INFEKSI

Di Bidang Bedah Saraf

Happy Kurnia
SMF Bedah Saraf Kariadi/FK.UNDIP
• 1928 : Alexander Flemmings discovered
accidentally : Penicillin
• 1942 The first patient was successfully treated
for streptococcal septicemia in the United
States
• Reduce the number of deaths and
amputations of troops during World War II
 Development of Antibiotics & More precise
surgical procedures → treatment of Intracranial
Infections has improved dramatically.
Inappropriate and not prudence antibiotics →
resistance
AIDS → microbes to parasite / fungi
How Ab become resistance
Ted.com :
Monro- Kellie
 Parenchym (Brain) Infection

• CNS is protected from infection of wide

variety of pathogens by
( Except SCALP and Cranium)

1. BBB
2. Humoral Immune Factor
3. Resident and Circulating Immune Cells
 BBB
• Composed of blood vessels – parenchymal
barrier
• Structure:
microvascular endothelial cell, pericyte,
astrocyte foot procceses (or ependymal cell
for blood-CSF barrier)
• Restrict the movement of pathogens from
intravascular space across the BBB into brain
parenchyma or CSF
 Routes of CNS Infection
• Natural
Predominantly mucosal surface: nasopharynk,
respiratory tree, GI tract, Cutis
Some hematogen
Direct Trauma

• Iatrogenic
Neurosurgeon
Perioperative: scalp, cranium, meninges, implants,
 How to entry across BBB?
1. Transcellular : E. Coli, Grup B Streptococci
2. Paracellular : Protozoa
3. 'Trojan Horse’, carriage within a
transmigrating of leucocyte : Listeria
Monocytogenes, Streptococcus,
Mycobacterium TBC, HIV
Pathways across BBB
E Coli binding and invasion of the BBB
Trojan Horse across BBB
 Consequences of CNS Infection
1. Brain Edema
2. Neurotoxicity:
 Neurotoxicity
• Direct Infection of the Neuron
• Collateral damage secondary to the immune
response
• Pathogen derivied Factors

In addition to alterations in BBB permeability,

Inflammation, brain edema, increased ICP, →
Neurons death
Roos, seminars in neurology 2000
 CNS Infection
Cranial
•Meningitis
•Encephalitis
•Ventriculitis
•Cerebral Abscess

Spinal :
Arachnoiditis, Poliomyelitis, Spondilitis TB (corpus
vertebra)
 Meningitis
• Umumnya disertai encephalitis
• Viral, TB ( Ind: terbanyak), Infeksi kuman non spesifik
Streptococcus, Haemophlus Influenzae tipe B,
Neisseria Meningitidis
• Klinis : demam, penurunan kesadaran,
kaku kuduk
Komplikasi (Bedah Saraf)
Hydrocephalus communicans
• Lab: LP -> analisa LCS : Sel MN/PMN, Protein, Glukosa
Darah : lekositosis
 Meningitis
Post Contrast: vascular and basal
Pre contrast arachnoid hiperdensity
 Bacterial Meningitis
Etiology, Pathophysiology, Diagnosis, Treatment,
Outcome
Haemophilus influenzae
• Small GN, pleomorphic,
coccobacilli
• H. flu type B causes almost
ALL invasive disease
• Nontypeable Hib can rarely
cause meningitis.
• Incidence of Hib decreased
by 97% after vaccine
Neisseria meningitidis
● - GN diplococci
● - Serotypes A,B,C,Y, and
W135 cause most invasive
disease.
● - Virulence depends on:
1. Capsular polysaccharide
2. LPS(endotoxin)
3. Pili
4. IgA protease
5. ompS gene
 Streptococcus
pneumoniae

● * Small, non-motile GPC

in pairs or chains.
● * 8 serotypes cause 90% of
invasive disease.
● 1, 4, 6, 9, 14, 18, 19 & 23
● * Virulence depends on
capsular polysaccharides
● * Associated with CSF leak
(skull fractures), asplenia,
HIV, cochlear implants
 Other Pathogens: GN bacilli

Neonatal GN sepsis/meningtisis is most commonly due to

E.coli
K1 capsular polysaccharide antigen is a marker of neurovirulence
Outside of neonates, GN meningitis is often nosocomial
Associated with GI infections, head trauma, NS procedures, immune
deficiency
Klebsiella, Salmonella, Enterobacter, and Pseudomonas
 Other Pathogens: GBS

Still a common cause of invasive neonatal disease

Six main serotypes: Type III causes most neonatal meningitis
Incidence is down in developed countries due to screening
and treatment of pregnant women
 Other Pathogens: Listeria
Listeria monocytogenes is a Gram positive rod and still an
important cause of neonatal sepsis
Can also be seen in older children with cellular immune
deficiencies
Associated with maternal consumption of unpasteurized
cheese or contaminated meats
 Other Pathogens: Anaerobes

● * Anaerobic meningitis occurs in only in certain conditions

● Rupture of brain abscess
● Chronic otitis, mastoiditis, sinusitis
● Head trauma, NS procedures
● Congenital dural defects
● GI infections, suppurative pharyngitis
● CSF shunts
● Immune suppression
● * Includes Bacteroides fragilis, Fusobacterium spp.,
Clostridum spp
Pathogenesis
 Pathophysiology

● * With acute CNS infection there is loss of autoregulation:

● Early increase in CBF, followed later by a decrease
● At risk for global cerebral hypoperfusion
● * Focal hypoperfusion can result from vasculitis leading to
ischemia
● Can occlude large vessels: carotid, MCA, ACA
● * Cerebral edema can be vasogenic, cytotoxic, or interstitial
● Interstitial edema is the main cause of obstructive hydrocephalous
in meningitis
 Clinical Presentation

Depends on the age of the patient and the offending

organism
✓ Generally more abrupt onset than viral
Infants have a variable presentation
✓ Fever, poor feeding, lethargy, irritability, high-pitched
cry, full fontanelle
Older children may have acute onset of fever, HA,
vomiting, photophobia, and altered mental status
✓ +/- Kernig or Brudzinski sign
 Clinical Presentation

● Seizures may be the presenting

feature in nearly 1 in 6 children
● Have a low index of
suspicion with seizures +
fever
● Papilledema is uncommon at
presentation
● Focal signs can be found in 14%
of cases
● Sudural epyema, cortical
infarction, cerebritis
● Rashes are not uncommon
● Petechial or purpuric rash
highly suggests
meningococcemia
 Diagnosis

● Definitive diagnosis is by analysis and culture of the CSF

● LP should be done at earliest opportunity
● Do not delay antibiotics – may alter culture and gram
stain but chemistry or cells

● WAIT on the LP if:

● Evidence of raised ICP (pupil changes, cushing’s,
kussmaul pattern, deep coma), focal neuro exam,
resp/CV instability, coagulopathy
● Get a head CT if there is focality or question about
diagnosis
 CT Head before LP?
– CT will be abnormal, if you have :

• Seizure
• clinical evidence of increased ICP
• Hx of CNS disease
• Immuncompromised status
• Age>60
• Abnormal neurological exam (including mental status)

Hasbun et al. CT head before LP in suspected meningitis. NEJM 345:1727, 2001

Kastenbauer et al. CT head before LP in suspected meningitis. NEJM 346:1248, 02
CT SCAN PRIOR TO LUMBAR PUNCTURE IN
SUSPECTED MENINGITIS

• 235 patients with suspected meningitis underwent CT

• 56/235 (24%) had abnormal CT; 11 (5%) with mass
effect

Hasbun et al. NEJM 2001;345:1727.

CT SCAN PRIOR TO LUMBAR PUNCTURE IN
SUSPECTED MENINGITIS

• 96 patients without above features who

underwent CT
– 93 had normal CT; 1 had mass effect
– All had lumbar puncture with no
evidence of brain herniation

Hasbun et al. NEJM 2001;345:1727.

 CT before LP
Nothing predicts herniation (Abnormal CT in 2/10
herniations and 27/65 w/ no herniation)

Kastenbauer et al. N Engl J Med 2002;346(16):1248-1251

 Diagnosis

CSF findings include high opening pressure,

pleocytosis, low glucose, and high protein
✓ Cloudy CSF with high opening pressure is diagnostic
✓ Glucose ratio of 0.4 is 80% sensitive and 98% specific

CSF WBC (predicted) = CSF RBC x (blood

WBC/blood RBC)
✓ Observed CSF WBC/ predicted <0.01 and WBC/RBC
ratio of <0.01 are 100% reliable in ruling out bacterial
meningitis
 Diagnosis

Gram stains are quick, cheap, and accurate

✓ 90% strep, 86% H. flu, 75% neisseria, 30%
Listeria
CSF culture will be positive in the majority of
untreated cases
Empiric diagnosis can be made if:
✓ CSF WBC > 300, with >60% poly’s
✓ Glucose < 50% of serum
✓ Absolute glucose < 30
 Diagnosis – CSF analysis
Parameter Bacterial Viral Neoplastic Fungal
(normal)

OP (<170 mm >300mm 200mm 200 300mm

CSF)
WBC >1000 <1000 <500 <500
(<5mononucle
ar)
%PMN’s (0) >80% 1-50% 1-50% 1-50%

Glucose <40 >40 <40 <40

(>40mg/dL)
Protein >200 <200 >200 >200
(<50mg/dL)
Gram stain (-) + _ - _

Cytology (-) _ _ + +
 Diagnosis: Viral vs. Bacterial

● Latex agglutination
● Helpful in partially treated meningitis
● Specific but not that sensitive
● Strep pneumo – 96% specific, 70 -100 % sensitive
● PCRs are available for neisseria and pneumococcus
● Both are sensitive and specific
● DNA load correlates with mortality for neisseria
● Very expensive
● CRP may be helpful but only if very high or very low
● Peripheral WBC, CSF lactate, limulus amebocyte lysate,
procalcitonin, and various cytokines are up in the air
 Complications
Raised ICP
Seizures
Subdural empyema
Infarcts
Cerebritis
Brain abscess
Hydrocephalous, ventriculitis
Cranial nerve involvement
Sensorineural hearing loss
 Treatment: By Age
Age Common pathogens Antimicrobial Therapy

< 1 month GBS, E. coli, Listeria, Klebsiella Amp + cefotaxime or an

aminoglycoside
1-23 months S.pneumoniae, N. meningitidis, Vanc + 3rd gen cephalosporin
GBS, H.flu, E.coli

2-50 years N. meningitidis, S. pneumoniae Vanc + 3rd gen cephalosporin

> 50 years S. pneumoniae, N. meningitidis, Vanc + amp + 3rd gen ceph

Listeria, GN bacilli

Emperic treatment from Emory University Children’s Healthcare of Atlanta

 Treatment: Head Trauma
Type of Trauma Pathogens Antimicrobial Therapy

Basilar skull fracture S.pneumo, H.flu, group A Vanc + 3rd gen ceph
strep

Penetrating trauma S.aureus, coag-neg staph, GN Vanc + cefepime, ceftaz,

bacilli (Pseudomonas) or meropenem

Post-neurosurgery GN bacilli, S. aureus, coag- Vanc + cefepime, ceftaz,

neg staph or meropenem

CSF shunt Coag-neg staph, GN bacilli, Vanc + cefepime, ceftaz,

propionibacterium acnes or meropenem

Emperic treatment from Emory University Children’s Healthcare of Atlanta

 Do we need a repeat LP?

Repeat LP’s are not routinely necessary if the patient gets

better and is afebrile
EXCEPT for neonatal GN meningitis
Consider repeat LP in these situations:
No clinical improvement after 3-4 days of abx
NEW focal neuro signs, AMS, or increased ICP
Initial culture had resistant/weird bugs and no improvement after 24-
48 hrs of appropriate therapy
 Prognosis

Mortality continues to be as high as 15-20%

Coma, raised ICP, seizures, and shock are significant
predictors of morbidity and mortality
Neurologic sequelae are common
Hydrocephalous, spasticity, vision/hearing loss, cognitive defects,
developmental delay
 Prevention

Isolation is necessary for H.flu and Neisseria for the first 24

hours of treament
Rifampin prophylaxis is indicated for household contacts of
H.flu if any of them is unvaccinated and <4yrs old
Rifampin is also recommended for household and daycare
contacts of Neisseria
Single oral dose of cipro or azithro is ok for adults
 Prevention

H.flu vaccine is awesome and has virtually eliminated H.flu

meningitis in developed countries
Heptavalent pneumococcus vaccine is good too
Don’t forget kids with asplenia, nephrotic syndome, sickle cell, and
cochlear implants need 23-valent
Quadrivalent meningococcal vaccine (A, C, Y, W135) is
recommended for high risk kids > 2 yrs and college
students/military
 Cerebral Abscess
• Soliter or multiple
Soliter:
Direct spreading dari :
Inf Sinus Fr/eth or teeth -> frontal/temp
Inf Sinus max -> temporal
Inf Sin sphenoid -> fr/temp
Inf otitis/mastoid -> abses di cerebelum
/temp
 Cerebral Abscess
-
• Multiple :
Remote Spreading/Hematogen : Penyakit
Jantung Kongestif (ToF), ASD-> bacteria not
filtered from their blood in the pulmonary
capilary bed
 Anatomic Sources for Brain Abscess
Predisposing Condition Common Pathogens

Otitis Media/Mastoiditis Streptococci, Bacterioides spp,Prevotella

spp, Enterobacteriaceae

Sinusitis Streptococci, Haemophilus Spp,

Enterobacteriaceae, Bacterioides spp,
Staphylococcus aureus

Dental Infection Fusobacterium spp, Prevotella spp,

Bacterioides spp, Streptococci

Direct Inoculation (trauma,surgery) Staphylococcus spp, Enterobacteriaceae,

Streptococci, Clostridium spp

Lung Infection Actinomyces spp, Streptococci

CHD , Endocarditis Streptococci, Haemophilus spp,

Staphylococcus aureus
 Cerebral Abcess
• Early Cerebritis : day 1-3
• Late Cerebritis : day 4-9
• Early Capsul Form : day 10-13
• Late Capsul Form : day> 14
 Cerebral Abscess
• Teraphy:
- Steroid -> decrease perifocal edema but
decrease efficacy antibiotic
- Antibiotic 4-6 wks
- Surgery :
more than 2.5 cm
easy reached location
non eloquent area
Abcess: Single and Multiple
 Tuberculoma : TB on the Brain
• Mycobacterium TB
• TB Pulmo or Lymphe (active/non active
• Hiperdens but not enhance contrast because :
necrotic caseosa
Clinical Finding:
General : raised ICP
Local : depend on location
Thorax Ro?
Lab : ICT TB/Mantoux ?, LED ?
 Tuberculoma

Necrosis caseosa

www.dodypriambada-bedahsaraf.blogspot.com
Tuberculoma

Necrotic area intra mass

 Tuberculous meningitis (TBM)
• Commonest form of neurotuberculosis (70 to 80%) .

• TBM is also the commonest form of chronic meningitis.

• Clinical features include h/o vague ill health for 2-8

weeks prior to development of meningeal irritation.

• Non specific symptoms include malaise, anorexia,

fatigue, low grade fever, myalgia and headache.

• Prodromal symptoms in infants and children include

irritability, drowsiness, poor feeling, and abdominal pain..

Contd…
Tuberculous meningitis (TBM) Contd…
• Meningeal irritation - neck stiffness, Kernig’s sign,
Bickelle’s sign and Brudzinski’s sign.

• Cranial nerve palsies (20-30%), fundus - papilloedema

or rarely choroid tubercles, seizures, focal neurological
deficits secondary to infarction.

• Visual loss may be due to optic nerve involvement,

optochiasmatic arachnoiditis, third ventricular
compression of optic chiasma, ethambutol toxicity and
occipital lobe infarction.

• Increasing lethargy, confusion, stupor, deep coma,

decerebrate or decorticate rigidity.
 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

Research 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,
blastomycosis, 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 India Ink stain.
• CSF culture on solid media: Egg or agar based
BACTEC systems.
• Adjunctive tests CSF tuberculostearic acid,
adenosine 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 (elderly 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 volume of CSF.
• Culture is +ve in 25-70%.
 Cerebrospinal fluid examination
• Repeat CSF frequently shows a falling glucose level, a
rising protein concentration 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 remain positive for a month.
 Investigations
• CSF examination:
• CSF Smear examination: Zeihl Nelson’s, Gram’s
and India Ink stain.
• CSF culture on solid media: Egg or agar based
BACTEC systems.
• Adjunctive tests : CSF tuberculostearic acid,
adenosine deaminase,
radiolabelled bromide partition test.
• Molecular diagnosis : Nucleic acid amplification,
DNA finger printing, PCR.
Sensitivity and specificity of adjunctive tests
for the diagnosis 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 TBM

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 oedema, 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 sign.

• Radiological findings also help in prognostication.

Imaging abnormalities in TBM
 Search for extra CNS TB

• An extra-neural focus should be sought clinically and

radiologically in all patients of CNS TB as it may indicate
safer and more accessible sites for diagnostic sampling
e.g. X-ray chest, FNAC of the enlarged lymphnodes,
abdominal USG, CT scan .

• 77% of HIV +ve TBM patients have extra-meningeal TB

compared to only 9% with HIV –ve patients.

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

 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 to

achieve therapeutic concentrations in CSF.

• Drugs should be taken on a regular basis for a

sufficient period to eradicate the CNS infection.

• Intrathecal therapy is not required.

• No general consensus regarding the choice of drug,

doses and duration of treatment.
 List of antitubercular drugs
First-Line Drugs Second-Line Drugs

INH Cycloserine
Rifampicin Ethionamide
Rifapentine Levofloxacin*
Rifabutin* Moxifloxacin*
Ethambutol Gatifloxacin*
Pyrazinamide p-aminosalicylic acid**
Streptomycin**
Amikacin/Kanamycin*
Capreomycin

* Not approved by U.S. FDA

** Included in second-line drugs due to toxicity, limited efficacy or difficulty in
administration.
 Treatment
• CNS tuberculosis is categorised under TB treatment
category I by WHO.

• Initial phase therapy ( 2 mths) with isoniazid, rifampicin,

pyrazinamide and streptomycin or ethambutol followed
by continuation phase (7 mths) with isoniazid and
rifampicin.

• The BTS and IDSA/ATS recommend 9-12 months of

ATT. Therapy should be extended to 18 months in
patients who do not tolerate pyrazinamide.

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

likelihood 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 would be worthwhile.
What is the best anti-tuberculous drug regimen?

• Isonaizid, rifampicin and pyrazinamide are considered

mandatory at the beginning of TBM treatment.

• Isoniazid penetrates the CSF freely and has potent early

bactericidal activity.

• Rifampicin penetrates the CSF less well (maximum

concentrations around 30% of plasma), but the high mortality
from rifampicin resistant TBM has confirmed its central role in
the treatment of CNS disease.

• There is no conclusive evidence to demonstrate that

pyrazinamide improves outcome of CNS tuberculosis, although
it is well absorbed orally 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,

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

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

renal 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 prolonged therapy are limited.

• Others-Ethionamide, prothionamide.
 Adjunctive steroid therapy

• The use of corticosteroids as adjunctive therapy in the

treatment of CNS tuberculosis began as early as the
1950s.

• The rationale behind the use of steroids includes the

reduction of inflammation within the subarachnoid space.

• The largest RCT in TBM recommends dexamethasone

treatment in patient with TBM for 6-8 weeks.

Thwaites GE et al. N Engl J Med 2004; 351: 1741-51;

Lancet Neurol 2007; 6: 280-6.
 Adjunctive steroid therapy

• A recent Cochrane review and meta-analysis of 7

randomised controlled trials involving 1140 participants
(with 411 deaths) concluded that corticosteroids improved
outcome in HIV-negative children and adults with TBM, but
the benefit in HIV infected individuals remains uncertain.

Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis.

Cochrane Database Syst Rev 2008;(1):CD002244.
 Role of surgery in CNS tuberculosis
• Hydrocephalus, tuberculous cerebral abscess and vertebral
tuberculosis with paraparesis are all indications for
neurosurgical referral (A,II).

• Early ventriculo-peritoneal shunting should be considered in

those with non-communicating hydrocephalus (A,II) and in
those with communicating hydrocephalus falling medical
management (B,II).

• Communicating hydrocephalus may be treated initially with

frusemide (40 mg/24 h adults, 1 mg/kg children) and
acetazolamide (10-20 mg/kg adults, 30-50 mg/kg children) (B,II)
or repeated lumbar punctures (B,III).

• Urgent surgical decompression should be considered in all

those with extra-dural lesions causing paraparesis (A,II).
 Prognosis
• Virtually all patients with no focal deficits and only minor
lethargy recover, most-without sequelae.

• Comatose patients have a mortality of 50% and a high

incidence of residual disability.

• The incidence of residual neurological deficits after

recovery from TBM varies from 10-30%.

• Late sequelae include cranial nerve deficits, gait

disturbance, hemiplegia, blindness, deafness, learning
disability, dementia and various syndromes of
hypothalamic or pituitary dysfunction.
 Poor prognostic factors

• Stage of disease.

• Presence of miliary disease

• Severe disease on admission

• Delay in initiation of treatment

• Extremes of age, preexistence of a debilitating condition

• Very abnormal CSF (very low glucose or elevated

protein)
 CSF Infection
• CSF Shunt Infection
1.Perioperative Contamination
2.Wound Dehiscence : direct contaminationat
erosion site and the shunt tract
3.Hematogenous Seeding (intravascular device),
can occur not intravascular device
4.Distal Port Contamination
• Abnormality of Physics and CSF Components
• Scan : More density on CSF appearance
Terimakasih