Microbial Infections of CNS

Ishtiaq Ahmed

Brain Abscess

• Direct extension from surroundings e.g.

calvarial fracture, infected leptomeninges

• Hematogenous: Bacteremia or septicemia

• Abscess usually occur in gray matter

• Disruption, destruction, displacement of

tissue

• Sever cases ventriculitis

• Staphylococcus, streptococcus ,

corynebacterium pale yellow to

yellow, watery to creamy exudate

• E.coli, klebsiella White to gray

• Pseudomonas: Green to bluish green

• Borders of abscess surrounded by

hyperemic zone.

Bovine Pituitary Abscess

The figure reveals a large and destructive pituitary abscess. The

inset shows the lesion extending into the hypothalamus after

fixation of the brain

Ovine Brain Abscess

Thalamus. A massive chronic abscess has created a deforming

space occupying lesion.

Ovine Brain Abscess

Cerebrum. Acute microabscesses resulting from hematogenous

bacterial infection

• Can be extension from otitis media ,

animals have facial nerve paralysis,

drooping ear

• Strangles cause brain abscess via

Hematogenous spread

Ependymitis & Choroid plexitis

• Coliform and streptococcus

• Gray white to yellow green thick to

gelatinous CSF

• Choroid plexus gray white, granular with

hyperemia and hemorrhage

• Bacteria may infect leptomeninges via

fourth ventricle.

• Exudate may block CSF flow

Feline Infectious Peritonitis - Lateral

ventricle- low magnification view of inflammatory infiltration of the choroid

plexus

Meningitis

• E.coli, streptococcus via Hematogenous

spread mostly, direct extension

• Mostly term used for leptomeninges

• While inflammation of dura mater is called

pachymeningitis

• Acute, subacute, chronic

• Suppurative, non-suppurative, eosinophillic,

granulomatous

• Pasteurella multocida & Actinomyces

pyogenes associated with pitutary fossa

abscess

Canine Bacterial Meningoencephalitis

Higher magnification views of areas of extensive cerebral necrosis,

hemorrhage and neutrophilic infiltration

Canine Bacterial Meningoencephalitis

Same case as the previous two figures and showing higher

magnification views of acute hemorrhage, necrosis and neutrophilic

infiltration. Note the capillary thrombosis in the left panel.

Canine Bacterial Meningoencephalitis

- Same case as the previous four figures. Higher magnification field

showing lymphocytes, macrophages and a few plasma cells and

neutrophils cuffing a vessel in the neuroparenchyma

Granulomatous

Meningoencephalomyelitis -

Mixed perivascular infiltrates in the leptomeninges.

Neonatal septicemia

• E.coli, Streptococcus spp, Salmonella,

Pasteurella spp, Haemophilous

• Endotoxin & LPS, teichoic acid,

proteoglycans in vasculature TNF,

IL-1, PAF, prostaglandin, thromboxane,

leukotriens neutrophil adhesion,

injury to endothelium and blood brain

barrier

• Brain swelling, edema , increased

intracranial pressure

• Fibrinopurulent inflammation of

membranous tissue

• Infections acquired perinataly

• Onset in few days to 2 week

• Congestion, hemorrhage, focal cloudiness

or opacity of meninges

• Fibrin in ventricles

• Microscopic: Except Salmonella, Fibrin

deposition and neutrophil infiltration

around blood vessels of leptomeninges,

choroid plexus & ependymal & Sub Ep.

• Epithelium of choroid plexus and ventricles

can be disrupted by degeneration &

necrosis

• Thrombosis & vasculitis feature of E.coli

• Salmonellosis generally limited to foals

and pigs

• Inflammatory response consist of

macrophages and lymphocytes

• Thrombosis, vasculitis, necrosis

• Haemophilus parasuis cause

leptomeningitis along polyserositis and

polyarthritis.

Suppurative meningitis, cerebral

hemispheres horse

Listeriosis

• Listeria monocytogenes

• Invade through the oral mucosa & into the

sensory and motor branches of trigeminal

nerve

• Other cranial nerves in the region may be

involved

• Via sensory axons using retrograde axonal

transport to trigeminal ganglion and then

brain.

• Or via motor axons directly into the mid

brain and medulla.

• Injury to neurons and axons due to

secondary bystander effect of

inflammation

• Immunological injury may also occur

• Organism also produces hemolysin

• In the brain, it can directly infect neurons,

glial cells, macrophages

• Bacteria spread cell to cell by producing

phospholipase

• Gross lesion usually absent

• Leptomeningeal opacity, foci of yellow

brown discoloration, hemorrhage, necrosis

in the terminal brainstem & cloudy csf

• Microscopically: Leptomeningitis centered

about the pons and medulla involving both

gray and white matter is characteristic

• Lesions may extend to diencephalon and

cervical spinal cord

• Early lesion: Loose clusters of microglial

cells

• Later neutrophils form microabscess

• In some foci macrophages may

predominate

• Necrosis and accumulation of gitter cells

• Gram positive bacilli can be detected

• Leptomeningitis with mononuclear cells

• 3 different disease forms

– Meningoencephalitis

– Abortion and still birth

– Septicemia

• Infection in humans do occur

• Dullness, torticollis, unilateral facial

paralysis, drooling caused by facial

paralysis

• Silage is most common source of infection

Ovine Listeriosis

Acute lesion in the medulla. Black arrows indicate a radix of cranial

nerve IX or X. There is locally extensive inflammatory infiltration

(inset) which at higher magnification is found to be predominantly

neutrophilic. Blue arrows indicate acute focal axonal swellings in the

intramedullary projection of the cranial nerve.

Ovine Listeriosis -

Caudal brainstem. Suppurative foci - numerous neutrophils and

some macrophages infiltrate the neuroparenchyma

Ovine Listeriosis -

Cervical spinal cord. Destructive inflammation, dominated in this

case by macrophages, many containing bacilli as shown by oil

immersion microscopy (arrows - right panel). Organisms are

difficult to find in many cases.

Ovine Listeriosis

Cervical spinal cord. Same case as the previous image. Inset -

bacilli within macrophages (arrows). Background - Specific

immunostaining reveals massive numbers of intracellular

organisms, often within neutrophils or macrophages. This case is

unusual in the number of organisms present.

Ovine Listeriosis

Caudal brainstem. Inset - diffuse neutrophilic infiltration of gray

matter with neuron cell bodies indicated by blue arrows. At higher

magnification bacilli are seen within a degenerating neuron (black

arrow)

Ovine Listeriosis

-Same case as the previous two figures. Higher magnification fields. Left

panel - a necrotizing pyo-granulomatous focal lesion within more diffuse

inflammatory infiltration. Right panel - degenerate neurons (arrows) have a

basophilic reticulated appearance due to dystrophic mineralization.

Bovine Listeriosis

Caudal brainstem. This figure is designed to illustrate

parenchymal changes suggestive of Listeriosis that might be

identified in cases in which suppurative foci with organisms are not

included in diagnostic samples. Left panel - scattered perivascular

cuffs to contain numerous plasma cells (arrows). Right panel -

mixed inflammatory cells including neutrophils cuffing a vessel.

Thrombotic

Meningoencephalitis• Histophilus somni

• Gram negative bacilli

• Septicemia

– Pneumonia

– Polyarthritis

– Myocarditis

– Abortion

– Meningoencephalitis

• More prevalent in feed lot cattle

• CNS form called TME

• Many cattle harbor in the upper digestive

tract

• Respiratory system is first site of

replication then Hematogenous spread to

CNS

• Once in circulation, emboli lodge at the

interface of white and gray matter in

microvessels

• Adherence to endothelial cells leading to

contraction and sloughing

• Subendothelial collagen is exposed

• Vasculitis, thrombosis and infarction

• Lipooligosaccharide, a bacterial toxin

protect it from defense of body

• Neutrophils, blood monocytes and alveolar

macrophages can not kill

• Irregular foci of hemorrhage & necrosis

scattered randomly

• Cerebrum, at cortical gray white interface

• Spinal cord has lesions

• Brain swelling due to edema

• Meningeal opacity

• Microscopically: Vasculitis, vascular

necrosis, thrombosis, infarction

• Clinically: Ataxic, circling, head pressing,

blindness, convulsions, comma

Fungi and Algae

• Aspergillus, Candida, Mucor

• Of the systemic fungi Coccidioides immitis,

Blastomyces dermatitides, Histoplasma

capsulatum, Cryptococcus neoformans

• Reach CNS by leukocyte trafficking and

hematogenous

• Granulomatous/pyogranulomatous

response

• Grossly, moderately well demarcated

expansile yellow brown foci

• Microscopically: neutrophils, epithelioid

macrophages, giant cells

• Organism in mononuclear cell

Canine Blastomycosis

Severely proliferative pyogranulomatous inflammation involves the

choroid plexus and ependyma of the fourth ventricle, lateral

apertures and meninges (left) and lateral and third ventricles (right).

Canine Blastomycosis - Lateral ventricle.

Pyogranulomatous choroid plexitis and ependymitis. Yeast bodies

are evident in the right panel (arrows).

Canine Blastomycosis - Lateral ventricle

. Left panel - high magnification view to show intraventricular

exudate with yeast bodies within multinucleated giant cells

(arrows). Right panel - in the area indicated by the arrow are

numerous yeast bodies highlighted by silver staining.

• Cat, dog, horse

• Pathogen enters in leptomeninges and

subarachnoid space by direct extension

from the cribriform plate nasal/sinus

infection

• Hematogenous by leukocyte trafficking

from lungs infection

• A thick muco-polysaccharide capsule

protects from host defense

• Meninges cloudy to viscous

• Leucocytic response vary from sparse to

granulomatous

• In cats there may be no response

sometimes

• Yeast is 2-10 mm, thick non-staining

capsule

• PAS, Gomori’s methenamine silver for

organism and alcian blue for capsule

• Two virulence factors

– Mucopolysaccharide capsule

– Biochemical pathway using catecholamine's

with specific transport pathway and

phenoloxidase enzyme producing melanin like

compound

• CSF lack alternative pathway of

• Grossly: Multiple small, viscous,

gelatinous cysts in meninges and CNS

• Microscopically: Loosely organized lacy

appearance with cryptococcal organsim

• Ventriculitis, choroiditis

• Neutrophils, eosinophils, macrophages,

giant cells depending upon immune status

• Immunosuppression by Felv, FIV,

Ehrlichia canis, long term glucocorticoid

therapy increases susceptibility

Feline Cryptococcosis -

Representative high magnification field from the gelatinous lesion

seen in the previous figure. Numerous yeast bodies with unstained

capsules are embedded in mucin with a minimal inflammatory

response.

Feline Cryptococcosis

In this case there are multiple cavitating lesions in the cerebellum

containing mostly organisms and mucin with a mild macrophage

response. (Original material courtesy of Dr. W. J. Hartley)