Click here to view next page of this article

 

New Treatments for Encephalitis

Encephalitis is an acute infection of brain parenchyma characterized clinically by fever, headache, and an altered level of consciousness encephalitis. There may also be focal or multifocal neurologic deficits, and focal or generalized seizure activity. The major causes of encephalitis are herpes simplex virus type 1 (HSV-1); herpes simplex virus type 2 (HSV-2) in neonates; and the arthropod-borne viruses, including La Crosse virus, St. Louis encephalitis virus (SLE), and Japanese B encephalitis virus. Rocky Mountain spotted fever (RMSF) is a tick-borne rickettsial infection that may also cause encephalitis. The causal agents of encephalitis in the patient that is immunocompromised from organ transplantation, the acquired immunodeficiency syndrome (AIDS), or chronic disease include HSV-1, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and the entero viruses.

Postinfectious encephalomyelitis is an acute, inflammatory demyelinating disease of brain, optic nerves, and spinal cord that typically occurs a few days or weeks after a respiratory tract infection or after a vaccination. Postinfectious encephalomyelitis is postulated to be an autoimmune disease rather than an acute viral infection of the central nervous system (CNS). Encephalitis and postinfectious encephalomyelitis cannot be distinguished from each other by clinical presentation, and the latter is often a diagnosis of exclusion after laboratory studies fail to detect a specific cause for the encephalitis.

A discussion of the clinical presentation, diagnosis, and treatment of HSV encephalitis and the arthropod-borne viral encephalitides is provided, as well as a review of RMSF. This is followed by a discussion of encephalitis in the immunosuppressed patient, an increasingly common entity encountered in clinical practice, and a discussion of postinfectious encephalomyelitis.


Herpes Simplex Virus Encephalitis

HSV infections were first documented in ancient Greece when Hippocrates used the word "herpes," meaning to creep or crawl, to describe the lesions. Immunosuppression is associated with an increased risk of reactivation of latent HSV infections in the CNS. Immunosuppressive agents have been shown to trigger HSV encephalitis in animal models. In an experimental model, rabbits latently infected with HSV-1 by nasal instillation developed a necrotizing and inflammatory HSV encephalitis limited to the temporal lobes after intravenous infusion of cyclophosphamide and dexamethasone. Of seropositive bone marrow transplant recipients, 80% develop cutaneous herpes lesions.

Treatment

The recommended treatment of HSV encephalitis is intravenous acyclovir in a dose of 10 mg/kg every 8 hours for 2 to 3 weeks. Acyclovir is relatively safe, but it should be used with caution in patients who have renal insufficiency. HSV can develop resistance to acyclovir through mutations in the viral gene encoding thymidine kinase. Acyclovir-resistant HSV isolates have been identified as the cause of encephalitis in organ-transplant recipients.


Prevention of neonatal herpes infections remains problematic. Standard practice has been to deliver the infant by Caesarian section if the mother has a primary or recurrent genital infection. The use of acyclovir prophylaxis in late pregnancy has also been suggested.
[43] Acyclovir crosses the placenta and is concentrated in amniotic fluid; therefore, there is the potential for fetal nephrotoxicity, but this has not been observed.


Arthropod-Borne Virus Encephalitis

In the United States, the La Crosse virus and the St. Louis encephalitis virus are the most common cause of arthropod-borne (arbovirus) encephalitis. Japanese B encephalitis virus is the most common cause of arthropod-borne human encephalitis worldwide. Eastern equine encephalitis virus causes the most severe arbovirus encephalitis, and the fatality rate is high.

Clinical Presentation

La Crosse Virus

The La Crosse virus belongs to the California group of encephalitis viruses. It is responsible for nearly all infections caused by California group viruses in the United States and is the most common cause of pediatric arboviral encephalitis in the United States. The largest number of cases occur in wooded areas of the midwestern and mid-Atlantic United States. Most cases occur in late summer to early fall. The vector, Aedes triseriatus, is a forest-dwelling mosquito. Clinically recognizable disease occurs primarily in children ages 4 to 11 years.

St. Louis Encephalitis

The virus named St. Louis encephalitis causes large urban epidemics of encephalitis in the midwestern and southeastern United States. Cases of St. Louis virus encephalitis appear chiefly in late August and September and are greatest in years with heavy spring rains followed by a

Japanese B Encephalitis

The virus named Japanese B encephalitis is a member of the St. Louis complex of flaviviruses. Epidemic disease occurs in China, northern parts of Southeast Asia, and areas of India and Sri Lanka. The principal vector for Japanese B encephalitis is the culicine mosquito, that breeds in the rice fields of Asia. The disease primarily affects children, but nonimmune adults who enter an

Eastern Equine Encephalitis

The eastern equine encephalitis virus causes encephalitis along the eastern coast from Massachusetts to Florida and along the Gulf Coast with peak activity in August and September. [8] Disease in horses or pheasants precedes human disease by 2 to 3 weeks.

Western Equine Encephalitis

Infecting horses and humans in western North America, most cases of western equine encephalitis virus occur between April and September with peak activity in July and August. Inapparent infections with western equine encephalitis virus are more common than symptomatic cases, and symptomatic disease is more common in young children than in older children and

Venezuelan Equine Encephalitis

Endemic in South America, Venezuelan equine encephalitis virus is a rare cause of encephalitis in Central America and the southwestern United States, particularly in Texas. Infection with Venezuelan encephalitis virus is typically mild, with encephalitis occurring only rarely. Children

Treatment

Treatment of arbovirus encephalitis is primarily supportive with management of seizures and increased intracranial pressure. Ribavirin is a synthetic nucleoside analogue that inhibits the
 

Rocky Mountain Spotted Fever

RMSF is caused by the bacteria Rickettsia rickettsii and is the most common rickettsial disease in the United States. It was first described in the Snake River valley of Idaho and was recognized as a distinct entity by physicians for at least 20 years before the first publication of a

Encephalitis in the Immunosuppressed Patient

Encephalitis in the patient who is immunosuppressed from organ transplantation, chronic illness, or AIDS may be caused by VZV, HSV-1, Epstein-Barr virus, HHV-6, CMV, measles virus, or enteroviruses. A review of encephalitis caused by each of these viruses is provided, followed by

Varicella-Zoster Virus

Encephalitis complicating chickenpox was first described in 1875. [36] The incidence of encephalitis complicating this infection is estimated to be 1 to 2 cases per 10,000 cases of chickenpox. The pathogenesis of the encephalitis is either an acute viral infection of the brain or an immune-mediated postinfectious process. Acute cerebellar ataxia is the most common

 Epstein-Barr Virus

Serologic studies demonstrate that 90% of the general population has had Epstein-Barr virus infection by the age of 40 years. Encephalitis may be a complication of primary EBV infection (infectious mononucleosis) or may be caused by reactivation of latent EBV infection. In immunocompromised patients, EBV induces dysregulated activation and growth of a

 Human Herpesvirus-6

HHV-6 is the causative agent of the common childhood infection roseola infantum (exanthem subitum or sixth disease). The virus was first isolated in 1986 from the peripheral blood lymphocytes of patients who had AIDS and from patients who had lymphoproliferative disorders. It is a member of the human herpesvirus family and shares DNA sequence homology with human cytomegalovirus.

Pathogenesis

The majority of the population is exposed to HHV-6 in infancy, and most adults are seropositive. The virus invades the brain during primary infection, establishes latency, and can reactivate causing acute infection. Human T lymphocytes are the primary cell type infected by

Cytomegalovirus

CMV encephalitis is an important opportunistic infection in organ transplant recipients, but is rare in immunocompetent individuals. [4] With the advent of highly active antiretroviral therapy, the prevalence of CMV encephalitis in HIV-infected individuals has

Measles

Encephalitis is a rare complication of measles infection and is of three distinct types: (1) postinfectious or autoimmune encephalomyelitis, which presents as a sudden recurrence of fever with an altered level of consciousness, seizure activity, and multifocal neurologic signs during convalescence from measles; (2) subacute sclerosing panencephalitis (SSPE), which

 
Enteroviruses

The enteroviruses are the most common causal agents of aseptic meningitis, and may cause a meningoencephalitis, particularly in individuals who have hypogammaglobulinemia or agammaglobulinemia. The enteroviruses include the coxsackieviruses A and B, the echoviruses, and the polioviruses and enteroviruses 70 and 71. The key clinical features of enteroviral encephalitis are fever, a macular or maculopapular rash, and seizures. [64] The difficulty, then, is


Postinfectious Encephalomyelitis

An acute inflammatory, demyelinating disease of the brain, optic nerves, and spinal cord that occurs after a respiratory tract infection, a viral exanthem (measles virus and varicella virus infections), or an immunization (historically the smallpox immunization with vaccinia virus) is called postinfectious encephalomyelitis. Postinfectious encephalomyelitis is also called acute disseminated encephalomyelitis, acute demyelinating encephalomyelitis, and postviral encephalomyelitis. The terms acute hemorrhagic leukoencephalitis and acute hemorrhagic necrotizing leukoencephalitis refer to a severe form of postinfectious encephalomyelitis.

Treatment

Postinfectious encephalomyelitis and acute hemorrhagic leukoencephalitis are treated with high-dose intravenous methylprednisolone. These patients often require critical care support with management of raised intracranial pressure. As of yet, pathogenic autoantibodies or immune complexes have not been identified in postinfectious encephalomyelitis, and a role for plasmapheresis or intravenous immune globulin therapy has not been demonstrated. The