Introduction:Infection of CNS

Viral meningitis and Encephalitis

 Infections of the central nervous system (CNS) range from
common to rare, acute to chronic, and benign to fatal, some are
self-limited prompt diagnosis and aggressive management afford
the best chance of recovery without sequelae.
The clinical hallmarks of CNS infection:
● fever
● headache
● alteration of mental status
● focal neurologic signs
RISK FACTORS FOR CENTRAL NERVOUS SYSTEM INFECTIONS
Concomitant illnesses (HIV infection or diabetes), alcoholism,
immunosuppressant medications, or cancer chemotherapy
CLUES ON PHYSICAL EXAMINATION
Physical examination of suspected CNS infection has three
purposes:
(a) to identify contraindications to lumbar puncture
(b) to identify concomitant sites of infection or pathology that
provide clues to the infectious etiology, and
(c) to define the site of CNS infection.

Identification of concomitant pneumonia, diarrhea, and skin or

bone lesions may offer clues to the etiology of infection.
Most importantly, findings on neurologic examination allow
for identification of the most likely site or sites of infection
among cerebrospinal fluid (CSF) space, brain, or spinal cord.
Acute Meningitis Syndrome: acute onset over a few hours to a few days of fever, headache,
vomiting, photophobia, stiff neck, and altered mental status. The latter may range from simple
irritability to confusion, obtundation, or coma.
In many cases → no warning, an acute upper respiratory tract infection may precede the onset of
meningitis by a few days.
The two leading causes of acute meningitis are bacteria and viruses.
Subacute or Chronic Meningitis Syndrome: course over weeks, months, or years.
The differential diagnosis for subacute and chronic meningitis:
● tuberculosis
● fungal infections (cryptococcosis, coccidioidomycosis, histoplasmosis)
● spirochetal infections (syphilis and Lyme disease)
Acute encephalitis syndrome: inflammation of the cerebral cortex, most commonly
caused by viruses. Acute encephalitis may be either diffuse or focal.
Focal encephalitis reflects tropism of some viruses for specific locations in CNS→
temporal lobe infection by herpes simplex virus type 1 (HSV-1), or the anterior horn
cells in flavivirus infections (West Nile).
ANATOMY AND PHYSIOLOGY OF THE CEREBROSPINAL FLUID COMPARTMENTS

The CSF is contained within two connecting compartments, the cerebral ventricles and
the subarachnoid space.
The Meninges and Subarachnoid Space: The brain and spinal cord are surrounded by
three layers of meninges. The outermost layer of the meninges is fibrous membrane, the
dura mater. The middle layer of meninges, the arachnoid. The third layer of
meninges, the pia mater, is continuous with the surface of the brain and spinal cord.
The CSF is contained in the subarachnoid space, enclosed between the arachnoid and
the pia. The subarachnoid space is normally a closed system. However, congenital or
posttraumatic communications may exist between the subarachnoid space and
superficial tissues and may provide a route for single or recurrent episodes of
meningitis.
 PHYSIOLOGY OF CEREBROSPINAL FLUID PRODUCTION AND REABSORPTION

CSF is produced by the choroid plexuses of the lateral, third, and fourth ventricles and,
to a lesser extent, by extrachoroidal sites. In adults, the choroid plexus produces ≈500
mL of CSF per day, with 150 mL present in the ventricular system at any time.

BRAIN AND CEREBROSPINAL FLUID BARRIER SYSTEM

The brain and CSF are contained within a series of barrier systems: the blood–brain
barrier (BBB), the blood–CSF barrier.
The endothelial cells and astrocytes of the BBB and the blood–CSF barrier→ important
sources of cytokines (including TNF).
The release of cytokines by endothelial cells and astrocytes in response to bacterial
endotoxins and other bacterial products is fundamental in the production of
inflammation and injury during CNS infections.
Indications for Lumbar Puncture

LP is essential in the diagnosis of bacterial, viral, or fungal meningitis and

encephalitis. LPs should not be done in patients with impending herniation
or with intracranial mass lesions with severe mass effect.
Clinicians have relied on the meningeal signs (nuchal rigidity, Kernig sign,
Brudzinski sign) for over 100 years to evaluate patients with suspected
meningitis to help them decide who should undergo a LP.

The absence of the meningeal signs should not defer the performance of LP
Meningeal signs:
Nuchal rigidity (Neck stifness): the inability to flex the neck forward due to rigidity of
the neck muscles.
Kernig's sign: positive when the thigh is bent at the hip and knee at 90 degree angles, and
subsequent extension in the knee is painful.
Brudzinski's neck sign: severe neck stifness causes a patient s hips and
kneees to flex when the neck is flexed
Technique of Lumbar Puncture:
The first was performed by Quincke in 1891.
The LP is generally performed with the patient in the lateral recumbent
position in a fetal position with the knees flexed toward the chest, and the
neck slightly flexed.
The landmarks used are the anterior superior iliac crests, which correlate with
the L4 to L5 interspace. The needle may be inserted between the L3 and L4,
L4 and L5, or L5 and S1 interspace.
The needle should not be inserted over a skin infection or abscess.
(potential of inserting bacteria into CSF)
The performer of the LP should follow a sterile technique (hand washing,
gloves, gown, and mask).
Major Complications of Lumbar Puncture

Herniation: to obtain a CT scan of the head prior to performing a LP in

patients with suspected meningitis, to ―rule out‖ the possibility of an
intracranial mass, hydrocephalus, edema, or any other signs of increased ICP
Risk for cerebral herniation after CSF removal during the LP → altered state
of consciousness, abnormalities in pupil reflexes, and decerebrate or
decorticate posturing.

Post–Lumbar Puncture Headache: the most frequent complication of LP,

occur in 10% to 60% of patients, bilateral headache that worsens while
sitting up and improves lying down, develops within 7 days after a LP, and
disappears within 14 days.
A ―blood patch‖→ injection of 20 to 30 mL of the patients fresh blood into
the epidural space (by closing the CSF leak by forming a clot).
Routine Studies of Cerebrospinal Fluid:

● Measurement of CSF pressure

● Gross examination of the fluid for turbidity or changes in color
● Measurement of CSF protein and glucose concentrations
● RBC and WBC counts
● Gram stain and bacterial culture of CSF
● CSF Acid-Fast Bacilli Stains and Cultures

Normal CSF is colorless and clear.

CSF may become turbid, discolored, or both.
The yellow discoloration is termed xanthochromia, often used to distinguish
between a so-called bloody tap and subarachnoid hemorrhage. It may also be
seen in the presence of increased amounts of protein.
Cell Count:
Normally, CSF contains fewer than five cells per cubic millimeter (lymphocytes).

The WBC count between 1,000 and 5,000/mm3 in untreated bacterial

meningitis, the most common three types of viral meningitis (enterovirus,WNV,
HSV)→ a median WBC count between 100 and 250 cells/mm3.

Differential White Blood Cell Count:

●bacterial meningitis→neutrophils→an average of 86.4% of cells counted
●aseptic meningitis→ neutrophils → 34.2%

In the early stages of meningitis, this distinction between bacterial and viral
etiologies may not be clear because a neutrophilic pleocytosis (>50%) may
accompany early viral meningitis or encephalitis.
Within 12 to 24 hours→a shift from a neutrophilic predominance to a
lymphocytic predominance, repeat LP if the first LP was nonspecific.

Lymphocytic pleocytosis→ viral meningitis, M. tuberculosis, B. burgdorferi,

Treponema pallidum, C. neoformans, neoplastic and drug induced meningitis
Red Blood Cells: the presence of RBCs may result from a traumatic LP or may
indicate subarachnoid or parenchymal hemorrhage.
A traumatic tap in the setting of CNS infection increase the numbers of WBCs.

Cerebrospinal Fluid Glucose: predictable reflection of blood glucose, the ratio of

CSF to blood glucose concentrations is approximately 0.6.

CNS infections may alter glucose transport across the blood–CSF barrier,
resulting in a low CSF glucose level→ hypoglycorrhachia→ meningitis caused
by bacteria, mycobacteria, or fungi.

The CSF glucose level is usually normal during viral infections, but low CSF
glucose levels →enteroviruses, mumps, lymphocytic choriomeningitis, HSV.
CSF glucose→ important parameter to follow in assessing response to therapy.
Cerebrospinal Fluid Protein: falsely elevated by deteriorating RBCs following
subarachnoid hemorrhage or traumatic LP. Changes in the concentration of
protein in CSF are the most common and least specific, in a wide variety of
infectious and noninfectious neurologic conditions, little specific value in the
diagnosis of CNS infections →may remain abnormal for months after
parenchymal infections.

Cerebrospinal Fluid Bacterial Culture: The CSF should be submitted to the

laboratory immediately after the LP and should be placed in culture promptly

Cerebrospinal Fluid Acid-Fast Bacilli Stains and Cultures: a positive acid-fast

stain for M. tuberculosis is highly suggestive of TB, positive results in only10%

Isolating mycobacteria in culture (Lowenstein-Jensen medium, automated

commercial system BACTEC Mycobacteria Growth Indicator Tube (MGIT)
ADJUNCTIVE AND MOLECULAR STUDIES OF CSF IN THE DIAGNOSIS OF CNS INFECTION

Bacterial Infections
Molecular tests are not routinely available, and Gram stain and culture of the
CSF→ gold standard for diagnosis

Lactic Acid: elevation of lactic acid levels more frequently in bacterial than in
viral meningitis (>3.5 to 4.2 mmol/L→bacterial infection)
C-Reactive Protein: serum and CSF CRP → for discriminating bacterial
meningitis from aseptic or viral meningitis.
Detection of Bacterial Antigens: latex agglutination assays rapidly detect
meningitis caused by H. influenzae type b, N. meningitidis serogroups A, B, C,
Y, W135, S. pneumoniae, E. coli K1, and Streptococcus agalactiae.
Detection of Cytokines: TNF, IL-1, and other cytokines mediators during
bacterial meningitis, can help distinguish between bacterial and viral meningitis
Viral infection:
PCR for enteroviruses, HSV, VZV, CMV, EBV, WNV
Viral Culture: isolation of viral agents by tissue culture methods

CSF antibody titers and determination of CSF/serum antibody ratios →

comparison of serum and CSF titers of IgG and IgM antiviral antibodies

Lyme Disease:
CDC recommends using a two-step process for testing serum.
I: screening with an enzyme-linked immunosorbent assay (ELISA) or
immunofluorescence assay.
II: all equivocal or positive results are subsequently confirmed by
immunoblotting (Western blot).
Fungal Infections: detection of cryptococcal antigen replaced India ink stains.
CHARACTERISTIC CEREBROSPINAL FLUID FINDINGS IN MAJOR CNS INFECTIONS

Bacterial Meningitis: neutrophilic pleocytosis, hypoglycorrhachia, an elevated

protein level. Numbers of PMN leukocytes usually range between 1,000 and
10,000 cells. An atypical CSF profiles → especially in Listeria monocytogenes.

Tuberculous Meningitis :
a). pleocytosis with lymphocytic predominance
b). lowered glucose level
c). elevated protein level
In approximately 70% of patients, the cell count is between 100 and 400 cells.

Viral and Other Acute Meningoencephalitis: lymphocytic pleocytosis (10 to

1,000 cells/mm3), mildly elevated protein and normal CSF glucose. PMN may
constitute more than 50% during the first 24 to 36 hours of the infection.
 Imaging of Intracranial Infections
Imaging plays an important role for the differential diagnosis and occasionally identifying a
particular entity that has a characteristic appearance (HSV encephalitis, pyogenic abscess, or
empyema). Imaging is also crucial for identifying complications and response to treatment.

Meningitis: usually normal in cases of bacterial meningitis (leptomeningeal enhancement)

Herpes Simplex Virus: infection usually begins in the anterior and medial aspects of the temporal lobe(s) but
may extend to the lateral temporal lobes, inferior frontal lobes, insular cortex, and frontal and parietal
cingulate gyri. Findings may be unilateral or bilateral.

VZV infection is distinct among viral infections in that it causes a vasculopathy.

Arboviruses: lesions are located in the basal ganglia and thalami bilaterally.

HIV: imaging findings related directly to HIV infection in the CNS or related to opportunistic infections.
+

HSV encephalitis
A: NCCT shows left temporal low density and volume explansion with petechial areas of hemorrage (arowhead)
B: Coronal FLAIR MR1 shows bilateral involvement of the anterior and medial temporal lobes and insula
Pathogenesis and Pathophysiology of Viral Infections of the CNS
Viral infections of CNS occur infrequently and most often result in relatively
benign, self-limited disease. The pathogenesis of viral infections is
multifactorial: age, immune status, cultural practices, and genetic.
The definition of viral CNS disease based on both viral tropism and duration.
Encephalitis refers to inflammation of parenchymal brain tissue.
Acute encephalitis occurs over a relatively short period of time (days), whereas
chronic encephalitis presents over weeks to months.

Viral disease in the CNS can also be classified by pathogenesis:

A primary encephalitis results from direct viral entry into the CNS that produces
clinically evident cortical or brainstem dysfunction.
Postinfectious or parainfectious encephalitis→ acute demyelinating process
temporally associated with a systemic viral infection but without evidence of
direct viral invasion in the CNS→ one of the causes of acute disseminated
encephalomyelitis (ADEM).
Inflammation of the spinal cord, leptomeninges, dorsal nerve roots, or nerves →
myelitis, meningitis, radiculitis, and neuritis.

Aseptic meningitis is frequently used to refer to a benign, self-limited, viral

infection causing inflammation of the leptomeninges. The definition fails to
differentiate between infectious (fungal, tuberculous, viral, or other infectious)
and noninfectious causes of meningitis.

CDC: notification of 7,200 to 14,500 cases of ―aseptic meningitis‖ annually.

Most → occurred from the late spring to autumn months, reflecting the increased
incidence of enteroviral and arboviral infections during these seasons.
 PATHOGENESIS

Viral Spread: viruses use two basic pathways with fundamentally different steps
to gain access to the CNS: hematogenous and neuronal.

Hematogenous Spread (enteroviruses and arboviruses): the initial steps involved

in hematogenous spread of virus to the CNS consist of replication at the local site
of entry and primary viremia.
Infection of a secondary tissue frequently ensues, permitting secondary
replication and an extensive viremia that seeds the CNS.

The nonkeratinized epithelial layer that constitutes the conjunctival, respiratory,

oral, and nasopharyngeal surfaces provides an ideal entry point for aerosolized
viruses or pathogens transmitted by large droplets. In the gastrointestinal and
urogenital systems, constant transit protects the mucosa.

Once virus breaches the epithelial barrier and finds a permissive cell, primary
replication occurs. Virus then can spread and replicate in the lymph node, or it
can bypass the node and enter the circulatory system, where it seeds other tissues.
Primary viremia allows virus to seed distant locations of the body and frequently
marks the onset of clinical illness. The liver and spleen provide ideal locations
for secondary viral replication because of their highly vascular structure. Viruses
infect tissues other than the liver and spleen (muscle, endothelium, blood cells).

Secondary viremia produces high titers of virus in the bloodstream for prolonged
periods of time, facilitating the seeding of target organs. Viral genetics and host
physiology determine the location and extent of infection at these secondary
sites. Virus must localize in the vessels of the CNS before crossing the blood–
brain or blood–CSF barrier.

Neuronal Spread: Rabies and HSV infection are prototypes, neuronal spread
occurs along peripheral or cranial nerves.
VIRAL REPLICATION IN THE CENTRAL NERVOUS SYSTEM

The clinical manifestations and the severity of illness reflect the location and extent of viral
replication in the CNS.
Attachment and viral entry → essential first steps in viral infection.

Viral Spread in the Central Nervous System:

Viruses can spread through the CNS in four prototypical ways:
(a) sequential cellular infection,
(b) movement in the extracellular space,
(c) neuronal axoplasmic transport,
(d) transit via migrating lymphocytes or glial cells

Host Defense and Immunopathogenesis

Interferon-mediated intrinsic antiviral pathways within cells can retard viral penetration,
uncoating, transcription, translation, and representing an important factor of host resistance to
viral infection. In postinfectious encephalitis, the immune response is misdirected against the
brain itself. There is no evidence of direct viral damage or viral antigens in the CNS.
Clinical Correlates to Disease
Patients with encephalitis→ clinical and laboratory evidence of parenchymal
disease, most patients with encephalitis have concomitant meningitis and
prodromal illness (myalgias, fever, anorexia)→systemic viremia.
Neurologic symptoms→ fever, headache, subtle neurologic deficits or change
in level of consciousness to severe disease with seizures, behavioral changes,
focal neurologic deficits, and coma.
Brainstem encephalitis leads to difficulty with autonomic functions(risk for
cardiac and respiratory instability)
Seizures are frequent during encephalitis (40%)
Encephalitis, unlike meningitis, has higher mortality and complication rates.
Viral meningitis
Central nervous system (CNS) viral infection with signs of meningeal
irritation (neck stiffness, Kernig and/or Brudzinski signs) and cerebrospinal
fluid (CSF) pleocytosis but without neurologic dysfunction due to brain
parenchymal involvement.

Patients with meningitis→ nonspecific symptoms such as fever (38° to 40°C)

of 3 to 5 days duration, malaise, and headache, 50% have nausea or vomiting.

Nuchal rigidity and photophobia are the hallmark sign and symptom for
meningitis, 33% of patients with viral meningitis have no meningismus.
ENTEROVIRUSES

Virology and Pathogenesis:

Four groups (A-D), more than 100 serotypes, majority of the EVs are
transmitted via a fecal-oral route, contaminated fomites, or ocular and
respiratory secretions, transplacental transmission (congenital infection).

Following ingestion of the EVs, infection of the cells of the nasopharynx

and, more significantly, the lower gastrointestinal (GI) tract occurs.

Seeding of EV to the deep cervical and mesenteric lymph nodes →spread

to the systemic circulation via the lymphatics→primary/minor viremia
leads to seeding of various organs (CNS, liver, lungs, skin, heart), and
replication in the tissues of those organs→ secondary/major viremia.

The majority of EV infections do not result in clinically apparent

infection, IFN responses may be crucial in limiting the spread of EV
Epidemiology: a ubiquitous worldwide distribution; humans are their only natural reservoir,
responsible for 80% to 90% of identifiable causes of viral meningitis (B species).

Clinical Manifestations: vary with the age and immune status of the patient.
In infants and children: an incubation period of 5 to 10 days, abrupt with fever (38° to 40°C), the
fever pattern may be biphasic, an exanthem may be present.

In adolescents and adults: headache is the most frequently symptom, photophobia, fever, signs of
meningeal irritation, nausea, vomiting, neck stiffness→ more than 60%
Less frequently → myalgia, exanthems, abdominal pain.

Treatment and Prevention: No specific treatment. Supportive measures (bed rest, antipyretics).
Administration of parenteral fluids. The promising results from clinical trials of pleconaril.
The EVs are spread primarily through a lack of good hygiene (hand washing).
ARBOVIRUSES: transmitted by the bite of an insect or tick (i.e., an arthropod vector).

Flaviviridae:
West Nile Virus (RNA viruses)
Infections occur during the summer months (from July through October) coinciding with periods
of increased activity of its vectors (mosquitoes).
Transmission to humans is incidental (transfusion of blood products and organ transplantation,
maternal–infant vertical transmission).
Approximately 80% infected with WNV remain asymptomatic.
The majority→ develops an acute, self-limited febrile illness→West Nile fever
Age is the most significant risk factor for West Nile neuroinvasive disease (WNND).
Analysis of the CSF shows a lymphocytic pleocytosis of generally less than 500 cells/mm3. If the
CSF is examined early in the course of the illness, a polymorphonuclear pleocytosis may be seen.

Tick-Borne Encephalitis Virus→ 3 subtypes of the virus European, Siberian, and Far Eastern.
Humans may be infected through the bite of an infected tick or, less commonly, the consumption
of virus-infected milk. The majority of cases occur from March to November. Vaccines are
available in Europe and Canada. No specific therapy.
HUMAN HERPESVIRUSES:
Herpesviruses—HSV types 1 and 2, varicella-zoster virus (VZV), Epstein-Barr
virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6 and HHV-7.

HSV-1 and HSV-2→ the major causes of aseptic meningitis

HSV-2 and, much less commonly, HSV-1 have been associated with aseptic
meningitis in patients with primary genital herpes infection.

VZV meningitis: complication of primary infection (chickenpox) and

reactivation (zoster).

HIV: aseptic meningitis as part of the clinical constellation of syndromes

associated with primary HIV infection.
Encephalitis
The term encephalitis generally refers to inflammation of the brain parenchyma.
Patients are often critically ill, and there are many potential etiologies, an etiology is only
identified in 40% to 70% of cases. Even when a cause is identified, there may be no effective
treatment. Mortality rates range from 3% to 15%, the frequency of sequelae (cognitive and motor
impairment, seizures) in 20% to 40% of patients.

Encephalitis:fever, headache, altered mental status, seizures, focal neurologic deficits.

Alteration in mental status distinguishes encephalitis from uncomplicated meningitis.

In practice, the distinction between these two entities is not always readily apparent, the terms
encephalitis or meningoencephalitis are often broadly applied.

Encephalopathy refers to any diffuse disease of the brain that results in changes in function.
The clinical hallmark of encephalopathy is an altered mental state.
HSE caused by HSV-1 → 10% to 20% of adult encephalitis cases,
most → result of HSV reactivation

The presence of herpes labialis has no diagnostic specificity for encephalitis, but
does serve as a marker of HSV infection.

The characteristic clinical presentation for HSE includes altered mental status
(97%), fever (90%), and headache (81%).

Other neurologic findings→personality change (85%), aphasia (40%), ataxia

(40%), hemiparesis (38%), cranial nerve deficits (32%), and seizures (31%).

HSV-2→disseminated encephalitis
Varicella-Zoster Virus: both primary infections with varicella-zoster virus and
endogenous reactivation (herpes zoster)

In children→ acute cerebellar ataxia

In adults→diffuse brain dysfunction, seizures, cranial nerve palsies

The presence of a diffuse varicella rash or a vesicular rash →an important clue to
diagnosing VZV encephalitis

Epstein-Barr: aseptic meningitis, Guillain-Barré syndrome, Bell palsy, transverse

myelitis, cerebellitis, and encephalitis, seizures (48%).

Enteroviruses (EVs): leading cause of encephalitis in children

Arboviruses:

West Nile virus→the most common cause of arboviral encephalitis in US

Most → subclinical infection (70% to 80%) or febrile illness (20% to 30%).

Less than 1% of infected individuals develop West Nile neuroinvasive disease
(meningitis, encephalitis, and/or acute flaccid paralysis)
Risk factors → older age, male gender, HTA, diabetes, renal disease, and
immunosuppression
Characteristic presentations→ altered mental status/ lethargy with or without
movement disorders (tremors, Parkinsonism, or myoclonus)

Tick-borne encephalitis virus (TBEV):

European virus subtype: the illness often biphasic, with the first stage
characterized by fever, fatigue, general malaise, headache, and body pain.
Rabies: one of the oldest known infectious diseases, the most deadly
The incubation period→ 20 - 60 days (from a few days to several years)
Approximately 80% of human rabies cases develop the encephalitic (―furious‖)
form (unusual behavior, extreme agitation, hydrophobia, delirium, and seizures).
The other develop the paralytic (―dumb‖) form (ascending paralysis followed by
confusion and coma).

Measles Virus: acute encephalitis in approximately 1 in 1,000 cases.

Measles→subacute sclerosing panencephalitis (SSPE), an indolent, progressive,
and often fatal form of encephalitis that typically occurs 7 to 12 years after the
initial infection and usually affects children between 10 and 14 years of age.

Influenza-associated encephalitis (IAE): sporadically and follow the seasonal

influenza pattern, more common in the pediatric population
DIAGNOSTIC APPROACH OF PATIENTS WITH ENCEPHALITIS

Anamnesis: highlighting ill contacts, occupational exposures, vector and animal

exposures, outdoor activities, ingestions, travel history, any recent or current
respiratory, gastrointestinal, or rash illness.

Lumbar puncture (LP) with cerebrospinal fluid (CSF) analysis (cell count with
differential analysis, glucose and protein concentrations).

The CSF profile: CSF mononuclear cell pleocytosis (cell counts 10-200 mg/dL).
CSF protein generally is elevated but is typically less than 100 mg/dL, whereas
the glucose level is almost always normal .

.
 ,

TESTING OF SELECTED ETIOLOGIES

Herpesviruses: the diagnostic test of choice is CSF HSV-1 DNA nucleic acid
(PCR) (can be falsely negative, early in course of illness, the pediatric agegroup).

Intrathecal antibodies: helpful in establishing the diagnosis later in the course.

Intrathecal synthesis of HSV-specific IgG antibodies can often be detected 10 to
14 days after the onset of illness.

VZV encephalitis: VZV testing should be performed in all adult patients, with or
without skin lesions.
.

Enteroviruses: PCR of both CSF and a throat specimen, culturing the stool

Arbovirus: serologic testing of CSF and serum is preferred to molecular testing

because peak viremia generally occurs prior to symptom onset.

WNV: detection of IgM capture enzyme-linked immunosorbent assay (ELISA)

● 90% of patients have CSF IgM antibody by days 8 to 10 after symptom onset
● Serologic cross-reactivity between the flaviviruses
.

MANAGEMENT:

Antiviral therapy is generally restricted to treatment of HSV and HIV infection.

Therapy with acyclovir should be started and continued until HSV-1 has been
reasonably excluded as a diagnosis. For IAE, oseltamivir may be beneficial.

Seizures, status epilepticus, and cerebral edema are important complications of

encephalitis and should be monitored closely in patients who are not improving.
Typical indicators of elevated intracranial pressure, such as poorly reactive
dilated pupils, decorticate or decerebrate posture, or Cushing triad (systolic
hypertension, bradycardia, and shallow respirations) are late findings.
Patients should also be monitored for the syndrome of inappropriate secretion of
antidiuretic hormone (SIADH).
.

OUTCOME:

The prognosis of encephalitis is highly dependent on the underlying cause.

HSV-1 encephalitis →35% of patients with severe sequelae or death.
EV encephalitis →good outcome, EV-71 is associated with fatalities and
neurologic sequelae.

SUMMARY:

In this era of modern medicine, so little progress has been made in the field of
encephalitis. An etiology is only identified in about half of the cases, and very
few specific antivirals are available for treatment.