Herpes Simplex Encephalitis (hse)

herpes simplex encephalitis (HSE) Background: Despite advances in antiviral therapy over the past 2 decades, herpes simplex encephalitis (HSE) remains a serious illness with significant risks of morbidity and death.

 In children beyond the neonatal period and in adults, HSE usually is localized to the temporal and frontal lobes and is caused by herpes simplex virus type 1 (HSV-1). In neonates, however, brain involvement is more often diffuse and the usual cause is HSV-2, which is acquired at the time of delivery.

Pathophysiology  Pathogenesis of HSE is poorly understood. Brain involvement is diffuse; petechial hemorrhage and necrosis are distributed in medial temporal and inferior frontal lobes.

 Brain infection is thought to occur primarily by direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve.

 In some cases HSE is thought to represent a reactivation of a latent infection within the brain. Asymptomatic HSV infection is very common, as evinced by the high prevalence of HSV antibodies in the general population. Latent HSV infection of the brain may be present in a significant proportion of neurologically asymptomatic individuals.

 In most cases, HSE is a rapidly progressive disease with profound neurologic derangement.

Frequency:  In the US: HSE accounts for about 10% of all encephalitis cases. It is the most common cause of sporadic fatal encephalitis, occurring in about 1 per 250,000-500,000 persons per year.  Mortality/Morbidity: The mortality rate in untreated patients is 70%. Among treated patients, the mortality rate is 19%, and more than 50% of survivors are left with moderate or severe neurologic deficits.

 Sex: Incidence in males and females is equal.  Age: Incidence peaks in childhood and again in middle-aged adults.

History  HSE is an acute or subacute illness causing general and focal signs of cerebral dysfunction. It is sporadic and occurs without seasonal pattern.

Symptoms        

Typical symptoms include the following: 1 ． Fever (90%) 2 ． Headache (81%) 3 ． Psychiatric symptoms (71%) 4 ． Seizures (67%) 5 ． Vomiting (46%) 6 ． Focal weakness (33%) 7 ． Memory loss (24%)

Findings  Typical findings on presentation include the following:  1 ． Alteration of consciousness (97%)  2 ． Fever (92%)  3 ． Dysphasia (76%)  4 ． Ataxia (40%)  5 ． Seizures (38%)

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6 ． Focal findings (28%) 7 ． Generalized findings (10%) 8 ． Hemiparesis (38%) 9 ． Cranial nerve defects (32%) 10 ． Visual field loss (14%) 11 ． Papilledema (14%)

Lab Studies:  Cerebrospinal fluid analysis  CSF analysis typically reveals a mononuclear pleocytosis with mildly elevated protein and normal or mildly reduced glucose.  Because of the hemorrhagic nature of the process within the brain parenchyma, the red blood cell (RBC) count is usually elevated.  HSV is rarely cultured from CSF in affected individuals.

 Magnetic resonance imaging  MRI of the brain is the preferred imaging study.  The MRI shows pathologic changes, which are usually bilateral, in the medial temporal and inferior frontal areas.  confirmation of the diagnosis depends on identification of HSV by means of PCR or brain biopsy.

Therapy    

Goals of therapy are (1) to shorten the clinical course, (2) to prevent complications, (3) to prevent development of subsequent recurrences.

Drug Category  Antiviral agents -- The treatment of choice for HSE is acyclovir, an antiviral agent that selectively inhibits viral replication without damage to normal cells.

 Acyclovir has relatively few serious adverse effects. The drug is excreted by the kidney, and the dose should be reduced in patients with renal dysfunction.

 Because of its high pH, intravenous acyclovir may cause phlebitis and local inflammation if extravasation occurs. Gastrointestinal disturbances, headache, and rash are among the more frequent adverse reactions.

 Acyclovir is considered to be appropriate for serious infections during pregnancy.

Complications:  Seizures are common, and some authorities recommend prophylactic treatment with anticonvulsant drugs in patients with severe HSE.  Cerebral edema is treated with hyperventilation and barbiturates.

 Patients with HSE are subject to the same complications as all seriously ill, immobilized patients with depressed levels of consciousness (eg, aspiration pneumonia, deep venous thromboses, decubiti).

Prognosis  Sequelae among survivors are significant and depend on age and neurologic status of the patient at time of diagnosis.  Patients who are comatose at diagnosis have a poor prognosis regardless of age.  In noncomatose patients, prognosis is age related, with better outcomes occurring in patients younger than 30 years.

 Neurologic outcomes in survivors treated with acyclovir are as follows:  1 ． No deficits or mild deficits, 46%  2 ． Moderate deficits, 12%  3 ． Severe deficits, 42%  4 ． About 5-10% of surviving patients relapse days to weeks after completion of treatment.