approch to Meningitis beyond neonatal age.ppt

Approach to pediatric meningitis

1. Meningitis & encephalitis
Beyond the
Neonatal Period
 Gashaw Gebre (MD)
1

2. Objectives
-Discuss meningitis & encephalitis
beyond the neonatal period
(defn,etiologies,pathogenesis,C/M,Dx,
Mx,Cxs, & prevention)
2

3. Acute Bacterial Meningitis Beyond the
Neonatal Period
3

4. DEFINITION
-Acute &diffuse bacterial infection of the CNS with
primary involvement of the meninges .
4

5. ETIOLOGY
● Pathogen is influenced by :
-Age of the host
-Immune status of the host
-Epidemiology of the pathogen
a) Birth - 2 months
Group B Streptococci (Streptococcus agalactiae)
Gram –negative enteric bacilli(E.coli,klebsiella)
Listeria Monocytogenes
Group D streptococci (Enterococcus)
5

6. Con…
b) 2 month - 12 years
S. Pneumoniae
N. Meningitidis
H.. influenza type B ( 70% of cases of
meningitis in <5 yr of age )
c) Other less common pathogens
- P. aeruginosa , S. aureus , CNS , Salmonella spp. ,
L.monocytogenes
6

7. EPIDEMIOLOGY
Risk factors
Lack of immunity to specific pathogens
associated with young age
-95% of cases occur between 1 mth – 5 yrs of age .
Recent colonization with pathogenic bacteria
Close contact
Black race
7

8. Male sex
Crowded living conditions
Poverty
Splenic dysfunction
CSF leak ( congenital or acquired )
……Pneumococcal meningitis
T-lymphocyte defects ( congenital or
acquired )
- Listeria Monocytogenes
8

9. Lumbosacral dermal sinus and
meningomyelocele
- Staphylococcal and gram negative enteric bacterial
meningitis
CSF shunt infections
- Staphylococci (especially CONS)
- Low virulence bacteria that colonize the skin
Mode of transmission
Person to person contact through respiratory tract
secretions or droplets
9

10. H. influenzae
Invasive infections occur primarily in the 1
st
2mth -2 yrs of life
Peak incidence 6 - 9 mth of age
Risk factors :
-Family or day care center contacts of patients with H . inf
type b disease
-Unvaccinated individuals
-Individuals with blunted immunologic response to vaccine
e.g. child with HIV infection
10

11. Con…
S. Pneumoniae
Invasive infection peaks during the first 2 yrs of life
Risk factors :
-Age < 2 yrs
-Asplenia (functional or anatomic )
-HIV infection
-Otitis media ,sinusitis,pneumonia
-CSF otorrhea or rhinorrhea
- Presence of cochlear implant
11

12. N. meningitidis
-Serogroups A ,B ,C,,W135,Y
Epidemic disease serogroup A
-Cases are common in winter & spring
-Nasopharyngeal carriage …1-15 % of adults
-Attack rate in family…..1 %
-Most infections of children are acquired from :
Contact in a day care facility
Colonized adult family member
Ill patient with meningococcal disease
12

13. PATHOLOGY AND PATHOPHYSIOLOGY
-Meningeal exudates ( with variable thickness )
-Ventriculitis
-Subdural effusions
-Occurs in later phase ; because of transudation of fluid .
-Subdural empyema
-Perivascular inflammatory infiltrates
-Ependymal membrane disruption
-Vascular and parenchymal cerebral changes
13

14. -Cerebral infarction
-Inflammation of the spinal nerves and roots
Produces meningeal signs
-Inflammation of the cranial nerves
Produces cranialneuropathies(2,3,7,8)
14

15. Con…
SIADH
Excessive water retention ……Increased
risk of elevated ICP
Hypotonicity of brain extra cellular
spaces……..cell swelling and lysis……
Cytotoxic edema
15

16. Increased ICP
Uncal herniation…..temporal lobe compression
of oculomotor nerve… 3 nerve palsy
Types of cerebral edema :
a) Cell death ( cytotoxic cerebral edema )
b) Cytokine-induced increased capillary permeability
( vasogenic cerebral edema )
c) Increased hydrostatic pressure ( Interstitial
cerebral edema)
16

17. -Tentorial , falx ,or cerebellar herniation
Does not usually occur because the increased ICP is transmitted to the
entire subarachnoid space and there is little structural displacement.
-Hydrocephalus
Communicating
- Most common form
- Due to adhesive thickening of the arachnoid villi around the cisterns at the base of
the brain. Thus, there is interference with the normal resor ption of CSF.
Obstructive
- Less common form
- Due to fibrosis and gliosis of the aqueduct of sylvius or the foramina of magendie
and luschka
17

18. -Raised CSF proteins
Increased vascular permeability of the blood brain barrier
……..loss of albumin rich fluid from the capillaries and veins
traversing the subdural space .
-Hypoglycorrhachia (reduced CSF glucose level)
Due to decreased glucose transport by the cerebral tissue
18

19. Damage to the cerebral cortex may be due to the focal or diffuse effects of :
vascular occlusion (infarction, necrosis, lactic acidosis),
hypoxia,
 bacterial invasion (cerebritis),
toxic encephalopathy (bacterial toxins),
 elevated ICP,
 ventriculitis, and
transudation (subdural effusions).
•These pathologic factors result in the clinical manifestations of:
 impaired consciousness, seizures, cranial nerve deficits, motor and sensory
deficits, and
 later psychomotor retardation.
19

20. PATHOGENESIS
a) Bacterial meningitis most commonly results from hematogenous
dissemination of microorganisms from a distant site of
infection .
Bacteremia usually precedes meningitis or occurs concomitantly
b)Meningitis rarely follows bacterial invasion from a
contiguous focus of infection
Para nasal sinusitis , otitis media , mastoiditis,orbital cellulitis , cranial or
vertebral osteomyelitis
c )Meningitis may occur after direct introduction of bacteria in
to subarachnoid space
Penetrating cranial trauma ,dermal sinus tracts , meningomyeloceles
20

21. Development of meningitis is influenced by interaction of :
Host factors : Age, Sex (more in males) , Underlying disorder e.g..
Immunodeficiency
The organism
-The organism must have an essential bacterial virulent factor
disclosed by having polyribophosphate (capsular )antigen.
-The environment
- Children living in crowded areas are at high risk
21

22. CLINICAL MANIFESTATIONS
Two patterns of onset :
a ) Dramatic onset (less common )
Shock , purpura ,DIC ,reduced level of consciousness,
death with in 24 hour.
b )Gradual onset (more common )
Meningitis is preceded by several days of fever
accompanied by URT or GI symptoms
-followed by nonspecific signs of CNS
infection like increased lethargy &
irritability .
22

23. Non-specific findings
- Fever ,anorexia ,poor feeding ,symptoms of URTI, myalgias ,
arthralgias , tachycardia, hypotension, petechiae , purpura ,
erythematous macular rash
Signs of meningeal irritation
- Back pain ,neck stiffness , kernig sign, brudzinski sign.
Papilledema , photophobia
Focal neurologic signs
10 - 20% of cases
Cranial neuropathies
23

24. Signs of increased ICP
- Headache ,emesis ,bulging fontanel , diastasis
(widening ) of the sutures
- Oculomotor or abducens nerve palsy
- HTN with bradycardia ; stupor ,coma
- Apnea or hyper ventilation ,signs of herniation
- Decorticate or decerebrate posturing
24

25. Seizures
- Focal or generalized
- 20 -30 % of cases
- Causes : cerebritis ,infarction ,or electrolyte disturbance
Alteration of mental status
- Common
- Causes : increased ICP , cerebritis ,hypotension
- Manifestations : irritability,lethargy,stupor,coma.
25

26. DIAGNOSIS
1) Lumbar puncture
Between L3 & L4 or L4 & L5
Confirms DX of meningitis
CSF
Pressure …..usually elevated to 100-300 mmH2O
( Nl =50-80 mmH2O )
Gross appearance……turbid (WBC >200-400
/mm3)
26

27. LP….
WBC count (Nl =less than 5 , lymphocyte > 75% or monocytes )
oUsually elevated to >1000/mm3 (100 – 10,000/mm3 or more )
oNeutrophil predominance ( 75- 95% )
oIn 20 % of cases WBC < 250/mm3
oAbsent pleocytosis …….sever overwhelming sepsis
with meningitis
oPleocytosis with lymphocyte predominance…….during
early stages
Elevated protein …usually 100-500 mg/dl (Nl = 20 - 45
mg/dl )
Reduced glucose….usually <40 mg/dl (or <50% of serum
glucose ) ( Nl =>50mg/dl or 75 %of serum glucose )
Gram stain : positive in 70-90 % of cases
Culture
27

28. Contraindications for LP
- Increased ICP
- Sever cardiopulmonary compromise
- Infection of the skin overlying the site of the LP
- Thrombocytopenia( < 20,000/mm3 ) : Relative c/I
Traumatic LP
- Affects CSF WBC & protein concentration
- Does not affect G/S , culture & Glucose level
- Repeat LP after sometime
28

29. 2) Latex particle agglutination
- Highly sensitive but less specific
3) Blood culture : Positive in 80 -90 % of cases
4) Countercurrent immuno electrophoresis (CIE)
-Rapid & very specific
29

30. DIFFERENTIAL DIAGNOSIS
A) INFECTIONS
1) Generalized infection of the CNS
Bacteria
oM . Tuberculosis (Tb meningitis)
oT . Pallidum (Syphilis )
Fungi
oHistoplasma ,Candida ,Cryptococcus , Aspergillus
Parasites
oT .godii , Cysticercosis
Viruses
oEnteroviruses , HSV( Viral meningoencephalitis )
30

31. 2) Focal infections of the CNS
Brain abscess
Para meningeal abscess
oSubdural empyema
oCranial epidural empyema
oSpinal epidural empyema
31

32. B) NON-INFECTIOUS ILLNESSES
-Cause generalized inflammation of the CNS
-Uncommon
oMalignancy
oCollagen vascular syndromes
oExposure to toxins
All acute febrile illnesses can be D.DX of acute
bacterial meningitis especially in its early phase.
32

33. TREATMENT
A) Antibiotics
Always use high dose ,parenteral (IV) antibiotics.
 Initial (empirical )choice of therapy
Vancomycin 60 mg/kg/24 hr, given every 6 hr
OR
Ceftriaxone 100 mg /Kg /24 hr once per day or
50 mg/Kg /dose every 12 hrs for 7 – 10 days
OR
Cefotaxime 200 mg /Kg /24 hr every 6 hr for 7- 10 days
33

34. Patient allergic to b-lactam antibiotics
-CAF 100 mg /Kg /24hr given every 6 hr
OR
- Patient can be desensitized to the
antibiotic
 If patient is immuno compromised
-Ceftazidime and aminoglycoside need to be included because of
risk of gram –ve bacterial meningitis e.g. P.aeruginosa ,E .coli
Duration of antibiotic therapy
34

35. a) Generally total of 10 days
b) Specific ( based on etiologic agent ) in uncomplicated cases
oN .meningitidis…….5 -7 days
oH .influenzae type b……….7 10 days
oS .Pneumoniae………..10-14 days
oCSF culture –ve………7- 10 days
oGram –ve bacilli……03 weeks or 2 weeks after CSF
sterilization
( usually after 2 – 10 days of treatment )
oNeonates ……..03 weeks
** N.B. In complicated cases of meningitis ,give antibiotics
for 10-14 days
35

36. PRACTICE IN ETHIOPIA
- Crystalline Na penicillin G 250,000 IU /Kg IV
stat…..loading dose
Then, 500,000 IU /Kg/24hr in 8 divided doses for 10
days .
oPLUS
CAF 50 mg/Kg IV stat …….loading dose
Then, 100 mg /Kg /24 hr in 4 divided doses for 10 days
OR
- Ceftriaxone 50 mg /Kg /dose every 12 hrs for 7- 10 days
36

37. B) Corticosteroids
Dexamethasone 0.15 mg/Kg/dose every 6 hrs for 2 days
Maximum benefit if given 1-2 hours before antibiotics are
initiated
Limit inflammatory mediators that worsen neurologic injury and CNS
symptoms & signs
C) Supportive care
Repeated medical and neurologic assessment esp. during the 1
st
72 hrs
(Use neuro-sign chart)
37

38. IV fluid
- Restrict to 1/ 2 - 2/3 of the maintenance
(800 -1000ml/m2 /24hr )
till we rule-out increased ICP or SIADH
- When serum Na is normal…… change IV fluid to normal (1500-
1700ml/m2/24hr)
- Systemic hypotension or shock……Rx aggressively with IV fluids
- Septic shock…..add also vasoactive agents
38

39. Lab Ix
- BUN ,serum Na, Cl ,K ,HCO3
- Urine ….output &Specific gravity ,CBC
- PT ,PTT, fibrinogen level for bleeding diathesis
Increased ICP
- Elevate head to 30 degree
- Endotracheal intubation & hyperventilation
(To maintain pCO2 at around 25 mmHg)
- Furosemide 1mg/Kg IV…..diuresis & venodilation
- Mannitol 20% 0.5 -1 gm/Kg/dose IV to run in 30 min , repeat 6
hourly if needed
39

40. Seizure control
- IV diazepam 0.1 -0.2 mg/Kg /dose OR
IV lorazepam 0.05 – 0.1 mg/Kg /dose
- Monitor serum glucose ,Na ,Ca
- Phenytoin 15 -20 mg/Kg loading dose .
- Then 5 mg /Kg /24 hr maintenance dose
OR
- Phenobarbitone 20 mg /Kg IV loading dose
- Then 5 mg/Kg /24 hr maintenance dose
** Phenytoin causes less CNS depression & permits
assessment of level of consciousness
40

41. COMPLICATIONS
Seizures
Increased ICP
Cranial nerve palsies
Stroke
Cerebral or cerebellar herniation
Thrombosis of the dural venous sinuses
Subdural effusions
-In 10 -30 % of patients
-Asymptomatic in 85-90 % of cases
- CT or MRI confirms the DX
-Increased or depressed level of consciousness i.e.
symptomatic
-Subdural tap
Hydrocephalus
41

42. SIADH
- Occurs in majority of patients
- In 30 - 50 %of patients
- Hyponatremia
- Decreased serum osmolality
-Its effects are :
- Exacerbation of cerebral edema
- Independently produces hyponatremic seizures
Pericarditis or arthritis occurs during RX of meningitis
-Infectious (bacterial dissemination )
-Immune mediated (immune complex deposition )
42

43. COMPLICATIONS ( CONT ‘D )
Thrombocytosis
Anemia
-Hemolysis
-Bone marrow suppression
Eosinophilia
Shock ,DIC
Symmetric peripheral gangrene
-sever hypotension +Endotoxemia +On going thrombosis
Sensorineural hearing loss
Visual impairment
Behavioral problems
Mental retardation
Delay in acquisition of language
43

44. PROGNOSIS
Mortality …< 10 % with antibiotic therapy and supportive care
Sever neurodevelopmental sequalae …10 -20 % of cases
Neurobehavioral morbidity ….50 % of cases
POOR PROGNOSTIC FACTORS
Pneumococcal meningitis
Age < 6 months
>10
6
colony – forming units of bacteria / ml of CSF
Seizure occurring after 4days of therapy
Coma or focal neurological signs on presentation
Most common neurologic sequalae
Hearing loss
Mental retardation , delay in acquisition of language
Seizures
Visual impairment , behavioral problems
44

45. PREVENTION
A ) Chemoprophylaxis
-Antibiotic prophylaxis of susceptible at-risk contacts
B ) Vaccination
N. MENINGITIDIS
a)Chemoprophylaxis
a)-All close contacts of patients with meningococcal meningitis regardless
of age or immunization status
-Rifampin 10 mg /kg /dose every 12 hr (max.600 mg) for 2 days
-Close contacts
oHouse hold ,day care center ,nursery school contacts, health care workers
-
45

46. Health education :
oEarly signs of disease
oThe need to seek prompt medical attention if these signs develop
b) Vaccination
-Meningococcal quadrivalent vaccine against serogroups A,C, Y,W 135
A) 11-12 year old adolescents
B) High risk children older than 2 years
f - Anatomic or functional asplenia
- Deficiencies of terminal complement proteins
C) Adjunct with chemoprophylaxis for exposed contacts and during
epidemics of meningococcal disease
46

47. H . INFLUENZAE
a)Chemoprophylaxis
a)-House hold contacts ,including adults
oIf any close family member < 48 months has not been fully
immunized
oIf an immuno compromised child resides in the house hold
-Rifampin 20 mg /kg /24 hr (max .600 mg ) given once daily for
4 days
Definition of house hold contact
- person who spent a minimum of 4 hr with the index case for at
least 5- 7 days preceding the patients hospitalization
47

48. b) Vaccination
-Conjugate vaccines

oEfficacy rates 70 - 100 % against invasive infections
oAll children should be immunized with H .influenza type b
conjugate vaccine beginning at 2 mo of age
S .PNEUMONIAE
a) Chemoprophylaxis
-Not indicated
48

49. b) Vaccination
-Heptavalent conjugate vaccine
-The initial dose is given at 2 month of age ( 2 ,
4 , 6 & 12 - 15 mth of age )
-Indications :
a)Routinely for all children < 2yr of age
b) High risk of invasive pneumococcal
infection :
- Functional / anatomic asplenia
- Underlying immunodeficiency
.HIV
.Primary immunodeficiency
. Immunosuppressive therapy
49

50. Tuberculous Meningitis
50

51. Etiology & Epidemiology
Etiology
Mycobacterium Tuberculosis
Non-spore forming ,non-motile , pleomorphic ,weakly gram-
positive , acid-fast bacilli
Epidemiology
Occurs in 0.3% of untreated TB infections
Peak age: 6 mo - 4 yr of age
BCG vaccination prevents it
51

52. Pathology and Pathophysiology
Lymphohematogenous dissemination of the primary (lung in > 90% of
cases) infection leads to formation of metastatic caseous lesion in the
cerebra cortex or meninges
Exudates formation
Salt wasting or SIADH result in abnormal electrolyte metabolism
Vasculitis ,Infarction , cerebral edema and hydrocephalus
Brain stem: site of greatest involvement
52

53. Clinical Manifestations
Clinical course :
1) Rapid progression
Infants & young children, occurs in several days
2) Slow progression
- Occurs in several weeks
- Has 3 stages
53

54. 1
st
Stage
-Lasts 1-2weeks
-Non specific symptoms
-2
nd
Stage
- abrupt in onset
- Lethargy ,+ve meningeal signs, seizures , hypertonia, vomiting , cranial nerve
palsy, other focal neurologic signs , signs of encephalitis with no meningeal signs
3
rd
Stage
- Coma , hemiplegia or paraplegia , hypertension
- Decerebrate posturing , deterioration of vital signs, and finally death.
54

55. Diagnosis
PPD: -ve in 50% of cases
CXR: NL in 20-50%of cases
CSF (Specimen volume:5-10 ml )
- WBC :10-500/mm3(Lym.predominant)
-Glucose : <40mg/dl (rarely <20mg/dl)
- Protein: 100-3000mg/dl
-Smear for AFB:+ve up to 30% of cases
- Culture:+ve in 50-70% of cases
- PCR : may be positive55

56. CT or MRI of the brain
- Normal in early stages of TB meningitis
- Basilar enhancement , communicating
hydrocephalus, signs of cerebral edema ,
early focal ischemia
- one or more clinically silent tuberculomas
may be seen in the cerebral cortex or
thalamic areas
N.B. Dx of TB meningitis can be difficult early in its course and requires high
degree of suspicion.
m
56

57. Treatment
Directly Observed Therapy (DOTs Regimen)
- 2RHZ E or S / 7-10 RH (Total: 9-12 mo )
Steroids
- prednisone, 1-2 mg/kg/day in 1-2 divided doses orally for 4-6
weeks , followed by gradual tapering
Rx of complications
- Increased ICP , Seizures, Hydrocephalus (CSF shunts)
57

58. Complications
- Blindness, deafness , paraplegia or hemiplegia , mental retardation , diabetes
insipidus , hydrocephalus , cranial nerve palsy , seizures
Prognosis
Correlates with clinical stage at time of initiation of Rx:
- 1
st
stage has excellent outcome
- 3
rd
stage survivors have permanent disabilities
Better for older child than for young infant
Prevention
Prevention of primary Tb infection :
- Vaccination (BCG) , early Dx & Rx of TB cases
58

59. Viral Meningoencephalitis
59

60. Definition
IT is an acute inflammatory process involving the meninges
and ,to a variable degree , brain tissue
Etiology
Enteroviruses
- Most common cause , small RNA viruses
- More than 80 serotypes
Herpes viruses
- HSV-1,HSV-2,VZV,CMV,EBV,HHV-6
Mumps
60

61. Arboviruses
-Mosquitoes and ticks are most common
vectors
-Birds or small animals ……Humans
e.g. West Nile virus
61

62. Other viruses/occasional causes/
- Rubella , rubeola , rabies
- Respiratory viruses : Adenovirus,
Influenza virus , parainfluenza virus
 Live virus vaccinations/rare causes/
- Polio , measles ,mumps , rubella
62

63. Epidemiology
- Enteroviruses :

- Direct spread from person to person, IP is 4-6 days
- Other factors : Season , geography , climate conditions ,
animal exposures , etc.
63

64. Pathogenesis and pathology
-Neuronal disruption , tissue necrosis , meningeal
congestion
-Neuronal damage from :
1) Direct invasion and destruction of neural
tissues by virus
2) Host reaction to viral agents
64

65. Clinical Manifestations
Determinant factors are :
1) Relative degree of meningeal &
parenchymal involvement 2) Specific etiology
Mild self-limited illness to severe encephalitis
with sequelae or resulting in death
65

66. Fever,headache,nausea,vomiting,photophobia,pain in
the neck , back and legs.
Nuchal rigidity, irritability , change in mental status ,
convulsions , bizarre movements , hallucinations
Exanthems precede or accompany CNS signs
66

67. Diagnosis
Mainly clinical :
- Nonspecific prodrome followed by
progressive CNS symptoms
CSF
- WBC : 10-100,mm3(up to 1000/mm3)
Mononuclear cells predominate later
- Protein : 50-200 mg/dl
- Glucose : normal (mumps <40mg/dl)
- PCR : for HSV & enteroviruses
- Culture : for enteroviruses(70% detection)
67

68. Serologic tests:
- For arboviruses
- Not practical for enteroviruses
EEG : diffuse slow-wave activity usually without focal changes
CT/MRI : swelling of the brain parenchyma
N.B. focal seizures or focal findings on EEG , CT, or
MRI ,especially involving the temporal lobes ,suggest HSV
encephalitis
68

69. Treatment
1) Supportive
- Rest
- Non-aspirin containing analgesics
( Acetaminophene is best )
- Reduction in room light ,noise
- IV fluids : if poor oral intake
- In severe cases : ICU care
2) Acyclovir for HSV encephalitis
3) Rx of complications :
- Increased ICP, SIADH ,seizures, etc.
69

70. Complications
Increased ICP(cerebral edema)
Coma
Convulsions
Fluid & electrolyte imbalance
Aspiration , Asphyxia
SIADH
Cardiac or respiratory arrest of central origin
70

71. Prognosis
Most children recover completely
Depends on :
1) Severity of clinical illness
2) Specific etiologic agent
3) Age of the child (Poor for infants)
Potential deficits in severe cases :
- Intellectual , motor, epileptic , psychiatric,
- Auditory , visual
71

72. Prevention
Vaccination
- Polio
- Measles
- Mumps
- Rubella
- Rabies
Control of insect vectors & minimizing mosquito bites
72