Continued...

Discussion :-

The herpes virus can also be acquired postnatally from contact with immediate family members who may be shedding virus from a symptomatic or asymptomatic oral-labial infection. Varicella-zoster virus causes a deadly encephalitis in immunocompromised patients and has an incidence of 1:2000 infected persons. Toxoplasma encephalopathy is prevalent among HIV+ patients.

Measles is responsible for two types of encephalitis, post-infectious, with an incidence of 1:1000 infected persons, and subacute sclerosing panencephalitis, with an incidence of 1:100,000 infected persons. Rabies accounts for 0-3 cases of encephalitis yearly in the US. The most common form of encephalitis outside the US is Japanese encephalitis, which affects persons in Japan, SE Asia, China, and India (2).

Arboviruses require a mosquito or tick vector (hence the name "arthropod borne" virus). In general, the virus replicates outside the CNS and gains entry by hematogenous spread. The herpes simplex virus (HSV) is a double-stranded DNA virus which can infect mucocutaneous surfaces, the central nervous system, and, less commonly, visceral organs. The virus may remain latent in neuronal ganglia and may subsequently be reactivated, resulting in viral replication. HSV is usually transmitted via contact with active ulcerative lesions. However, individuals with subclinical disease may also shed infectious virus. Subclinical transmission of HSV may partially account for the continued rise in worldwide seroprevalence. HSV gains entry at mucosal surfaces or abraded skin and replicates within the epidermis and dermis. Often, the primary infection is subclinical. However, sufficient numbers of virus may still be present to infect peripheral sensory or autonomic nerve endings. Once inside the neuron, the virus travels intra-axonally to the nerve cell bodies in ganglia, where replication occurs. The virus can also migrate to other tissues either proximally, by contiguous spread, or distally through a neuronal network. After the primary infection has resolved, the herpes simplex virus can no longer be found in the ganglia. However, about 10 to 50 percent of ganglion cells in the area of the initial infection may harbor viral DNA. Approximately 1 percent of these cells possess latency-associated transcripts of RNA. The molecular mechanisms of latency and reactivation are not well understood. Factors linked to reactivation include: ultraviolet light, immunosuppression, and trauma to the skin or ganglia. The maintenance of latency, the frequency of reactivation, and the severity of illness ultimately depend upon the host immune response (3).

The exact pathogenesis of HSV encephalitis is not well known. One hypothesis is that the virus gains entry into the CNS directly from a peripheral route via either the trigeminal or olfactory nerve. HSV encephalitis is the result of a primary infection in about 1/3 of cases (4).

In children and in adults, HSV encephalitis is generally localized to the inferior and medial regions of the temporal lobe and the orbital gyri of the frontal lobes. In neonates, brain involvement tends to be more diffuse. The disease is necrotizing and often in general, a patient with encephalitis presents with diffuse or focal neurologic signs and symptoms, including an altered mental state and level of consciousness, behavioral or personality changes, nuchal rigidity, photophobia, and generalized or focal seizures. Depending upon the type of virus, the patient may present with additional signs and symptoms. For example, patients with varicella zoster or measles encephalitis will typically have a rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement. Patients with St. Louis encephalitis will present with dysuria and pyuria (2).In the case of HSV encephalitis, the patient will generally present with an altered state of consciousness, an abnormal mental state, and focal neurologic signs and symptoms, in addition to the acute febrile illness characteristic of viral meningitis. The level of consciousness may vary from mild lethargy to a comatose state. The patient is not mentally alert and is often confused, delirious, or disoriented. The patient may also suffer hallucinations and exhibit personality and/or behavioral changes, sometimes escalating into frank psychosis. Focal neurologic changes depend upon the site of infection within the brain. Common neurologic abnormalities include: aphasia, ataxia, cranial nerve deficits, hemiparesis, hyperactive tendon reflexes, and involuntary movements, such as myoclonic jerks (1). Prolonged seizures, or status epilepticus, which are refractory to anticonvulsants are also common in the presentation of encephalitis. In children and adults, there is no relationship between the presence of mucocutaneous lesions and HSV encephalitis (4). In fact, only about 10% of patients have a positive history of prior labial herpes (5).

Thus, the presence or absence of such lesions is of no diagnostic value. By contrast, neonates often have pathognomonic lesions. Neonates with HSV encephalitis may present with lethargy, poor feeding, irritability, tremors, seizures, temperature instability, a bulging fontanelle, and pyramidal tract signs. With disseminated disease, the neonate may present with systemic signs and symptoms such as jaundice, shock, bleeding, or respiratory distress (4). Once the diagnosis of encephalitis is suspected, the patient should be given intravenous acyclovir immediately. The cause of the encephalitis is assumed to be HSV until proven otherwise. HSV encephalitis has specific antiviral chemotherapy and the patient's prognosis relies heavily upon the expediency of this treatment. The clinician must be wary of non-viral causes of encephalopathy, including infectious and non-infectious agents. Among the non-viral infectious etiologies are abscesses, as well as bacterial, fungal, parasitic, rickettsial, and tuberculous infections. Non-infectious causes of encephalopathy include tumors, hematomas, vascular insults, toxic encephalopathy, and systemic lupus erythematosus. Hundreds of viruses have been implicated in viral encephalitis and it is difficult to clinically distinguish HSV encephalitis from the other viral forms. Therefore, confirmation of HSV encephalitis depends upon laboratory work-up; however, this should not delay the immediate initiation of acyclovir treatment. The CSF profile in viral encephalitis mimics that of viral meningitis, with a lymphocytic pleocytosis, an elevated protein content, and a normal glucose level. The lymphocytic pleocytosis is found in more than 95 percent of patients with viral encephalitis.