Intracranial Infection

in infant and children

Sunartini
INT Prog. FM UGM
22042010

Infections of the CNS (2)

Infection of the central nervous system (CNS)
can be viral, bacterial, fungal, or parasitic in
origin. Infectious microorganisms most often
enter the CNS by direct penetration after
trauma or by travelling in the bloodstream
There are three major categories of CNS infections
treated by a neuro-ICU:
Encephalitis
Meningitis
Brain Abscess

Infections of the CNS (4)

Cerebritis means inflammation of all tissues in the
brain substance, and is used to indicate a stage
preliminary to abscess formation. Thus, cerebritis is a
very destructive process and implies bacterial infection.

Encephaltitis, on the other hand, means

inflammation of brain tissue secondary to viral infection.
Inflammation in encephalitis is not usually as intense as
in cerebritis, and the destruction, while still profound, is
not usually as great.

Myelitis is the counterpart of encephalitis in the spinal

cord.

Infections of the CNS

two broad categories
- those which involve primarily the meninges,
and
- those which are confined primarily to the
parenchyma.
Under the heading of meningeal infections, we
will consider general concepts after which
three basic categories will be discussed:
- pyogenic meningitis,
- granulomatous meningitis,
- lymphocytic meningitis.

Infections of the CNS(3)

In contrast to the organization of meningeal infections,
parenchymal infections have been organized in terms
of the various types of organisms which include
syphilis, parasites, fungi, viruses, and prions
(scrapie, kuru & Creutzfeldt-Jakob disease).
The definitions of at least two terms should be made
clear for parenchymal infections:
cerebritis and encephalitis.
Both of these terms imply inflammation of parenchyma
in the cerebrum, and on occasion are used
interchangeably. However, by convention these terms
do have specific and different meanings among
practicing neuropathologists

Encephalitis
What is encephalitis?
Encephalitis is defined as inflammation of the brain due
to an infection.
This inflammation is commonly the result of a viral
infection. Viruses can gain access to the central
nervous system (CNS) through the blood or by traveling
within nerve cells (neurons).
The neuro-ICU deals primarily with acute viral
encephalitis.
There are approximately 20,000 cases of encephalitis
in America each year.
In Indonesia no exact data.

Meningitis
What is meningitis?
Meninges is a membranous covering the inner
surface of the skull of the brain
A fluid known as cerebrospinal fluid (CSF) circulates
around the brain and serves to cushion the brain
against injury.

Meningitis is an inflammation of the meninges due

to infection.
It occurs when a foreign pathogen invades the
subarachnoid space and populates the CSF.
The foreign microorganisms can either be bacteria or
viruses.
meningitis can be classified as either
bacterial or viral.
Since bacterial infection is much more serious, a
neuro-ICU is specialized towards the treatment of
this type of meningitis.

Cont
Epidemiology :

1995 : bacterial as the etiology of 2800 cases of
meningitis in children under 18 years in USA

1986 : cases were children of 1 mo -5 yr old,
in1995 meningitis cases in this group 87%
decreased and median age of bacterial
meningitis bakterialis meningkat increased to
15% in the age of 15 -25 yr old

2001: India, from 54 of children with acute
bacterial meningitis 78% were in the age of 1
year and 52 % under 6 months old.

Cont
What are the causes of bacterial meningitis?
Generally, bacterial meningitis is more dangerous than
the viral form and can constitute a medical emergency.
Two of the major forms of bacteria
* Streptococcus pneumoniae and
Neisseria meningitidis . ------>
Therefore, bacterial meningitis usually occurs in either a
pneumococcal or a meningococcal form.
Pneumococcal meningitis is typically observed in adults.
It can arise following brain trauma, and is predisposed by
sickle cell anemia, alcoholism, and diabetes.
Meningococcal meningitis most often occurs in children,
adolescents, and young adults.

Organism Identified Most Frequently

as a Cause of Bacterial Meningitis
Acute Bacterial
Meningitis

Chronic Bacterial
Meningitis

Streptococ.
Streptococ. pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Escherichia coli
Other gramgram-negatif
bacilli
Listeria monocytogenes
Salmonella species
Leptospira species
Staphylococcus aureus
Group B streptococci

Mycobact.
Mycobact. tuberculosis
Treponema pallidum
Borrelia burgdorferi

Etiologi :
 1982- 2001 : bacterial the
study in Public Health
Laboratory Service (PHLS)
Neisseria meningitidis.
 3 type of bacterial cause of
acute bacterial meningitis ,
are Streptococcus
pneumoniae, Neisseria
meningitidis, and
Haemophilus influenza b
(Hib).

The Age distribution of 4 important types of acute bacterial

meningitis in a tropical African Country where meningococcal
meningitis is prevalent at a later age than in developed countries
countries

E. coli

S. pneumoniae

H. influenzae

N. meningitis
0

1
12
MONTHS

AGE

10
YEARS

20

40

60 or >

What are the clinical features of bacterial

meningitis?

Patofisiology
Infection
(ENT))

Multiplication
of bscteria

Inflamation
Edema
CNS Dysfunction

Entrance
tp CNS

Hematogenic
spread out

Immune system
not good

Severe Headacge
Neckstiffness
Photophobia
Convulsion
(classic symptom)

Bacterial meningitis presents as an acute disease.

It is characterized by three main features:
- headache,
- high persistent fever, and
- neck stiffness (an inability to bow the head, known as
nuchal rigidity).
Bacterial meningitis can also be accompanied by a variety
of other symptoms including
- rashes,
- nausea,
- lethargy, and
- general malaise.
- In addition, seizures occur in about 20% of patients and
- coma occurs in 5-10% of patients.
The latter development is associated with a particularly
poor prognosis.

Table 3. Diagnosis and treatment of meningitis

Depend on the result of CSF examination

CLINICAL PICTURE

 Cardinal Symptom
 Headache
 High fever persistent
 Neck stiffness (an inability to bow the head,
known neckas nuchal rigidity)

other symptoms including

- rashes,
-

CLINICAL SIGN
The first signs : convulsion, irritabel,
delirium, somnolent, letargi, & maybe
coma

Specific Symptoms :
Petechie & purpura: Meningococcemia
some times H. infl.
Progresive hemorrhage : Meningococc
Rash Str. Pneumonie
Arthralgie : Meningococcemie & H. influenzae
Pathognomonis Sign : Meningeal Sign
Neckstiffness, Brudzinsky I,II Sign, Kernig sign : (+)

nausea,
lethargy, and
general malaise.
seizures occur in about 20% of patients
coma occurs in 5-10% of patients.

Neonates
Very difficult -- various clinical sign
If there is a sign of sepsis --> consider
intracranial infection
Large fontanel : bulging

Baby (3(3-12 bulan)

bulan)
High fever, vomiting, irritabel, convulsion,
somnolent highpitch cry
Specific : Large Fontanel bulging,
tenderness Difficult to find meningeal sign e.g
neck stiffness Brudzinsky and Kernig sign

DIAGNOSIS

Cont..

LUMBAR PUNCTURE : indication, contraindications,

LCS:
Oppalescent / unclear
WBC increase
Protein increase
Glucose ratio between LCS : blood decerase
Intracranial pressure on LCS increase
Gram stain : positif bacteria
Culture: Gold standard: positif
Fast Diagnosis : latex partile agglutination

Laboratory Examination
CSF

Normal Baby Bacterial

Viral
Meningitis
Meningitis
Leucocyte < 10 per m3 200-100.000/m3 25-1000/ m3
Neutroph.

NEJM, 2008

<10%

80-100%

<50%

Glucose

>50% serum

<40% serum

>40% serum

Protein

< 40 mg/dL

100-500 mg/dL 50-100 mg/dL

JAMA 2007

TREATMENT

Fluid and electrolyte management

Antibiotik
Steroid dexametason
Glucose 40%

JAMA, 2007

TREATMENT
1. Nursing Care
2. In critical period --->
---> PICU
3. treatment
a. Homeostasis  ivfd
b. Convulsion / st. convulsivus
 Stop seizure immediately
 Adequate Oxygenation
 Airway
c. Corticosteroids for Bacterial M-is
d. Antibiotics

II. Antibiotic for Bacterial Meningitis

Bacteriae
N. Influensa
S. Pneumonia

N. Meningitis
Gram Negatif

Staphylococus

THE PRINCIPAL OF ANTIBIOTIC

Drugs
- Kloramfenikol, ampisilin
- Seftriakson, Sefotaksim
- Penisilin, Kloramfenikol
- Sefuroksim, Seftriakson
- Vankomisin
- Penisilin, Kloramfenikol
- Sefuroksim, Seftriakson
- Sebutaksim, Septazidin
- Seftriakson, Amikasin
- Gentamysin, netilmisin
- Nafsilin, Vankomisin
- Rifampisin

ANTIBIOTIC ARE GIVEN IN 2 FASE

I.v  min 5 DAYS (fever free), continued oral

1. Choose the proper AB

2. Maintain the therapeutic level in CSF
3. Use AB which can entrance through BBB
4. The Ratio of AB level in CSF and blood are:
Kloramfenikol 9 : 1 Cefaloridin 1 : 70
Cefalotin
1 : 7 Ampisilin 1 : 56
 Influence with
 Inflamation of meninges
 Protein bound

I.
II.

Result of culture : not yet ------> EMPIRIC

Result of culture positif : --> drugs sensitive
Culture (+)

Drugs

Neonates and babies:

-(1) Ampisilin 200 400 mg/kg BB

Combination of (1)

- + Kloramfenikol 100 mg/lg BB

or

-(2) Ampisilin 200 400 mg/kg BB

-+ Sefurokxim 100 200 mg/kg BB

Neonates

-Ampisilin 200 400 mg/kg BB

-+ Gentamycin 6 mg/kg BB

TABEL 4
Pengobatan yang direkomendasikan untuk
meningitis aseptik
Etiologi

Pengobatan

Cytomegalovirus

Ganciclovir (Cytovene) (clinical

research trial)

Enterovirus

Immune globulin (possibly

pleconaril)

Herpes simplex virus

Acyclovir (Zovirax)

Hu man
immunodeficiency virus

Multidrug antiretroviral
regimens

Lyme disease

Ceftriaxone (Rocephin)

Syphilis

High - dose penicillin

Toxoplasmosis

Pyrimethamine (Daraprim) and

sulfadiazine

Tuberculosis

Multidrug anti mycobacterial

regimens
Tunkel et al, 2004

How is bacterial meningitis treated in a neuroICU?

The first step :

to obtain a CSF sample via lumbar puncture and
to then initiate antibiotic therapy.
The antibiotic regimen should be specific to the type of
bacteria causing the meningitis.
- a regimen of ampicillin and a third-generation
cephalosporins such as ceftriaxone
- Dehydration and/or shock ---> by blood volume
expansion and the use of pressors to increase blood
pressure.
- Cerebral edema and increased intracranial pressure
- depressed level of consciousness,
- severe headache, and
- projectile vomiting.
- ICP monitoring.
- Seizures are treated by the use of rapid acting
anticonvulsants such as diazepam and lorazepam.
Lorazepam infusion is commonly followed-up with a
longer lasting anticonvulsant known as phenytoin (Dilantin).

Manajemen
Admitted to the hospital, Antibiotic
in the dose of intracranial infection
For bacterial meningitis : combination of
Ampicillin and Cefotaxime or
Chloramphenicol
Empiric : acyclovir for neonates and baby
with lesion in buccal or ginggiva /stomatitis
or vesicle cause by herves virus, suspected
virus ensefalitis, sepsis, without positif
culture, or sepsis with HIV infection of the
parent.

Dose Guidelines of Intravenous Antimicrobials in Infants

and Children With Bacterial Meningitis
Antibiotic

Dose (mg/kg/d)
IV

Maximum Daily
Dose

Dosing Interval

Ampicillin

400

6-12 g

q6h

Vancomycin

60

2-4 g

q6h

Penicillin G

400,000 U

24 million

q6h

Cefotaxime

200-300

8-10 g

q6h

Ceftriaxone

100

4g

q12h

Ceftazidime

150

6g

q8h

Cefepime*

150

2-4 g

q8h
q6h

Imipenem

60

2-4 g

Meropenem

120

4-6 g

q8h

Rifampin

20

600 mg

q12h

*Minimal experience in pediatrics and not licensed for treatment of meningitis.

Caution in use for treatment of meningitis because of possible seizures.

Management
Aseptic meningitis : symptomatic
As general : minimize the symptom such as
analgetics, fluid and treatment for prevention of
sequele
Adequate oxigenation , fluid and electrolite
Specific treatment for bactertial meningitis
Antibiotics for Gram (+ and -) + Dexamethasone
For virus used acyclovir or gancyclovir depend
on the etiology with or without immunoglobulin

What is the prognosis for bacterial

meningitis?
Prognosis directly depends on the speed with which therapy
is initiated.
It is also dependent on the identity of the invading bacteria
- the age and
- medical status of the patient.

With rapid and effective treatment mortality rates

vary between 5-25%.
Delayed long-term sequelae such as :
deafness and

intellectual deterioration.
death.
The earlier a diagnosis is made and treatment instituted, the
greater the chance of survival without neurological
disabilities.

What are the complications of bacterial

meningitis?
o) shock, a condition known as the WaterhouseFriderichsen syndrome.
p) cerebral edema.
This can translate into a dangerous increase in
the pressure within the skull (the intracranial
pressure or ICP). Both of these complications
are life-threatening and mandate treatment in
an intensive care unit.

Herpes Simplex Encephalitis

ENCEPHALITIS

NN

Neonatal Herpes Simplex (1)

Incidence of neonatal HSV infection varies
inexplicably from country to country e.g.
from 1 in 4000 live births in the U.S. to 1 in
10000 live births in the UK
The baby is usually infected perinatally
during passage through the birth canal.
Premature rupturing of the membranes is a
well recognized risk factor.

Herpes Simplex encephalitis is one of the most

serious complications of herpes simplex disease.
There are two forms:
Neonatal there is global involvement and the brain
is almost liquefied. The mortality rate approaches
100%.
Focal disease the temporal lobe is most commonly
affected. This form of the disease appears in children
and adults. It is possible that many of these cases
arise from reactivation of virus. The mortality rate is
high (70%) without treatment.
It is of utmost importance to make a diagnosis of
HSE early. It is general practice that IV acyclovir is
given in all cases of suspected HSE before laboratory
results are available.

Neonatal Herpes (2)

The risk of perinatal transmission is
greatest when there is a florid primary
infection in the mother.
There is an appreciably smaller risk from
recurrent lesions in the mother, probably
because of the lower viral load and the
presence of specific antibody
The baby may also be infected from other
sources such as oral lesions from the
mother or a herpetic whitlow in a nurse.

Neonatal Herpes Simplex (3)

The spectrum of neonatal HSV infection
varies from a mild disease localized to the
skin to a fatal disseminated infection.
Infection is particularly dangerous in
premature infants.
Where dissemination occurs, the organs
most commonly involved are the liver,
adrenals and the brain.
Where the brain is involved, the prognosis
is particularly severe. The encephalitis is
global and of such severity that the brain
may be liquefied.

Neonatal Herpes (4)

A large proportion of survivors of neonatal
HSV infection have residual disabilities.
Acyclovir should be promptly given in all
suspected cases of neonatal HSV infection.
The only means of prevention is to offer
caesarean section to mothers with florid
genital HSV lesions.

Other Manifestation (2)

Other Manifestations..(1)
Disseminated herpes simplex are
much more likely to occur in immuno
compromised individuals.
The widespread vesicular resembles
that of chickenpox. Many organs other
than the skin may be involved e.g.
liver, spleen, lungs, and CNS.

Other cutaneous manifestations include

eczema herpeticum which is potentially a
serious disease that occurs in patients with
eczema.
Herpetic whitlow which arise from implantation
of the virus into the skin and typically affect the
fingers.
zosteriform herpes simplex". This is a rare
presentation of herpes simplex where HSV
lesions appear in a dermatomal distribution
similar to herpes zoster.

Laboratory Diagnosis.(2)

Laboratory Diagnosis (1)

Direct Detection
Electron microscopy of vesicle fluid - rapid result
but cannot distinguish between HSV and VZV
Immunofluorescence of skin scrappings - can
distinguish between HSV and VZV
PCR - now used routinely for the diagnosis of
herpes simple encephalitis

Virus Isolation
HSV-1 and HSV-2 are among the easiest viruses to
cultivate. It usually takes only 1 - 5 days for a result
to be available.

Serology
Not that useful in the acute phase because it takes
1-2 weeks for before antibodies appear after
infection. Used to document to recent infection.

Management
At present, there are only a few indications of
antiviral chemo-therapy, with the high cost of
antiviral drugs being a main consideration.
Generally, antiviral chemotherapy is indicated
where the primary infection is especially severe,
where there is dissemination, where sight is
threatened, and herpes simplex encephalitis.

MANAGEMENT.
Acyclovir this the drug of choice for most
situations at present. It is available in a number of
formulations:
Intra Vena (HSV infection in normal and immuno
compromised patients)
Oral (treatment and long term suppression of
mucocutaneous herpes and prophylaxis of
HSV in immunocompromised patients)
Cream (HSV infection of the skin and mucous
membranes)
Ophthalmic ointment

Management
Famciclovir and valacyclovir oral only, more
expensive than acyclovir.
Other older agents e.g. idoxuridine,
trifluorothymidine, Vidarabine (ara-A).
These agents are highly toxic and is
suitable for topical use for opthalmic
infection only

babi
Vector :
Cx. tritaeniorhynchus
Cx.gelidus
Cx. pseudovishnui
Cx. fuscocephalus
Cx.wishnui
Cx.annulirostris
etc

Nyamuk

Dead-end host

Human

babi

Transmisi berlanjut

Nyamuk lain
aedes sp.

Bird migration

Note acyclovir is effective in crrelation with thymidinekinase

Nyamuk

Spring

Bird
Black crowned night heron

Temperatur zone

Fall

Local winter reservoir

Transporarial
transmission in mosquitos
Snake, birts bats

GEJALA KLINIK
Gejala klinik :
agak bervariasi tergantung dari berat
ringanya kelainan SSP, umur penderita &
lain-lain.
Spektrum penyakit dapat hanya berupa
panas disertai sakit kepala, meningitis
aseptik dan meningoencepahlitis. Masa
inkubasi 4-14 hari.

Perjalanan penyakit dapat dibagi menjadi 3

stadium:
Stadium prodromal
Berlangsung 2-4 hari, dengan keluhan
timbulnya gejala-gejala terserang SSP
dengan gejala dominan panas, sakit
kepala, menggigil. Gejala lain berupa
malaise, anoreksi, keluhan traktus
respiratorius seperti batuk, pilek dan
keluhan traktus gastrointestinal seperti
mual, muntah dan nyeri di dalam
epigastrium

 Stadium encephalitis
panas, bingung, kejang-kejang, kaku
kuduk dan gejala lain dari kelainan
susunan syaraf pusat (SSP), seperti
kesadaran menurun, delirium, stupor,
photophobia, kelumpuhan pada mata,
facial dan ekstremitas, kemudian masuk
ke stadium koma dan meninggal dalam
waktu kurang 10 hari.
Gejala lain juga tanpak antara lain
adalah ditemukannya kelainan syaraf
motoris dan kekurangan cairan tubuh
(dehidrasi)

Stadium Konvalesens (kesembuhan)

Stadium ini dimulai bila suhu badan
dan sedimentation rate dari butirbutir darah merah normal.
Gejala neurologi menunjukan
adanya gejala-gejala perbaikan
atau tetap tidak ada perubahan.

DIAGNOSIS
Diagnosa laboratoium dapat dilakukan
dengan beberapa cara; secara serologi,
biologi, identifikasi virus, pemeriksaan
darah dan cairan sumsum.
Secara serologis dapat dilakukan
pemeriksaan Haemoglutination Inhibition
Test (HI Test), Complement Fication Test
(CFT), Neutralizing Antibody Test (NAT)
pada anak mencit , ELISA, Agar Gel
Diffuion (AGD), Single Radial Haemolysis
Test.

PENATALAKSANAAN
JE tidak ditemukan dalam peredaran
darah atau cairan sekresi pada setiap
stadium,  Tak perlu diisolasi dan
desinfektan khusus
Belum ditemukan obat tepat.
Pengobatan
simptomatis
dan
tindakan-tindakan
suportif

kesembuhan penderita

DIAGNOSIS banding

Malaria serebral
Meningitis bakteri
Meningitis aseptik
Kejang demam
Ensefalitis oleh flavivirus lainnya
Rabies
Sindroma Reye
Encephalopati toksik

Obat-obat dan perawatan yang dianjurkan

untuk Japanese Encephalitis (JE) adalah :
Obat anti kejang
Obat penurun panas/anti piretik
Tata laksana penanganan kesulitan pada
alat pernafasan
Mempertahankan keseimbangan cairan
tubuh (fluid balance)
Oedema Cerebral
Infeksi saluran air seni
Fisioterapi dan rehabilitasi

Gejala Klinik

myoclonus,
areflexia,
hypotonia, and
dysautonomia (hypertension and
tachycardia).

Nipah virus berhubungan dengan encephalitis

(inflammation of the brain) ditandai dengan
fever dan drowsiness dan lebih serius pada
SSP dapat menimbulkan coma, seizures, and
inability to maintain breathing.
Nipah virus terjadi 3-14 hari fever dan
headache diikuti drowsiness and disorientation
ditandai dengan mental confusion.
Tanda dan gejala dengan cepat menjadi koma
dari 24-48 jam beberapa pasien mengalami
gangguan pernafasan sampai pertengahan
infeksi

Diagnosis
Cairan Serebrospinal tidak normal 75%
kasus
EEG menunjukkan diffuse secara pelan
slow dengan abnormalities focal over
temporal regions (75%),
Tomogram computer normal dan
magnetic resonance otak sampai phase
akut menunjukkan perluasan sebaran
lesi-lesi focal pada subcortical dan deep
white matter.

Penyakit nervous serius oleh nipah virus

encephalitis telah perlihatkan ditunjukkan
oleh beberapa sequelae, juga
convulsions persistent dan personality
changes.
Dari tahun 1998-1999 (outbreak) : 40 %
pasien terkena penyakit nervous serius
dan banyak menimbulkan kematian

PENCEGAHAN
Obat ribavirin menunjukkan hasil yang
effektif terhadap virus dalam uji coba in
vitro

DAFTAR PUSTAKA
Petrus Nahak, SKM., Mkes, 2001
Japanese Encephalitis (JE) Buletin
Epidemiologi Propinsi NTT
www.cdc.co.id/travel/ diseases/japence
A Chaudhuri and P G E Kennedy 2002
Diagnosis and treatment of viral
encephalitis Postgraduate Medical
Journal 78:575-583

mmmm

Sunartini

REFFERENCES
Shah,SS (editor) 2009 Pediatric Practice Infectious disease
Krugman, 2003 Infectious disease