Viral encephalitis
   HOME

TheInfoList



OR:

Viral encephalitis is
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
of the brain parenchyma, called
encephalitis 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, ...
, by a
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
. 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 The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's
inflammatory response Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior. Viral encephalitis can be diagnosed based on the individual's symptoms, personal history, such as travel history, and different clinical tests such as
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
,
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
, and
lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...
s. A
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
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 Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following tran ...
. 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
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, memory loss, and intellectual impairment. Encephalitic viruses are typically transmitted either from person-to-person or are
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
-borne viruses, called
arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more spe ...
es. 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: *
California encephalitis virus ''California encephalitis orthobunyavirus'' type strain California encephalitis virus was discovered in Kern County, California, and causes encephalitis in humans. Encephalitis is an acute inflammation of the brain that can cause minor symptoms, ...
*
Chandipura virus ''Chandipura vesiculovirus'' (CHPV) is a member of the ''Rhabdoviridae'' family that is associated with an encephalitic illness in humans. It was first identified in 1965 after isolation from the blood of two patients from Chandipura village in ...
* ''
Chikungunya virus Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a ra ...
'' * ''
Cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
'' * ''
Dengue virus ''Dengue virus'' (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family ''Flaviviridae''; genus ''Flavivirus''. Four serotypes of the virus have been found, a reported fifth has yet to be co ...
'' * '' Eastern equine encephalitis virus'' *
Enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it ma ...
es * Epstein-Barr virus *
Herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
*
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
*
Human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for ''human betaherpesvirus 6A'' (HHV-6A) and ''human betaherpesvirus 6B'' (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primar ...
*
Human herpesvirus 7 ''Human betaherpesvirus 7'' (HHV-7) is one of nine known members of the ''Herpesviridae'' family that infects humans. HHV-7 is a member of ''Betaherpesvirinae'', a subfamily of the ''Herpesviridae'' that also includes HHV-6 and ''Cytomegalovirus ...
*
Influenza virus ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ...
es * Inkoo virus *
Jamestown Canyon virus 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. T ...
* ''
Japanese encephalitis virus Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include he ...
'' *
La Crosse virus La Crosse encephalitis is an encephalitis caused by an arbovirus (the La Crosse virus) which has a mosquito vector ('' Ochlerotatus triseriatus'' synonym ''Aedes'' ''triseriatus''). La Crosse encephalitis virus (LACV) is one of a group of m ...
* ''
Lymphocytic choriomeningitis mammarenavirus Lymphocytic choriomeningitis (LCM) is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is ''lymphocytic choriomeningitis mammarenavirus'' (LCMV), a member of th ...
'' *
Measles virus ''Measles morbillivirus'' (MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus ''Morbillivirus'' within the family ''Paramyxoviridae''. It is the cause of measles. Human ...
*
Mumps virus The mumps virus (MuV) is the virus that causes mumps. MuV contains a single-stranded, negative-sense genome made of ribonucleic acid (RNA). Its genome is about 15,000 nucleotides in length and contains seven genes that encode nine proteins. The g ...
* ''
Murray Valley encephalitis virus ''Murray Valley encephalitis virus'' (MVEV) is a zoonotic flavivirus endemic to northern Australia and Papua New Guinea. It is the causal agent of Murray Valley encephalitis (MVE; previously known as Australian encephalitis or Australian X diseas ...
'' *
Nipah virus Nipah virus, scientific name ''Nipah henipavirus'', is a bat-borne virus that causes Nipah virus infection in humans and other animals, a disease with a high mortality rate. Numerous disease outbreaks caused by Nipah virus have occurred in Sout ...
* ''
Powassan virus ''Powassan virus (POWV)'' is a ''Flavivirus'' transmitted by ticks, found in North America and in the Russian Far East. It is named after the town of Powassan, Ontario, where it was identified in a young boy who eventually died from it. It can ca ...
'' *
Rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
* ''
Rubella virus Rubella virus (RuV) is the pathogenic agent of the disease rubella, transmitted only between humans via the respiratory route, and is the main cause of congenital rubella syndrome when infection occurs during the first weeks of pregnancy. Rube ...
'' *
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
*
Snowshoe hare virus Snowshoes are specialized outdoor gear for walking over snow. Their large footprint spreads the user's weight out and allows them to travel largely on top of rather than through snow. Adjustable bindings attach them to appropriate winter footwe ...
* St. Louis virus * Tahyna virus * ''
Tick-borne encephalitis virus Tick-borne encephalitis virus (TBEV) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus '' Flavivirus''. Classification Taxonomy TBEV is a member of the genus '' Flavivirus''. Other close relatives, members ...
'' *
Varicella-zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
, which causes both
chickenpox Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab ...
and
shingles Shingles, also known as zoster or 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. ...
* ''
Venezuelan equine encephalitis virus Venezuelan equine encephalitis virus is a mosquito-borne viral pathogen that causes Venezuelan equine encephalitis or encephalomyelitis (VEE). VEE can affect all equine species, such as horses, donkeys, and zebras. After infection, equines may ...
'' * ''
West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...
'' * ''
Western equine encephalitis virus The Western equine encephalomyelitis virus is the causative agent of relatively uncommon viral disease ''Western equine encephalomyelitis'' (WEE). An alphavirus of the family '' Togaviridae'', the WEE virus is an arbovirus (arthropod-borne vir ...
'' * ''
Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...
''


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
arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more spe ...
es. An example of person-to-person transmission is the herpes simplex virus, which is transmitted by means of intimate physical contact. An example of arboviral transmission is the West Nile virus, which usually is incidentally transmitted to people from the bites of ''
Culex ''Culex'' is a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans, and other animals. The diseases they vector include arbovirus infections such as West Nile virus, Japanese encep ...
'' mosquitos, especially ''
Culex pipiens ''Culex pipiens'', commonly referred to as the common house mosquito, is a species of mosquito. House mosquitoes are some of the most common mosquitoes in the United States. More specifically, ''Culex pipiens'' is considered as the northern hous ...
''.


Pathogenesis

Viruses that cause viral encephalitis first infect the body and replicate outside of the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS). Thereafter, most reach the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
and brain via the circulatory system. Exceptions to this include
herpesvirus ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...
es 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 The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...
, and
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
. Widespread presence of
white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s and
microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
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 Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include he ...
, there may be a significant amount of
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
of nerve cells. Following encephalitis caused by arboviruses,
calcification Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Mat ...
may occur in the CNS, especially among children. Herpes simplex encephalitis tends to produce necrotic lesions in the CNS.


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, 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,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, 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. Virus-specific symptoms may also exist or tests may indicate one virus. Specific examples include: *
Enterovirus 71 Enterovirus 71 (EV71), also known as Enterovirus A71 (EV-A71), is a virus of the genus ''Enterovirus'' in the ''Picornaviridae'' family, notable for its role in causing epidemics of severe neurological disease and hand, foot, and mouth disease i ...
may cause
tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
s, twitching, impaired balance and coordination, fluid accumulation in the lungs, and
cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and ...
palsies. * Epstein-Barr virus encephalitis is usually accompanied by enlargement of the lymph nodes and enlargement of the spleen *
Herpes zoster Shingles, also known as zoster or 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. ...
encephalitis may be accompanied by rash and skin vesicles, and because it involves the
frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betwe ...
and
temporal lobe The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe ...
, is often characterized by psychiatric features, memory deficits, and loss of language faculties. * Many arboviral encephalitides, such as Japanese encephalitis, primarily affect the
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
, sometimes causing motor symptoms such as involuntary movements and movements similar to those observed in
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. * Nipah virus may produce brainstem and cerebellar signs, hypertension, and segmental myoclonus, or twitching of a group of connected muscles. * Zika virus characteristically may cause
microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
among newborn children if a pregnant woman is infected.


Histology

The brain histology of viral encephalitis shows dead neurons with nuclear dissolution and elevated
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
count, called hypereosinophilia, within cells' cytoplasm when viewed with an
optical microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsco ...
. Because encephalitis is an inflammatory response, inflammatory cells situated near blood vessels, such as
microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
,
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
, and
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
, are visible.
Virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
s within neurons are visible via
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
s.


Clinical evaluation

Neuroimaging and
lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...
(LP) are both essential methods of diagnosing viral encephalitis. Computed tomography (CT) or
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) help identify increased intracranial pressure and the risk of
uncal herniation Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the te ...
before performing an LP. Cerebrospinal fluid (CSF), if analyzed, should be analyzed for opening pressure, cell counts, glucose, protein, and
IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
and
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
antibodies. CSF testing should also include
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) testing for herpes simplex viruses 1 and 2 and enteroviruses. About 10% of patients have normal CSF results. Additional testing, such as
serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
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 Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
(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. Test results specific to certain viruses include: * For herpes simplex virus encephalitis, a CT scan may show low-density lesions in the temporal lobe. These lesions usually appear 3 to 5 days after the start of the infection. * Japanese encephalitis often has distinct EEG patterns, including diffuse delta activity with spikes, diffuse continuous delta activity, and alpha coma activity.


Differential diagnosis

A broad
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
can be performed that looks at many potential causes of the encephalitis, infectious and noninfectious. Potential alternatives to viral encephalitis include
malignancy Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
, autoimmune or paraneoplastic diseases such as
anti-NMDA receptor encephalitis Anti-NMDA receptor encephalitis is a type of encephalitis, brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with delusions, false b ...
, a
brain abscess Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone ...
,
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
or drug-induced
delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
, exposure to certain drugs or
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...
s,
neurosyphilis Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurologic ...
, vascular disease, metabolic disease, or encephalitis from infection caused by a bacterium, fungus, protozoan, or parasitic worm. In children, differential diagnosis may not be able to distinguish between viral encephalitis and immune-mediated inflammatory CNS diseases, such as
acute disseminated encephalomyelitis Acute disseminated encephalomyelitis (ADEM), or acute Demyelinating disease, demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the ...
, as well as immune-mediated encephalitis, so other diagnostic methods may need to be used.


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 An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
disturbance, autonomic disregulation, and renal and hepatic dysfunction, as well as for seizures and non-compulsive
status epilepticus Status epilepticus (SE), or status seizure, is a single seizure lasting more than 5 minutes or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The s ...
. A very specific exception is herpes simplex virus (HSV) encephalitis, which can be treated with
acyclovir Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following tran ...
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 Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhib ...
should be used. Although not as effective,
nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide ...
analogs are used for other herpesviruses as well, such as acyclovir, with possible adjunctive
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s for immunocompetent individuals, for varicella-zoster virus encephalitis and a combination of
ganciclovir Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir was patented in 1980 and approved for medical use in 1988. Medical use Ganciclovir is indicated f ...
and foscarnet for cytomegalovirus encephalitis. 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 Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to lower ...
, though there is limited data of the efficacy of such treatment with regards to viral encephalitis. Seizures can be managed with
valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
or
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
. Status epilepticus may required
benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...
.
Antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
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.


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 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 A persistent vegetative state (PVS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative stat ...
. 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 Neurosurgery or neurological surgery, known in common parlance as brain surgery, is the medical specialty concerned with the surgical treatment of disorders which affect any portion of the nervous system including the brain, spinal cord and peri ...
. Prognoses related to specific viruses include: * For Eastern equine encephalitis, some children may experience seizures, severe intellectual disability, and various forms of paralysis. * For Japanese encephalitis, extrapyramidal symptoms relating to motor function may remain. * For St. Louis encephalitis, low blood sodium level and excess, unsuppressable release of antidiuretic hormone * For Western equine encephalitis, some children may experience seizures and behavioral changes. * For pregnant women infected with Zika virus, the newborn child may have microcephaly. Other potential complications following viral encephalitis include: *
Encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
*
Flaccid paralysis Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associated ...
* Impaired intelligence * Low blood sodium level *
Mononeuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
* Mood and behavioral changes * Residual neurological deficits


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. 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 Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
,
organ transplantation Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
, and
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, which have increased the number of
immunocompromise Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
d people who have weakened immune systems or who are susceptible to
opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...
s. 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.


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. Some vaccines that are included in standard vaccination programs, such as the
MMR vaccine The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles), abbreviated as ''MMR''. The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, ...
, which prevents measles, mumps, and rubella, are also capable of preventing viral encephalitis.


See also

*
List of central nervous system infections There are five main causes of infections of the central nervous system (CNS): bacterial, viral, fungal, protozoal, and prionic. Fungal * Cryptococcal meningitis * Brain abscess * Spinal epidural infection Protozoal * Toxoplasmosis * Malaria ...


References


External links

{{Diseases of the nervous system *