Block 4 Flashcards
Selective neuronal cell death; brighter pink = dead, blue= normal
Infarction (left-side), Right side is normal
Global ischemic injury in cerebellum
Global cerebral Ischemia: laminar necrosis
Global cerebral ischemia: end-arterial (watershed) distribution; darker areas (in red circle) are injured due to acute ischemia
MCA distribution
MCA distribution
PCA (bilateral)
This is a cross-section of the brain with occipital view
PCA (basilar artery)
MCA infarcts affecting parietal lobe
Both ACA (medially) and MCA (laterally)
Lacunar infarct (small artery); multiple small holes
Hemorrhagic Infacts; can be venous (thrombus) or arterial (ischemia and reperfusion)
Venous Infarcts; most commonly seen parasagittally (in superior sagittal sinus distribution) or distribution of transverse sinus
Top: bilateral PCA infarcts from emboli can often become hemorrhagic (and can be multifocal)
Bottom: small clot/embolus (arrow) with surrounding hemorrhagic infarct
Hypertensive hemorrhage; tend to occur more centrally in brain (basal ganglia, thalamus)
Top R: Charcot-Bouchard aneurysm of lenticulostriate vessels of BG, associated wit HTN
Bottom R: thickened BV wall, loss of SM
Spinal cord infarct
anterior spinal artery (red arrow)
posterior spinal artery (blue arrow)
PSA infarction (green circle)
Infarcts evolve over time:
Left: acute MCA infarct, tissue expanded due to edema
Right: months later, infarcted tissue gone, left with cavity
Penumbra:
see infarct in posterior temporal lobe on left
arrows point to penumbra; tissue on the margins of an infarct that is at risk for dying
goal is to rescue penumbra tissue with acute therapy
Fibromuscular Dysplasia: hyperplasia of smooth muscle and fibrous tissue alternating with thin, fibrotic regions; at risk for developing occlusions, dissection, aneurysm
CADASIL: cerebral autosomal dominant arteriopathy with subcortical ischemia and leukoencephalopathy
see small lacunar infarcts (red circle)
Subdural hematoma
Subarachnoid hemorrhage
Anterior communicating artery aneurysm
Hemorrhagic conversion of Ischemia
Thalamic hemorrhage, 2nd most common site of hypertensive bleed, presents with HA, vomitting, sensory deficits, oculomotor signs
Intracranial hemorrhage, lobar: presents with HA (70%), N/V, site specific signs (hemparesis, aphasia, neglect)
Arteriovenous Malformation; forms during gestation, risk of bleeding
Bottom: late phase angiogram, showing AVM
Top: early phase, normal appearing
Lobar Intracranial Hemorrhage (ICH)
Far left image: the CT in an acute stroke will look normal!
Middle image is 1-2 days after stroke
Image on Right shows hemorrhage
intra-axial or extra-axial lesions?
Left= intra-axial
Right= extra-axial
Is there Mass Effect on surrounding brain structures?
Left= epidural hematoma= yes mass effect
Right= pineal cyst= no mass effect
Glioblastoma; intra-axial, high-grade glioma, malignant
Uncal herniation;
“B” on image of brain; uncus of mesial temporal obe herniates over tentorial incisura; see CN3 palsy–>pupils fixed/dilated, ptosis, EOM palsy (down and out); also see contralat. motor signs, and PCA infarct
Uncal herniation
Central tentorial herniation: displacement of brainstem shears perforating arteries; see progressive pupillary/motor/ventillartory dysfxn
Sub-falcine herniation: cingulate gyrus herniates under falx cerebri resulting in midline shift; ACA at risk
Tonsillar (cerebellar) herniation: results in severe ICP elevation and hydrocephalus, bilateral SDH; can lead to sudden apnea/death
MS plaques (foci of demyelination); gray or yellow appearance, distinct borders, slightly depressed/granular
Located in WM > GM but can occur anywhere; often adjacent to lateral ventricle
Top: small plaques located everywere
Bottom: periventricular plaque (blue arrow) and plaque near thalamus (black arrow)
Periventricular MS plaques
MS plaques:
Top L: granular, depressed, old plaques
Top R: myelin-stain showing areas of demyelination in MS plaques
Bottom: plaques around thalami
MS plaque on pons
Myelin-stain of MS plaque near ventricle in a cross-section of pons
MS plaque on spinal cord; image on R shows myelin-stain of spinal cord cross section; see lack of myeling almost everywhere except anterolaterally
Active MS Plaques; see perivascular inflammation w/ T cells > B cells, macrophages, +/- activated complement; BBB dysfunction leads to edema
Red arrow/Yellow arrow: macrophages
Green arrow: T cells (and B cells)
Active MS plaques showing demyelination (macrophages); also see oligodendrocyte depletion (apoptosis) in active plaques
Left=macrophages filled with pink-stained lipid
Right: myelin-staining (yellow arrows); see focal area of demyelination (red circle)
Active MS plaque; see tons of macrophages (green arrow) and reactive astrocytes (yellow arrows) which regulate extracell fluid balance, BBB.
Active MS plaque showing axonal injury; see anterograde degen. of axons and retrograde degen. of cell bodies; mechanism not well understood
Inactive MS plaques; hypocellular compared to normal and to active MS plaques; see lack of inflammation and lack of oligodendrocyte
Inactive MS plaques; see demyelation (image on R, blue= myelin) and axonal loss (image on L, axons=black); breakdown products of myeling inhibit axonal regeneration.
Shadow MS plaques; show remyelination (thin myelin) of an active plaque; may have repeated and/or concurrent demyelination and remyelination.
Reye Syndrome: post-viral syndrome of childhood characterized by acute liver failure and decreased mental status; associate with ASA use;
Histo: see tissue accumulation of neutral lipids due to liver damage (appears as lots of vacuoles filled with fat)
Grossly, see cerebral edema, multifocal ischemic lesions; herniations
Subacute combined degeneration of spinal cord due to B12 deficiency; see spinal cord WM vacuolization and demyelination, affects posterior columns and corticospinal tracts, see 2’ axonal injury
Peripheral neurons and cerebral WM also affected
Cerebellar vermis atrophy secondary to ethanol
Marchiafava-Bignami; cystic cavity in corpus callosum seen in malnourished alcoholis
Wernicke encephalopathy; seen in malnourished (B1 def.) alcoholics;
pathology shows hemorrhage/necrosis in mammillary bodies and periaqueductal, also see neuron loss in thalamus
clinical syndrome: dry beriberi (polyneuropathy) and Wernicke-Korsakoff (ophthalmoplegia, nystagmus, ataxia, alt. of conciousness, amnesia).
Ethanol associated peripheral neuropathy
Ethanol-liver damage (left)–> hepatic encephalopathy, hyperammonemia, and Alzheimer Type II astrocytes (irregular/large, red arrow)
Methanol toxicity; see selective necrosis of the putamen –> movement disorders, also see retinal blindness
Carbon monoxide toxicity; see selective bilat. necrosis of globus pallidus, diffuse hypoxia (CO competes with O2 for binding to Hg) leads to neuronal cell death
Wilson’s Dz; see striatal cavitary lesions including super flat/atrophic caudate (green arrow), and putamen necrosis (red arrow).
PKU: phenylalanine hydroxylase def. (liver enzyme) –> tyrosine deficiency, effects on aa transport, NT effects
Top: baby w/ maternal PKU showing microcephaly, WM loss, and neuron loss 2’ to sz
Bottom: age-matched normal brain
Leigh Syndrome: Subacute Necrotizing Encephalitis
Subcortical structures targeted: BG, medial thalamus, hypothalamus, periaqueductal gray, midbrain, pontine tegmentum and medulla
Green arrows: caudate head destruction
Red arrows: periaqueductal gray destruction
Tay Sachs; hexoaminidase A deficiency, resulting in accumulation of GM2 ganglioside in CNS/ANS neurons (other tissues too)
Cherry red spot: contrast of the normally red macula against surrounding pale retina (ganglion cells with storage material). Not specific for type of material, but seen in 50% of pts with Nieman-Pick type A
Gaucher Dz; glucocerebrosidase deficiency—> glucocerebrosidase accumulates in phagocytic cells –> splenomegaly, thrombocytopenia, anemia, leukopenia (type I dz), also see acute neuronopathic dz (type II) with rapidly progressive motor dysfxn and early death.
Metachromatic Leukodystrophy (MLD): lysosomal storage d/o, arylsulfatase A deficiency, see cortical and subcortical volume loss (blue arrows) and increased WM signal bilaterally on T2 mri (red arrows)
Metachromatic Leukodystrophy: see loss of myelin, gliosis, 2’ axon loss, accumulation of “metachromatic” sulfated cerebrosides in marcophages (CNS/PNS) and Schwann cells (PNS)
Krabbe dz: globoid cell leukodystrophy, most severe form, deficiency in galactocerebroside beta-galactosidase shuttling galactocereboside to alternate catabolic pathway producing toxic metabolite to oligodendrocytes and Schwann cells
see accumulation of perivascular macrophages–> “globoid cells” and loss of myelin, gliosis, 2’ axon loss
Adrenoleukodystrophy; peroxisomal d/o resulting in elevated levels of long-chain FA’s, see myelin loss, most prominent in parietal-occipital lobes; hence posterior > anterior involvement of WM on T2; perivascular inflammation (blue arrow)
Pelizaeus-Merzbacher Dz: x-linked leukodystrophy, with mt in PLP (a myelin protein); see patchy areas of residual myelin (dark colored), with near complete loss of myelin.
Alzheimers Dz; see sulci widening and gyri shrinking externally
Alzheimer’s Dz; see big spaces between gyri and ventricles are 2-3x larger than normal
AD plaques (larger brown spots), surrounding smaller cells are glia.
Amyloid Angiopathy; AD beta amyloid plaques in blood vessels of the brain; stained here with congo red.
Neurofibrillary tangles of tau, seen in AD; bottom R photo shows beta amyloid plaque as well as NFT.
Amyloid fibrils seen in AD; fibrils are comprised of aggregates of amyloid beta peptides with beta-sheet conformation
Parkinson’s Dz; see loss of DA production in substantia nigra (top left) and see Lewy bodies (cytoplasmic inclusions of alpha-synuclein) in substantia nigra and locus ceruleus.
Lewy Body Dz; staining (red) for alpha-synuclein, the cytoplasmic inclusions of LB’s.
ALS of spinal cord: see loss of myelin in LCST and ventral CST (descending myelinated tracts)
Bunina bodies (green arrows), cytoplasmic inclusions of ubiquitin, found in anterior horn cells of spinal cord in ALS. Top R is ubiquitin staining.
frontal lobe and temporal lobe atrophy associated with frontotemporal dementia seen in many cases of ALS.
Ubiquitin inclusions seen in the hippocampus in FTLD-U (Frontotemporal Lewy Body Dementia–Ubiquitin)
Spongiform (hole-like) changes seen in the cerebral cortex in CJD.
Bacteria leptomeninges; see erythema and white exudates on external brain.
Bacterial Meningitis sequelae: venous thrombosis, 2’ vasculitis leading to infarction, and meningeal scarring leading to hydrocephalus (bottom photo).
Purpura fulminans, a sign of disseminated meningococcus
Tuberculosis Meningitis;
Green arrow: dilated ventricles secondary to fibrosis and obstruction of CSF outflow
Red circle: acid-fast bacillius (TB)
Blue arrow: granuloma in caudate region of striatum
Brain abscess; mixed flora and anarobes most common organisms
Bright ring = fluid/blood surrounding a lesions (abscess, cancer, cyst, etc.)
Subdural Empyema; mostly frontal, direct extension from sinusitis; seen clinically with fever, HA, stick neck, and mass lesion (like a subdural hematoma)
Tabes Dorsalis; sign of neurosyphilis; damage to sensory ganglia, see 2’ changes in dorsal columns; sxs = pain or paresthesias, loss of pain/proprioception leading to ataxia and recurrent jt trauma.
Meningovascular syphilis; meningitis rich in plasma cells, periarteritis; see gummas( purple arrow) which are TB-like lesions, and fibrosis of BV wall (red arrow).
sxs: HA, apathy, irritability, focal deficits (arteritis)
Paretic neurosyphilis; parenchymal involvement, microglial nodules, neuron loss
Top: rod-shaped cells are microglia
Bottom: tad-pole shaped cells are microglia
Sxs: slow loss of consciousness, attention, psych disturbances, sz, loss of motor control, severe dementia.
Vasculitis and encephalitis due to fungal infections (aspergillosis, zygomycetes sp)
Top: aspergillus vasculitis
Bottom: inflammed BV due to zygomycetes
Right: fungal forms
Cryptococcus neoformans: subacute meningoencephalitis
see small holes in brain (blue arrow), “soap-bubble” cavities filled with organism (green arrow), exclusion of ink-staining around organism (yellow), and mucinous capsule stained for organism (red arrow)
Toxoplasmosis: see reactivation in IC patients; variable intensity of inflammation
Green arrow: toxo cyst, predominates in smouldering infection
Black arrow: rupture cyst with scattered organisms
Red arrow: focus of necrosis
Cysticercosis; pork tapeworm
red arrow: aqueductal cyst (leading to hydrocephalus)
blue arrows: cysts with organism within
presents as calicified nodules, granulomatous encephalitis (ruptured cysts), or CSF cysts
Herpes Simplex Encephalitis; see characterstic neuronal intranuclear inclusions; and necrotizing encephalitis
Herpes Simplex Encephalitis; redness= hemorrhage and inflammation
CMV–> congenital infection may cause a necrotizing encephalitis/microcephaly/periventricular calcifications (green arrow)
Rabies virus; see prominent brainstem/cerebellar involvemen; see Negri bodies (green arrow), classic cytoplasmic inclusions
virus proliferates at site of innoculation, delays, then travels along sensory nerves to CNS.
Measles Virus:
3 manifestations–
Acute measles encephalitis (neonates, IC pts)
Post-infectious Encephalomyelitis
Subactue Sclerosing Panencephalitis (SSPE)
Subacute sclerosing Panencephalitis (SSPE)
slowly progressive dz occurs years after measles infection; virus defective in M protein (can’t bud mature virus), see cell to cell spread of defective virus
Path: small ground glass inclusions (green arrow)
AIDS:
HIV encephalitis/leukoencephalopathy (see microglia–red arrow)
Vacuolar myelopathy (green arrow)
Opportunitist infections: CMV, PML, crypto, toxo, TB
Progressive Multifocal Leukoencephalitis (PML)
polyoma virus (JC virus) reactivation in IC pt; multifocal to confluent demyelination; tropic to glial cells–see “ground glass” intranuclear inclusions in oligodendrocytes, astrocytes with atypical transformation
Enterovirus (polio virus)—> poliomyelitis, polioencephalitis; 2’ viremia with tropism for spinal cord neurons
other enteroviruses causing polio (coxsackie, echo), also arbovirus (West nile virus)
Spina bifida occulta
Spina bifida cystica: meningocele and meningomyelocele
Spina bifida aperta (left) and craniorachisis (Right, variant of SBA)
neural plate never develops into NT
Anencephaly; area cerebrovasculosa, combo of abnml development and 2’ destructive process –> granulation process
Area cerebrovasculosa; pathology seen in anencephaly; combo of abnormal development and 2’ inflammatory process
Encephalocele; defect in skull that allow brain to herniate, in this picture is a posterior herniation, can also have a frontonasal encephalocele
Frontonasal encephalocele
Holoprosencephaly; when brain doesn’t divide into two hemispheres; see continuous cortex and ventricles
can be lobar, alobar, or semilobar
Holoprosencephaly
HPE spectrum:
alobar (left)
semilobar (middle)
lobar (right)
Abnormal facies seen in HPE, can be more mild (upper pictures) vs more severe (bottom)
Absent cerebellar vermis seen in Dandy-Walker spectrum of neurodevelopmental abnormalities
Arnold-Chiari (Chiari II): see downward protrusion of cerebellum and brainstem
Porencephaly; focal hemisphere necrosis occurring before 26 wk GA, before adult gyri patterns forms, see massive smooth-walled cyst
Hydranencephaly; massive bilateral hemispheric necrosis in the fetus
Schizencephaly; abnormal hemispheric clefts due to destruction inutero, w/ abnml cell proliferation, and/or abnormal migration
Encephalomalacia; focal hemispheric necrosis occurring after 26 weeks GA (perinatal/postnatal), caused by vacular insufficiency or degenerative changes; gliosis with cystic components
Germinal matrix hemorrhage; ruptures into ventricles; dz seen in premature babies
Germinal Matix inutero (red arrow)
at 13 weeks GM is huge!
at 32 wks, very little GM left
histo: large lumen/thin-walled BV’s, susceptible to bleeding seen in GM hemorrhage
WM injury (periventricular leukomalacia, WM gliosis);
see cystic cavities in WM around lateral ventricles (red arrows), necrosis (green arrow), and gliosis (reactive astrocytes, blue arrow)
Seen in cerebral palsy
