Central nervous system infections can cause fever and signs of neurological dysfunction. The most common types are meningitis (inflammation of the meninges) and encephalitis (inflammation of the brain). Acute bacterial meningitis is commonly caused by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Clinical manifestations include fever, headache, neck stiffness, and altered mental status. Diagnosis involves lumbar puncture and CSF analysis. Treatment involves supportive care, antibiotics, and management of increased intracranial pressure. Complications can include hearing loss, seizures, and intellectual disability. Prevention is through vaccination and chemoprophylaxis of close contacts for certain bacteria.

1. Central Nervous
System Infections
Dr. Wassihun T.
( MD )
05/24/18
1

2. Outline
• Introduction
• Acute bacterial meningitis
– Definition
– Etiology
– Risk factors
– Pathology and
pathogenesis
– Clinical
manifestations
– Diagnosis
– Management
– Complication
– Prognosis
– Prevention
2

3. CNS Infections
• Most common cause of fever associated with
signs and symptoms of CNS disease
• Viral > bacterial > fungal and parasitic
infections
• Regardless of etiology, most patients with CNS
infection have similar clinical manifestations
3

4. Cont…
1. Diffuse
 Meningitis
 Encephalitis
 Meningoencephalitis
2. Focal
 Brain abscess
 Parameningeal abscess
 subdural empyema,
 spinal epidural abscess
4

5. SS

6. Acute Bacterial Meningitis
• Definition-Inflammation of the leptominges
surrounding the brain and spinal cord: pia,
arachnoid and subarachnoid matter
• Occurs at all ages but is commonest during infancy
(greatest risk 6-12 months)
6

7. Con…...
• Bacterial meningitis is one of the most potentially
serious infections occurring in infants and older
children.
• This infection is associated with a high rate of acute
complications and risk of long-term morbidity.
• The incidence of bacterial meningitis is sufficiently
high in febrile infants that it should be included in
the differential diagnosis of those with altered
mental status and other evidence of neurologic
dysfunction

8. SS

9. ETIOLOGY
Neonatal period
• Groups B streptococci
• Gram-negative enteric bacilli (E. coli,
Klebsiella), and
• Listeria monocytogenes
9

10. ETIOLOGY…..
Children 2 mo to 12 yr of age
• N. meningitidis
• H. influenzae type b
• S. pneumoniae
10

11. Etiology…
• Alterations of host defense
– Pseudomonas aeruginosa
– Staphylococcus aureus, Coagulase-
negative staphylococci
– Salmonella spp
– L. monocytogenes
11

12. EPIDEMIOLOGY
Predisposing Factors
Major risk –Lack of immunity to specific pathogens associated
with young age
Additional risk factors
• Recent colonization with pathogenic bacteria
• Close contact with patients having invasive disease caused
by N. meningitidis and H. influenzae type b,
• Crowding
• Poverty
• Male sex
 Person to person contact through respiratory secretions or
droplets.
12

13. Risk factors …
Congenital or acquired CSF leak
 Middle ear or inner ear fistulas
 Basal skull fracture into the cribriform plate or increased risk
of pneumococcal meningitis.
• Lumbosacral dermal sinus and meningomyelocele:
staphylococcal and gram-negative enteric meningitis.
13

14. Streptococcus pneumonia
• Commonly occurs during the first 2yrs of life
• Peak 6-12 months
• Highest in children with
• HIV- infection
• Anatomic or functional asplenia
• Other risk factors include
• Otitis media
• Sinusitis
• Pneumonia
• CSF otorrhea or rhinorrhea
14

15. Neisseria Meningitides
Occurs
• Sporadically or as epidemics
• Serogroups A,B,C,Y, W-135,X are responsible
• Contact infection
• Epidemics is defined as the occurrence of 3
cases in 3 months time with attack rate of 10
cases per 100,000 population in the same
community
• Epidemics is usually caused by serogrup A
15

16. Haemophilus influenza type B
• Primarily occurs in infants 2month to 2 yrs
• 50% of cases occur in the 1st year of life
• Peak at 6-9 months of age
• Risk increased
among family or day care center contacts of
patients with HIB disease.
unvaccinated and
those with blunted immunologic responses to
vaccine
( HIV- Infection)
16

18. Pathogenesis
Routes of infection
• Hematogenous dissemination of micro-organisms
from a distant site of infection-Most common route.
• Direct invasion of the CNS from
 contiguous focus of infection: otitis media,
mastoditis, sinusitis,osteomyelitis (cranial,vertebral)
through anatomic abnormalities
head trauma
neurosurgical procedures
18

19. Pathogenesis
• Bacterial colonization of the nasopharynx
• Hematogenous dissemination
• Bacteremia
• Prior or concurrent viral upper respiratory tract
infection may enhance the pathogenicity of bacteria
producing meningitis

20. Pathogenesis…..
• Bacteria gain entry to the CSF
• Multiply rapidly and incite local inflammatory
response, with polymorphonuclear cell
infiltration.
• Marked inflammatory response with local
production of TNF, IL-1, and other cytokines
• Inflammatory response in characterized by
– Neutrophilic infiltration
– Altered BBB
– Increased vascular permeability
– Vascular thrombosis and vasculitis
• Inflammation of spinal nerves and roots
produces meningeal signs
• Inflammation of the cranial nerves produces
cranial neuropathies
20

21. Nasopharyngeal colonization
Local invasion
Bacteremia
Meningeal invasion
Bacterial replication in the subarachnoid space
Release of bacterial components (cell wall, LOS)
Cerebral microvascular endothelium Macrophages, neutrophils, other CNS Cells
Cytokines
Subarachnoid space inflammation
Cerebral
vasculitis
Increased CSF outflow resistance
Hydrocephalus
Interstitial edema
Increased intracranial pressure
Decreased cerebral blood flow and loss of cerebrovascular autoregulation
Cytotoxic edema
Cerebral
infarction
Increased BBB
permeability
Vasogenic
edema
21

22. Clinical manifestations
Infants
• Fever
• Poor feeding
• Projectile Vomiting
• Altered level of consciousness
• Convulsions
• Neck stiffness ( hyper extension)
• Bulging fontanel
• Rash (Purpuric)
• Meningeal signs are not consistently present
22

23. Clinical manifestations…..
Older children
• Classic signs are preceded upper respiratory
or GIT symptoms
• Fever
• Headache
• Projectile Vomiting
• Poor feeding
• Seizures are common-20-30% of patients
before or during the first 3 days after
diagnosis
23

24. P/E
• Neck stiffness
• Positive Kerning’s sign
• Positive Brudzinski’s sign
• Altered state of consciousness
• CN palsies
• Meningococcal meningitis
-generalized purpuric rash
-Peripheral cyanosis
-Toxic and comatose
-Tachycardia, Hypotension
- DIC
24

25. • Alterations of mental status
– Irritability, lethargy to coma may be due to:
• Increased ICP
• Cerebritis
• Hypotension
• Factors that lead to Death or Brain Damage in
Meningitis
– SIADH secretion With resultant Hyponatremia
– Brain edema → Acute Brainstem Compression
– Subdural Effusion/Empyema/Brain Abscess
– Seizures
25

26. Kerning Vs Brudzinski signs
26

27. Diagnosis
Lumbar Puncture- CSF analysis
• Leukocyte count (>1000/mm3
) with neutrophilic
predominance (75–95%).
• Turbid CSF when WBC count is >200–400/mm3
.
– <250/mm3
in as many as 20% of patients
– pleocytosis may be absent in severe overwhelming
sepsis and meningitis and is a poor prognostic sign
– lymphocyte predominance may be present during the
early stage
• Elevated protein
 Gram stain-positive in 70–90% of untreated patients
• Culture
27

28. Conditions Pressure
(mmH2O)
Leukocyte
(mm3)
Protein
(mg/dl)
Glucose
(mg/dl)
Normal 50-80 <5, ≥75%
Lymphocytes
20-45 >50 (or 75%
Serum
Glucose)
Acute
Bacterial
Usually
elevated
(100 -300)
>100-10,000 ;
usually 300-2,000;
PMNs
Usually
100-500
usually <40
(or <50%
serum
glucose)
Partially
Rxed Bact.
Normal or
elevated
5-10,000; PMNs
early/Mon
dominate most of
the course
Usually
100-500
Normal or
decreased
Viral Normal/slight
ly (80-150)
Rarely >1,000,
Mon predominate
Usually 50-
200
Generally
normal; but
mumps
Tuberculou
s
Usually
elevated
10–500;lymp
predominate
through most of the
100-3,000;
may be
higher
<50 in most
cases
28

29. Diagnosis……
• CBC- Leukocytosis, with polymorph
predominance
• Blood culture- reveals organisms in
~80-90% of cases
» CXR if pneumonia or TB is suspected
29

30. Contra-indications for Lumbar Puncture
• Elevated ICP and focal Neurologic deficit
• Severe cardio respiratory compromise – postpone
LP
• Infection of the overlying skin
• Thrombocytopenia ( relative)
30

31. DDX
• Aseptic meningitis
• Tuberculous meningitis
• Cerebral malaria
• Brain abscess
• Brain tumor
31

32. Management
I. Supportive Measures
 Vital Signs _ 15-30 min.
 Frequent Neurologic assessment -Follow patient with
neurosign chart
– Level of consciousness(GCS)
– Pupillary size and reactivity
– Pattern of breathing
– Posture
– Occulocephalic reflex
– Seizure
– Cranial nerve palsies or focal Neurologic deficits
– Daily HC measurement –for children<18 months
32

33. Management…..
 Strict input/output recording
 Serum electrolytes
 Body weight
 Antipyretics ,Cold sponging
• Fluid restriction to 2/3rd maintenance for fear of syndrome
of inappropriate ADH secretion
- fluid restriction should be avoided in the presence of
hypotension
• Coma care- bowel, bladder, skin, air way
• Seizure control
– Active SZ –arrest with diazepam 0.1 -0.3
mg/kg/IV or PR
– Prevention of recurrence of seizure
» Phenytoin- 20mg/kg loading then 5mg/kg/ 24
hrs – bid
– Phenobarbitone can be added for refractory SZ
33

34. Management…..
II. Specific Measures
• Shock
– in meningo coccemia or due to
vomiting
– IV NS/RL /Plasma
• Antibiotic therapy
34

35. Antibiotic therapy
Empirical treatment
• Cyst.pencillin plus
• Chloramphenicol or
• Ceftriaxone 100mg/kg/24hrs Bid
• Vancomycin – penicillin/ceftriaxone resistant
S.pneumoniae
• According to culture and sensitivity result
35

36. Antibiotics
• Duration of therapy
– 5-7 days for meningococcal meningitis
– 7-10 days for H. influenzae meningitis
– 10-14 days for pneumococcal meningitis
– Gram-negative meningitis should be treated
for 3 wk or for at least 2 wk after CSF
sterilization
36

37. Corticosteroids
• Corticosteroid:
– decrease ICP by decreasing meningeal
inflammation and brain water content
– modulate the production Of cytokines, lessens the
meningeal inflammatory response
– decrease incidence of sensorineural hearing loss
or other neurologic complications
• Dexamthasone
• 0.15 mg/kg/dose Qid for 2 days before the 1st
dose of antibiotic for those older than 6wks
37

38. Complications
Increased Intracranial pressure(ICP)-
• Common acute complication
1. Increase ICP is due to:-
– Cytotoxic cerebral edema- due to cell swelling→cell
death
– Vasogenic cerebral edema- due to cytokine induced
increased capillary vascular permeability
– Interstitial cerebral edema- increased hydrostatic
pressure after impaired reabsorption or obstruction of
CSF flow (Hydrocephalus)
38

39. Management of Increased ICP
– Elevating head by 300
– 20%Manitol 0.5-1g/kg/dose over 30min, Q6hrs or
Frusemide 1mg/kg or hypertonic saline(3% Saline)
– Dexamethasone 0.25 -0.5mg/kg QID
– Endotracheal intubation and hyperventilation (Pco2
25-30mmHG)
– Treat fever aggressively
39

40. 2 .Hydrocephalus
• Communicating
– Ocurrs most commonly
– due to adhesive thickening of arachnoid villi
around the cisterns - impaired CSF
reabsorption
• Obstructive
– Less often
– due to fibrosis and gliosis of the aqueduct of
sylvius
40

41. 3 .Subdural effusion
• 10-30% of cases
• Highest in infants ,and H.influenzae
meningitis(45% of cases)
• 85-90% are asymptomatic
• C/Fs
o bulging fontanel
o diastasis of sutures
o enlarging HC
o Persistence /recurrence of emesis
o Persistent/focal seizures
o persistence of fever
• Symptomatic - subdural tap
41

42. Complications…..
4 . Cranial nerve palsies
– Inflammation of cranial nerves results cranial
neuropathies of Optic ,Oculomotor, Facial ,Auditory
Nerves
– Increased ICP Produces oculomotor and abducens
nerve palsies
5. Seizure
– focal or generalized
– 20–30% of patients
– occurs due to cerebritis, infarction, or
electrolyte disturbances
_ on presentation or within the 1st 4 days of
onset is usually of no prognostic significance
42

43. Complications…..
6 .Syndrome of inappropriate ADH
secretion
7 .Cerebral herniation
8 .Stroke
43

44. chronic complications
• Sensorineural hearing loss– mainly cochlear injury
• Ataxia
• Hemiparesis/Quadriparesis
• Epilepsy
• Spinal cord infarction
• Cortical blindness - Optic arachnoiditis
• Diabetes insipidus
• Intellectual deficits
44

45. Prognosis
Poor prognostic factors
1. Infants <6 months
2. Delayed/Late presentation
3. >106
CFU/ml of CSF
4. Seizure that persist after 4 days of illness and
difficult to treat/control
5. Coma or focal Neurologic signs at
presentation.
6. Delayed sterilization of CSF
45

46. Prevention
Chemoprophylaxis /vaccination
Neisseria meningitides
Chemoprophylaxis
• All close contacts regardless of age & immunization
• Meningococcal quadrivalent vaccine
( Serogroups A,C,Y,W-135)
46

47. Prevention…
H. Influenza
– Rifampin 20mg/kg/daily for 4 day for all close
contacts
if any close family member younger than
48 mo has not been fully immunized or if an
immunocompromised person, of any age,
resides in the household
– HIB vaccine - Prevents development of HIB
Infection – If given for all < 2yrs
Pneumococcal
• Conjugate vaccine against S.pneumoniae ( PCV10) for
all younger than 2 yrs.
47

48. References
• Nelson Text book of pediatrics, 20th
ed
• UpTodate 21.4
48

49. 49