Viral encephalitis is an inflammation of the brain caused by a virus. Some viral diseases, such as measles and rubella, can also progress to involve inflammation of the brain. Other micro-organisms, such as bacteria, fungi and parasites, are capable of triggering encephalitis, but viruses – particularly the group known as enteroviruses – are the leading cause.

Once inside the blood, the viruses migrate to the brain where they start to multiply. The body notices the invasion and mounts an immune system response. This causes the brain to swell. The combination of infection and immune response creates the typical symptoms of viral encephalitis.

The most serious potential complication from viral encephalitis is permanent brain damage. Children aged under one year and adults aged over 55 years are more vulnerable to life-threatening complications.

A number of different viruses and subviral particles can cause diseases that affect the nervous system. Viral diseases tend to be more common than bacterial infections of the nervous system today. Fortunately, viral infections are generally milder than their bacterial counterparts and often spontaneously resolve. Some of the more important acellular pathogens of the nervous system are described in this section.

Viral Meningitis

Although it is much more common than bacterial meningitis, viral meningitis is typically less severe. Many different viruses can lead to meningitis as a sequela of the primary infection, including those that cause herpes, influenza, measles, and mumps. Most cases of viral meningitis spontaneously resolve, but severe cases do occur.

Arboviral Encephalitis

Several types of insect-borne viruses can cause encephalitis. Collectively, these viruses are referred to as arboviruses (because they are arthropod-borne), and the diseases they cause are described as arboviral encephalitis. Most arboviruses are endemic to specific geographical regions. Arborviral encephalitis diseases found in the United States include eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis, and West Nile encephalitis (WNE). Expansion of arboviruses beyond their endemic regions sometimes occurs, generally as a result of environmental changes that are favorable to the virus or its vector. Increased travel of infected humans, animals, or vectors has also allowed arboviruses to spread into new regions.

In most cases, arboviral infections are asymptomatic or lead to a mild disease. However, when symptoms do occur, they include high fever, chills, headaches, vomiting, diarrhea, and restlessness. In elderly patients, severe arboviral encephalitis can rapidly lead to convulsions, coma, and death.

Mosquitoes are the most common biological vectors for arboviruses, which tend to be enveloped ssRNA viruses. Thus, prevention of arboviral infections is best achieved by avoiding mosquitoes—using insect repellent, wearing long pants and sleeves, sleeping in well-screened rooms, using bed nets, etc.

Diagnosis of arboviral encephalitis is based on clinical symptoms and serologic testing of serum or CSF. There are no antiviral drugs to treat any of these arboviral diseases, so treatment consists of supportive care and management of symptoms.

Eastern equine encephalitis (EEE) is caused by eastern equine encephalitis virus (EEEV), which can cause severe disease in horses and humans. Birds are reservoirs for EEEV with accidental transmission to horses and humans by Aedes, Coquillettidia, and Culex species of mosquitoes. Neither horses nor humans serve as reservoirs. EEE is most common in US Gulf Coast and Atlantic states. EEE is one of the more severe mosquito-transmitted diseases in the United States, but fortunately, it is a very rare disease in the United States.

Western equine encephalitis (WEE) is caused by western equine encephalitis virus (WEEV). WEEV is usually transmitted to horses and humans by the Culex tarsalis mosquitoes and, in the past decade, has caused very few cases of encephalitis in humans in the United States. In humans, WEE symptoms are less severe than EEE and include fever, chills, and vomiting, with a mortality rate of 3–4%. Like EEEV, birds are the natural reservoir for WEEV. Periodically, for indeterminate reasons, epidemics in human cases have occurred in North America in the past. The largest on record was in 1941, with more than 3400 cases.

(a) A false color TEM of a mosquito salivary gland cell shows an infection of the eastern equine encephalitis virus (red). (b) CT (left) and MRI (right) scans of the brains of children with eastern equine encephalitis infections, showing abnormalities (arrows) resulting from the infection.

St. Louis encephalitis (SLE), caused by St. Louis encephalitis virus (SLEV), is a rare form of encephalitis with symptoms occurring in fewer than 1% of infected patients. The natural reservoirs for SLEV are birds. SLEV is most often found in the Ohio-Mississippi River basin of the central United States and was named after a severe outbreak in Missouri in 1934. The worst outbreak of St. Louis encephalitis occurred in 1975, with over 2000 cases reported. Humans become infected when bitten by C. tarsalis, C. quinquefasciatus, or C. pipiens mosquitoes carrying SLEV. Most patients are asymptomatic, but in a small number of individuals, symptoms range from mild flu-like syndromes to fatal encephalitis. The overall mortality rate for symptomatic patients is 5–15%.

Japanese encephalitis, caused by Japanese encephalitis virus (JEV), is the leading cause of vaccine-preventable encephalitis in humans and is endemic to some of the most populous countries in the world, including China, India, Japan, and all of Southeast Asia. JEV is transmitted to humans by Culex mosquitoes, usually the species C. tritaeniorhynchus. The biological reservoirs for JEV include pigs and wading birds. Most patients with JEV infections are asymptomatic, with symptoms occurring in fewer than 1% of infected individuals. However, about 25% of those who do develop encephalitis die, and among those who recover, 30–50% have psychiatric, neurologic, or cognitive impairment. Fortunately, there is an effective vaccine that can prevent infection with JEV. The CDC recommends this vaccine for travelers who expect to spend more than one month in endemic areas.

As the name suggests, West Nile virus (WNV) and its associated disease, West Nile encephalitis (WNE), did not originate in North America. Until 1999, it was endemic in the Middle East, Africa, and Asia; however, the first US cases were identified in New York in 1999, and by 2004, the virus had spread across the entire continental United States. Over 35,000 cases, including 1400 deaths, were confirmed in the five-year period between 1999 and 2004. WNV infection remains reportable to the CDC.

WNV is transmitted to humans by Culex mosquitoes from its natural reservoir, infected birds, with 70–80% of infected patients experiencing no symptoms. Most symptomatic cases involve only mild, flu-like symptoms, but fewer than 1% of infected people develop severe and sometimes fatal encephalitis or meningitis. The mortality rate in WNV patients who develop neurological disease is about 10%. More information about West Nile virus can be found in Modes of Disease Transmission.

The symptoms of viral encephalitis include:

• high temperature
• headache
• sensitivity to light (photophobia)
• general malaise
• stiff neck
• stiff back
• vomiting
• changes to personality
• confusion
• memory loss (amnesia)
• seizures
• paralysis
• coma

Some of the viruses that are capable of causing encephalitis include:

• enteroviruses – such as coxsackievirus, poliovirus and echovirus
• herpes simplex virus
• varicella zoster virus
• Epstein-Barr virus
• cytomegalovirus
• adenovirus
• rubella
• measles
• Murray Valley encephalitis (MVE) virus and Kunjin virus
• Japanese encephalitis virus.

Viruses spread by different means, and some are more infectious than others. Some of the modes of viral transmission include:

• coughs or sneezes from an infected person that release airborne viruses, which are then inhaled by others
• infected insects (such as mosquitoes or ticks) and animals, which can transfer some viruses directly into the bloodstream via their bite
• eating contaminated food or drink
• the transfer of some viruses can occur through touching an infected person
• there is evidence to suggest that some cases of viral encephalitis are caused by a dormant viral infection (such as herpes simplex virus) becoming active again.

Once viruses have gained access to the bloodstream, they can multiply and spread to other parts of the body, including to the spinal cord and brain (the central nervous system). Access to the brain is by blood or nerves. After breaching the blood–brain barrier, the viruses slip inside brain cells. This disrupts, damages and ultimately ruptures the infected brain cells.

Certain viruses have a preference for different areas of the brain. For example, the herpes simplex virus likes to target the temporal lobes located near each ear.

The cells of the immune system rush to the brain and start attacking the viruses. This causes the characteristic brain swelling (cerebral oedema). Both the infection and the attempts of the body to fight the infection are responsible for the symptoms of viral encephalitis.

Babies, older people and people with reduced immunity are at increased risk of developing complications of viral encephalitis. Some of these complications include:

• low blood pressure (hypotension)
• low oxygen levels in the blood (hypoxemia)
• bleeding inside the brain (intracerebral hemorrhage)
• permanent brain damage
• death

Viral encephalitis is diagnosed using a number of tests including:

• physical examination
• blood tests
• laboratory examination of cerebrospinal fluid (clear liquid that bathes the brain and spinal cord) removed via a lumbar puncture (a procedure in which a small needle is inserted into the lower part of the spine)
• computed tomography (CT) scan
• electroencephalography (EEG) to measure brain waves
• magnetic resonance imaging (MRI).

Unlike bacteria, viruses are difficult to treat. Antiviral medications only work on a limited number of viruses. Treatment aims to reduce the severity of the symptoms and may include:

• hospitalisation
• antiviral medication, given intravenously, if the virus is known to be susceptible to treatment with antiviral medication (such as the herpes simplex virus)
• intravenous administration of medications to help reduce brain swelling
• pain-relieving medication
• medication to prevent vomiting
• medication to prevent seizures (anticonvulsant)
• medication to reduce fever, such as paracetamol
• fluids to prevent dehydration, but not too much as this can worsen cerebral oedema (swelling of the brain).

The severity of viral encephalitis depends on the particular virus and how quickly treatment was given. Generally, the acute phase of the illness lasts around one or 2 weeks, and the symptoms either disappear quickly or subside slowly over a period of time.

In many cases, the person makes a full recovery. In other cases, the person can be left with varying degrees of brain damage, which may require long-term supportive care and therapy.