Intro to Neuro Flashcards
Match: round and oval, oligodendrocytes and astrocytes (subset of glial cells)
astrocytes–>oval
oligodendrocytes–>round
What stain picks up astrocytes?
GFAP
gliofibrillary acidic protein
Describe selective vulnerability in astrocytes
set of neurons sharing 1+ properties responding to an insult (not necessarily located together)
What is the term for neurons that undergo acute neuronal response to injury?
RED neurons, less than 24 hours
earliest morphologic indicator of acute injury
Describe neurons in acute neuronal response to injury
pyknosis (cell body shrinks)
loss of nucleolus and nissl substance–> get fuzzy
intense eosinophilia in cytoplasm
What are some injuries that cause acute neuronal response to injury?
hypoxia
hypoglycemia
trauma
Describe subacute and chronic neuronal response to injury
DEGENERATION, progressive
best indicator of neuronal injury
cell loss and reactive gliosis
apoptosis
can have abnormal protein accumulation–> ALS, Alzheimers
When do you find gliosis?
chronic CNS injury, looks like scar tissue but not
What is the axonal reaction?
increased protein synthesis associated with axonal sprouting
What do neurons look like in an axonal reaction to injury?
enlarged, round cell body
peripheral displacement of nucleus
enlarged nucleolus
central chromatolysis: nissl removed from center of cell to periphery
When do you see central chromatolysis?
axonal reaction to CNS injury
What are neuronal inclusions?
accumulation of substances in neurons d/t injury or infection
What are examples of intranuclear neuronal inclusions?
Herpes–> Cowdry body
CMV–> Owl’s eye (both intranuclear and cytoplasmic)
What are examples of intracytoplasmic neuronal inclusions?
lipofuscin, proteins, carb
Rabies–> Negri body
Alzheimers–> neurofibrillary tangles
Parkinson–> Lewy body
CJD–> vacuolization of perikaryon and neuronal processes
Are chromatolysis and neuronal inclusions normal?
YES, normal process when injured
What is the most important histopathologic indicator of CNS injury?
gliosis
What is gliosis
hypertrophy and hyperplasia of astrocytes in response to CNS injury
also can cause gemistocyte formation
What act as metabolic buffers and detoxifiers in the brain, with foot processes contributing to the BBB?
astrocytes
What are bright pink astrocytes with enlarged, vesicular, dislocated nucleus and prominent nucleoli?
gemistocyte
what astrocytes can turn into during gliosis
When do you see Alzheimers 2 astrocytes?
hyperammonemia states (chronic liver disease)
wilson disease
hereditary metabolic urea cycle disorder
Describe Alzheimers 2 astrocytes
in gray matter
very large nucleus and nucleolus with pale staining
intranuclear glycogen droplet
What are 2 examples of reactive astrocytes?
gemistocytes
Alzheimers 2 astrocytes
Gliosis is a common reaction to what common supratentorial tumor of childhood?
craniopharyngioma
Describe craniopharyngioma
benign, slow growing supratentorial tumor
derived from remnants of Rathke’s pouch (ectoderm)
Calcification (can have teeth)
cholesterol crystals found in motor-oil fluid within tumor
Describe Rosenthal fibers
thick, elongated, pink (eosin), corkscrew/sausage structures in astrocytic processes
B crystalline and HSP27 with ubiquitin
Where are Rosenthal fibers found?
slow growing, benign process
areas of longstanding gliosis
What is a common tumor that you can find Rosenthal fibers in?
pilocytic astrocytoma
What is a disease that you can find Rosenthal fibers in?
Alexander disease
–> leukodystrophy; perivascular, periventricular, subpial rosenthal fibers
What polyglucosan bodies are found in normal aging?
corpora amylacea
increase with increased age
represent degenerative change
Describe corpora amylacea
PAS +
round, onion skin adjacent to end process of astrocyte
subpial and perivascular
glycosaminoglycan polymers with HSP and ubiquitin
What are the macrophages of the CNS and what markers are on their surface?
microglia
CR3 and CD68 (same as peripheral macrophages)
What are microglia responses to injury?
Proliferation
Elongated “rod cell” nuclei–> seen in neurosyphillis
Microglial nodules
Neuronophagia
When would you see elongated nuclei in microglia?
neurosyphillis
What are microglial nodules?
microglia aggregate around small foci of necrosis
What is neuronophagia?
microglia congregate around cell bodies of dying neurons
What are ciliated columnar cells that line ventricles?
ependymal cell
What are ependymal granulations?
small irregularities on ventricular surface (blebs off ependymal lining)
What damages ependymal cells and creates viral inclusions?
CMV
What is oligodendrocyte response to injury?
demyelinating disorder
leukodystrophies
–> progressive multifocal leukoencephalopathy (intranuclear inclusions)
–> multiple system atrophy with glial cytoplasmic inclusions of alpha-synuclein
Define cerebral edema
accumulation of fluid in brain parenchyma
can be vasogenic or cytotoxic
Describe vasogenic cerebral edema
increased extracellular fluid (d/t BBB disruption–> increased vascular permeability) causes shift from intravascular to intercellular spaces
NO LYMPH to resorb excess fluid
can be localized or generalized
often follow ISCHEMIC INJURY (d/t damaged vessel walls)
Describe cytotoxic edema
increased intracellular fluid secondary to neuronal, glial or endothelial CELL MEMBRANE INJURY
–> via generalized hypoxic/ischemic insult or metabolic derangement
What will you see structurally in cerebral edema
flattened gyri and narrow sulci (smooth surface)
ventricles compressed d/t fluid
can lead to HERNIATION
In clinical practice, you will see what types of cerebral edema?
both vasogenic and cytotoxic
What can cause herniation?
cerebral edema
Describe hydrocephalus ex vacuo
excess fluid as brain compensates for decreased brain mass (degenerative disease)
Describe the pathogenesis of hydrocephalus
increased production of CSF from choroid plexus papilloma (rare)
obstruction (exudate, tumor, blood clot, congenital stenosis/atresia, INFECTIONS)
decreased absorption d/t outflow obstruction (CSF doesn’t reach the point of absorption d/t block before it)
What are responses to increased CSF/hydrocephalus?
PAPILLEDEMA (increased ICP)
enlargement of third ventricle downward
stretching/perf of septum pellucidum that separates horns of ventricles
thinning of cerebral mantle
elevation of corpus callosum
dilation of frontal and temporal horns of ventricles
absorption in transventricular and nerve root sleeves
Craniopharyngioma can compress the optic chiasm leading to ________
bilateral hemianopsia
Pyogenic meningitis causes supprative exudate that covers the brainstem and cerebellum, thickens the leptomeninges and leads to ________
obstructive hydrocephalus
What are congenital causes of hydrocephalus?
TORCH infections (preg) agenesis/atresia/stenosis AV malformation Arnold Chiari malformations Dandy Walker syndrome cranial defects
What are acquired causes of hydrocephalus?
Infections–> meningitis, meningoencephalitis, cysticercosis
Mass lesions–> medulloblastoma, astrocytomas
Inflammation–> brain abscess
Post Hemorrhage–> IVH, SAH, injury
choroid plexus papilloma
hypervitaminosis A
idiopathic
What type of hydrocephalus occurs when CSF is not absorbed at dural sinus level and leads to symmetric dilated ventricles?
communicating
What hydrocephalus has normal CSF pressure?
hydrocephalus ex-vacuo
Why does the brain shrink in hydrocephalus ex vaco?
frontal atrophy with increased age
stroke or other injury
chronic neurodegenerative disease (alz, park, huntington)
What is the mnemonic for normal pressure hydrocephalus?
wet, wacky, wobbly
Describe normal pressure hydrocephalus
symmetric, blockage occurs slowly over time
over 60 years, mimics dementia of Alz and gait of Park
idiopathic (main) or secondary to hemorrhage, trauma, tumor, infection
Is normal pressure hydrocephalus reversible?
yes
Symptoms of normal pressure hydrocephalus
gait disturbance–> magnetic gait, broad based
dementia (much less impaired recognition vs Alz but misdiagnosed anyway)
urinary incontinence
How does increased ICP cause ischemia to the brain?
after brain can’t compensate anymore, venous sinuses have minimal blood to reduce pressure
cerebral swelling–> herniation that (depending on which kind) causes torsion of brainstem and reduced local blood flow to brain–> no perfusion to the brain–> death
What can cause increased ICP?
generalized brain edema
expanding mass lesion (tumor, abscess, hemorrhage)
increased CSF volume
What are the 3 types of herniations that can occur with increased ICP/CSF?
subfalcine (cingulate?
transtentorial (central vs uncal)
tonsillar
What herniation can cause cardiac and respiratory depression?
tonsillar
cerebellar tonsils through foramen magnum–>compress brainstem
What herniation compresses temporal lobe against tentorium?
uncal/transtentorial
What herniation causes dilated pupil and impaired eye movement?
uncal type of transtentorial
compresses oculomotor nerve (CN 3)
What herniation causes displacement of cingulate gyrus under falx and anterior cerebral artery compression?
subfalcine/cingulate
falx separates hemispheres
What is a consequence of central vs uncal transtentorial herniation?
central–> Duret hemorrhage (fatal)
uncal–> Kernohan phenomenon
Describe Duret hemorrhage
transtentorial herniation central/ downward so displaces brainstem caudally
ruture of paramedian basilar artery brances–> hemorrhagic lesions in midbrain and pons
often fatal
Describe Kernohan phenomenon
compression of cerebellar peduncle d/t uncal transtentorial herniation–> makes notch in peduncle called Kernohan notch
ipsilateral hemiparesis or hemiplegia (on side of herniation)
Why is the Kernhoan phenomenon unique
false localizing sign (injury on opposite side of brain to notch) and also ipsilateral sx
Right herniation–> causes notch in left peduncle–> right sided motor impairment
Compare early vs late uncal herniation
early: ipsilateral blown pupil with contralateral heimparesis (d/t crossing fibers in peduncle)
late: Kernohan (contralateral blown pupil, ipsilateral hemiparesis)
If R herniation–> L Kernohan notch (compresses L side of peduncle which sends info to R brain)—> R hemiparesis
What’s the effect of injury to cerebellum and cerebellar peduncles (generally)?
cerebellum affects ipsilateral side
cerebellar peduncle crosses fibers to cerebellum (attaches both) so contralateral
Low partial pressure of oxygen
hypoxia
Impairment of blood’s oxygen carrying capacity or inhibition of oxygen use
ischemia
area of necrosis resulting from sudden insufficiency of arterial or venous blood supply
infarct
what can cause cessation of blood flow
decreased perfusion pressure (hypotension)
small or large vessel obstruction
both
Describe purkinje and pyramidal cell response to hypoxia
shrunken, eosinophilic, pyknotic (red neurons)
pyramidal cells of sommer’s sector (CA1 and CA2) have decreased number of cells
What type of necrosis is found in the CNS (also abscesses)?
liquefactive
liquid viscous mass of dead tissue, no architectural remains
What causes CNS liquefactive necrosis?
CNS infarct (all other organs have coagulative necrosis with intact architecture remains)
What can you see histologically in cerebral infarction?
No myelin or decreased
dead red neurons
PMNs (neut, bas, eos)
macrophages (microglia)
gliosis
missing, pale neuropil (decreased cells)
Define hygroma
separation of arachnoid from dura d/t contraction of underlying brain parenchyma s/p infarct
Old vs new infarct
old: hygroma (may have shifted structures in brain) or cavitation
new: liquefactive necrosis
Examples of posterior fossa anomalies
Arnold-Chiari (type 1 and 2)
Dandy-Walker
Joubert syndrome
Syringomyelia (syrix)
What malformation creates a small posterior fossa
Chiari
Which Chiari is more severe with a misshapen midline cerebellum with downward extension of vermis through foramen magnum?
type 2
usually has non-comm hydrocephalus (d/t aqueductal stenosis from entry into foramen magnum) and myelomeningocele
Which Chiari is silent but d/t low lying cerebellar tonsil extension into vertebral canal?
type 1
What malformation has an enlarged posterior fossa and expanded roofless fourth ventricle>
Dandy-Walker
Is the cerebellar vermis present in Dandy-Walker?
no- absent or rudimentary
replaced by a cystic enlargement of 4th ventricle
What syndrome has hypoplasia of vermis, elongation of cerebellar peduncles (molar tooth sign) and deepened interpeduncular fossa?
Joubert syndrome
What can occur with Dandy Walker malformation?
non-comm hydrocephalus
spina bifida
Describe syringomyelia/syrinx
fluid-filled, cleft-like cavity (cystic cavity) in the inner portion of the cord
–> loss of pain and temp in BL UE
What fibers are damaged in syringomyelia?
spinothalamic tract (pain and temp) that cross the anterior white commissure
CAPE-LIKE distribution
What is syringomyelia associated with?
Chiari type 1
What forebrain anomaly has decreased number of gyri with a sooth, cobblestone surface?
lissencephaly
What is microcephaly associated with?
fetal alcohol syndrome
HIV acquired in utero
Zika virus
What has entrapment of meningeal tissue d/t irregularly formed, numerous gyri?
polymicrogyria
What cause forebrain anomalies?
abnormal generation or migration of neurons
What are neuronal heterotopias associated with?
epilepsy
neurons in inappropriate places
x chromosome
What is cyclopia and arrhinenceophaly (absence of olfactory CN) associated with?
holoprosencephaly
incomplete separation of cerebral hemispheres midline (prosencephalon wk 5-6)
What is holoprosencephaly associated with?
trisomy 13 and FAS
sonic hedgehog signaling pathway
What does moderate holoprosencephaly have?
cleft lip/palate
What is associated with bat-wing lateral ventricles?
agenesis of corpus callosum
MR or normal mentation
What is the most common CNS malformation, when does it occur, and what is it due to?
Neural tube defects
–> normal close by day 28
folate deficiency
What are examples of neural tube defects?
spina bifida meningocele myelomeningocele myeloschisis anencephaly
Define spina bifida/occulta
asymptomatic
failure of caudal neuropore to close (bones don’t fuse), no herniation of spinal cord
dura intact, tuft of hair common
Define meningocele
only meninges (no neural tissue) protrude from opening in bone
Define meningomyelocele
CNS tissue goes through opening in bone along with meninges
motor and sensory deficits of LE, bower and bladder implications, superimposed infections d/t exposed cord
Define encephalocele
brain tissue extends through defect in cranium in posterior fossa (ball at back of head)
nasal glioma–> extension through the cribriform plate (ball between eyes)
Define anencephaly
absence of most of brain and calvarium
d/t disruption of forebrain around 28 days
Define myeloschisis
exposed, unfused neural tissue without skin/meningeal covering
What is a non-progressive neuro motor defect a/w insult occurring during the prenatal and perinatal period?
cerebral palsy
What perinatal brain injury causes spasticity, dystonia, ataxia/athetosis and paresis?
cerebral palsy
What perinatal brain injury is seen in the germinal matrix of premature infants between the thalamus and caudate nucleus?
intraparenchymal hemorrhage
d/t fragile matrix in babies
Describe intraparenchymal hemorrhage
germinal matrix of premies
goes into ventricles b/t thalamus and caudate nucleus, can progress to subarachnoid hemorrhage
What perinatal brain injury is infarcts in supratentorial white matter of premies? What do the infarcts look like?
periventricular leukomalacia
chalky yellow plaques represent necrosis and calcification
What is perinatal brain injury with extensive ischemic damage of white AND gray matter–> large destructive cystic lesions?
multicystic encephalopathy
cystic spaces with widespread ischemia
What is a perinatal brain injury with perinatal ischemic lesions in the depths of sulci that lead to thinned-out gliotic gyri?
ulegyria
Describe awake vs LOC skull fractures?
awake–>fall backward, so occipital fx
LOC–> pass out and fall forward, frontal fx
What is a diastatic fracture?
fracture that crosses a suture
How can you tell if a fracture is new or old?
newer fracture lines DON’T extend across previous fracture lines
Describe a displaced or depressed skull fracture
Bone displaced into cranial cavity BY A DISTANCE weighs more than the thickness of a bone
What is a good indication that you have a basal skull fx?
CSF drainage from ear or nose (oto/rhinorrhea)
raccoon eyes (orbital/mastoid hematomas)
hemotympanum
battle sign behind ears
Are head injury and TBI synonymous?
NO
TBI is altered LOC w/ or w/o altered brain fxn d/t external mechanical trauma
What causes chronic traumatic encephalopathy?
repeated head blows or concussive injuries
must be dx after death
What is the pathology behind chronic traumatic encephalopathy?
tau build-up in brain w/ neurofibrillary tangles
depigmentation of substantia nigra
What is a direct parenchymal injury?
hit to head–> crests of gyri most susceptible
contusion to brain (wedge-shaped, broad base at point of impact)
What are the different types of contusions?
coup (contusion at point of impact)
contrecoup (opposite side of coup, seen in sudden deceleration)
plaque jaune ( old yellow-brown trauma lesions of countercoup in inferior frontal cortex, temporal and occipital lobes)
Define diffuse axonal injury (DAI)
direct action of mechanical forces–> axonal swelling w/ or w/o focal hemorrhagic lesions
appear within hours and persist
increased microglia and degeneration of involved tracts (later on)
What picks up DAI?
silver stain, APP (amyloid) or alpha-synuclein
What can produce DAI even in absence of impact?
angular acceleration
–> why babies so easily get this when shaken, decreased myelin–> no structure or protection
50% of people that have coma, even without cerebral contusions, have what?
DAI/ diffuse axonal injury
Where can you see axonal spheroids?
DAI
Shaken baby overview
shaking violently stops crying d/t brain damage
most don’t die but live with brain damage
several occasions–> second concussion syndrome (die hours after d/t DAI and brain swelling)
How to recognize shaken baby syndrome
DAI/cerebral edema
subdural hematomas
retinal hemorrhages
subgaleal hemorrhages (extracranial)
microscopic iron (detect old bleed)
NEVER normal after shaking
What type of hematoma is a/w skull fracture in adults, ARTERIAL, with rapidly evolving neuro sx (immediate intervention)?
epidural hematoma
middle meningeal artery rupture often
What type of hematoma is a/w mild trauma, VENOUS, slowly evolving neuro sx with delay from time of injury?
subdural hematoma
What type of hematoma is a/w SUDDEN ONSET of severe headache, rapid neuro degeneration and often secondary injury d/t vasospasm/reperfusion?
subarachnoid (trauma, AV malformation, aneurysm)
often on crests of gyri w/ contusions
What is a common presentation for epidural hematoma?
transient LOC–> recovery/ lucid interval–> rapid deterioration d/t expansion
Where can you see transtentorial herniation and CN III palsy?
epidural hematoma
expansion of blood against brain pushes it to side–> herniation
What hematoma is seen in shaken babies?
subdural hematoma
Crescent shaped vs Biconvex (almost circular) hemorrhages
subdural–> crescent
epidural–> convex
Which hematoma crosses suture lines?
subdural
What hemorrhage is most commonly caused by systemic HTN?
intraparenchymal hemorrhage
