Encephalitis viralEncephalitis viralEncephalitis viralEncephalitis viral

Dr. Kiking Ritarwan MKT, SpSDr. Kiking Ritarwan MKT, SpS

Email: kritarwan@ yahoo.comEmail: kritarwan@ yahoo.com

ENCEPHALITIS VIRUSENCEPHALITIS VIRUS

Virus Representative virus for Neurologic DiseaseVirus Representative virus for Neurologic Disease

�� DNADNA

-- Herpesviruses HSV,VZV,CMV,EBVHerpesviruses HSV,VZV,CMV,EBV

-- Papovavirus PMLPapovavirus PML

-- Posvirus VacciniaPosvirus Vaccinia

-- Adenovirus Adenovirus serotypeAdenovirus Adenovirus serotype

�� RNARNA�� RNARNA

-- Enterovirus ( Picornavirus) Poliovirus, coxsackivirus, echovirus, enterovirus 70Enterovirus ( Picornavirus) Poliovirus, coxsackivirus, echovirus, enterovirus 70--71, Hepatitis A71, Hepatitis A

-- Togavirus, alphavirus ( arbovirus) Equine encephalitisTogavirus, alphavirus ( arbovirus) Equine encephalitis

-- Flavivirus (arbovirus) St louis enceph, Japanese and Tic Borne encephFlavivirus (arbovirus) St louis enceph, Japanese and Tic Borne enceph

-- Orbovirus (Arbovirus) Colorado Tick feverOrbovirus (Arbovirus) Colorado Tick fever

-- Bunyavirus (arbovirus) California encephBunyavirus (arbovirus) California enceph

-- Togavirus, rubivirus RubellaTogavirus, rubivirus Rubella

-- Orthomyxovirus InfluenzaOrthomyxovirus Influenza

-- Rhabdovirus RabiesRhabdovirus Rabies

-- Retrovirus HIV, HTLVRetrovirus HIV, HTLV

R��� I�������R��� I�������V���� ����� �� ����� ����� �������V���� ����� �� ����� ����� �������

�� Saluran pernafasan : parotitis, varicella, Saluran pernafasan : parotitis, varicella,

morbillimorbilli

�� Saluran makanan : polio, enterovirusSaluran makanan : polio, enterovirus

�� Mukosa kelamin : Herpes simpleksMukosa kelamin : Herpes simpleks

�� Inokulasi : spt gigitan binatang (rabies a Inokulasi : spt gigitan binatang (rabies a

nyamuk)nyamuk)

�� Placenta : CMV + RubellaPlacenta : CMV + Rubella

HIV and the brain (1)HIV and the brain (1)

�� MeningitisMeningitis�� HIV itselfHIV itself

�� TB TB

�� CryptococcalCryptococcal�� CryptococcalCryptococcal

�� SyphiliticSyphilitic

�� Space occupying lesionsSpace occupying lesions�� ToxoplasmosisToxoplasmosis

�� TuberculomasTuberculomas

�� Lymphoma Lymphoma

HIV and the brain (2)HIV and the brain (2)

�� EncephalitisEncephalitis

�� HIV dementiaHIV dementia

Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy �� Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy

(PML)(PML)

�� CMV, HSV, HZV encephalitisCMV, HSV, HZV encephalitis

�� ToxoplasmosisToxoplasmosis

�� Strokes and intracerebral haemorrhageStrokes and intracerebral haemorrhage

HIV and the spinal cordHIV and the spinal cord

�� Vacuolar myelopathyVacuolar myelopathy

�� SyphilisSyphilis

�� HZV, HSV, CMV, HTLVHZV, HSV, CMV, HTLV--11

TBTB�� TBTB

�� LymphomaLymphoma

HIV and the peripheral nervous system (1)HIV and the peripheral nervous system (1)

�� RadiculopathyRadiculopathy

�� TBTB

�� CMVCMV

�� Inflammatory demyelinating Inflammatory demyelinating polyneuropathiespolyneuropathies

�� GuillainGuillain--BarreBarre

�� CIDPCIDP

HIV and the peripheral nervous system (2)HIV and the peripheral nervous system (2)

�� Distal sensory neuropathyDistal sensory neuropathy

�� Mononeuropathies, mononeuritis multiplexMononeuropathies, mononeuritis multiplex

�� DrugsDrugs�� INHINH

�� D4T, ddID4T, ddI

�� D4T associated HIV neuromuscular weakness D4T associated HIV neuromuscular weakness syndromesyndrome

�� Diffuse Infiltrative Lymphocytosis Syndrome Diffuse Infiltrative Lymphocytosis Syndrome (DILS)(DILS)

�� Nutritional neuropathiesNutritional neuropathies

Mekanisme kerusakan neuron pada infeksi HIVMekanisme kerusakan neuron pada infeksi HIV

�� Untuk masuk ke dalam SSP, HIV harus terlebih dahulu menginfeksi sel Untuk masuk ke dalam SSP, HIV harus terlebih dahulu menginfeksi sel

yang memiliki reseptor CD4 yang memiliki reseptor CD4

�� Mekanisme masuknya virus HIV kedalam SSP adalah dengan cara Mekanisme masuknya virus HIV kedalam SSP adalah dengan cara

menumpang pada monosit yang terinfeksi virusmenumpang pada monosit yang terinfeksi virus

�� Selanjutnya di dalam SSP, monosit yang telah terinfeksi Selanjutnya di dalam SSP, monosit yang telah terinfeksi

berdeferensiasi menjadi mikrogliaberdeferensiasi menjadi mikroglia

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,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 Japanese –– B B

�� Russian tickRussian tick--borneborne

�� RabiesRabies

Etiology viral encephalitisEtiology viral encephalitis

��Viral is the most common causeViral is the most common cause

��The 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 epidemics�� It may occur sporadically or in epidemicsIt may occur sporadically or in epidemics

��5050--70% mortality if untreated70% mortality if untreated

��So 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�� 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

EpsteinEpstein--BarrBarr

CoxsackieCoxsackieCoxsackieCoxsackie

HIVHIV

MorbilliMorbilli

EchovirusEchovirus

khoriomeningitis limfositikkhoriomeningitis limfositik

paravirus paravirus

�� Neurogen Herpes simpleksNeurogen Herpes simpleks

BB--virusvirus

VariselaVarisela--ZosterZoster

RabiesRabiesRabiesRabies

Gambaran klinik:Gambaran klinik:

�� Tanda dan gejala bervariasi tergantung Tanda dan gejala bervariasi tergantung virus penyebab.virus penyebab.

�� Umumnya: demam akut disertai tanda rangUmumnya: 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 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 (Veneequine encephalitis) sampai rendah (Vene--zuelan equine encephalitis).zuelan equine encephalitis).

�� Gejala sisa termasuk kejang2Gejala sisa termasuk kejang2

�� Komplikasi : Komplikasi : -- perubahan kepribadianperubahan kepribadian

-- ggn ekstrapiramidalggn ekstrapiramidal

-- demensiademensia-- demensiademensia

-- ggn motorik ggn motorik -- sensoriksensorik

Kriteria diagnosis ensefalitis viralKriteria diagnosis ensefalitis viral

1.1. Bentuk asimptomatik Bentuk asimptomatik �� analisis LPanalisis LP

2.2. Bentuk abortif : Nyeri kepala, demam yg tdk Bentuk abortif : Nyeri kepala, demam yg tdk tinggi, kaku kuduk. ISPA/ Infeksi GITtinggi, kaku kuduk. ISPA/ Infeksi GIT

3.3. Bentuk fulminan: Berlangsung bbrp jam Bentuk fulminan: Berlangsung bbrp jam sampai dengan beberapa hari yg berakhir sampai dengan beberapa hari yg berakhir 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 ( 80atau sedikit meninggi ( 80--200 mg/dl200 mg/dl

�� MRI atau CT scan MRI atau CT scan �� SOL (?)SOL (?)�� MRI atau CT scan MRI atau CT scan �� SOL (?)SOL (?)

�� EEGEEG

�� Liquor 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 Virus kadang2 dikultur dari liquor,feces,urine nasofaring atau darah.liquor,feces,urine 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�� Jalan nafas diawasiJalan nafas diawasi

�� Keseimbangan cairan dan elektrolit dijagaKeseimbangan cairan dan elektrolit dijaga

�� Atasi kejangAtasi kejang

�� Atasi peninggian ICP Atasi peninggian ICP

Komplikasi neurologi HIVKomplikasi neurologi HIV

�� Brain Predominantly nonfocalBrain Predominantly nonfocal

AIDS dementia complexAIDS dementia complex

Acute HIVAcute HIV--related encephalitisrelated encephalitis

Cytomegalovirus encephalitisCytomegalovirus encephalitisCytomegalovirus encephalitisCytomegalovirus encephalitis

VaricellaVaricella--zoster virus 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 leukoencephaloProgressive multifocal leukoencephalo--

pathypathy

CryptococcomaCryptococcomaCryptococcomaCryptococcoma

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 meningitisCryptococcal 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 immuneVirus or immune--relatedrelated

acute and chronic inflammatory HIV polyacute and chronic inflammatory HIV poly--

neuritisneuritisneuritisneuritis

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 (2Infeksi virus (2--3 minggu) 3 minggu) �� sindroma sindroma retroretro-- viral akut (2viral akut (2--3 minggu) 3 minggu) �� gejala gejala menghilang + serokonversi menghilang + serokonversi �� infeksi infeksi kronis HIV asimpto matik (rata2 8 thn) kronis HIV asimpto matik (rata2 8 thn) ��infeksi HIV / AIDS simptomatik (rata2 1,3 infeksi HIV / AIDS simptomatik (rata2 1,3 infeksi HIV / AIDS simptomatik (rata2 1,3 infeksi HIV / AIDS simptomatik (rata2 1,3 thn) thn) �� kematian.kematian.

�� Window period Window period �� masa dimana masa dimana pemeriksapemeriksa-- an test serologis utk antibodi an test serologis utk antibodi HIV masih negatif, tapi virus sdh ada dlm HIV masih negatif, tapi virus sdh ada dlm darah (sudah mampu menularkan kpd darah (sudah mampu menularkan kpd orang lain)orang lain)

CEREBRAL TOXOPLASMOSISCEREBRAL TOXOPLASMOSIS

�� Reactivation of latent infectionReactivation of latent infection

�� Toxo seroprevalence 12Toxo seroprevalence 12--46% (SA)46% (SA)

�� IgG indicates past infection (FN <3IgG indicates past infection (FN <3--6%)6%)

CD4 > 200 virtually excludes ToxoCD4 > 200 virtually excludes Toxo�� CD4 > 200 virtually excludes ToxoCD4 > 200 virtually excludes Toxo

�� Over 80% have CD4 < 100Over 80% have CD4 < 100

�� Typically multiple ring enhancing lesions on CT/MRITypically multiple ring enhancing lesions on CT/MRI

�� 2727--43% have single lesions43% have single lesions

�� Up 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 H IV/A IDS

Notes:

MRI

CT Scan

Atrofi Meningeal hidrosefalus SOL

Keluhan intrakranial

Skema-1. Algoritme Penatalaksanaan Keluhan Intraserebral bagi

Penderita HIV-AIDS

normal Atrofi Meningeal

enhancement

hidrosefalus SOL

Evaluasi LCS Shunt

(kalau perlu)

Positif Negatif

Terapi sesuai

etiologi

Observasi

Lesi massa(-) Lesi massa (+)

Skema 2

normal

Lesi massa intrakranial

Alert-lethargic

stabil

Steroid ? Stupor-koma

Perburukan cepat, massa besar

Dengan resiko herniasi

Lesi multipel Lesi tunggal

Serologi

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

Terapi toksoplasmosis

Seumur hidup

Terapi sesuai

etiologi

Dekompresi dan

biopsi terbuka

Serologi

toksoplasma

NegatifPositif

Obat antitoksoplasmosis

Perbaikan

Ya Tidak Biopsi stereotaktik

Ancaman herniasi

Toxoplasmosis Toxoplasmosis –– Clinical FeaturesClinical Features

�� Usually subacute over weeksUsually subacute over weeks

�� Headache Headache 50%50%

�� Fever Fever 45%45%�� Fever Fever 45%45%

�� Behaviour changes Behaviour changes 40%40%

�� Confusion Confusion 1515--52%52%

�� Focal signsFocal signs

�� Seizures Seizures 2424--29%29%

Toxoplasmosis treatmentToxoplasmosis treatment

�� Sulphadiazine and Pyrimethamine is first choiceSulphadiazine and Pyrimethamine is first choice

�� CoCo--trimoxazole (80/400mg) 4 tablets BD x 4/52trimoxazole (80/400mg) 4 tablets BD x 4/52

then 2 tablets BD x 8/52then 2 tablets BD x 8/52

�� Long term secondary prophylaxis 2 tabs DLYLong term secondary prophylaxis 2 tabs DLY

�� Till sustained CD4 > 200Till sustained CD4 > 200

�� 86% show clinical improvement by 7 days86% show clinical improvement by 7 days

�� 95% show CT improvement by 14 days95% show CT improvement by 14 days

CT CT -- Multiple ring enhancing lesionsMultiple ring enhancing lesions

�� Toxo more likelyToxo more likely

�� Tuberculomas still Tuberculomas still possiblepossiblepossiblepossible

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 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 disorders

Gangguan kognitif, kesulitan konsentrasi, Gangguan kognitif, kesulitan konsentrasi, forgetfullness, cognitive slowing. Kadang2 agitasi, forgetfullness, cognitive slowing. Kadang2 agitasi, forgetfullness, cognitive slowing. Kadang2 agitasi, forgetfullness, cognitive slowing. Kadang2 agitasi, mania. mania.

Pd std awal sulit membedakan dgn keluhan psikiatri.Pd std awal sulit membedakan dgn keluhan psikiatri.

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

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

Herpes simplex encephalitisHerpes simplex encephalitis

Encephalitis non virus:Encephalitis non virus:

�� Bakteri:Strepto,staphylo,meningo, salmonella, Bakteri:Strepto,staphylo,meningo, salmonella,

E.coliE.coli

�� Protozoa: P.Falcifarum, ToxoplasmosisProtozoa: P.Falcifarum, Toxoplasmosis�� Protozoa: P.Falcifarum, ToxoplasmosisProtozoa: P.Falcifarum, Toxoplasmosis

�� Cacing: CystisercosisCacing: Cystisercosis

�� Jamur: Aspergillus, ActinomycosisJamur: Aspergillus, Actinomycosis

�� Rickettsia: RickettsiosisRickettsia: Rickettsiosis

Matur nuwonMatur nuwon

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