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%)
 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.