Encephalitis

Viruses causing primary encephalitis directly invade the brain. These infections may be

Mosquito-borne arboviral encephalitides infect people during the spring, summer, and early fall when the weather is warm (see table Some Arboviral Encephalitides Some Arboviral Encephalitides ). Incidence in the US varies from 150 to > 4000 cases yearly, mostly in children. Most cases occur during epidemics.

In the US, the most common sporadic encephalitis is caused by herpes simplex virus Herpes Simplex Virus (HSV) Infections Herpes simplex viruses (human herpesviruses types 1 and 2) commonly cause recurrent infection affecting the skin, mouth, lips, eyes, and genitals. Common severe infections include encephalitis... read more (HSV); hundreds to several thousand cases occur yearly. Most are due to HSV-1, but HSV-2 may be more common among immunocompromised patients. HSV encephalitis occurs at any time of the year, tends to affect patients < 20 or > 40 years, and is often fatal if untreated.

Rabies Rabies Rabies is a viral encephalitis transmitted by the saliva of infected bats and certain other infected mammals. Symptoms include depression and fever, followed by agitation, excessive salivation... read more remains a significant cause of encephalitis in developing countries and still causes a few cases of encephalitis in the US.

Encephalitis can also occur as a late reactivation of latent or subclinical viral infection. The best known types are

Encephalitis can occur as a secondary immunologic complication of certain viral infections or vaccinations. Inflammatory demyelination of the brain and spinal cord can occur 1 to 3 weeks later (as acute disseminated encephalomyelitis); the immune system attacks one or more central nervous system (CNS) antigens that resemble proteins of the infectious agent. The most common causes of this complication used to be measles, rubella, chickenpox, and mumps (all now uncommon because childhood vaccination is widespread); smallpox vaccine; and live-virus vaccines (eg, the older rabies vaccines prepared from sheep or goat brain). In the US, most cases now result from influenza Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more A or B virus, enteroviruses Overview of Enterovirus Infections Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more , Epstein-Barr virus Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more , hepatitis A Hepatitis A Hepatitis A is caused by an enterically transmitted RNA virus that, in older children and adults, causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Young... read more or hepatitis B Hepatitis B, Acute Hepatitis B is caused by a DNA virus that is often parenterally transmitted. It causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and... read more virus, or HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more . Immunologically mediated encephalitis also occurs in patients with cancer and other autoimmune disorders.

Rarely, apparent encephalitis has developed in patients with COVID COVID-19 COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. COVID-19 was first reported in late 2019 in Wuhan, China and has since spread extensively... read more -19 COVID-19 COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. COVID-19 was first reported in late 2019 in Wuhan, China and has since spread extensively... read more , caused by the novel pandemic severe acute respiratory syndrome coronavirus (SARS-CoV2); the mechanism is not clear, but an immunologic contribution to the mechanism of apparent encephalitis is possible, as is direct viral invasion of the brain.

Encephalopathies caused by autoantibodies to neuronal membrane proteins (eg, N-methyl-d-aspartate receptors [NMDAR] ) may mimic viral encephalitis. Studies indicate that anti-NMDAR encephalitis is more common than viral encephalitides. Anti-NMDAR encephalitis was first described in young women with ovarian teratomas but can occur in both sexes and at any age. Anti-NMDAR encephalitis also occurs as a postinfectious complication of HSV encephalitis, resulting in clinical decline within weeks of the HSV infection.

Contrast-enhanced MRI is sensitive for early HSV encephalitis, showing edema in the orbitofrontal and temporal areas, which HSV typically infects. MRI shows demyelination in progressive multifocal leukoencephalopathy and may show basal ganglia and thalamic abnormalities in West Nile and eastern equine encephalitis. MRI can also exclude lesions that mimic viral encephalitis (eg, brain abscess Brain Abscess A brain abscess is an intracerebral collection of pus. Symptoms may include headache, lethargy, fever, and focal neurologic deficits. Diagnosis is by contrast-enhanced MRI or CT. Treatment is... read more , sagittal sinus thrombosis).

CT is much less sensitive than MRI for HSV encephalitis but can help because it is rapidly available and can exclude disorders that make lumbar puncture risky (eg, mass lesions, hydrocephalus, cerebral edema).

Lumbar puncture Lumbar Puncture (Spinal Tap) Lumbar puncture is used to do the following: Evaluate intracranial pressure and cerebrospinal fluid (CSF) composition (see table Cerebrospinal Fluid Abnormalities in Various Disorders) Therapeutically... read more (spinal tap) is done. If encephalitis is present, CSF is characterized by lymphocytic pleocytosis, normal glucose, mildly elevated protein, and an absence of pathogens after Gram staining and culture (similar to CSF in aseptic meningitis). Pleocytosis may be polymorphonuclear in severe infections. CSF abnormalities may not develop until 8 to 24 hours after onset of symptoms. Hemorrhagic necrosis can introduce red blood cells (RBCs) into CSF and elevate protein. CSF glucose levels may be low when the cause is varicella-zoster virus, mumps, or lymphocytic choriomeningitis virus.

CSF samples should be sent for viral identification using PCR or, in certain cases, detection of antiviral antibodies in CSF. PCR testing of CSF is the diagnostic test of choice for HSV-1, HSV-2, varicella-zoster virus, cytomegalovirus, enteroviruses, and JC virus. PCR for HSV in CSF is particularly sensitive and specific. However, results may not be available rapidly, and despite advances in technology, false-negative and false-positive results may still occur because of a variety of conditions; not all are technical failures (eg, the blood in a mildly traumatic CSF tap may inhibit the PCR amplification step). False-negative results can occur early in HSV-1 encephalitis; if a false-negative result is suspected based on clinical findings, testing should be repeated in 48 to 72 hours. A recently developed multiplex PCR process, which can detect multiple viral and other infectious agents simultaneously, provides diagnostic information within a few hours. Multiplex PCR results may need to be confirmed by conventional PCR.

CSF viral cultures grow enteroviruses but not most other viruses. For this reason, CSF viral cultures have been superseded by PCR and are rarely used in diagnosis.

CSF viral IgM titers are often useful for diagnosing acute infection, especially West Nile encephalitis, for which they are more reliable than PCR. CSF IgG and IgM titers may be more sensitive than PCR for encephalitis due to reactivated varicella-zoster virus infection. Paired acute and convalescent serologic tests of CSF and blood must be drawn several weeks apart; they can detect an increase in viral titers specific for certain viral infections.

Brain biopsy may be indicated for patients who

However, brain biopsy has a low yield unless it targets an abnormality seen on MRI or CT.