I Wayan Tunjung, dr. Sp.S.BAGIAN NEUROLOGIRSU KOTA MATARAM

INFEKSI SUSUNAN SARAF PUSAT (MENINGITIS DAN ENCEPHALITIS).

PENYAKIT INFEKSI SSP Encephalitis Meningitis MyelitisCerebral Abscess

Tulang : kranium dan vertebraSelaput otak (meningen)Ruang Subarahnoid: cairan otak (liquor cerebrospinal/LCS)

SSP dilindungi oleh:

1. Otak (ensepalon): 1. Serebrum : telensepalon dan diensepalon 2. Batang otak : mesensepalon, pons, medula oblongata 3. Serebelum : paleo, neo dan arki

* Sumsum tulang belakang (medulla spinalis): servikal, torakal, lumbal, sakral, koksigeal.SUSUNAN SARAF PUSAT

2. MENINGEN (selaput otak)Dura mater (pakimening), paling luar Araknoid materPia mater, paling dalam 2 & 3 leptomening

Meningen(Lentnek, 2007)

Meningen

3. SISTEM VENTRIKELTerapat 4 rongga (kavitas) : 2 Ventrikel lateralisVentrikel IIIVentrikel IV

Ventrikel

Akut Meningitis : Meningitis Bacterial Akut Meningitis Viral Akut

Meningitis Kronis :Meningitis TuberkulosisINFEKSI MENINGEN

MENINGITIS BAKTERIAL

Hasil LP Meningitis

No.Pembeda M. B.M. V.M. T.1.Tekanan bukaN2.WBCPMN > 100 sel/dlPleositosis limfositikPleositosis limfositik 10-50 sel/mm33.Glukosa N4.ProteinSdkt 10- 500

Hasil Analisis CSS pada Meningitis Bakterial Akut(Jusuf dkk., 2006; Miller, 2008)

NormalBakterialTekanan< 180mmH2O>180mmH2OWarnaJernihkeruh kekuninganJumlah leukosit0-5/mm3>100/mm3, bisa sampai >1000/mm3-10.000/mm3, terutama PMNProtein20-45 mg/dl> 45mg/dlGlukosa45-80 mg/dl< 40 mg/dl atau

Tabel 1. Terapi Emperis Meningitis Bakterial

OrganismeKarakteristik PasienAntibiotikaStreptococcus group B, Listeria monocytogenes, E. colliNeonatusAmpicillin + cefotaximeN. Meningitidis, S. Pneumoniae, H. Influenza2 bl - < 18 tahunCeftriaxone atau Cefotaxime + VancomycinS. Pneumoniae, N Meningitis18 50 tahunCeftriaxone + VancomycinS. Pneumoniae, L. Monocytogenes, gram negatives> 50 tahunVancomycin + Ampicillin + CeftriaxoneL. Monocytogenes, gram negativesGangguan imunitas selulerAmpicillin + CeftazidimeCoagulase positive atau negativeStaphylococci gram negativeS. PneumoniaeKerusakan dura/shuntVancomycin + Ceftazidime

Tabel 2. Terapi Spesifik Meningitis Bakterial

OrganismeDurasi dari terapiKomentarH. Influenzae7 10 hariResistensi ampicillin biasa terjadiN. Meningitidis5 7 hariJika organisme sensitive, gunakan penicillin dosis tinggi secara IV. Bila resistensi penicillin meningkat; signifikansi secara klinis tidak pastiS. Pneumoniae14 21 hariAngka resistensi terhadap penicillin meningkat. Jika sensitive terhadap penicillin, ceftriaxone atau cefotaxime, hentikan penggunaan terapi empiris vancomycin. Adanya resistensi terhadap cephalosporin, gunakan ceftriaxone atau cefotaxinme ditambah vancomycin dan periksa CSF setelah 36 48 jam. Jika sensitive terhadap rifampin, gunakan rifampin jika secara klinis keadaan pasien memburuk, infeksi persisten pada CSF, dan penggunaan dosis MIC ceftriaxone atau cefotaxime yang terlalu tinggi. Perhatikan penambahan rifampin pada regimen empiris jika terdapat penggunaan deksametason, karena deksametason mungkin menyebabkan penurunan penetrasi CSF terhadap antibiotik.L.Monocytogenes14 21 hariGunakan ampicillin atau penicillin ditambah gentamisin pada infeksi yang berat. Gunakan trimethoprimsulfame-thoxazole jika alergi terhadap penicillin.

Pemberian Antibiotika Berdasarkan Usia

(Jusuf dkk., 2006)

UsiaBakteri PenyebabAntibiotika< 50 tahunS. pneumoniaeN. meningitidisL.monocytogenesCefotaxime 2 g/6 jam/iv, maksimal 12 g/hari, atau ceftriaxone 2 g/12 jam/iv + ampicillin 2 g/4 jam/iv (200mg/kgBB/hari/iv)Bila S.pneumoniae resisten cephalosporin, diberikan : cefotaxime/ceftriaxone + vancomycin 1 g/12 jam/iv, maksimal 3 g/hari 50 tahunS. pneumoniaeH.influenzaeL.monocytogenes P.aAerogenosaN. meningitidisCefotaxime 2 g/6 jam/iv, maksimal 12 g/hari, atau ceftriaxone 2 g/12 jam/iv + ampicillin 2 g/4 jam/iv (200mg/kgBB/hari/iv)Bila S.pneumoniae resisten cephalosporin, diberikan : cefotaxime/ceftriaxone + vancomycin 1 g/12 jam/iv, maksimal 3 g/hariCeftazidime 2 g/8 jam/iv

Definisi -Radang/inflamasi pada lapisan pembungkus (meningen) otak dan sumsum tulang belakang. - salah satu komplikasi dari TB primer

Epidemiologi- Indonesia ketiga terbesar dengan masalah TBC di dunia. - Bertambah seperempat juta kasus baru/tahun. - 140.000 kematian terjadi setiap tahun

EtiologiMeningitis TBC Mycobacterium tuberculosis jenis Hominis, jarang oleh Bovinum atau Aves.

PATOFISIOLOGI

PATOFISIOLOGI (cont)

PatofisiologiPerkembangan meningitis TB ada dua tahap.Tahap I: basil M tuberculosis masuk ke dalam tubuh host melalui droplet inhalation, titik awal infeksi adalah di makrofag elveoli.

Infeksi yang terlokalisir meluas di dalam paru dengan penyebaran ke limfonodi regional sehingga membentuk kompleks primer. Selama tahap ini, bakterimia yang singkat tapi signifikan terjadi.

penyebaran bibit basil tuberkel ke organ lain dalam tubuh

(Ramachandran, 2007).

Pada meningitis TB, basil TB menyebar ke meningen dan parenkim otak, membentuk fokus kecil di subpial atau subependimal (Fokus Rich).

Tahap II:Pecahnya fokus Rich dalam rongga subarakhnoid. Lokasi tuberkel yang meluas menentukan tipe dari keterlibatan CNS. Tuberkel yang pecah ke rongga subarakhnoid menyebabkan meningitis.

MANIFESTASI KLINIS

PEMERIKSAAN PENUNJANGSputum basil tahan asamThorax foto PA dan lateral gambaran hilar lymphadenopathy, simple pneumonia, infiltrat, fibronodular infiltrat/kavitas, dan/atau efusi pleura.Tuberculin tes; Masih kontroversial. Hampir 60% kasus meningitis TB tidak reaktif terhadap tes ini (Ramachandran, 2007).

Lumbal pungsi

Perbedaan Interpretasi Cairan Serebrospinal (Saharso, 2006)

TesMeningitis BakterialMeningitis VirusMeningitis TBCTekanan

Warna

sel

Jenis sel

Protein

GlukosaMeningkat

Keruh

> 1000/ml

Predominan PMN

Sedikit meningkat

Normal/menurunBiasanya normal

Jernih

< 100/ml

Predominan MN

Normal/meningkat

Biasanya normalBervariasi

Xanthochrom

Bervariasi

Predominan MN

Meningkat

Rendah

Lini pertama : Isoniazid (INH), Rifampin (RIF), Pyrazinamid (PZA), Streptomisin (SM) dan Ethambutol (E) kurang efektif untuk meningeal disease kecuali pada dosis tinggi).Semua obat tersebut bersifat bakterisidal dan dapat memasuki CSF jika terjadi inflamasi meningeal. Lini kedua : Ethionamide, Cyclocerine, Ofloxacin dan Para-amino salicylic acid (PAS). (Ramachandran, 2007).PENATALAKSANAAN

PENATALAKSANAAN

Nama ObatDosisCatatanIsoniazid (H)2 bulan pertama: 5mg/kgBB po. (maks 450 mg p.o)Plus 7 bulan: 450 mg p.oBerikan piridoksin 50 mg/hr untuk mencegah neuropati primerRifampisin (R)2 bulan pertama: 10 mg/kg p.o. (maks. 600 mg)Plus 7 bulan: 600 mg p.o.Paling sering menyebabkan hepatitisPirazinamid (Z)2 bulan pertama: 25 mg/kg p.o(maks 2 g/hr)Etambutol (E)2 bulan pertama: 20 mg/kg p.o *(maks 1,2 g/hr)Streptomisin (S)20 mg/kg i.m (maks 1 g/hr)Hany diberikan pada pasien yang mempunyai riwayat pengobatan TB sebelumnya

PENATALAKSANAAN (contd)Terapi kortikosteroid pada meningitis TB sebagai tambahan obat anti TB masih kontroversial

Mgg ke

GRADE12345678I0,3 mg/kgBB/hr i.v0,2 mg/kgBB/hr i.v 0,1 mg/kgBB/hr i.vTotal 3 mg/kgBB/hr p.oTotal 2 mg/kgBB/hr p.oTotal 1 mg/kgBB/hr p.o--II / III0,4 mg/kgBB/hr i.v0,3 mg/kgBB/hr i.v0,2 mg/kgBB/hr i.v0,1 mg/kgBB/hr i.vTotal 4 mg/kgBB/hr p.oTotal 3 mg/kgBB/hr p.oTotal 2 mg/kgBB/hr p.oTotal 1 mg/kgBB/hr p.o

KomplikasiAdesi/perlekatan palsy nervi kranialis (terutama N. II, III, IV, VI, VII dan VIII).Konstriksi pada a. carotis interna strokeObstruksi CSF peningkatan tekanan intrakranial, penurunan kesadaran, dan hidrosefalus. Infark (30% kasus), biasanya di kapsula interna dan ganglia basalishemiparese sampai gangguan pergerakan.

PROGNOSISStadium penyakitUmurKeadaan gizi Keadaan sosial ekonomi Pengobatan yang adekuat, dan Infeksi penyerta seperti diare, HIV, pneumonia.

ENCEPHALITIS

EnterovirusAnggota enterovirusPenularan: kontaminasi fekal oral dan dropletsArbovirusPenularan: gigitan nyamuk atau kutuHerpes Simplek VirusMeningitis primer atau episode rekurenETIOLOGI

Epstein-Barr VirusHuman Immunodeficiency Virus 1Kelumpuhan saraf cranialis >>Lymphocytic choriomeningitis virusMumps virusVaricella Zoster Virus

ENSEFALITIS VIRUSV. RNA (V.Parotitis, V.Morbili, V.Rabies, V. Rubela) V. DNA (Herpes Zoster-Varisela, V. Epstein-Barr, Variola, AIDS)

Gejala:Demam, sakit kepala, vertigo, nyeri badan, mual, kesadaran kejang.Def. neurologi tgt lokasi

Nyeri kepalaDemamKesadaran Ggn n.kranialis KK

Gejala

Cerebral Abscess

Abses otak tdd jar. nekrosis supuratif parekhim otakArea infeksi difus tidak berbatas langsung berhub dg edema & kerusakan jar.otakTahap-tahap perkembangan abses :Serebritis awal (hari 1-3)Gliosis (-), edema (+)Serebritis akhir (hari 49)Gliosis mulai, edema max Kapsul awal (hari 1014) Jaringan gliotik, edema PATOFISIOLOGI

Kapsul Akhir (stlh hari 10)Gliosis max, edema Faktor penting terbentuknya abses adalah rusaknya BBB dan jaringan otak di sekelilingnya.

DIAGNOSIS 1Klinis :75% : Sakit kepala65% : Defisit fokal60% : Altered mental status40% : Kejang30% : Demam20% : TIK (muntah, papil edema)20% : Kaku kuduk

DIAGNOSIS 2Lab :Lekosit, LED, Kultur, HIV

Radiologi :- Skull foto, foto thorax, foto sinus, gigi, telinga- CT/MRI dengan kontras

Patologi Anatomi : biopsi

MEDIKAMENTOSA 11. Kontrol peningkatan ICP : Steroid kontroversial penetrasi antibiotik ke dalam area infeksi. Pemberian singkat, dosis tinggi rasional pada kondisi edema serebri yang signifikan.

2. Aspirasi atau eksisi ICP dan dx. mikrobiologi. Antibiotik ditunda klinis stabil, jika aspirasi cepat dikerjakan

MEDIKAMENTOSA 23. Setelah drainase, antibiotik parenteral 68 minggu 23 bulan p.o

4. Terapi medis tunggal kurang optimal, tetapi dapat diberikan pada:abses dengan diameter < 2 cm, abses serebri tanpa kapsul, multipel.lesi tak dapat dioperasi dan durasi lebih panjang

5. Antikonvulsan bila ada kejang

MEDIKAMENTOSA 36. Anti edema : Manitol 0,5 1 g/mg BB IV 20 30 Dexametason 16 24 mg/hari

7. Bedah : Aspirasi Exisi total

TOXOPLASMOSIS

Gambaran klinis

Tanda dan GejalaJumlahDemam40 70 %Nyeri Kepala50 60 %Hemiparesis, Hemianopsia dan Afasia20 80 %Parese nervus cranialis10 20 %Gangguan penglihatan10 15 %Subacute confusion, kehilangan konsentrasi dan orientasi, perubahan perilaku dan lethargi15 45 %Kejang dan ataxia15 30 %Tanda dan gejala serebellum, gangguan berbicara, chorea, mual dan muntah~

Sulfadiazin 100 mg/kg BB & Pirimetazin 1mg/ kg BB 1 blnSpiramisin 3 x 500 mg/hr

Terapi

Terapi

HIV/AIDS SUSUNAN SARAF PUSAT

HIV/AIDS SUSUNAN SARAF PUSATAIDS (Acquired Immune Deficiency Syndrome) retrovirus .Menyerang limposit T, monosit, endothel, neuron dan sel glia.

CNS Manifestations of HIVSpace Occupying Lesions (SOL)ToxoplasmosisLymphomaPMLTuberculomaCryptococcomaPyogenic abscessNocardiaCNS Syphilis (gumma)Diffuse DiseaseCryptococcal MeningitisAcute InfectionHIV DementiaTuberculous MeningitisCNS SyphilisToxoplasma encephalitisCytomegalovirus encephalitis

Two key things to ALWAYS remember in the management of HIV infected patientsHIV infection does not prevent the development of a non-HIV related problemOpportunistic problems are related to the CD4 (+) cell count.If the count is > 200-300, the problem is probably not related to the HIV infection.

Space Occupying Lesions (SOL)

ToxoplasmosisThe most common in the west of the CNS space occupying lesions in a person with a CD4 count

ToxoplasmosisOther than a biopsy there is no good diagnostic testAntibody testing is very non-specific and occasionally insensitiveUsual diagnostic test is response to RxExpect response to treatment in 2 weeks

ToxoplasmosisThings that make toxo unlikelyNegative toxo serologyPatient taking Co-trimoxazole prophylaxisCD4 count > 100TreatmentPyrimethamine (50-100 mg QD) plus leucovorin and Sulfadiazine (1 gm QID)AlternativesFansidar 2-3 dailyAtovoquone 750 mg QIDAzithromycin 1200 mg QDClindamycin 600 QIDCo-trimoxazole 10mg/kg/day of trimethoprimDapsone 100 mg QD

Primary CNS LymphomaSubacute and focalCD4 count typically

PML Progressive Multifocal LeucoencephalopathyReactivation of JC virus (Papova virus)CD4 counts typically

TuberculomaPresents like any other mass lesionCT appearanceLooks like an abscess or a tumorNothing characteristic about CT appearanceMay be ring enhancingCSFNon-specifically abnormal or completely normalDiagnosis: brain biopsyTreatment: standard drugs though the duration has not been studiedMany people treat longer than pulmonary TB

Pyogenic Brain AbscessPresents like a mass rather than like infectionMay not have feverCTRing enhancing lesion(s)CSFNon-specifically abnormal

Pyogenic Brain AbscessMicrobiologyDepends upon the underlying causeSinusitis or otitis or mastoiditis or dental: mixed organismsBronchiectasis or lung abscess or empyema: mixed organismsParadoxical embolus: single organismEndocarditis: single organism usually Staphylococcus aureusAbout 30% do not have an underlying cause.These tend to have multiple organisms so are presumed to come form sub-clinical sinus, ear, or pulmonary source

Pyogenic Brain AbscessDiagnosisBrain aspirate or biopsy to prove abscess and obtain proper microbiologyAnti-microbiol managementIf known single bacterium: treat the bugIf mixed or presumed mixed focusChloramphenicol 50 mg/kg/day in 4 divided doses ORCefotaxime 2 gm Q4H and metronidazole 500 mg Q6HTreat for several months until CT scan is normal or looks inactive

NocardiaNocardia brain abscessPresents like other brain abscesses, but some predisposition to involve the brain stemCan only be diagnosed by biopsyOften diagnosed presumptively by finding nocardia elsewhereTreatmentInitialCefotaxime 2 gm Q6H and Amikacin 7.5mg/kg Q12H orCo-trimoxazole15 mg/kg/day IV x 3-6 weeksContinuationCo-trimoxazole 480/2400 BD PO x 6-12 months

Syphilis (gumma)Rare manifestationPresents as a massLooks like a brain tumorDiagnosis suggested by positive serologyDiagnosis proven by biopsyTreatmentPen G 18-24 million units/day x 14 days

NON-FOCAL CNS DISEASE

Cryptococcal MeningitisClinical PresentationsTypicalSubacute onset of fever and headachePhotophobia and/or meningeal signs in only 25%Less typicalSeizuresConfusionProgressive dementiaVisual or hearing impairmentFUODiagnosisVery rare if CD 4 (+) cell count is > 100CSF: may be deceptively normalSerum CRAG: > 99% sensitive in AIDS patients

Cryptococcal MeningitisIn 2003 there were 193 (+) CSF cultures for cryptococcus from PMH *LeucocytesNo leucocytes in 31%Only 1-10 leucocytes in 23%7% had > 250 leucocytes30% of these had predominately PMNs95% (+) India Ink1% (-) cryptococcal antigen*Bisson et al., 2003

Cryptococcal MeningitisTreatmentPressure managementPEOPLE DIE OF PRESSURE NEED TO BE AGGRESSIVEAntimicrobialsAmphotericin B 0.7 mg/kg/day X 2 weeks and if improvingFluconazole400 mg QD x 6 weeks200 mg QD until CD 4 > 200

Treatment**Modified IDSA GuidelinesImmunosuppressed (pulmonary, cutaneous, or meningitis)InductionAmphotericin B 0.7-1 mg/kg/day plus 5-flucytosine 100mg/kg/day x 2 weeks thenConsolidationFluconazole 400 mg/day x 6-10 weeks thenSuppression Fluconazole 200 mg/day.

Cryptococcal Meningitis TreatmentOne More ThingAnti-fungal: induction, consolidation, maintenancePressure managementElevated pressure75% > 20025% > 350Repeated lumbar puncturesIncreased pressure: daily until normal x several daysNormal pressure: recheck at 2 weeks prior to switching to fluconazoleLumbar drainVP shunt: if still elevated at 1 monthNo role foracetazolamide, mannitolSteroids: ?

Acute HIV InfectionAseptic MeningitisIndistinguishable from other causes of aseptic meningitis unless associated with the other features of the acute syndromeAdenopathyRashPharyngitisEncephalitisNeeds to be considered in the differential diagnosis of acute encephalitisRemember as with other manifestations of the acute infection HIV antibody may be negative. So consider:SeroconversionPCRP24 antigen

HIV DementiaDiagnosis of exclusion that is supported byAtrophy on CT scanCSF normal or elevated proteinTypical feature is withdrawn appearance but can be anythingCan have a dramatic response to ARVs

Tuberculous MeningitisSimilar presentation to cryptococcal meningitis, though can be a bit more acuteDiagnosis made by CSF, but insensitiveTypically lymphocytic predominance, but may have PMNs earlyModerate low glucoseAFB smear (+) in 5%Culture (+) in 50%Usually diagnosed by finding a sub-acute onset lymphocytic meningitis that is cryptococus and cytology negative.Treatment the same as pulmonary TB

CNS SyphilisSecondaryAseptic meningitisTertiaryMeningovascularGeneral ParesisTabes DorsalisAsymptomatic neurosyphilis

Toxoplasma encephalitisToxoplasma may occasionally present as diffuse CNS disease rather than an abscessCMV encephalitisRelatively rareDiagnosed by PCR on CSF, NOT BY SEROLOGY

TERIMA KASIH....

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