Narong Narong AuervitchayapatAuervitchayapat,,MDMD.,., Assist Assist ProfProfDepartment of PediatricsDepartment of Pediatrics

Faculty of MedicineFaculty of MedicineKKUKKU

1. Bacterial meningitis

2. Tuberculous meningitis

3. Aseptic meningitis

4. Viral encephalitis

5. Brain abscess

5 common diseases:-

Definitions* Meningitis: Inflammation of meninges

Abnormal number of WBCs in CSF* Bacterial meningitis: Meningitis and evidence of a

bacterial pathogen in CSF* Aseptic meningitis: Meningitis in the absence of

bacterial pathogen in the CSF by usual laboratory techniques

Definitions

* Encephalitis: Inflammation of the brain

* Meningoencephalitis: Inflammation of the brain accompanied by meningitis

Bacterial Meningitis

Introduction

1. Common

2. High morbidity & mortality rates

3. Emergency condition

EpidemiologyThe causative organism depends on

* Age

* Place

* Underlying disease

Sirinavin S et al 420 cases of bacterial meningitis in 14 hospitalsAge 0 mo 1-6 mo 7-11 mo 1-5 yr 6-15 yr

PathogensGram negative bacilli 37 8 0 0 0

Strep group B (GBS) 13 8 0 0 0

Salmonella 3 35 6 0 0

H.influenzae 2 87 47 26 0

S.pneumoniae 2 43 19 28 16

N.meningitidis 0 9 2 2 5

Underlying diseasesUnderlying diseasesSplenectomy & asplenia: S.pneumoniae, H.influenzae type b

,gram negative enteric

Hemoglobinopathies: S.pneumoniae, H.influenzae type b

C5-8 deficiency: Meningococcal infection, Salmonella

Underlying diseasesUnderlying diseasesCSF leak eg. middle ear defect ; base of skull fracture:

pneumococcal meningitis

Dermal sinus, meningomyelocele: staphylococci,

gram- negative enteric

CSF shunt: staphylococci ( esp. coagulase -ve)

Pathology

Clinical manifestations* Fever

* Headache

* Meningeal signs

+

+

Acute onset

Signs of increased intracranial pressure

- Stiffneck

- Kernig’s sign

- Brudzinski’s sign

Clinical manifestations- Consciousness

- Seizures

- Nausea, vomiting

- Diarrhea

- Poor feeding

Diagnosis

Lumbar puncture

Beware herniation in:-

1. Papilledema

2. Tensed anterior fontanel

3. Localizing signs

Fever + headache + meningeal signs

CSF findings- Pressure: Normal, > 300 mmH2O- Appearance: Turbid, xanthochromia- WBCs: 100-50,000, PMN 70-100%- Protein: > 40 mg/dl, most > 150mg/dl

- Sugar: < 50% of blood sugar, < 40 mg/dl- Gram stain, culture/sensitivity

Bacterial Antigen:

1. Latex agglutination

2. CIE ( Counter-Immuno-Electrophoresis )

TreatmentSpecific treatment * Emergency antibiotics *

Empiric antibiotics

- Newborn: Ampicillin + gentamicinAmpicillin + cefotaxime

- Beyond the neonatal period:Ampicillin + chloramphenicolCefotaxime or ceftriaxone + vancomycin?

Dosage of antibiotics for bacterial meningitisIncreased from systemic dosage

Penicillin group: Increase 3-4 folds

Cephalosporins: Increase 2 folds

Chloramphenicol: As same as systemic dosage

Amonoglycosides: As same as systemic dosage

Duration of antibioticsH.Influenzae

S.pneumoniae

Group B streptococci

Gram negative enteric bacilli

N.meningitidis

Salmonella

10-14 days10-14 days14-21 days

21 days7-10 days42 days

*Adjunctive Dexamethasone Therapy*

The use of corticosteroidsThe use of corticosteroids

• Antibiotics and pediatric intensive care:

MR = 5% but 20-30%: long-term sequalae esp. hearing

impairment

• Dexamethasone substantially reduced levels of

cytokines IL-1, TNF & PGE2 within CSF of infected

animal: reduction of ICP, brain edema & CSF lactate:

decreased MR and sequalae in animals.

Bacterial meningitis

Rapid lysis of bacteria:-Release of endotoxin (H.influenzae)Lipoteichoic acid (S.pneumoniae)

Release of cytokines:*Interleukin 1β*Tumor necrotic factor-α*Platelet activating factorProstaglandin E-2Phospholipase A2

Neutrophil recruitment

Neutrophil induced inflammation

Cerebral edemaVasculitis

Decreased cerebral perfusion

DeadSequelae

Antibiotics

Dexamethasone

OdioOdio C et al N C et al N EngEng J J MedMed 19911991• 101 children, 6 weeks- 13 years• 79 H. influenzae, 8 S. pneumoniae, 2 N. meningitidis• Cefotaxime + dexa vs Cefotaxime + placebo• Dexamethasone 0.15 mg/kg every 6 hr for 4 days• Given 15 min prior to cefotaxime• rate of neurologic and audiologic sequalae in children

received dexa was significantly lower ( 14%vs 38%)

WaldWald EE,, Pediatrics Pediatrics 19951995• 143 children, 8wk - 12 yr• 83 H. influenzae, 33 S. pneumoniae, 24 N. meningitidis• Ceftriaxone + dexa vs Ceftriaxone + placebo• Dexamethasone 0.15 mg/kg every 6 hr for 4 days• No significant difference in rate of neurologic and audiologic

sequalae• Bilateral deafness was significantly lower in H. influenzae

meningitis receiveing dexa( 0%) vs placebo (7%)

Bonadio WA, Pediatrics 1996

“Rate of neurologic and audiologic sequalae in children received dexa was significantly lower”

Supportive treatment*Critical peroid: first 3-4 days*

Monitor: Vital signs

Neurological signs

Intake-output

Electrolytes

Body weight

Urine specific gravity

SIADH

Bacterial meningitis with subdural effusion

Brudzinski’s sign positive

GBS meningitis

Meningococcemia

Aseptic meningitisEtiology

- Viral: Enteroviruses

- Postviral: Mumps, measles, chickenpox

- Bacterial: Partially treated bacterial meningitis

- Rickettsiae: Scrub typhus

- Spirochetes: Leptospirosis

- Mycoplasma: M.pneumoniae

Clinical manifestations

“ As same as that of bacterial meningitis”

CSF findings

“ As same as that of viral encephalitis”

Treatments- Viral & postviral: Supportive treatments

- Bacterial: Partially treated bacterial meningitis

- Continue the most appropriated antibiotics

- Rickettsiae: Scrub typhus - doxycycline, chloramphenicol

- Spirochetes: Leptospirosis - doxycycline

- Mycoplasma: M.pneumoniae - macrolides eg. erythromycin

Tuberculous MeningitisIntroduction

- Common in tropical countries

- HIV

- The result of treatment depended on

the stage of disease

Clinical manifestationsChronic meningitis: 3 stages

1. Prodromal stage: nonspecific symptoms (low grade

fever, anorexia, nausea, vomiting )2. Transitional stage: prominent neurological symptoms

meningeal signs, CN palsy, fever3. Terminal stage: coma, fixed and dilated pupil,

decreased RR, PR, dead

Diagnosis

1. History & physical examination

2. Family history

3. CSF findings

4. Other sources of TB (pulmonary, lymph node, miliary TB)

5. Tuberculin test

6. CT brain, ELISA, PCR

CSF findings of TB meningitisCSF findings of TB meningitis

• Pressure: high

• Appearance: Turbid, xanthochromia

• WBCs: 50-500 cells/mm3 , lymphocytes predominate

( >50% )

• Protein: 200-500 mg/dl, may be 1-2 gram or slightly increased

• Sugar: < 50% of blood sugar, or < 40 mg/dl

• AFB stain

• Culture

TreatmentGood clinical respond depended on:-

1. Early diagnosis & early treatment

2. Good medications & adequate duration

INH + rifampicin + pyrazinamide + streptomycin for 2 months

INH + rifampicin for 10 months

3. Reduction of the increased intracranial pressure

Keep CSF pressure < 200 mmH2O

3.1 Lumbar puncture

3.2 Dexamethasone

3.3 Acetazolamide

3.4 Ventriculostomy or ventriculoperitoneal shunt

4. Good supportive treatments

4.1 Nutrition

4.2 Aspiration

4.3 Bed sore

4.4 Fever

4.5 Seizures

4.6 rehabilitation

EncephalitisEtiology:-

- Viral: Japanese B encephalitis - 50%

CMV, HSV, EBV, Poliovirus, rabies

- Postviral: Measles, mumps, chickenpox, rubella

- Postvaccinal: Rabies vaccine

Japanese B encephalitis

- Most common cause of encephalitis in the world

- Common in southeast Asia esp. Thailand

- Northeast Thailand is 2nd common

- Severe, morbidity and mortality rates are high

- No medication for treatment

- Outbreak

Global distribution of major Global distribution of major neurotropicneurotropic flavivirusesflaviviruses

Clinical manifestations1. Prodromal stage (2-3 days): Fever, headache, malaise, nausea,

vomiting 2. Acute encephalitic stage (3-4 days): Fever, conscious change,

seizures, neurosigns, meningeal signs (meningoencephalitis)3. Subacute stage (7-10 days): Neurosigns improved, complications

eg. Pneumonia, UTI4. Late stage and sequalae (4-7 weeks): Stable or improved

neurosigns, sequale eg. spastic paralysis, atrophy

Diagnosis

Fever + conscious change + seizures

CSF findings

- Pressure: 300-400 mmH2O

- WBCs: 10-1,000 cells/mm3 , lymphocytes predominate

- Protein: normal or slightly increased (50-80 mg/dl)

- Sugar: normal

Treatment

No specific treatmentSupportive treatment directed to brain edema

1. Airway and breathing

2. Fever

3. Seizures

Treatment

4. Brain edema: 20%manitol 0.5-1 gm/kg/dose

Steroids - no benefit

5. Complications: Pneumonia, bed sore, SIADH, UTI

6. Nutrition

7. Rehabilitation

Brain abscess- Common in Thailand

- High morbidity and mortality rates

- Often delayed diagnosis and treatment

- Usually recur

Clinical manifestations

3 Main groups of signs and symptoms:-1. Infection: Fever, anorexia, fatigue, increased WBCs and

ESR2. Increased ICP: Most common:- headache, vomiting,

diplopia, papilledema3. Focal neurodeficit: Depend on location of the abscess,

silent area - no neurodeficit

Diagnosis

Fever + headache + neurodeficit

Underlying disease

CT or MRI brain

Treatment1. Antibiotics

-Empiric: cefotaxime + metronidazole

-Depended on underlying diseases:-

COM: aminoglycosides or 3rd gen cephalosporins

Compound fracture: cloxacillin

Treatment2. Drainage

All patients except2.1 Small abscess diameter < 2 cm2.2 Multiple abscesses2.3 Abscess in vital area

3. Supportive treatment4. Treatment of the underlying disease