Infeksi pada Sistem Sa

raf Pusat

Meningitis,
Ensefalitis, Spondilitis TB
Overview
Overview
Infectious diseases of the nervous system
constitute a unique challenge for the
practicing clinician; they are relatively
uncommon, and are often serious enough to cause disab
ility or death, yet frequently are
treatable.
Meningitis
Meningitis Bakteri Akut
Insiden: 4-10 kasus / 100. 000 per tahun (USA)
Agent penyebab bervariasi
Mortalitas: kira-kira 20%
Gejala klasik: sakit kepala, demam, leher kaku, dan pe
rubahan tingkat kesadaranseizure, kelumpuhan sara
f kranial, defisit neurologis fokal, edema papil, hernias
i otak dan koma
Etiologi
Streptococcus pneumoniae
Penyebab paling umum dari meningitis pada orang dewasa> 2
0 tahun
Neisseria meningitidis
Enterik gram negatif basil
Grup B. streptokokus
Monocytogenes Lysteria
Haemophillus influenzae
KL. Roos. Harrison Neurologi di Clinical Medicine. 2006
Diagnosis Meningitis Bakteri
Onset sakit kepala akut, leher kaku, kebingungan, lethargi atau k
oma, dan demam
Petekie berimplikasi penyebab meningokokus
Kemungkinan besar organisme tergantung pada usia pasien, statu
s imun dan faktor risiko
Analisis cairan serebrospinal (CSF) menunjukkan tekanan pembu
kaan tinggi, penurunan glukosa, > 10 WBC / mikroliter (terutama
PMN)
Organisme berkapsul divisualisasikan dengan pewarnaan Gram
Barbara, SK. Saat Diagnosis & Treatment di Neurology. 2007
Diagnosis Banding Meningitis Bakteri Akut

A. Chauduri et al. 2008 EFNS European Journal of Neurology 15, 649-659

Patogenesis Meningitis bakteri dan perkembangan cedera otak

Scheld, W. 2004. Infeksi Sistem Saraf

Pusat. 3rd edisi
Lumbar Pungsi
Comparison of CSF finding in Meningitis

A. Chauduri et al. 2008 EFNS European Journal of Neurology 15, 649–659

 Flow chart manajemen pasien darurat dengan dugaan meningitis bakteri akut

A. Chauduri et al. 2008 EFNS European Journal of Neurology 15, 649-659

Epidemiologi
 Tuberkulosis meningitis ( TMB ) adalah bentuk serius TB ekst
ra paru .
Prevalensi TMB 20 % pada pasien dari bentuk TB paru
Selain itu, data terbaru menunjukkan bahwa meskipun di bany
ak negara tuberkulosis paru telah menurun, tetapi
Prevalensi TBM pada tingkat kematian tetap tinggi , dengan 6-
65 % dari pasien kritis karena TBM meskipun terapi yang efekt
if dan banyak lainnya menderita sequele
Pathophysiology
 CNS tuberculosis is secondary to disease elsewhere in the b
ody.

 Mycobacteria reach the brain by hematogenous route.

 Initial small tuberculous lesions (Rich foci) develop in mening

es, subpial or subependymal surface of the brain or the spinal
cord, and may remain dormant for years.

 Reactivation may be due to endogenous factors:

Innate immunological and non immunological defenses
Level of function of cell mediated immunity.

 Tumour necrosis factor ά may have a role.

Clinical presentation of TBM
Clinical Features Children (%) Adults (%)

History
Tuberculosis 55 8-12
Symptoms
Headache 20-50 50-60
Nausea/vomiting 50-75 8-40
Apathy/behavioural changes 30-70 30-70
Seizures 10-20 0-15
Signs
Fever 50-100 60-100
Meningismus 70-100 60-70
Cranial nerve palsy 15-30 15-40
Coma 30-45 20-30
Zuger A. Tuberculosis. In: Scheld WN, Whitley RJ, Marra CM, editors. Infections of
Central Nervous System. Philadelphia: Lippincott, 2004. pp. 441-9.
Staging of TBM
TBM is classified into 3 stages according to the British Medical Re
search Council (MRC) criteria
Stage I: Prodromal phase with no definite neurologic
symptoms.

Stage II: Signs of meningeal irritation with slight or no

clouding of sensorium and minor (cranial nerve
palsy) or no neurological deficit.

Stage III: Severe clouding of sensorium, convulsions, focal

neurological deficit and involuntary movements.
 Modified MRC criteria

Grade I: Alert and oriented (GCS 15) without focal

neurological deficit.

Grade II: GCS 14-10 with or without focal neurological

deficit or GCS 15 with focal neurological deficit.

Grade III: GCS less than 10 with or without focal

neurological deficit.
Diagnostic rule for TBM
Variable Score
Age (years) >36 2
<36 0
Blood WBC count (103/ ml) >15000 4
≤15000 0

History of illness (days) >6 -5

≤6 0

CSF WBC count (103 / ml) ≥ 750 3

< 750 0
CSF neutrophil % ≥ 90 4
< 90 0

Score : < 4 –TBM; > 4 - Non TBM

Differential diagnosis of TBM
 

 Fungal meningitis (cryptococcosis, histoplasmosis, blast

omycosis, coccidioidal mycosis)
 Viral meningoencephalitis (herpes simplex, mumps)
 Partially treated bacterial meningitis
 Neurosyphills
 Focal parameningeal infection
 CNS toxoplasmosis
 Neoplastic meningitis (lymphoma, carcinoma)
 Neurosarcoidosis
Investigations
CSF examination
CSF Smear examination: Zeihl Nelson’s, Gram’s and In
dia Ink stain.
CSF culture on solid media: Egg or agar based, ACTEC s
ystems.
Adjunctive tests : CSF tuberculostearic acid, adenosin
e deaminase, radiolabelled bromide partition test.
Molecular diagnosis : Nucleic acid amplification, DNA
finger, printing, PCR.
Cerebrospinal fluid examination
 Predominantly lymphocytic pleocytosis, with increased proteins
and low CSF/ blood glucose ratio.

 WBC count can be normal in presence of depressed CMI (elde

rly and HIV positive individuals).

 CSF protein (> 150 mg/dl) should always raise the suspicion of
tuberculosis or fungal infection, rarely seen in viral meningitis.

 Smear is +ve in 10%, can be increased by examining large vol

ume of CSF.

 Culture is +ve in 25-70%.

 Cerebrospinal fluid examination
 Repeat CSF frequently shows a falling glucose level, a rising protein concen
tration and a shift to mononuclear predominance.

 CSF cell counts decrease by 50% during the first month but may not become
normal for a year.

 CSF glucose becomes normal in 1 to 2 months and protein becomes normal

by 12 months or longer.

 CSF cultures should be sterile by the first month, but PCR results may remai
n positive for a month.
Sensitivity and specificity of adjunctive tests for the diagnosi
s of TBM

Tests Sensitivity (%) Specificity (%) Time Required (h)

Biochemical
Radiolabelled bromide partition ratio 90-94 88-96 48
CSF adenosine deaminase level 73-100 71-99 <24
CSF tuberculostearic acid level 95 99 <24

Immunologic test (ELISA)

Antigen ELISA 38-94 95-100 <24
Antibody ELISA 52-93 38-94

Kalita J, Misra UK. Tuberculosis Meningitis. In Misra UK, Kalita J (Eds) Diagnosis and
Management of Neurological Disorders. Wolter Kluwers Health New Delhi 2011; pp. 145-
66.
Sensitivity & specificity of various diagnostic tests for TB
M

Diagnostic test Sensitivity Specificity

ZN staining 10-20% 100%
LJ Culture 15% (25-80) 100%
BACTEC Culture 55% 100%
ELISA 52.3% 91.6%
TB PCR 56% 98%
TST 73% 56%
QTF-GOLD 76% 98%
ELISPOT 87% 92%

Menzies et al, Ann Int Med. 2007; 146: 340-354.

Diagnostic criteria for TBM

Class Definition
Definite Acid-fast bacilli seen in the cerebrospinal fluid.
Probable Patients with one or more of the following:
i. Suspected active pulmonary TB on chest radiography.
ii. AFB found in any specimen other than the CSF.
iii. Clinical evidence of extrapulmonary tuberculosis.
Possible Patients with at least four of the following:
i. History of tuberculosis.
ii. Predominance of lymphoytes in the cerebrospinal fluid.
iii. A duration of illness of more than six days.
iv. A ratio of CSF glucose to plasma glucose of less than 0.5.
v. Altered consciousness
vi. Turbid cerebrospinal fluid.
vii. Focal neurologic signs.

Thwaites GE et al. Diagnosis of adult tuberculosis meningitis by use of clinical and laboratory features.
Lancet 2002; 360: 1287-92.
Imaging in TBM
 CT/ MRI confirm the presence and extent of basal arachnoiditis, cerebral oe
dema, infarction, ventriculitis and hydrocephalus.

 Abnormalities depend upon stage of disease:

I (normal in 30%), II (Normal in 10%), III (Abnormal in all).

 Hydrocephalus (70-85%), basal meningeal enhancement (40%), infarction

(15-30%), tuberculoma (5-10%).

 Meningeal enhancement, tuberculoma or both have a sensitivity of 89% and

specificity of 100%.

 Precontrast hyperdensity in basal cisterns is the most specific radiological si

gn.

 Radiological findings also help in prognostication.

Imaging abnormalities in TBM
Principles of treatment of TBM
Treatment should be started early in suspected TBM
.

Multiple antimicrobial drugs are required.

Drugs must adequately cross the blood-CSF barrier t

o achieve therapeutic concentrations in CSF.

Drugs should be taken on a regular basis for a sufficie

nt period to eradicate the CNS infection.

Intrathecal therapy is not required.

 No general consensus regarding the choice of drug,

doses and duration of treatment.
Treatment
 CNS tuberculosis is categorised under TB treatment category I b
y WHO.

 Initial phase therapy ( 2 mths) with isoniazid, rifampicin, pyrazina

mide and streptomycin or ethambutol followed by continuation ph
ase (7 mths) with isoniazid and rifampicin.

 The BTS and IDSA/ATS recommend 9-12 months of ATT. Therap

y should be extended to 18 months in patients who do not tolerat
e pyrazinamide.

 Short duration therapy (6 mths) might be sufficient if the likelihoo

d of drug resistance is low.

 However as the emergence of neurological deficit has been seen

in some of the studies so a minimum of 12 months treatment wou
ld be worthwhile.
What is the best anti-tuberculous drug regimen?
 Isonaizid, rifampicin and pyrazinamide are considered mandatory at th
e beginning of TBM treatment.

• Isoniazid penetrates the CSF freely and has potent early bactericidal
activity.

• Rifampicin penetrates the CSF less well (maximum concentrations ar

ound 30% of plasma), but the high mortality from rifampicin resistant T
BM has confirmed its central role in the treatment of CNS disease.

• There is no conclusive evidence to demonstrate that pyrazinamide im

proves outcome of CNS tuberculosis, although it is well absorbed orall
y and achieves high concentration in the CSF.

Thwaites GE et al. J Neurol Neurosurg Psychiatry 2000; 68: 289-99;

Lancet Neurol 2005; 4: 160-70.
Choice of the fourth drug
 No data from controlled trials.

 Most authorities recommend either streptomycin or ethambutol, althou

gh neither penetrates the CSF well in the absence of inflammation.

 Streptomycin should not be given to those who are pregnant or have re

nal impairment.

 Ethambutol should be avoided where optic neuropathy is a concern.

 The fluoroquinolones may represent an effective fourth agent, although

data concerning their CSF pharamacokinetics and safety during prolon
ged therapy are limited.

 Others-Ethionamide, prothionamide.
ENSEFALITIS
Definisi
Ensefalitis adalah inflamasi pada parenkim otak yang me
nyebabkan disfungsi otak.
Meningen (meningoencephalitis), brainstem (rhombence
phalitis), atau sumsum tulang belakang (encephalomyelit
is) dapat bersamaan terlihat.
Dapat berupa disfungsi neurofisiologis fokal atau difus.
Epidemiologi
Dunia : 3.5-7.4/ 100.000 populasi per tahun.
Anak : 16/100.000 populasi per tahun
Health Protection Agency : 1.5 kasus/100.000 populasi dan anak 2
.8 kasus/100.000 populasi
LK : PR  2.9 : 2.8 / 100.000 populasi
Negara industri : paling banyak adl. virus herpes simpleks (HSV)
(1: 250.000-500.000 populasi).
↑ pada anak-anak dan lansia.
Etiologi
Gejala Prodormal
Headache
Malaise
Anorexia
Nausea and Vomiting
Abdominal pain
Altered LOC – mild lethargy to deep coma.
AMS – confused, delirious, disoriented.
Mental aberrations:
hallucinations
agitation
personality change
behavioral disorders
occasionally frank psychosis
Focal or general seizures in >50% severe cases.
Severe focused neurologic deficits.
Gejala Neurologis
Afasia
Ataxia
Hemiparesis dengan hiperefleks tendon
Gerakan involunter
Defisit saraf kranialis (ocular palsies, kelemahan pada wajah)
 Dema
Sakit m
Kepala

Perubah
an status
mental

Trias Klinis
Pemeriksaan Penunjang
Laboratorium

Lumbal Pungsi

EEG

Neuroimaging
Analisis Cairan Serebrospinal pada Infeksi SSP
Neuroimaging EEG
Dapat menyingkirkan penyakit
lain

CT Scan dan MRI

EEG menunjukkan gambar

HSV  edema dan perdarahan abnormal pada >80% asien
pada lobus temporal dengan ensefalitis virus akut
Flavivirus dan Eastern equine virus  MRI: pola
intensitas campuran atau lesi hipodens pada
gambar T1 di talamus, ganglia basal dan midbrain

Enterovirus ensefalitis  MRI: hipeintense T2

dan lesi FLAIR yang berlokasi di midbrain, pons,
dan medulla
Terapi
Cairan IV
Antifungi

Antipiretik

Kortikostero
id

Anti Epilepsi

Antibiotik
SPONDYLITIS TB
 Tuberkulosis tulang belakang = Spondylitis TB = Pott-
disease
 Spondilytis TB disebabkan oleh Mycobacterium tuberculosis
 M. tuberculosis adalah organisme aerobik yang tumbuh
lambat
 Dalam kondisi yang tidak menguntungkan, ia akan tumbuh
hanya sesekali atau tetap aktif untuk waktu yang lama untuk
tumbuh kembali setiap kali sistem imun host menurun.

2019/07/05 89
 Gejala klinis

 Tahap aktif: malaise, penurunan

berat badan, kehilangan nafsu
makan, berkeringat di malam hari
dan kenaikan suhu malam hari

 tulang belakang kaku dan nyeri

pada pergerakan, dengan deformitas
kyphotic yang akan nyeri pada
perkusi
2019/07/05 91
  Tahap sembuh: pasien tidak
terlihat sakit atau terasa sakit,
mendapatkan kembali berat
badan yang hilang dan tidak ada
kenaikan suhu tubuh saat malam
atau berkeringat di malam hari.
 Tidak ada rasa sakit atau nyeri
di tulang belakang dan spasme
otot paraspinal membaik.

2019/07/05 92
 Terapi

Dibagi menjadi: Operative Operative dan Non Operative

 Modalitas pengobatan saat ini sangat efektif jika gangguan

tersebut tidak disertai deformitas berat atau defisit neurologis
menetap

 Terapi kepatuhan dan resistensi obat TB merupakan faktor

tambahan yang secara signifikan mempengaruhi hasil
individu.

93
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3. Pusat untuk Pengendalian Penyakit dan Pencegahan (CDC), 2013
4. Organisasi Kesehatan Dunia (WHO) 2014
5. Dian S., Tetanus., 2011., Infeksi PADA Sistim Saraf., Kelompok Studi
neuro Infeksi. Perdossi
6. Prof.Dr. sayaGst. Ng. Gd.Ngoerah; 1991;Dasar-Dasar ilmu penyakit
Saraf; Airlangga university Press
7. Jose A Hidalgo, MD; 2014;Pott Penyakit; Medscape
8. Clifford R. Wheeless, III, MD. 2013;yg bersakit paru-paru Spondilytis;
DukeOrtopedi
9. Vinod Agrawal, PR Patgaonkar, SP Nagaria2010 Juli-Desember; 1 (2):
74-85, JCraniovertebr Junction Spine
10. Pusat untuk Pengendalian Penyakit dan Pencegahan (CDC), Global
Health - Polio, 2013 98
Matur Suksma