2. OUTLINE
Acute CNS infections: Pyogenic meningitis
Sub acute Infections: Tuberculous CNS infection
Syphilis and Neurosyphilis-
3. INTRODUCTION
ACUTE CNS INFECTIONS
Acute infections of the nervous system are among the most
important problems in medicine.
These include acute bacterial meningitis, viral meningitis,
encephalitis, focal infections such as brain abscess and
subdural empyema, and infectious thrombophlebitis.
CNS infections may predominantly involve the
subarachnoid space (meningitis) or there may be evidence
of either generalized or focal involvement of brain tissue in
the cerebral hemispheres, cerebellum, or brainstem.
4. When brain tissue is directly injured by a viral infection,
the disease is referred to as encephalitis.
Whereas focal infections involving brain tissue are
classified as either cerebritis or abscess.
Key goals of early management are to emergently
distinguish between these conditions, identify the
responsible pathogen, and initiate appropriate
antimicrobial therapy.
5. ACUTE BACTERIAL MENINGITIS
An acute inflammatory disease of the leptomeninges
Specifically infection of the arachnoid mater and the CSF
in both the subarachnoid space and the cerebral
ventricles.
Bacteria may gain access to the ventriculo-subarachnoid
space:
Invasion of the CNS following bacteremia due to a
localized source.
Colonization of the nasopharynx with subsequent
bloodstream invasion and subsequent CNS invasion.
Direct entry of organisms into the CNS from a contiguous
infection, trauma, neurosurgery, or medical devices (eg,
shunts or intracerebral pressure monitors)
7. ETIOLOGY
Up to age 60:
- S. pneumoniae is responsible for 50-60 percent of cases
- N. meningitidis (20 percent),
- H. influenzae (10 percent),
- L. monocytogenes (6 percent), and
- group B streptococcus (4 percent).
Age 60 and above,
- Almost 70 percent of cases were due to S. pneumoniae,
- Approximately 20 percent to L. monocytogenes, and
- 3 to 4 percent each to N. meningitidis, group B streptococcus, and H. influenzae.
8. ETIOLOGY AND PREDISPOSING FACTORS
S. pneumoniae:
The most common cause of meningitis in adults >20
years of age, accounting for nearly half the reported
cases.
Pneumococcal pneumonia, the most important Predisposing
conditions that increase the risk of pneumococcal
meningitis.
Additional risk factors include coexisting acute or chronic
pneumococcal sinusitis or otitis media, alcoholism, diabetes,
splenectomy, hypogammaglobulinemia, complement
deficiency.
The mortality rate remains 20% despite antibiotic
therapy.
9. N. meningitidis
The incidence of meningitis due to N. meningitidis has
decreased with the routine immunization of 11- to 18-
year-olds with the tetravalent (serogroups A, C, W-
135, and Y) meningococcal glycoconjugate vaccine.
Vaccine usually prevent 2-10years.
The vaccine does not contain serogroup B, which is
responsible for one-third of cases of meningococcal
disease.
10. Infection may be initiated by nasopharyngeal
colonization, which can result in either an
asymptomatic carrier state or invasive meningococcal
disease.
The risk of invasive disease following nasopharyngeal
colonization depends on both bacterial virulence
factors and host immune defense mechanisms.
11. 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
(Haemophilus sp., Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, Kingella
kingae), or Enterococci.
Group B streptococcus, or S. agalactiae- in individuals >50
years of age, particularly those with underlying diseases.
12. L. monocytogenes - pregnant women, individuals >60 years,
and immunocompromised individuals of all ages.
Infection is acquired by ingesting foods contaminated by
Listeria.
H. influenzae b causes meningitis in unvaccinated children and
older adults, and non-b H. influenzae is an emerging pathogen.
Staphylococcus aureus and coagulase-negative staphylococci
are important causes of meningitis that occurs following invasive
neurosurgical procedures.
14. PATHOPHYSIOLOGY
Three major mechanisms for developing meningitis:
Invasion of the CNS following bacteremia due to a localized source,
such as pneumonia infective endocarditis or pyelonephritis
Colonization of the nasopharynx with subsequent bloodstream
invasion and subsequent central nervous system invasion
Direct entry of organisms into the CNS from a contiguous infection (eg,
sinuses, mastoid), trauma, neurosurgery, or medical devices (eg, shunts
or intracerebral pressure monitors)
Host factors predisposing to meningitis:
- Asplenia, complement deficiency, corticosteroid excess, HIV
infection
15. S. pneumoniae and N. meningitidis, initially colonize the nasopharynx
by attaching to nasopharyngeal epithelial cells.
Bacteria are transported across epithelial cells in membrane-bound
vacuoles to the intravascular space or invade the intravascular space.
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.
Some bacteria, such as S. pneumoniae, can adhere to cerebral
capillary endothelial cells and subsequently migrate through or
between these cells to reach the CSF.
16. 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.
The paucity of the latter two prevents effective opsonization of
bacteria, an essential prerequisite for bacterial phagocytosis by
neutrophils.
Phagocytosis of bacteria is further impaired by the fluid nature of
CSF, which is less conducive to phagocytosis than a solid tissue
substrate.
17. A critical event in the pathogenesis of bacterial meningitis
is the inflammatory reaction induced by the invading
bacteria.
Many of the neurologic manifestations and complications
of bacterial meningitis not from direct bacteria-induced
tissue injury.
Direct consequence of elevated inflammatory cytokines
and chemokines is major pathologic mechanism in
pyogenic meningitis.
As a result, neurologic injury can progress even after the
CSF has been sterilized by antibiotic therapy.
19. CLINICAL FEATURES
The classic clinical triad of meningitis is fever, headache, and
nuchal rigidity over a period of hours.
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.
The absence of all of the classic findings- excludes Dx of bacterial
meningitis.
Nausea, vomiting, and photophobia are also common complaints.
20. 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.
21. Raised ICP
Signs of increased ICP include a deteriorating or
reduced level of consciousness, papilledema, dilated
poorly reactive pupils, sixth nerve palsies, decerebrate
posturing, and the Cushing reflex.
The most disastrous complication of increased ICP is
cerebral herniation.
Focal neurologic deficits in 20 to 33 percent.
22. Certain bacteria, particularly N. meningitidis, can
cause characteristic skin manifestations, such as
petechiae and palpable purpura.
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.
23. Bacterial meningitis tends to spare other organs unless
severe sepsis ensues.
However, if meningitis is the sequela of an infection
elsewhere in the body, there may be features of that
infection still present at the time of diagnosis of meningitis
(e.g., otitis or sinusitis).
Examination for meningeal irritation sign :
- Nuchal rigidity/neck stiffness (sen 30% & spe 68%)
- Kerning and Brudzininski signs(For each sens 5% & spe
95%)
24. INVESTIGATION
Laboratory features
CBC
Blood culture- often positive
- Very useful in the event that LP can’t be
performed due contraindications
- ~ 70-75% - positive
CSF analysis- Pressure, appearance, biochemical,
microbiologic studies.
25. INDICATIONS FOR CT BEFORE LP
- History of CNS disease (mass lesion, stroke, or focal
infection)
- New onset seizure (within one week of presentation)
- Papilledema
- Abnormal level of consciousness
- Focal neurologic deficit
Should LP be delayed for cranial imaging- antibiotics
should be started empirically before the imaging
26. A normal CT scan does not always mean that performance of an LP is
safe.
Certain clinical signs of impending herniation (ie, deteriorating level of
consciousness, particularly a Glasgow Coma scale <11; brainstem
signs including pupillary changes, posturing, or irregular respirations;
or a very recent seizure) may be predictive of patients in whom an LP
should be delayed irrespective of CT findings
27. Antibiotic therapy initiated a few hours prior to LP will not
significantly alter the CSF WBC count or glucose
concentration, nor is it likely to prevent visualization of
organisms by Gram's stain or detection of bacterial nucleic
acid by polymerase chain reaction assay.
28. THE CLASSIC CSF ABNORMALITIES IN
BACTERIAL MENINGITIS
1. Opening pressure >180 mmH2O in 90%.
2. White blood cells =10 to 10,000/uL; predo. pmn
PMN leukocytosis (>100 cells/uL in 90%).
3. Decreased glucose concentration [<2.2 mmol/L (<40 mg/dL)
and/or CSF/serum glucose ratio of <0.4 in 60%.
4. Increased protein concentration [>0.45 g/L (>45 mg/dL) in
90%],
29. 5. CSF bacterial cultures are positive in >80% of patients.
6. CSF Gram's stain demonstrates organisms in >60%.
7. Latex agglutination=May be positive in patients with meningitis
due to S. pneumoniae, N. meningitidis, H. influenzae type b, E.
coli, group B streptococci.
8. Limulus lysate=Positive in cases of gram-negative meningitis.
9. PCR broad range/specific bacterial primer= Detects bacterial
nucleic acid
30. Gram’s stain and culture
- Gram’s stain- advantage of suggesting bacterial etiology
one day prior to culture
- findings:
- Gram-positive diplococci suggest pneumococcal infection
- Gram-negative diplococci suggest meningococcal infection
Gram’s stain- positive in 10-15% of culture negatives
31. Latex agglutination test for the detection of: -
- very useful for making rapid DX- especially in pts who
have been pretreated with antibiotics
- specificity of 95-100% for the detection of S.
pneumoniae and N. meningitidis.
- A positive test is diagnostic of bacterial meningitis
- sensitivity- 70-100% for S.pneumoniae and 33-70%
for N.meningitidis
- negative test doesn’t r/o bacterial meningitis
32. Limulus amebocyte lysate assay- rapid diagnostic test for
the detection of Gram negative endotoxin
- high sensitivity/nearly 100%/ and specificity /85-
100%/
- Positive in all pts with Gram negative meningitis
BUT false positive may occur.
Petechial skin lesions should be biopsied- may reveal
meningococci
33. PROGNOSIS
Mortality rate is 3–7% for meningitis caused by H. influenzae, N.
meningitidis, or group B streptococci; 15% for that due to L.
monocytogenes; and 20% for S. pneumoniae.
In general, the risk of death from bacterial meningitis increases with
(1) Decreased level of consciousness on admission,
(2) Onset of seizures within 24 h of admission,
(3) Signs of increased ICP,
(4) Young age (infancy) and age >50,
(5) She presence of comorbid conditions including shock and/or the
need for mechanical ventilation, and
(6) Delay in the initiation of treatment.
34. Moderate or severe sequelae occur in 25% of survivors,
although the exact incidence varies with the infecting
organism.
Common sequelae include decreased intellectual function,
memory impairment, seizures, hearing loss and dizziness,
and gait disturbances.
35. GENERAL PRINCIPLES OF THERAPY
IV antibiotics should be directed against the presumed pathogen
empirically then, modify treatment after the culture and sensitivity
result
If Gram positive cocci seen in community acquired meningitis- consider
pneumococci
- If in the setting of neurosurgery, head trauma, a neurosurgical
device, or a CSF leak- Staphylococci are common and Rx with
vancomycin.
-In patients with Gram –ve rods- replace ceftriaxone with ceftazidime:
- history of neurosurgery, head trauma, a neurosurgical device
& a CSF leak
38. CENTRAL NERVOUS SYSTEM MYCOBACTERIUM
TUBERCULOSIS DISEASES
Forms of central nervous system Mycobacterium tuberculosis infection
include:
- Meningitis
- Tuberculoma
- Spinal arachnoiditis
Among patients with TB, approximately 1 to 5 percent are complicated by
CNS TB
TB meningitis
Case fatality ratio- remains high- 15-40% despite effective RX
Early recognition of TB meningitis- important- b/c outcome depends on the
stage Rx is initiated
39. PATHOGENESIS
During the bacillemia that follows primary infection or late
reactivation TB, scattered tuberculous foci (tubercles) are established
in the brain, meninges, or adjacent cranial bone.
The establishment of a cortical or meningeal tubercle (Rich focus), with
subsequent rupture into the subarachnoid space, is the critical event in
the development of TB meningitis.
Tuberculous meningitis in adults doesn’t develop acutely from
hematogenous tubercle bacilli to the meninges.
Rather From chronic reactivation bacillemia in adults with immune
deficiency: HIV, aging, alcoholism, malnutrition, malignancy
40. Spillage of TB proteins in to SAS- cause
hypersensitivity reaction giving rise to intense
inflammatory changes most marked at the base of
the brain.
Formation of thick exudates at the basilar cisterns
and surrounds the CN & Major blood vessels at the
base of the brain.
Since meningeal involvement is pronounced at the
base of the brain, paresis of cranial nerves (ocular
nerves in particular) is a frequent finding, and the
involvement of cerebral arteries may produce focal
ischemia.
41. THREE FEATURES DOMINATE THE PATHOLOGY AND
EXPLAIN THE CLINICAL MANIFESTATIONS:
1) Thick gelatinous exudate, most marked at the basal part of the
brain, eventually produces a fibrous mass that encases adjacent cranial
nerves and vessels of Circle of Willis, leading to cranial nerve palsies
and periventricular infarcts, respectively.
Proliferative arachnoiditis, produces a fibrous mass involving cranial
nerves and penetrating vessels.
2) Tuberculous vasculitis with resultant inflammatory vascular changes
leads to spasm, constriction, thrombosis, and occlusion of intracerebral
vessels, resulting in infarction of the brain parenchyma.
Infarcts in tuberculous meningitis are typically small, multiple, bilateral,
and frequently located in the periventricular regions
42. The most involved structures are the basal ganglia, thalamus, and
internal capsule and variety of stroke syndromes involving the BG,
cerebral cortex, pons, and cerebellum can also occur.
3) Hydrocephalus eventually develops in the majority of patients with
tuberculous meningitis.
Communicating hydrocephalus results from extension of the
inflammatory process to the basilar cisterns and impedance of
cerebrospinal fluid circulation and resorption.
Noncommunicating or obstructive hydrocephalus caused by
obstruction of the aqueduct develops less frequently, from contraction
of exudate surrounding the brainstem or because of a brainstem
tuberculoma that blocks drainage.
43. CLINICAL MANIFESTATIONS
Typical presentation —
●Patients with tuberculous meningitis commonly present with stiff neck,
headache, fever, and vomiting
●Subacute presentation over 90 % give history of illness more than a
week.
●Altered consciousness, personality changes, and coma
●Presence of cranial nerve palsies (most frequently involving cranial
nerve II and VI) are common.
44. Patients with tuberculous meningitis typically progress through three
discernible phases:
- A prodromal phase, lasting one to three weeks, is
characterized by the insidious onset of malaise, lassitude, headache,
low-grade fever, and personality change.
- The meningitic phase follows with more pronounced
neurologic symptoms, such as meningismus, protracted headache,
vomiting, confusion, and varying degrees of cranial nerve and long-
tract signs.
- The paralytic phase is the stage during which the pace of
illness may accelerate rapidly; confusion gives way to stupor and
coma, seizures, and often hemiparesis.
45. DISEASE STAGES
— Patients may be categorized by the stage of illness, based on
mental status and neurologic signs:
●Stage I – Alert and oriented with no focal neurologic signs.
●Stage II – Conscious but with inattention, confusion, lethargy; they
may have mild focal signs such as cranial nerve palsies or hemiparesis
(Glasgow coma score 11 to 15).
●Stage III – Advanced illness with delirium, stupor, coma, seizures,
multiple cranial nerve palsies, and/or dense hemiplegia (Glasgow
coma score ≤10)
46. For the majority of untreated pts- death ensues with in 5-8 weeks
Signs of active TB outside the CNS- of diagnostic aid- but often absent
- CXR abnormalities- seen in 50% of cases
Patients may present due to complications
Atypical presentations:
- Pts may present with and acute, rapidly progressive illness mimicking
pyogenic meningitis
- some- slowly progressive dementia over months; personality change, social
withdrawal, loss of libido, and memory deficits
- less common- encephalitic picture with stupor coma, and convulsions
without signs of meningitis
47. Diagnosis:
- Maintaining a high degree of suspicion & do Routine
test CBC,HIV,… Electrolyte determinations
- CSF- typical formula:
-Turbid CSF, high protein, low glucose, and
with a mononuclear pleocytosis.
- protein- 100- 800mg/dl
- glucose- < 40mg/dl
- cell count- 100-1000/ul
- Early in the course- may be PMN cell predominant –
rapidly change to mononuclear on subsequent analysis
48. However, any of these three parameters can be
within the normal range.
AFB are seen on direct smear of CSF sediment in
up to one-third of cases(10-40%), but repeated
lumbar punctures increase the yield.
Recommendation- a minimum of 3 LPs at daily
intervals
It is best to use the last fluid removed at lumbar puncture,
and recovery of the organism improves if a large volume
(10 to 15 mL) is removed
49. SENSITIVITY OF AFB MAY BE ENHANCED
Organisms can be demonstrated most readily in a smear of the
clot/ Cobweb like clot/ or sediment.
If no clot forms, the addition of 2 mL of 95 percent alcohol
gives a heavy protein precipitate that carries bacilli to the
bottom of the tube upon centrifugation.
0.02 mL of the centrifuged deposit should be applied to a
glass slide in an area not exceeding one centimeter in diameter
and stained by the standard Kinyoun or Ziehl-Neelsen method.
Between 200 and 500 high-powered fields should be
examined (approximately 30 minutes), preferably by more than
one observer.
50. …CTD
Culture of CSF is diagnostic in up to 80% of cases and
remains the gold standard.
•Polymerase chain reaction (PCR) has a sensitivity of up to 80%,
but rates of false-positivity reach 10%.
•Neuroradiology:
- CT with contrast- can define the presence and extent of:
- basilar arachnoiditis and abnormal enhancement of
basal cisterns or ependyma.
- cerebral edema and infarction
- hydrocephalus
- MRI- superior to CT in detecting lesions of the BG, BS, and
midbrain
51. TREATMENT
Specific anti-TB Rx should be started on the basis of
strong clinical suspicion
- shouldn’t be delayed until proof of infection
Clinical outcome depends on the stage at which Rx is
initiated
Anti Tb treatment for up to 9-12mts
52. …CTD
Recommended steroid regimen:
- prednisolone- 60mg/day tapered gradually over 6weeks
- Dexamethasone- IV for the first 3weeks-0.4mg/kg then tapering
to 1mg/kg/day.
- followed by oral administration-4mg/d
Complications: Hydrocephalus occurs in up to 80 percent of patients
with tuberculous meningitis, Hyponatremia, Vision loss, Cognitive
disorders, motor weakness and Seizure disorder.
53. TUBERCULOMA
Conglomerate of caseous foci with in the substance of the brain
From deep seated tubercles acquired during a recent or remote
hematogenous bacillemia
Radiologically- single or multiple enhancing nodular lesions often apparent
on CT.
A distinct clinical syndrome- with focal neurologic symptoms and signs and
signs of an intracranial mass lesion
Dx- by clinical and radiographic findings or by needle biopsy
Surgery- often complicated by sever, fatal meningitis
- indication- obstructive hydrocephalus or brainstem
compression.
Corticosteroids: when cerebral edema contributes to altered mentation and
focal deficits
54. SPINAL TB ARACHNOIDITIS
Seen more in developing countries
Pathogenesis- similar to TB meningitis with focal inflammatory disease at
single or multiple levels- produces gradual encasement of the SC
Symptoms- develop and progress slowly –over weeks to months-
terminate with meningitis syndrome
Patients present with a subacute onset of nerve root and cord
compression:
- spinal or radicular pain, hyperesthesia
- lower motor neuron paralysis
- bladder and rectal dysfn
Vasculitis- may lead to thrombosis of ASA- infarction
55. DIAGNOSIS
- finding of abnormal CSF protein- spinal block
- MRI changes of nodular arachnoiditis
- tissue biopsy
Treatment- like TB meningitis
![THE CLASSIC CSF ABNORMALITIES IN
BACTERIAL MENINGITIS
1. Opening pressure >180 mmH2O in 90%.
2. White blood cells =10 to 10,000/uL; predo. pmn
PMN leukocytosis (>100 cells/uL in 90%).
3. Decreased glucose concentration [<2.2 mmol/L (<40 mg/dL)
and/or CSF/serum glucose ratio of <0.4 in 60%.
4. Increased protein concentration [>0.45 g/L (>45 mg/dL) in
90%],](https://image.slidesharecdn.com/infectiousdisordersofcns-250809204117-ea2843ca/85/Cns-infection-for-medical-students-c-I-lecture-28-320.jpg)
