INFECTIONS OF THE INFECTIONS OF THE CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM

Dr. Kiking Ritarwan, SpS(K), MKTDr. Kiking Ritarwan, SpS(K), MKT

Departement of Neurology Medical Departement of Neurology Medical Faculty of University of Sumatera UtaraFaculty of University of Sumatera Utara

CNS INFECTIONCNS INFECTIONMENINGITISMENINGITIS

- 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.

ENCEPHALITIS VIRALENCEPHALITIS VIRALMYELITISMYELITISABSCESS CEREBRIABSCESS CEREBRICEREBRAL MALARIACEREBRAL MALARIANCCNCC

ANATOMI MENINGSANATOMI MENINGS

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 pyogenic meningitisMany org. can produce pyogenic meningitisIt 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.

Tuberculous meningitisTuberculous meningitisThe 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 (TBM)TB meningitis (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 Mycobacterium tuberculosis.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%

3% of All Deaths in Developed 3% of All Deaths in Developed Countries Are Due to TuberculosisCountries Are Due to Tuberculosis

HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome.

OtherOther27%27%

Cancer Cancer 12%12%

StrokeStroke10%10%

InjuryInjury9%9%

Respiratory tractRespiratory tractinfection 7%infection 7%

HIV/AIDS 5%HIV/AIDS 5%

Chronic obstructive Chronic obstructive pulmonary disease 5%pulmonary disease 5%

Perinatal causes

Diarrheal diseaseTuberculosis

3%3%3%3%4%4%

2%2%

Malaria

Coronary heartCoronary heartdiseasedisease

13%13%

Adapted with permission from MacKay J, Mensah GA. The Atlas of Heart Disease and Stroke. Available at: http://www.who.int/cardiovascular_diseases/en/cvd_atlas_16_death_from_stroke.pdf Accessed February 27, 2006.

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 UVMati dgn pemanasan & sinar UV

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

Size :0,3-,0,6 to 1-4 umSize :0,3-,0,6 to 1-4 um

Shape: Shape: Rods, straight or Rods, straight or slightly curved, occurring slightly curved, occurring singly or in occasional singly or in occasional threads threads

Temperature: 33-39Temperature: 33-39oo C C

pH 6,6-6,8pH 6,6-6,8

PATHOLOGYPATHOLOGY

Aerosol transmission of TuberculosisAerosol transmission of Tuberculosis Tuberculosis is spread by droplet nuclei which are expelled when a person with infectious TB coughs, sneezes, speaks, or sings

PathologyPathologyTBM is always secondary to TB elsewhere in the TBM is always secondary to TB elsewhere in the body. The primary focus of infection is usually in the body. The primary focus of infection is usually in the lungs but may be in the lymph glands, bones, nasal lungs but may be in the lymph glands, bones, nasal sinuses, GIT, or any organ in the body.sinuses, GIT, or any organ in the body.

The bacilli usually enter the body by The bacilli usually enter the body by inhalationinhalation. . Transmission through the skin or by ingestion are rare Transmission through the skin or by ingestion are rare cause of infection.cause of infection.

The organisms undergo The organisms undergo multiflication and multiflication and hematogenous disseminationhematogenous dissemination and it is during this and it is during this stage that the meninges are most likely to become stage that the meninges are most likely to become involved.involved.

Cell mediated immunityCell mediated immunity with migration of with migration of macrophages at the site of infection leads macrophages at the site of infection leads to the development of tubercles.to the development of tubercles.

When the immune response fails, the When the immune response fails, the subarachnoid space is infected by rupture subarachnoid space is infected by rupture of meningel tuberclesof meningel tubercles followed by release followed by release of bacilli and the development of of bacilli and the development of meningitis.meningitis.

The presence of bacilli in the subarachnoid space is The presence of bacilli in the subarachnoid space is followed by followed by an intense granulomatous inflamation of an intense granulomatous inflamation of the leptomeninges and subjacent cortex.the leptomeninges and subjacent cortex.

A thick, heavy fibrous and necrotic exudateA thick, heavy fibrous and necrotic exudate is is produced, which tends to collect at the produced, which tends to collect at the base of the base of the brain.brain.

The arteries at the base of the brain are involved, and The arteries at the base of the brain are involved, and there is inflamation of the adventitia and media, with there is inflamation of the adventitia and media, with narrowing and thrombosis of the lumen.narrowing and thrombosis of the lumen.CN II and III, occasionally CN VII, VIII, are subject to CN II and III, occasionally CN VII, VIII, are subject to compression by the heavy exudate.compression by the heavy exudate.

Clinical features TBMClinical features TBM

The disease occurs in all ages, but the incidence The disease occurs in all ages, but the incidence is higher in infants, young children, and the is higher in infants, young children, and the aged. It is more common amomg the aged. It is more common amomg the undernourished and in those areas of the world undernourished and in those areas of the world characterized by characterized by poor hygiene and poor hygiene and overcrowdingovercrowding..

History of contact with an infected individual or a History of contact with an infected individual or a history previous active tuberculosis in history previous active tuberculosis in 30 to 50 30 to 50 percent of patients.percent of patients.

Clinical staging of patients with Clinical staging of patients with TBMTBM

(terminus/ advance)

The course of the illness depends:The course of the illness depends:

- on the extend of meningeal involvement,- on the extend of meningeal involvement,

- the immune response of the host,- the immune response of the host,

- the virulence of the organism,- the virulence of the organism,

- and the stage at which treatment is - and the stage at which treatment is

administered.administered.

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.

Differential DXDifferential DX

Viral encephalitisViral encephalitis

Partially treated pyogenic meningitisPartially treated pyogenic meningitis

Fungal infectionFungal infection

Other inflammatory disordersOther inflammatory disorders

The presence of active TB elsewhere, and The presence of active TB elsewhere, and the results of CSF examination are usually the results of CSF examination are usually sufficient to establish the dx.sufficient to establish the dx.

Diagnostic ProseduresDiagnostic Prosedures

1. Lumbal Puncture1. Lumbal Puncture

CSF Parameter TB meningitisCSF Parameter TB meningitis• WBC Count < 500/ ul, MNWBC Count < 500/ ul, MN• Gluco moderate or marked decreaseGluco moderate or marked decrease• Protein marke increseProtein marke increse• Gram stain + +.-Gram stain + +.-• CSF lactic acid > 35 mg/dl.CSF lactic acid > 35 mg/dl.

2. Laju endap Darah2. Laju endap Darah3. Radiologic3. Radiologic

3a. Chest x ray: detect pulmonary involvement3a. Chest x ray: detect pulmonary involvement 3b. CT scan8 3b. CT scan8 enhancement of the enhancement of the basal cistern.basal cistern. 3b. MRI are more sensitive than CT 3b. MRI are more sensitive than CT sans in detecting basal meningitis sans in detecting basal meningitis infarction owing to arteritis hydrocephalus infarction owing to arteritis hydrocephalus and parenchymal tuberculomas often in and parenchymal tuberculomas often in combination in AIDS patient.combination in AIDS patient. 4. Arteriografi4. Arteriografi

Images of CT ScansImages of CT Scans

file 1:  file 1:  Contrast-Contrast-enhanced computed enhanced computed tomography (CT) scan in tomography (CT) scan in a patient with a patient with tuberculous meningitis tuberculous meningitis demonstrating marked demonstrating marked enhancement in the enhancement in the basal cistern and basal cistern and meninges, with dilatation meninges, with dilatation of the ventricles.of the ventricles.

file 2:  file 2:  Petechial Petechial hemorrhages in the hemorrhages in the subcortical white matter of subcortical white matter of the brain as a result of the brain as a result of tuberculous meningitis–tuberculous meningitis–associated vasculitis.associated vasculitis.

file 3:  file 3:  Extensive infarcts of Extensive infarcts of the right basal ganglia and the right basal ganglia and internal capsule after the internal capsule after the appearance of vasculitis in appearance of vasculitis in the thalamoperforating the thalamoperforating arteries in a child treated for arteries in a child treated for tuberculous meningitis.tuberculous meningitis.

TreatmentTreatment1. Combination of antituberculous drug1. Combination of antituberculous drug

Therapy WHO GILROY ATSTherapy WHO GILROY ATS - Initial - Initial INH+R+PZA+E INH+R+PZA INH+R+PZA atau SINH+R+PZA+E INH+R+PZA INH+R+PZA atau S

atau R+ PZA+Satau R+ PZA+S

-2MO - 2 MO - 2 MO-2MO - 2 MO - 2 MO - Continued INH+R INH+R INH+R- Continued INH+R INH+R INH+R -7 MO - 9 MO - 9 MO-7 MO - 9 MO - 9 MO Pyridoxine 50 mg/ hrPyridoxine 50 mg/ hr

2. Spinal arachnoiditis and arteritis may show 2. Spinal arachnoiditis and arteritis may show improvement when terated with corticosteroid.improvement when terated with corticosteroid.3. Seizure 3. Seizure anticonvulsant anticonvulsant4. ventriculoperitoneal shunt.4. ventriculoperitoneal shunt.

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 oercent make have 20% mortality and only 20 oercent make complete recovery.complete recovery.

Viral meningitisViral meningitisViral meningitis shares clinical features with Viral meningitis shares clinical features with bacterial meningitis, but patients appear less ill bacterial meningitis, 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 herpes simplex-1 The most pathogens include herpes simplex-1 (HSV1), mumps, enterovirus, herpes zoster, (HSV1), 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.

FUNGAL MENINGITISFUNGAL MENINGITISETIOLOGYETIOLOGY

Fungi invade of CNS producing meningitis in a small fraction of Fungi invade of CNS producing meningitis in a small fraction of patients with systemic fungal infection (mycoses)patients with 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.

MyelitisMyelitis

Inflamation of the spinal cordInflamation of the spinal cord

I. Transverse Myelitis, II. Disseminata, III. I. Transverse Myelitis, II. Disseminata, III. DifussaDifussa

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

MYELITIS

Gray matter…… Poliomyelitis.White matter …. Leukomyelitis.The whole crossectional are…Tranversemyelitis.Lesions are multiple and wide spreadOver a long vertical extent….. DiffuseOr Disseminated.Combined meninges and spinal cord…Meningomyelitis.Combined meninges and root--- meningpradiculitis.Inflammatory disease limited to the spinal dura…. Pachymeningitis.Infected material collects in the epidural or subdural space… Epidural spinal Or subdural spinal abcess or Granulomatous.

CLASSIFICATION OF INFLAMMATORY DISEASEOF THE SPINAL CORD … SEE TRANSPARANTS

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.

BRAIN ABSCESS DefinitionBRAIN 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 MacEwen in 1893 [published:” started with MacEwen in 1893 [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

-

RISK FACTORS AND PATHOGENESIS RISK FACTORS AND PATHOGENESIS CEREBRAL ABSCESSCEREBRAL ABSCESS

Directly from the paranasal sinuses, mastoid, middle ear or Directly from the paranasal sinuses, mastoid, middle ear or via hematogenous spread e.g. via hematogenous spread e.g. colonic diverticulae, pulmonary colonic diverticulae, pulmonary infection, periodontal infection, bacterial endocarditis, except rabies infection, periodontal infection, bacterial endocarditis, except rabies (infiltration along peripheral nerve), Naegleria and herpes via the (infiltration along peripheral nerve), Naegleria and herpes via the olfactory bulbsolfactory bulbs

Bacterial caused by aerobic and anaerobic gram Bacterial caused by aerobic and anaerobic gram negative/positivenegative/positiveThe source of inoculation of CNS remain unknown in up to The source of inoculation of CNS remain unknown in up to one-thirdone-thirdHead trauma : CSF leak, reoperation, delay in care or Head trauma : CSF leak, reoperation, delay in care or basilar skull fracturebasilar skull fractureImplantation of a foreign body : shunt, high-grade glioma, Implantation of a foreign body : shunt, high-grade glioma, irradiationirradiationImmunocompromised : Immunocompromised : transplant, cancer, chemotherapy, transplant, cancer, chemotherapy, retroviral infectionretroviral infection

Neuropatologi (4 Neuropatologi (4 stages)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 penderitaGlasgow coma scale : utk kesadaran penderita

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

EEGEEG

CT Scan/ MRICT Scan/ MRI

Cerebritis results in a non homogeneous mass Cerebritis results in a non homogeneous mass with irregular margins and diffuse enhancementwith irregular margins and diffuse enhancement

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

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

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

TEMPORAL LOBE ABSCESSTEMPORAL LOBE ABSCESSCT scan showing ring enhancement in temporal sinistraCT scan showing ring enhancement in temporal sinistra

(hyperdense capsule differentiated from central low density (hyperdense capsule differentiated from central low density (pus) and marked surronding edema)(pus) and marked surronding edema)

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.

7272

Pengobatan abses otakPengobatan abses otak

Konservatif:Konservatif: - - Pemberian AB yg tepat : 6-8 mgg Pemberian AB yg tepat : 6-8 mgg mengecilkan abses.mengecilkan 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 diberikan anak : loading dose 10-12 mg/kg diberikan

satu kali IVsatu 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 , jika konsul Bedah Saraf , jika terapi konservatif gagal.terapi konservatif gagal.

SURGICAL MANAGEMENT CEREBRAL ABSCESSSURGICAL MANAGEMENT CEREBRAL ABSCESS

Stereotactic aspiration Stereotactic aspiration Advantages :Advantages :

Avoidance of general anesthesiaAvoidance of general anesthesiaAccess to multiple lesions without an increase in surgical Access to multiple lesions without an increase in surgical complexitycomplexityAbility to decompress lesions in eloquent areas such as the Ability to decompress lesions in eloquent areas such as the thalamus and basal gangliathalamus and basal ganglia

Simple cystic structure ; size <1.5 cm ; deep gray matter ; no Simple cystic structure ; size <1.5 cm ; deep gray matter ; no air/fluid level ; no fistulaair/fluid level ; no fistulaComplication : intracerebral hematoma 0.4% to 1.6%Complication : intracerebral hematoma 0.4% to 1.6%Mortality less than 0.2% ; morbidity 1-4%Mortality less than 0.2% ; morbidity 1-4%

Open craniotomy with or without excision of the capsule Open craniotomy with or without excision of the capsule Posterior fossa masses indicate for open craniectomy ; Posterior fossa masses indicate for open craniectomy ; encapsulated ; silent cortex or white matterencapsulated ; silent cortex or white matter

Multiloculated abscesses, which are difficult to fully Multiloculated abscesses, which are difficult to fully decompress stereotactically, should open ; size >2.5 cm ; decompress stereotactically, should open ; size >2.5 cm ; air/fluid level in abscess ; fistulaair/fluid level in abscess ; fistulaMortality 1% to 11% ; morbidity 4% to 30%Mortality 1% to 11% ; morbidity 4% to 30%

The goal treatment in brain abscesses :The goal treatment in brain abscesses :

Reduce mass effectReduce mass effect

Decrease intracranial pressureDecrease intracranial pressure

Prevent herniation or intraventricular Prevent herniation or intraventricular rupture and ventriculitisrupture and ventriculitis

Identify the causative microorganismIdentify the causative microorganism

Establish antibiotic sensitivitiesEstablish antibiotic sensitivities

Antibiotic treatment for brain abscessAntibiotic treatment for brain abscessRational Administration Rational Administration ::Timing of initial therapy, Choice of agents,Timing of initial therapy, Choice of agents,

Penetration of various agents into the brain, Duration of therapyPenetration of various agents into the brain, Duration of therapy

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 treatment

Teeth, 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

NEUROLOGICAL SEQUELAENEUROLOGICAL SEQUELAE

Most likely due to :Most likely due to :Delayed diagnosisDelayed diagnosis

Poor initial neurological conditionsPoor initial neurological conditions

Larger sizeLarger size

Common neurological sequelae are cognitive Common neurological sequelae are cognitive defisits, hemiparesis, and seizuresdefisits, hemiparesis, and seizures

Infants and children have a worse outcome than Infants and children have a worse outcome than adults ,IQ lower than 80, 70% children had adults ,IQ lower than 80, 70% children had difficulties with school performance, 38% had difficulties with school performance, 38% had severe hemiparesissevere hemiparesis

Adult : 87% were able to continue their normal Adult : 87% were able to continue their normal work and none had severe hemiparesiswork and none had severe hemiparesis

Seizure disordersSeizure disorders3 to 4 years after treatment (15% to 92%)3 to 4 years after treatment (15% to 92%)

Children are more likely than adultsChildren are more likely than adults

Most common lesion at frontal and temporal Most common lesion at frontal and temporal lobes ; occipital lobe are unusual ; cerebellar lobes ; occipital lobe are unusual ; cerebellar do not predispose to seizuresdo not predispose to seizures

Anticonvulsant for at least 6 months Anticonvulsant for at least 6 months

Rates of recurrence 10% to 50%Rates of recurrence 10% to 50%

PROGNOSIS Cerebral AbscessPROGNOSIS Cerebral Abscess

Mortality > 60% if sign of brain herniation are Mortality > 60% if sign of brain herniation are presentpresentMortality rate <29% among alert patientsMortality rate <29% among alert patients90% among comatose patients90% among comatose patientsMortality rate 12.5% in posttrauma without signs of Mortality rate 12.5% in posttrauma without signs of herniationherniationMortality rate 4.3% since CT became a routine Mortality rate 4.3% since CT became a routine diagnotic testdiagnotic testSex and ethnic origin is no evidence for mortalitySex and ethnic origin is no evidence for mortalityHigh mortality rate in :High mortality rate in :

Patients related to immaturityPatients related to immaturityVirulence of the gram-negative organismsVirulence of the gram-negative organismsCoexistent systemic diseaseCoexistent systemic disease

Defenition Viral encephalitisDefenition 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 alteration of consciousness, focal producing alteration of consciousness, focal neurological signs and seizures.neurological 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....

Komplikasi neurologi HIVKomplikasi neurologi HIV

Brain Predominantly nonfocalBrain Predominantly nonfocal

AIDS dementia complexAIDS dementia complex

Acute HIV-related encephalitisAcute HIV-related encephalitis

Cytomegalovirus encephalitisCytomegalovirus encephalitis

Varicella-zoster virus Varicella-zoster virus encephalitisencephalitis

Herpes simplex virus Herpes simplex virus encephalitisencephalitis

Metabolic encephalopathies Metabolic encephalopathies

Predominantly focalPredominantly focal Cerebral toxoplasmosisCerebral toxoplasmosis Primary CNS lymphomaPrimary CNS lymphoma Progressive multifocal leukoencephalopathyProgressive multifocal leukoencephalopathy CryptococcomaCryptococcoma Brain abcess / tuberculomaBrain abcess / tuberculoma Neurosyphilis (meningovascular)Neurosyphilis (meningovascular) Vascular disorders Vascular disorders

Spinal cordSpinal cord Vacuolar myelopathyVacuolar myelopathy Herpes simplex or zoster myelitis Herpes simplex or zoster myelitis

Meninges Meninges Aseptic meningitis (HIV)Aseptic meningitis (HIV) Cryptococcal meningitisCryptococcal meningitis Tuberculous meningitisTuberculous meningitis Syphilitic meningitisSyphilitic meningitis Metastatic lymphomatous meningitisMetastatic lymphomatous meningitis

Peripheral nerve and root and rootPeripheral nerve and root and root infectiousinfectious herpes zosterherpes zoster cytomegalovirus lumbar polyradiculopathycytomegalovirus lumbar polyradiculopathy

Virus or immune-relatedVirus or immune-related acute and chronic inflammatory HIV poly- acute and chronic inflammatory HIV poly- neuritisneuritis mononeuritis multiplexmononeuritis multiplex sensorimotor demyelinating polyneuropathysensorimotor demyelinating polyneuropathy distal painful sensory polyneuritisdistal painful sensory polyneuritis

Muscle Muscle polymyositis and other myopathies polymyositis and other myopathies

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 (AIDS Dementia HIV dementia (AIDS Dementia Complex)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 HIV:Manifestasi klinis demensia HIV:

Cognititive disordersCognititive disordersGangguan 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 past infection (FN <3-6%)IgG indicates past infection (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:

MRI

CT Scan

Atrofi Meningeal enhancement

hidrosefalus SOL

Evaluasi LCS Shunt(kalau perlu)

Positif Negatif

Terapi sesuai etiologi

Observasi

Lesi massa(-) Lesi massa (+)

Skema 2

Keluhan intrakranial

Skema-1. Algoritme Penatalaksanaan Keluhan Intraserebral bagi Penderita HIV-AIDS

normal

Terapi toksoplasmosisSeumur hidup

Terapi sesuaietiologi

Dekompresi dan biopsi terbuka

Lesi massa intrakranial

Alert-lethargic stabil

Steroid ? Stupor-komaPerburukan cepat, massa

besarDengan resiko herniasi

Lesi multipel Lesi tunggal

Serologi toksoplasma

NegatifPositif

Obat antitoksoplasmosis

Perbaikan

Ya Tidak Biopsi stereotaktik

Ancaman herniasi

Skema-2. Algoritme Penatalaksanaan Lesi massa Intrakranial pada penderita HIV-AIDS

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.

Fase akut (3-6 minggu)

Pemeliharaan/rumatan

Pilihan pertama

Pilihan kedua

Pilihan ketiga

Pyrimethamine oral 200 mg hari pertama, selanjutnya 50-75 mg/hr + leucovorin oral 10-20 mg/hr + sulfadiazine oral 1000-1500 mg/hr

Pyrimethamine + leucovorin (dosis di atas) + clindamycin oral atau IV 4 x 600 mg

Pyrimethamine + leucovorin (dosis di atas) + salah satu :Atovaquone oral 2 x 1500 mgAzithromycin oral 1 x 900 – 1200 mgClarithromycin oral 2 x 500 mgDapson oral 1 x 100 mgMinocyclin oral 2 x 150-200 mg

Pyrimethamine oral 25-50 mg/hr + leucovorin oral 10-20 mg/hr + sulfadiazine oral 500-1000 mg/hr.

Pyrimethamine + leucovorin (dosis di atas) + clindamycin oral 4 x 300 mg – 450 mg

Pyrimethamine + leucovorin (dosis di atas) + salah satu antibiotika tersebut dosis sama.

107107

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)

Malaria Serebral (MS)Malaria Serebral (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

Comparison of diagnosis methodComparison of diagnosis method

Clinical diagnosis

Microscopic RDTs

Sensitivity 60-75% 60-95% 44-100%

Specificity 30-40% 75-95%95% (only for Pf

or Pv or Pan)

Infrastructure needed

Minimal High Moderate

Skill needed Minimal High Moderate

Cost Cheap Moderate Expensive

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 Pengobatan lini kedua diberikan

jika pengobatan lini pertama tidakjika pengobatan lini pertama tidak efektif,efektif, dimana 28 dimana 28

hari setelah pemberian obat :hari setelah 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)

Neurocisticercosis (NCC)Neurocisticercosis (NCC)

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

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