Download Viral Encephalitis

Viral Encephalitis
Introduction
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Encephalitis is an acute inflammatory process
affecting the brain
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Encephalitis can be caused by bacterial infection and,
most often, by viral infection with over 100 viruses
implicated worldwide.
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Encephalitis is the most serious manifestation of viral
CNS infection.

Encephalitis is distinguished from aseptic meningitis
by the extent and severity of cerebral dysfunction,
independent of signs of meningeal inflammation.
Introduction
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Many more cases of encephalitis actually occur each
year than those reported.
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Incidence of 3.5-7.4 per 100,000 persons per year
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Symptoms
 Fever
 Headache
 Behavioral changes
 Altered level of consciousness
 Focal neurologic deficits
 Seizures
Causes of Viral Encephalitis
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Herpes viruses: HSV-1, HSV-2, VZV, CMV, EBV,
HHV-6
Adenoviruses
Influenza
Enteroviruses including polioviruses
Measles, mumps, and rubella viruses
Rabies virus
Arboviruses: Japanese encephalitis, St. Louis
encephalitis, West Nile encephalitis, Eastern and
Western equine encephalitis, Venezuelan equine
encephalitis, Lacrosse encephalitis, Colorado tick
fever, and lymphocytic choriomeningitis viruses
Etiology and Pathology

There are two types of encephalitis, primary which
is caused by direct viral infection, and secondary
which results from complication of a current or a
recent viral infection.
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Primary infection can be focal or diffuse and
secondary encephalitis is acute and disseminated
that often occurs 2 to 3 weeks following the initial
infection
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Most cases of primary encephalitis are caused by
enteroviruse, herpes viruses, arboviruses and
rabies virus

Secondary encephalitis, usually a complication of viral
infection, is considered to have an immunologic
mechanism.

Examples are encephalitides secondary to measles,
chickenpox, influenza, rubella, vaccinia, and many
other less well defined viral infections.

These parainfectious or postinfectious encephalitides
typically develop 5 to 20 days after onset of illness and
are characterized by perivascular demyelination seen
at autopsy; a virus is rarely isolated from the brain.
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Very rarely, encephalitis or other encephalopathies
occur as a late consequence of viral infections.
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The best known is subacute sclerosing
panencephalitis and progressive rubella
panencephalitis, associated with measles and
rubella viruses respectively.
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Direct viral invasion of the brain is likely to result in
neuronal necrosis, frequently with visible inclusion
bodies.
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In parainfectious and postinfectious
encephalomyelitis, perivenous demyelinating
lesions are characteristic.
Epidemiology
 Viruses
causing primary encephalitis may
spread in epidemics (arboviruses, polioviruses,
echoviruses, and coxsackieviruses) or
sporadically (herpes simplex, varicella -zoster,
and mumps viruses).
 Mosquito-borne
arboviral encephalitides (St.
Louis, eastern and western equine, and
Lacrosse) infect humans only during warm
weather.
Pathogenesis

The pathogenesis of encephalitis due to herpes
simplex virus, arboviruses, and rabies virus is different
for each virus.
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In neonates, herpetic encephalitis is predominantly
due to HSV-2, and irrespective of serotype, the acute
generalized necrotizing encephalitis is often
accompanied by evidence of systemic infection of the
liver, adrenals, and other organs.
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In children and adults, herpetic encephalitis is caused
by HSV-1 and is usually localized.
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HSV Encephalitis in an immune host results either
from the entry of a new virus, possibly across the
olfactory mucosa, or from reactivation of latent virus in
the trigeminal ganglia, which spread along sensory
nerve fibers to the base of the anterior and middle
fossa.
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In either case, infection is localized to the orbital,
frontal, and medial temporal lobes.
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Because the host is immune, virus presumably
spreads from cell to cell over a contiguous localized
area, infecting neurons and glial cells.
 In
contrast, arboviruses (mainly togaviruses,
flaviviruses, and bunyaviruses) spread to the
brain from the blood.
 The
systemic infection causes few, if any,
symptoms.
 Depending
on the virus, between 1 in 20 and 1 in
1000 infections are complicated by CNS
infection.
 The
encephalitis is diffuse, but is localized largely
to neurons.
Clinical Course of Encephalitis
 Encephalitis
may produce fever and malaise
without meningeal signs, or it may cause
meningeal signs with cerebral dysfunction.
 As
brain parenchyma becomes involved, there
is an alteration of consciousness; personality
changes, ataxia, seizures, cranial nerve
abnormalities, and paralysis followed by coma.
 In
addition to headache and fever,
hallucinations and bizarre behavior are
common, and these are sometimes confused
with psychiatric illness.
 Focal
seizures and hemiparesis are frequent,
and aphasia develops if the disease is localized
to the dominant temporal lobe.
 Herpes
simplex virus-1 encephalitis in the nonneonate typically causes focal signs that may
evolve over a period of up to 1 or 2 weeks.
 Herpes
simplex encephalitis is clinically similar
to other viral encephalitides but is strongly
suggested by repeated seizures occurring early
in the course of disease and by signs indicating
temporal or frontal lobe involvement.
 Arbovirus
infections cause a more diffuse and
acute disease, with a rapid depression of
consciousness, greater frequency of
generalized seizures, and multifocal signs.
 At
times, however, arbovirus or any other form
of encephalitis may localize to the temporal
areas, producing signs very similar to those of
herpes simplex virus encephalitis.
Diagnosis
 Viral
infections must be differentiated from other
infections (bacterial, rickettsial, spirochetal, and
parasitic) and noninfectious disorders
 The
major problem is to distinguish viral
encephalitis from acute or partially treated
bacterial meningitis
 Diagnosis
is usually based on CSF changes,
including normal glucose and absence of
bacteria on culture.
 Cultures
(eg, from the nasopharynx or stool)
and attention to epidemic agents in the
community may help.
 Because
of public health implications, serum
should be drawn and preserved whenever the
diagnosis of encephalitis or aseptic meningitis
of uncertain etiology is first suspected.
 The
CSF examination in acute encephalitis may
or may not show an increase in pressure, but
usually reveals an inflammatory response of
mononuclear cells.
 RBCs
in CSF after an atraumatic spinal tap
suggest herpes simplex infection because of
the necrotizing pathology of the disease, but
they are not universally present nor are they
specific to the disease.
 Viruses
are occasionally isolated directly from
CSF or from other tissues but are identified in
fewer than half of the cases.
 Herpes
simplex virus is rarely isolated from
CSF but it can be precisely identified by
polymerase chain reaction in CSF.
A
prompt, definitive diagnosis of HSV-1
encephalitis requires brain biopsy of the area
where typical encephalitis with inclusion bodies
is seen.
 The
diagnosis is confirmed by either
immunocytochemical staining of herpes simplex
virus antigens in brain cells or virus isolation.
 Biopsy
is, however, rarely indicated and should
be reserved for patients who are worsening,
have an undiagnosed lesion after CT or MRI, or
have a poor response to acyclovir.
 The
electroencephalogram (EEG) is helpful in
the diagnosis of herpes simplex virus
encephalitis because periodic spikes and slow
waves often localize to the infected temporal
lobe. In other forms of encephalitis slowing is
more diffuse.
 Computerized
tomography (CT) in cases of
herpes simplex virus encephalitis usually shows
an attenuated area in the medial temporal lobes
and sometimes a mass effect, but these
findings, like the CSF and EEG changes, are
not diagnostic.
 MRI
may detect inferior-frontal and medialtemporal lobe inflammation earlier than EEG,
CT, or radionuclide brain scanning, prompting
antiviral therapy before neurological
deterioration occurs.
 MRI
can exclude brain abscess, subdural
empyema, subdural hematoma, tumor, and
sagittal sinus thrombosis, which can clinically
mimic encephalitis.
Prognosis and Treatment

The only treatable cause of viral encephalitis is
Herpes viruses. Therefore, until HSV encephalitis is
ruled out by PCR, the patient must be treated with
acyclovir.
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The mortality rate varies with etiology, and epidemics
due to the same virus vary in severity in different
years.
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Permanent cerebral sequelae are more likely to occur
in infants and young children improve in a shorter time
than adults with similar infections.
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Permanent sequelae include mental retardation,
epilepsy, blindness and deafness.
Post-infectious Viral Syndromes of the CNS
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Post infectious encephalitis is seen in
approximately 1:1000 cases of measles, mumps,
vaccinia, etc., and is immunologically mediated.
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Reye’s syndrome follow infections with influenza,
varicella, adenovirus and other viruses. It chiefly
affects children between the ages of 2 and 16.
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Guillain-Barré syndrome is an acute
inflammatory demyelinating polyneuropathy often
following one of many antecedent viral and nonviral illness.