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin. Arch Med Res. 2005 Jan-Feb;36(1):83-6. [abstract]
5. Chaudhuri A, Kennedy PG; Diagnosis and treatment of viral encephalitis.; Postgrad Med J. 2002 Oct;78(924):575-83. [abstract]
6. Whitley RJ, Gnann JW; Viral encephalitis: familiar infections and emerging pathogens.; Lancet. 2002 Feb 9;359(9305):507-13. [abstract]

Internet and further reading

• Encephalitis Information Resource
• Gondim FA, deOliveira GR, Thomas FP; Viral Encephalitis. eMedicine, Jan 2007.
• Oxford Textbook of Medicine 4th edition; Section 24.37; Viral infections of the central nervous system; D. A. Warrell and J. J. Farrar.

Acknowledgements