neuropathology-non viral infection.ppt

7/25/2019 Neuropathology-Non Viral Infection.ppt

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Part One--Bacteria

Neuropathology: Non-viral Infections


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Mechanisms of CNS injury by infections

A. direct destruction of CNS tissue

1. necrosis2. abscess

B. inflammation and edema compromise neural function

C. edema and mass effect from abscess cause herniationD. effects on vasculature lead to infarction

E. effects on CSF flow lead to hydrocephalus


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Routes of Injury of the Nervous System

Hematogenousarteriesemissary veins from face or scalp

Direct implantationtrauma, iatrogenic

Local extensiondental abscess

cranial air sinus (mastoid or frontal sinuses most common)Effects at a distance mediated by neurotoxinsdiphtheriaClostridium tetani (muscle rigidity and spasms)

Clostridium botulinum (paralysis at neuromuscular junction, blocksneurotransmitter release)shigellosis (encephalopathy with convulsions, lethargy, confusion,

severe headache)

legionellosis (encephalopathy,acute ataxia, dysarthria)


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Acute Bacterial Meningitis

Meningitis is an inflammation of meninges,especially the leptomeninges.

Meningoencephalitis is an inflammation of boththe meninges and brain parenchyma.

Cerebritis is an inflammation of the brainparenchyma and may accompany bacterial

meningitis.


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CNS Drugs. 2001;15(12):909-19

Organisms causing bacterial meningitis

Vaccinations againstH. influenzae type B in infants have dramaticallyreduced this organism as a cause of meningitis. Similar reductions areoccurring with S. pneumoniae andN. meningitidis.


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Effect ofH. influenzaevaccine on causes of

bacterial meningitis

1986, beforeH. inf. vaccine

1995, afterH. inf. vaccine

Postgrad.

Med.11

4:43(2003)


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http://www.cdc.gov/nip/recs/child-schedule.htm


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Meningococcal Polysaccharide Vaccine

Recommendations

Not recommended for rout ine vaccination ofcivilians

Recommended for certain high-riskpersons:

Terminal complement deficiency

Functional or anatomic aspleniaCertain laboratory workers

Travelers to and U.S. citizens residing incountr ies in which N. meningiditis ishyperendemic or epidemic (e.g., Africanmeningitis belt)

Meningococcal Polysaccharide Vaccine

Recommendations

Control of outbreaks

Outbreak definition:

3 or more confirmed or probablecases

Period 10 cases per

100,000 population*

*Population-based rates should be used rather

than age-specific attack rates

Meningococcal Endemic Areas 2000

Equator

http://www.cdc.gov/nip/ed/slides/mening8p.ppt


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Signs and symptoms of meningitisHeadachePhotophobia

IrritabilityImpaired consciousness

Neck stiffness

CSF characteristicsInflammatory cells

Increased pressure

Increased protein

Reduced glucose


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Gross appearanceInflammatory exudate within the arachnoid andperivascular spaces (Virchow-Robin spaces),extending to ventricles

Congestion of blood vesselsLocalization of exudate varies with organisms

Microscopic appearanceMultitudes of neutrophils in the subarachnoid space,particularly around leptomeningeal blood vessels

Cerebritis from local extension into brainThrombosis of involved vessels with cerebralinfarction

Gram stain should always be performed


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Pneumococcal meningitis


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Meningitis at base of brain

exudate with H. influenzae is more pronounced at base of brain


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N. meningitides (Gram neg diplococci) in CSF


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Route of entryinto CSF by

N. meningitidis


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(A) Meningitis from S. pneumoniae begins with

invasion of mucosal epithelium. (B)

Neutralization of IgA protease facilitates this

step. The organisms then enter the bloodstream

and evade destruction by the alternativecomplement pathway because its polysaccharid

capsule resists binding of factor B to C3b,

preventing activation of C5-C9. (C) It is

hypothesized that at the blood-brain barrier

during infection, activated endothelial cells

release cytokines that stimulate increased

surface expression of platelet activating factor

(PAF) receptors. The organisms bind to PAF

receptors via their cell-wall phosphorylcholine.

(D) PAF receptor cycling brings the pathogen

across the endothelium and into the

extracellular matrix, where it binds to

fibronectin, proliferates and spreads to the CSF.

Route of entry

into CSF by

N. meningitidis


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Lancet Infect Dis. 2002 Dec;2(12):721-36

Pathogenic steps leading topneumococcal meningitis

IgR=immunoglobulinreceptor


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Cerebral infarcts with pneumococcal meningitis


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Neonatal meningiti

(group B

streptococcus)


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Ventriculitis from shunt infection with S. aureus


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Inflammatory exudate of meningitis

inflammation around perivascular spaces (Virchow-Robin spaces)


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Inflammatory exudate of meningitis


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Meningitis is often preceded by a prodromal respiratoryinfection, the neurologic signs and symptoms come on quickly

leading to changes in consciousness and coma. Dehydration iscommon and vascular collapse may lead to shock (Waterhouse-Friderichsen syndrome).

http://aci.mta.ca/Courses/Biology/Images/bacterial%20folder/Meningitis43.jpeg


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http://aci.mta.ca/Courses/Biology/Images/bacterial%20folder/Meningitis44.jpeg

Rash of meningococcemia

(sepsis caused byNeisseria meningitidis)


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Suppurative Infections

Brain abscessOrganisms: Streptococci and staphylococci

Context: Local extension of neighboringinfection, hematogenous spread frominfections in heart (especially valves), lungs,

or bonesRisk factors: cyanotic congenital heart disease

(right-to-left shunt) and chronic pulmonarysepsis.

Gross and microscopic pathology: Liquefactivenecrosis with fibrous reaction at gray whitejunction or white matter


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Brain abscesses

Chronic frontal sinus infectionRight-to-left shunt


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Subdural empyemaPus in the dural space but not involving the

underlying leptomeninges

Risk of thrombosis and infarction

Extradural (epidural) abscessAssociated with neighboring bone or sinus

infectionDangerous because of mass effect (herniation)


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Subdural empyema from S. aureus


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Subdural empyema

Loculated collections of pus in the subdural space with mass effec


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Epidural abscess

CT scan with contrast

enhancement.

meninges surrounding the

abscess enhances


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Acute cerebritis adjacent to petrous temporal bone infection


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Chronic Bacterial Infections

TuberculosisClinical picture: Chronic meningitisCSF with moderately increased number of cells

and increased protein

Gross and microscopic pathology:Base of brainTuberculomas

Chronic inflammatory cells with granulomas andacid-fast bacilli

Arachnoid fibrosis leads to hydrocephalus

Obliterative endarteritis leads to infarction


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Tuberculousmeningitis atbase of brain


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Tuberculousmeningitis

Acid-fast staining


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Neurosyphilis

1. Meningeal-meningovascular neurosyphilis:

rich in perivascular plasma cells and iscommonly at the base of the brain, cerebralconvexities, and spinal meninges

2. Paretic neurosyphilis: invasion of thebrain by Treponema pallidum with loss of

brain function (general paresis of the insane(GPI))


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Neurosyphilis

3. Tabes dorsalis (spinal cord)

Loss of axons and myelin in the dorsal columns

because of damage by T. pallidum to dorsal

roots. Impaired sense of joint position and ataxia

Loss of pain sensation leading to joint damage

(Charcot joints) Sensory disturbances (lightning pains)

Absence of deep tendon reflexes

Hi t f hili i t


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History of syphilis in stages

JAMA. 2003 Sep 17;290(11):1510-4

S hiliti t iti f iddl b l t


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Syphilitic arteritis of middle cerebral artery


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Gumma of tertiary syphilis


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Gumma of tertiary syphilissoft, gummy mass with tissue resembling granulation tissue and

central necrosis

Paretic neurosyphilis


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Paretic neurosyphilisatrophy of the frontal gyri

P ti hili


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perivascular inflammationwith plasma cells proliferation of microglia

Paretic neurosyphilis


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Lyme diseaseSymptoms:

aseptic meningitis

7th nerve palsy

encephalopathy

polyneuropathy

Microscopic pathologymicroglial proliferation

vasculitis

L di i l i i h l


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Lyme disease involving peripheral nerve


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Neuropathology: Non-viral Infections

Part TwoFungi, Protozoa, Helminths, andRickettsiae


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Rhinocerebralmucormycosis

often in diabeticswith ketoacidosis

Rhinocerebral m corm cosis


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Rhinocerebral mucormycosis

A i i


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Aspergillosis

V l i i b A ill


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Vascular invasion byAspergillus

Candida abscess in patient with AIDS


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Candida abscess in patient with AIDS

C t i i b l li


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Cryptococcosis in basal ganglia


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Histoplasmosis

yellow-gray exudate over

base of brain at optic

chiasm and left temporal

pole


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Histoplasma yeastsin meningeal

exudate

Coccidioidomycosis spherules with endospore


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Coccidioidomycosis spherules with endospore

Trophozoite ofEntamoeba histolytica in cerebral abscess (PAS)


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p y ( )

Primary amebic meningoencephalitis (Naegleria fowleri)


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Granulomatousamebic encephalitis

(Acanthamoeba)

Slate gray brain in cerebral malaria


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g yPlasmodium falciparum

Red blood cells with malaria parasites


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p

Toxoplasma gondii cyst with bradyzoites


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Microglial nodule in African trypanosomiasisSl i i k d b T b i h d i


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Sleeping sickness caused by Trypanosoma brucei rhodesiense or

T. b. gambiense

Morular cells of African trypanosomiasisplasma cells with globules of immunoglobulin characteristic but not specific


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plasma cells with globules of immunoglobulin--characteristic but not specific


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Trypanosoma cruziChagas disease in heart

Parasites in amastigote stage

in cardiac myofiber

Trypanosoma cruzi


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yp

Chagas disease in brain

abundant amastigoteparasites mostly in astrocytes

and macrophages

necrotizing lesion of T.

cruzi in patient with AIDS

Cysticerosis (larval form of Taenia solium


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Cysticerosis (larval form of Taenia solium

Intraventricular cysticerci of Taenia solium


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Intraventricular cysticerci of Taenia solium

Scolex of Taenia solium


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Visceral larva migrans in brain(Toxocara canis = dog ascarid)


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( g )


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Schistosomiasis

granuloma from

Schistosoma japonicum

Red structures indicate immunohistological staining of Rickettsia rickettsiiin endothelial cells of a blood vessel from a patient with fatal RockyMountain spotted fever


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Mountain spotted fever

http://www.cdc.gov/ncidod/dvrd/rmsf/Laboratory.htm

neuropathology-non viral infection.ppt

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