Infectious Diseases Of The Ne... Health Article

Arboviruses are found in ticks and mosquitos. They include Eastern and Western equine, Venezuelan, St. Louis, Japanese B, Powassan, California, La Crosse, Jamestown Canyon, Snowshoe hare, Rift Valley, and Orbivirus 1 agent of Colorado tick fever. Enteroviruses such as polio, coxsackievirus, and echovirus, and the viruses responsible for rubella, measles, chickenpox, mononucleosis, mumps, viral hepatitis, and influenza can all produce a more or less similar clinical picture because of direct parenchymal invasion of the nervous system and the subsequent antibody reaction.

In North America, herpes simplex, enteroviruses (polio, echovirus, and coxsackievirus), and arboviruses are the most common causative agents, with LCM and mumps the next most frequently identified causes. The prognosis in mumps and LCM is excellent, but arbovirus and herpes simplex infections are sometimes lethal or result in severe sequelae. Epstein-Barr virus is another cause of encephalitis, especially in younger subjects.

Enteroviral infection is most common in the summer months; the arbovirus infections spread by ticks occur mainly in the spring and those by mosquitos in the late summer. Mumps is the most common cause of encephalitis in the earlier part of the year, whereas LCM is more common in the fall and winter. During the great influenza pandemic of 1917, many patients developed the syndrome of von Economo encephalitis characterized by marked drowsiness (sleeping sickness), which often developed years later into a form of Parkinson's disease with oculogyric crises. It is not certain whether such an illness still exists sporadically because the virus was never isolated.

In North America, arboviruses other than St. Louis and Eastern and Western equine (see Box 165-1) are rare indeed, as are protozoal and metazoal infections. Bacteria, meningovascular syphilis, and fungi cause encephalitis usually only in association with frank meningitic signs. Although herpes and other arbovirus infections are often exceedingly severe, most other viruses produce a milder illness. Tertiary neurosyphilis smolders to produce the features of general paresis or tabes or meningovascular syphilis. Obviously many of the causative agents listed are unlikely causes of encephalitis in, for example, Eastern Canada, but one always must ask about visits a patient may have made to another country in these days of frequent air travel.

Typical features of encephalitis include fever, meningism, and signs of raised ICP. Reduction in consciousness level from drowsiness to coma, seizures that are often focal, and various other focal signs also occur, depending on which areas of brain are affected by the inflammatory process. As with cerebral abscesses, the combination of fever and meningism with evidence of cerebral dysfunction, either generalized (delirium, seizures, coma) or focal (hallucinations, hemiparesis, and so forth) must make one consider encephalitis.

Major pathologic features include edema and petechiae within the brain, with mononuclear perivascular cuffing and neuronal degeneration, mainly in the grey matter, cortex, and deep nuclei of the brainstem.

The list of differential diagnoses is rather long. Any form of meningitis may be accompanied by evidence of cortical inflammation. Abscesses, septic emboli, cortical septic thrombophlebitis, and postinfectious and toxic encephalopathies may be hard to distinguish from encephalitis; all are described here. Subdural and subarachnoid hemorrhage, bleeding into a tumor, porphyria, poisoning, and even multiple sclerosis can produce encephalopathy with meningism and sometimes fever.

Encephalopathy without actual invasion of the brain substance occurs with bacterial endocarditis, pertussis, and typhoid. These cannot be differentiated by their neurologic signs from viral encephalitis, but other clinical findings may allow diagnosis.

CSF taken during the acute stage of encephalitis shows a moderate rise in protein and contains lymphocytes up to about 250/mm ³. The sugar level is usually normal, except in mumps (and occasionally in herpes simplex virus [HSV] and LCM) encephalitis, when it is low, as it is in bacterial, fungal, and carcinomatous meningitis.

Specific laboratory diagnosis requires a fourfold increase in the level of viral antibody titers between acute and convalescent sera or virus isolation from the CSF or brain. Specimens must be frozen immediately after collection and shipped on dry ice to a laboratory for direct virus isolation, whereas acute and convalescent paired serum specimen can be sent unfrozen. If enterovirus infection is suspected, feces, CSF, or throat washings may be used for virus isolation. Throat washings and CSF are used for mumps identification, blood and CSF are used to detect LCM, and CSF or occasionally brain biopsy material is used to check for herpes simplex. Other viruses may be isolated from blood or CSF, and CMV can be found in the urine, saliva, or liver biopsy specimens. Cryptococcal or other fungal antigens may need to be sought as well. The heterophile test and tests for IgM antibody to viral capsid antigen should be positive in cases of Epstein-Barr virus encephalitis.

PCR is so sensitive for the diagnosis of herpes simplex virus encephalitis that brain biopsy is now rarely, if ever, necessary to diagnose this serious infection.

The treatment of encephalitis is improving. General measures include maintaining the patient's hydration and metabolic status, reducing fever, and preventing seizures. Antiviral agents are now available for treatment of herpes simplex (see below) and varicella-zoster forms of encephalitis.

In North America, herpes simplex is the most common single cause of acute, sporadic, severe encephalitis. Both human and monkey types of herpesvirus occur, and both can cause severe neurologic infection, although the latter is usually seen only in laboratory workers or monkey handlers. Infections occur at any age, but particularly in the first three decades. Of the two serologic types of human herpesvirus, type I causes sporadic encephalitis and oral ulcers, whereas type II produces aseptic meningitis and genital ulceration. In adults, nearly all cases of herpes simplex virus encephalitis (HSVE) are caused by type I virus.