Neuropathology Flashcards
neuropathology
study of pathological mechanisms underlying diseases of CNS/PNS and their clinical manifestations
selective vulnerability of the CNS
-different cells/regions respond differently to injury
-ex: neurons more sensitive than glial cells
limited regenerative capacity of CNS
*neurons incapable of cell division (injury to a few essential neurons may produce neurologic deficit)
*axonal regeneration varies (myelin debris inhibits regeneration)
why do PNS axons regenerate quickly
macrophages clear myelin debris (myelin debris inhibits regeneration)
why do CNS axons regenerate slowly
microglia cells cannot phagocytose myelin debris quickly (myelin debris inhibits regeneration)
characteristics of neurons
*highly metabolic: continuous supply of O2 and glucose
*postmitotic cells incapable of proliferation
neuron injury: red neurons
*acute injury to neurons
*early ischemic insult (6-12 hours)
*nuclear pyknosis, loss of Nissl
*intense cytoplasmic eosinophilia
neuron injury: neuron degeneration
*subacute/chronic injury to neurons
*progressive change (months/years)
*apoptotic death with neuropil vacuolization
neuron injury: inclusions
*degenerative diseases (mis-folded proteins)
examples:
-neurofibrillary tangles (Alzheimer’s)
-Lewy bodies (Parkinson’s)
-abnormal vacuolization of perikaryon (Creutzfeldt-Jakob)
-TDP inclusion (FTD-ALS)
gliosis
*astrocytic hypertrophy AND hyperplasia
*“scar” formation in neuropil
*develop numerous stout, ramifying processes
*increased GFAP (glial fibrillary acidic protein)
*basically, the astrocytes proliferate to try to help out the neurons and prevent damage
demyelination of oligodendrocytes
*oligodendroglial cell loss
*various causes:
-immune-mediated (MS, SLE)
-infectious (HIV, PML, neurosyphilis)
-toxic/metabolic (B12 deficiency)
-myelin disorders (leukodystrophies)
microglial nodules
aggregates around foci of necrosis
neuronophagia
congregate around red neurons
cerebral edema
*accumulation of fluid in the brain parenchyma
*BBB disruption / permeability leading to increased extracellular fluid (lack of lymphatics impairs resorption of excess extracellular fluid)
*may be localized or generalized
causes of cerebral edema
-inflammation
-ischemic or toxic injury
-space-filling lesions (tumors)
clinical signs/symptoms of cerebral edema
*variable: subtle neurologic defects to loss of consciousness
*severe edema causes herniation
hydrocephalus
*accumulation of excessive CSF within ventricular system
*impaired flow and/or resorption of CSF
*expands ventricles and increases ICP
communicating hydrocephalus
*primarily a failure to REABSORB CSF (it can still flow in the ventricles but cannot get into venous system)
*characterized by enlargement of entire ventricular system
*commonly occurs due to arachnoid fibrosis following meningitis
*could be due to CSF overproduction (choroid plexus tumor)
noncommunicating (obstructive) hydrocephalus
*focal obstruction
*examples: third ventricle mass; aqueductal stenosis
normal pressure - ex vacuo hydrocephalus
*loss of brain parenchyma (atrophy) causes the ventricles to appear larger than normal
*ICP is normal
clinical signs/symptoms of hydrocephalus
*variable with age and chronicity
*infants: rapid increase in head size
*older people: headaches, vomiting, papilledema, mental impairment
cerebral herniation
*displaced brain tissue
*increased intracranial pressure
subfalcine (cingulate) cerebral herniation
*cerebral hemisphere pushed cingulate gyrus under falx
*compresses anterior cerebral artery
descending transtentorial (uncinate) cerebral herniation
*temporal lobe compressed against tentorium free margin
*compresses third cranial nerve = pupillary dilation / blown pupil
*could also compress PCA
tonsillar cerebellar herniation
*cerebellar tonsils push through the foramen magnum
*compresses brain stem = respiratory and cardiac failure (coma & death)
extracranial cerebral herniation
*brain tissue external to calvaria through skull bone defect
*post-traumatic or post-surgical
red staining in red neurons is caused by:
a combination of protein denaturation and loss of RNA within the cytoplasm of the affected neuron
acute infarct appearance
*swollen appearance from edema
*accumulation of fluid within the necrotic cells and within the interstitium
remote (old) infarct appearance
cavitary defects
organizing infarcts appearance
*presence of lipid-laden macrophages (characterized by foamy cytoplasm)
*organization of the infarct begins within the first week
cerebrovascular disorders
*brain injury as a consequence of altered blood flow
*compromised blood supply to brain leads to tissue infarction
major mechanisms of cerebrovascular disorder
- ischemia/hypoxia
- hemorrhage (CNS vessel rupture)
stroke
neurologic signs and symptoms explained by vascular mechanism
*acute onset and persist > 24 hours
*if symptoms disappear < 24 hours = TIA
ischemia & cerebrovascular disorders
*impairment of blood supply/oxygenation of CNS
*clinical manifestations: determined by anatomic distribution of damaged area, rather than underlying cause
*develop rapidly ~ minutes
focal cerebral ischemia
*partial/complete arterial obstruction to localized area
*extend of injury is influenced by duration of ischemia and adequacy of collateral flow
*causes: thrombotic occlusion, embolism, and/or hypertension
focal cerebral ischemia - morphology
*pale, nonhemorrhagic at onset
*evolve into red hemorrhagic lesions (if damage to collateral small blood vessels in affected area)
acute focal cerebral ischemia
*immediate edematous gelatinous, friable tissue
*red neurons = cytoplasmic eosinophilia
organizing focal cerebral ischemia
*liquefaction
*infiltration of neutrophils and then monocytes
remote focal cerebral ischemia
*cystic cavity
*surrounding astrocytes are activated (reactive gliosis)
global cerebral ischemia/hypoxia
*generalized reduction of cerebral perfusion
*diffuse hypoxic/ischemic encephalopathy
causes of global cerebral ischemia/hypoxia
*decreased perfusion (cardiac arrest, shock, severe hypertension)
*decreased O2 carrying capacity of blood
mild global cerebral ischemia/hypoxia - clinical manifestations
*transient confusional state
*complete recovery
moderate global cerebral ischemia/hypoxia - clinical manifestations
*border zone / “watershed” infarcts
*between anterior and middle cerebral arteries
*bilateral cortical hemorrhagic infarcts
severe global cerebral ischemia/hypoxia - clinical manifestations
*widespread neuronal death
*survival = persistent vegetative state
*brain may gradually undergo widespread liquefaction (so-called “respiratory brain)
acute epidural hematoma
*occurs after rupture of middle meningeal artery
*almost always the result of skull fractures
danger of epidural hematomas
*arterial in origin (due to rupture of middle meningeal artery), epidural hematomas tend to enlarge very rapidly
*cause increased ICP and decreased brain perfusion
subdural hematomas
*develop between the arachnoid mater and the inner surface of the dura whenever tears occur in the VEINS
pathogenesis of subdural hematomas
*head trauma (milder head trauma in elderly patients)
*preexisting cerebral atrophy increased the risk of subdural hemorrhage
chronic subdural hematomas
*hematoma may organize over time to form encapsulated masses between the arachnoid and inner surface of the dura mater
*often bilateral
intracranial hemorrhage
*tearing of blood vessels leading to focal collection of blood
epidural and subdural hematomas
*secondary to trauma that does not extend into the brain
*epidural = arterial
*subdural = venous
subarachnoid hemorrhage
*due to ruptured saccular (berry) aneurysms
parenchymal hemorrhages
*arteriosclerosis of small arteries
*typically affects basal ganglia, thalamus, pons, and cerebellum
*hypertension is the most common cause
*other causes = trauma, tumors, ischemic infarcts, angiopathy
parenchymal brain injury
injury associated with transmission of kinetic energy to brain
contusion
blunt trauma tissue ecchymosis
coup injury
*contusion at site of impact
contrecoup injury
*contusion opposite impact site
*brain strikes opposite surface of skull after sudden deceleration
laceration
object penetration with tissue tearing
routes of CNS infection
1) hematogenous spread
2) direct implantation
3) local extension
4) peripheral nervous system
CNS infection - meningitis
*inflammation of leptomeninges and CSF
*most common agents: bacterial or viral
acute septic meningitis
bacterial
acute aseptic meningitis
viral
clinical presentation of meningitis
triad: headache, nuchal rigidity, fever
other: photophobia, vomiting, altered mental status
most common causes of bacterial meningitis in infants
*group B strep
*E. coli
*listeria monocytogenes
*haemophilus influenza
most common causes of bacterial meningitis in children/young adults
*neisseria meningitidis
*coxsackievirus
most common causes of bacterial meningitis in adults/elderly
strep pneumo
most common causes of bacterial meningitis in immunocompromised
*fungi
*mycoplasma tuberculosis
CNS infection: encephalitis (acute bacterial abscess)
*acute focal suppurative infections (STREP AND STAPH MOST COMMON)
*discrete lesions
*CSF with high neutrophil count
*risk = acute bacterial endocarditis, congenital heart disease, and systemic disease with immunosuppression
chronic bacterial encephalitis
1) tuberculosis (granulomas with caseous necrosis and giant cells)
2) neurosyphilis (obliterative arteritis with plasma cells)
viral encephalitis
*neural/glial tropism (specific cell types or specific areas)
*perivascular lymphocytes
*microglial nodules
causes of viral encephalitis
1) HSV - predilection for medial temporal lobes
2) polio
3) rabies
4) HIV
5) JC
6) arboviruses
fungal encephalitis
*cryptococcus, candida, mucor, aspergillus
*present as meningitis/vasculitis
*parenchymal invasion as granulomas or abscesses
*usually presents in immunocompromised pts
toxoplasmosis encephalitis
*adults = opportunistic infection (HIV)
-abscesses with central necrosis
*congenital = transplacental (chorioretinitis, hydrocephalus, and intracranial calcifications)
*usually presents in immunocompromised pts
amebiasis encephalitis
*rapidly fatal necrotizing encephalitis
*history of freshwater exposure
*organisms identified in CSF
*caused by naelgeria fowleri
demyelinating diseases
*characterized by preferential damage to myelin with relative preservation of axons
*limited capacity of CNS to regenerate normal myelin
*clinical defects due to effect of myelin loss on axon impulse transmission
groups of demyelinating diseases
- immune-mediated myelin destruction (MS)
- infections (PML from JC virus; subacute sclerosing panencephalitis from measles)
- metabolic (leukodystrophies or inherited diseases)
multiple sclerosis
*autoimmune destruction of myelin
*most common demyelinating disorder
*episodic disease activity, separated in time, from white matter lesions separated in space
pathogenesis of multiple sclerosis
*CD4+ Th1 and Th17 T-cells recognize myelin and active myelin-destroy macrophages
*antibodies against myelin or oligodendrocytes contribute to the demyelination
risk factors of multiple sclerosis
HLA-DRB11501
*latitude dependence and decreased vitamin D in winter
*smoking
*EBV ?
clinical features of multiple sclerosis
*typically young adult onset with vision loss, paresthesias or weakness of extremities, or abnormal gait and balance
*relapse-remitting and progression
CSF presentation in multiple sclerosis
*elevated protein from IgG antibodies (oligoclonal bands)
-moderate lymphocytosis
-presence of myelin basic protein
morphology of multiple sclerosis
*plaques = area of myelin loss
*active lesion = inflammatory macrophages with myelin debris
*inactive lesion = areas of demyelination and gliosis but preservation of axons!
