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8/12/2019 CNS Infection 2012
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Central nervous system
Infection
Setyo Handryastuti
Neurology Division
Department of Child Health
Faculty of Medicine
University of Indonesia
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Objective
Viral infection :
Aseptic meningitis
Encephalitis
Bacterial infection :
Bacterial meningitis
Tuberculous meningitis
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Anatomy of Central nervous
system
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Fig. 1. Coronal view illustrating meningeal layers and common sites of central nervous system
infections. (Reproduced from Lewin JJ, LaPointe M, Ziai WC. Central nervous system infections
in the critically ill. Journal of Pharmacy Practice 2005;18(1):2541; with permission.)
Meningitis
Enchephalitis
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Viral infection
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Aseptic meningitis
Non purulen meningitis
Fever
Meningeal sign
Mild unconsciousness
Cerebrospinal fluid (CSF) : Pleiocytosis with
limphocytosis differential count , gram stained :
negative Self-limiting disease
Good prognosis without sequele
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Encephalitis
Etiology :
Most common : Herpes simplex, arbovirus, Eastern &
Western Equine St.Louis encephalitis
Rare : Enterovirus, parotitis, adeovirus, rabies, CMV 60% : etiology is still unknown
40% :
67% : parotitis, varicella, measles, rubella
20% : arbovirus and herpes simplex
5% : enterovirus
Lewis P, Glaser CA.Pediatr Rev 2005Fenichel GM.Pediatric Neurology in clinicalpractice.2009
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Pathogenesis
Primary encephalitisPost/parainfectious
Two forms
Direct invasion to brainparenchyma
Gray matterPrimary
Host immune response White matter
Post/para
infectious
Whitley RJ,Kimberlin DW. Pediatr Rev 1996Lewis P, Glaser CA.Pediatr Rev 2005
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Pathogenesis & predilection
Direct invasion to brain parenchyma
Hematogenic spread (viremia)
Arbovirus Reticuloendotelial system CNS.
Acute
Neurogenic spread
Herpes simplex, rabies, polio retrograde transport
at the neuron. Acute/chronic (reactivation)
Whitley RJ,Kimberlin DW. Pediatr Rev 1996
Lewis P, Glaser CA.Pediatr Rev 2005
Unconsciousness is
faster /main
symptoms
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Pathogenesis & predilection
Herpes simplex : temporal & orbitofrontal lobe
Rabies : Pons, medulla,
cerebellum,hippocampus Japanese encephalitis (JE) : brain stem, basal
ganglia
Whitley RJ,Kimberlin DW. Pediatr Rev 1996
Lewis P, Glaser CA.Pediatr Rev 2005
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Clinical manifestations Pathogenesis and
predilection
Acute infection sign/Prodromal symptoms Fever, diarrhea, sore throat, skin rash, cough-runny
nose
Neurological deficit (global/focal) Seizures, behavioural changes, aphasia,hemiparesis, cranial nerve paresis, diplopia, ataxia,
disarthrya
Increasing of intracranial pressure (ICP) Cephalgia, vomiting, unconscious
Lewis P, Glaser CA.Pediatr Rev 2005Schwaimann.Pediatric Neurology 2006Ziai WC,Lewin JJ. Neurol Clin 2008
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Rabies/JE : brain-stem encephalitis Disarthrya, diplopia, ataxia
Arbovirus :Global signs
Fever, vomiting, unconscious
Herpes simplex : Focal signs
Hemiparesis, focal seizures, cranial nerve paresis
aphasia,anosmia
Lewis P, Glaser CA.Pediatr Rev 2005Schwaimann.Pediatric Neurology 2006Ziai WC,Lewin JJ. Neurol Clin 2008
Clinical manifestations Pathogenesis and
predilection
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Diagnosis
Viral identification : PCR/ CSF culture
Clinical manifestations , CSF analysis
CSF : Clear, cell 50-200/mm3 until 1000/mm3 ,
limphocytosis, protein normal/slightly increased,normal glucosa
EEG : global/focal slowing
CT-Scan/MRI : diffuse brain edema , focal inHSE
Lewis P, Glaser CA.Pediatr Rev 2005
Menkes . Textbook of Clinical Neurology 2006Ziai WC,Lewin JJ. Neurol Clin 2008
EEG and CT-
Scan/MRI not
specific , except for
HSV
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Management
Intensive Care Unit Supportive therapy :
Airway, Breathing,Circulation
Nutrition, fluid and electrolyte balance
Anticonvulsion and antipyretic
Etiology therapy : HSV and varicella : Acyclovir
Adenovirus : cidofovir/ribavirin
Enterovirus : pleconaril
Hyperthermia surface cooling
Dexametason is not used for encephalitisLewis P, Glaser CA.Pediatr Rev 2005
Schwaimann.Pediatric Neurology 2006
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Management
Decreasing intracranial pressure caused bycytotoxic edema Mannitol 20% : 0,251 gr/kgBW/dose, every 6-8
hours, Rapid infusion in 30 minutes.
Withdrawn fluid from brain parenchyma
Monitoring GCS, fluid and electrolyte balance
Monitoring vital signs and diuresis
Serious side effects : dehydration and shock
Increase the dose gradually if GCS does not
improved Head elevation 30 degrees, avoid invasive procedure
Ranger-Castillo L, Robertson CR.Crit Care Clin 2007.
Schwaimann. Pediatric Neurology 2006
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Complication
Depends on etiology and age of patients
Cerebral palsy
Mental retardation
Epilepsy, encephalitis HSV : focal epilepsy
Behavioral problems
Schwaimann.Pediatric Neurology 2006
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HSV Encephalitis
The etiology can be cured
Encephalitis clinical manifestations and focalneurological deficit : focal seizures , hemiparesis
Adolescence : behavioral changes EEG : focal slowing at temporal region, PLEDS
(periodic lateralizing epileptiform discharge)
Head CT/MRI : Focal edema
Bleeding/necrosis at temporal region.
Therapy : Acyclovir 10-20 mg/kgBW/dose IV, every8 hours for 10-14 days.
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Leonard, J. R. et al. Am. J. Roentgenol. 2000;174:1651-1655
Baby girl , 11 months with fever, letargy, focal seizure at the left side,
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Leonard, J. R. et al. Am. J. Roentgenol. 2000;174:1651-1655
Baby girl , 11 months with fever, letargy, focal seizure at the left side,
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Leonard, J. R. et al. Am. J. Roentgenol. 2000;174:1651-1655
Baby girl , 11 months with fever, letargy, focal seizure at the left side,
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Focal slowing
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PLED
Sphelman. Atlas of EEG.
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Bacterial Meningitis
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Introduction
Mortality : 18-40%, morbidity: 30-50%
Inflammation of the meningens,
polymorphonuclear pleocytosis of the CSF , proved
by positive CSF culture
Boys > girls
80% in children
70% of them are child with 1-5 years of age
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Pathogenesis
Germ colonization at the upper respiratory tract
Pneumonia, septicemiaHematogenic
Direct invasion
Sinusitis, mastoiditis, sinus cavernosusthrombosis, CSOMPercontinuitatum
Head trauma with opened fracture, cochlearimolant
Neurosurgery, lumbal punctureDirect Implantation
Amnion fluid aspiration (amnionitis) /normal germcolonization
Transplacental infectionNeonates
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005
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Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005
Cough,runny
nose, fever
Sinusitis,
CSOM,
Pneumonia
Neurological
deficit
Meninegal sign
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Common etiology :
Streptococcus B haemolyticus,Escherichia coli, Listeriamonocytogenes, enterobacter
Neonates
E. coli, L. monocytogenes, Neisseriameningitides, S. agalactiae, S.pneumoniae, Haemophyllus influenzaetype B
1 months5 years
N.meningitidis, S.pneumoniae, H.influenzae type B> 5 years
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005Mann K, Jackson MA.Pediatr rev 2008
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Clinical manifestations Pathogenesis
Depends on age, duration of illness before
diagnosis, host response against infection.
Neonates meningitis neonatus-3 months of age :
High risk : premature, intrapartum infection, Prematurerupture of membrane
Not specific
Fever,letargy, not doing well , vomitus,hypothermia,
unconscious, bulging fontanel, apneu, seizures.
High suspicion of meningitis in neonates with
sepsis/pneumonia with seizures.
Schwaimann. Pediatric Neurology 2007
JJ Volpe. Neurology of the newborn 2009
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3 months-2 years Fever, vomitus, iritabel, seizures, high pitched cry, ,
bulging fontanel, meningeal sign difficult to evaluate
Consider meningitis : complex febrile seizures
> 2 years of age Classic clinical manifestations
Fever, vomitus, cephalgia, seizures, behavioralproblems, unconscious could happened, meningealsigns are really obvious
Cranial nerve paresis (N.III, N,IV, N.VI, N.VII)
Schwaimann. Pediatric Neurology 2007
Clinical manifestations Pathogenesis
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Diagnosis
Cerebrospinal fluid
Macroscopic : cloudy, purulent
Pleiocytosis > 1000 cell/mm3, diff count :
polymorphonuclear predominance
Early phase : normal cells until hundreds of cells ,
lymphocytosis pfedominance
Increasing protein and decreasing glucose
(< 60% blood glucose) Gram satined, culture and sensitivity test
PCR (Sensitivity 86%, specifivity 97%)
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005Schwaimann. Pediatric Neurology 2007
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Management
Suportive: IVFD, nutrition, antipyretic, anticonvulsion.
Increasing ICP : mannitol 20% caused by cytotoxic brain
edema
Dexametason to suppress cytokine inflammation : 0,6-1
mg/kgBW/day divided in 3-4 dose, injection before (15-30
minutes/concomitant with antibiotics injection, for 2-4 days.
Dexametason : reduce complication of hearing problems,
decreasing morbidity and mortality
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005Mann K, jackson MA. Pediatr Rev 2008
Van de Beek D, De Gans J, Mc Intyre P, Prasad K. CochraneDatabase review 2008
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Management
Dexametason is not been used in neonatal meningitis
Empirical antibiotics therapy first before the result of culture
and sensitivity test
Conventional antibiotics (ampicilin and chloramphenicol)
can be used if cephalosporin is not available
Duration of antibiotics therapy
Neonates : 21 days
Infants and children : 14 days
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005Mann K, jackson MA. Pediatr Rev 2008Prasad K. Kumar A, Singhal t, Gupta PK. Cochrane Database
Review 2008
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Empirical antibiotics therapy
Neonates Ampicilin (150-200 mg/kg/days) divided in 3 or 4) +
cefotaxim (150-200 mg/kg/days) in 3 or 4
Ampicilin + Gentamycin (5-7,5 mg/kg/days in 2 or 3)
Late-onsetmeningitis : vancomycin (30-45mg/kgBW/days in 3 or 4)+ cefotaxim/ceftazidim
> 1 months Vancomycin (60 mg/kgBB/days in 3 or 4 + Ceftriaxon 80-
100 mg/kgBW/days : 2 dose (max. 4 gr/days) Vancomycin + Cefotaxim 200-300 mg/kgBW/days in 3 or
4 (max. 12 gr/days)
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005
Mann K, jackson MA. Pedaitr Rev 2008Fenichel GM.Pediatic neurology in clinical parctice 2009
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Complications
Delayed /uncomplete treatment Consider if there is no clinical improvement in the first
week of adequate treatment Complications during hospitalization : Ventriculitis
Subdural effusion Subdural empyema Brain abscess Fluid and electrolyte imbalance
Long-term sequele : deafness (5-10% caused byH.influenzae, 25-35% caused by S.Pneumoniae),hydrochephalus,motori/learning/speech/behaviourproblems (10%)
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005
Schwaimann. Pediatric Neurology 2007
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Subdural empyema
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Subdural effusion
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Brain abscess
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Hydrocephalus and periventricular edema
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Prognosis
Depends on :
Age
Clinical manifestations : seizures and unconscious
The amounts and types of microorganism
Cells counts and CSF glucose
Time needed to sterilize CSF
Duration of illness before treatment
Bacterial sensitivity against antibiotics treatment
Chavez-Bueno S, Mc Cracken JH. Pediatr Clin N Am 2005Schwaimann. Pediatric Neurology 2007
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Tuberculous Meningitis
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Introduction
Meningoensefalitis
The most common chronic TBC in developing countries
High mortality and morbidity
All ages High incidence : 6 months6 years of age
Often preceded by measles, pertussis and head
1 of 300 untreated TB infection cases .
Ramachandran TS. Tuberculous meningitis.http://www.emedicine 2007Schwaimann. Pediatric Neurology 2007
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PathogenesisFirst stage
Second stage
Ramachandran TS. Tuberculous meningitis.http://www.emedicine 2007
Pertussis, meales,
head trauma, HIV
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First stage (prodromal) Fever, nausea, apathy, iritabel, neurological deficit negative
Second stage (transision/meningitis)
Unconsciousness until sopor, meningeal signs,
tetraparesis/hemiparesis, cranial nerve paresis (III,IV,VI,VII),clonus, tubercle at choroid, funduscopy : papil edema
/atrophy
N.VI paresis is the most common
Third stage (terminal) Coma, unresponsive pupil , hyperthermia, irreguler breathing
Delayed/ unadequate treatment
Soetomenggolo T. Buku Ajar Neurologi Anak1996Ramachandran TS. Tuberculous meningitis.http://www.emedicine 2007
Clinical manifestations Pathogenesis
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Diagnosis
Clinical manifestations Routine CSF
Clear and sedimentation, xantochrome, cells 200-500/mm3, lymphocytosis, increasing protein and low
glucosa (
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Diagnosis
ELISA and PCR examinations
CSF culture difficult, needs more CSF(6-10 ml) with
positive findings in 50% cases.
EEG : diffuse or focal slowing
Head CT-Scan/MRI : meningens enhancement at basal
ganglia, ventriculomegali until hydrocephalus, infarc.
Combinations of hydrochephalus, basal enhancement,
and infarct : 100% specific and 41% sensitive for TB
meningitis
Soetomenggolo T. Buku Ajar Neurologi Anak1996Ramachandran TS. Tuberculous meningitis.http://www.emedicine 2007Pediatric radiology 2004;34.
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Tuberculous Meningitis - CT
http://images.google.com/imgres?imgurl=www.traveldoctor.co.uk/images/squita.gif&imgrefurl=http://www.traveldoctor.co.uk/malaria.htm&h=150&w=138&prev=/images?q=japanese+b+encephalitis+&svnum=10&hl=en&lr=&ie=UTF-8&sa=Nhttp://www.crystalgraphics.com/powerpictures/gallery.MEDP2023.asp8/12/2019 CNS Infection 2012
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Exsudate at basal
d h l b l
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Hydrocephalus tuberculousmeningitis
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Head MRI : infarct of basal ganglia
2 yrs,FCh
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Management
Supportive therapy : IVFD, nutrition, antipyretic,anticonvulsion.
Increasing ICP : mannitol 20%
Prednison to suppress inflammation reaction for 2-
3 weeks then tappering-off gardually in 1 week
INH 5-10 mg/kgBW/days for 9-12 months
Rifampicin 10-20 mg/kgBW/days for 9-12 months
Pirazinamid 20-40 mg/kgBW/days for 2 months
Etambutol 15-25 mg/kgBW/days for 2 months
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Management
Hydrocephalus VP-shunt procedure
Monitoring side effect of anti tuberculosis drugs by
serial liver function test
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Complication
Hydrocephalus
Cerebral palsy
Mental retardation
Epilepsy
Motor coordination disorder,ataxia
Sensory problems
Vision and hearing problems
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Prognosis
Mortality is high in untreated patients
Depends on :
Stage of the diseases when the treatment is started
< 3 years of age : worst prognosis
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Differential diagnosis of CNS infection
Clin./Lab. Encephalitis Bacterial
meningitis
TBC Meningitis Viral
Meningitis
Encephalopaty
Onset Acute Acute Chronic Acute Acute/chronic
Fever < 7 days < 7 days > 7 days < 7 days 7 days/(-)
Seizures Gen./focal Gen. Gen. Gen. Gen.
Unconsc. Somnolence- sopor Apathy Apathy - sopor CM -Apathy Apathy -Somnolence
Paresis +/- +/- ++/- - -
GCSimprovement
Slow Fast Slow Fast Fast/slow
Etiology Diff. toidentify
++/- TBC/history ofcontact
- Extra CNS
Therapy Simpt/antiviral
Antibiotics Tuberculostatic Simpt. Man. Ofprimarydiseases
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CSF examination in CNS infection
Bact.men Viral men TBC men Encephalitis Encephalopathy
Pressure Normal/
Macros. Cloudy Clear Xantochrome
Clear Clear
Leuco. > 1000 10-1000 500-1000 10-500 < 10
PMN (%) +++ + + + +
MN (%) + +++ +++ ++ -
Protein Normal/ Normal Normal
Glucosa Normal Normal Normal
Gram/Rapid T.
Positive Negative Negative Negative Negative
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