Introduction

1. Introduction • Encephalitis is an acute inflammatory process affecting the brain • Viral infection is the most common and important cause, with over 100 viruses implicated worldwide • Symptoms • Fever • Headache • Behavioral changes • Altered level of consciousness • Focal neurologic deficits • Seizures • Incidence of 3.5-7.4 per 100,000 persons per year

2. Herpes Simplex Encephalitis • Commonest and gravest form of sporadic acute encephalitis. • Between 30 and 70 percent are fatal, and the majority of patients who survive are left with serious neurologic abnormalities. • Sporadically throughout the year and in patients of all ages and in all parts of the world. • Almost always to HSV-1, which is also the cause of the common herpetic lesions of the oral mucosa. • The type 2 virus may also cause acute generalized encephalitis, usually in the neonate and in relation to genital herpetic infection in the mother.

3. Pathology • With reactivation in the trigeminal ganglia, the infection may spread along nerve fibers that innervate the leptomeninges of the anterior and middle fossae. • Both direct virus-mediated and indirect immune-mediated mechanisms play a role in producing CNS damage • Intense hemorrhagic necrosis of the inferior and medial temporal lobes and the medioorbital parts of the frontal lobes • Temporal lobe lesions are usually bilateral but not symmetrical • Intranucleareosinophilic inclusions are found in neurons and glial cells.

4. Clinical Features • Over several days • Fever, headache, seizures, confusion, stupor, and coma. • Findings that betray the predilection of this disease for the inferomedial portions of the frontal and temporal lobes. • Olfactory or gustatory hallucinations, anosmia, temporal lobe seizures, personality change, bizarre or psychotic behavior or delirium, aphasia, and hemiparesis. • Swelling and herniation of one or both temporal lobes through the tentorium may occur • Status epilepticus is rare.

5. Herpes Simplex Encephalitis • The CSF is typically under increased pressure • Almost invariably shows a pleocytosis (range, 10 to 200 cells per cubic millimeter, infrequently more than 500). • The cells are mostly lymphocytes, • In a few cases, 3 to 5 percent in some large series, the spinal fluid has been normal in the first days of the illness. • In only a minority of cases, red cells, sometimes numbering in the thousands, and xanthochromia are found • The protein content is increased in most cases. • Rarely, the CSF glucose levels may be reduced to slightly less than 40 mg/dL, creating confusion with tuberculous and fungal meningitides

6. Diagnosis • CT scans show hypodensity of the affected areas in 50 to 60 percent of cases • MRI shows signal changes in almost all (increased signal in T2-weighted images). • T1-weighted images demonstrate areas of low signal intensity with surrounding edema and sometimes with scattered areas of hemorrhage occupying the inferior parts of the frontal and temporal lobes. • Almost always the lesions enhance with contrast

11. Diagnosis • Detection of HSV antigen in the CSF by the application of PCR • The test has extremely high sensitivity (98 percent) and specificity (94 to 100 percent) • Antiviral treatment did not appear to affect the test. • False-negative tests are most likely to occur in the first 48 h of febrile infection. • Fluorescent antibody study and by viral culture of cerebral tissue obtained by brain biopsy

12. Treatment • Acyclovir significantly reduces both mortality and morbidity from the disease • Initiate treatment while confirmatory testing is being carried out. • Early treatment • Before loss of consciousness • Within 24 hours of the onset of symptoms • Glasgow Coma Scale score of 9 to 15 • The duration of treatment of HSV encephalitis in immunocompetent patients should be 14 to 21 days

13. Herpes Simplex Encephalitis • Antiviral therapy may be discontinued if a negative CSF HSV PCR result is obtained after 72 hours following onset of neurological signs and symptoms. • Clinicians must consider alternative reasons for a false-negative CSF PCR result, including early testing after the onset of symptoms, or presence of PCR inhibitors (eg, hemoglobin degradation products in bloody CSF)