cns infection 2012

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



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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


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.


19/59Copyright 2006 by the American Roentgen Ray Society

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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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.


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)




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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)


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%)




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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



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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.asp


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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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cns infection 2012

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