Central Nervous System Infections
Infectious Agents leading to CNS Infections

Bacterial
o Acute Pyogenic (Bacterial) Infection
 Neonates
 Eschericia coli
 Group B Streptococci
o Streptococcus pyogene
o Streptococcus agalactiae
 Infant
 Hemophilus influenza (before vaccination)
 Streptococcus pneumoniae
 Adolescent and young adults
 Nisseria meningitidis
 Elderly
 Streptococcus pneumoniae
 Listeria monocytogene
o Chronic Granulomatous Infection
 Mycobacterium spp
 Spirochete
 Treponema pallidum
Fungal
o Chronic Meningitis
 Cryptococcus spp.
o Vasculitis
 Mucor
 Aspergillus spp.
o Parenchymal Infection
 Granulomatous
 Cryptococcus spp.
 Abcess
 Candida spp.
 Unclassified
 Mucor (in Diabetic Ketoacidocis)
 Viral (Asceptic)
o Echovirus
o Coxsackievirus
o Nonparalytic poliomyelitis
o Herpes simplex
o Rabies
 Protozoal
o Malaria
o Toxoplasma spp.
o Entameoba histolytica
o Trypanosome spp.

Types of CNS Infections
1. Bacterial Infections
a. Acute Pyogenic Meningitis
b. Chronic Granulomatous Meningitis
i. Tuberculous meningitis
ii. Neurosyphilis
iii. Neurborelliosis
iv. Tabes dorsalis
c. Abscess
i. Epidural abscess
ii. Subdural abscess
iii. Brain abscess
2. Fungal Infections
a. Chronic fungal meningitis
3. Viral Infections
a. Acute asceptic meningitis
b. Viral encephalitis
c. Herpes simplex encephalitis
4. Protozoal Infection
a. Toxoplasmosis
5. Prions Diseases
a. Creutzfeldt-Jakob Disease (CJD)
b. Gerstman-straussler Syndrome (GSS)
c. Fatal familial insomnia
d. Kuru
Bacterial Infections
Disease
Acute
Pyogenic
Meningitis

Bacterial
infection of the
o Arachnoid
membrane
o Subarachnoid
space
o CSF
Morphology
Macroscopic
Microscopic
Pathogenesis
Heamatogenous spread
(the most common)
o The etiological agents
spread from distant area
of the body and lodged
at the CNS
 Direct implantation of
organisms
o Trauma
o Congenital
malformation –
ventricular septal defect
o Iatrogenic
 Lumbar puncture
 Local extension
o Sinusitis
 Mastoid sinus
 Frontal sinus
o Infected tooth
o Osteomyelitis of the
 Cranium
 Spine

Pathophysiology
Vasculitis of the
leptomeningeal arteries
lead to an ischemic attack
of the brain
o Hypoxic-Ischemic
Encephalopathy (HIE)
will then develop
 Infection hs led to
disturbance in vascular
permeability of the brain
o This has led the to brain
edema and leakage of
protein into the CSF
o Ultimately, increased in
ICP


Yellow-tan exudate
o This purulent exudate
covers the cerebral
hemispheres
o It usually settles at
 Along the base
of the brain
 Around cranial
nerves
 Openings to the
4th ventricle




Meningeal arteries
appeared engorged
Neutrophilic exudate
is seen involving the
meninges
Prominent dilated
blood vessels
especially the
Leptomeningeal
vessels
Edema and focal
inflammation
extending into the
superficial brain
parenchyma
(Virchow-Robin
space)
Complications
1. Cranial Nerves deficits and ischemic infarction
a. During infection, veins may inflamed and lead
to Phlebitis
b. Phlebitis may disrupt blood flow, turbulance
may lead to formation of blood clot
c. Blood clot may ultimately occlude smaller
vessels and lead to liquefactive necrosis of the
brain
2. Hydrocephalus
a. Purulent fibrinous exudate of infection may
organize into fibrous tissue
b. This fibrous tissue may block the exit of CSF at
the 4th ventricle and lead to communicating
hydrocephalus
Complications take times to develop, sometimes it
develops long after the disease subsides
Clinical
Manifestation
Initial symptoms
 Fever
 Severe
headache
 Stiff neck
Progression of
disease
 Confusion
 Coma
 Seizure
o Due to
 ↑ICP
 HIE
 Toxic
Metabolic
Encephalop
athy
Later complications
 Cranial nerve
deficits
 Ischemic
infarction
 Hydrocephalus
Laboratory
Findings
Lumbar puncture
o Increased in
ICP
o Abundant
neutrophils
o Elevated
proteins
o Reduced
glucose
Lumbar puncture is
only indicated in pts
without sign of
Papiloedema

Bacterial Infections
Disease


Brain
Abscess
Morphology
Macroscopic
Microscopic
Pathogenesis


Local extension
o Sinusitis

Mastoid sinus

Frontal sinus
o Infected tooth
o Osteomyelitis of the

Cranium

Spine
Heamatogenous spread (the most common)
o The etiological agents spread from distant area of the
body and lodged at the CNS
Direct implantation of organisms
o Trauma
Post meningitis


Descrete lesion with
liquefactive necrosis
Edema
o Presented with
expanded white
matter adjacent
to the abscess
Dense aggregates
of neutrophils
Necrotic area
surrounded with
granulation tissue
Neovascularization
Outside the capsule
of abscess is the
zone of gliosis
o With numerous
Gemistocytic
Astrocytes




Disease
Pathogenesis

Subdural
Abscess



Evolution of the Abscess
1. The brain undergoes acute inflammatory response after
come into contact with foreign agents, characterized with
a. Neutrophilic infiltration
b. Cerebritis
2. When the brain tries to heal the lesion, granulation tissue
forms at the peripheral of the lesion; middle zone undergoes
liquefactive necrosis
3. Sattellite abscess has a very poor capsulation at the medial
side; therefore it is easily rupture and the pus may enter the
ventricle
Epidural
Abscess
Clinical Manifestation


Ussually occurs due to complication of vertebral
osteomyelitis
Sometimes due to complications of
o Spinal surgery
o Trauma
o Spinal anesthesia
Extension of bacterial or fungal infection of the
o Cranium
o Sinuses
o Middle ear
Etiological agents




Staphylococcus aureus (most
cases)
Gram negative rods
o Bacteroides
Streptococci spp.
Mycobacterium tuberculosis
Most commonly affected
area
o Frontal lobe
o Parietal lobe
o Cerebellum
Features
o Progressive focal deficit

Loss of neurological
function due to
destruction of the
brain tissue
o Subsequent increased in
ICP
o Progrssive herniation
If the abscess ruptures, it will
lead to
o Ventriculitis
o Meningitis
o Venous sinous thrombosis
Clinical Manifestation








Initially presented with
o Fever
o Back pain
Progression
o Weakness of the lower extremities
o Impaired

Bowel function

Bladder function
Ends up with paralysis
Headache
Fever
Neck stiffness
Signs and symptoms of origin infection
Ultimately will lead to mass effect if the pus is massive
Bacterial Infections
Disease
Tuberculous
Infection of
CNS
Pathogenesis

Spreaded
through
heamatogenous
route and usually
comes about
from
disseminated
pulmonary
tuberculosis

o
o
o


o


1.
2.
Morphology
Microscopic
Macroscopic
Mixture of
 Subarachnoid
Lymphocytes
space contains
Plasma cells
o Gelatinous
Macrophages
o Fibrinous exudate
Florid cases show
 This exudate most
well-formed
often finds at the
granulomas
base of brain,
Often presented with
obliterating
caseating necrosis
o Cisterns
and giant cells
o Encasing cranial
Mimicking the
nerves
morphology of
 May present with
pulmonary
descrete white
tuberculosis
granules scattered
Obliterative
over the
endarteritis of artery
Leptomeninges
running through
 Tuberculoma may
subarachnoid space
have a bigger
Same appearance
lesion
for Tuberculoma
Complications
Hydrocephalus
a. Exudate may organize and form
arachnoid fibrosis which may occlude
the arachnoid granulation leading to
communicating hydrocephalus
Obliterative Endarteritis
a. Artery may become occluded during
healing and subsequently leads to
cerebral infarction
Clinical
Manifestation
Generalized
 Headache
 Malaise
 Mental
confusion
 Vomiting
Laboratory
Findings
Lumbar puncture
 Elevated
protein
 Glucose may
be
o Moderately
reduced
o Normal
Bacterial Infections
Disease
Neurosyphilis
Types
1. Meningovascular
neurosyphilis
2. Paretic
neurosyphilis
3. Tabes dorsalis
Morphology
Pathogenesis
Happens during
the tertiary syphilis
 This occurs in
about 10% of
syphilitic patients
who didn’t have
proper treatment
 It is caused by
spirochete
o Treponema
pallidum
Microscopic

Macroscopic
Meningovascular Neurosyphilis (Meninges)
Lymphocytes and
plasma cells appeared
at the peripheral to
blood vessels
 Heubner Arteritis
o Marked endothelial
thickening, thickened
 Tunica media
 Tunica adventitia


Primarily involved the
meninges of the
o Base of the brain
o Subarachnoid
space
o Blood vessels
Paretic Neurosyphilis (Brain Parenchyma)
Loss of neurons with
microglial (rod cells)
proliferation
 Gliosis
 Loss of Ependymal lining
with subependymal
gliosis
o Granular ependymitis

Brain appeared
o Shrunken
o Firm
 Frontal lobe is
atrophic
 Leptomeninges is
thickened
 With or wihout
hydrocephalus

Tabes Dorsalis (Spinal Cord)

Loss of axons and myelin
sheath at the Dorsal
Column

Pallor and atrophy of
the Dorsal Column
Clinical Manifestation
Meningovascular
Neurosyphilis
 Apathy
 Seizures
 General paresis with
dementia
Paretic Neurosyphilis
 Insidious loss of mental
and physical function
 Mood alteration
o Delusion of
grandeur
 Terminating with severe
dementia
Tabes Dorsalis
 Impaired joint position
sense
 Locomotor ataxia
 Loss of pain sensation
 Charcot’s joint
o Skin and joint
damage
 Lightning pains
 Loss of deep tendon
reflex
Fungal Infections

Primarily happens in
Immunocompromised patients
o HIV patients
o Debilitated patients
o Patients undergoing chemo
Disease
Pathogenesis


Chronic
Fungal
Meningitis

Characterized by 3 patterns
o Parenchymal Invasion
o Chronic fungal meningitis
 Abscess forming lesion
 Cryptococcus spp.
 Candida spp
o Vasculitis
 Granulomatous lesion
 Mucor
 Cryptococcus
 Aspergillus spp.
 Invasion of the blood vessel
leading to
o Heamorrhage
o Thrombosis
 Branching of hyphae can be
seen invading the cerebral
vessels
Morphology
Clinical
Laboratory
Manifestation
Findings
Microscopic
Macroscopic
 Usually well-formed
 Tubercle like nodule  The infections
 CSF findings
granuloma is hardly
on the
can be
o High protein
seen
Leptomeninges at
o Fulminant
concentrati
 Infiltration of chronic
the base of the
and fatal
on
inflammatory cells
brain
within 2
o Few cells
including
weeks
 Presence of
o Fibroblasts
o Indolent and
mucoid
o Mononuclear
evolving up
encapsulated
giant cells
to months or
yeast in Indian
o With presence of
years
Ink
Cryptococci spp.

Usually caused by
Cryptococcus
spp.
Brain usually one
of the latest
organs to
infected after
disseminated
fungal infection
Spreaded
through
heamatogenous
route
Viral Infections
Disease

Acute
Aseptic
Meningitis
Generally viral in origin
Echovirus
Coxsackievirus
Nonparalytic poliomyelitis
Sometimes can be non-viral in
origin (drug-induced)
o
NSAIDs
o
Antibiotics

Nervous system tropism
Certain virus affects certain
cells
o Others have preference
towards particular area of
the brain

Temporal lobe/ limbic
system

Herpes simplex
Capacity of latency
o Varicella-zoster may remain
dormant at the dorsal root
ganglia
It may also follow an immune
mediated disease pathway
o This has no evidence of
direct viral invasion
o For example Acute
Disseminated Encephalitis
Intrauterine infection
o May lead to congenital
malformation
May follow a slowly
degenerating disease
o Postencephalitic
Parkinsonism
General characteristics

Perivascular and parenchymal
mononuclear cells infiltration
o Lymphocytes
o Plasma cells
o Macrophages

Gliosis with/out nodules

Neurophagia

Nuclear/cytoplasmic inclusion
bodies can be found
Herpex Simplex Encephalitis

Large eosinophilic intranuclear
inclusion
Rabies

Negri bodies
o Round to oval in shape
o Eosinophilic cytoplasmic
inclusion
o Found in

Neurons in
Hippocampus

Pyramidal cells of
the Cerebellum
CMV

Owl eyes
o Intranuclear and
cytoplasmic inclusion
Measles

Warthin Finkeldey Bodies in
Subacute Sclerosing
Panencephalitis (SSPE)
JC Virus

Progressive Multifocal
Leucoencephalopathy (PML)
o
o
o


o


Viral
Encephalitis
Morphology
Microscopic
Macroscopic
Pathogenesis



Usually no abnormalities can be
found
Sometimes mild to moderate
lymphocytic infiltration of the
Leptomeninges


No distinctive
changes can be
seen on the brain
Sometimes, brain
appears
edematous
General characteristics

Almost invariably
with meningeal
inflammation
o
Meningoence
phalitis

Sometimes with the
involvement of the
spinal cord
o
Encephalomy
elitis
Herpex Simplex
Encephalitis

Petechiae are seen
on the Temporal
lobe
Rabies

Intense edematous
brain

Vascular
congestion
Clinical
Manifestation

Less fulminant, and
usually self-limiting
Laboratory Findings

CSF findings
Increased in pressure
Clear color
Increased numbers of
Lymphocytes
o
Slightly increased
protein
o
Normal glucose level
Smear and culture
appear negative for
bacteria
o
o
o

Protozoal Infections
Disease
Pathogenesis
Cerebral Toxoplasmosis
can be either
o Acquired Toxoplasmosis
o Congenital
Toxoplasmosis
 Ingestion of the cysts will
lead to infection
 The initial infection takes
place at the intestion and
regional lymph nodes
 The cysts formation occurs
at the
o CNS
o Eyes
o Cardiac muscle
o Skeletal muscle

Toxoplasmic
Encephalitis


Morphology
Microscopic
Macroscopic
Toxoplasma
 Abscess
pseudocyst
formation
with
 Often present
bradyzoites
with multiple foci
With/out
of calcification
granuloma
Clinical Manifestation
During an acute infection, patients
usually appear assymptomatic
 But when the cysts forms in the CNS,
patients will develop
o Fever
o Headache
o Lethargy
o Altered mental status
o Focal neurological deficits
o Convulsions
 May end with fatality
 Single or multiple lesions can be seen
at the
o Basal Ganglia
o Junction between the white and
gray matter

Prions Diseases
Disease
Prions Diseases
a. CreutzfeldtJakob Disease
(CJD)
b. Gerstmanstraussler
Syndrome
(GSS)
c. Fatal familial
insomnia
d. Kuru
Pathogenesis
Groups of diseases with abnormal form
of a specific protein, Prion Protein (PrP)
o It is itself transmissable particles
o Can be directly inoculated
 PrP undergoes conformational change
from
Normal α-helix-containing isoform (PrPc) 
Abnormal β-helix-pleated sheet isoform
(PrPsc)
 PrPsc is located at the Chromosome 20
 Accumulation of PrPsc in the neurons
appear to be the cause of pathology
Largely how does this happens, remains
unknown




Morphology
Microscopic
Macroscopic
Spongiform
 Brain atrophy
cerebral cortex  The progression of
o Small
disease can be either
vacoules in
o Very slow
dendritic
o Rapid
cytoplasm
o Grape-like
cluster
Astrocytocis
Neuronal loss
Clinical Manifestation

Most patients
develop Dementia
Cause
Appearance
Polymorphonuclear cell
Lymphocyte
Protein
Glucose
Pyogenic bacterial
meningitis
Yellowish, turbid
Markedly increased
Slightly increased or
Normal
Markedly increased
Decreased
Viral meningitis
Clear fluid
Slightly increased or
Normal
Markedly increased
Slightly increased or
Normal
Normal
Tuberculous meningitis
Yellowish and
viscous
Slightly increased or
Normal
Markedly increased
Increased
Decreased
Fungal meningitis
Yellowish and
viscous
Slightly increased or
Normal
Markedly increased
Slightly increased or
Normal
Normal or
decreased