Neuropathology: Non-viral Infections

Part One--Bacteria

Mechanisms of CNS injury by infections

A. direct destruction of CNS tissue
1. necrosis
2. abscess
B. inflammation and edema compromise neural function
C. edema and mass effect from abscess cause herniation
D. effects on vasculature lead to infarction
E. effects on CSF flow lead to hydrocephalus

Routes of Injury of the Nervous System

Hematogenous
arteries
emissary veins from face or scalp

Direct implantation
trauma, iatrogenic

Local extension

dental abscess
cranial air sinus (mastoid or frontal sinuses most common)

Effects at a distance mediated by neurotoxins

diphtheria
Clostridium tetani (muscle rigidity and spasms)
Clostridium botulinum (paralysis at neuromuscular junction, blocks
neurotransmitter release)
shigellosis (encephalopathy with convulsions, lethargy, confusion,
severe headache)
legionellosis (encephalopathy,acute ataxia, dysarthria)

Acute Bacterial Meningitis

Meningitis is an inflammation of meninges,
especially the leptomeninges.
Meningoencephalitis is an inflammation of both
the meninges and brain parenchyma.
Cerebritis is an inflammation of the brain
parenchyma and may accompany bacterial
meningitis.

Organisms causing bacterial meningitis

Vaccinations against H. influenzae type B in infants have dramatically

reduced this organism as a cause of meningitis. Similar reductions are
occurring with S. pneumoniae and N. meningitidis.

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

Effect of H. influenzae
vaccine on causes of
bacterial meningitis

Postgrad. Med. 114:43 (2003)

1986, before H. inf. vaccine

1995, after H. inf. vaccine

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

Meningococcal Polysaccharide Vaccine

Recommendations
Not recommended for routine vaccination of
civilians
Recommended for certain high-risk
persons:
Terminal complement deficiency
Functional or anatomic asplenia
Certain laboratory workers
Travelers to and U.S. citizens residing in
countries in which N. meningiditis is
hyperendemic or epidemic (e.g., African
meningitis belt)

Meningococcal Polysaccharide Vaccine

Recommendations
Control of outbreaks
Outbreak definition:
3 or more confirmed or probable
cases
Period <3 months
Primary attack rate >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

Signs and symptoms of meningitis

Headache
Photophobia
Irritability
Impaired consciousness
Neck stiffness

CSF characteristics
Inflammatory cells
Increased pressure
Increased protein
Reduced glucose

Gross appearance
Inflammatory exudate within the arachnoid and
perivascular spaces (Virchow-Robin spaces),
extending to ventricles
Congestion of blood vessels
Localization of exudate varies with organisms

Microscopic appearance
Multitudes of neutrophils in the subarachnoid space,
particularly around leptomeningeal blood vessels
Cerebritis from local extension into brain
Thrombosis of involved vessels with cerebral
infarction
Gram stain should always be performed

Pneumococcal meningitis

Meningitis at base of brain

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

N. meningitides (Gram neg diplococci) in CSF

Route of entry
into CSF by
N. meningitidis

Route of entry
into CSF by
N. meningitidis

(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 alternative
complement pathway because its polysaccharide
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.

IgR=
immunoglobulin
receptor

Pathogenic steps leading to

pneumococcal meningitis

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

Cerebral infarcts with pneumococcal meningitis

Neonatal meningitis
(group B
streptococcus)

Ventriculitis from shunt infection with S. aureus

Inflammatory exudate of meningitis

inflammation around perivascular spaces (Virchow-Robin spaces)

Inflammatory exudate of meningitis

Meningitis is often preceded by a prodromal respiratory

infection, the neurologic signs and symptoms come on quickly
leading to changes in consciousness and coma. Dehydration is
common and vascular collapse may lead to shock (WaterhouseFriderichsen syndrome).

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

Rash of meningococcemia
(sepsis caused by Neisseria meningitidis)

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

Suppurative Infections
Brain abscess
Organisms: Streptococci and staphylococci
Context: Local extension of neighboring
infection, hematogenous spread from
infections in heart (especially valves), lungs,
or bones
Risk factors: cyanotic congenital heart disease
(right-to-left shunt) and chronic pulmonary
sepsis.
Gross and microscopic pathology: Liquefactive
necrosis with fibrous reaction at gray white
junction or white matter

Brain abscesses

Chronic frontal sinus infection

Right-to-left shunt

Subdural empyema
Pus in the dural space but not involving the
underlying leptomeninges
Risk of thrombosis and infarction

Extradural (epidural) abscess

Associated with neighboring bone or sinus
infection
Dangerous because of mass effect (herniation)

Subdural empyema from S. aureus

Subdural empyema

Loculated collections of pus in the subdural space with mass effect

Epidural abscess
CT scan with contrast
enhancement.

meninges surrounding the

abscess enhances

Acute cerebritis adjacent to petrous temporal bone infection

Chronic Bacterial Infections

Tuberculosis
Clinical picture: Chronic meningitis
CSF with moderately increased number of cells
and increased protein

Gross and microscopic pathology:

Base of brain
Tuberculomas
Chronic inflammatory cells with granulomas and
acid-fast bacilli
Arachnoid fibrosis leads to hydrocephalus
Obliterative endarteritis leads to infarction

Tuberculous
meningitis at
base of brain

Tuberculous
meningitis

Acid-fast staining

Neurosyphilis
1. Meningeal-meningovascular neurosyphilis:
rich in perivascular plasma cells and is
commonly at the base of the brain, cerebral
convexities, and spinal meninges
2. Paretic neurosyphilis: invasion of the
brain by Treponema pallidum with loss of
brain function (general paresis of the insane
(GPI))

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

History of syphilis in stages

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

Syphilitic arteritis of middle cerebral artery

Tabes dorsalis

degeneration of the posterior columns

Gumma of tertiary syphilis

soft, gummy mass with tissue resembling granulation tissue and
central necrosis

Paretic neurosyphilis
atrophy of the frontal gyri

Paretic neurosyphilis

perivascular inflammation
with plasma cells

proliferation of microglia

Lyme disease
Symptoms:
aseptic meningitis
7th nerve palsy
encephalopathy
polyneuropathy
Microscopic pathology
microglial proliferation
vasculitis

Lyme disease involving peripheral nerve

Neuropathology: Non-viral Infections

Part TwoFungi, Protozoa, Helminths, and
Rickettsiae

Rhinocerebral
mucormycosis
often in diabetics
with ketoacidosis

Rhinocerebral mucormycosis

Aspergillosis

Vascular invasion by Aspergillus

Candida abscess in patient with AIDS

Cryptococcosis in basal ganglia

Histoplasmosis
yellow-gray exudate over
base of brain at optic
chiasm and left temporal
pole

Histoplasma yeasts
in meningeal
exudate

Coccidioidomycosis spherules with endospores

Trophozoite of Entamoeba histolytica in cerebral abscess (PAS)

Primary amebic meningoencephalitis (Naegleria fowleri)

Granulomatous
amebic encephalitis
(Acanthamoeba)

Slate gray brain in cerebral malaria

Plasmodium falciparum

Red blood cells with malaria parasites

Toxoplasma gondii cyst with bradyzoites

Microglial nodule in African trypanosomiasis

Sleeping sickness caused by Trypanosoma brucei rhodesiense or
T. b. gambiense

Morular cells of African trypanosomiasis

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

Trypanosoma cruzi
Chagas disease in heart

Parasites in amastigote stage

in cardiac myofiber

Trypanosoma cruzi
Chagas disease in brain

necrotizing lesion of T.
cruzi in patient with AIDS

abundant amastigote
parasites mostly in astrocytes
and macrophages

Cysticerosis (larval form of Taenia solium)

Intraventricular cysticerci of Taenia solium

Scolex of Taenia solium

Visceral larva migrans in brain

(Toxocara canis = dog ascarid)

Schistosomiasis
granuloma from
Schistosoma japonicum

Red structures indicate immunohistological staining of Rickettsia rickettsii

in endothelial cells of a blood vessel from a patient with fatal Rocky
Mountain spotted fever

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