INFECTIONS OF THE

CENTRAL NERVOUS SYSTEM

Dr. Kiking Ritarwan, SpS, MKT
Departement of Neurology Medical
Faculty of University of Sumatera
Utara

CNS INFECTION
MENINGITIS
- Inflamation of the meningeal covering of
Brain and spinal cord.
- LEPTOMENINGITIS (arachnoid + pia)
PACHYMENINGITIS (duramater)
- TYPE OF MENINGITIS : Bacterial, TB, Viral,
fungal.

ENCEPHALITIS
MYELITIS

Acute Pyogenic Meningitis

= Bacterial meningitis
Is an inflamatory response to bacterial infections
involving the pia and arachnoid membrane covering
the brain and spinal cord.
Many org. can produce pyogenic meningitis
It can be categorised into:
a. Spontaneous community acquired meningitis
b. Post traumatic meningitis following neurosurgery or fx of the skull.
c. Device associated meningitis particularly in assoc.
With CSF Shunts and drain.

The causative org. of meningitis can be

predicted based on the patients age, exposure
to an epidemic, vacc. Against common agents
(eg. H. Influenza, Streptococcus pneumonie, N.
meningitidis) and Immune state.
Pathology is characterized by inflammation of
the meninges and cortical blood vessels.

Etiology of Bacterial meningitis

Age
- Neonate ( 0-2 bln)

- Child
- Youth ( 6-20th)
- Adult ( > 20 thn)

Microorg.
Streptococ group B, E coli, list.
Stap. Aureus, Enterobacter,
Pseudomonas, Haemofilus
S. pneumonie, N. meningitidis,
H. influenzae.
N. meningitidis, S. pneumonie,H. infl.
S. pneu, N. meningi, Streptococ,Staph.

Clinical Picture
The conditions occurs equally in both sexes
Children aged 6 month to 1 year are at the greatest
risk and children under 15 years of age comprise 75%
of all cases. Patients aged 60 and older may be
atypical.
Symptoms and signs
I. early infection: fever, headache, malaise,vomite
II. Higher ICP: vomite, headache, seizure, alteration of
consciousness, papiledema
III. Meningeal irritation: nuchal rigidity, Kernig and
Brudzinski +
IV. CSF:neutrophilic pleocytosis, low glucose level,
elevated protein concentration

CSF Findings
CSF Parameter
WBC Count
Glucose
Protein
Gram stain +
Culture +

Bacterial meningitis
> 2000/ ul, >60% PMN
< 40 mg/ dl
> 200 mg/ dl
80%
> 90%

Diagnostic Prosedure
Lumbal Puncture
Blood should be drawn for blood culture before
administration of antibiotic.
Bacterial antigen
Chest, skull mastoid and paranasal sinus x rays
MRI or CT
Neuroimaging shoul be performed before LP in
the following settings:60 yo or older, Depressed
LOC, Focal neurologic signs, papilledema,
Patients is immunocompromised.

Treatment
1.Antibiotic therapy should be administrated. A minimum of 2
weeks of therapy is recommended.
Age
Antibiotic
0 4 mgg
Cefotaxim + Ampi
4-12 mgg
Gen III. Cephalos+ Ampi
3 bln- 18 thn
Gen III. Ceph + Ampi atau
Ampi + chloramph.
18 thn 50 thn
Gen III. Ceph + Ampi
50 thn
Gen III. Ceph + ampi.
2. When possible etiologies for meningitis include H. Influenza or
S Pneumoniae in child, or S Pneumoniae in adults, give
dexamethasone 0,15 mg/kg (IV) every 6 hours for 2-4 days in
child and 10 mg IV every 6 hours for 4 days in adults.

Complication Bacterial meningitis

Cerebral abscess
Empyema subdural
Convulsie
Shock septic
Cerebral edema
Infarck serebral
Herniation

Sequele bacterial meningitis

Mental retardation
Hydrocephalus
Convulsie, psikose
Parese, deafness, blind.

Tuberculous meningitis
The first clinical description of tuberculous meningitis
in the late 18th Century is credited to the Scottish physiologist
Sir Robert Whytt , even before Robert Koch isolated
mycobacterium tuberculosis in 1882.
Almost 40 years later, Rich and McCordock demonstrate the
presence of minute caseous tubercles known as Rich-foci
within the brain or meninges, which formed the basis for
understanding the pathogenesis of CNS tuberculosis.
Tuberculosis of the central nervous system (CNS) is the most
serious complication of tuberculosis, especially in children.
TB hematogenous spread infection to the brain
parenchyma or meninges.

TB meningitis (TBM)
Definition:
TBM is an infection of the meninges caused by
the acid-fast bacillus Mycobacterium
tuberculosis.
In the west country,the first make not much
difference again, but lately incident mount
drastically in all the world.
TBM happened at all of age.
Before important HIV factor in prevalens is age

+ 1,7 milyar people ( 1/3 worldwide

people) Mycobacterium tuberculosa
infected.
Reported CDC 2002 was 5,36 cases per
100.000 people, but worldwide the
infection rate is much higher.
TB in Indonesian occupy 3rd rank from 22
high burden countries.

Indonesia
22 High Burden Countries
1.
2.

India
China

3. Indonesia

Indonesia 10%

China
15%

Bangladesh 4%
Pakistan 4%

India
30%

Philippines 3%
Nigeria 3%
South Africa 2%
Russia 1%

Other
28%

4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.

Bangladesh
Nigeria
Pakistan
South Africa
Philippines
Russia
Ethiopia
Kenya
DR Congo
Viet Nam
UR Tanzania
Brazil
Thailand
Zimbabwe
Cambodia
Myanmar
Uganda
Afghanistan
Mozambique

3% of All Deaths in Developed

Countries Are Due to Tuberculosis
Tuberculosis

Diarrheal disease
Perinatal causes
3%
Chronic obstructive
pulmonary disease
HIV/AIDS
Respiratory tract
infection

3%

Malaria

2%

4%

5%
Other
27%

5%
7%
Injury
9%

Stroke
10%

Coronary heart
disease
13%
Cancer
12%

HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome.

Adapted with permission from MacKay J, Mensah GA. The Atlas of Heart Disease and Stroke.
Available at: http://www.who.int/cardiovascular_diseases/en/cvd_atlas_16_death_from_stroke.pdf
Accessed February 27, 2006.

Etiologi
Mycobacterium tuberculosis
gol ordo Actinomycetales, famili
Mycobacteriaceae, genus
Mycobacterium
Sifat : aerob, spora (-), motil (-),
berkembang biak lambat
Mati dgn pemanasan & sinar UV
Bakteri batang tahan asam dgn
pewarnaan ZiehlNeelsen
/Auramin leading to nickname
red snapper.

Size :0,3-,0,6 to 1-4 um

Shape: Rods, straight or
slightly curved, occurring
singly or in occasional
threads
Temperature: 33-39o C
pH 6,6-6,8

PATHOLOGY

Aerosol transmission of Tuberculosis

Tuberculosis is spread by droplet nuclei which are expelled when a person with
infectious TB coughs, sneezes, speaks, or sings

Pathology
TBM is always secondary to TB elsewhere in the
body. The primary focus of infection is usually in the
lungs but may be in the lymph glands, bones, nasal
sinuses, GIT, or any organ in the body.
The bacilli usually enter the body by inhalation.
Transmission through the skin or by ingestion are rare
cause of infection.
The organisms undergo multiflication and
hematogenous dissemination and it is during this
stage that the meninges are most likely to become
involved.

Cell mediated immunity with migration of

macrophages at the site of infection leads
to the development of tubercles.
When the immune response fails, the
subarachnoid space is infected by rupture
of meningel tubercles followed by release
of bacilli and the development of
meningitis.

The presence of bacilli in the subarachnoid space is

followed by an intense granulomatous inflamation of
the leptomeninges and subjacent cortex.

A thick, heavy fibrous and necrotic exudate is

produced, which tends to collect at the base of the
brain.
The arteries at the base of the brain are involved, and
there is inflamation of the adventitia and media, with
narrowing and thrombosis of the lumen.
CN II and III, occasionally CN VII, VIII, are subject to
compression by the heavy exudate.

Clinical features TBM

The disease occurs in all ages, but the incidence
is higher in infants, young children, and the
aged. It is more common amomg the
undernourished and in those areas of the world
characterized by poor hygiene and
overcrowding.
History of contact with an infected individual or a
history previous active tuberculosis in 30 to 50
percent of patients.

Clinical staging of patients with

TBM

(terminus/ advance)

The course of the illness depends:

- on the extend of meningeal involvement,
- the immune response of the host,
- the virulence of the organism,
- and the stage at which treatment is
administered.

Kategori diagnosis Ogawa

Definite
- bila kultur positi
- otopsi positip, atau keduanya
Probable
- likuor pleiositosis (>5/mm3), kultur bakteri dan jamur negatip + salah satu:
1. test tuberkulin positip
2. TB diluar SSP atau TB aktip sebelumnya
3. glukosa likuor < 40 mg/dl
4. protein likuor > 60 mg/dl

Complication
Arteritis thrombosis of a major artery
cerebral infarction.
Hydrocephalus
Seizures
Focal motor deficits and impaired cognitive
Hypopituitarism in childhood.

Differential DX
Viral encephalitis
Partially treated pyogenic meningitis
Fungal infection
Other inflammatory disorders
The presence of active TB elsewhere, and
the results of CSF examination are usually
sufficient to establish the dx.

Diagnostic Prosedures

1. Lumbal Puncture
CSF Parameter
TB meningitis
WBC Count
< 500/ ul, MN
Gluco
moderate or marked decrease
Protein
marke increse
Gram stain +
+.CSF lactic acid
> 35 mg/dl.

2. Laju endap Darah

3. Radiologic
3a. Chest x ray: detect pulmonary involvement
3b. CT scan8 enhancement of the
basal cistern.
3b. MRI are more sensitive than CT
sans in detecting basal meningitis
infarction owing to arteritis hydrocephalus
and parenchymal tuberculomas often in
combination in AIDS patient.
4. Arteriografi

Images of CT Scans
file 1: Contrastenhanced computed
tomography (CT) scan in
a patient with
tuberculous meningitis
demonstrating marked
enhancement in the
basal cistern and
meninges, with dilatation
of the ventricles.

file 2: Petechial
hemorrhages in the
subcortical white matter of
the brain as a result of
tuberculous meningitis
associated vasculitis.

file 3: Extensive infarcts of

the right basal ganglia and
internal capsule after the
appearance of vasculitis in
the thalamoperforating
arteries in a child treated for
tuberculous meningitis.

Treatment
1. Combination of antituberculous drug
Therapy
WHO GILROY ATS
- Initial
INH+R+PZA+E
INH+R+PZA
INH+R+PZA atau S
atau R+ PZA+S

-2MO - 2 MO
- 2 MO
- Continued INH+R INH+R INH+R
-7 MO - 9 MO
- 9 MO
Pyridoxine 50 mg/ hr
2. Spinal arachnoiditis and arteritis may show
improvement when terated with corticosteroid.
3. Seizure anticonvulsant
4. ventriculoperitoneal shunt.

Prognosis
Mortality 10 & 20%
The prognosis is poor in infants, the elderly,
when treatment is delayed, and in patients with
poor nutrition or debilation from HIV infection or
other chronic disease.
The outcome is clearly associated with the stage
of the disease at dx and the introduction of early
treatment. Those who are conscious and without
neurological deficits have a good prognosis;
those in coma at the beginning of treatment
have 20% mortality and only 20 oercent make
complete recovery.

Viral meningitis
Viral meningitis shares clinical features with
bacterial meningitis, but patients appear less ill
and the disease follows a more benign course.
Headache, often meningismus and photophobia,
is often the presenting symptoms.
The most pathogens include herpes simplex-1
(HSV1), mumps, enterovirus, herpes zoster,
adenoviruses and Epstein barr virus.

Dx procedure Viral meningitis

Lumbal Puncture
Cells Glucose Protein
Smear CSF lactic
< 500 Normal Mild incr No org < 35 mg/dl
MN /mm3
PCR
MRI predominant temporal lobe and insular
changes in HSE-1 and basal ganglia lesion in
japanese encephalitis.

Treatment
Aciclovir 10 mg/ kg iv every 8 hours for 1014 days.

FUNGAL MENINGITIS
ETIOLOGY
Fungi invade of CNS producing meningitis in a small fraction of
patients with systemic fungal infection (mycoses)
The most pathogens are Cryptococcus neoformans,

Coccidiodes immitis, Candida albicans, Aspergillus, H.

Capsulatum, Blastomyces, and Mucor
Mucormycosis and aspergillosis usually spreads to the CNS

from infected sinuses and generally cause local inflamation and

necrosis rather than a diffuse meningitis

Fungi can cause infection in patients with:

1. Cancer
2. Receiving corticosteroids
3. Other immunosuppressive drugs
(Diabetes, malignancy, immunosuppressive
th., or AIDS)
4. IV drug abuse.

Route of entry
A. Haematogenous: from the heart, lung, GIT and skin
B. Direct: from the orbit and paranasal sinuses.

Clinical Picture
Symptoms progress over days, sometimes
weeks, with headache, nausea, vomiting and
mild encephalopathy.
Neurologic examination:
1. meningeal irritation (+) 5, Visual loss
2. papilledema
6. Confusional state
3. Cranial nerve palsies 7. Focal paralysis
4. Ptosis

Investigations
Lab investigations:
1. Blood culture
2. Serum glucose
3.Arterial blood gases
4. Electrolyte
5. Liver function test
6. Urinalysis
CSF Examinations:
Imaging

Invest..
CSF Exam:
- Pressure: Increased
- Appearance: varies with organism
- White Blood cells: 50 10.000 (mixed or
lymphocytic).
- Glucose :Normal
- Protein: increased
- Cryptoccal antigen is more sensitive
- Fungal culture of CSF(+)

Invest.
Chest X-ray : Hilar lymphadenopathy,
cavitation, effusion.
CT or MRI: mass lesion (Cryptococcus)

Treatment
Amphotericin B
- Protocol, starting with 1 mg/ day
- doubling the dose daily until reaching 16
mg per day, than increasing at increments
of 10 mg until reaching full therapeutic
dose of 0,5 to 1,5 mg/ kg per day IV.