CENTRAL NERVOUS SYSTEM

INFECTION

Oleh :

EFRIDA WARGANEGARA
 Introduction
The brain and spinal cord are
* protected from mechanical
pressure or deformation by enclosure
in rigid containers (skull and vertebral
colum which also
* act as barriers to spread of
infection
 Introduction
I. The main route of m.o.invasion that tranverse
the wall of skull and vertebra colum
a. via blood vessels : commonest (polio

virus, meningococcus
b. via peripheral nerve,s : less common
(HSV, VZV, Rabies V)
II. Local Infection from infected ears/
sinuses; local injury; congenital defect
III. Olfactory Tract amoebic meningitis
rare
 The Response to
Invasion
Respons to invading virus is reflected
by :
- increase in lymphocyt (mostly T cells)
and monocyt in the CSF.
- A slight increase in protein also occurs
- the CSF remaining clear
this term aseptic meningitis
 The Response to
Invasion
Respons to invading pyogenic
bacteri is more spectaculer and more
rapid increasing in :
- PMN leucocyt, and
- protein

- the CSF become visibly turbid

this term septic meningitis
 The Response to
Invasion
Respons to certain slowers
growing or less pyogenic m.o.
induce :
- less dramatic changes
such as in tuberculous or
listerial meningitis
 The Response to
Invasion
In the CSF itself Virus can infected neural
cells :
polio and rabies invade neurones
because there is very little extraceluller
space, spread is mostly direct from cell to
cell along nervous pathway
Invading Bacteria and Protozoa generally
induce more dramatic inflamatory events
which limit local spread,
spread so that infection is
soon localized to form abscesses
Meningitis
- Bakterial
- Viral
Bacterial meningitis
Acute bacterial meningitis a life-
threatening infection, needing
urgent spesific treatment
It is more severe, but fortunetely
less comon than viral meningitis
The important causative agent are :
- Neisseriae meningitidis
- Haemophilus influenzae
- Streptococcus pneumonia
have several virulence factor,
including possesion a
polysacharida capsule, IgA protease,
Bakterial Meningitis
Penyebab yang umum dari Neonatal
Meningitis adalah :
- Streptococcus agalactica
- Escherichia coli

Penyebab tidak Umum :

- Listeria monocytogenes
- Pseudomonas aeruginosa
- Staphylococcus aureus
Bakterial Meningitis
Pathogenesis :

- Penyebaran dari Sal. Nafas atas

secara hematogen adalah rute
yang penting dimana m.o.
umumnya menyebabkan meningitis
- Penyebaran secara hematogen dari
sal. Cerna adalah rute yang
mungkin terjadi oleh E.coli sbg
penyebab meningitis pada
neonatus
 Bakterial Meningitis
* Meningitis bakterial mungkin
merupakan hasil penyebaran
contagius dari infeksi :
- Trauma kepala, dapat merusak
pertahan anatomik normal dan
membiarkan m.o. pada nasofaring
masuk ke meningen

- Bakteri pada fokal infeksi dalam

sinus paranasalis, mastoid, otot psoas
atau jar. otak dapat menyebar secara
contagius ke meningen
 a) Haemophilus

influenzae
Gram (-), btk batang, membutuhkan faktor
X dan V, dan tumbuh pada chocolate agar

* Gejala Klinik : Mengingitis

- Terjadi terutama pada anak umur 3 bln 2

thn yg tidak divaksinasi

- Progresif secara cepat, Menghasilkan
gangguan pada CNS dlm 1/3 kasus
(hydrocephalus, mental retardation,
paresis,
problem bicara & mendengar)
 a) Haemophilus
influenzae
Diagnosis :
* Diagnosis cepat dibuat dengan
mengidentifikasi Antigen kapsul
polyribitol phosphate (PRP) dalam
CSF menggunakan latex particle
agglutination atau counter-
immunoelectrophoresis bersama-
sama dengan pengecatan
gram dari sedimen CSF
 b) Neisseria
meningitidis
Kharakteristik Umum :
* Gram (-), diplokokus, oxidase (+),
mampu menggunakan baik glucose
dan maltose
* Menyebabkan penyakit sangat
fulminant, umumnya sporadik,
terdapat pada umur 6 bln 2 thn, dgn
kdg2 timbul wabah pd kamp militer
* Berkolonisasi pd membran sal. Nafas
atas sebelum menyebabkan
meningococcemia
 b) Neisseria
meningitidis
Faktor Patogenisitas :
1. Memp. st capsular polysaccharida yg
menghambat phagocytosis
2. Memp. st LPS menyebabkan extensive
tissue necrosis, hemorrhage, circulatory
collaps, intravascular coagulation and
shock
3. Memp. IgA-ase yg mendegradasi IgA1;
ini mungkin penting sebab penyebab
infeksi dimulai pada mucosal membranes
Klasifikasi Memp. 9 serogroup capsular,
dan kebanyakan penyebab infeksi adalah
tipe B dan Y
 b) Neisseria
meningitidis
Gejala Klinik :
- dimulai sbg pharyngitis ringan, dgn
kdg2 demam ringan
- pd kel. umur yg peka, m.o. menyebar ke
kebanyakan jar. Khususnya kulit,
meningen, sendi, mata dan paru-paru)
menghasilkan
fulminant meningococcemia yg dapat
jadi
fatal dalam 1 sp 5 hr
 b) Neisseria
meningitidis
Gejala Klinik (lanjutan) :
- Gejala awal dan simptom : demam,
vomitus, skt kepala dan kaku kuduk.
- Erupsi petechiae dan berkembang secara
progresdari makula erithematous sp frank
purpura; vasculitic purpura berbahaya
(hallmark)
- LPS dr organisms menyebabkan
intravascular coagulation, circulatory
collaps dan shock
- Kematian dpt terjadi dgn atau tanpa
penyebaran ke meningens
 b) Neisseria
meningitidis
Gejala Klinik (lanjutan) :
- Waterhouse-Friderichsen-syndrome
adalah fulminating meningococcemia
dengan hemorrhage, circulatory failure,
dan adrenal insufficiency

- sequelae setelah sembuh melibatkan tuli

nervus 8, kerusakan CNS (keterbatasan
belajar dan seizures), dan nekrosis kulit
berat yg menyebabkan skin grafting
atau amputation
 b) Neisseria
Diagnosismeningitidis
Laboratorium :

- gram-negative diplococcus pd CSF dan

aspirasi lesi kulit
- identification dpt cepat : countercurrent
immunoelectrophoresis atau reaksi
agglutination utk mendeteksi capsular
polysaccharida dlm darah dan CSF
- Kaldu nutrient (dr darah & CSF) atau
Thayer Martin chocolate agar (dr lesi
kulit, usap pharyng dpt diinokulasi dan
diinkubasi dlm kadar CO2 tinggi
 b) Neisseria
meningitidis
Diagnosis Laboratorium :
- Meningococcus adalah oxidase positive
- N.meningitidis menggunakan glucose
dan maltose; N.gonorrhoeae hanya
menggunakan glucose
Spesimen Klinik :
- Harus ditransportasi ke lab. dengan
cepat dan diproses
- Pengecatan Gram dari CSF, centrifuse
mungkin dibutuhkan utk megendapkan
m.o.
 b) Neisseria
meningitidis
Prevention :
- Memberikan rifampin pada
pasien (bersama penicillin) dan
pada semua anggota famili dan
org yg berkontak erat utk
menghilangkan carrier

- Dengan vaksin
c) Streptococcus
pneumoniae
Kharakteristik Umum :
* Sebagai bagian dari flora normal
vagina & mulut pd wanita
dewasa
* Kolonisasi pd sal. Genital wanita
merupakan predisposisi infeksi
neonatus, sepsis dan meningitis
* Ada 5 serotype (Ia, Ib, Ia/c, II &
III) berdasarkan diferensiasi Ag
capsular polysaccharida
c) Streptococcus
pneumoniae
* Kokus Gram (+), beta-hemolytic

* Dapat dideferensiasi dari streptococci

lain dengan antiserum group B,
menghidrolisis sodium hippurate, dan
resistance terhadap bacitracin

* Bekerja secara sinergis dengan

hemolisin staphylococcal
c) Streptococcus
pneumoniae
Faktor Patogenitas :
* capsule
* Influks PMN dapat dinegated oleh
inaktivasi peptidase dari C5a
* AB anticapsular adalah melindungi
keberadaan dari competent
phagocytic cells and complement
d) Group B Streptococcus =
Streptococcus agalactiae
Group B Streptococcus (Streptococcus
agalactiae) normal pada saluran genital
dewasa, dan memungkinkan neonatus
terinfeksi

Gejala Klinik :
1) Onset cepat sepsis neonatal (birth7 hr):
* terjadi segera pada newborn
* Berhubungan dgn komplikasi obstetric,
lahir premature, respiratory distress
* Memp. angka kematian lebih dari 50%
 d) Group B Streptococcus =
Streptococcus agalactiae
2). Onset lambat sepsis neonatal (7 hr 3 bln)
* Kharakteristik : meningitis
* Umumnya menyebabkan kerusakan
neurologi yg permanent
* Disebabkan terutama oleh serotipe III
* Mempunyai angka kematian dari 15 sp
20%

Treatment : penicillin G
Vaccine : Digunakan terbatas sebab responnya
sedikit
Viral Meningitis
Ini tipe meningitis yang paling umum,
penyakit lebih ringan daripada bakterial
meningitis, dgn keluhan sakit kepala,
demam, penyakit umum tp kurang gejala
kaku kuduk

CSF jernih, tak ada bakteri, sel lymphosit yg

terutama walau PMN dapat dijumpai pada
tahap awal
Viral Meningitis
Penyebab Viral meningitis adalah :
HS, Mumps, Polio, Coxsackie, Echo, yg
sering di Indo tp virus2 ini kurang dr 50%
kasus yg dpt diisolasi dr CSF

Hal ini krn banyaknya tipe2 dr EnteroVdan

krn infeksi umumnya asimptomatik, virus dpt
diisolasi dr tenggorokan/feses dgn meningitis
ringan dan mgkn tak ada etiologi yg
bermakna
ENCEPHALITIS
ENCEPHALITIS
Nearly all encephalitis is caused
by virusses

Characteristically, there are signs

of cerebral dysfunction such as :
abnormal behavior, seizures and
altered consciousness, often with
nausia, vomiting, and fever
 ENCEPHALITIS
Virus causes of Encephalitis :
a. Sporadic occurence : HS, Mumps, VZ,
Rabies, HIV
b. May be outbreaks : Polio & enteroV
lain, Eastern & Western equine E V, St.
Louis E V, japanesse E V, California E V
c. Slow viruses : Rubella, Measles
Bakteri causes of Encephalitis : Treponema
pallidum, Mycoplasma pneumoniae rare
Fungi causes of Encephalitis :
Cryptococcus neoformans
VIRAL ENCEPHALITIS
Herpes simpleks :
- This is the commonest of severe
sporadic encephalitis
- and another, seen in adult, is probably
due to virus reactivation in the
trigeminal ganglia, the infection then
passing back to the temporal lobe of
the brain
Herpetic skin or mucosal lesions may
be present
VIRAL ENCEPHALITIS
The mumps virus :
- is a common cause of mild
encephalitis
- symptomatic CNS invasion may be
common, because there are increased
numbers of cells in the CSF in about
half those patients with parotitis;
- on the oher hand meningitis and
encephalitis is often seen without
parotitis
VIRAL ENCEPHALITIS
Poliovirus :
- Poliovirus was once a common cause of
encephalitis
- After an initial 1-4 days of fever, sore
throat, malaise, meningeal sign and
symptom appears, followed by
involvement of motor neurones and
paralysis
The disease is completely preventable by
vaccination and has been disappearing in
developed countries since vaccination
programmes
 Poliovirus
Enterovirus Echovirus
Coxsackievirus
Picornaviridae

Rhinovirus
Etiology of poliomyelitis, pleurodynia,
myocarditis, meningitis, encephalitis, & ARTI.
Pathogenesis
Port of entry ; per oral
- droplet infection
- food & drink
- mechanic : fly, cockroach, ant
Primary replication at oropharynx & GI tract.,
followed by viremia.
Damage in CNS & muscle
Local Ig A & Ig M/G formation after natural
infection
 Virus characteristic :
- Can be found in milk, ice cream
pasteurization.
- Based on antigenic differentiated in 3 type :
Type I = Brunhilde the most virulent
Type II = Lansing
Type III = Leon

The disease can be mild illness, aseptic

meningitis to flaccid paralysis
- Incubation period 1-2 weeks (sometimes 5-6 weeks)
- Kind of infections :
1. Inapparent infection :
- Clinical sign (-).
- Virus can be isolated from feces.
- increased antibody titter.
2. Minor Illness : = poliomyelitis abortive
- Pharyngitis, fever; + diarrhea, + headache.
- Virus isolation : throat swab & feces.
3. Major Illness :
- Non paralytic poliomyelitis
- Paralytic poliomyelitis
- Clinical appearance biphasic : Dromedaris fever
Diagnosis :
a. LCS examination
b. isolation : throat swab at initial of

infection and feces at late hase

c. serologic : Nt & Cf tests
 Disease : Rabies CNS inflammation
Spread by infected animal-bite.
Animal susceptibility & Virus growing
- Wide susceptibility host all animal
poikilothermic & human could be infected.
- Virus : CNS, saliva, urine, lymph, milk &blood
Strain :
1. Long incubation period strain (21-60 days)
inclusion bodies in cytoplasm
2. Short incubation period strain (4-6 days)
hasnt inclusion bodies.
Rabies : primary animal disease human, through
1. Infected-animal bite
2. Contact with infected-salivary animal
Incubation period 1- 6 weeks
The sign divided into 4 phases :
1. Prodormal phase: fever, malaise, anorexia, headache,
nausea & vomiting
2. Sensory phase : Lacrimation, hallucination, muscle
rigidity.
3. Excitement phase : photophobia , sound, & water.
4. Paralytic phase : ascending muscle paralytic
 Laboratory Diagnosis
A. Microscopic:
Immunofluorescensi : rabies hamster antisera
Brain or cornea impression.
Pathognomonic : negri bodies(+) in
muscle /MS

B. Virus isolation:
Infected tissue (saliva) inoculate to mouse
intra cerebral.
(+) : Leg flaccid paralyzed, encephalytic &
death.
CNSs mouse examination Negri bodies &
rabies Ag
 Laboratory Diagnosis
C. Serology :
- Ab test against rabies : IF, CF
or Nt test.
- Ab : (+) in human / animal along
sick.

D. Animal observation:
1. Suspected animal rabies
killed
tissue examination.
2. Other animal rabies possibility
Immunity & Preventing
Rabies preventing pathophysiology
through vaccine:
1. Virus replication in muscle closed from
inoculation site virus enough to
cause
infection of CNS.
2. Giving vaccine / immunogenic
substance
promptly depress virus replication &

prohibit invasion to CNS.

3. Action of passive ab :
a. inoculated infected virus & virus
 Brain abscesses
Since the development of antibiotics brain
abscesses have become rare, and usually
follow surgery or trauma, chronic
osteomyelitis of neighbouring bones, septic
emboli or chronic cerebral anoxia

They are also seen in children with

congenital cyanotic heart disease, where
the lungs fail to filter off circulating bacteria.

they are diagnosed clinically and by scan

 Brain abscesses
Accute absceses are caused by
various bacteria, generally of
oropharyngeal origin, including
anaerobes there is usually
mixed bacterial flora

Chronic abscesses are often due to

M. tuberculose or C. neoformans
TETANUS AND BOTULINUM

Oleh :

Efrida Warganegara
INTRODUCTION
Several bacteria release
toxin act on the nervous
system, but do not themselves
invade the CNS
In case of Clostridium tetani
and Clostridium botulinum
major clinical impact is
neurological
 TETANUS
Etiology : Clostridium tetani
Characteristic : Gram-positive sporeforming rod
with terminal round spore (drumstick); strict
anaerob (obligat)
Diseases : Tetanus (lockjaw) severe disease
characterized by tonic muscle spasms and
hyperflexia, trismus, opistotonus and convulsions
Transmission : m.o. widespread in soil; acquired
by man by implantation of contaminated soil into
wound; no person-to-person spread

38
 TETANUS
Pathogenesis
Tetanus spora are widespread in soil, and
originated from feces of domestic animal.
Spores enter a wound when the
necrotic tissue / presence of a foreign body
local and anaerob growth of bacteria
toxin tetanospasmin is produced all strain
The wound : anything from a small gardens
scratch or cut, to a large automobile or
battlefield injury (about 20% no history of
injury)
 TETANUS
Pathogenesis (continued ..)
The toxin carried in peripeheral nerve axons
and probably in the blood to the CNS it binds to
neurones and block the release of inhibitory
mediators in spinal synapses (blocking
neurotransmitter release) overactivity of motor
neuron, continously stimulate causes
convulsive/spastic contraction of voluntary
muscles
It can also pass up sympathetic nerve axons and
lead to overactivity of the sympathetic nervous
system
/ TETANUS
Clinical features and diagnosis
After period of 3-21 days, but sometimes
longer, there are exaggregated reflexes,
muscle rigidity and uncontrolled muscle
spasms.
Lockjaw (trismus) is due to contraction of
jaw muscles, and dysphagia, rhisus-
sardonicus (a sneering appearance),
neck-stiffness and opisthotonus
(especially in neonatal tetanus) are also
seen
 TETANUS
Clinical features and diagnosis (cont)
Muscle spasms may lead to injury and
eventually there is respiratory failure.
Tachycardia and sweating can result from
effect on the sympathetic nervous system
Mortality is up to 50%, depending on severity
and the quality of treatment
The diagnosis is clinical
Organism are rarely isolated from the wound,
and only a small number ofbacteria are
needed to form enough toxin to cause disease
 TETANUS
Treatment
Human anti-tetanus immunoglobulin
should be given as soon as the
clinical diagnosis is suspected
The wound should be excised if
neccesary and penicillin given to
inhibit bacterial replication.
Muscle relaxant are used and if
neccesary respiratory support in an
intensive care unit
 TETANUS
Prevention
Immunization with toxoid prevent
tetanus, the effect of the vaccine
lasting for 5 years after the last dose
Wounds should be cleansed, necrotic
tissue and foreign bodies removed.
And a tetanus toxoid booster given
Those with badly contaminated
wounds should also be given tetanus
immunoglobulin and penicillin
 TETANUS
Laboratory Identification :
- Grows on blood agar in anaerobic
conditions as a fine spreading
colony ground glass appaerance
- Has very little biochemical activity
useful for identification purpose
 Botulinum
Etiologi :
spores of Clostridium botulinum
widespread in soil and contaminated
vegetables, meat, fish, and so on

When foods are canned or preserved

without adequate sterilization (often at
home) contaminating spores survive
and can germinate in the anaerobic
environtment, leading to the formation of
toxin
 Botulinum
Pathogenesis
Pre-formed botulism toxin is ingested
via intestine, absorbed from the gut and
crossing the gut wall, into the blood.

The toxin affect peripheral nerve ending at

the neuromuscular junction (synapses),
blocking presynaptic release of
acetylcholine This prevent muscle
contraction, causing flaccid paralysis
 Botulinum
It is, there fore, a type of food poisoning
that effects the motor and autonomic
nervous system
Sometime spores contaminate a wound
and the toxin is then absorbed from this
side
If the organism is ingested by infant, in the
honey smeared on pacifiers for instance, it
can multiply in the gut and produce the
toxin, causing infant botulism
 Botulinum
Clinical features and diagnosis
After incubation period of 2-72 hours, there is
descending weakness and paralysis, with
dysphagia, diplopia, vomiting, vertigo, and
respiratory muscle failure. There is no
abdominal pain, diarrhoea or fever. Infants
develop generalized weakness (floppy
babies), but usually recover.
Diagnosis is mainly clinical
The toxin can be demonstrated in
contaminated food and occasionally in the
patients serum
 Botulinum
Prevention
By avoidance of imperfectly sterilized canned or
preserved food.
Contaminated cans are often swollen due to the
release of gas by clostridial enzymes.
Home preserved foods are often incriminated,
but fruit, with its acidic pH, usually prevents the
development of the spores
The toxin is heat labile and is destroyed by
adequate cooking (80oC for 4 minutes).
The spores, however, can survive for up 2 hours
at boiling points (100oC)
Terima kasih