Pathology of CNS Infections

CNS Viral Infections

HSV – represents an acute viral infection; HIV – represents a chronic viral infection

(1) Rabies (a model for viral infections)

Enters the body through an animal bite, then spreads intraxonally
Perivascular lymphocytic infiltrate

Cytotoxic lymphocytes

Cause microglial nodules
Can get viral inclusions, intranuclear inclusions, microglial nodules, and Negri bodies
Rabies can mutate.

Pathology: cytotoxic (CD8+) T-lymphocytes, encephalitis, microglial nodules (Macrophages of CNS circle around neurons), intracytoplasmic inclusions

(2) Herpes

Pathogenesis: intra-axonal spread

Initial vesicular lesions in the mouth or on the faceÞ virus travels up axon trans-synaptically and becomes latent in trigeminal ganglionÞ recurrence occurs by nerve when induced by fever, sunlight, stress, etc.

Medial temporal lobe stuctures, black necrotic tissue, high mortality rate.

Skin lesions – different serotype than the type that causes HSE, so transmission may not be through trigeminal nerve, transmission may occur through nasal epithelium and olfactory nerve

Treat first, ask questions later

Febrile syndrome

Pathology – hemorrhagic necrosis within the limbic system, accompanied by perivascular lymphocytic infiltrates, and occasionally intranuclear viral inclusions.

Can be seen with Immunohistochemical staining

(3) HIV

cellular targets of HIV: mononuclear cells of the CNS = microglia, macrophages, macrophage-like giant cells (note: neurons NOT affected directly, but indirectly due to change in environment)

HIV infected macrophages and microglia – vacuolar change, microglial nodules, multinucleated giant cells, HIV leukoencephalopathy and diffuse myelin pallor – breakdown of BBB, mild astrocytosis

Mediators of HIV Neurotoxicity

macrophage-produced diffusible toxins, NMDA receptor, HIV proteins, envelope glycoprotein (gp120), excitotoxic mechanism

Pathogenesis of HIV:

HIV gp 120 (glycoprotein on HIV virus) binds to CD4 receptor (expressed by microglial cells) Þ Replicates within microglial cells Þ Spreads via CD4 receptor with formation of syncytial multinucleated cells – does not infect neurons or macroglia.

hematogenous spread

patients exhibit dementia with mental slowing, memory loss, mood disturbances, apathy and depression. Motor abnormalities may be present.

Trojan horse hypothesis – monocytes carry HIV into the brain by infecting microglial cells (monocytes of CNS)

Cells fuse and form multi-nucleated microglial cells called syncitial cells (pathonemonic of HIV), older texts just call these multinucleated giant cells.

Infection localizes first to globus pallidus Þ caudateÞ putamen, thalamus

CNS Bacterial Infections

(1) Acute Meningitis

general pathogenesis: mucosal colonization Þ local invasion Þ bacteremia Þ meningeal invasion Þ bacterial replication Þ subarachnoid space inflammation

Gross structure: cloudy meninges, marked vascular dilatation, cerebral edema(end product of inflammation cascade)

Bacteria is pretty much kept in the meninges, not in the brain, no neurologic dissemination

Bacteria does not need to be alive to cause meningitis, teichoic acid or LPS in cell wall can cause cascade

Virulence factors: Teichoic acid, LPSÞ microglia, astrocytesÞ TNF, IL-1 Þ leukocyute recruitmentÞ neutrophil degranulation of BBB

Not just a matter of killing bacteria but stopping the bacteria from releasing toxins after

Need antbiotics that are bacteriocidal not bacteriolytic; steroids can lessen inflammatory response dead

Age and association with disease

Newborns – don’t have IgG antibodies so at increased risk of Group B Strep and H. flu
Age 5 to 29 have IgG. Threat is N. meningitides – very contagious and dangerous. College dorms, military barricks.
over 29 – Move out to the suburbs – Strep. Pnemoniae (pneumococcus)

Histopathology: spongy, cerebral edema, clear vacuolar spaces, inflammatory infiltrate (neutrophils)

Bugs:

H. influenzae: Transmitted by respiratory droplets

Polysaccharide capsule is main virulence factor, IgA protease produced
Hemophilus influenzae was a problem for children until vaccine

Strep. Pneumoniae

Conditions associated with pneumococcal meningitis

Pneumonia (~15-25% of patients), otitis media, sinusitis, CSF fistulae/leak, head injury, alcoholism/cirrhosis, sickle-cell disease/thalassemia major, other asplenic states, Wiskott-Aldrish Syndrome, Multiple Myeloma

Transmitted by respiratory droplets

Induces inflammatory response

Problem Þ when treat gram(-) rods with antibiotics will break up and endotoxin will kill you too! So usually treat first with IV steroids before antibiotics to reduce this effect.

(2) Brain Abcess

Pathology: some bacteria will lodge in a blood vessel and create a focal area of cerebritis, proliferation of blood vessels, adventitial fibroblasts wall-off the abcess
central area of pus, granulation tissue, astrocytes; granulation tissue is a hallmark of brain abcess
can cause herniation
mass effect is the problem in abcess (not the destruction of tissue), caused by osmosis and more particles needed to fight infection

Opportunistic Infections

Toxoplasmosis Gondi

Tissue protozoan

Pathogenesis: humans ingest and organism invades cell wallÞ infect macrophages and form trophozoites (tachyzoities) which multiply rapidly, kill cells, and infect other cells Þ cysts form containing bradyzoities Þ cats ingest cysts in raw meat Þ bradyzoities excyst, multiply Þ excreted in cat feces.

Pathology: abcesses have coagulative necrosis in the middle with granulation tissue on the outer rim, this is surrounded by proliferating astrocytes. Granulation tissue will have variable number of cysts and dilated blood vessels.

Cryptococcus Neoformans

Fungus, heavily encapsulated yeast

Pathogenesis: inhalation of airborne yeast cells Þ cause influenzalike syndrome or pneumoniaÞ spread via bloodstream to the meninges

Pathology: involve basal leptomeninges which are opaque and thickened by reactive connective tissue and may obstruct the CSF. Sulci are widened. Parenchymal lesions consist of aggregates of organisms (small rounded yeast cells) within expanded perivascular spaces (Virchow-Robin) spaces associated with minimal or absent inflammation or gliosis.

Aspergillus

Fungus, mold with septal hyphae
Can present with hemorrhagic infarcts on the brain
Pathogenesis and pathology similar to Cryptococcus except the aggregates are septate hyphae (which branch at a V-angle) and may have hemorrhage.

Prion Disease (Jakob-Creutzfeldt Disease)