CNS Infections

Dr. Sriram T
 Anatomy of CNS
 Our bodies couldn’t operate without the nervous system - the complex
network that coordinates our actions, reflexes, and sensations.
 Broadly speaking, the nervous system is organised into two main parts,
the central nervous system (CNS) and the peripheral nervous
system (PNS).
 The CNS is the processing centre of the body and consists of the
brain and the spinal cord.
 Both of these are protected by three layers of membranes known as
meninges.
 For further protection, the brain is encased within the hard bones of the
skull, while the spinal cord is protected with the bony vertebrae of our
backbones.
 A third form of protection is cerebrospinal fluid, which provides a
buffer that limits impact between the brain and skull or between
spinal cord and vertebrae.
 Infections of CNS
 The central nervous system (CNS) may be infected by various agents,
including
 viruses,
 bacteria,
 fungi,
 protozoa, and
 helminths.
 In addition, numerous noninfectious etiologies may account for
syndromes that mimic CNS infections. These include
 neoplastic diseases,
 intracranial tumors and cysts,
 medications,
 collagen vascular disorders, and other systemic illnesses, and following
various procedures that invade the CNS.
 Infections of CNS
 The clinical presentation of a CNS infection may be
acute,
subacute, or
chronic, depending on the virulence of the infecting
agent and the location of the infection.
 Because CNS infections occur within the confines of
the cranium or spinal column, they may be associated
with significant morbidity and mortality, often
necessitating emergent interventions to improve
outcome.
 Clinical Manifestations
 The clinical presentation of a specific CNS infection depends
on the pathogenesis of spread of the infection to the CNS, the
virulence of the etiologic agent, and the area of CNS
involvement.
 Most patients with CNS infections present with the clinical
features of fever, headache, altered mental status, or focal
neurologic deficits.
 These findings are nonspecific, however, and not all patients
with CNS infections develop all of these clinical
manifestations.
 The likelihood of any specific clinical finding depends on the
CNS syndrome caused by the infectious agent.
 Acute Bacterial Meningitis
DEFINITION
 Bacterial meningitis is an acute purulent infection within the subarachnoid space.
It is associated with a CNS inflammatory reaction that may result in decreased
consciousness, seizures, raised intracranial pressure (ICP), and stroke. The
meninges, the subarachnoid space, and the brain parenchyma are all frequently
involved in the inflammatory reaction (meningoencephalitis).
EPIDEMIOLOGY-
 Currently, the organisms most commonly responsible for community acquired
bacterial meningitis are
 Streptococcus pneumoniae (∼50%),
 N. meningitidis (∼25%),
 group B streptococci (∼15%), and
 Listeria monocytogenes (∼10%).
 H. influenzae now accounts for <10% of cases of bacterial meningitis in most
series.
 Acute Bacterial Meningitis
Etiology-
S. pneumoniae is the most common cause of meningitis
in adults >20 years of age
N. meningitidis
Enteric gram-negative bacilli
Group B streptococcus
L. monocytogenes
H. influenzae type b
Staphylococcus aureus
coagulase-negative staphylococci
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 Acute Bacterial Meningitis
CLINICAL PRESENTATION
 Meningitis can present as either an acute fulminant illness that
progresses rapidly in a few hours or as a
 Subacute infection that progressively worsens over several days.
 The classic clinical triad of meningitis is
 fever,
 headache, and
 nuchal rigidity.
 A decreased level of consciousness occurs in >75% of patients
and can vary from lethargy to coma.
 Nausea, vomiting, and photophobia are also common
complaints.
 Acute Bacterial Meningitis
CLINICAL PRESENTATION
 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.
 Acute Bacterial Meningitis
CLINICAL PRESENTATION
Signs of increased ICP include a-
 deteriorating or reduced level of consciousness, papilledema,
 dilated poorly reactive pupils,
 sixth nerve palsies,
 decerebrate posturing, and
 Cushing’s reflex (bradycardia, hypertension, and irregular
respirations).
 The most disastrous complication of increased ICP is cerebral
herniation. The incidence of herniation in patients with
bacterial meningitis has been reported to occur in as few as
1% to as many as 8% of cases.
 Acute Bacterial Meningitis
CLINICAL PRESENTATION
 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.
 Acute Bacterial Meningitis
Laboratory Diagnosis-
Samples needed-
1. Blood (for culture and sensitivity)
2. CSF ( Microscopy- For Organisms & Cell count / Biochemical analysis-
Sugars/ Protein/ Chloride levels)
3. CSF- Culture & sensitivity[the yield of CSF cultures in suspected cases is
low 28. Another disadvantage of CSF bacterial culture is that it requires up to
72 hours for final identification.]
4. CSF- Molecular tests.
Radiological diagnosis-
5. CT
6. MRI
Obtaining CSF Sample- Lumber Puncture
https://www.uptodate.com/contents/lumbar-puncture-technique-indications-c
ontraindications-and-complications-in-adults
 Trans-Isolate (T-I) medium.

CSF Collection Kit

Work
Flow
Chart
With
CSF
Samples
 Acute Bacterial Meningitis
Lab Diagnosis- Interpreting Glucose Levels-
 CSF glucose concentrations <2.2 mmol/L (<40 mg/dL) are abnormal, and
a CSF glucose concentration of zero can be seen in bacterial meningitis.

 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, an carcinomatous meningitis.
 Acute Bacterial Meningitis
 A broad-range PCR can detect small numbers of viable and nonviable
organisms in CSF and is expected to be useful for making a diagnosis of
bacterial meningitis in patients who have been pretreated with oral or
parenteral antibiotics and in whom Gram’s stain and CSF culture are
negative.
 When the broad-range PCR is positive, a PCR that uses specific bacterial
primers to detect the nucleic acid of S. pneumoniae, N. meningitidis,
Escherichia coli, L. monocytogenes, H. influenzae, and S. agalactiae can
be obtained based on the clinical suspicion of the meningeal pathogen.
 The latex agglutination (LA) test for the detection of bacterial antigens of
 S. pneumoniae,
 N. meningitidis,
 H. influenzae type b,
 group B streptococcus, and
 E. coli K1 strains in the CSF
 Acute Bacterial Meningitis
 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 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.
 The Limulus amebocyte lysate assay is a rapid diagnostic test for the
detection of gram-negative endotoxin in CSF and thus for making a
diagnosis of gram-negative bacterial meningitis.
 The test has a specificity of 85–100% and a sensitivity approaching
100%.
 Thus a positive Limulus amebocyte lysate assay occurs in virtually all
patients with gram-negative bacterial meningitis.
 Almost all patients with bacterial meningitis will have Neuro-imaging
studies performed during the course of their illness. MRI is preferred
over CT because of its superiority in demonstrating areas of cerebral
 Acute Bacterial Meningitis
Differential Diagnosis-
1. (HSV) encephalitis
2. Rocky Mountain spotted fever
3. Ehrlichioses
4. Subarachnoid hemorrhage
5. cystic glioma or craniopharyngioma epidermoid
6. sarcoid, systemic lupus erythematosus
7. Behçet’s syndrome
8. Drug hypersensitivity
 ACUTE VIRAL MENINGITIS
CLINICAL MANIFESTATIONS
 Patients with viral meningitis usually present with
 headache,
 fever, and
 signs of meningeal irritation coupled with
 an inflammatory CSF profile.
 The headache of viral meningitis is usually frontal or retroorbital
and is often 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.
 ACUTE VIRAL MENINGITIS
 Patients often have mild lethargy or drowsiness;
however,
 profound alterations in consciousness, such as stupor,
coma, or marked confusion, are unusual in viral
meningitis and suggest the presence of encephalitis or
other alternative diagnoses.
 Similarly, seizures or focal neurologic signs or symptoms
or neuro-imaging 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 of Viral
Meningitis &
Encephalitis
 ACUTE VIRAL MENINGITIS
Lab Diagnosis-
1. Viral Culture- Poor sensitivity & specificity
2. Serologic Studies-
 For some viruses, including many arboviruses such as WNV, serologic studies
remain a crucial diagnostic tool.
 Serum antibody determination is less useful for viruses with high
seroprevalence rates in the general population such as HSV, VZV,CMV, and
EBV.
 Documentation of synthesis of virus-specific antibodies in CSF, as shown by an
increased IgG index or the presence of CSF IgM antibodies, is more useful than
serum serology alone and can provide presumptive evidence of CNS infection.
 Although serum and CSF IgM antibodies generally persist for only a few
months after acute infection, there are exceptions to this rule.
 For example, WNV IgM has been shown to persist in some patients for >1 year
after acute infection.
 ACUTE VIRAL MENINGITIS
 Polymerase Chain Reaction Amplification of Viral Nucleic
Acid-
 Amplification of viral-specific DNA or RNA from CSF using PCR
amplification has become the single most important method for
diagnosing CNS viral infections.
 In both enteroviral and HSV infections of the CNS, PCR has
become the diagnostic procedure of choice.
 CSF PCR is also used routinely to diagnose CNS viral infections
caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV),
VZV, and human herpesvirus 6 (HHV-6).
 CSF PCR tests are available for WNV but are not as sensitive as
CSF IgM.
 PCR is also useful in the diagnosis of CNS infection caused by
Mycoplasma pneumoniae, which can mimic viral meningitis.
 ACUTE VIRAL MENINGITIS
Treatment-
 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. Oral or intravenous
acyclovir may be of benefit in patients with meningitis caused by HSV-1
or -2 and in cases of severe EBV or VZV infection.
 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.
 Patients who are less ill can be treated with oral drugs alone.
 HIV meningitis - highly active antiretroviral therapy.
 VIRAL ENCEPHALITIS
Definition-
In contrast to viral meningitis, where the infectious
process and associated inflammatory response are
limited largely to the meninges, 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).
 VIRAL ENCEPHALITIS
Clinical Manifestations-
 In addition to the acute febrile illness with evidence of meningeal
involvement characteristic of meningitis,
 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.
 VIRAL ENCEPHALITIS
Clinical Manifestations-
 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).
 VIRAL ENCEPHALITIS
Laboratory diagnosis-
1. CSF Examination- same as Viral meningitis
2. CSF culture- >95% culture negative
3. Serology- HSV-1 & WNV-IgM
4. CSF PCR- CMV, EBV,VZV, HHV-6, and
enteroviruses
5. MRI/ CT/ EEG
 VIRAL ENCEPHALITIS
Treatment-
 Vital functions, including respiration and blood pressure, should be
monitored continuously and supported as required. In the initial
stages of encephalitis, many patients will require care in an intensive
care unit.

 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.
 VIRAL ENCEPHALITIS
 Acyclovir- HSV/VZV/EBV-Adults should receive a dose of
 10 mg/kg of acyclovir intravenously every 8 h (30 mg/kg per
day total dose) for a minimum of 14 days. it is recommended
that
 neonates with HSV encephalitis receive 20 mg/kg of acyclovir
every 8 h (60 mg/kg per day total dose) for a minimum of 21
days.
 Ganciclovir and foscarnet, either alone or in combination, are
often utilized in the treatment of CMV-related CNS infections,
although their efficacy remains unproven. Cidofovir may
provide an alternative in patients who fail to respond to
ganciclovir and foscarnet.
 CHRONIC AND RECURRENT
MENINGITIS
 Chronic inflammation of the meninges (pia, arachnoid, and dura) can produce
profound neurologic disability and may be fatal if not successfully treated.
 The condition is most commonly diagnosed when a
 characteristic neurologic syndrome exists for >4 weeks and is associated
with
 a persistent inflammatory response in the cerebrospinal fluid (CSF) (white
blood cell count >5/μL).
 The causes are varied, and appropriate treatment depends on identification of
the etiology.
 Five categories of disease account for most cases of chronic meningitis:
(1) MENINGEAL INFECTIONS,
(2) MALIGNANCY,
(3) NONINFECTIOUS INFLAMMATORY DISORDERS,
(4) CHEMICAL MENINGITIS, AND
(5) PARAMENINGEAL INFECTIONS.
 BRAIN ABSCESS
Definition-
 A brain abscess is a focal, suppurative infection within the brain
parenchyma, typically surrounded by a vascularized capsule. The
term cerebritis is often employed to describe a nonencapsulated brain
abscess.
 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.
 BRAIN ABSCESS
Etiology-
 Associated with Mastoiditis-
 streptococci, Bacteroides spp., Pseudomonas spp.,
Haemophilus spp., and Enterobacteriaceae.
 Associated with paranasal sinusitis-
 streptococci (especially S. milleri), Haemophilus spp.,
Bacteroides spp., Pseudomonas spp., and S. aureus.
 Dental infections- streptococci, staphylococci, Bacteroides
spp., and Fusobacterium spp.
 BRAIN ABSCESS
 Heamatogenous-
 brain abscesses that develop as a complication of infective endocarditis
are often due to viridans streptococci or S. aureus.

 Abscesses associated with pyogenic lung infections such as lung abscess

or bronchiectasis are often due to streptococci, staphylococci,
Bacteroides spp., Fusobacterium spp., or Enterobacteriaceae.

 Abscesses that follow penetrating head trauma or neurosurgical

procedures are frequently due to methicillin-resistant S. aureus (MRSA),
S. epidermidis, Enterobacteriaceae, Pseudomonas spp., and Clostridium
spp.

 Enterobacteriaceae and P. aeruginos aare important causes of abscesses

associated with urinary sepsis.
 BRAIN ABSCESS
 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.

 Microbiologic diagnosis of the etiologic agent is most accurately

determined by Gram’s stain and culture of abscess material obtained
by stereotactic needle aspiration.

 Aerobic and anaerobic bacterial cultures and mycobacterial and

fungal cultures should be obtained.

 Up to 10% of patients will also have positive blood cultures.

 BRAIN ABSCESS
Diagnosis-
 LP should not be performed in patients with known or
suspected focal intracranial infections such as abscess or
empyema; CSF analysis contributes nothing to diagnosis or
therapy, and LP increases the risk of herniation.
 About 50% of patients have a peripheral leukocytosis,
 60% an elevated ESR, and
 80% an elevated C-reactive protein.
 Blood cultures are positive in ∼10% of cases overall but
may be positive in >85% of patients with abscesses due to
Listeria.
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