2 IntroductionEncephalitis is an acute inflammatory process affecting the brainEncephalitis can be caused by bacterial infection and, most often, by viral infection with over 100 viruses implicated worldwide.Encephalitis is the most serious manifestation of viral CNS infection.Encephalitis is distinguished from aseptic meningitis by the extent and severity of cerebral dysfunction, independent of signs of meningeal inflammation.
3 IntroductionMany more cases of encephalitis actually occur each year than those reported.Incidence of per 100,000 persons per yearSymptomsFeverHeadacheBehavioral changesAltered level of consciousnessFocal neurologic deficitsSeizures
4 Causes of Viral Encephalitis Herpes viruses: HSV-1, HSV-2, VZV, CMV, EBV, HHV-6AdenovirusesInfluenzaEnteroviruses including poliovirusesMeasles, mumps, and rubella virusesRabies virusArboviruses: Japanese encephalitis, St. Louis encephalitis, West Nile encephalitis, Eastern and Western equine encephalitis, Venezuelan equine encephalitis, Lacrosse encephalitis, Colorado tick fever, and lymphocytic choriomeningitis viruses
5 Etiology and Pathology There are two types of encephalitis, primary which is caused by direct viral infection, and secondary which results from complication of a current or a recent viral infection.Primary infection can be focal or diffuse and secondary encephalitis is acute and disseminated that often occurs 2 to 3 weeks following the initial infectionMost cases of primary encephalitis are caused by enteroviruse, herpes viruses, arboviruses and rabies virus
6 Secondary encephalitis, usually a complication of viral infection, is considered to have an immunologic mechanism.Examples are encephalitides secondary to measles, chickenpox, influenza, rubella, vaccinia, and many other less well defined viral infections.These parainfectious or postinfectious encephalitides typically develop 5 to 20 days after onset of illness and are characterized by perivascular demyelination seen at autopsy; a virus is rarely isolated from the brain.
7 Very rarely, encephalitis or other encephalopathies occur as a late consequence of viral infections. The best known is subacute sclerosing panencephalitis and progressive rubella panencephalitis, associated with measles and rubella viruses respectively.Direct viral invasion of the brain is likely to result in neuronal necrosis, frequently with visible inclusion bodies.In parainfectious and postinfectious encephalomyelitis, perivenous demyelinating lesions are characteristic.
8 EpidemiologyViruses causing primary encephalitis may spread in epidemics (arboviruses, polioviruses, echoviruses, and coxsackieviruses) or sporadically (herpes simplex, varicella -zoster, and mumps viruses).Mosquito-borne arboviral encephalitides (St. Louis, eastern and western equine, and Lacrosse) infect humans only during warm weather.
9 PathogenesisThe pathogenesis of encephalitis due to herpes simplex virus, arboviruses, and rabies virus is different for each virus.In neonates, herpetic encephalitis is predominantly due to HSV-2, and irrespective of serotype, the acute generalized necrotizing encephalitis is often accompanied by evidence of systemic infection of the liver, adrenals, and other organs.In children and adults, herpetic encephalitis is caused by HSV-1 and is usually localized.
10 HSV Encephalitis in an immune host results either from the entry of a new virus, possibly across the olfactory mucosa, or from reactivation of latent virus in the trigeminal ganglia, which spread along sensory nerve fibers to the base of the anterior and middle fossa.In either case, infection is localized to the orbital, frontal, and medial temporal lobes.Because the host is immune, virus presumably spreads from cell to cell over a contiguous localized area, infecting neurons and glial cells.
11 In contrast, arboviruses (mainly togaviruses, flaviviruses, and bunyaviruses) spread to the brain from the blood.The systemic infection causes few, if any, symptoms.Depending on the virus, between 1 in 20 and 1 in 1000 infections are complicated by CNS infection.The encephalitis is diffuse, but is localized largely to neurons.
12 Clinical Course of Encephalitis Encephalitis may produce fever and malaise without meningeal signs, or it may cause meningeal signs with cerebral dysfunction.As brain parenchyma becomes involved, there is an alteration of consciousness; personality changes, ataxia, seizures, cranial nerve abnormalities, and paralysis followed by coma.
13 In addition to headache and fever, hallucinations and bizarre behavior are common, and these are sometimes confused with psychiatric illness.Focal seizures and hemiparesis are frequent, and aphasia develops if the disease is localized to the dominant temporal lobe.Herpes simplex virus-1 encephalitis in the non-neonate typically causes focal signs that may evolve over a period of up to 1 or 2 weeks.
14 Herpes simplex encephalitis is clinically similar to other viral encephalitides but is strongly suggested by repeated seizures occurring early in the course of disease and by signs indicating temporal or frontal lobe involvement.Arbovirus infections cause a more diffuse and acute disease, with a rapid depression of consciousness, greater frequency of generalized seizures, and multifocal signs.At times, however, arbovirus or any other form of encephalitis may localize to the temporal areas, producing signs very similar to those of herpes simplex virus encephalitis.
15 DiagnosisViral infections must be differentiated from other infections (bacterial, rickettsial, spirochetal, and parasitic) and noninfectious disordersThe major problem is to distinguish viral encephalitis from acute or partially treated bacterial meningitisDiagnosis is usually based on CSF changes, including normal glucose and absence of bacteria on culture.
16 Cultures (eg, from the nasopharynx or stool) and attention to epidemic agents in the community may help.Because of public health implications, serum should be drawn and preserved whenever the diagnosis of encephalitis or aseptic meningitis of uncertain etiology is first suspected.The CSF examination in acute encephalitis may or may not show an increase in pressure, but usually reveals an inflammatory response of mononuclear cells.
17 RBCs in CSF after an atraumatic spinal tap suggest herpes simplex infection because of the necrotizing pathology of the disease, but they are not universally present nor are they specific to the disease.Viruses are occasionally isolated directly from CSF or from other tissues but are identified in fewer than half of the cases.Herpes simplex virus is rarely isolated from CSF but it can be precisely identified by polymerase chain reaction in CSF.
18 A prompt, definitive diagnosis of HSV-1 encephalitis requires brain biopsy of the area where typical encephalitis with inclusion bodies is seen.The diagnosis is confirmed by either immunocytochemical staining of herpes simplex virus antigens in brain cells or virus isolation.Biopsy is, however, rarely indicated and should be reserved for patients who are worsening, have an undiagnosed lesion after CT or MRI, or have a poor response to acyclovir.
19 The electroencephalogram (EEG) is helpful in the diagnosis of herpes simplex virus encephalitis because periodic spikes and slow waves often localize to the infected temporal lobe. In other forms of encephalitis slowing is more diffuse.Computerized tomography (CT) in cases of herpes simplex virus encephalitis usually shows an attenuated area in the medial temporal lobes and sometimes a mass effect, but these findings, like the CSF and EEG changes, are not diagnostic.
20 MRI may detect inferior-frontal and medial-temporal lobe inflammation earlier than EEG, CT, or radionuclide brain scanning, prompting antiviral therapy before neurological deterioration occurs.MRI can exclude brain abscess, subdural empyema, subdural hematoma, tumor, and sagittal sinus thrombosis, which can clinically mimic encephalitis.
21 Prognosis and Treatment The only treatable cause of viral encephalitis is Herpes viruses. Therefore, until HSV encephalitis is ruled out by PCR, the patient must be treated with acyclovir.The mortality rate varies with etiology, and epidemics due to the same virus vary in severity in different years.Permanent cerebral sequelae are more likely to occur in infants and young children improve in a shorter time than adults with similar infections.Permanent sequelae include mental retardation, epilepsy, blindness and deafness.
22 Post-infectious Viral Syndromes of the CNS Post infectious encephalitis is seen in approximately 1:1000 cases of measles, mumps, vaccinia, etc., and is immunologically mediated.Reye’s syndrome follow infections with influenza, varicella, adenovirus and other viruses. It chiefly affects children between the ages of 2 and 16.Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy often following one of many antecedent viral and non-viral illness.