Viral encephalitis

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Viral encephalitis
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Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

Contents

Viral encephalitis can be diagnosed based on the individual's symptoms, personal history, such as travel history, and different clinical tests such as histology, medical imaging, and lumbar punctures. A differential diagnosis can also be done to rule out other causes of the encephalitis. Many encephalitic viruses often have characteristic symptoms of infection, helping to aid diagnosis. Treatment is usually supportive in nature while also providing antiviral drug therapy. The primary exception to this is herpes simplex encephalitis, which is treatable with acyclovir. Prognosis is good for most individuals who are infected by an encephalitic virus but is poor among those who develop severe symptoms, including viral encephalitis. Long-term complications of viral encephalitis typically relate to neurological damage, such as experiencing seizures, memory loss, and intellectual impairment.

Encephalitic viruses are typically transmitted either from person-to-person or are arthropod-borne viruses, called arboviruses. The young and the elderly are at the highest risk of viral encephalitis. Many cases of viral encephalitis are not identified either because of lack of testing or mild illness, and serological surveys indicate that asymptomatic infections are common. Various ways of preventing viral encephalitis exist, such as vaccines that are either in standard vaccination programs or which are recommended when living in or visiting certain regions, and various measures aimed at preventing mosquito, sandfly, and tick bites in order to prevent arbovirus infection.

Etiology

Many viruses are capable of causing encephalitis during infection, including: [1]

Transmission

Encephalitic viruses vary in their manner of transmission. Some are transmitted from person-to-person, whereas others are transmitted by animals, especially bites from arthropods such as mosquitos, sandflies, and ticks, such viruses being called arboviruses. [12] An example of person-to-person transmission is the herpes simplex virus, which is transmitted by means of intimate physical contact. [13] An example of arboviral transmission is the West Nile virus, which usually is incidentally transmitted to people from the bites of Culex mosquitos, especially Culex pipiens . [14]

Pathogenesis

Viruses that cause viral encephalitis first infect the body and replicate outside of the central nervous system (CNS). Thereafter, most reach the spinal cord and brain via the circulatory system. Exceptions to this include herpesviruses and the rabies virus, which travel from nerve endings to the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural cell function, including causing fluid buildup in the brain, vascular congestion, and bleeding. Widespread presence of white blood cells and microglia in the CNS is common as a response to CNS infection. For some forms of viral encephalitis, such as Eastern equine encephalitis and Japanese encephalitis, there may be a significant amount of necrosis of nerve cells. Following encephalitis caused by arboviruses, calcification may occur in the CNS, especially among children. Herpes simplex encephalitis tends to produce necrotic lesions in the CNS. [1]

Diagnosis

Examination

If viral encephalitis is suspected, then questions can be asked about the individual's history and physical examination can be performed. Important aspects of one's history include immune status, exposure to animals, including insects, travel history, vaccination history, geography, and time of year. Symptoms usually occur acutely, [4] and the most common symptoms of infection are fever, headache, altered mental status, sensitivity to light, stiff neck and back, vomiting, confusion, and, in severe cases, seizures, paralysis, and coma. Neuropsychiatric features such as behavioral changes, hallucinations, or cognitive decline are frequent. Severe symptoms are most common among infants and the elderly. Most infections are asymptomatic, lacking symptoms, whereas most symptomatic cases are mild illnesses. [1] [12]

Virus-specific symptoms may also exist or tests may indicate one virus. Specific examples include: [1]

Histology

The brain histology of viral encephalitis shows dead neurons with nuclear dissolution and elevated eosinophil count, called hypereosinophilia, within cells' cytoplasm when viewed with an optical microscope. Because encephalitis is an inflammatory response, inflammatory cells situated near blood vessels, such as microglia, macrophages, and lymphocytes, are visible. Virions within neurons are visible via electron microscopes. [1]

Clinical evaluation

Preferred diagnostic test according to suspected etiology. [4]
VirusPreferred diagnostic test
CytomegalovirusCSF PCR or CSF-specific IgM
Dengue/Chikungunya/ZikaCSF PCR or CSF-specific IgM
EnterovirusStool and throat PCR are preferred over CSF PCR
Epstein-Barr virusSerum EBV capsid antigen IgG and IgM (VCA)
and EBV nuclear antigen IgG (EBNA)
Herpes simplex virusCSF PCR, can be repeated within 2 to 7 days
of disease onset if negative with high clinical suspicion;
or CSF for HSV-IgG after 10–14 days of disease onset
HHV-6CSF PCR paired with serum PCR to exclude viral
integration into host DNA that causes false positives
InfluenzaCulture, antigen test, PCR of respiratory secretions
MeaslesCSF-specific IgG
Varicella-zoster virusCSF-specific IgG

Neuroimaging and lumbar puncture (LP) are both essential methods of diagnosing viral encephalitis. Computed tomography (CT) or magnetic resonance imaging (MRI) help identify increased intracranial pressure and the risk of uncal herniation before performing an LP. Cerebrospinal fluid (CSF), if analyzed, should be analyzed for opening pressure, cell counts, glucose, protein, and IgG and IgM antibodies. CSF testing should also include polymerase chain reaction (PCR) testing for herpes simplex viruses 1 and 2 and enteroviruses. About 10% of patients have normal CSF results. Additional testing, such as serology for various arboviruses and HIV testing, may also be performed based on the individual's history and symptoms. Brain biopsy and body fluid specimen cultures and PCR may also be useful in some cases. Electroencephalography (EEG) is abnormal in more than 80% of viral encephalitis cases, including those who are experiencing seizures, and may need to be monitored continuously to identify non-convulsive status. Lack of testing resources may prevent accurate diagnosis. [1] [4]

Test results specific to certain viruses include: [1]

Differential diagnosis

A broad differential diagnosis can be performed that looks at many potential causes of the encephalitis, infectious and noninfectious. Potential alternatives to viral encephalitis include malignancy, autoimmune or paraneoplastic diseases such as anti-NMDA receptor encephalitis, a brain abscess, tuberculosis or drug-induced delirium, exposure to certain drugs or toxins, neurosyphilis, vascular disease, metabolic disease, or encephalitis from infection caused by a bacterium, fungus, protozoan, or parasitic worm. [1] [6] [13] In children, differential diagnosis may not be able to distinguish between viral encephalitis and immune-mediated inflammatory CNS diseases, such as acute disseminated encephalomyelitis, as well as immune-mediated encephalitis, so other diagnostic methods may need to be used. [4]

Treatment

Treatment of viral encephalitis is primarily supportive with intravenous antiviral therapy due to there being no specific medical therapy for most viral infections involving the central nervous system. Individuals may require intensive care for frequent neurological exams or respiratory support, and treatment for electrolyte disturbance, autonomic disregulation, and renal and hepatic dysfunction, as well as for seizures and non-compulsive status epilepticus. [1] [4]

A very specific exception is herpes simplex virus (HSV) encephalitis, which can be treated with acyclovir for 2 to 3 weeks if it is provided early enough. Acyclovir significant decreases morbidity and mortality of HSV encephalitis and limits the long-term behavioral and cognitive impairments that occur with illness. As such, and because HSV is the most common cause of viral encephalitis, acyclovir is often administered as soon as possible to all patients suspected of having viral encephalitis even if the exact viral origin is not yet known. Viral resistance to acyclovir rarely occurs, primarily among the immunocompromised, in which case foscarnet should be used. Although not as effective, nucleoside analogs are used for other herpesviruses as well, such as acyclovir, with possible adjunctive corticosteroids for immunocompetent individuals, for varicella-zoster virus encephalitis and a combination of ganciclovir and foscarnet for cytomegalovirus encephalitis. [1] [13]

Serial intracranial pressure (ICP) is important to monitor as elevated ICP is associated with poor prognosis. Elevated ICP can be relieved with steroids and mannitol, though there is limited data of the efficacy of such treatment with regards to viral encephalitis. Seizures can be managed with valproic acid or phenytoin. Status epilepticus may required benzodiazepines. Antipsychotic drugs may be needed for a short time period if behavior alternations are present. Given the possibility of complications developing from viral encephalitis, an interdisciplinary team consisting of the clinicians, therapists, rehabilitation specialists, and speech therapists is important in order to help patients. [1]

Prognosis

If treated, most individuals recover from viral encephalitis without long-term problems related to the illness. Mortality rates vary for those who do not receive treatment, for example being about 70% for herpes encephalitis [13] but low for the La Crosse virus. Individuals who remain symptomatic after initial infection may have difficulty concentrating, behavior or speech disorders, or memory loss. Rarely, individuals may remain in a persistent vegetative state. The most common long-term complication of viral encephalitis is seizures that may occur in 10% to 20% of patients over several decades. These seizures are resistant to medical therapy. However, individuals who have unilateral mesial temporal lobe seizures after viral encephalitis have good results following neurosurgery. Prognoses related to specific viruses include: [1]

Other potential complications following viral encephalitis include: [1]

Epidemiology

While the etiology of many cases of encephalitis is unknown, viruses account for about 70% of confirmed encephalitis cases, with the herpes simplex virus being the most common cause at about 50% of encephalitis cases. [13] The incidence of viral encephalitis is about 3.5 to 7.5 per 100,000 people, with the highest incidence among the young and the elderly. Viral encephalitis caused by some viruses, such as the measles virus and the mumps virus, has become less common due to widespread vaccination. For others, such as Epstein-Barr virus and cytomegalovirus, incidence has increased due to the increased prevalence of AIDS, organ transplantation, and chemotherapy, which have increased the number of immunocompromised people who have weakened immune systems or who are susceptible to opportunistic infections. Time of the year, geography, and animal, including insect, exposure are also important. For example, arbovirus infections are seasonal and cause viral encephalitis at the highest rate during the summer and early fall when mosquitos are most active. Similarly, those who live in warm, humid climates where there are more mosquitos are more likely to experience viral encephalitis. [1] [6]

Prevention

As many encephalitic viruses are transmitted by mosquitos, many prevention efforts revolve around preventing mosquito bites. In areas where such arboviruses are widespread, people should use protective clothing and should sleep under a mosquito net. Removing containers of stagnant water and spraying insecticides can be beneficial. Activities that increase the likelihood of tick bites should be avoided. Vaccines against some arboviruses that cause viral encephalitis exist, such as those against Eastern equine encephalitis, Western equine encephalitis, and Venezuelan equine encephalitis. Although these vaccines are not perfectly effective, they are recommended for people who live in or travel to high-risk areas. [1] [6] Some vaccines that are included in standard vaccination programs, such as the MMR vaccine, which prevents measles, mumps, and rubella, are also capable of preventing viral encephalitis. [15]

See also

Related Research Articles

<span class="mw-page-title-main">Encephalitis</span> Inflammation of the brain

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<span class="mw-page-title-main">Viral meningitis</span> Medical condition

Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges. Symptoms commonly include headache, fever, sensitivity to light and neck stiffness.

<span class="mw-page-title-main">Shingles</span> Viral disease caused by the varicella zoster virus

Shingles, also known as herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within two to four weeks, but some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.

<span class="mw-page-title-main">Arbovirus</span> Class of viruses which are transmitted by arthropods

Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.

La Crosse encephalitis is an encephalitis caused by an arbovirus which has a mosquito vector.

<span class="mw-page-title-main">Aseptic meningitis</span> Inflammation of the meninges not due to common bacterial infection

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause.

<span class="mw-page-title-main">Herpetic gingivostomatitis</span> Inflammation of the mouth, lips, and gums, often due to herpes infection

Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.

<span class="mw-page-title-main">Meningoencephalitis</span> Medical condition

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain tissue.

<span class="mw-page-title-main">Genital herpes</span> Infection by herpes simplex viruses of the genitals

Genital herpes is a herpes infection of the genitals caused by the herpes simplex virus (HSV). Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

<span class="mw-page-title-main">Mollaret's meningitis</span> Medical condition

Mollaret's meningitis is a recurrent or chronic inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Since Mollaret's meningitis is a recurrent, benign (non-cancerous), aseptic meningitis, it is also referred to as benign recurrent lymphocytic meningitis. It was named for Pierre Mollaret, the French neurologist who first described it in 1944.

The central nervous system (CNS) controls most of the functions of the body and mind. It comprises the brain, spinal cord and the nerve fibers that branch off to all parts of the body. The CNS viral diseases are caused by viruses that attack the CNS. Existing and emerging viral CNS infections are major sources of human morbidity and mortality.

<span class="mw-page-title-main">Mosquito-borne disease</span> Diseases caused by bacteria, viruses or parasites transmitted by mosquitoes

Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people contract mosquito-borne illnesses each year, resulting in more than a million deaths.

<span class="mw-page-title-main">Herpes</span> Viral disease caused by herpes simplex viruses

Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herpes, though other forms also exist.

<span class="mw-page-title-main">Neonatal herpes</span> Medical condition

Neonatal herpes simplex, or simply neonatal herpes, is a herpes infection in a newborn baby, caused by the herpes simplex virus (HSV). It occurs mostly as a result of vertical transmission of the HSV from an affected mother to her baby. Types include skin, eye, and mouth herpes (SEM), disseminated herpes (DIS), and central nervous system herpes (CNS). Depending on the type, symptoms vary from a fever to small blisters, irritability, low body temperature, lethargy, breathing difficulty, and a large abdomen due to ascites or large liver. There may be red streaming eyes or no symptoms.

<span class="mw-page-title-main">Herpes meningitis</span> Medical condition

Herpes meningitis is inflammation of the meninges, the protective tissues surrounding the spinal cord and brain, due to infection from viruses of the Herpesviridae family - the most common amongst adults is HSV-2. Symptoms are self-limiting over 2 weeks with severe headache, nausea, vomiting, neck-stiffness, and photophobia. Herpes meningitis can cause Mollaret's meningitis, a form of recurrent meningitis. Lumbar puncture with cerebrospinal fluid results demonstrating aseptic meningitis pattern is necessary for diagnosis and polymerase chain reaction is used to detect viral presence. Although symptoms are self-limiting, treatment with antiviral medication may be recommended to prevent progression to Herpes Meningoencephalitis.

<span class="mw-page-title-main">Herpes simplex encephalitis</span> Encephalitis associated with herpes simplex virus

Herpes simplex encephalitis (HSE), or simply herpes encephalitis, is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, and some studies suggest an incidence rate of 5.9 cases per 100,000 live births.

Neurovirology is an interdisciplinary field which represents a melding of clinical neuroscience, virology, immunology, and molecular biology. The main focus of the field is to study viruses capable of infecting the nervous system. In addition to this, the field studies the use of viruses to trace neuroanatomical pathways, for gene therapy, and to eliminate detrimental populations of neural cells.

<span class="mw-page-title-main">Neonatal meningitis</span> Medical condition

Neonatal meningitis is a serious medical condition in infants that is rapidly fatal if untreated. Meningitis, an inflammation of the meninges, the protective membranes of the central nervous system, is more common in the neonatal period than any other time in life, and is an important cause of morbidity and mortality globally. Mortality is roughly half in developing countries and ranges from 8%-12.5% in developed countries.

Jamestown Canyon encephalitis is an infectious disease caused by the Jamestown Canyon virus, an orthobunyavirus of the California serogroup. It is mainly spread during the summer by different mosquito species in the United States and Canada.

References

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  5. ↑ Chen, Z.; Zhong, D.; Li, G (2019). "The role of microglia in viral encephalitis: a review". J Neuroinflammation. 16 (1): 76. doi: 10.1186/s12974-019-1443-2 . PMC   6454758 . PMID   30967139.
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  8. 1 2 Pastula, D. M.; Smith, D. E.; Beckham, J. D.; Tyler, K. L. (2016). "Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases". J Neurovirol. 22 (3): 257–260. doi:10.1007/s13365-016-0428-5. PMC   5087598 . PMID   26903031.
  9. ↑ Lavergne, A.; de Thoisy, B.; Tirera, S.; Donato, D.; Bouchier, C.; Catzeflies, F.; Lacoste, V. (2016). "Identification of lymphocytic choriomeningitis mammarenavirus in house mouse (Mus musculus, Rodentia) in French Guiana". Infect Genet Evol. 37: 225–230. doi: 10.1016/j.meegid.2015.11.023 . PMID   26631809.
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  11. ↑ Carod-Artal, F. J. (1 May 2020). "Neurological Complications of Coronavirus and COVID-19". Revista de Neurología. 70 (9): 311–322. doi:10.33588/rn.7009.2020179. PMID   32329044. S2CID   226200547.
  12. 1 2 "Encephalitis, Viral". World Health Organization. Archived from the original on May 16, 2006. Retrieved 27 March 2020.
  13. 1 2 3 4 5 Bradshaw, M. J.; Venkatesan, A. (2016). "Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management". Neurotherapeutics. 13 (3): 493–508. doi:10.1007/s13311-016-0433-7. PMC   4965403 . PMID   27106239.
  14. ↑ "West Nile Virus". World Health Organization. 3 October 2017. Retrieved 27 March 2020.
  15. ↑ "Understanding encephalitis -- prevention". WebMD. 26 March 2019. Retrieved 27 March 2020.
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