Meningitis, Encephalitis, Brain Abscess, and Empyema

Acute infections of the nervous system are include: acute bacterial

meningitis, viral meningitis,
encephalitis, focal
infections such as brain abscess and subdural empyema, and
infectious thrombophlebitis.

Each may present with a nonspecific prodrome of fever and headache until
altered consciousness, focal neurologic signs, or seizures appear.

Key goals of early management are to emergently distinguish between these

conditions, identify the responsible pathogen, and initiate appropriate antimicrobial
therapy.

Approach to the Patient

The first task is to identify whether an infection predominantly involves the

subarachnoid space (meningitis) or whether there is evidence of either
generalized or focal involvement of brain tissue
When brain tissue is directly injured by a viral infection, the disease is referred to
as encephalitis
Nuchal rigidity ("stiff neck") is the pathognomonic sign of meningeal irritation
and is present when the neck resists passive flexion.

Kernig's and Brudzinski's signs are also classic signs of meningeal irritation.

Kernig's sign is positive -attempts to passively extend the knee elicit pain when
meningeal irritation is present. Brudzinski's sign is positive when passive flexion of
the neck results in spontaneous flexion of the hips and knees.

Both may be absent or reduced in very young or elderly patients,

immunocompromised individuals, or patients with a severely depressed mental
status.

Initial management can be guided by several considerations:

(1) Empirical therapy -bacterial meningitis is a significant diagnostic consideration.

(2) recent head trauma, immunocompromised,

malignant lesions or CNS neoplasms, or
focal neurologic findings,
papilledema or
a depressed level of consciousness -CT or MRI of the brain prior to lumbar
puncture (LP). In these cases empirical antibiotic therapy -prior to neuroimaging
and LP.

(3) Coma, seizures, or focal neurologic deficits hospitalized for further evaluation
and treated empirically for bacterial and viral meningoencephalitis.
Failure of a patient with suspected viral meningitis to improve within 48 h
should prompt a reevaluation

Acute Bacterial Meningitis

Definition

An acute purulent infection within the sub-arachnoid space. It is associated

with a CNS inflammatory reaction that may result in decreased consciousness,
seizures, raised intracranial pressure (ICP), and stroke.

Epidemiology

Bacterial meningitis is the most common form of suppurative CNS infection

The organisms most often responsible for community-acquired bacterial

meningitis are:

Streptococcus pneumoniae (50%),

Neisseria meningitidis (25%),

Group B streptococci (15%), and

Listeria monocytogenes (10%).

Haemophilus influenzae type b accounts for <10% of cases of bacterial meningitis

in most series.

N. meningitidis is the causative organism of recurring epidemics of meningitis

every 8 to 12 years.
Etiology

S. pneumonia is the most common cause of meningitis in adults >20 years of age

Predisposing conditions -pneumococcal pneumonia(most common).

Additional risk factors include coexisting acute or chronic pneumococcal sinusitis

or otitis media, alcoholism, diabetes, splenectomy, hypogammaglobulinemia,
complement deficiency, and head trauma with basilar skull fracture and CSF
rhinorrhea.

The mortality rate remains 20% despite antibiotic therapy.

The incidence of meningitis due to N. meningitidis has decreased with the routine
immunization of 11- to 18-year-olds with the tetravalent meningococcal
glycoconjugate vaccine.

The presence of petechial or purpuric skin lesions can provide an important clue to
the diagnosis of meningococcal infection.

Infection may be initiated by nasopharyngeal colonization

The risk of invasive disease following nasopharyngeal colonization depends on both

bacterial virulence factors and host immune defense mechanisms

Enteric gram-negative bacilli cause meningitis in individuals with chronic and

debilitating diseases such as diabetes, cirrhosis, or alcoholism and in those with
chronic urinary tract infections.

Meningitis complicating endocarditis may be due to viridans streptococci, S.

aureus, S. bovis, the HACEK group, or enterococci.

Group B streptococcus, or S. agalactiae-increasing frequency in individuals >50

years of age, particularly those with underlying diseases.
L. monocytogenes -neonates (<1 month of age), pregnant women, individuals >60
years, and immunocompromised individuals of all ages.

Infection is acquired by ingesting foods contaminated by Listeria.

Staphylococcus aureus and coagulase-negative staphylococci - following invasive

neurosurgical procedures

Pathophysiology

S. pneumoniae and N. meningitidis, initially colonize the nasopharynx by attaching

to nasopharyngeal epithelial cells. Once in the bloodstream, bacteria are able to
avoid phagocytosis by neutrophils and classic complement-mediated bactericidal
activity because of the presence of a polysaccharide capsule.

Bloodborne bacteria can reach the intraventricular choroid plexus, directly infect
choroid plexus epithelial cells, and gain access to the CSF.

Bacteria are able to multiply rapidly within CSF because of the absence of
effective host immune defenses. Normal CSF contains few white blood cells
(WBCs) and relatively small amounts of complement proteins and immunoglobulins.

Phagocytosis of bacteria is further impaired by the fluid nature of CSF, which is

less conducive to phagocytosis than a solid tissue substrate.

A critical event in the pathogenesis of bacterial meningitis is the inflammatory

reaction induced by the invading bacteria. As a result, neurologic injury can
progress even after the CSF has been sterilized by antibiotic therapy.
Bacterial cell-wall components, such as the LPS and teichoic acid and
peptidoglycans induce meningeal inflammation by stimulating the production of
inflammatory cytokines and chemokines by microglia, astrocytes, monocytes,
microvascular endothelial cells, and CSF leukocytes.

In addition, bacteremia and the inflammatory cytokines induce the production of

excitatory amino acids, reactive oxygen and nitrogen species, and other mediators
that can induce death of brain cells, especially in the dentate gyrus of the
hippocampus.

Much of the pathophysiology of bacterial meningitis is a direct consequence of

elevated levels of CSF cytokines and chemokines.

TNF- and IL-1 act synergistically to increase the permeability of the blood-brain
barrier, resulting in induction of vasogenic edema and the leakage of serum
proteins into the subarachnoid space.

The subarachnoid exudate of proteinaceous material and leukocytes obstructs

the flow of CSF through the ventricular system and diminishes the resorptive
capacity of the arachnoid granulations in the dural sinuses, leading to obstructive
and communicating hydrocephalus and concomitant interstitial edema.

The adherence of leukocytes to capillary endothelial cells increases the

permeability of blood vessels, allowing for the leakage of plasma proteins into the
CSF, which adds to the inflammatory exudate. Neutrophil degranulation results in
the release of toxic metabolites that contribute to cytotoxic edema, cell injury,
and death.

CSF leukocytes probably do little to contribute to the clearance of CSF bacterial

infection.

During the very early stages of meningitis, there is an increase in cerebral blood
flow, soon followed by a decrease in cerebral blood flow and a loss of
cerebrovascular autoregulation
The combination of interstitial, vasogenic, and cytotoxic edema leads to raised ICP
and coma. Cerebral herniation usually results from the effects of cerebral edema

Clinical Presentation
Meningitis can present as either an acute fulminant illness or as a subacute
infection that progressively worsens over several days.

The classic clinical triad of meningitis is fever, headache, and nuchal rigidity,
but the classic triad may not be present.

A decreased level of consciousness occurs in >75% of patients and can vary

from lethargy to coma.

Fever and either headache, stiff neck, or an altered level of consciousness will be
present in nearly every patient with bacterial meningitis. Nausea, vomiting, and
photophobia are also common complaints.

Seizures occur as part of the initial presentation of bacterial meningitis or

during the course of the illness in 20–40% of patients.

Focal seizures are usually due to focal arterial ischemia or infarction, cortical
venous thrombosis with hemorrhage, or focal edema.

Generalized seizure activity and status epilepticus may be due to hyponatremia,

cerebral anoxia, or, less commonly, the toxic effects of antimicrobial agents such
as high-dose penicillin.

Raised ICP is an expected complication of bacterial meningitis and the major

cause of obtundation and coma in this disease. More than 90% of patients will
have a CSF opening pressure >180 mmH2O, and 20% have opening pressures >400
mmH2O.

Signs of increased ICP include : deteriorating or

reduced level of consciousness, papilledema,
dilated poorly reactive pupils, sixth nerve
palsies, decerebrate posturing, and
the Cushing reflex (bradycardia, hypertension, and irregular respirations).
The most disastrous complication of increased ICP is cerebral herniation. The
incidence is as few as 1% to as many as 8% of cases.

Specific clinical features may provide clues to the diagnosis of individual

organisms.

The most important of these clues is the rash of meningococcemia, which begins as
a diffuse erythematous maculopapular rash resembling a viral exanthem; however,
the skin lesions of meningococcemia rapidly become petechial. Petechiae are found
on the trunk and lower extremities, in the mucous membranes and conjunctiva, and
occasionally on the palms and soles.

Diagnosis

The diagnosis of bacterial meningitis is made by examination of the CSF. The

need to obtain neuroimaging studies (CT or MRI) prior to LP requires clinical
judgment.

In an immunocompetent patient with no known history of recent head trauma, a

normal level of consciousness, and no evidence of papilledema or focal neurologic
deficits, it is considered safe to perform LP without prior neuroimaging studies.

If LP is delayed in order to obtain neuroimaging studies, empirical antibiotic

therapy should be initiated after blood cultures are obtained.
(2) decreased glucose concentration [<40 mg/dL) and/or CSF/serum glucose ratio
of <0.4 in 60%],
(3) increased protein concentration (>45 mg/dL) in 90%, and
(4) increased opening pressure (>180 mmH2O in 90%).
CSF bacterial cultures are positive in >80% of patients, and CSF Gram's stain
demonstrates organisms in >60%.

Use of the CSF/serum glucose ratio corrects for hyperglycemia that may mask a
relative decrease in the CSF glucose concentration. The CSF glucose concentration
is low when the CSF/serum glucose ratio is <0.6.

A CSF/serum glucose ratio <0.4 is highly suggestive of bacterial meningitis but

may also be seen in other conditions, including fungal, tuberculous, and
carcinomatous meningitis. It takes from 30 min to several hours for the
concentration of CSF glucose to reach equilibrium with blood glucose levels;
therefore, administration of 50 mL of 50% glucose (D50) prior to LP, as commonly
occurs in emergency room settings, is unlikely to alter CSF glucose concentration
significantly unless more than a few hours have elapsed between glucose
administration and LP.

The CSF LA test has a specificity of 95–100% for S. pneumoniae and N.

meningitidis, so a positive test is virtually diagnostic of bacterial meningitis
caused by these organisms.

However, the sensitivity of the CSF LA test is only 70–100% for detection of S.
pneumoniae and 33–70% for detection of N. meningitidis antigens, so a negative
test does not exclude infection by these organisms.

Almost all patients with bacterial meningitis will have neuroimaging studies
performed during the course of their illness. MRI is preferred over CT because of
its superiority in demonstrating areas of cerebral edema and ischemia.

Petechial skin lesions, if present, should be biopsied.

Differential Diagnosis

Viral meningoencephalitis(HSV encephalitis)

Headache, fever, altered consciousness, focal neurologic deficits (e.g., dysphasia,

hemiparesis), and focal or generalized seizures.

Lymphocytic pleocytosis with a normal glucose concentration, in contrast to PMN

pleocytosis and hypoglycorrhachia characteristic of bacterial meningitis.

Rocky Mountain spotted fever

The disease may present acutely with high fever, prostration, myalgia,
headache, nausea, and vomiting. Most patients develop a characteristic rash
within 96 h of the onset of symptoms. The rash is initially a diffuse erythematous
maculopapular rash that may be difficult to distinguish from that of
meningococcemia. It progresses to a petechial rash, then to a purpuric rash and, if
untreated, to skin necrosis or gangrene. The color of the lesions changes from
bright red to very dark red, then yellowish-green to black. The rash typically
begins in the wrist and ankles and then spreads distally and proximally within a
matter of a few hours, involving the palms and soles.

Diagnosis is made by immunofluorescent staining of skin biopsy specimens.

Focal suppurative CNS infections , including subdural and epidural empyema and
brain abscess

A number of noninfectious CNS disorders can mimic bacterial meningitis.

Subarachnoid hemorrhage is generally the major consideration.

Lumbar puncture: Technique; indications; contraindications; and complications in

adults

TECHNIQUE — An LP can be performed with the patient in the lateral

recumbent position or sitting upright. The lateral recumbent position is
preferred because it allows accurate measurement of the opening pressure.

The spinal needle can be safely inserted into the subarachnoid space at the
L3/4 or L4/5 interspace, since this is well below the termination of the spinal
cord.

Once CSF appears and begins to flow through the needle, the patient should
be instructed to slowly straighten or extend the legs to allow free flow of CSF
within the subarachnoid space. A manometer should then be placed over the
hub of the needle and the opening pressure should be measured

A total of 8 to 15 mL of CSF is typically removed during routine LP.

INDICATIONS

Suspected CNS infection (with the exception of brain abscess or a

parameningeal process).

Suspected subarachnoid hemorrhage (SAH) in a patient with a negative CT

scan

A nonurgent LP is indicated in the diagnosis

Idiopathic intracranial hypertension (pseudotumor cerebri)

Carcinomatous meningitis

Tuberculous meningitis

Normal pressure hydrocephalus

CNS syphilis

CNS vasculitis

CONTRAINDICATIONS-no absolute contraindications

Possible raised intracranial pressure

Thrombocytopenia or other bleeding diathesis (including ongoing anticoagulant

therapy)

Suspected spinal epidural abscess

COMPLICATIONS

Post-LP headache

Infection

Bleeding

Cerebral herniation

Minor neurologic symptoms such as radicular pain or numbness

Late onset of epidermoid tumors of the thecal sac

Back pain
The neurologic complications of bacterial meningitis include:

Impaired mental status

Increased intracranial pressure and cerebral edema

Seizures

Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis)

Cerebrovascular abnormalities

Sensorineural hearing loss

Intellectual impairment

Treatment: Acute Bacterial Meningitis

Empirical Antimicrobial Therapy

Bacterial meningitis is a medical emergency. The goal is to begin antibiotic therapy

within 60 min of a patient's arrival in the emergency room. Empirical antimicrobial
therapy is initiated in patients with suspected bacterial meningitis before the
results of CSF Gram's stain and culture are known.
S. pneumoniae and N. meningitidis are the most common etiologic organisms of
community-acquired bacterial meningitis.

combination of dexamethasone, a third- or fourth-generation cephalosporin (e.g.,

ceftriaxone, cefotaxime, or cefepime), and vancomycin, plus acyclovir, as HSV
encephalitis is the leading disease in the differential diagnosis, and doxycycline
during tick season to treat tick-borne bacterial infections.

Ampicillin should be added to the empirical regimen for coverage of L.

monocytogenes in individuals <3 months of age, those >55, or those with suspected
impaired cell-mediated immunity. Metronidazole is
to cover gram-negative anaerobes in patients with otitis, sinusitis, or mastoiditis.
In hospital-acquired meningitis, and following neurosurgical procedures,
staphylococci and gram-negative organisms including P. aeruginosa are the most
common etiologic organisms. In these patients,
empirical therapy should include a combination of vancomycin and ceftazidime.
Objectives
-Rapidly clear the organisms from the CSF
-Prevent acute complications and long term sequelae Non pharmacologic
-Close supervision with regular monitoring of vital signs and neurological state.
-Institution of coma care for complicated cases.

Pharmacologic

A.Community acquired, bacterial etiology unknown First line

Ceftriaxone, 4g/day, I.V., divided in 2 doses for 10-14 days PLUS
Where Penicillin resistance is common, Empiric treatment should include:
Vancomycin, 1gm IV BID for 10-14days Alternative
Benzyl penicillin, 20-24 million IU/day I.V. in 4-6 divided doses for 7 –10
days. PLUS
Chloramphenicol, 500mg I.V. QID.
In severe infections, up to 100mg/kg/day in 4 divided doses, may be used for
7 days If >50 y or
alcoholic: for Listeria monocytogens Ampicillin, 2g IV q4h OR(if beta-lactam
allergic) Trimetoprime/Sulphamethoxazole, 20mg/kg per day divided Q6-12
B.Empiric treatment, hospital acquired meningitis or penetrating trauma
without basillar skul fructure First line
Vancomycin, 15mg/kg IV Q8h PLUS Ceftazidime, 2g IV q8h
Alternative
Vancomycin, 15mg/kg IV Q8h PLUS Meropenem,
2gm IV Q8hr Dosage forms:
Powder for reconstitution 500mg/vial and 1000mg/vial
C.Immunosuppressed
Ceftazidime, 2g IV q8h PLUS Vancomycin, 15mg/kg IV Q8h PLUS Ampicillin,
2g IV q4h PLUS Acyclovir 10mg/kg (infuse over
1h) Q8h for 14-21d Early diagnosis and treatment are imperative.
Mortality is reduce from >70% to <20% with IV acyclovir treatment.

Adjuvant Therapy:
Dexamethasone,10mg IV QID for 4 days
Reduce neurologic disability and mortality by about 50% particularly in patients
with S. pneumoniae meningitis and & GCS 8–11.

Specific Antimicrobial Therapy

Meningococcal Meningitis
Penicillin G remains the antibiotic of choice for meningococcal meningitis caused by
susceptible strains.
If resistance is found, cefotaxime or ceftriaxone should be substituted for
penicillin. A 7-day course of intravenous antibiotic therapy is
adequate for uncomplicated meningococcal meningitis.
The index case and all close contacts should receive chemoprophylaxis with a 2-day
regimen of rifampin (600 mg every 12 h for 2 days in adults and 10 mg/kg every 12
h for 2 days in children >1 year).
Rifampin is not recommended in pregnant women.
Alternatively, adults can be treated with one dose of azithromycin (500 mg), or one
intramuscular dose of ceftriaxone (250 mg).

Pneumococcal Meningitis
A 2-week course of intravenous antimicrobial therapy is recommended.
Patients should have a repeat LP performed 24–36 h after the initiation of
antimicrobial therapy to document sterilization of the CSF.
Failure to sterilize the CSF should be considered presumptive evidence of
antibiotic resistance. Patients with penicillin-G and cephalosporin-resistant strains
of S. pneumoniae who do not respond to intravenous vancomycin alone may benefit
from the addition of intraventricular vancomycin.

Listeria Meningitis
-is treated with ampicillin for at least 3 weeks.
Gentamicin is added in critically ill patients (2 mg/kg loading dose, then 7.5 mg/kg
per day given every 8 h and adjusted for serum levels and renal function).
The combination of trimethoprim (10–20 mg/kg per day) and sulfamethoxazole (50–
100 mg/kg per day) given every 6 h may provide an alternative in penicillin-allergic
patients.

Staphylococcal Meningitis
Vancomycin is the drug of choice for MRSA and for patients allergic to penicillin.
If the CSF is not sterilized after 48 h of intravenous vancomycin therapy, then
either intraventricular or intrathecal vancomycin, 20 mg once daily, can be added.

Gram-Negative Bacillary Meningitis

A 3-week course of intravenous antibiotic therapy is recommended for meningitis
due to gram-negative bacilli.
Adjunctive Therapy
Dexamethasone (10 mg IV) 15–20 min before the first dose of an antimicrobial
agent, and the same dose repeated every 6 h for 4 days.
Dexamethasone inhibits the production of TNF by macrophages and microglia only
if it is administered before these cells are activated by endotoxin.
Dexamethasone does not alter TNF production once it has been induced.
Dexamethasone may decrease the penetration of vancomycin into CSF, and it
delays the sterilization of CSF.
Alternatively, vancomycin can be administered by the intraventricular route.
(5) the presence of comorbid conditions including shock and/or the need for
mechanical ventilation, and

(6) delay in the initiation of treatment.

Decreased CSF glucose concentration (<40 mg/dL) and markedly increased CSF
protein concentration (> 300 mg/dL) have been predictive of increased mortality
and poorer outcomes.

Common sequelae include decreased intellectual function, memory impairment,

seizures, hearing loss and dizziness, and gait disturbances.

Acute Viral Meningitis

Clinical Manifestations

Immunocompetent adult patients with viral meningitis usually present with

headache, fever, and signs of meningeal irritation coupled with an inflammatory
CSF profile.

Headache is almost invariably present and often characterized as frontal or

retroorbital and frequently associated with photophobia and pain on moving the
eyes.

Nuchal rigidity is present in most cases but may be mild and present only near the
limit of neck anteflexion.

Constitutional signs can include malaise, myalgia, anorexia, nausea and vomiting,
abdominal pain, and/or diarrhea.

Stupor, coma, or marked confusion do not occur in viral meningitis and suggest
the presence of encephalitis or other alternative diagnoses.
Similarly, seizures or focal neurologic signs or symptoms or neuroimaging
abnormalities indicative of brain parenchymal involvement are not typical of
viral meningitis and suggest the presence of encephalitis or another CNS
infectious or inflammatory process.

Etiology

A specific viral cause can be found in 75–90% of cases of viral meningitis.

The most important agents are enteroviruses (including echoviruses and

coxsackieviruses), HSV type 2 (HSV-2), HIV, and arboviruses .

CSF cultures are positive in 30–70% of patients

Epidemiology

In temperate climates, there is a substantial increase in cases during the summer

and early fall months

Laboratory Diagnosis

CSF Examination

The most important laboratory test in the diagnosis of viral meningitis is

examination of the CSF.

The typical profile is a

Lymphocytic pleocytosis (25–500 cells/L),

A normal or slightly elevated protein concentration [0.2–0.8 g/L (20–80 mg/dL)],

A normal glucose concentration, and a normal or mildly elevated opening pressure
(100–350 mmH2O). Organisms are not seen on Gram's stain of CSF.

Rarely, PMNs may predominate in the first 48 h of illness, especially with

infections due to echovirus 9, West Nile virus, eastern equine encephalitis (EEE)
virus, or mumps.

Polymerase Chain Reaction Amplification of Viral Nucleic Acid

In both enteroviral and HSV infections of the CNS, PCR has become the diagnostic
procedure of choice and is substantially more sensitive than viral cultures.

Viral Culture

Enteroviruses and adenoviruses may be found in feces; arboviruses, some

enteroviruses, and LCMV in blood; mumps and CMV in urine; and enteroviruses,
mumps, and adenoviruses in throat washings.

Serologic Studies

Differential Diagnosis

(1) untreated or partially treated bacterial meningitis;

(2) early stages of meningitis caused by fungi, mycobacteria, or Treponema

pallidum (neurosyphilis), in which a lymphocytic pleocytosis is common, cultures may
be slow growing or negative, and hypoglycorrhachia may not be present early;
(3) meningitis caused by agents such as Mycoplasma, Listeria spp., Brucella spp.,
Coxiella spp., Leptospira spp., and Rickettsia spp.;

(4) parameningeal infections;

(5) neoplastic meningitis; and

(6) meningitis secondary to noninfectious inflammatory diseases,

Treatment: Acute Viral Meningitis

Treatment of almost all cases of viral meningitis is primarily symptomatic and

includes use of analgesics, antipyretics, and antiemetics.

Fluid and electrolyte status should be monitored. Patients with suspected bacterial
meningitis should receive appropriate empirical therapy pending culture results .

Immunocompromised patients; patients with significant alteration in consciousness,

seizures, or the presence of focal signs and symptoms suggesting the possibility of
encephalitis or parenchymal brain involvement; and those patients who have an
atypical CSF profile should be hospitalized. Seriously ill
patients should probably receive intravenous acyclovir (15–30 mg/kg per day in
three divided doses), which can be followed by an oral drug such as acyclovir (800
mg, five times daily), famciclovir (500 mg tid), or valacyclovir (1000 mg tid) for a
total course of 7–14 days.
Prognosis

In adults, the prognosis for full recovery from viral meningitis is excellent.

Viral Encephalitis

Definition

In encephalitis the brain parenchyma is also involved. Many patients with

encephalitis also have evidence of associated meningitis (meningoencephalitis) and,
in some cases, involvement of the spinal cord or nerve roots (encephalomyelitis,
encephalomyeloradiculitis).

Clinical Manifestations

In addition to evidence of meningeal involvement, the patient with encephalitis

commonly has an altered level of consciousness (confusion, behavioral
abnormalities), or a depressed level of consciousness ranging from mild lethargy to
coma, and evidence of either focal or diffuse neurologic signs and symptoms.

Patients with encephalitis may have hallucinations, agitation, personality change,

behavioral disorders, and, at times, a frankly psychotic state.

Focal or generalized seizures occur in many patients with encephalitis.

The most commonly encountered focal findings are aphasia, ataxia, upper or lower
motor neuron patterns of weakness, involuntary movements (e.g., myoclonic jerks,
tremor), and cranial nerve deficits (e.g., ocular palsies, facial weakness).

Involvement of the hypothalamic-pituitary axis may result in temperature

dysregulation, diabetes insipidus, or the development of the syndrome of
inappropriate secretion of antidiuretic hormone (SIADH).

Etiology

The most commonly identified viruses causing sporadic cases of acute

encephalitis in immunocompetent adults are herpesviruses (HSV, VZV, EBV).

Epidemics of encephalitis are caused by arboviruses

Laboratory Diagnosis

CSF Examination

CSF examination should be performed in all patients with suspected viral

encephalitis unless contraindicated by the presence of severely increased ICP. The
characteristic CSF profile is indistinguishable from that of viral meningitis
Brain Biopsy

Brain biopsy is now generally reserved for patients in whom CSF PCR studies fail to
lead to a specific diagnosis, who have focal abnormalities on MRI, and who continue
to show progressive clinical deterioration despite treatment with acyclovir and
supportive therapy.

Treatment: Viral Encephalitis

Specific antiviral therapy should be initiated when appropriate. Vital functions,

including respiration and blood pressure, should be monitored continuously and
supported as required.

Basic management and supportive therapy should include careful monitoring of ICP,
fluid restriction, avoidance of hypotonic intravenous solutions, and suppression of
fever. Seizures should be treated with standard anticonvulsant regimens, and
prophylactic therapy should be considered in view of the high frequency of
seizures in severe cases of encephalitis.

Sequelae

Residual seizure disorder, persistent hemiparesis.

Patients with severe neurologic impairment (Glasgow coma score 6) at initiation of

therapy either died or survived with severe sequelae.
Cognitive impairment; weakness; and hyper- or hypokinetic movement disorders,
including tremor, myoclonus, and parkinsonism.

Subacute Meningitis

Clinical Manifestations

Have an unrelenting headache, stiff neck, low-grade fever, and lethargy for
days to several weeks before they present for evaluation. Cranial nerve
abnormalities and night sweats may be present. This syndrome overlaps that of
chronic meningitis

Etiology

Common causative organisms include M. tuberculosis, C. neoformans, H.

capsulatum, C. immitis, and T. pallidum.

Tuberculous meningitis in adults does not develop acutely from hematogenous

spread of tubercle bacilli to the meninges. Rather, millet seed–sized (miliary)
tubercles form in the parenchyma of the brain during hematogenous dissemination
of tubercle bacilli in the course of primary infection.

These tubercles enlarge and are usually caseating. The propensity for a caseous
lesion to produce meningitis is determined by its proximity to the subarachnoid
space (SAS) and the rate at which fibrous encapsulation develops. Subependymal
caseous foci cause meningitis via discharge of bacilli and tuberculous antigens into
the SAS.
Fungal infections are typically acquired by the inhalation of airborne fungal spores.
The initial pulmonary infection may be asymptomatic or present with fever, cough,
sputum production, and chest pain. The pulmonary infection is often self-limited. A
localized pulmonary fungal infection can then remain dormant in the lungs until
there is an abnormality in cell-mediated immunity that allows the fungus to
reactivate and disseminate to the CNS.

The most common pathogen causing fungal meningitis is C. neoformans.

Syphilis is a sexually transmitted disease that is manifest by the appearance

of a painless chancre at the site of inoculation. T. pallidum invades the CNS
early in the course of syphilis. Cranial nerves VII and VIII are most frequently
involved.

Laboratory Diagnosis

The classic CSF abnormalities in tuberculous meningitis are as follows:

(1) elevated opening pressure,

(2) lymphocytic pleocytosis (10–500 cells/L),

(3) elevated protein concentration in the range of 1–5 g/L, and

(4) decreased glucose concentration in the range of 1.1–2.2 mmol/L (20–40 mg/dL).
The combination of unrelenting headache, stiff neck, fatigue, night sweats, and
fever with a CSF lymphocytic pleocytosis and a mildly decreased glucose
concentration is highly suspicious for tuberculous meningitis.

The last tube of fluid collected at LP is the best tube to send for a smear for acid-
fast bacilli (AFB).

Positive smears are typically reported in only 10–40% of cases of tuberculous

meningitis in adults

The characteristic CSF abnormalities in fungal meningitis are a mononuclear or

lymphocytic pleocytosis, an increased protein concentration, and a decreased
glucose concentration. There may be eosinophils in the CSF in C. immitis meningitis.

Treatment: Subacute Meningitis

Empirical therapy of tuberculous meningitis

Initial therapy is a combination of isoniazid (300 mg/d), rifampin (10 mg/kg per
day), pyrazinamide (30 mg/kg per day in divided doses), ethambutol (15–25 mg/kg
per day in divided doses), and pyridoxine (50 mg/d).

Chronic Encephalitis

Progressive Multifocal Leukoencephalopathy

Clinical Features and Pathology

Zed pathologically by multifocal areas of demyelination of varying size

distributed throughout the brain but sparing the spinal cord and optic nerves.

Patients often present with visual deficits (45%), typically a homonymous

hemianopia; mental impairment (38%) (dementia, confusion, personality change);
weakness, including hemi- or monoparesis; and ataxia.

Seizures occur in 20% of patients, predominantly in those with lesions

abutting the cortex.

Almost all patients have an underlying immunosuppressive disorder. In recent

series, the most common associated conditions were AIDS (80%),
hematologicmalignancies (13%), transplant recipients (5%), and chronic
inflammatory diseases (2%).

Diagnostic Studies

The diagnosis of PML is frequently suggested by MRI. MRI reveals multifocal

asymmetric, coalescing white matter lesions located periventricularly, in the
centrum semiovale, in the parietal-occipital region, and in the cerebellum.

Subacute Sclerosing Panencephalitis (SSPE)

SSPE is a rare chronic, progressive demyelinating disease of the CNS associated
with a chronic nonpermissive infection of brain tissue with measles virus. The
frequency has been estimated at 1 in 100,000–500,000 measles cases.

Most patients give a history of primary measles infection at an early age (2 years),
which is followed after a latent interval of 6–8 years by the development of a
progressive neurologic disorder. Some 85% of patients are between 5 and 15 years
old at diagnosis.

Initial manifestations include poor school performance and mood and personality
changes. Typical signs of a CNS viral infection, including fever and headache, do
not occur.

Patients develop progressive intellectual deterioration, focal and/or generalized

seizures, myoclonus, ataxia, and visual disturbances. In the late stage of the
illness, patients are unresponsive, quadriparetic, and spastic, with hyperactive
tendon reflexes and extensor plantar responses.

Brain Abscess

Definition

Focal, suppurative infection within the brain parenchyma, typically surrounded

by a vascularized capsule.

Cerebritis -nonencapsulated brain abscess.

Epidemiology
A bacterial brain abscess is a relatively uncommon intracranial infection, with an
incidence of 0.3–1.3:100,000 persons per year.

Predisposing conditions include

Otitis media and mastoiditis,

Paranasal sinusitis,

Pyogenic infections in the chest or other body sites, penetrating head trauma or
neurosurgical procedures, and dental infections.

In immunocompetent individuals the most important pathogens are

Streptococcus spp. (40%), Enterobacteriaceae (25%), anaerobes [e.g., Bacteroides
spp., Fusobacterium spp. (30%)], and staphylococci (10%).

In immunocompromised hosts, most brain abscesses are caused by Nocardia spp.,

Toxoplasma gondii, Aspergillus spp., Candida spp., and C. neoformans.

Etiology

A brain abscess may develop (1) by direct spread from a contiguous cranial site of
infection, such as paranasal sinusitis, otitis media, mastoiditis, or dental infection;

(2) following head trauma or a neurosurgical procedure; or

(3) as a result of hematogenous spread from a remote site of infection.

In up to 25% of cases, no obvious primary source of infection is apparent
(cryptogenic brain abscess).

Approximately one-third of brain abscesses are associated with otitis media and
mastoiditis, often with an associated cholesteatoma. Otogenic abscesses occur
predominantly in the temporal lobe (55–75%) and cerebellum (20–30%).

Hematogenous abscesses account for 25% of brain abscesses. Hematogenous

abscesses are often multiple, and multiple abscesses often (50%) have a
hematogenous origin.

predilection for the territory of the middle cerebral artery (i.e., posterior frontal
or parietal lobes). often l

Located at the junction of the gray and white matter and are often poorly
encapsulated.

brain abscesses that develop as a complication of infective endocarditis are often

due to viridans streptococci or S. aureus.

Abscesses that follow penetrating head trauma or neurosurgical procedures are

frequently due to methicillin-resistant S. aureus (MRSA),

P. aeruginosa are important causes of abscesses associated with urinary sepsis.

Clinical Presentation

A brain abscess typically presents as an expanding intracranial mass lesion

rather than as an infectious process.

Most patients present to the hospital 11–12 days following onset of symptoms.

The classic clinical triad of headache, fever, and a focal neurologic deficit is
present in <50% of cases. The most common symptom in patients with a brain
abscess is headache, occurring in >75% of patients.

The headache is often characterized as a constant, dull, aching sensation, either

hemicranial or generalized, and it becomes progressively more severe and
refractory to therapy. Fever is present in only 50% of patients at the time of
diagnosis, and its absence should not exclude the diagnosis. The new onset of focal
or generalized seizure activity is a presenting sign in 15–35% of patients.

Focal neurologic deficits including hemiparesis, aphasia, or visual field defects are
part of the initial presentation in >60% of patients.

Hemiparesis is the most common localizing sign of a frontal lobe abscess. A

temporal lobe abscess may present with a disturbance of language (dysphasia) or an
upper homonymous quadrantanopia.

Nystagmus and ataxia are signs of a cerebellar abscess.

Signs of raised ICP—papilledema, nausea and vomiting, and drowsiness or confusion

—can be the dominant presentation of some abscesses, particularly those in the
cerebellum.

Meningismus is not present unless the abscess has ruptured into the ventricle or
the infection has spread to the subarachnoid space.

Diagnosis
Diagnosis is made by neuroimaging studies.

MRI is better than CT for demonstrating abscesses in the early (cerebritis)

stages and is superior to CT for identifying abscesses in the posterior fossa.

Differential Diagnosis

Conditions that can cause headache, fever, focal neurologic signs, and seizure
activity include brain abscess, subdural empyema, bacterial meningitis, viral
meningoencephalitis, superior sagittal sinus thrombosis, and acute disseminated
encephalomyelitis.

When fever is absent, primary and metastatic brain tumors become the major
differential diagnosis. Less commonly, cerebral infarction or hematoma can have an
MRI or CT appearance resembling brain abscess.

Treatment: Brain Abscess

Optimal therapy of brain abscesses involves a combination of high-dose parenteral

antibiotics and neurosurgical drainage.

Nonbacterial Causes of Infectious Focal CNS Lesions

Etiology
Neurocysticercosis is the most common parasitic disease of the CNS worldwide

Toxoplasmosis is a parasitic disease caused by T. gondii and acquired from the

ingestion of undercooked meat and from handling cat feces.

Clinical Presentation

The most common manifestation of neurocysticercosis is new-onset partial

seizures with or without secondary generalization

Primary Toxoplasma infection is often asymptomatic. Reactivation of CNS infection

is almost exclusively associated with immunocompromised hosts, particularly those
with HIV infection.

During this phase patients present with headache, fever, seizures, and focal
neurologic deficits.

Diagnosis

The lesions of neurocysticercosis are readily visualized by MRI or CT scans.

Subdural Empyema

collection of pus between the dura and arachnoid membranes.

Epidemiology

SDE is a rare disorder that accounts for 15–25% of focal suppurative CNS
infections. Sinusitis is the most common predisposing condition and typically
involves the frontal sinuses, either alone or in combination with the ethmoid and
maxillary sinuses.
Etiology

Aerobic and anaerobic streptococci, staphylococci, Enterobacteriaceae, and

anaerobic bacteria are the most common causative organisms of sinusitis-
associated SDE. Staphylococci and gram-negative bacilli are often the etiologic
organisms when SDE follows neurosurgical procedures or head trauma.

Clinical Presentation

A patient with SDE typically presents with fever and a progressively worsening
headache. The diagnosis of SDE should always be suspected in a patient with known
sinusitis who presents with new CNS signs or symptoms. Patients with underlying
sinusitis frequently have symptoms related to this infection. As the infection
progresses, focal neurologic deficits, seizures, nuchal rigidity, and signs of
increased ICP commonly occur.

Headache is the most common complaint at the time of presentation; initially it is

localized to the side of the subdural infection, but then it becomes more severe
and generalized.

Contralateral hemiparesis or hemiplegia is the most common focal neurologic

deficit and can occur from the direct effects of the SDE on the cortex or as a
consequence of venous infarction. Seizures begin as partial motor seizures that
then become secondarily generalized.

In untreated SDE, the increasing mass effect and increase in ICP cause
progressive deterioration in consciousness, leading ultimately to coma.

Diagnosis
MRI

Glasgow coma scale

Eye opening

Spontaneous 4

Response to verbal command 3

Response to pain 2

No eye opening 1

Best verbal response

Oriented 5

Confused 4

Inappropriate words 3

Incomprehensible sounds 2

No verbal response 1

Best motor response

Obeys commands 6

Localizing response to pain 5

Withdrawal response to pain 4

Flexion to pain 3

Extension to pain 2

No motor response 1

The GCS is scored between 3 and 15, 3 being the worst, and 15 the best.

It is composed of three parameters: best eye response (E), best verbal response
(V), and best motor response (M).

The components of the GCS should be recorded individually; for example, E2V3M4
results in a GCS score of 9.

A score of 13 or higher correlates with mild brain injury; a score of 9 to 12

correlates with moderate injury; and a score of 8 or less represents severe
brain injury

Miesso(MD)