Meningitis, pediatrics meningitis ,,,,,,

09/03/2024 MENINGITIS 1
Meningitis
BY: BERHANE G/HER (MD,PED.Y3R)
LECTURE SLIDES FOR C1 MEDICAL STUDENTS OF ADIGRAT UNIVERSITY
2015

Objectives of the lecture
At the end of this lecture,you are expected to:
1. Elaborate the different causes of meningitis
2. Describe clinical manifestations of bacterial meningitis beyond neonatal age
3. Interprete findings of CSF analysis
4. Outline management of bacterial meningitis
5. Describe complications of meningitis
6. Outline the prognosis and prevention

Outline of presentation
1. Basic anatomy
2. Introduction
3. Bacterial meningitis
4. Predisposing factors
5. Mode of transmission
6. Pathogenesis
7. Pathology
8.Clinical manifestations
9.Diagnosis
10.Differential diagnosis
11. Treatment
14.Complications
15.Prognosis
16.Prevention
17. References

1.Basic anatomy
Meninges
are connective tissue layers covering the brain
and spinal cord which also form the blood-
brain barrier.
 Dura
 Arachnoid
 Pia maters

2. introduction
Definition
Meningitis - Infection of Arachnoid Mater and CSF
◦ Subarachnoid Space
◦ Cerebral ventricles
Encephalitis - indicates brain parenchymal involvement.
Meningoencephalitis
These are examples of diffuse infection of the CNS.

Cont…
Epidemiology
1.2 million cases worldwide.
135,000 deaths per year worldwide.
One of the top 10 most common infections.
Can affect all age groups but some are at higher risk. (young age)
Male = Female

Cont…
Etiology
varies with different age groups and other predisposing factors.
o Bacterial Infections
o Viral Infections
o Fungal Infections(Cryptococcus neoformans)
o Inflammatory diseases (SLE)
o Chemicals (pb, Hg)
o Protozoans
o Rickettsial
o Malignancies
In general, viral causes > bacterial > fungal & parasitic.

3. Bacterial meningitis
Etiology
Causative organisms vary with patient age, while three bacteria accounting for
over three-quarters of all cases:
◦ Neisseria meningitidis (meningococcus)
◦ Haemophilus influenzae (if very young and unvaccinated)
◦ Streptococcus pneumoniae ( pneumococcus)

Cont…
◦ Immunocompromised
◦ Listeria monocytogenes
◦ Gram negative bacteria
◦ Hospital-acquired infections
◦ Klebsiella
◦ Escherichia coli
◦ Pseudomonas
◦ Staphylococcus aureus

Cont…
The most common organisms
◦ Neonates and infants under the age of 2months
◦ Escherichia coli
◦ Pseudomonas
◦ Group B Streptococcus
◦ Staphylococcus aureus

Cont…
Children over 2 months
◦ Haemophilus influenzae type b
◦ Neisseria meningitidis
◦ Streptococcus pneumoniae
Children over 12 years
◦ Neisseria meningitidis
◦ Streptococcus pneumoniae

4.Predisposing Factors
Inadequate immunity esp. young age – A major risk factor
Recent colonization of Nasopharynx
Close contact, crowding, poverty
Complement deficiency ( C5-C8 – recurrent meningococcal infection)
Splenic dysfunction(Asplenia, Sickle cell anemia)
- pneumococcal, H. influenza B, rarely Meningococcal
T- lymphocyte defect (congenital, acquired)
CSF leak (congenital, acquired)
- Meningomyocele (S. aures, Gram –ves)
- Basal skull fracture ( pneumococcal)

Cont…
Lack of immunizations
Contagious focus – rarely become a source
 Otitis media
 Mastoditis
 Orbital cellulitis
 Cranial / vertebral osteomyelitis
 etc

Cont…
STREPTOCOCCUS PNEUMONIAE
Children with anatomic or functional asplenia
Infection with HIV - 20- to 100-fold higher risk
Otitis media
Sinusitis
Pneumonia
CSF otorrhea or rhinorrhea,
The presence of a cochlear implant, and chronic graft versus host disease following bone
marrow transplantation.

Cont…
NEISSERIA MENINGITIDIS
Five serogroups of meningococcus:
A, B, C, Y, and W-135
May be sporadic or may occur in epidemics.
Epidemic disease, especially in developing countries, is usually caused by serogroup A.
Most infections - contact in a daycare facility, a colonized adult family member, or an ill
patient with meningococcal disease.
Children younger than 5 yr have the highest rates of meningococcal infection.
A 2nd peak in incidence occurs in persons between 15 and 24 yr of age.

Pathogenesis of Meningococcal Infections
(Better prognosis)

Cont…
HAEMOPHILUS INFLUENZAE TYPE B
Invasive infections occurs primarily in infants 2 mo–2 yr of age
peak incidence is at 6–9 mo of age, and
50% of cases occurs in the 1st yr of life.
Incompletely vaccinated children, and
Blunted immunologic responses to vaccine (children with HIV
infection)

5.Mode of transmission
Person to person contact via respiratory secretions or droplets
Maternal flora – during the first months of life

6.PATHOGENESIS
Most commonly results from hematogenous dissemination of
microorganisms from a distant site of infection.
Bacteremia usually precedes meningitis or occurs concomitantly.
Bacterial colonization of the nasopharynx with a potentially
pathogenic microorganism is the usual source of the bacteremia.
Uncommonly - meningitis occurs by direct extension from nearby
focus

Cont…
Attachment of pathogenes to mucosal epithelial cell through their pilli
Penetrate the mucosa and enter into the circulation
Bacterial survival in blood stream enhanced by capsules (interfer opsonic phagocytosis)
Opsonic phagocytosis may be impaired
o In young infant – lack of preformed IgM or Ig G
o In immunodeficient and with complement defect

Cont…
Bacteria enter CSF through choroid plexus of the lateral ventricle and meninges
Complement and antibody concentration in the CSF is inadequate:
 Rapid multiplication

bacterial colonization of nasopharynx
attach to mucosal epith. cell receptors by pili
breach mucosa& enter circulation
to CSF through choroid plexus of ventricles
extracerebral CSF & subarachinoid space
bacterial proliferation
inflammation-cytokines
large capsules interfere phagocytosis

Cont…
Bacterial toxins and Inflammatory mediators are released.
◦ Bacterial toxins
◦ Lipopolysaccharide, LPS
◦ Teichoic acid
◦ Peptidoglycan
◦ Inflammatory mediators
◦ Tumor necrosis factor, TNF
◦ Interleukin-1, IL-1
◦ Prostaglandin E2, PGE2

Cont…
Bacterial toxins and inflammatory mediators cause suppurative inflammation.
◦ Inflammatory infiltration
◦ Increased Vascular permeability
◦ Tissue edema
◦ Blood-brain barrier alteration
◦ Thrombosis

7.PATHOLOGY
Meningeal exudates in different part of the brain
Ventriculitis (purulent material within the ventricles)
Infiltrates extending to the subintimal region of the small arteries
and veins
= Vasculitis
= Thrombosis of small cortical veins

Cont…
Cerebral infarction - microscopic / entire hemisphere
Inflammation of spinal nerves and roots
Inflammation of the cranial nerves
Increased ICP
cytotoxic cerebral edema
vasogenic cerebral edema
interstitial cerebral edema
The SIADH secretion may produce excessive water retention and
potentially increase the risk of elevated ICP

Cont…
Hydrocephalus is a common complication of meningitis.
◦ Communicating hydrocephalus , most often
◦ Obstructive hydrocephalus
Raised CSF protein level
– due to increased vascular permeability of the blood-brain barrier and the loss of albumin-rich fluid
from the capillaries and veins
- subdural effusion
Hypoglycorrhachia (reduced CSF glucose levels) - is due to decreased glucose transport by the cerebral
tissue.

Cont…
Inflammatory process may result in cerebral edema and damage of
the cerebral cortex.
◦ Conscious disturbance
◦ Convulsion
◦ Motor disturbance
◦ Sensory disturbance and
◦ later psychomotor retardation

8.Clinical manifestation
More often, meningitis is preceded by several days of systemic
infection manifestations
less common, sudden onset with rapidly progressive manifestations
of shock, purpura, DIC, and progressing to coma or death within 24
hr.
Meningococcemia with
meningitis

Cont…
The signs and symptoms of meningitis are related to:
 Nonspecific findings of systemic infection and
 Manifestations of meningeal irritation.

Nonspecific findings

Cont…
Meningeal irritation sign
◦ is found because the spinal nerve root is irritated.
◦ Neck stiffness
◦ Positive Kernig’s sign
◦ Positive Brudzinski’s sign
◦ in those younger than 12–18 mo, Kernig and Brudzinski signs are not consistently
present.

Cont…
Kernig’s sign
Vladimir Kernig was a Russian physician
Kernig sign is present if the patient, in the
supine position with the hip and knee flexed at
90º, cannot extend the knee more than 135º
and/or there is flexion of the opposite knee.

Cont…
Brudzinski’s signs
Jozef Brudzinski was a Polish physician
Symphyseal sign
Cheek phenomenon
Contralateral reflex
Neck sign- With the patient lying on the back:
if the neck is forcibly bended forward, there
occurs a reflexive flexion of the knees.

Cont…
Increased intracranial pressure
Headache, Projectile vomiting
Hypertension ,Bradycardia
Bulging fontanel
Cranial sutures diastasis
Coma ,Decerebrate rigidity
Cerebral hernia
Cranial nerve palsy Oculomotor nerve
Abducen nerve - usually the first nerve to be compressed
focal neurologic signs occur in 10-20%- ↑to 30% in pneumococcal
meningitis

Cont…
Seizures
Seizures occur in about 20%-30% of children with bacterial
meningitis.
Seizures is often found in haemophilus influenzae and pneumococcal
infection.
Seizures is correlative with the inflammation of brain parenchyma,
cerebral infarction and electrolyte disturbances.

Cont…
-In some children, particularly young infants under the age of 3 months, symptom and signs
of meningeal inflammation may be minimal.
◦ Fever is generally present, but its absence or hypothermia in a infant with meningeal
inflammation is common.
◦ Only irritability, restlessness, dullness, vomiting, poor feeding, cyanosis, dyspnea,
jaundice, seizures, shock and coma may be noted.
◦ Bulging fontanel may be found, but there is not meningeal irritation sign.

9.DIAGNOSIS
Confirmed by CSF analysis – lumbar puncture
Contraindications for an immediate LP include:
(1) Evidence of increased ICP (other than a bulging fontanel)
(2) Severe cardiopulmonary compromise requiring prompt resuscitative
measures for shock or in patients in whom positioning for the LP
would further compromise cardiopulmonary function; and
(3) Infection of the skin overlying the site of the LP.
(4) Thrombocytopenia is a relative contraindication for LP.

Cont…
Neonate Infants and older children
PRESSURE (mm H2O) 50–80
50–80
LEUKOCYTES (mm3
) < 30 <5
WBC differential <60% neutrophils ≥75% lymphocytes
0% neutrophil
PROTEIN (mg/dL) <90 20–45
GLUCOSE (mg/dL) 70-80 >50 (or 75% serum glucose)
Normal values of CSF

Cont…
CSF – Findings in meningitis
Usually in bacterial meningitis the WBC is >1000/mm3 (75-95% neutrophils)
Cell count in CSF might be less than 100
 Neutropenia
 Gram negatives
 Early disease
The CSF become turbid when the leukocyte count exceeds 200- 400/mm3.

Cont…
CSF – Findings in meningitis
Pleocytosis may be absent in severe overwhelming sepsis and meningitis
Gram stain is positive in 70-80% of cases
Blood culture is positive in 80 – 90% of cases
In failed/traumatic LP – repeat after 6 – 8 hrs at a higher interspace .
In traumatic CSF: Gram stain, culture, and glucose level may not be influenced.
Latex agglutination – partially treated meningitis

Further CSF Finding Comparison
Pathogen WBC’s % Neut Glucose Protein + Gram
present
Pyogenic >500 >80 Low >100 ~70
Listeria
Monoctyogenes
>100 ~50 Normal >50 ~30
Partial Treated
Pyogenic
>100 ~50 Normal >70 ~60
Aseptic, Often
Viral
10 –
1, 000
Early: >50
Late: <20
Normal <200 N/A
TB 50-500 <30 Low >100 Rare
Fungal 50-500 <30 Low Varies High in
Crypto
Banmberger, David, Diagnosis, Initial Management, and Prevention of Meningitis Am Fam Physician. 2010 Dec 15;82(12): 1491-1498.

Cont…
↑ opening pressure
- elevated protein- 100-500mg/dl,
-reduced glucose
Other lab findings
↑ total WBC count
Anemia, low platelet count - DIC

10.Differential Diagnosis
Aseptic meningitis
 refers to patients who have clinical signs and laboratory evidence for meningeal inflammation with
negative routine bacterial cultures
Infectious or non infectious
Enteroviruses
Herpes Simplex virus (HSV)
HIV
Lymphocytic Choriomeningitis virus (LCM)
Mumps
Other

Cont…
Viral meningoencephalitis
- less ill
-classic CSF profile:
- normal/mild inc. opening pressure
- mononuclear cells, <1000/mm3
- protein usu. 50-200mg/dl
- glucose- normal.
Partially treated bacterial meningitis
- cells 5-10000/mm3,
glucose normal/decreased, culture negative.

Cont…
Enteroviral Meningitis
Enteroviruses are thought to be the most common cause of viral meningitis
Are a diverse group of RNA viruses including Coxsackie A & B, Echoviruses, and
polioviruses.
Account for >50% of cases and approximately 90% of cases in which a specific
etiologic agent is identified.
Majority of cases are in children or adolescents, but patients of any age can be
affected.
Transmitted primarily by fecal-oral route, but can also be spread by contact with
infected respiratory secretions.

Cont…
Tuberculous meningitis
Usually occurs early, 2 – 6 months after the infection
Suspected in :
Fever persisting for 14 days and above
Fever persisting for more than 7 days and there is a family member with tuberculosis
A chest x ray suggests tuberculosis
The patient remains unconscious
Children with known or suspected HIV infection (cryptococcal meningitis also – Indian ink)
CSF continue to have <500 cells/ml,mostly lymphocytes, elevated proteins (0.8-4g/l) and low glucose
(<40mg/dl)

11.Treatment
Immediate treatment of associated multiple organ system failure ,
shock, and acute respiratory distress syndrome is also indicated.
Drugs administered IV throughout the course of treatment
Dose should be antimeningeal
Reinstall the antibiotic based on culture and drug sensitivity
Until the culture result arrives – emperical Rx
If there are signs of increased ICP or focal neurologic findings,
antibiotics should be given without performing an LP

Cont…
Initial Antibiotic Therapy
Crystalline penicillin= loading dose of 250,000 IU/kg IV stat followed by 500,000IU/Kg/24hrs IV
divided in 8 doses PLUS
Chloramphenicol = 50mg/Kg IV stat followed by 100mg/Kg/day IV Q 6 hourly
L.monocytogenes –
ampicillin (200 mg/kg/24 hr) given every 6 hr.
Immunocompromised and gram-negative meningitis
ceftazidime or an aminoglycoside

Cont…
Duration Of Antibiotic Therapy
Depends on the etiology but in general course of treatment ranges between 10 – 14 days
S.pneumoniae- penicillin (400,000 U/kg/24 hr) 10-14 days
N.meningitidis- penicillin (400,000 U/kg/24 hr) 5-7 days
HIB-chloramphenicol 7-10 days
Gram negatives - 3 wk or for at least 2 wk after CSF sterilization

Cont…
Supportive care
Control fever
Maintain a clear airway
Turn the child every 2 hours
Fluid management
Half to 2/3 rd of the maintainance
Management of increased ICP
Hyperventilation
Mannitol/lasix
Seizure should be treated with IV diazepam or phenytoin (if not controled)
Strict follow up – esp. during the first 72 hours

Cont…
Corticosteroids
Rapid killing of bacteria releases toxic cell products. →
cytokine mediated infl. Response, edema & neutrophilic
response.
- This will lead to additional neurologic injury with
worsening of CNS Sx:
- Dexamethasone- 0.15mg/kg/dose q6hr-2days (benefit
max if given 1-2 hr before antibiotics)
- Decreases permanent auditory nerve damage.
- H. influenzae +/- pneumococcus

12.Complications
Acute
-Seizure
-↑ ICP
-CN palsies,
-cerebral & cerebellar herniation;
-Subdural effusion- in 10-30%,
(asymptomatic in 85-90% of cases, esp in infants)
symptoms- bulging fontanel,enlarging HC, emesis, Sz, fever, cranial
transillumination
aspiration indicated in ↑ ICP/decreased LOC

Cont…
SIADH (Cerebral hyponatremia)
◦ Restriction of fluid
◦ supplement of serum sodium
◦ Diuretic
Pericarditis, arthritis- due to bacterial dissemination, or immune
complex deposition.
DIC

Cont…
Chronic complications
◦ Mental retardation
◦ Spasticity and/or paresis
◦ Seizures

13.Prognosis
-MR- <10%- highest in pneumococcal
-severe neurodevelopmental abn.-in 10-20%
-Poor prognosis in:
. < 6mo of age
. >1mill.CFU bact./ml
. Seizure for >4 days into Rx
. Coma/ focal neurologic sign at admission
. Absence of pleocytosis
. Pneumococcal meningitis

14.Prevention
Vaccination and chemoprophylaxis
N.meningitidis-
Rifampin 10mg/kg/dose q12 hr for 2 days –for all close contacts of patients with meningococcal
meningitis,
Quadrivalent vaccine - A,C,Y,W135 for high risk children >2yr
HIB-
 Rifampin 20mg/kg/day,once, 4 days for all household contacts
Conjugate vaccine (Pentavalent)- from 2mo of age

Cont…
S.pneumoniae
PCV 10 – from 2mo of age
No chemoprophylaxis

15.References
1. Nelson text book of pediatrics,19th
ed.
2. Nelson essentials of pediatrics, 5th
ed.
3. Current Pediatric diagnosis and treatment,18th
ed.
4. Rudolph’s pediatrics, 21st
ed

Meningitis, pediatrics meningitis ,,,,,,

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