CNS INFECTION

dr. Sri Indah Aruminingsih, Sp.Rad

Infectionsite
1.parenchyma: encephalitis , myelitis
encephalomyelitis.
2.meninges: meningitis, pachymeningitis,
leptomeningitis.
3.both of parenchyma and meninges :
meningoencephalitis.

Infections pathway
1.infection through circulation
2.direct infection : trauma ,otitis media
3.retrograde along peripheral nerves

ASEPTIC MENINGITIS
Viral, atypical bacteria, fungal, TB

Etiologies: Viruses and Bacteria

- Adenovirus
- Arbovirus
- Enteroviruses
- Herpesviruses
- HIV
- Influenza A/B
- Japanese encephalitis
- Measles
- Mumps
- Rubella
- Rabies
- Lymphocytic
choriomeningitic virus

Bartonella henslae
Bordetella pertussis
Borrelia burgdorferi
Brucella spp.
Chlamydia spp.
Ehrlichia, Leptospria spp.
Mycobacteria spp.
Mycoplasma spp.
Rickettsia spp.
Treponema pallidum

Etiologies: Fungal and Others

Aspergillus fumigatus
Blastomyces
dermatitidis
Candida spp.
Crytococcus
neoformans
Coccidioides immitis
Histoplasma
capsulatum

Toxoplasma gondii
Entamoeba histolytica
Acanthamoeba
Trichinella
Naegleria

TB Meningitis
Most serious complication of TB
infection
Fatal without effective treatment,
significant morbidity even with
treatment
In children CNS involvement occurs
during primary infection (rather than
reactivation)
Usually results from hematogenous
spread from a primary focus (lungs)
Variable presentation, but usually
onset is insidious
More rapid in infants and young

TB Meningitis

Clinical Staging
Stage

Signs and Symptoms

Stage 1 (Early)
Days to weeks

Fever, HA, malaise

Lethargy, behavior changes
No neuro deficits
No alteration of consciousness

Stage 2 (intermediate)
Weeks to months

Meningeal irritation
Minor neuro deficits (CN)

Stage 3 (late)
Months to years

Abnormal movements
Convulsions
Stupor or coma
Severe neuro deficits

ENCEPHALITIS AND
MYELITIS

Encephalitis
* Refers to inflammation of the brain
parenchyma
* Pathology shows:
Inflammation and destruction of neurons
Pathogen detection by direct visualization,
staining, etc
* Referred to as postinfectious encephalitis
when in temporal association with viral
infection or immunization
ADEM when it includes spinal cord
* Can cause significant alterations in
sensorium and seizures
Many patients require ICU

Etiology
* In neonates, the most common etiology is
HSV (usually type 2), but also entero- and
adenovirus
* In older children arthropod-borne viruses
(arboviruses) and enteroviruses are the
most common
Arbo: EEE, WEE, St. Louis, West Nile, JE
Entero: polio, echo, coxsackie, etc
* Subacute sclerosing panencephalitis is a
now rare complication of measles infection
* Tick borne bacteria can also be implicated
Borrelia, Rickettsia, ehrlichiosis

Pathogenesis
* Once a virus crosses the epithelium (usually at
a mucosal surface) viral replication occurs,
followed by viremia
* Viruses can penetrate the CSF from the blood,
or by spread from peripheral neurons (rabies and
HSV)
* Once in the CNS the virus attaches to host cells
Viral genome replication takes over, affecting
the other functions of the cell
* Interferon in particular inhibits viral
penetration, replication, translation, and
assembly
The inflammatory process may turn on the host

Clinical Manifestations
* Varies depending on affected site, severity,
and host factors
May or may not involve meninges (rabies)
* Nonspecific symptoms in neonates
May not have maternal h/o HSV
* Older children have acute onset of fever,
HA, seizures, behavior changes, AMS, or
coma, +/- prodrome
Depends on site of involvement
May have paralysis or paraplegia if spinal
cord involved
Look for rashes (erythema migrans)

Neuroimaging
Etiology
HSV
Japanese encephalitis
Rabies
Eastern equine
encephalitis

Site of involvement on
MRI
Inferomedial temporal
and frontal lobes
Bilateral thalami and
basal ganglia
Hippocampal, cerebellar,
mesencephalic areas
Disseminated brain stem
and basal ganglia

HSV Encephalitis
HSV is the most common cause of
fatal encephalitis in childhood
Mostly HSV-1 after neonatal period
Encephalitis can result from both
primary and recurrent HSV infection
Primary CNS if via olfactory and
trigeminal nerves
Disseminated HSV in the neonate
affects the CNS by hematogenous
spread

HSV: Clinical Presentation

Neonatal

Older children

Skin vesicles, scarring

Eye involvement
(chorioretinitis, optic
atrophy)
Brain (microcephaly,
encephalomalacia)
Disseminated disease
(sepsis, ARDS, MODS)

Older children have

typical symptoms of
encephalitis
Behavior, personality,
and speech changes
are particular to HSV
Progression may still
be rapid and fatal in
non-neonates

Diagnosis
* Swabs from conjunctiva,
nasopharynx, rectum,
skin lesions
* MRI may show temporal
or frontal involvement
* PLEDs on EEG
* HSV PCR is 95 %
sensitive and 100%
specific (gold standard)
* Please dont do a brain
biopsy

Herpes simplex encepalitis CT(A) and MRI (B-F) temporal lobe

involvement

BRAIN AND SPINAL CORD

ABSCESS

Brain and Spinal Cord

Abscess
May occur as a primary infection or
as a complication of bacterial
meningitis (more rare)
Rogers says that intensivists like
them because they are a serious,
potentially fatal infection that
requires immediate intervention

Abscesses: Etiologies
* Most common pathogens include
anaerobes, GNs, streptococci, and staph
* Neonates most commonly get GNs:
Citrobacter, Enterobacter, Proteus
* In other populations the organism
depends on predisposing factors:
CHD a-hemolytic strep
Endocarditis strep, S. aureus
Post-trauma staph
Otitis/sinusitis strep, Bacteroides
fragilis, Proteus spp., pseudomonas,
H.flu

Abscesses:
Pathogenesis
* May occur via hematogenous or direct spread
* Cyanotic heart disease is the most common
underlying condition (esp. TOF)
Polycythemia higher viscosity
microinfarcts
Bacteria love it!
* Chronic pulm infection, bacterial endocarditis,
and immune compromise also increase risk
* Direct spread may occur from chronic otitis,
mastoiditis, sinusitis, trauma, NS procedures
* Meningitis is a rare cause if treated
appropriately
Except in neonates with GN meningitis

Abscesses:
Pathogenesis
* Bugs localize at the gray-white junction
cerebritis
* Stage 1: Early cerebritis (Day 1-3)
Leukocyte infiltration, focal edema, no
clear demarcation
* Stage 2: Late cerebritis (Day 4-9)
Central liquefaction necrosis (yum!),
fibroblast infiltration, capsule formation
* Stage 3: Early capsule formation
* Stage 4: Late capsule formation (2
weeks out)
Dense fibrous capsule, marked edema

Abscesses:
Pathogenesis
Entire process may take 4-6 weeks
May progress faster or rupture into
ventricular system
Sites of infection vary but cerebral
are most common
Kids with CHD get them in MCA
distribution
Otitis can spread to unilateral
temporal lobe or cerebellum

Abscesses: Diagnosis
LP would be contraindicated in a
patient with brain or spinal cord
abscess
ButCSF may show pleocytosis,
protein, normal glc
Blood cultures and cultures from
other potential foci would help
Get imaging

Pathogenesis
Direct spread from contiguous foci (4050%)
Hematogenous (25-35%)
Penetrating trauma/surgery (10%)
Cryptogenic (15-20%)

27

MICROBIOLOGY OF BRAIN ABSCESS

AGENT
FREQUENCY (%)
Streptococci (S. intermedius, including S. anginosus) 6070
Bacteroides and Prevotella spp.
2040
Enterobacteriaceae
2333
Staphylococcus aureus
1015
Fungi *
1015
Streptococcus pneumoniae
<1
Haemophilus influenzae
<1
Protozoa, helminths (vary geographically)
<1
*Yeasts, fungi (Aspergillus Agents of mucor Candida Cryptococci Coccidiodoides
Cladosporium trichoides Pseudallescheria boydii)

Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus

Cysticerci)

CTID,2001

IMAGING STUDIES
MRI
more sensitive for early
cerebritis, satellite lesions,
necrosis, ring, edema,
especially posterior fossa &
brain stem

CT scan
99m Tc brain scan

very sensitive; useful

where CT or MRI not
available
Skull x-ray : insensitive,
if air seen, consider
possibility of brain abscess

Abscesses: Imaging

Abscesses: Imaging

Cerebritis Vasculitis

Shunt Infections
2/3 of all shunt infections are caused
by staph spp
Staph epi, aureus, and other coagnegative types have been
frequently isolated in several
series
GN enterics (E.coli, Klebsiella,
Proteus, Pseudomonas) make up 620%
Strep causes 8-10%
Multiple organisms are found in 1015%
Incidence has declined over the past

Pathogenesis
* Shunts are foreign bodies and interfere
with natural host defense mechanisms
Chemotaxis and phagocytosis
* Staph can also form biofilm which
increases bacterial adherence and
decreases effect of antibiotics
* Infection may occur through different
mechanisms:
Wound or skin breakdown over shunt
Colonization at the time of surgery
Retrograde from the distal end of shunt
Hematogenous seeding (infrequent)

Clinical Presentation
Fever, headache, vomiting, lethargy,
altered mental status
Check for wounds and look for
cellulitis along the shunt
Infection may spread to the distal
end of the shunt and cause
peritonitis

CNS FUNGAL INFECTIONS

Aspergillus, Cryptococcus

CNS Fungal Infections

Predisposing Condition

Fungal Pathogen

Prematurity

Candida albicans

Primary immunodeficiency (CGD,

SCID)

Candida, Cryptococcus,
Aspergillus

Corticosteroids

Cryptococcus, Candida

Cytotoxic agents

Aspergillus, Candida

Secondary immunodeficiency
(AIDS)

Cryptococcus, Histoplasma

Iron chelator therapy

Zygomycetes

IV drug abuse

Candida, Zygomycetes

Ketoacidosis, renal acidosis

Zygomycetes (Mucor)

Trauma, foreign body

Candida

CNS Fungal Infections

Dont forget about the fungi that can
cause disease in a healthy host:
Cryptococcus, Histoplasma,
Blastomyces, Coccidioides,
Sporothrix
Fungal infections are on the rise
worldwide due to increasing
prevalence of HIV

Fungal Meningitis
Most common causes are
Cryptococcus neoformans, C.
immitis, Candida, and Aspergillus
Fungal meningitis in general has a
more insidious onset than bacterial
Symptoms may develop over days
Always consider it with
subacute/chronic presentation
C.neoformans may develop more
quickly in patients on high-dose
steroids or with HIV

Fungal Meningitis
Rhinocerebral syndrome is a major
presentation of zygomycosis
Rhizopus and Mucor spp
Associated with poorly controlled
DM
Orbital pain, nasal discharge, facial
edema, proptosis
May invade carotids, trigeminal nerve
and adjacent brain structures
May also present with sudden
neuro deficit due to vasculitis
Can rarely cause mycotic
aneurysmal bleed

PARASITIC CNS
INFECTIONS
Neurocysticercosis
and Cerebral Malaria

Neurocysticercosis
- Most common parasitic
CNS infection.
Important cause of epilepsy in
the tropics.

- Most cases present with

seizures.
1/3 present with raised ICP.

- Endemic in Latin America,

Mexico, India, sub-Saharan
Africa, and China.
Including developed countries.
>1000 new cases are
diagnosed in the US each year.

Taenia solium Life Cycle

Neurocysticercosis
Parenchymal

Extraparenchymal

Seizures in 70-90% of
patients
1/3 will have raised
ICP
4% have focal neuro
deficits
May have encephalitis

Rare in children
Obstructive
hyrdocephalous or
chronic meningitis
Spinal involvement

Numerous cysts
Diffuse cerebral edema
Poor prognosis

Radicular pain
Cord compression
Transverse myelitis

Ophthalmic
involvement
Vision deficits

Neurocysticercosis

Organisme

bentuk kalsifikasi

Toxoplasmosis

Bercak-bercak dan irreguler

Rubella

Punctate atau Massive

CMV

Curvilinear dan periventrikuler

HSV

Massive + diffus seluruh otak.

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

Toxoplasmosis
Gambaran radiologis

Kalsifikasi : punctate bercak-bercak

irreguler extensif, lokasi : terutama basal
ganglia
Cerebral atrophy
Hydrocephalus / ventriculomegaly.
Porencephaly multiple

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

1.

Rubella
Gambaran radiologis

2.
3.

Kalsifikasi : punctate massive, lokasi :

terutama basal ganglia dan cortex
Gliosis porencephaly destruksi
cerebral luas
Mikrosefal.

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

CMV
Gambaran radiologis
1.

2.
3.
4.
5.

Kalsifikasi : curvilinear,
periventrikuler
Cerebral atrophy + gliosis + ggn.
myelinasi
Hydrocephalus / ventriculomegaly.
Hypoplasia cerebellar
Microcephaly + cortical dysplasia
( relatif sering ) polymicrogyria
lissencephaly

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

Herpes Simplex
Virus
Gambaran radiologis

1. Kalsifikasi : punctate, gyriform, massive

2. Cerebral atrophy berat + porencephaly /

encephalomalacia
3. Hydrocephalus / ventriculomegaly.
4. Perluasan cepat area yang tereinfeksi
sampai ke seluruh jaringan otak

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

Herpes
Simplex
Virus

Dr.med. Luqman Adji Saptogino,SpRad(K),SpKN.

Terima kasih