CHAPTER 360: MENINGITIS,
ENCEPHALITIS, BRAIN ABSCESS,
EMPYEMA
• Prodrome of fever, headache are
benign until altered consciousness,
focal neurologic deficits or seizures
appear.
• Approach to the patient: first
identify if infection is in the
subarachnoid space.
• Viral: encephalitis
• Bacterial/ fungal: cerebritis or
abscess
• Nuchal rigidity is the
pathognomonic sign of meningeal
irritation.
• Kernigs’ sign
• Brudzinski’s sign
• Failure of a patient suspected with
viral encephalitis to improve should
prompt reevaluation.
• Bacterial meningitis is an acute
purulent infection within the
subarachnoid space.
• Bacterial meningitis may result to
decreased consciousness,
seizures, raised ICP and stroke.
• Meningoencephalitis – the
parenchyma, meninges ad
subarachnoid
• Bacterial meningitis is the most
common form of suppurative CNS
infection.
• S. pneumoniae is the most
common cause in adults >20
• N. meningitides is common in ages
2-20 with petechial and purpuric
lesions.
• Group B or S. agalactiae
predominates in neonates and
elderly >50
• Listeria predominates in neonates
and pregnant women due to
organisms in ready to eat foods
• H. influenzae in unvaccinated
children
• Staph aureus and CN-staph are
causes of infection following an
invasive neurosurgical procedure
• Pathophysiology: Bacteria are able
to avoid phagocytosis because of a
polysaccharide capsule.
• A critical event in the pathogenesis
of bacterial meningitis is the
inflammatory reaction induced by
the invading bacteria.
• Lysis of bacteria with the
subsequent release of cell wall
components into the subarachnoid
space is the initial step in the
induction of the inflammatory
response.
• Cytokine response is followed by
an increase in CSF protein
concentration and leukocystosis.
• Much of the pathophysiology of
bacterial meningitis is a direct
consequence of elevated levels of
CSF cytokines and chemokines.
TNF and IL1 act synergistically to
increase the permeability of the
blood brain barrier resulting in
vasogenic edema and the leakage
of serum proteins into the
subarachnoid space.
• During the very early stages of
meningitis there is an increase in
cerebral blood flow followed by a
decrease in blood flow and loss of
cerebrovascular autoregulation.
• Combination of cytotoxic,
vasogenic and interstitial edema
lead to increased ICP and coma.
• Clinical presentation: clinical triad
of meningitis: fever, headache and
nuchal rigidity.
• Focal seizures may be due to focal
arterial ischemia, infarction, and
cortical venous thrombosis with
hemorrhage or focal edema.
• Generalized seizures or status
epilepticus may be due to
hyponatremia and cerebral anoxia.
• Raised ICP is an expected
complication and is the major
cause of obtundation and coma.
• Signs of increased ICP are:
papilledema, dilated poorly reactive
pupils, 6th nerve palsies,
decerebrate posturing and
Cushing’s reflex ( bradycardia,
hypotension, irregular respirations)
• Most disastrous complication is
cerebral herniation.
• Diagnosis: made by examination of
CSF
• Classic CSF abnormalities:
leukocystosis (>100 cells),
decreased glucose <2.2 mmol/L or
serum glucose of <0.4, increased
 protein concentration >0.45 g/L and
increased opening pressure >180
mmH2O
• CSF latex agglutination test has a
specificity of 95-100% for S.
pneumoniae and N. meningitides,
so a + test is virtually diagnostic of
bacterial meningitis.
• Limulus amoebocyte lysate assay
is a rapid diagnostic test for the
detection of gram – endotoxin in
CSF
• MRI is preferred than Ct because of
its superiority in demonstrating
areas of cerebral edema and
ischemia,
• Differential diagnosis: findings on
CSF studies, neuroimaging and
EEG distinguishes HSV
encephalitis from bacterial
meningitis
• Viral CSF infections: lymphocytic
pleocytosis with a normal glucose
• Bacterial: PMN pleocytosis and
hypoglycorrhachia
• Subacutely evolving meningitis may
on occasion be considered as
differentia diagnosis of acute
meningitis. Principal causes include
M. tuberculosis, C. neoformans, H.
capsulatum, C. immitis and T.
pallidum
• Treatment: bacterial meningitis is a
medical emergency.
• Goal is to begin antibiotic therapy
within 60 min.
• Ceftriaxone + vancomycin or
Cefotaxime + vancomycin
• Cefepime has greater activity
against Enterobacter and P.
aeruginosa
• Ampicillin to cover Listeria
• In meningitis following
neurosurgical procedures:
vancomycin and ceftazidime
• Ceftazidime is the only
cephalosporin with adequate
activity against CNS infections with
P. aeruginosa.
• Meropenem is a carbapenem
antibiotic that is highly active in
vitro against Listeria, P. aeruginosa
and penicillin resistant
pneumococci.
• Meningococcal meningitis: Pen G,
if resistant Ceftriaxone.
Chemoprophylaxis with Rifampicin.
Rifampicin is CI in pregnant.
• Pneumococcal meningitis:
cephalosporin + vancomycin, MICs
> 0.5 ug/mL treat with cefotaxime
or ceftriaxone, MICs of >1 ug/mL
vancomycin
• Patients with penicillin and
cephalosporin resistant strains of S.
pneumoniae who don’t respond to
vancomycin may be given
intraventricular vancomycin
• L. monocytogenes meningitis:
ampicillin/ gentamicin. In penicillin
allergic patients give cotrimoxazole
• Staphylococcal meningitis: nafcillin,
for MRSA use vancomycin
• Gram – bacillary meningitis: 3rd gen
cephalosporins but with P.
aeruginosa use ceftazidime
• Adjunctive therapy:
Dexamethasone
• For increased ICP: elevate head to
30-45 degrees, intubation,
hyperventilation and mannitol.
• Acute Viral Meningitis: fever,
headache and meningeal irritation
accompanied by arthralgia, malaise
and anorexia.
• Photophobia and pain on moving
the eyes.
• Kernig’s and brudzinski’s sign are
absent.
• Enteroviruses account for 75-90%
of aseptic meningitis.
• Laboratory Diagnosis of CSF:
lymphocytic pleocytosis and slightly
elevated protein concentration with
normal glucose.
• As a rule, lymphocytic pleocytosis
with a low glucose concentration
should suggest fungal, listerial or
tuberculous meningitis.
• PCR – diagnostic procedure of
choice
• HSV PCR- for recurrent episodes
of aseptic meningitis
• Oligoclonal bands can also be
found in noninfectious neurologic
diseases.
• Enterovirus infection can have
exanthema, foot and mouth
disease, herpangina, pleurodynia,
myopericarditis and hemorrhagic
 conjunctivitis ( stigmata of
enterovirus infection)
• Arbovirus – bird deaths
• HSV meningitis- HSV2, Mollaret’s
meningitis
• VZV meningitis: chickenpox and
shingles, acute cerebral ataxia.
• EBV infections may also produce
aseptic meningitis characterized by
atypical lymphocytosis in peripheral
blood.
• HIV meningitis: aseptic meningitis
is a common manifestation.
• Mumps: orchitis, oophoritis,
parotitis and pancreatitis, also
elevations in serum lipase and
amylase
• LCMV infection: exposure to house
mice presenting with leucopenia,
thrombocytopenia or abnormal liver
function tests.
• Treatment is symptomatic
• Hyponatremia may develop due to
inappropriate vasopressin secretion
(SIADH)
• Oral acyclovir may be of benefit in
meningitis caused by HSV, EBV or
VZV
• Patients with HIV should be given
HAART.
• Vaccination is an effective method
• Prognosis: prognosis for full
recovery from viral meningitis is
excellent.
• Viral encephalitis: involvement of
the brain parenchyma
• Involvement of the spinal cord is
encephalomyelitis
• Nerve root involvement is
encephalomyeloradiculitis
• Confusion, altered level of
consciousness, hallucinations,
agitations, personality change,
behavioral disorders and a frankly
psychotic state is seen.
• Focal findings include: ataxia,
aphasia, hemiparesis
• Temperature dysregulation,
diabetes insipidus, SIADH
• Most common viruses causing
sporadic cases are HSV1, VZV and
enteroviruses.
• Epidemics of encephalitis are
caused by arboviruses.
• Laboratory: lymphocytic
pleocytosis, mildly elevated protein
and normal glucose concentration.
• Hemorrhagic encephalitis is seen in
HSV and Colorado tick fever virus.
• CSF PCR is the primary diagnostic
test for CNS infections caused by
CMV, EBV, and VZV.
• Demonstration of WNV IgM
antibodies is diagnostic of WNV
encephalitis.
• Focal neurologic findings always
point to HSV as the etiologic agent.
• Brain biopsy was once considered
the gold standard.
• Differential Diagnosis: differentiate
from vascular diseases, abscess,
empyema, fungal, parasitic,
rickettsial, tuberculous infections,
tumors, Reye’s syndrome, toxic
encephalopathy, subdural
hematoma and SLE.
• Primary amebic
meningoencephalitis – Naegleria
fowleri
• Subacute or chronic granulomatous
amebic meningoencephalitis –
Acanthamoeba and Balamuthia
• Raccoon exposure
• Bartonella sp- agents of cat scratch
fever which is the most common
bacterial infection mimicking viral
encephalitis.
• Involvement of the inferomedial
frontotemporal regions of the brain
is present in HSV encephalitis.
• If deep gray matter, basal ganglia
and thalamus are affected suspect
flaviviruses.
• Deaths in crows and corvid birds
are due to WNV.
• Treatment: acyclovir is the
treatment for HSV.
• Ganciclovir and foscarnet are used
for CMV related CNS infections.
• Cidofovir if it doesn’t respond to
Ganciclovir.
• Side effects of Ganciclovir:
granulocytopenia and
thrombocytopenia, retinal
detachment.
• IV Ribavarin for California
encephalitis (Lacrosse) virus.
• Side effect: hemolysis, anemia
• Subacute Meningitis: typically
manifest with unrelenting
 headache, stiff neck, fever and
lethargy
• Common causative agents: M.
tuberculosis, C. neoformans, H
capsulatum, C. immitis, T. pallidum.
• The most common pathogen
causing fungal encephalitis is C.
neoformans.
• T. pallidum invades the CNS in the
early course of the illness, affecting
cranial nerves VII & VIII.
• Culture remains to be the gold
standard in the diagnosis of
tuberculous meningitis
• Eosinophils may be seen in C.
immitis meningitis.
• Cryptococcal polysaccharide
antigen tests for cryptococcal
meningitis is highly sensitive.
• Diagnosis of syphilic meningitis is
made when a reactive treponemal
test is associated with lymphocytic
pleocytosis.
• A negative CSF FTA ABS or MHA
TP rules out neurosyphilis.
• Treatment: initial therapy of
Rifampicin, isoniazid, pyrazinamide
and ethambutol.
• Dexamethasone if with
hydrocephalus.
• C. neoformans- amp B and
flucytosine
• H. capsulatum- amp B and
itraconazole
• C. immitis- IV amp B
• The most common complication of
fungal meningitis is hydrocephalus.
• Syphilitic meningitis is treated with
aq. Pen G.
• Chronic Encephalitis: Progressive
multifocal leukoencephalopathy is
pathologicaly characterized by
multifocal areas of demyelination.
• Astrocytes and oligoendrocytes are
enlarged.
• PCR analysis is diagnostic.
• No therapy is available
• Subacute Sclerosing
Panencephalitis: measles
• Treatment: Isoprinosine and
interferons
• Progressive Rubella
Panencephalitis: primarily affects
males with congenital rubella
syndrome.
• No therapy is available.
• Brain abscess – is a focal
suppurative infection within the
brain parenchyma typically
surrounded by a vascularized
capsule.
• Caused by Toxoplasma,
Aspergillus, Nocardia,
Mycobacteria and C. neoformans
• Taenia solium in Latin America
• Direct spread from a contiguous
cranial site of infection such as
paranasal sinusitis, otitis media,
mastoiditis or dental infection
• Otogenic abscesses usually in the
temporal lobe.
• Cryptogenic abscesses are due to
dental infections.
• Enterobacteriaceae and P.
aeruginosa are important causes of
abscesses associated with urinary
sepsis.
• Tetralogy of Fallot
• Intact brain is resistant to
infections; only in the presence of
ischemia, hypoxia and infarct will it
be able to be penetrated.
• Early cerebritis – infiltrates
• Late cerebritis- pus formation
• 3rd stage: is early capsule formation
• Late capsule stage characterized
with a well formed necrotic center
• Marked gliosis will cause the
sequelae – seizures.
• Brain abscess presents as a mass.
• Triad: fever, focal Neurologic
deficits and fever
• Headache is the most common
complaint.
• Hemiparesis seen in frontal lobe
lesion
• Dysphasia is seen in temporal lobe
lesion
• Nystagmus and ataxia are
cerebellar lesions.
• MRI is used for diagnosis.
• When fever is absent suspect
tumors.
• Treat with 3rd gen cephalosporins,
ceftazidime for P. aeruginosa and
vancomycin for staphylococci.
• Non bacterial causes of infectious
focal cns lesions:
neurocysticercosis is the most
 common parasitic disease of the
CNS worldwide
• T. gondi from cat feces
• Associated with resolution of the
inflammatory response
• Toxoplasma infection is usually
asymptomatic.
• MRI or CT scans.
• Parenchymal calcifications and
scolex ca be visualized.
• Albendazole and praziquantel.
• CNS toxoplasmosis is treated with
combination of sulfadiazine +
pyrimethamine
• Folinic acid to prevent
megaloblastic anemia
• Clindamycin + pyrimethamine are
an alternative for patients who
cannot tolerate sulfadiazine.
• Subdural empyema – is a rare
disorder characterized by a
collection of pus between the dura
and arachnoid membrane.
• Sinusitits is the most common
predisposing condition and typically
involves the frontal sinuses.
• Young males are more affected.
• Also may develop as complication
of head trauma or neurosurgery
• Presents with fever and
progressively worsening headache
• Headache is the most common
complaint
• Contralateral hemiparesis and
hemiplegia is the most common
focal Neurologic deficit.
• MRI or CT scan. CT may show a
crescent shaped hypodensity over
one or both hemispheres.
• SDE is a medical emergency.
• Burr-hole drainage or craniotomy is
the management.
• 3rd gen cephalosporins and
vancomycin and metronidazole.
• Epidural abscess- is a suppurative
infection occurring in the potential
space between the inner skull table
and dura.
• Develops as a complication of
craniotomy or infectious from an
area with osteomyelitis.
• Staph is usually the etiologic agent.
• MRI is the procedure of choice.
• Neurosurgical drainage is
indicated.
• 3rd gen cephalosporins+nafcillin or
vancomycin+ metronidazole
• Ceftazidime is used for
neurosurgical patients.
• Suppurative Thrombophlebitis- is
septic venous thrombosis of cortical
veins and sinuses
• Occur as a complication of bacterial
meningitis, SDE, epidural abscess.
• Superior sagittal sinus is the largest
of the venous sinuses.
• Bacterial meningitis is a common
predisposing condition for septic
thrombosis of the superior sagittal
sinus.
• Thrombosis of the superior sagittal
sinus is often associated with
thrombosis of superior cortical
veins and small parenchymal
hemorrhages. Septic thrombosis of
the superior sagittal sinus with
headache, fever, nausea, vomiting
and confusion and seizures.
• There maybe a rapid development
to stupor or coma.
• Nuchal rigidity, Kernig’s and
Brudzinski’s may be present.
• Septic cavernous sinus thrombosis
presents with fever, headache
frontal and retroorbital pain and
diplopia.
• Classic signs are ptosis, proptosis,
chemosis and extraocular
dysmotility due to deficits of cranial
nerves II, IV and VI, hyperesthesia
of the 5th nerve and decreased
corneal reflex, papilledema.
• Headache and earache are the
most frequent symptoms of
transverse sinus thrombosis. it may
also present with Gradinego’s
syndrome ( facial pain ).
• Sigmoid sinus and internal jugular
vein thrombosis may present with
neck pain.
• Cerebral angiography for definitive
diagnosis.
• Septic venous sinus thrombosis is
treated with antibiotics and
hydration.
• Dose adjusted heparin
• Aseptic venous sinus thrombosis
through urokinase therapy, rTPa
and IV heparin.
Liz IIIB