In the name of God

Encephalitis

Fadakar Nima M.D.

Assistant professor of neurology
SUMS
 ENCEPHALITIS

Encephalitis refers to inflammation of the brain parenchyma and is caused

by a wide range of infectious and autoimmune conditions.

The ensuing inflammation may be focal, multifocal, or diffuse and may

also involve the meninges (meningoencephalitis) or spinal cord
(encephalomyelitis).
clinical syndrome of encephalitis is highly variable, and, hence, case
definitions have been challenging to construct.

Nevertheless, a common requirement for the diagnosis of encephalitis is

altered mental status, defined as sustained alteration in consciousness,
lethargy, or personality change, typically for greater than 24 hours.
 Other supportive elements
fever

seizures not attributable to a preexisting seizure disorder

new-onset focal neurologic findings

CSF pleocytosis

new-onset neuroimaging abnormalities

electroencephalographic abnormalities compatible with encephalitis.

 temporal course

The temporal course of neurologic changes in infectious encephalitis is

typically categorized as acute to subacute (ie, days to weeks) to distinguish
acute encephalitis from mimics, including prion disorders and tauopathies,
which can result in similar symptoms but evolve more slowly.

Autoimmune encephalitis may develop over a longer time span and

alterations in mental status may consist solely of short-term memory loss
or new-onset psychiatric changes
 Epidemiology

The incidence of encephalitis is 5 to 10 per 100,000 individuals annually,

with rates highest in children.

Infections account for up to half of all cases

autoimmune causes are identified in 20% to 30%

the remaining 20% to 30% of cases, a specific cause is not ascertained

Herpes simplex virus (HSV) is the most commonly identified sporadic
cause of encephalitis, occurring globally and without regard for
seasonality.

In recent years, several factors have altered the epidemiology of

encephalitis.

Changes in climate, human population growth and migration, and farming

practices have resulted in the emergence and spread of arthropod-borne
viruses (arboviruses), such as West Nile virus, chikungunya virus, and tick-
borne encephalitis virus.
Widespread use of immunotherapeutics for rheumatologic and other
autoimmune conditions has resulted in a larger proportion of the
population who are immunocompromised and, thus, at risk of opportunistic
infections that can cause encephalitis.
“Type a quote here.”

–Johnny Appleseed
 Clinical Features

Common clinical features of infectious encephalitis include fever and

headache.

The disturbance of brain function that is a core feature of encephalitis can

manifest in a multitude of ways, including :

altered level of consciousness, confusion, disorientation, amnesia,

personality or behavioral change, psychiatric symptoms, movement
disorders, aphasia, other focal neurologic deficits, or seizure
 HUMAN HERPESVIRUSES

The human herpesviruses (HHVs) are a family of DNA viruses that

includes:

HSV

VZV

EBV

CMV
 HERPES SIMPLEX VIRUS

HSV is acquired through mucous membranes or broken skin, where the

virus infects sensory neurons and subsequently travels via retrograde
axonal transport to the dorsal root ganglion, establishing latency.

Entry into the CNS may occur during primary infection or viral
reactivation.
“Type a quote here.”

–Johnny Appleseed
More than 90% of cases of HSV encephalitis are caused by HSV-1with
patients older than 50 years most commonly affected.

The incidence of HSV encephalitis is also high in children younger than 3

years, in whom HSV-2 is the predominant cause
Many patients with HSV-1 encephalitis present with prodromal symptoms
suggesting upper respiratory tract or other systemic infection

Signs and symptoms of encephalitis, including altered mental status,

behavioral changes, and aphasia, then progress over the course of several
days.

Alterations in mental status can range from subtle confusion to profound

depression of consciousness, including coma.

Seizures with temporal lobe symptomatology are a common manifestation,

and olfactory hallucinations can also occur because of the early
involvement of limbic structures.
Early in the course, some patients may have fever and headaches without
encephalopathy or focal neurologic deficits, even when parenchymal brain
involvement is demonstrated by neuroimaging or EEG.
The most common reason for delay in acyclovir therapy is the failure to
consider herpes simplex virus in the differential diagnosis, despite
suggestive clinical features.

The mortality rate of HSV encephalitis reaches up to 70% in patients who

are not treated.
 Imaging & EEG
CT scan was abnormal in roughly half of all patients with HSV-1
encephalitis

whereas MRI was abnormal in nearly all patients.

Brain MRI typically demonstrates T2 hyperintensity and swelling of limbic

structures including mesiotemporal, orbitofrontal, and insular regions, with
associated restriction of diffusion on diffusion-weighted imaging (DWI)
sequences.

Early in the disease course, findings are often unilateral

when bilateral, asymmetry may help to distinguish HSV-1 encephalitis
from autoimmune causes of limbic encephalitis, which more commonly
cause symmetrical changes.

Electroencephalographic findings may also demonstrate abnormalities of

the temporal lobe, including lateralized periodic discharges, focal slowing,
or electrographic seizures,
it is important to recognize that up to 5% of patients with HSV encephalitis
will have a normal MRI

therefore, imaging alone should not exclude a diagnosis of encephalitis

 LP

lumbar puncture with CSF HSV polymerase chain reaction (PCR) is

required to confirm the diagnosis.

A typical CSF profile includes :

moderate lymphocytic pleocytosis (10 cells/mm 3 to 200 cells

modestly elevated protein (50 mg/dL to 100 mg/dL),

normal to slightly low glucose

HSV PCR has a sensitivity of 96% and specificity of 99%.

It is important to note that an absence of pleocytosis and a false-negative

PCR are both possible early in the course of HSV encephalitis and in
patients who are immunocompromised.

When suspicion is high, patients should continue treatment and HSV PCR
should be repeated in 3 to 7 days.
 VARICELLA-ZOSTER VIRUS

After HSV, VZV is the second most commonly reported cause of sporadic
viral encephalitis worldwide.

Children with primary VZV infection (chickenpox) can develop

encephalitis, typically a cerebellitis, either before or after onset of the rash

in rare cases, other parts of the brain can be affected.

Similar to HSV, VZV can establish latency in sensory ganglia after initial
infection, with the potential for reactivation particularly in the setting of
immunocompromise or advanced age.

In such cases of VZV encephalitis, a painful rash (known as herpes zoster

or shingles) often precedes the neurologic manifestations.

Notably, however, rash may be absent in up to one-third of cases

 Neurologic features

Neurologic features are variable and can include encephalopathy, focal

neurologic signs, seizures, and cranial neuropathies, although a subset of
patients will have temporal lobe signs and symptoms similar to HSV
encephalitis.

In contrast to HSV-1 encephalitis, the primary pathologic process in the

CNS may be vasculopathy.
 Diagnosis

Sensitivity of PCR for VZV is lower than that of HSV, and, thus in some
cases, the diagnosis is made by detection of anti-VZV antibodies in the
CSF.
 OTHER HERPESVIRUSES
Other herpesviruses frequently infect humans and can, in rare instances,
cause encephalitis, including EBV, CMV, and HHV-6.

In people who are immunocompetent, encephalitis associated with EBV

and HHV-6 occurs more often in childhood

HHV-6 can also cause encephalitis in adults who are

immunocompromised, most commonly in patients who have undergone
hematopoietic stem cell transplantation

CMV encephalitis can cause a CSF neutrophilic pleocytosis, in contrast to

the more common viral pattern of lymphocytic pleocytosis.
 ARBOVIRUSES

Arboviruses refer to a diverse group of viruses transmitted by arthropod

vectors (eg, mosquitos, ticks, sandflies)

They are represented by several viral families, including flaviviruses,

togaviruses, bunyaviruses, and reoviruses.

After an arthropod bite, replication and amplification of the virus occur in

the lymphatics with subsequent viremia and, in some cases, entry into the
CNS.
 Clinical features

The resultant human disease is quite variable

Many cases of arboviral infection are asymptomatic.

In symptomatic cases, a febrile illness along with headache and myalgias is

common.

Potential neurologic manifestations include meningitis, encephalitis, and

myelitis
 Diagnosis

Involvement of the deep gray matter is commonly seen on MRI and often
accompanied clinically by movement disorders.

Regarding diagnostics, because peak viremia typically precedes the onset

of neurologic symptoms, viral RNA has often cleared from the CSF and
blood by the time laboratory investigations are performed.

As a result, laboratory diagnosis often rests on detection of virus-specific

IgM in CSF and blood.
 WEST NILE VIRUS

West Nile virus has emerged as the most common epidemicviral encephalitis in
the United States over recent decade with prominent outbreaks also occurring in
central and southern Europe.

most individuals infected with West Nile virus will remain asymptomatic or
develop systemic symptoms such as fever, myalgia, and diffuse maculopapular
rash

small proportion (less than 1%) will develop West Nile neuroinvasive disease in
the form of meningitis, encephalitis, or acute flaccid myelitis.

Risk factors for developing West Nile neuroinvasive disease include older age,
diabetes or other chronic illness, or an immunocompromised state
 WEST NILE VIRUS
West Nile virus has emerged as the most common epidemicviral encephalitis in
the United States over recent decade with prominent outbreaks also occurring in
central and southern Europe.

most individuals infected with West Nile virus will remain asymptomatic or
develop systemic symptoms such as fever, myalgia, and diffuse maculopapular
rash

small proportion (less than 1%) will develop West Nile neuroinvasive disease in
the form of meningitis, encephalitis, or acute flaccid myelitis.

Risk factors for developing West Nile neuroinvasive disease include older age,
diabetes or other chronic illness, or an immunocompromised state
 Diagnosis

West Nile virus encephalitis preferentially affects the basal ganglia and
thalamus, and thus can present with parkinsonism, tremors, or other
movement disorders

Accompanying brainstem involvement can result in cranial neuropathies,

bulbar dysfunction, or respiratory failure.

CSF studies demonstrate a neutrophilic pleocytosis in up to half of

patients.
Approximately 90% of patients with neuroinvasive disease have detectable
CSF IgM antibody within 10 days of symptom onset.

However, West Nile virus IgM may persist for prolonged periods, with
detectable IgM titers for longer than 1 year

thus, in some cases, the finding of West Nile virus IgM may reflect
previous exposure rather than current illness.
 JAPANESE ENCEPHALITIS VIRUS

Japanese encephalitis virus is the most important cause of encephalitis in

South and Southeast Asia

typically affecting children younger than 10 years.

After a characteristic prodrome of fever and headache, mental status

changes, seizures, focal neurologic deficits, and movement disorders
develop.

Masklike facies, tremor, and rigidity are often present, and other features
typical of basal ganglia involvement including opsoclonus-myoclonus,
dystonia, and chorea may also occur.
 JAPANESE ENCEPHALITIS VIRUS
Japanese encephalitis virus is the most important cause of encephalitis in
South and Southeast Asia

typically affecting children younger than 10 years.

After a characteristic prodrome of fever and headache, mental status

changes, seizures, focal neurologic deficits, and movement disorders
develop.

Masklike facies, tremor, and rigidity are often present, and other features
typical of basal ganglia involvement including opsoclonus-myoclonus,
dystonia, and chorea may also occur.