INFECTIONS OF THE INFECTIONS OF THE CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM

Dr. Kiking Ritarwan, SpS(K), MKTDr. Kiking Ritarwan, SpS(K), MKTDepartement of Neurology Medical Departement of Neurology Medical

Faculty of University of Sumatera UtaraFaculty of University of Sumatera Utara27February 201327February 2013

CNS INFECTIONCNS INFECTIONI. MENINGITIS (I. MENINGITIS (Bacterial, Tuberculosa, Viral, JamurBacterial, Tuberculosa, Viral, Jamur))

- Inflamation of the meningeal covering of - Inflamation of the meningeal covering of Brain and spinal cord.Brain and spinal cord. - LEPTOMENINGITIS (arachnoid + pia)- LEPTOMENINGITIS (arachnoid + pia) PACHYMENINGITIS (duramater)PACHYMENINGITIS (duramater) - TYPE OF MENINGITIS : Bacterial, TB, Viral, - TYPE OF MENINGITIS : Bacterial, TB, Viral, fungal.fungal.

2. ENCEPHALITIS VIRAL2. ENCEPHALITIS VIRAL3. MYELITIS3. MYELITIS4. ABSCESS CEREBRI4. ABSCESS CEREBRI5. CEREBRAL MALARIA5. CEREBRAL MALARIA6. NCC6. NCC

I.a. I.a. Acute Pyogenic MeningitisAcute Pyogenic Meningitis= Bacterial meningitis= Bacterial meningitis

Is an inflamatory response to bacterial infections Is an inflamatory response to bacterial infections involving the pia and arachnoid membrane covering involving the pia and arachnoid membrane covering the brain and spinal cord.the brain and spinal cord.

Many org. can produce Many org. can produce pyogenic meningitispyogenic meningitis

It can be categorised into:It can be categorised into: a. Spontaneous community acquired meningitisa. Spontaneous community acquired meningitis b. Post traumatic meningitis following neurosur-b. Post traumatic meningitis following neurosur- gery or fx of the skull.gery or fx of the skull. c. Device associated meningitis particularly in assoc. c. Device associated meningitis particularly in assoc. With CSF Shunts and drain.With CSF Shunts and drain.

The causative org. of meningitis can be The causative org. of meningitis can be predicted based on the patient’s age, exposure predicted based on the patient’s age, exposure to an epidemic, vacc. Against common agents to an epidemic, vacc. Against common agents (eg. (eg. H. Influenza, Streptococcus pneumonie, N. H. Influenza, Streptococcus pneumonie, N. meningitidismeningitidis) and Immune state.) and Immune state.

Pathology is characterized by inflammation of Pathology is characterized by inflammation of the meninges and cortical blood vessels.the meninges and cortical blood vessels.

Etiology of Bacterial meningitisEtiology of Bacterial meningitis

Age Microorg.Age Microorg. - Neonate ( 0-2 bln) Streptococ group B, E coli, list.- Neonate ( 0-2 bln) Streptococ group B, E coli, list. Stap. Aureus, Enterobacter,Stap. Aureus, Enterobacter, Pseudomonas, HaemofilusPseudomonas, Haemofilus - Child S. pneumonie, N. meningitidis,- Child S. pneumonie, N. meningitidis, H. influenzae.H. influenzae. - Youth ( 6-20- Youth ( 6-20thth) N. meningitidis, S. pneumonie,H. infl.) N. meningitidis, S. pneumonie,H. infl. - Adult ( > 20 thn) S. pneu, N. meningi, Streptococ,Staph.- Adult ( > 20 thn) S. pneu, N. meningi, Streptococ,Staph.

Clinical PictureClinical PictureThe conditions occurs equally in both sexesThe conditions occurs equally in both sexesChildren aged 6 month to 1 year are at the greatest Children aged 6 month to 1 year are at the greatest risk and children under 15 years of age comprise 75% risk and children under 15 years of age comprise 75% of all cases. Patients aged 60 and older may be of all cases. Patients aged 60 and older may be atypical.atypical.Symptoms and signsSymptoms and signs

I. early infection: fever, headache, malaise,vomiteI. early infection: fever, headache, malaise,vomite II. Higher ICP: vomite, headache, seizure, alteration of II. Higher ICP: vomite, headache, seizure, alteration of consciousness, papiledemaconsciousness, papiledema III. Meningeal irritation: nuchal rigidity, Kernig and III. Meningeal irritation: nuchal rigidity, Kernig and Brudzinski +Brudzinski + IV. CSF:neutrophilic pleocytosis, low glucose level, IV. CSF:neutrophilic pleocytosis, low glucose level, elevated protein concentrationelevated protein concentration

CSF FindingsCSF Findings

CSF Parameter Bacterial meningitisCSF Parameter Bacterial meningitis• WBC Count > 2000/ ul, >60% PMNWBC Count > 2000/ ul, >60% PMN• Glucose < 40 mg/ dlGlucose < 40 mg/ dl• Protein > 200 mg/ dlProtein > 200 mg/ dl• Gram stain + 80%Gram stain + 80%• Culture + > 90%Culture + > 90%

Diagnostic ProsedureDiagnostic Prosedure

Lumbal PunctureLumbal PunctureBlood should be drawn for blood culture before Blood should be drawn for blood culture before administration of antibiotic.administration of antibiotic.Bacterial antigenBacterial antigenChest, skull mastoid and paranasal sinus x raysChest, skull mastoid and paranasal sinus x raysMRI or CT MRI or CT

Neuroimaging shoul be performed before LP in Neuroimaging shoul be performed before LP in the following settings:60 yo or older, Depressed the following settings:60 yo or older, Depressed LOC, Focal neurologic signs, papilledema, LOC, Focal neurologic signs, papilledema, Patients is immunocompromised.Patients is immunocompromised.

TreatmentTreatment1.Antibiotic therapy should be administrated. A minimum of 2 1.Antibiotic therapy should be administrated. A minimum of 2

weeks of therapy is recommended.weeks of therapy is recommended. Age AntibioticAge Antibiotic 0 – 4 mgg Cefotaxim + Ampi0 – 4 mgg Cefotaxim + Ampi 4-12 mgg Gen III. Cephalos+ Ampi4-12 mgg Gen III. Cephalos+ Ampi 3 bln- 18 thn Gen III. Ceph + Ampi atau3 bln- 18 thn Gen III. Ceph + Ampi atau Ampi + chloramph.Ampi + chloramph. 18 thn – 50 thn Gen III. Ceph + Ampi18 thn – 50 thn Gen III. Ceph + Ampi 50 thn Gen III. Ceph + ampi.50 thn Gen III. Ceph + ampi.

2. When possible etiologies for meningitis include H. Influenza or 2. When possible etiologies for meningitis include H. Influenza or S Pneumoniae in child, or S Pneumoniae in adults, give S Pneumoniae in child, or S Pneumoniae in adults, give dexamethasone 0,15 mg/kg (IV) every 6 hours for 2-4 days in dexamethasone 0,15 mg/kg (IV) every 6 hours for 2-4 days in child and 10 mg IV every 6 hours for 4 days in adults.child and 10 mg IV every 6 hours for 4 days in adults.

Complication Bacterial meningitisComplication Bacterial meningitis

Cerebral abscessCerebral abscess

Empyema subduralEmpyema subdural

ConvulsieConvulsie

Shock septicShock septic

Cerebral edemaCerebral edema

Infarck serebralInfarck serebral

HerniationHerniation

Sequele bacterial meningitisSequele bacterial meningitis

Mental retardationMental retardation

HydrocephalusHydrocephalus

Convulsie, psikoseConvulsie, psikose

Parese, deafness, blind.Parese, deafness, blind.

I.b.Tuberculous meningitisI.b.Tuberculous meningitis

The first clinical description of tuberculous meningitis in the late 18th Century is credited to the Scottish physiologist

Sir Robert Whytt , even before Robert Koch isolated mycobacterium tuberculosis in 1882.

Almost 40 years later, Rich and McCordock demonstrate the presence of minute caseous tubercles known as “Rich-foci” within the brain or meninges, which formed the basis for understanding the pathogenesis of CNS tuberculosis.

Tuberculosis of the central nervous system (CNS) is the most serious complication of tuberculosis, especially in children.

TB TB hematogenous spread hematogenous spread infection to the brain infection to the brain parenchyma or meninges.parenchyma or meninges.

TB meningitis TB meningitis (TBM)(TBM)

Definition:Definition: TBM is an infection of the meninges caused by TBM is an infection of the meninges caused by

the acid-fast bacillus the acid-fast bacillus Mycobacterium tuberculosis.Mycobacterium tuberculosis. In the west country,the first make not much In the west country,the first make not much

difference again, but lately incident mount difference again, but lately incident mount drastically in all the world.drastically in all the world.

TBM happened at all of age.TBM happened at all of age. Before important HIV factor in prevalens is ageBefore important HIV factor in prevalens is age

++ 1,7 milyar people ( 1/3 worldwide 1,7 milyar people ( 1/3 worldwide people) people) Mycobacterium tuberculosa Mycobacterium tuberculosa infected.infected.

Reported CDC 2002 was 5,36 cases per Reported CDC 2002 was 5,36 cases per 100.000 people, but worldwide the 100.000 people, but worldwide the infection rate is much higher.infection rate is much higher.

TB in Indonesian occupy 3TB in Indonesian occupy 3rdrd rank from 22 rank from 22 high burden countries.high burden countries.

Indonesia Indonesia 22 High Burden Countries22 High Burden Countries

Indonesia Indonesia 22 High Burden Countries22 High Burden Countries

1. India2. China

3. Indonesia4. Bangladesh5. Nigeria6. Pakistan7. South Africa8. Philippines9. Russia10. Ethiopia11. Kenya12. DR Congo13. Viet Nam14. UR Tanzania15. Brazil16. Thailand17. Zimbabwe18. Cambodia19. Myanmar20. Uganda21. Afghanistan22. Mozambique

Indonesia 10%Indonesia 10%Indonesia 10%Indonesia 10%

Bangladesh 4%

China15%

China15%

India30%India30%

Other28%

Philippines 3%

Pakistan 4%

Nigeria 3%

South Africa 2%

Russia 1%

INTRACRANIALINTRACRANIAL Tuberculous Meningitis (TBM)Tuberculous Meningitis (TBM) TBM with milliary tuberculosisTBM with milliary tuberculosis Tuberculous EncephalopathyTuberculous Encephalopathy Tuberculous VasculopathyTuberculous Vasculopathy Space-occupying lesions: Tuberculoma ( single or multiple), multiple small tuberculoma with Space-occupying lesions: Tuberculoma ( single or multiple), multiple small tuberculoma with

milliary tuberculosis, tuberculous abscessmilliary tuberculosis, tuberculous abscess

SPINALSPINAL Pott’s spine and Pott’s paraplegiaPott’s spine and Pott’s paraplegia Tuberculous arachnoiditis (myeloradiculopathy)Tuberculous arachnoiditis (myeloradiculopathy) Non-osseous spinal tuberculomaNon-osseous spinal tuberculoma

SPECTRUM OF CNS TBSPECTRUM OF CNS TB

Hankey, GJ, Wardlaw JM. Clinical Neurology,2008

EtiologiEtiologiMycobacterium tuberculosisMycobacterium tuberculosis

gol ordo Actinomycetales, familigol ordo Actinomycetales, famili

Mycobacteriaceae, genus Mycobacteriaceae, genus MycobacteriumMycobacterium

Sifat : aerob, spora (-), motil (-), Sifat : aerob, spora (-), motil (-), berkembang biak lambatberkembang biak lambat

Mati dgn pemanasan & sinar UV, Mati dgn pemanasan & sinar UV, uk 0,4 X 3uk 0,4 X 3 m m

Bakteri batang tahan asam dgn Bakteri batang tahan asam dgn pewarnaan Ziehl–Neelsen pewarnaan Ziehl–Neelsen /Auramin /Auramin leading to nickname leading to nickname “ red snapper”.“ red snapper”.

PathogenesisPathogenesis

1919

• Aerob intrasel obligatAerob intrasel obligat• Transmisi from dropletTransmisi from droplet• Alveoli Alveoli multiply multiply• Hematogen disseminasi Hematogen disseminasi 2-4 weeks 2-4 weeks• T limfosit and makrofagT limfosit and makrofag• ‘‘Rich focus’Rich focus’• Expanding tubercleExpanding tubercle

PathophysiologyPathophysiology

MENINGITISMiliary TB

PRIMARY COMPLEXPRIMARY COMPLEX

DISSEMINATION to the regional lymph node

ALVEOLAR MACROPHAGE

DROPLET INHALATION

10% PPT

Bacteremia

Seed to the meningesOr brain parenchyma

RICH FOCI

Rupture of a rich focus into theSubarachnoid space

PATHOGENESIS

Innoculation of bacilli into the subarachnoid space

DENSE BASAL MENINGEAL EXUDATE

ADHESION FORMATIONOBLITERATIVE

VASCULITISEncephalitis/myelitis

Obstruction of the CSFInterpendicular fossa

Infarction/ stroke syndrome

PATHOGENESIS

CLINICAL FEATURESCLINICAL FEATURES Headache, Lethargy, Confusion, DrowsinessHeadache, Lethargy, Confusion, Drowsiness Fever, Stiff Neck, Kernig and Brudzinski signsFever, Stiff Neck, Kernig and Brudzinski signs

ANALYSIS OF CSFANALYSIS OF CSF Pressure: increasedPressure: increased Cells: 50-500 white cells/mm3; lymphocyte predominateCells: 50-500 white cells/mm3; lymphocyte predominate Raised Protein: 1-2 gr/lRaised Protein: 1-2 gr/l

Glucose: < 2,22 mmol/ l (< Glucose: < 2,22 mmol/ l (< 40 mg/dl)40 mg/dl)

FUTURE OF DIAGNOSISFUTURE OF DIAGNOSISo History of treatment of TBHistory of treatment of TBo TB extra-organ (clinically and radiology)TB extra-organ (clinically and radiology)

DIAGNOSIS TBMDIAGNOSIS TBM

Thwaites et al, J Infect 2009; 59: 167-187

Neck Stiffness in meningitisNeck Stiffness in meningitis

Kernig Sign’sKernig Sign’s

Lumbar Puncture: the diagnosis is made by Lumbar Puncture: the diagnosis is made by demonstration of acid-fast bacilli by Ziehl-Neelsen demonstration of acid-fast bacilli by Ziehl-Neelsen (ZN) stain of the CSF. Positive stain 3-6 weeks. (ZN) stain of the CSF. Positive stain 3-6 weeks. Sensitivity :80-85%, spesifisity:98%Sensitivity :80-85%, spesifisity:98%

Polymerase Chain Reaction Polymerase Chain Reaction (PCR)(PCR) - - Based approachBased approach

- Advantages:positive results after medication - Advantages:positive results after medication

until 1 monthuntil 1 month

- Estimate PCR is quantitative will hold enough - Estimate PCR is quantitative will hold enough

role important in inspection of curative role important in inspection of curative

response, and not for diagnostic.response, and not for diagnostic.

- Pai et al (2003): PCR sensitivity : 56%, spesifisity - Pai et al (2003): PCR sensitivity : 56%, spesifisity

98%.98%.

DIAGNOSIS TBMDIAGNOSIS TBM

Pai et al, Lancet Infect Dis 2003; 3(10): 633-43

Characteristically, we find a clear or xanthochromic Characteristically, we find a clear or xanthochromic fluid with pleocytosis, fluid with pleocytosis, increased protein level and increased protein level and decreased glucose leveldecreased glucose level

Cell count between Cell count between 10 – 50010 – 500, usually no more than , usually no more than 1000/ mm3, may be predominant lymphocytic, but 1000/ mm3, may be predominant lymphocytic, but not alwaysnot always

Protein content Protein content 100-500mg%100-500mg%, in Supartini (2002) , in Supartini (2002) and Mulyono (2002) studies average 283-498 mg%and Mulyono (2002) studies average 283-498 mg%

Definite diagnosis must be based on presence of Definite diagnosis must be based on presence of M.tuberculosis M.tuberculosis in CSF.in CSF.

CSF FINDINGS-TBMCSF FINDINGS-TBM

Clinical staging of patients with Clinical staging of patients with TBMTBM

(terminus/ advance)

1948 1948 Relevan British Medical Research Relevan British Medical Research Council (MRC) Staging SystemCouncil (MRC) Staging SystemStage IStage I– Fully conscious and no deficite neurologic signFully conscious and no deficite neurologic sign

Stage IIStage II– Grade 2a: GCS 15 with deficite neurologic focalGrade 2a: GCS 15 with deficite neurologic focal– Grade 2b: GCS 10 – 14Grade 2b: GCS 10 – 14 (Confused) with hemiparesis (Confused) with hemiparesis

or single cranial nerve palsyor single cranial nerve palsy

Stage IIIStage III– Comatose or Stuporous, GCS < 10Comatose or Stuporous, GCS < 10 with multiple with multiple

cranial nerve palsies or complete hemiplegi or cranial nerve palsies or complete hemiplegi or paraplegiaparaplegia

CLINICAL FEATURES TBM:CLINICAL FEATURES TBM:

Clinical FeaturesClinical FeaturesMisra UK (2001) Educational Course Literatur

Kategori diagnosis Ogawa

DefiniteDefinite - bila kultur - bila kultur positi - otopsi positip, atau keduanya- otopsi positip, atau keduanya

Probable Probable - likuor pleiositosis (>5/mm- likuor pleiositosis (>5/mm33), kultur bak-), kultur bak- teri dan jamur negatip + salah satu:teri dan jamur negatip + salah satu: 1. test tuberkulin positip1. test tuberkulin positip 2. TB diluar SSP atau TB aktip sebelumnya2. TB diluar SSP atau TB aktip sebelumnya 3. glukosa likuor < 40 mg/dl3. glukosa likuor < 40 mg/dl 4. protein likuor > 60 mg/dl4. protein likuor > 60 mg/dl

ComplicationComplication

Arteritis Arteritis thrombosis of a major artery thrombosis of a major artery cerebral infarction.cerebral infarction.

HydrocephalusHydrocephalus

SeizuresSeizures

Focal motor deficits and impaired cognitiveFocal motor deficits and impaired cognitive

Hypopituitarism in childhood.Hypopituitarism in childhood.

50-60% has sign of active pulmonary 50-60% has sign of active pulmonary tuberculosistuberculosis

13-24% have Milliary Pulmonary 13-24% have Milliary Pulmonary TuberculosisTuberculosis

Chest X-RaysChest X-Rays

CT Scan/MRICT Scan/MRI- Enhancement of the basal cisterns 90% of cases interpeduncular Enhancement of the basal cisterns 90% of cases interpeduncular

fossa, the ambient cistern & Chismatic regions are particularly fossa, the ambient cistern & Chismatic regions are particularly involvedinvolved

- Communicating hydrocephalus in 50-80%Communicating hydrocephalus in 50-80%- Infarct on CT -20,5-38%, most common basal ganglia and the Infarct on CT -20,5-38%, most common basal ganglia and the

territories of the medial striate and thalamoperforating arteriesterritories of the medial striate and thalamoperforating arteries- MRI more sensitive than CT- meningeal ( basal enhancement) and MRI more sensitive than CT- meningeal ( basal enhancement) and

parenchymal (infarct) involvement, hydrocephalus detected equaly parenchymal (infarct) involvement, hydrocephalus detected equaly by CT and MRIby CT and MRI

NeuroimagingNeuroimaging

1. Use of anti tuberculosis drugs 1. Use of anti tuberculosis drugs (chemoterapy-TB)(chemoterapy-TB)

2. Symptomatic and supportive measures2. Symptomatic and supportive measures

3. Preventing and management of 3. Preventing and management of complicationcomplication

Management of TBMManagement of TBM

DRUGS Dosage Child Dosage Adult Route

Isoniazid 10 – 20 mg/kg ( max 500 mg)

300 mg Oral

Rifampicine 10 – 20 mg/kg(max 600 mg)

450 mg (< 50 kg)600 mg (> 50 kg)

Oral

Pyrazinamide 30 – 35 mg/kg(max 2gr)

1,5 gr (< 50 kg)2,0 gr (> 50 kg)

Oral

Ethambuthol 15 – 20 mg/kg(max 1 gr)

15 mg/kg Oral

ANTI TUBERCULOSIS DRUGS- ANTI TUBERCULOSIS DRUGS- Recommended Treatment RegimenRecommended Treatment Regimen

WHO recommended Combination ATD, Initial Treatment ( 2 month) : INH+R+PZA+E orR+PZA+S; Continued ( 7 month):INH+ R.

ATS recommended Combination ATD, Initial ( 2month): INH+R+PZA or S; Continued ( 9 month): INH+ RATS recommended Combination ATD, Initial ( 2month): INH+R+PZA or S; Continued ( 9 month): INH+ R

CSF Consentration of certain CSF Consentration of certain antituberculosis drugsantituberculosis drugs

ATD….ATD….

DRUGS Daily DoseMg/ kg

SerumUg/dl

Normal MeningensUg/ms

Inflammated menigens ug/ms

Isoniazid 5 - 10 3 - 5 0,6- 1,6 2,0 – 3,2

Rifampicine 10 - 20 0,4 – 1,2 0 0,4-1,0

Ethambutol 15 - 25 1,0 -7,7 0 0,5-2,5

Pyrazinamide 25 - 30 15 - 50 10 30 – 50

Streptomycine 15 - 40 25 – 50 trace 2.0 – 9.0

Misra ,UK. Tuberculous meningitis. XVII World Congress of neurology, London,(2001)

Good penetration in CSF Treatment: Good penetration in CSF Treatment: Isoniazid, Isoniazid, Rifampicine,Pyrazinamide,prothianamide/ethiRifampicine,Pyrazinamide,prothianamide/ethionamide and cycloserine.onamide and cycloserine.

Only in the presence of meningeal Only in the presence of meningeal inflamation: kanamycin, amikacin and inflamation: kanamycin, amikacin and capreomycincapreomycin

Poor or no penetration: PAS and ethambutolPoor or no penetration: PAS and ethambutol

PRINCIPLES THERAPHYPRINCIPLES THERAPHY

Differentiated Corticosteroid Differentiated Corticosteroid Regimen in TBMRegimen in TBM

Thwaites et al, J Infect 2009; 59: 167-187

Dexamethasone (adults 12 mg/ day, child < 25 kg, Dexamethasone (adults 12 mg/ day, child < 25 kg, 8 mg/ day) given for 3 weeks ( in conjuction with 8 mg/ day) given for 3 weeks ( in conjuction with anti TB Therapy) then tapered over further 3 weeks anti TB Therapy) then tapered over further 3 weeks may reduce the incidence of sequele in patients may reduce the incidence of sequele in patients who are culture positive, particularly those who who are culture positive, particularly those who have a decreased conscious level at presentation.have a decreased conscious level at presentation.

Prednisolone 60-80 mg/ day tapering after 2 weeks Prednisolone 60-80 mg/ day tapering after 2 weeks to finish 4-6 weeks, is an alternative.to finish 4-6 weeks, is an alternative.

Corticosteroid-Additional TreatmentCorticosteroid-Additional Treatment

Hankey GJ, Wardlaw, JM. Clinicl neurology,2008

Meta-analysis of 7 RCT involving 1140 Meta-analysis of 7 RCT involving 1140 participant participant

(with 411 death) concluded that CS improved (with 411 death) concluded that CS improved outcome in HIV-negative child and adults with outcome in HIV-negative child and adults with TBM, but the benefit in HIV infected individuals TBM, but the benefit in HIV infected individuals remains uncertainremains uncertain

CS were effective in reducing the risk of death CS were effective in reducing the risk of death in children (RR,0,77; 95% CI, 0,62 to 0,96)in children (RR,0,77; 95% CI, 0,62 to 0,96)

Corticosteroid…Corticosteroid…

Cochrane Database Syst Rev, 2000;3: CD00224

PrognosisPrognosis

Mortality 10 & 20%Mortality 10 & 20%The prognosis is poor in infants, the elderly, The prognosis is poor in infants, the elderly, when treatment is delayed, and in patients with when treatment is delayed, and in patients with poor nutrition or debilation from HIV infection or poor nutrition or debilation from HIV infection or other chronic disease.other chronic disease.The outcome is clearly associated with the stage The outcome is clearly associated with the stage of the disease at dx and the introduction of early of the disease at dx and the introduction of early treatment. Those who are conscious and without treatment. Those who are conscious and without neurological deficits have a good prognosis; neurological deficits have a good prognosis; those in coma at the beginning of treatment those in coma at the beginning of treatment have 20% mortality and only 20 percent make have 20% mortality and only 20 percent make complete recovery.complete recovery.

I.C.Viral meningitisI.C.Viral meningitis

Viral meningitis Viral meningitis shares clinical features with shares clinical features with bacterial meningitisbacterial meningitis, but patients appear less ill , but patients appear less ill and the disease follows a more benign course.and the disease follows a more benign course.

Headache, often meningismus and photophobia, Headache, often meningismus and photophobia, is often the presenting symptoms.is often the presenting symptoms.

The most pathogens include The most pathogens include herpes simplex-1 herpes simplex-1 (HSV1)(HSV1), mumps, enterovirus, herpes zoster, , mumps, enterovirus, herpes zoster, adenoviruses and Epstein barr virus.adenoviruses and Epstein barr virus.

Dx procedure Viral meningitisDx procedure Viral meningitis

Lumbal PunctureLumbal Puncture

Cells Glucose Protein Smear CSF lactic Cells Glucose Protein Smear CSF lactic

< 500 Normal Mild incr No org < 35 mg/dl< 500 Normal Mild incr No org < 35 mg/dl

MN /mm3MN /mm3 PCRPCR MRI MRI predominant temporal lobe and insular predominant temporal lobe and insular

changes in HSE-1 and basal ganglia lesion in changes in HSE-1 and basal ganglia lesion in japanese encephalitis.japanese encephalitis.

TreatmentTreatment

Aciclovir 10 mg/ kg iv every 8 hours for 10-Aciclovir 10 mg/ kg iv every 8 hours for 10-14 days.14 days.

I. d. FUNGAL MENINGITISI. d. FUNGAL MENINGITIS

ETIOLOGYETIOLOGY Fungi invade of CNS producing meningitis in a small fraction of Fungi invade of CNS producing meningitis in a small fraction of

patients with patients with systemic fungal infection (mycoses)systemic fungal infection (mycoses)

The most pathogens are The most pathogens are Cryptococcus neoformans, Cryptococcus neoformans, Coccidiodes immitis, Candida albicans, Aspergillus, H. Coccidiodes immitis, Candida albicans, Aspergillus, H. Capsulatum, Blastomyces, and MucorCapsulatum, Blastomyces, and Mucor

Mucormycosis and aspergillosis Mucormycosis and aspergillosis usually spreads to the CNS usually spreads to the CNS from infected sinuses and generally cause local inflamation and from infected sinuses and generally cause local inflamation and necrosis rather than a diffuse meningitisnecrosis rather than a diffuse meningitis

Fungi can cause infection in patients with:Fungi can cause infection in patients with: 1. Cancer1. Cancer 2. Receiving corticosteroids2. Receiving corticosteroids 3. Other immunosuppressive drugs3. Other immunosuppressive drugs (Diabetes, malignancy, immunosuppressive (Diabetes, malignancy, immunosuppressive th., or AIDS)th., or AIDS) 4. IV drug abuse.4. IV drug abuse.

Route of entryRoute of entry A. Haematogenous: from the heart, lung, GIT and skinA. Haematogenous: from the heart, lung, GIT and skin B. Direct: from the orbit and paranasal sinuses.B. Direct: from the orbit and paranasal sinuses.

Clinical PictureClinical Picture

Symptoms progress over days, sometimes Symptoms progress over days, sometimes weeks, with headache, nausea, vomiting and weeks, with headache, nausea, vomiting and mild encephalopathy.mild encephalopathy.

Neurologic examination:Neurologic examination:

1. meningeal irritation (+) 5, Visual loss1. meningeal irritation (+) 5, Visual loss

2. papilledema 6. Confusional state 2. papilledema 6. Confusional state

3. Cranial nerve palsies 7. Focal paralysis3. Cranial nerve palsies 7. Focal paralysis

4. Ptosis4. Ptosis

InvestigationsInvestigations

Lab investigations:Lab investigations: 1. Blood culture1. Blood culture 2. Serum glucose 2. Serum glucose 3.Arterial blood gases3.Arterial blood gases 4. Electrolyte4. Electrolyte 5. Liver function test5. Liver function test 6. Urinalysis6. Urinalysis

CSF Examinations:CSF Examinations:ImagingImaging

Invest…..Invest…..

CSF Exam:CSF Exam: - Pressure: Increased- Pressure: Increased - Appearance: varies with organism- Appearance: varies with organism - White Blood cells: 50 – 10.000 (mixed or - White Blood cells: 50 – 10.000 (mixed or lymphocytic).lymphocytic). - Glucose :Normal- Glucose :Normal - Protein: increased- Protein: increased - Cryptoccal antigen is more sensitive- Cryptoccal antigen is more sensitive - Fungal culture of CSF(+)- Fungal culture of CSF(+)

Invest….Invest….

Chest X-ray : Hilar lymphadenopathy, Chest X-ray : Hilar lymphadenopathy, cavitation, effusion.cavitation, effusion.

CT or MRI: mass lesion (Cryptococcus)CT or MRI: mass lesion (Cryptococcus)

TreatmentTreatment

Amphotericin BAmphotericin B

- Protocol, starting with 1 mg/ day- Protocol, starting with 1 mg/ day

- doubling the dose daily until reaching 16 - doubling the dose daily until reaching 16

mg per day, than increasing at increments mg per day, than increasing at increments

of 10 mg until reaching full therapeutic of 10 mg until reaching full therapeutic

dose of 0,5 to 1,5 mg/ kg per day IV.dose of 0,5 to 1,5 mg/ kg per day IV.

2. Myelitis2. Myelitis

Inflamation of the spinal cordInflamation of the spinal cord

I. Transverse Myelitis, I. Transverse Myelitis,

II. Disseminata, II. Disseminata,

III. DifussaIII. Difussa

Transverse myelitis (MYELOPATHY) is a Transverse myelitis (MYELOPATHY) is a syndrome characterized by acute spinal cord syndrome characterized by acute spinal cord dysfunction both halves the cord in transverse dysfunction both halves the cord in transverse section.section.

Myelitis transversalisMyelitis transversalis– inflamasi akut atau sub akut inflamasi akut atau sub akut – mengenai suatu area fokal di medula spinalis mengenai suatu area fokal di medula spinalis – karakteristik klinis disfungsi neurologis pada karakteristik klinis disfungsi neurologis pada

saraf motorik, sensorik dan otonom dan saraf motorik, sensorik dan otonom dan traktus saraf di medula spinalistraktus saraf di medula spinalis

ACUTE TRANSVERSE ACUTE TRANSVERSE MYELITISMYELITIS

IS USUALLY BILATERAL AND TENDS IS USUALLY BILATERAL AND TENDS TO CAUSE MORE SEVERE WEAKNESS TO CAUSE MORE SEVERE WEAKNESS THAN THE TYPICAL ATTACKS OF THAN THE TYPICAL ATTACKS OF PARTIAL MYELITIS.PARTIAL MYELITIS.The condition may be peri infectious or The condition may be peri infectious or postinfectious process and has been postinfectious process and has been associated with many viral infection, associated with many viral infection, including poliovirus, echovirus and including poliovirus, echovirus and coxsackieviruses.coxsackieviruses.

Etiologie Transverse myelitisEtiologie Transverse myelitis

1. Congenital – vascular malformation1. Congenital – vascular malformation2. Infectious – viral infection2. Infectious – viral infection3. Autoimune- peri or post infection or vaccinial myelitis.3. Autoimune- peri or post infection or vaccinial myelitis.4. Multiple sclerosis4. Multiple sclerosis5. Neoplastic5. Neoplastic6. Toxic- secondary to heroin injection6. Toxic- secondary to heroin injection7. Vascular7. Vascular8. Degenerative- irradiation8. Degenerative- irradiation9. Idiopathic.9. Idiopathic.

PATOLOGIPATOLOGI

JHTMC (John Hopkins Transverse Myelitis Center) JHTMC (John Hopkins Transverse Myelitis Center) kondisi inflamasi yang berhubungan dengan mekanisme kondisi inflamasi yang berhubungan dengan mekanisme immune-mediatedimmune-mediated

Pasien myelitis transversalisPasien myelitis transversalis perubahan inflamasi perubahan inflamasi pada medula spinalisnyapada medula spinalisnya

Abnormalitas patologi ( bervariasi )Abnormalitas patologi ( bervariasi )– infiltrasi lokal oleh limfosit dan monosit dalam segmen medula infiltrasi lokal oleh limfosit dan monosit dalam segmen medula

spinalis dan daerah perivaskuler spinalis dan daerah perivaskuler – adanya aktifitas yang bervariasi dari mikroglia dan astrogliaadanya aktifitas yang bervariasi dari mikroglia dan astroglia

Besar dan luasnya gambaran inflamasi Besar dan luasnya gambaran inflamasi faktor etiologi dan profile perubahan faktor etiologi dan profile perubahan myelopati :myelopati :– Myelitis post infeksius Myelitis post infeksius perubahan perubahan white white

mattermatter, demielinasi, gangguan aksonal, demielinasi, gangguan aksonal– myelitis transversalis myelitis transversalis gambaran yang gambaran yang

melibatkan keduanya secara bersamaan melibatkan keduanya secara bersamaan baik baik whitewhite maupun maupun grey mattergrey matter

Viral causes of acute myelitisViral causes of acute myelitis

Herpesvirus: HSV2, Varicella Zoster, Herpesvirus: HSV2, Varicella Zoster, HSV1, Epstein barr, Cytomegalo, human HSV1, Epstein barr, Cytomegalo, human herpes6.herpes6.

Enterovirus: Poliovirus, Enterovirus 70, Enterovirus: Poliovirus, Enterovirus 70, Echovirus, Coxsackievirus.Echovirus, Coxsackievirus.

Arbovirus: west nile virusArbovirus: west nile virus

Other: Mumps, HIV, Dengue.Other: Mumps, HIV, Dengue.

Affinities virus in myelitisAffinities virus in myelitis

EnterovirusEnterovirus anterior horn or nuclei of the anterior horn or nuclei of the brain stembrain stem

Herpes zosterHerpes zoster dorsal root ganglion dorsal root ganglion

Clinical manifestationClinical manifestation

Acute paraplegic or Quadriplegic.Acute paraplegic or Quadriplegic.

Urinary retention.Urinary retention.

Sensory disturbancesSensory disturbances

Diagnostic prosedureDiagnostic prosedure

CSF examination:CSF examination:

- mild to moderate lymphocytic pleocytosis (10-1000 - mild to moderate lymphocytic pleocytosis (10-1000 cell/mm3), elevated protein (100-500 mg/dl), and normal cell/mm3), elevated protein (100-500 mg/dl), and normal or mildly depressed glucose level.or mildly depressed glucose level.

• PCR- virus spesific PCR and antibody titer should be PCR- virus spesific PCR and antibody titer should be performed.performed.

• MRI-T2 weighted shows increased signal intensity MRI-T2 weighted shows increased signal intensity involving gray matter and surronding white matter.involving gray matter and surronding white matter.

DIAGNOSIS BANDING :DIAGNOSIS BANDING :

Multiple sclerosisMultiple sclerosisPenyakit sistemik (SLE, Sjorgen disease)Penyakit sistemik (SLE, Sjorgen disease)Venous infarctVenous infarctMalformasi vaskuler (fistula AV, AVM, angioma Malformasi vaskuler (fistula AV, AVM, angioma kavernosa)kavernosa)Fibrocartilagenous embolismFibrocartilagenous embolismMyelopati radiasiMyelopati radiasi

Treatment Viral myelitisTreatment Viral myelitis

Antiviral treatment:Antiviral treatment:

GlucocorticoidGlucocorticoid

Spasticity: baclofen (lioresal) 10 mg q6h, Spasticity: baclofen (lioresal) 10 mg q6h, benzodiazepin and tizanidine.benzodiazepin and tizanidine.

3. BRAIN ABSCESS Definition3. BRAIN ABSCESS Definition

Brain abscess is Brain abscess is a a focal intracerebral focal intracerebral infectioninfection that begin as a localized area of that begin as a localized area of cerebritiscerebritis and develops into a collection of and develops into a collection of pus pus surrounded by a weil-vascularized surrounded by a weil-vascularized capsule.capsule.Abscess of the brain has been known for Abscess of the brain has been known for over 200 years, and surgical treatment over 200 years, and surgical treatment started with started with MacEwen in 1893 MacEwen in 1893 [published:” [published:” pyogenic infective disease of the Brain”].pyogenic infective disease of the Brain”].

Parenchymal brain infection can arise from Parenchymal brain infection can arise from hematogenous delivery of infected material, hematogenous delivery of infected material, which often results in multiple abscess. which often results in multiple abscess. Especially at risk are patients with congenital Especially at risk are patients with congenital heart disease or valve infection.heart disease or valve infection.Pathogenesis: abscess begin with local Pathogenesis: abscess begin with local cerebritis, causing necrosis and surronding cerebritis, causing necrosis and surronding edema.edema.Epidemiology: Epidemiology: 0,3 – 1,3 per 100.000 / tahun0,3 – 1,3 per 100.000 / tahunMale to female ratio of 2:1 to 3:1Male to female ratio of 2:1 to 3:1

Common etiologic factorsCommon etiologic factorsCommon etiologic factors Distingushing

characteristics

Middle ear,paranasal sinus, or mastoid infection

Ear inf: temporal lobe abscess, sinus inf: frontal lobe abscess, mastoid inf: cerebellar abscess

Metastatic embolic from lung, pulmonary abscess, bronchietasis, or chronic empyema

Multiple abscess

Head trauma or Neurosurg. Gunshot wounds are the most common head trauma assc. With abscess

Endocarditis Drug abuser

Rare cause: dental procedures, Metastatic emboli from abdominal inf. Or PID, osteomyelitis of skull

-

Common etiologic factors Microorgnism involved

Aerobes Anaerob

Middle ear,paranasal sinus, or mastoid infection

Streptococci, Streptococci

Staph aureus Bacteriodes

Metastatic embolic from lung, pulmonary abscess, bronchietasis, or chronic empyema

Staph aureus, Klebsiela Streptococci,

S.Pneumoniae Fusobacteria

Head trauma or Neurosurg.

Staph aureus, streptococci

Pseudomonas

Endocarditis Staph aureus -

Rare cause: dental procedures, Metastatic emboli from abdominal inf. Or PID, osteomyelitis of skull

-

Neuropatologi (4 stages)Neuropatologi (4 stages)

1.1. Early Early cerebritiscerebritis ( days 1-3) ( days 1-3) infection of the brain with surronding white matter edema.infection of the brain with surronding white matter edema.2.2. Late cerebritis ( days 4-9)Late cerebritis ( days 4-9) The core of the cerebritis becomes The core of the cerebritis becomes necrotic and enlargesnecrotic and enlarges

and capsular fibroblasts begin to form.and capsular fibroblasts begin to form.3. 3. Early capsule formation ( days10-13)Early capsule formation ( days10-13) The The capsule is well developedcapsule is well developed, with proliferation of , with proliferation of

fibroblasts, a surronding astrocytic proliferation, and fibroblasts, a surronding astrocytic proliferation, and edemaedema

4. 4. Late capsule formation (days 14 or more).Late capsule formation (days 14 or more). A mature, thick capsule surronds the central cavity A mature, thick capsule surronds the central cavity

containing debris and PMN cells. There is usually marked containing debris and PMN cells. There is usually marked cerebral edema in the surronding brain tissue in the cerebral edema in the surronding brain tissue in the presence of a presence of a mature abscess.mature abscess.

Gejala dan tanda klinis:Gejala dan tanda klinis:

Sakit kepala (70-90%)Sakit kepala (70-90%)

Muntah (25-50%)Muntah (25-50%)

Kejang(30-50%)Kejang(30-50%)

Gejala pusing, vertigo, ataksia ( pd abses Gejala pusing, vertigo, ataksia ( pd abses cerebelli)cerebelli)

Ggn bicara (19,6%), hemianopsia (31%), Ggn bicara (19,6%), hemianopsia (31%), unilateral midriasis (20,5%)unilateral midriasis (20,5%)

Gejala fokal (61%) pd penderita abses Gejala fokal (61%) pd penderita abses supratentorial.supratentorial.

Pemeriksaan utk Diagnosa:Pemeriksaan utk Diagnosa:

Glasgow coma scale : utk kesadaran Glasgow coma scale : utk kesadaran penderitapenderita

Rontgen foto kepala, sinus, mastoid, thoraks.Rontgen foto kepala, sinus, mastoid, thoraks.

EEGEEG

CT Scan/ MRICT Scan/ MRI

Angiografi : utk menentulan lokasi abses Angiografi : utk menentulan lokasi abses (24%).(24%).

Lab: jlh leukosit 10.000-20.000/ cm3 (60-Lab: jlh leukosit 10.000-20.000/ cm3 (60-70%)70%)

LED meningkat 45 mm/jam (75-90%).LED meningkat 45 mm/jam (75-90%).

Head Ct SanHead Ct San

A. Multiple brain abscesses associated with bacterial endocarditis (Staphylococcus aureus) in a55-year-old man. The large abscess in the left hemisphere shows a characteristic ring enhancement.

B. ContrastenhancedCT scan 4 months after institution of antibiotic treatment. The abscesses have resolved.

A B

Komplikasi Abses OtakKomplikasi Abses Otak

Robeknya kapsul abses kedalam Robeknya kapsul abses kedalam ventrikel atau keruangan ventrikel atau keruangan subarakhnoid.subarakhnoid.

Penyumbatan cairan serebrospinal Penyumbatan cairan serebrospinal hidrosefalushidrosefalus

Edema otakEdema otak

Herniasi tentorial oleh massa abses Herniasi tentorial oleh massa abses otak.otak.

7676

Pengobatan abses otakPengobatan abses otakKonservatif:Konservatif:

- - Pemberian AB yg tepat : 6-8 mgg Pemberian AB yg tepat : 6-8 mgg mengecilkan mengecilkan abses.abses.

-- Prinsip pemberian AB: bakterisid thdp organisme Prinsip pemberian AB: bakterisid thdp organisme hasil hasil kultur, dapat melewati BBB.kultur, dapat melewati BBB.

- Pemberian kortikosteroid:- Pemberian kortikosteroid: dewasa : loading dose 10-12 mg secara IVdewasa : loading dose 10-12 mg secara IV maintenance dose 4 mg secara IV setiap 6 maintenance dose 4 mg secara IV setiap 6

jamjam anak : loading dose 10-12 mg/kg anak : loading dose 10-12 mg/kg

diberikan satu kali IVdiberikan satu kali IV maintenance dose 1-1,5 mg/kg/hari IVmaintenance dose 1-1,5 mg/kg/hari IV - Pemberian antikonvulsan- Pemberian antikonvulsan

Operatif: Aspirasi dan eksisi.Operatif: Aspirasi dan eksisi. konsul Bedah Saraf , konsul Bedah Saraf , jika terapi konservatif gagal.jika terapi konservatif gagal.

Antibiotic treatment for brain Antibiotic treatment for brain abscessabscess

Ear, mastoid, sinus

Streptococcal species, Ps anaerobes, Enterobaceteriacea

Metronidazole 7.5 mg IV every 6 h + Cefepime 2 gr IV every 6 h or meropenem 2gr IV every 8 h

Lung S. pneumoniae Same as above

AB treatmentAB treatmentTeeth, mouth Anaerobic

streptococci, Eikenella, Prevotella, Actinomyces

Metro 7,5 mg/kg IV every 12 h + PNC G 4million units IV every 4 h or ceftizoxime 3 gr IV every 6 h

Post operative infection, furuncles or decubiti

Staphiloc Cefepime 2 gr IV every 8 h, or Nafcillin or oxacillin 2 g IV every 4 h

4. Defenition Viral encephalitis4. Defenition Viral encephalitis

Is an acute febrile illness with evidence of Is an acute febrile illness with evidence of damage to the parenchymal tissue of the CNS, damage to the parenchymal tissue of the CNS, producing producing alteration of consciousness, focal alteration of consciousness, focal neurological signs and seizuresneurological signs and seizures..Etiology:viral infection of the nervous system,Etiology:viral infection of the nervous system,– Herpes simpleksHerpes simpleks– Eastern equineEastern equine– Venezuela St LouisVenezuela St Louis– Japanese – B Japanese – B – Russian tick-borneRussian tick-borne – RabiesRabies

Etiology viral encephalitisEtiology viral encephalitis

Viral is the most common causeViral is the most common causeThe commonest is HSV type I in adults The commonest is HSV type I in adults

and type 2 in neonates.and type 2 in neonates.It may occur sporadically or in epidemicsIt may occur sporadically or in epidemics50-70% mortality if untreated50-70% mortality if untreatedSo establishment of on early specific So establishment of on early specific

diagnosis and early initiation of antiviral diagnosis and early initiation of antiviral chemotherapy is of great importancechemotherapy is of great importance

2/3 of cases involve patients over 40 yo.2/3 of cases involve patients over 40 yo.

Patogenesis.Patogenesis.

Bila virus patogen masuk kedalam tubuhBila virus patogen masuk kedalam tubuh

pada SSP dapat terjadi:pada SSP dapat terjadi:

Radang akutRadang akut

Radang kronisRadang kronis

NeoplasmaNeoplasma

Virus hidup dalam keadaan latenVirus hidup dalam keadaan laten

Cara penyebaran ke SSP:Cara penyebaran ke SSP:Cara penyebaran Contoh virusCara penyebaran Contoh virus

Hematogen herpes simplexHematogen herpes simplex sitomegalovirussitomegalovirus Epstein-BarrEpstein-Barr CoxsackieCoxsackie HIVHIV MorbilliMorbilli EchovirusEchovirus khoriomeningitis limfositikkhoriomeningitis limfositik paravirus paravirus

Neurogen Herpes simpleksNeurogen Herpes simpleks

B-virusB-virus

Varisela-ZosterVarisela-Zoster

RabiesRabies

Gambaran klinik:Gambaran klinik:

Tanda dan gejala bervariasi tergantung Tanda dan gejala bervariasi tergantung virus penyebab.virus penyebab.Umumnya: demam akut disertai tanda rang- Umumnya: demam akut disertai tanda rang- sang meningeal, sakit kepala, mual, fotofobi, sang meningeal, sakit kepala, mual, fotofobi, muntah, ggn kesadaran, defisit neurologik muntah, ggn kesadaran, defisit neurologik fokal dan kejang2.fokal dan kejang2.Mortalitas bervariasi dari tinggi (eastern Mortalitas bervariasi dari tinggi (eastern equine encephalitis) sampai rendah (Vene- equine encephalitis) sampai rendah (Vene- zuelan equine encephalitis).zuelan equine encephalitis).

Gejala sisa termasuk kejang2Gejala sisa termasuk kejang2

Komplikasi : - perubahan kepribadianKomplikasi : - perubahan kepribadian

- ggn ekstrapiramidal- ggn ekstrapiramidal

- demensia- demensia

- ggn motorik - sensorik- ggn motorik - sensorik

Kriteria diagnosis ensefalitis viralKriteria diagnosis ensefalitis viral

1.1. Bentuk asimptomatik Bentuk asimptomatik analisis LP analisis LP2.2. Bentuk abortif : Nyeri kepala, demam yg tdk Bentuk abortif : Nyeri kepala, demam yg tdk

tinggi, kaku kuduk. ISPA/ Infeksi GITtinggi, kaku kuduk. ISPA/ Infeksi GIT3.3. Bentuk fulminan: Berlangsung bbrp jam Bentuk fulminan: Berlangsung bbrp jam

sampai dengan beberapa hari yg berakhir sampai dengan beberapa hari yg berakhir dengan kematian.dengan kematian.

4.4. Bentuk khas ensefalitis: NK, demam, Bentuk khas ensefalitis: NK, demam, keasadaran menurun, kejang fokal atau keasadaran menurun, kejang fokal atau umum, hemiparesis, ggn koordinasi, umum, hemiparesis, ggn koordinasi, disorientasi, ggn bicara, ggn mentaldisorientasi, ggn bicara, ggn mental

Prosedur diagnostik.Prosedur diagnostik.LP : CSF jernih, tekanan normal atau LP : CSF jernih, tekanan normal atau meningkat, Pleositosis limfositik < 1000/ul, meningkat, Pleositosis limfositik < 1000/ul, glukosa dan klorida nornal, protein normal glukosa dan klorida nornal, protein normal atau sedikit meninggi ( 80-200 mg/dlatau sedikit meninggi ( 80-200 mg/dlMRI atau CT scan MRI atau CT scan SOL (?) SOL (?)EEGEEGLiquor Liquor virus DNA dg “polymerase chain virus DNA dg “polymerase chain reaction” (prosedur cepat, sensitif, akurat)reaction” (prosedur cepat, sensitif, akurat)Virus kadang2 dikultur dari liquor,feces,urine Virus kadang2 dikultur dari liquor,feces,urine nasofaring atau darah.nasofaring atau darah.Titer antibodi thd virus tertentu.Titer antibodi thd virus tertentu.

Pengobatan.Pengobatan.

Tidak bisa diidentifikasi Tidak bisa diidentifikasi dianggap dianggap sebagai ensefalitis herpes simpleks dan sebagai ensefalitis herpes simpleks dan terapi dgn. Acyclovir atau ganciclovirterapi dgn. Acyclovir atau ganciclovir

Jalan nafas diawasiJalan nafas diawasi

Keseimbangan cairan dan elektrolit dijagaKeseimbangan cairan dan elektrolit dijaga

Atasi kejangAtasi kejang

Atasi peninggian ICP Atasi peninggian ICP

Spektrum NeuroAIDSSpektrum NeuroAIDS

Primary complicationPrimary complication (non- (non-opportunistic disease)opportunistic disease)– HIV-DementiaHIV-Dementia– HIV-Sensory neuropathyHIV-Sensory neuropathySecondary complicationSecondary complication (opportunistic disease)(opportunistic disease)– Cerebral Toxoplasmosis Cerebral Toxoplasmosis – TB Meningitis / tuberculomaTB Meningitis / tuberculoma– Cryptococcal meningitisCryptococcal meningitis– Other opportunistic diseases....Other opportunistic diseases....

Perjalanan penyakit infeksi HIVPerjalanan penyakit infeksi HIV

Infeksi virus (2-3 minggu) Infeksi virus (2-3 minggu) sindroma retro- sindroma retro- viral akut (2-3 minggu) viral akut (2-3 minggu) gejala menghilang gejala menghilang + serokonversi + serokonversi infeksi kronis HIV asimpto infeksi kronis HIV asimpto matik (rata2 8 thn) matik (rata2 8 thn) infeksi HIV / AIDS infeksi HIV / AIDS simptomatik (rata2 1,3 thn) simptomatik (rata2 1,3 thn) kematian. kematian.Window period Window period masa dimana pemeriksa- masa dimana pemeriksa- an test serologis utk antibodi HIV masih an test serologis utk antibodi HIV masih negatif, tapi virus sdh ada dlm darah (sudah negatif, tapi virus sdh ada dlm darah (sudah mampu menularkan kpd orang lain)mampu menularkan kpd orang lain)

HIV dementia HIV dementia (AIDS Dementia Complex)(AIDS Dementia Complex)

This progressive dementia occurs in AIDS, This progressive dementia occurs in AIDS, owing to a direct primary HIV infection of owing to a direct primary HIV infection of neurons or an indirect neurotoxicity neurons or an indirect neurotoxicity induced by presence of the virus in the induced by presence of the virus in the brainbrain

Pathology: the virus may be transported Pathology: the virus may be transported into the brain by infected peripheral into the brain by infected peripheral monocytes (Trojan horse theory).monocytes (Trojan horse theory).

Manifestasi klinis demensia HIVManifestasi klinis demensia HIV::Cognititive disordersCognititive disorders

Gangguan kognitif, kesulitan konsentrasi, Gangguan kognitif, kesulitan konsentrasi, forgetfullness, cognitive slowing. Kadang2 forgetfullness, cognitive slowing. Kadang2 agitasi, mania. agitasi, mania. Pd std awal sulit membedakan dgn keluhan Pd std awal sulit membedakan dgn keluhan psikiatri.psikiatri.

Motor abnormalities: Motor abnormalities: ataksia, hiperreflels. ataksia, hiperreflels. Babinski refleks srg muncul. Pada std lanjut : Babinski refleks srg muncul. Pada std lanjut : paraparese dgn inkontinansia urin et alviiparaparese dgn inkontinansia urin et alvii

Behavioural dysfunction : ABehavioural dysfunction : Apathy, altered pathy, altered personality, disorientasi. Std akhir personality, disorientasi. Std akhir MutismMutism

CEREBRAL TOXOPLASMOSISCEREBRAL TOXOPLASMOSIS

Reactivation of latent infectionReactivation of latent infectionToxo seroprevalence 12-46% (SA)Toxo seroprevalence 12-46% (SA)IgG indicates post infection IgG indicates post infection (FN <3-6%)(FN <3-6%)

CD4 > 200 virtually excludes ToxoCD4 > 200 virtually excludes ToxoOver 80% have CD4 < 100Over 80% have CD4 < 100

Typically multiple ring enhancing lesions on CT/MRITypically multiple ring enhancing lesions on CT/MRI27-43% have single lesions27-43% have single lesionsUp to 10% may have diffuse encephalitis without any Up to 10% may have diffuse encephalitis without any visible focal lesionsvisible focal lesions

The course of HIV/AIDS

Notes:

Toxoplasmosis – Clinical FeaturesToxoplasmosis – Clinical Features

Usually subacute over weeksUsually subacute over weeks

Headache Headache 50%50%Fever Fever 45%45%Behaviour changes Behaviour changes 40%40%Confusion Confusion 15-52%15-52%Focal signsFocal signsSeizures Seizures 24-29%24-29%

TREATMENTTREATMENT

Acute treatment : 3-6 weeks.Acute treatment : 3-6 weeks.– Induction : pyrimethamine 200 mg Induction : pyrimethamine 200 mg – First line :First line :

Pyrimethamin 75-100 mg/day + sulfadiazine + Pyrimethamin 75-100 mg/day + sulfadiazine + folinic acid orfolinic acid orPyrimethamin + clindamycin + folinic acid.Pyrimethamin + clindamycin + folinic acid.

– Second line :Second line :Azithromycin, clarithromycin, or atovaquone can Azithromycin, clarithromycin, or atovaquone can substitute for sulfadiazine.substitute for sulfadiazine.

– Glucocorticoid Glucocorticoid life threatening condition. life threatening condition.

TREATMENTTREATMENT

Maintenance : Maintenance : – Until the immune system has sufficiently Until the immune system has sufficiently

reconstituted.reconstituted.– Pyrimethamine and sulfadiazine orPyrimethamine and sulfadiazine or– Pyrimethamine and clindamycin.Pyrimethamine and clindamycin.

Stop :Stop :– Asymptomatik.Asymptomatik.– CD4+ > 200/cmm until 6 months.CD4+ > 200/cmm until 6 months.

CT - Multiple ring enhancing lesionsCT - Multiple ring enhancing lesions

Toxo more likelyToxo more likely

Tuberculomas still Tuberculomas still possiblepossible

Differential DiagnosisDifferential Diagnosis

ToxoplasmosisToxoplasmosis P CNS LP CNS LLocationLocation Basal ganglia.Basal ganglia.

Gray-white junctionGray-white junction

PeriventricularPeriventricular

Number of lesionNumber of lesion MultipleMultiple Solitary>multipleSolitary>multiple

Enhancement patternEnhancement pattern RingRing Heterogeneous or Heterogeneous or homogeneous.homogeneous.

EdemaEdema Moderate to markedModerate to marked VariableVariable

T2-weighted image T2-weighted image (lesion relative to (lesion relative to white matter)white matter)

HyperintenseHyperintense Isointense to Isointense to hyperintense.hyperintense.

Diffusion-weighted Diffusion-weighted imageimage

Usually hypointenseUsually hypointense Often hyperintense Often hyperintense (positive)(positive)

Differential DiagnosisDifferential Diagnosis

ToxoplasmosisToxoplasmosis P CNS LP CNS L

MR perfusionMR perfusion DecreasedDecreased IncreasedIncreased

MR spectroscopyMR spectroscopy Markedly elevated Markedly elevated lactate.lactate.

Markedly elevated Markedly elevated cholinecholine

SPECT thallium SPECT thallium (lesion relative to (lesion relative to white matter)white matter)

““Cold”-no thallium Cold”-no thallium uptakeuptake

““Hot”-increased Hot”-increased thallium uptake.thallium uptake.

OtherOther Toxoplasma IgG Ab Toxoplasma IgG Ab (+) (90% of patients)(+) (90% of patients)

EBV DNA amplified EBV DNA amplified by PCR in CSF by PCR in CSF (most patients)(most patients)

5. Definisi Malaria Serebral 5. Definisi Malaria Serebral (MS)(MS)

MS adalah malaria dengan penurunan MS adalah malaria dengan penurunan kesadaran kesadaran ( dewasa GCS < 9 dan anak ( dewasa GCS < 9 dan anak

Blantyre coma score < 3) atau koma lebih dari Blantyre coma score < 3) atau koma lebih dari 30 menit setelah serangan kejang yg tidak 30 menit setelah serangan kejang yg tidak disebabkan oleh penyakit lain.disebabkan oleh penyakit lain.

MS MS komplikasi dari malaria falcifarum berat, komplikasi dari malaria falcifarum berat, dijumpai st ensefalopati difus dengan penurunan dijumpai st ensefalopati difus dengan penurunan kesadaran dan berhubungan dengan kesadaran dan berhubungan dengan sequestrasi mikrovaskuler serebral.sequestrasi mikrovaskuler serebral.

Blantyre coma scale(0-7)Blantyre coma scale(0-7)

Oculer responseOculer response - Follow mother’s facial reaction …1- Follow mother’s facial reaction …1 - non reaction ……………………0- non reaction ……………………0

Verbal responseVerbal response - Normal crying ……………………2- Normal crying ……………………2 - Whimpering ………………………1- Whimpering ………………………1 - no sound ……………………….. 0- no sound ……………………….. 0

Motoric responseMotoric response - Localize pain ……………………2- Localize pain ……………………2 - rettraction of limb ……………..1- rettraction of limb ……………..1 - non reaction ……………………0- non reaction ……………………0

Plasmodium falcifarumPlasmodium falcifarummorphology in stained preparationmorphology in stained preparation

Ring formRing form: vary in : vary in shape; double shape; double chromatin, double chromatin, double infection, accoleinfection, accole

TrophozoitTrophozoit: rare in : rare in peripheral blood peripheral blood after half grownafter half grown

Plasmodium falciparumPlasmodium falciparumMorphology of all stadiumsMorphology of all stadiums

PatogenesePatogenese

Ada 3 teori:Ada 3 teori: 1. Teori mekanis :1. Teori mekanis : tjdnya penyumbatan pemb drh otak akibat tjdnya penyumbatan pemb drh otak akibat tjdnya sitoadherens, sekuester, rosetting dan tjdnya sitoadherens, sekuester, rosetting dan faktor rheologi.faktor rheologi. 2. Teori Toksik 2. Teori Toksik menghasilkan TNF menghasilkan TNF 3. Teori Permeabilitas: tjdnya adhesi parasit pd 3. Teori Permeabilitas: tjdnya adhesi parasit pd

endothel, vasculer serta banyak faktor toksik yg endothel, vasculer serta banyak faktor toksik yg lepas serta radikal bebas terutama Nitric oxide lepas serta radikal bebas terutama Nitric oxide (NO).(NO).

Diagnosa Malaria SerebralDiagnosa Malaria Serebral

Gjl Klinik : Trias malaria ( demam, menggigil, dan Gjl Klinik : Trias malaria ( demam, menggigil, dan berkeringat), Sakit kepala, ggn mental, nyeri berkeringat), Sakit kepala, ggn mental, nyeri tengkuk, kaku otot dan kejang umumtengkuk, kaku otot dan kejang umumSering dijumpai splenomegali dan hepatomegaliSering dijumpai splenomegali dan hepatomegaliGgn kesadaran atau koma ( biasanya 24-72 jam)Ggn kesadaran atau koma ( biasanya 24-72 jam)Pemr darah (thin/thick smear) dijumpai bentuk Pemr darah (thin/thick smear) dijumpai bentuk aseksual P. Falcifarumaseksual P. FalcifarumTidak ditemukan infeksi lainTidak ditemukan infeksi lainLain-lain:hipoglicaemia, hiponatremia, Lain-lain:hipoglicaemia, hiponatremia, hipofosfatemia, pleocytosis sampai 80 cel/ micron hipofosfatemia, pleocytosis sampai 80 cel/ micron kubik, limfosit sampai 15 cel/ mikron kubikkubik, limfosit sampai 15 cel/ mikron kubikCT/ MRI: edema serebri.CT/ MRI: edema serebri.

LaboratoriumLaboratorium

Pemeriksaan dengan mikroskopPemeriksaan dengan mikroskop - sediaan darah tebal dan tipis- sediaan darah tebal dan tipis

Test diagnostik lainTest diagnostik lain - Metode immunokromatografi- Metode immunokromatografi - Analisa cairan Serebrospinal- Analisa cairan Serebrospinal pd pd Malaria serebral didapti peningkatan Malaria serebral didapti peningkatan limfosit > 15/ul.limfosit > 15/ul. - CT dan MRI: edema serebral- CT dan MRI: edema serebral

Pengobatan Malaria Tanpa KomplikasiPengobatan Malaria Tanpa Komplikasi

Malaria FalsiparumMalaria Falsiparum

Lini pertama Lini pertama = Artesunat + Amodiakuin + Primakuin= Artesunat + Amodiakuin + Primakuin

Lini kedua Lini kedua = Kina + Doksisiklin atau Tetrasiklin + Primakuin= Kina + Doksisiklin atau Tetrasiklin + Primakuin

Pengobatan lini kedua diberikan jika Pengobatan lini kedua diberikan jika

pengobatan lini pertama tidakpengobatan lini pertama tidak efektif,efektif, dimana 28 hari setelah dimana 28 hari setelah

pemberian obat :pemberian obat :

Gejala klinis memburuk dan parasit aseksual positif, atauGejala klinis memburuk dan parasit aseksual positif, atau

Gejala klinis tidak memburuk tetapi parasit aseksual tidak Gejala klinis tidak memburuk tetapi parasit aseksual tidak

berkurang (persisten) atau timbul kembali (rekurensi)berkurang (persisten) atau timbul kembali (rekurensi)

6. Neurocisticercosis6. Neurocisticercosis

Def: Def: cysticercosis cellulosacysticercosis cellulosa is the larval is the larval stage of development of the cestode stage of development of the cestode Taenia soliumTaenia solium (pork tapeworm). (pork tapeworm).

More than 60 million people are infected More than 60 million people are infected with with T. saginataT. saginata world wide and about 4 world wide and about 4 million are infected with million are infected with T. soliumT. solium

Life cycleLife cycle

In IndonesiaIn Indonesia

North Sumatra

Lampung

Jakarta

Bali Flores

East Timor

Irian Jaya

North SulawesiWest Kalimantan

Fig. I. Geographic distribution of in Indonesia until 1995. Areas endemic with taeniasis are indicated in colour.( Modified from the unpublished report CDC & EH. Ministry of Health, Indonesia, 1983 – 1996 )

Pathology :3 Form cysticercosis in Pathology :3 Form cysticercosis in CNSCNS

1. A cystic form involving the 1. A cystic form involving the ventricles and brain parenchymaventricles and brain parenchyma

2. A racemose form involving the 2. A racemose form involving the meningesmeninges

3. A miliary form that is common in 3. A miliary form that is common in childrenchildren

PATOGENESISPATOGENESIS

Human NCC : ingest food contaminated Human NCC : ingest food contaminated with with T.soliumT.solium egg egg

Parasite survive over period of yearParasite survive over period of year

It secretes protease inhibitor, taeniastatin It secretes protease inhibitor, taeniastatin that inhibit complement activation, that inhibit complement activation, neutrophyl, lymphocyte and cytokine neutrophyl, lymphocyte and cytokine production.production.

Minimal inflammation around viable cystMinimal inflammation around viable cyst

Inflammatory respons attacks the parasite, Inflammatory respons attacks the parasite, leads to degeneration and calcificationleads to degeneration and calcification

CLINICAL MANIFESTATION

Number of the cysts

Location (parenchimal/spinal)

Parasite activity

Immune respons of the host

DIAGNOSISDIAGNOSIS

Definitive Definitive

Present of the scolex on Present of the scolex on histologic examination or on CT histologic examination or on CT scan/MRIscan/MRI

MRIMRI

More sensitif for detect More sensitif for detect parenchymal cyst, parenchymal cyst, intraventricular and intraventricular and subarachnoid cystsubarachnoid cyst

MANAGEMENT NCCMANAGEMENT NCC

Anti parasitic drugAnti parasitic drug

Symptomatic and anti-inflamatorySymptomatic and anti-inflamatory

SurgerySurgery

ANTI PARASITIC DRUGANTI PARASITIC DRUG

Praziquantel : Praziquantel :

50mg/kg/day, two weeks.50mg/kg/day, two weeks.

Albendazol : Albendazol :

15mg/kg/day, one month.15mg/kg/day, one month.

SYMPTOMATIC/SYMPTOMATIC/

ANTIINFLAMMATIONANTIINFLAMMATION

Corticosteroid :Corticosteroid :

Dexamethasone 4,5 – 12 mg/day, Dexamethasone 4,5 – 12 mg/day, oror

Prednisone 1mg/kg/day.Prednisone 1mg/kg/day.Decrease neurological symptoms Decrease neurological symptoms

due to due to the death of the parasitethe death of the parasite..Manitol 2g/kg/day, for acute intracranial Manitol 2g/kg/day, for acute intracranial

hypertension.hypertension.

First line antiepilepticFirst line antiepileptic

SURGERYSURGERY

For excision of large cysts or cyst For excision of large cysts or cyst in the ventriclesin the ventricles