RADANG II

DR dr Kiking Ritarwan SpS(K), MKT

Departemen Neurologi FK USU/ RSUP
Haji Adam Malik
2016
 TOPIK RADANG II
• SPEKTRUM NEURO HIV
• Cerebral toksoplasmosis
• Cytomegalovirus
• Malaria serebral
• Neurocysticercosis
• Spinal Tuberculosis
• TETANUS
• Poliomielitis
• Rabies
Spektrum NeuroAIDS

• Primary complication (non-

opportunistic disease)
– HIV-Dementia
– HIV-Sensory neuropathy
• Secondary complication
(opportunistic disease)
– Cerebral Toxoplasmosis
– TB Meningitis / tuberculoma
– Cryptococcal meningitis
– Other opportunistic diseases....
 HIV Neuropathogenesis
• Chronic CNS infection begins during primary
systemic infection and continues in nearly all
untreated seropositive individuals
• progress to HIV-1 encephalitis (HIVE)
• manifests as a clinical syndrome of cognitive,
motor, and behavioral dysfunction known as
the HIV-dementia
HIV Entry into CNS

Blood

Brain parechyma Scarano et al Nature Vol 5 Jan 2005

Blood BBB CNS Neuronal Cognitive

Infections damage Motor weakness
Encephalopathy
Komplikasi neurologi HIV
• Brain Predominantly nonfocal
AIDS dementia complex
Acute HIV-related encephalitis
Cytomegalovirus encephalitis
Varicella-zoster virus encephalitis
Herpes simplex virus encephalitis
Metabolic encephalopathies
Predominantly focal
Cerebral toxoplasmosis
Primary CNS lymphoma
Progressive multifocal leukoencephalo-
pathy
Cryptococcoma
Brain abcess / tuberculoma
Neurosyphilis (meningovascular)
Vascular disorders
• Spinal cord
Vacuolar myelopathy
Herpes simplex or zoster myelitis
• Meninges
Aseptic meningitis (HIV)
Cryptococcal meningitis
Tuberculous meningitis
Syphilitic meningitis
Metastatic lymphomatous meningitis
• Peripheral nerve and root and root
infectious
herpes zoster
cytomegalovirus lumbar polyradiculopathy
• Virus or immune-related
acute and chronic inflammatory HIV poly-
neuritis
mononeuritis multiplex
sensorimotor demyelinating polyneuropathy
distal painful sensory polyneuritis
• Muscle
polymyositis and other myopathies
Perjalanan penyakit infeksi HIV
• Infeksi virus (2-3 minggu)  sindroma retro-
viral akut (2-3 minggu)  gejala menghilang +
serokonversi  infeksi kronis HIV asimpto
matik (rata2 8 thn)  infeksi HIV / AIDS
simptomatik (rata2 1,3 thn)  kematian.
• Window period  masa dimana pemeriksa-
an test serologis utk antibodi HIV masih
negatif, tapi virus sdh ada dlm darah (sudah
mampu menularkan kpd orang lain)
 HIV dementia (AIDS Dementia Complex)

• This progressive dementia occurs in AIDS,

owing to a direct primary HIV infection of
neurons or an indirect neurotoxicity induced
by presence of the virus in the brain
• Pathology: the virus may be transported into
the brain by infected peripheral monocytes
(Trojan horse theory).
 AIDS DEMENTIA
COMPLEX
Manifestasi klinis demensia HIV:
Cognititive disorders
Gangguan kognitif, kesulitan konsentrasi, forgetfullness,
cognitive slowing. Kadang2 agitasi, mania.
Pd std awal sulit membedakan dgn keluhan psikiatri.
Motor abnormalities: ataksia, hiperreflels. Babinski refleks
srg muncul. Pada std lanjut : paraparese dgn
inkontinansia urin et alvii
Behavioural dysfunction : Apathy, altered personality,
disorientasi. Std akhir Mutism
 Anti Retroviral
• ARV reduce the opportunistic infection

• ARV can arrest HIV-dementia and reverse its

neurological disability.(Price J Infect Dis. 2008 May 15 )

• Neurologist should have a competency in

prescribing ARV
 Anti Retroviral Treatment
• HAART (highly active antiretroviral treatment )
– Combination of three ARV
• ARV indication
– AIDS defining illness
– CD4 < 350 cell/uL
– Viral load > 50.000 copy/ml
• When to start ? (first : treat opportunistic
infection, than start ARV)
 First Line ARV
(HAART : 3 drugs combination)
HAART : highly active antiretroviral therapy

Stavudine
Zidovudine

Lamivudine

Nevirapine Efavirenz
ARV Lini Satu
 First Line ARV (1)

Stavudine 2 X 1 . Neuropati, pankreatitis, atrofi otot

Lamivudin 2 X1
Efavirens 600 1 X 1, vivid dream, ngantuk, imbalance,
wanita hamil
 First Line ARV (2)

Stavudine sda
Lamivudin sda
Nevirapin 1 X 1 2 minggu pertama, selanjutnya 2 X 1
Alergi, fungsi hati
 First Line ARV (3)

Duviral : 2 X 1 (Zidovudin dan lamivudin)

Anemia, sakit kepala
Nevirapin sda
First Line ARV (4)
Second line ARV
ARV brain penetration
• Low
• Tenofovir
• Didanosine
• Ritonavir
• Medium
• Stavudine
• Lamivudine
• Efavirenz
• Emtricitabine
• High
• Zidovudine
• Nevirapine
 Initiation of ARV Therapy
• Indication
– AIDS defining illness
– CD4 < 350 cell/uL
– Viral load > 50.000 copy/ml
• Patients preparation before starting ARV
– Longlive treatment
– Rule-out and treat opportunistic infection first
– ARV adverse effect
• Side effect
• IRIS
Focal Brain Lesion (FBL)

HIV positif

Simptom intrakranial

Lesi fokal otak pd imaging ?

tidak

YA

Efek desak ruang ?

 CEREBRAL TOXOPLASMOSIS
• Reactivation of latent infection
• Toxo seroprevalence 12-46% (SA)
• IgG indicates past infection (FN <3-6%)

• CD4 > 200 virtually excludes Toxo

• Over 80% have CD4 < 100

• Typically multiple ring enhancing lesions on CT/MRI

• 27-43% have single lesions
• Up to 10% may have diffuse encephalitis without any visible
focal lesions
The course of HIV/AIDS

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

Keluhan intrakranial

MRI

CT Scan

Atrofi Meningeal hidrosefalus SOL

normal
enhancement

Evaluasi LCS Shunt

(kalau perlu)

Positif Negatif
Lesi massa(-) Lesi massa (+)

Terapi sesuai Observasi

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

Lesi massa intrakranial

Alert-lethargic Steroid ? Stupor-koma

stabil Perburukan cepat, massa besar
Dengan resiko herniasi

Lesi multipel Lesi tunggal

Serologi
toksoplasma

Positif Negatif

Obat antitoksoplasmosis Ancaman herniasi

Perbaikan

Ya Tidak Biopsi stereotaktik

Terapi toksoplasmosis Terapi sesuai Dekompresi dan

Seumur hidup etiologi biopsi terbuka
 Toxoplasmosis – Clinical Features
• Usually subacute over weeks
• Headache 50%
• Fever 45%
• Behaviour changes 40%
• Confusion 15-52%
• Focal signs
• Seizures 24-29%
 TREATMENT
• Acute treatment : 3-6 weeks.
– Induction : pyrimethamine 200 mg
– First line :
• Pyrimethamin 75-100 mg/day + sulfadiazine + folinic
acid or
• Pyrimethamin + clindamycin + folinic acid.
– Second line :
• Azithromycin, clarithromycin, or atovaquone can
substitute for sulfadiazine.
– Glucocorticoid  life threatening condition.
 TREATMENT
• Maintenance :
– Until the immune system has sufficiently
reconstituted.
– Pyrimethamine and sulfadiazine or
– Pyrimethamine and clindamycin.
• Stop :
– Asymptomatik.
– CD4+ > 200/cmm until 6 months.
 CT - Multiple ring enhancing lesions

• Toxo more likely

• Tuberculomas still
possible
 Differential Diagnosis
Toxoplasmosis P CNS L
Location Basal ganglia. Periventricular
Gray-white junction
Number of lesion Multiple Solitary>multiple
Enhancement pattern Ring Heterogeneous or
homogeneous.
Edema Moderate to marked Variable
T2-weighted image Hyperintense Isointense to
(lesion relative to hyperintense.
white matter)
Diffusion-weighted Usually hypointense Often hyperintense
image (positive)
 Differential Diagnosis
Toxoplasmosis P CNS L
MR perfusion Decreased Increased
MR spectroscopy Markedly elevated Markedly elevated
lactate. choline

SPECT thallium “Cold”-no thallium “Hot”-increased

(lesion relative to uptake thallium uptake.
white matter)
Other Toxoplasma IgG Ab EBV DNA amplified
(+) (90% of patients) by PCR in CSF
(most patients)
 Cytomegalovirus infections
• Central or peripheral nervous system
• In adults occur in immunocompromised individual
• Etiology: CMV (DNA Virus) of the herpetic group
• Clinical features:
-Encephalitis  complication of organ
transplantation and AIDS. CD 4 < 50 cell/ mm3
- Symptoms enceph: headache, fever and seizure
• Treatment: antiviral agent (ganciclovir or foscarnet)
 Definisi Malaria Serebral (MS)
MS adalah malaria dengan penurunan kesadaran  (
dewasa GCS < 9 dan anak -Blantyre coma score < 3)
atau koma lebih dari 30 menit setelah serangan
kejang yg tidak disebabkan oleh penyakit lain.
MS  komplikasi dari malaria falcifarum berat,
dijumpai st ensefalopati difus dengan penurunan
kesadaran dan berhubungan dengan sequestrasi
mikrovaskuler serebral.
 Blantyre coma scale(0-7)
• Oculer response
- Follow mother’s facial reaction …1
- non reaction ……………………0
• Verbal response
- Normal crying ……………………2
- Whimpering ………………………1
- no sound ……………………….. 0
• Motoric response
- Localize pain ……………………2
- rettraction of limb ……………..1
- non reaction ……………………0
 Plasmodium falcifarum
morphology in stained preparation
• Ring form: vary in
shape; double
chromatin, double
infection, accole

• Trophozoit: rare in
peripheral blood
after half grown
Plasmodium falciparum
Morphology of all stadiums
 Patogenese
• Ada 3 teori:
1. Teori mekanis :
tjdnya penyumbatan pemb drh otak akibat
tjdnya sitoadherens, sekuester, rosetting dan
faktor rheologi.
2. Teori Toksik  menghasilkan TNF
3. Teori Permeabilitas: tjdnya adhesi parasit pd
endothel, vasculer serta banyak faktor toksik yg lepas
serta radikal bebas terutama Nitric oxide (NO).
 Diagnosa Malaria Serebral
• Gjl Klinik : Trias malaria ( demam, menggigil, dan
berkeringat), Sakit kepala, ggn mental, nyeri tengkuk, kaku
otot dan kejang umum
• Sering dijumpai splenomegali dan hepatomegali
• Ggn kesadaran atau koma ( biasanya 24-72 jam)
• Pemr darah (thin/thick smear) dijumpai bentuk aseksual P.
Falcifarum
• Tidak ditemukan infeksi lain
• Lain-lain:hipoglicaemia, hiponatremia, hipofosfatemia,
pleocytosis sampai 80 cel/ micron kubik, limfosit sampai 15
cel/ mikron kubik
• CT/ MRI: edema serebri.
 Laboratorium
• Pemeriksaan dengan mikroskop
- sediaan darah tebal dan tipis
• Test diagnostik lain
- Metode immunokromatografi
- Analisa cairan Serebrospinal pd
Malaria serebral didapti peningkatan
limfosit > 15/ul.
- CT dan MRI: edema serebral
» Pengobatan Malaria Tanpa Komplikasi

» Malaria Falsiparum

» Lini pertama = Artesunat + Amodiakuin + Primakuin

» Lini kedua = Kina + Doksisiklin atau Tetrasiklin + Primakuin

» Pengobatan lini kedua diberikan jika pengobatan lini

pertama tidak efektif, dimana 28 hari setelah pemberian obat :

 Gejala klinis memburuk dan parasit aseksual positif, atau

 Gejala klinis tidak memburuk tetapi parasit aseksual tidak

berkurang (persisten) atau timbul kembali (rekurensi)

 Neurocisticercosis
• Def: cysticercosis cellulosa is the larval stage of
development of the cestode Taenia solium
(pork tapeworm).
• More than 60 million people are infected with
T. saginata world wide and about 4 million are
infected with T. solium
Life cycle
In Indonesia

North Sumatra West Kalimantan North Sulawesi

Irian Jaya

Lampung

Jakarta

Bali Flores

East Timor

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 NCC
• Pathology :3 Form cysticercosis in CNS
1. A cystic form involving the ventricles
and brain parenchyma
2. A racemose form involving the
meninges
3. A miliary form that is common in
children
 PATOGENESIS
• Human NCC : ingest food contaminated with
T.solium egg
• Parasite survive over period of year
• It secretes protease inhibitor, taeniastatin that
inhibit complement activation, neutrophyl,
lymphocyte and cytokine production.
• Minimal inflammation around viable cyst
• Inflammatory respons attacks the parasite,
leads to degeneration and calcification
 CLINICAL MANIFESTATION

Number of the cysts

Location (parenchimal/spinal)
Parasite activity
Immune respons of the host
 DIAGNOSIS NCC
• Definitive
Present of the scolex on histologic examination or
on CT scan/MRI
• Major criteria: CT scan cysticercus 0,5 – 2 cm;
EITB(enzym liked immuno transfer blot (+)
• Minor criteria:Clinical symptom, Intracerebral
punctata< subcuatenous nodule
Diagnose : 2 major or 1 major criteria + 2 minor
criteria
 MRI
• More sensitif for detect
parenchymal cyst, intraventricular
and subarachnoid cyst
 MANAGEMENT NCC

Anti parasitic drug

Symptomatic and anti-inflamatory
Surgery
 ANTI PARASITIC DRUG
Praziquantel :
50mg/kg/day, two weeks.
Albendazol :
15mg/kg/day, one month.
 SYMPTOMATIC/
ANTIINFLAMMATION
Corticosteroid :
Dexamethasone 4,5 – 12 mg/day, or
Prednisone 1mg/kg/day.
Decrease neurological symptoms due to
the death of the parasite.
Manitol 2g/kg/day, for acute intracranial
hypertension.
First line antiepileptic
 SURGERY
• For excision of large cysts or cyst in the
ventricles
 Spinal Tuberculosis
(Pott’s Disease).
Sinonim

Pott’s disease
David’s disease
Angular kyphosis
Kyposis secondary to tuberculosis
Tuberculosis of the spine

Kiking Ritarwan
 POTT’S DISEASE
• The first found Pervicall Pott (England,1779),
triad of pott’s disease: abscess, gibuss,
paraplegia
• Single or multiple vertebral involvement by
tuberculosis is frequently followed by spinal cord
compression due to development of cold abscess
in epidural space (Pott disease)
• The most common site of infection is
thoracolumbar spine, rarely cervical spine.
 Lokasi
1
Spondilitis TB
1
5
1.Paradiscal type >
2. Central type
2
3. Anterior type
4. Post Facet joint
3
4 5. Appendicial
Spondilitis Tuberkulosa
 Pathogenese
• Begin from existence of primary focus outside vertebra [
extrapulmoner], later;then disseminate by hematogen to vertebra
and usually [regarding/ hit] part of corpus vertebrae anterior at
elbow intervertebralis discus.
• Peaky earn happened just where as long as vertebra, but at most [at]
mid and under thoracalis vertebra and lumbal vertebra.
• Can [regarding/ hit] one segment or some vertebra segment. [At] the
place can happened cheese that happened effect of forming [of]
granulasi network and destruction on corpus vertebra little by little
from anterior to posterior.
• This Destruksi can generate anguler gibbus. Besides also earn also
happened " Cool abscess [ Cold Abcess]. Most [is] often met [by] cool
[by] abscess [at] thorakal vertebra 8 until lumbal 3.
Patofisiologi Spondilitis Tuberkulosa
Patofisiologi

• Rute Penyebaran ke
Vertebra :
– Arteri/hematogen
– Vena (batson plexus)
– Percontinuitatum
 Clinical manifestasion
• Back Pain (79%)
• Paraparese (66%)
• Kyphosis (52%)
• Fever (45%)
• Sensory disturbances (34%)
• Bowel and Bladder dysfunction (31%).
 Manifestasi Klinis
• Keadaan Umum
– Sakit kronis, demam, keringat
malam, anorexia, Penurunan
berat badan
• Gejala Lokal
– Nyeri lokal atau radikuler
– Spasme otot punggung
– night cries pada anak
– Defisit neurologis
– Deformitas
Manifestasi Klinis
• Pemeriksaan Klinis
– Deformitas, gibbus
– Spasme otot
paravertebral
– Defisit neurologis
 Diagnostic procedure
• Pemeriksaan darah : LED meninggi> 100mm/jam
• Tuberculin skin test (Purified Protein Derivative/ PPD)  biasanya
positif
• Biopsi kelenjar leher
• Sputum utk BTA (+) dan kultur Mycobacterium tuberculosa
• Radiologi
- proses spesifik di paru Thorax foto
- Vertebra : gibbus dan kyphosis
- CT Scan Vertebra :  destruksi vertebra, soft tissue calcification, narrow
disc space, bone erosion (scalloping).
- MRI vertebra:
a. membedakan TB spondilitis atau pyogenic spondylitis,
b. melihat adanya kompresi saraf.
Foto Rontgen
CT Scan
MRI
 Treatment Pott’s Disease
• 1. Immobilisasi, best rest total, extrafeeding, brace, korset
• 2. Antituberculous drugs
Berdasarkan Pedoman Penatalaksanaan TB paru:
termasuk kategori I ( TB diluar paru):
# 2 bln pertama : Streptomycin, INH, Rif dan PZA
# Bulan 3-12 : INH dan Rifampin

• 3. Operative
- Indikasi operasi pada pott’s disease:
adanya defisit neurologis
adanya abses paravertebra [Cold Abses]
terapi konservatif gagal
severe kyposcoliosis
cord/ nerve compression
- Tindakan bedah yang dilakukan:
requires anterior abscess drainage
anterior spinal arthrodesis.
posterior spinal arthrodesis.
PROGNOSA
• Dari 100 penderita ,yang mengalami disability
2 penderita mengalami reccurence paraplegia
setelah 3 tahun berobat, 1 penderita akibat
granuloma ekstramedularis dan 1 orang
dengan kifosis yang berat.
• Angka mortalitas 20%.
 Tetanus
= Bacterial Toxins

• Localized or generalized muscle stiffness

• Superimposed paroxysmal tonic spasm
(tetanospasmin)
• Tetanospasmin blocks inhibitory interneurons
• Autonomic instability
• Normal mental status
Tetanus is a toxic infection caused by the anaerobe
Clostridium tetani.

Spores exist in the soil and faeces, portal of entry resulting in

human disease include traumatic and surgical wound,
injection side (parenteral drug abusers), skin ulcers, burn
and injected umbilical cords.

Producing exotoxins (tetanospasmin and tetanolysin).

Tetanospasmin is a very potent neurotoxin probably is

solely responsible for the disease.

Tetanolysin has no recognised pathogenic activity.

Tetanus germs are found everywhere, usually in soil,
dust, and manure.
Enter a wound  produce a poison
 spreads throughout the body.
The first signs :
Headache and spasms of the jaw muscles.
Irritable
Muscle spasms : neck, arms, legs, stomach.
Convulsions  broken bones.
 Etiologi Clostridium tetani

Ada 2 bentuk :
1. Vegetatif : basil gram positif, obligat anaerob
ukuran :0,5-1,7 µm x 2,1-18,1 µm
motil, flagel
2. Spora : bentuk squash racket
tahan terhadap panas, resisten terhadap
berbagai desinfektan, dapat hidup bertahun
☺ Spora tumbuh saat bersentuhan dengan luka (potensial
redox ↓) Eksotoksin :
 Tetanospasmin (Tetanus toksin)
 Tetanolysin
Clostridium tetani : bentuk spora dan vegetatif

An aerobic gram positive bacillus

Noncapsulated

Sporm forming

Found in soil, house dust, animal

Intestine and human feces
 Epidemiologi

☺ Negara terbelakang, iklim tropis, lembab >>>

☺ Seluruh usia  neonatus, usia muda >>>
☺ WHO, 1995  eradikasi : 800.000-1 juta/thn  †
 ½ kematian  tetanus neonatal
 Afrika, Asia Tenggara  endemik

Insidens 18 per 100.000 populasi/ tahun

☺ Cvjetanovic :
 Afrika : 28/100.000
 Asia : 15/100.000
 Eropa : < 0,1/100.000
 Amerika Utara : < 0,1/100.000
 Patofisiologi
C.tetani masuk ketubuh melalui LUKA

dalam kondisi anaerob spora berkembang

toksin diproduksi(TETANOSPASMIN)

Retrograde intraneuronal transport/ axon  terminal

Motor neuron perifer/ med spinalis/ batang otak  memblokade pelepasan inhibitory
neurotransmitter glycine and GABA di terminal presinaptik
akibatnya eksitasi firing rate motor neuron meningkat tanpa ada inhibisi sehingga
otot lebih meningkat tonus dan spasmenya

Jk blokade di MNJ maka toxin menginhibisi pelepasan Ach

presinaptik bisa menjadi PARALISIS
Tahapan tetanospasmin : berikatan, internalisasi dan aktifitas
 Focus of infection
• Infected laceratioof puncture wound
• Infected chronic wound and abscesses
• Exposure via intravenous drug abuse
• Neonates
• No identifiable cause
• Possible causes: otitis media, Burns, Intranasal
foreign bodies, corneal abrasion, dental or
surgical procedures.
 Gambaran Klinis

☺Masa inkubasi :  jumlah toksin dan status imunisasi

MI  biasanya ± 8 hari (3 – 21 hari)
semakin jauh tempat trauma dari SSP  MI >>
☺Periode of onset : 1- 7 hari
☺MI dan periode of onset <<  keparahan >>

☺Klasifikasi tipe klinis (4) :

► Generalized tetanus (Tetanus umum)
► Localized tetanus (Tetanus lokal)
► Cephalic tetanus (Tetanus sefalik)
► Tetanus neonatorum
 Tetanus Umum

☺Paling umum : 80% dari kasus

☺Paling karakteristik : Lock jaw/ trismus
☺Dapat disertai : kaku kuduk, disfagia, rigiditas abdomen,
↑ temperatur (2-40C)
☺Kasus berat  risus sardonicus, opisthotonos
☺Karakteristik : spasme akut, paroksismal, nyeri, kejang
rangsang
☺Problem  spasme  obstruksi jalan nafas  apneu
☺ Masa inkubasi : 7-21 hari (tergantung jarak luka dengan CNS).
☺ Pemulihan  ± 4 minggu
 Tetanus Lokal

☺ Bentuk paling ringan

☺ Simptom awal : kaku, spt diikat, nyeri otot disekitar
luka,
twitching & spasme singkat
☺ Sering  luka di tangan atau lengan

☺ Manufer diagnostik  Recruitment spasm

☺  mendahului onset Tetanus umum

☺ Angka kematian  1%
☺ Prognosa : Baik
 Tetanus Sefalik

☺ Bentuk yang tidak lazim

☺ Terjadi dgn Otitis media atau trauma kepala
☺ Disfungsi saraf kranial  N.VII >>>
☺ Berkembang  tetanus umum atau tetap lokal
☺ Masa Inkubasi : 1 atau 2 hari
☺ Otot yang terkena  paralisa
☺ Sering fatal  prognosis buruk
 Tetanus Neonatorum

☺  = tetanus umum akibat infeksi pada neonatus

☺ Di negara miskin  ½ dari seluruh kematian neonatus
☺ MI : 3 – 10 hari sesudah lahir
☺
Disease of the seventh day
☺ Terjadi karena imunitas maternal ↓
☺ Tanah, kotoran hewan  tali pusat
tehnik aseptik yang kurang
☺ Tanda-tanda : ► lemah, tidak mampu menghisap
► spasme, rigiditas  opisthotonos
☺ Angka kematian : > 70%
 Tingkat keparahan

Table 1. Klasifikasi keparahan tetanus : Kriteria Patel-Joag

• Kriteria 1 : Lockjaw, isolaterd spasm ,dysphasia, stiffness of muscle back
• Kriteria 2 : Spasme, tanpa mempertimbangkan frekuensi atau keparahan
• Kriteria 3 : Masa inkubasi ≤ tujuh hari (waktu diantara trauma dan tanda pertama)
• Kriteria 4 : Periode of onset ≤ 48 jam (waktu antara tanda pertama(lockjaw) dan
• kejang pertama)
• Kriteria 5 : Peningkatan temperature : rectal 1000F, atau aksiler 990F

Grading :
• Grade 1 : Kasus ringan : terdapat satu criteria, biasanya kriteria 1 atau 2 (tidak ada
kematian)
• Grade 2 : Kasus sedang : terdapat 2 kriteria, biasanya kriteria 1 dan 2. Biasanya
masa inkubasi lebih dari 7 hari dan onset lebih dari 48 jam (kematian 10%)
• Grade 3 : Kasus berat : terdapat 3 kriteria, biasanya masa inkubasi kurang dari 7
hari atau onset kurang dari 48 jam (kematian 32%)
Grade 4 : Kasus sangat berat : terdapat 4 kriteria (kematian 60%)
• Grade 5 : Calculated mortality : kelima criteria, termasuk puerperal dan tetanus
neonatorum (kematian 84%)
 DIAGNOSA

Hanya secara klinis

Tes untuk konfirmasi (-)

Studi bakteriologi ± 1/3 pasien

Tetanus lokal mengenai Penyebab nerve

> 1saraf cranial palsy lain

TEST SPATULA
 Diagnosa Banding

1. Keracunan striknin
2. Reaksi Distonia
3. Meningitis
4. Penyakit temporomandibuler joint, proses inflamasi gigi,
mulut, tonsil dan faring
5. Rabies
6. Tetani
7. Stiff-man syndrome
8. Psychogenic disorders
Tabel 2. Diagnosa banding tetanus

Simptom Diagnosa banding

• Trismus Alveolar/dental patologi
Temporo-mandibular disease
• Kaku kuduk Muscle spasm
• Meningitis
• Disfagia Acute pharyngeal disease
• Spasme Keracunan striknin
Lesi intrakranial
Drug-induced dystonic reactions
• Neonatal tetanus Sepsis
Meningitis
Konvulsi
 PENATALAKSAAN

☺ Rawat di ICU
☺ Ruang rawat yang tenang  stimulasi <<<
☺ Prinsip manejemen :
eradikasi kuman
netralisit toksin diluar SSP
minimalisir efek toksin di SSP

Portal of entry
☺ eksisi luka
☺ gangren (+)  amputasi
☺ debridement  spasme terkontrol
 Imunoterapi

☺ pengobatan untuk menetralisir Tetanospasmin

imunisasi aktif

☺ Human Tetanus Immunoglobulin (HTIG)

 3.000 – 5.000 IU/ i.m.
☺ Equine Antitetanus serum (ATS)
 uji hipersensitifitas, desensitisasi
 harga lebih murah
 Sebaiknya 20.000 U diberikan IM sedgkan 10.000 U
diberikan IV sesudah 48 jam pemberian pertama
☺ Intravenous Immune globulin (IVIG)
pemberian antitoksin sebelum debridement
 Kontrol Jalan nafas dan Ventilasi
☺ spasme tetanik  obstruksi jalan nafas
☺ Endotracheal tube (ETT)
☺ Trakeostomi  moderate & severe

Antibiotika
mengurangi bentuk vegetatif
☺ Sensitif  Metronidazole, PNC, Sefalosporin,
Imipenem, makrolid, tetrasiklin
☺ PNC  central GABA antagonist => sdh ditinggalkan
Dosis : 100.000-200.000 IU/kg/hari
☺ Metronidazole  antibiotik pilihan
Dosis : 500 mg/ 8 jam/IV + dgn
clindamisin, erithromisin, tetrasiklin, vancomysin
 Kontrol Rigiditas & Spasme

☺ Benzodiazepine : agonis GABA

dosis ~ 500 mg/ hari
tetanus neonatorum  15-40mg/kg/hr
☺ Diazepam,Lorazepam, Midazolam
Diazepam 0,1 mg/kg IV/ 4 jam (dewasa 500
mg/ hr dan neonatus 15-40 mg/ hr), atau
midazolam 0,1 mg/ kgBB IV/ IM/ 4 jam, atau
midazolam 2- 10 mg/ jam IV, atau propanolol
infuse 1-10 mg / jam.
 Blokade NMJ

☺ Obat GABAergik gagal  blok NMJ

☺ Vecuronium (0,1 mg/kg IV 6-8mg/jam)
☺ Pancuronium :  takikardi, hipertensi, ↑CO
 mengaburkan efek otonom

Terapi disfungsi otonom

sympathetic overactivity (SOA)

☺ Labetolol, esmolol, clonidine, morfin sulfat

☺ Magnesium sulfat
 Nutrisi
☺ aktifitas otot & otonom ↑  kebutuhan nutrisi >>
☺ ganggguan gastric emptying time  nutrisi vena sentral

Komplikasi

komplikasi penyakit & komplikasi terapi

☺ komplikasi pernafasan
☺ komplikasi kardiovaskuler dan otonom
☺ komplikasi sistemik lain
Tabel 3. Komplikasi tetanus
Sistim Komplikasi
Jalan nafas Aspirasi *
Laryngospasm/obstruction*
Sedative associated obstruction*

Respirasi Apnu*
Hipoksia*
Gagal nafas tipe I* (atelektasis, aspirasi,pneumonia)
Gagal nafas tipe II* (spasme laring, prolonged
truncal spasm, sedasi berlebihan)
ARDS*
Komplikasi ventilasi bantuan yang lama
(mis.pneumonia)
Komplikasi trakeostomi (mis.stenosis trakea)

Kardiovaskuler Takikardi* Hipertensi* Iskemia*

Hipotensi* Bradikardi*
Takiaritmia, bradiaritmia*
Asistole*
Gagal jantung*
Tabel 3. (lanjutan)

Ginjal High output renal failure*

Oliguric renal failure*
Urinary stasis and infection

Gastrointestinal Gastric stasis

Ileus
Diare
Pendarahan*

Lain-lain Berat badan menurun*

Tromboemboli*
Sepsis dan multiple organ failure*
Fraktur vertebra selama spasme
Avulsi tendon selama spasme
 Pencegahan

Imunisasi Aktif Profilaksis

☺ Tetanus Toksoid  imunitas ± 5 thn
☺ Imunisasi ibu hamil  mencegah tetanus
neonatorum
☺ Imunitas ditransfer secara pasif : ibu  fetus

Imunisasi paska trauma

☺ Rekomendasi profilaksis : - kondisi luka
- riwayat imunisasi
☺ Antitoksin : HTIG  250 unit
ATS  1500 unit
TABLE 12.1 Immunization against tetanus
----------------------------------------------------------------------------------------------------------------------------------------
Subject/vaccine and dose Age/interval
----------------------------------------------------------------------------------------------------------------------------------------
Children (age less than 7 years)*
1-DPT 6-8 weeks of age
2-DPT 4-8 weeks after previous dose
3-DPT 4-8 weeks after previous dose
4-DPT 1 year after previous dose
Booster – DPT 4-6 years of age
Booster – Td every 10 years after previous dose
Adults and children older than 7 years not previously immunized*
1-Td first encounter
2-Td 4-8 weeks after previous dose
3-Td 6 months–1 year after previous dose
Booster-Td every 10 years after previous dose
Pregnant women*
Previously immunized :
Booster –TT during first 6 months of pregnancy (optimal)
Or as late as 6 weeks before delivery
Previously unimmunized :
1-TT first encounter during pregnancy
2-TT 4 weeks after previous dose
----------------------------------------------------------------------------------------------------------------------------------------
* American Academy of Pediatrics (Peter et al. 1994); * World Health Organization, Expanded Programme on
Immunization (Whitman et al. 1992)
Abbreviations ; DPT, diphtheria and tetanus toxoids and pertussis vaccine adsorbed : Td, tetanus and reduced-
dose diphtheria toxoids adsorbed; TT, tetanus toxoid.
TABLE 12.2. Guidelines for tetanus prophylaxis in wound management
______________________________________________________________________
Vaccination status Clean, minor wounds Tetanus-prone wounds*
Td+ TIG Td+ TIG++
______________________________________________________________________

Unknown or <3 doses Yes No Yes No

≥ 3 doses
Last booster < 5 years No No No No
Last booster 5-10 years No No Yes No
Last booster > 10 years Yes No Yes Yes

Recommendations of the Advisory Committee on Immunization Practices-United States (CDC,

1992).

* Wounds contaminated with dirt, faeces, soil, saliva; puncture wounds; avulsions; and wounds
resulting from missiles, crushing, burns and frostbite. Wounds presenting after delay or
requiring debridementdue to the presence of necrotic tissue.

* Td : tetanus and reduced-dose diphthetia toxoids adsorbed; for children less than 7 years, DPT
(diphtheria and tetanus toxoids and pertussis vaccine adsorbed) is preffered.
++ 250-500 units human tetanus immune globulin; given intramuscularly in another area than the
Td.
 Prognostic Score for Tetanus of Gallais et al
Parameter Finding Score
incubation < 7 days 1
>= 7 days 0

extension < 2 days 1

>= 2 days 0

portal of entry intramuscular injections 2

umbilical uterine surgical burn compound fracture 1

all other portals or unknown 0

paroxysms >= 4 per hour 1

present but < 4 per hour 0

rectal temperature > 38.4° C 1

<= 38° C 0

pulse in beats per minute adults > 120 neonate > 150 1
adults <= 120 neonate <= 150 0
Score Mortality Rate
0 0%
1 4.22%
2 13.63%
3 30.43%
4 57.14%
5 70.73%
6 94.73%
7 100%
 POLIOMYELITIS
• Sinonim : Acute Anterior Poliomyelitis,
Infantile Paralysis, Penyakit Heine Medin
• Definition: Poliomyelitis is caused by
enterovirus that invades motor neurons in the
spinal cord and brain stem.
• Polio virus menginfeksi melalui jalur fekal oral
(dari tangan ke mulut) tetapi dapat juga
melalui kontak langsung.
 Etiology and Pathology
• Virus enterovirus (RNA virus)
• Virus that invades motor neurons in the spinal
cord and brainstem
• Neuronal death results in the atropy of muscles
fibers supplied by the affected motor unit, unless
there is a compensatory sprouting of new fibers
by surviving axons that contact and innervate
some of the newly denervates muscle fibers 
effect is loss muscle fibres, muscle wasting and
weakness
 Clinical Features
• Systemic features (rash, pharyngitis, diarrhea)
• Muscle weakness
• Muscle pain
• Unaccustomed fatigue
• Post polio syndrome occurs in approximately 30
% of patients who survive acute pomiomyelitis.
• More common in women, 10% < 2 years, 70% <
10 years old.
• Type of Infection: asymptomatic, abortif, aseptic
non paralytic, paralytic
• Asymptomatic poliomyelitis :
–Infeksi polio paling banyak
–Virus masuk ke sal pencernaan 
keluar dlm feses
–Tanpa tanda infeksi nyata
–Hanya : panas, anoreksia, mencret,
batuk
• Abortive poliomyelitis :
–Diagnosa ditegakkan bila ada wabah polio
–Gejala :
• Panas, malaise, anoreksia, nausea, muntah,
sakit kepala, konstipasi, sakit-perut,
faringitis, batuk, diare
–Diagnosa pasti :
• Isolasi virus polio
–Selama wabah :
–Anak tersangka : istirahat 1 mgg  1 bln
kmd evaluasi otot
• Non paralytic poliomyelitis :
–Gejala: spt tipe abortive
–Terutama :
• Sakit kepala
• Kekakuan otot :
– Belakang leher
– Badan
– Tungkai
 Paralytic poliomyelitis
• Poliomyelitis paralitic spinal: nyeri kepala,
demam, terjadi nyeri otot hebat. Dalam 1 – 2
hari, timbul paresis atau paralisis flaksid
simetris.
• Poliomyelitis bulbar: disfungsi saraf cranial dan
medula spinalis. Ggn pernafasan + paralisis otot
ekstraokuler, wajah dan pengunyah.
• Poliomyelitis bulbopsinal. Poliomyelitis bulbar+
paralitic
• Polioensefalitis: Kejang, koma dan paralisis
spastik
 Diagnosis
• Muscle biopsy
• Pemeriksaan neurologis :
- Kelemahan otot (otot tubuh terserang paling
akhir, sensorik biasanya normal, Refleks
tendon menurun atau tidak sama sekali, atrofi
otot mulai terlihat 3-5 minggu setelah
paralisis, gangguan fungsi otonom, ganguan
saraf kranial.
 Pemeriksaan penunjang
• Isolasi virus
• Serologi
• Cairan serebrospinal
 Treatment
• There is no effective treatment
 RABIES
• Is an acute, almost invariably fatal infectious
illness caused by a neurotrophic of the
rhabdovirus family
• Rabies is zoonotic disease
• Bats, skunks, racoons and dog are implicated
human rabies
• Occasionally rabies can be transmitted by other
means than an animal bite, including inhalation
of airbone virus in caves contaminated by bat
secretion
 Etiology and pathology
• The rabies virus is a bullet shaped, enveloped
RNA containing virus that usually gains acces
to the body by a bite from a rabid animal.
• The virus then replicated locally in muscle
cells, penetrates nerve ending, and travels in
retrograde fashion up the nerve axons to the
CNS.
Karakteristik Virus Rabies
 Ordo
Mononegavirales
 Family
Rhabdoviridae –
‘bullet’ shaped
 Genus Lyssavirus
 Species Rabies virus

Gambar dari Centers for Disease Control and Prevention

www.cdc.gov/ncidod/dvrd/rabies
 PATOGENESIS
• Transmisi:
Utama: Gigitan (saliva)
Lainnya: scratch, oral, aerosol, transplantasi kornea
(iatrogenik)
• Virus rabies tidak dapat penetrasi ke kulit yang tidak
terluka
• Virus tidak menyebar melalui pembuluh darah
• Waktu inkubasi bervariasi antar individu dan spesies
(minggu – bulan – tahun)
 PATOGENESIS
1. Penyebaran menuju Sistem Saraf
pusat
2. Penyebaran di dalam Sistem Saraf
Pusat
3. Penyebaran dari Susunan Saraf
Pusat
 6. Virus bereplikasi di SSP,
5. Otak terinfeksi
kemudian disebarkan ke
organ lain: kelenjar adrenal,
nasal mucosa, kelenjar
4. Virus menginvasi ludah; virus disekresikan di
spindle saliva
neurotendinous,
masuk ke CNS dan
paravertebral ganglia 3. Virus bereplikasi local
melalui axoplasmic pd neuromuscular junction
flow melalui konjugasi retro-
vesicular ganglion (RVG)
1. Virus masuk ke dengan nicotine
dalam tubuh melalui acetylcholine receptor
gigitan
2. Virus menginvasi sel-sel otot di
sekitar luka gigitan untuk waktu
yang singkat, kemudian
menembus membran plasma

Diadaptasi dari Jubb, Kennedy, and Palmer’s, 2007 dan http://pathmicro.med.sc.edu/virol/route.jpg

 Clinical features
• Incubation period 20 -90 days
• Prodromal phase – flu like symptoms, tingling,
burning, depression, bizzare behavior,
halucination, insomnia, hyperactivity
• Excitation phase - muscle function, speech,
vision, anxiety, hydrophobia
• Paralytic phase - muscles weaken,
consciousness fades, death
 Differential Diagnosis
• Tetanus
• Post vaccinal encephalomyelitis
 Treatment
Human diploid cell rabies vaccine (HDCV) or
rabies vaccine adsorbed (RVA)
COMBINATION THERAPY :
• RABIES VACCIN (MULTIPLE-SITE INTRADERMAL
ROUTE)
• HIRG (INTRAMUSCULER)
• RIBAVIRIN (IV AND INTRAVENTICULER)
• IFN_a (IV AND INTRATHECAL)
• KETAMIN (INTRAVENOUS INFUSION)
 Supportive :sedative, analgetica-
narcotica,anticonvulsant, neuromuscular blocker
 WOUND TREATMENT
• Rabies virus easy killed by sunlight, soap

• Transmission can be almost completely

prevented by local wound treatment given
within the first 3 hours after exposure
 Post-exposure prophylaxis
• The aim :
Is to neutralise inoculated virus before it can
enter the nervous system of the patients
 PENCEGAHAN
• Vaksinasi sesudah paparan
Dosis VAR pada anak dan dewasa sama.
Hari 0 : 0,5ml deltoid kanan dankiri.
Hari 7 : 0,5ml IM di deltoid
Hari 21 : 0,5ml IM di deltoid

• Pemberian bersama SAR, diberi VAR 0,5ml pada hari

ke 90.
 PENCEGAHAN SETELAH TERPAPAR
Dapat dgn VAR saja atau (VAR+ SAR).
• VAR saja bila :
Luka tidak berbahaya (jilatan, ekskoriasi/lecet)
terletak di tangan/kaki.
(VAR + SAR) bila :
Luka berbahaya jilatan/luka pada mukosa
terletak di atas bahu (muka, kepala, leher).
 CARA PEMBERIAN SAR
• Serum heterolog :
Tes kulit terlebih dahulu.
Infiltrasi pada luka sebanyak-banyaknya,
sisanya disuntik IM.
Dosis : 40 IU/kgBB
 CARA PEMBERIAN SAR
• Serum homolog
Infiltrasi pada luka sebanyak-banyaknya,
sisanya disuntikkan secara IM.
Dosis : 20 IU/kgBB.
Pemberian hari pertama kunjungan.
 VAKSINASI SEBELUM PAPARAN
• Hari 0 : 0,5 ml.IM
• Hari 28 : 0,5 ml.IM

Vaksin ulangan setelah 1 tahun diulangi

seterusnya setiap 3 tahun.

Injeksi di area deltoid pada dewasa, di area

paha anterolateral pada anak