Intro to Neuropathology Flashcards
Why is gliosis important?
- Histopathologic indicator of CNS injury
What is gliosis characterized by?
- Hypertrophy and hyperplasia of astrocytes (astrocytes act as a metabolic buffer and detoxifer)
How do gemistocytes differ from dead red neurons?
- Gemistocytes have a nucleus whereas dead red neurons do not
What are rosenthal fibers?
- Thick, elongated, brightly eosinophilic, irregular structures occurring within astrocytic processes
What do rosenthal fibers contain?
- Heat shock proteins( alpha-beta crystalline and HSP27)
- Ubiquitin
Where are rosenthal fibers typically seen?
- In areas of long standing gliosis
What is corpora amylacea?
- Polygucosan bodies
What stain is used for corpora amylacea?
- PAS
What does corpora amylacea look like?
- Round, faintly basophilic
- Concentrically laminated strictures located adjacent to astrocytic end processes (resembles onion skinning)
What does corpora amylacea contain?
- Glycosaminoglycan polymers
- Heat shock proteins
- Ubiquitin
What is a correlation with corpora amylacea?
- Increased with age (represents degenerative change)
What do rosenthal fibers look like?
- Beaded sausage to cork-screw shaped hyaline bodies of variable size
What is the job of microglia?
- Macrophages of the CNS
What surface markers are seen with microglia?
- CR3
- CD68
What are microglial nodules?
- When microglia aggregate around small foci of necrosi
What is neuronophagia?
- Microglia concregate around cell bodies of dying neurons
What are ependymal granulations?
- Small irregularities on ventricular surfaces
- Disruption of ependymal lining and proliferation of subependymal astrocytes
What is vasogenic edema?
- Increased extracellular fluid due to BBB disruption and increased vascular permeability
What are some causes of vasogenic edema?
- Fluid shift from intravascular compartment to intercellular spaces
- Paucity of lymphatics impairs resorption of excess extracellular fluid
- Localized or generalized injury
- Often follows ischemic injury
What is cytotoxic edema?
- Increased intracellular fluid secondary to neuronal, glial, or endothelial cell membrane injury
What are some causes of hydrocephalus?
- Increased production –> choroid plexus papilloma
- Obstruction –> interventricular foramina, congenital, or secondary
- Decreased absorption –> outflow obstruction
What is an external sign of hydrocephalus?
- Papilledema
What does a choroid plexus papilloma look like?
- Broccoli stalk
What is pyogenic meningitis?
- Suppurative exudate covering brainstem and cerebellum
How can pyogenic meningitis cause hydrocephalus?
- Thickened leptomeninges
What should you think when you see pyogenic meningitis covering the base of the brain?
- TB or neurosyphilis
What are some congenital causes of hydrocephalus?
- Intrauterine infections (TORCH)
- Agenesis/atresia/stenosis
- AV malformation
- Arnold chiari malformation
- Dandy-Walker syndrome
- Cranial Defects
What are some acquired causes of hydrocephalus?
- Infections
- Mass lesions
- Inflammation
- Post hemorrhage
- Choroid plexus papilloma
- Sagittal sinus thrombosis
- Hypervitaminosis A
- Idiopathic
What is communicating hydrocephalus?
- CSF is not absorbed properly at the dural sinus level
- Ventricles tend to be symmetrically dilated
How does aqueductal stenosis cause hydrocephalus?
- Aqueduct is 1/3 the size of normal so it reduces the flow significantly
What is seen in hydrocephalus ex-vacuo?
- Dilation of the ventricles
- Shrinkage of brain substance
- CSF pressure is normal (makes it different)`
What are some causes of the shrinkage of brain substance in hydrocephalus ex-vacuo?
- Atrophy with increasing age
- Stroke or other injury
- Chronic neurodegenerative (huntington dz or Alz)
What is normal pressure hydrocephalus?
- Symmetric type of hydrocephalus that usually occurs in patients older than 60
- Develops slowly
What is normal pressure hydrocephalus typically confused with?
- Alzheimers or Parkinson
What are the classic symptoms of normal pressure hydrocephalus?
- Wet –> Urinary incontinence
- Wacky –> Dementia
- Wobbly –> Gait disturbances
What generally causes increased cranial pressure?
- Generalized brain edema
- Expanding mass lesion
- Increased CSF volume
What is herniation?
- Increased pressure beyond the compensatory ability of venous system to compress and displacement of CSF
What are some types of herniation?
- Subfalcine
- Transtentorial
- Tonsillar
What is a subfalcine herniation?
- Cingulate gyrus displaced under the falx
What is a transtentorial herniation?
- Medial aspect of the temporal lobe compressed against the tentorium
What signs may be seen in a transtentorial herniation?
- CN3 –> dilated pupil and impaired eye movement
What is a tonsillar herniation?
- Cerebellar tonsils displaced through the foramen magnum
Why is a tonsillar herniation life threatening?
- Respiratory and cardiac centers are compressed
What are some signs of increased intracranial pressure?
- Headache, change in behavior, N/V
- Change in pupil reaction
- False localizing signs
- Seizures
- Decreased coordination, ataxia
- Papilledema
What causes Kernohan’s notch phenomenon?
- Compression of the cerebral peduncle against the tentorium cerebelli due to transtentorial herniation
What is seen in Kernohan’s notch phenomenon?
- Ipsilateral hemiparesis or hemiplegia (on side of herniation)
- Caused by compression of the contralateral peduncle
What is special about Kernohan’s notch phenomenon?
- As it progresses, it may compress the other side against kernohan’s notch (cerebral peduncle and CNIII) causing ipsilateral weakness, contralateral dilated pupil (relative to original herniation)
What is a duret hemorrhage?
- Progression of transtentorial herniation often accompanied by secondary hemorrhagic lesions in the midbrain and pons
What causes a duret hemorrhage?
- Mass effect displaces the brain downward causing a disruption of the vessels that enter the pons along the midline, leading to hemorrhage
What kind of necrosis does the brain go through?
- Liquefactive (no architecture remains)
What is the progression seen in cerebral infarcts?
- First red dead neurons will show up
- Around day 10, foamy macrophages are seen
- Then there is tissue loss and gliosis
What is a hygroma?
- Separation of arachnoid from dura due to contraction of underlying brain parenchyma
What accounts for most CNS malformations?
- Neural tube defects
What may be a big cause to neural tube defects?
- Folate deficiency
What is spina bifida occulta?
- Asymptomatic, bony defect
- Flattened disorganized segment of cord associated with meningeal pouch
What is a myelomeningocele?
- Extension of CNS tissue through a defect in vertebral column (lumbosacral most common)
What is a meningocele?
- Only meninges protrude
What symptoms are seen in a myelomeningocele?
- Motor and sensory deficits of LE
- Bowel and bladder control
- Superimposed infections (through thin coverings of cord)
What is an encephalocele?
- Diverticulum of disorganized brain tissue extending through defect in cranium (usually posterior fossa)
What is a nasal glioma?
- Misnomer for extension of brain tissue through cribiform plate
What is anencephaly?
- Absence of most of the brain and calvarium
- Forebrain development disrupted at around 28 days GA
What are some defects in neural tube formation in the first trimester?
- Anencephaly
- Encephalocele
- Holoprosencephaly
What are some defects of neuronal proliferation in the second trimester?
- Microcephaly
- Megalencephaly
- Lissencephaly
- Agenesis of corpus callosum
What are some major causes of microcephaly?
- Chromosome abnormalities
- Fetal alcohol syndrome
- HIV-1 acquired in utero
- maybe Zike virus
What is lissenencephaly?
- Decreased number of gyri
- Brain looks smooth or has a cobblestone surface
What is polymicrogyria?
- Small, usually numerous, irregularly formed convolutions
What is neuronal heterotopias associated with?
- Epilepsy
What are neuronal heterotopias?
- Collections of neurons in inappropriate places along the pathway of migration
What genes are implicated in neuronal heterotopias?
- X chromosome (filamin A and DCX)
- Lissencephaly in males and subcortical band heterotopias in females
What is holoprosencephaly?
- Incomplete separation of cerebral hemispheres across midline
What does someone look like with holoprosencephaly?
- Cyclopia
- Arhinencephaly –> absence of olfactory cranial nerves
What pathway causes holoprosencephaly?
- SHH
What genetic abnormality is most likely seen with holoprosencephaly?
- Trisomy 13
What does agenesis of the corpus callosum look like?
- Bat wing on CT
What is seen in Chiari type 2?
- More severe, misshapen midline cerebellum with downward extension of vermis through foramen magnum
What is associated with Chiari type 2?
- Hydrocephalus
- Lumbar myelomeningeocele
What is seen in Chiari type 1?
- Low-lying cerebellar tonsils extend down vertebral canal
How does Chiari type 1 present?
- May be silent and show up incidentally
- May have headache or migraine due to CSF flow impairment
What is seen in Dandy-Walker malformation?
- Enlarged posterior fossa
- Expanded roofless fourth ventricle
- Cerebellar vermis absent or rudimentary
What replaces the vermis in Dandy-Walker malformation?
- Cyst with ependymal lining that is contiguous with leptomeninges on its outer surface
What is Joubert syndrome?
- Hypoplasia of vermis
- Elongation of cerebellar peduncles
- Altered brainstem shape
How does Joubert syndrome look on scans?
- “Molar tooth sign”
What is syringomyelia (or syrinx)?
- Fluid filled cleft like cavity in the inner portion of the cord
What are the classic symptoms of syrinx?
- Isolated loss of pain and temperature sensation in UE (cape like distribution)
How is a syrinx treated?
- Inserting a shunt to help drain the fluid OR
- Removing some of the bone (either from vertebrae or base of skull depending on the location of the syrinx)
What is cerebral palsy?
- Non-progressive neurologic motor deficit attributable to insults occurring during the prenatal and perinatal period
What does cerebral palsy look like?
- Spasticity
- Dystonia
- Ataxia/athetosis
- Pareis
Where does an intraparenchymal hemorrhage occur?
- Seen in germinal matrix of premature infants
- Junction between thalamus and caudate nucleus
When does an intraparenchymal hemorrhage occur?
- Usually a few hours after birth but can occur at any time
What is periventricular leukomalacia?
- Infarcts in supratentorial white matter
What does periventricular leukomalacia look like?
- Chalky yellow plaques due to necrosis and calcification
What is multicystic encephalopathy?
- Extensive ischemic damage of both white and gray matter –> large destructive cystic lesions
What is ulegyria?
- Perinatal ischemic lesions in the depths of sulci
- Causes thinned out gliotic gyri
How do people fall when awake vs loss of consciousness?
- Awake: Fall backward onto occipital
- LOC: Fall forward onto frontal
What is a diastatic fracture?
- Fracture that crosses a suture
Why is the timing of fractures important?
- New fractures lines do not extend across previous fracture lines
What are some signs of a basal skull fracture?
- Orbital or mastoid hematoma
- Otorrhea/rhinorrhea –> CSF drainage
What could battle sign or raccoon eyes help point to?
- Basilar skull fracture
What is a concussion?
- Clinical syndrome
- Altered consciousness secondary to head injury
What are some direct parenchymal injuries?
- Contusions (blunt trauma)
- Lacerations (penetrations or tearing of the tissue)
What are the most common locations for direct parenchymal injuries?
- Frontal lobes/orbital ridges and temporal lobes
- Regions of the brain that overlie rough and irregular inner skill surface
- Crests of gyri are most susceptible where direct force is greatest
What does a contusion look like grossly?
- Wedge shaped –> Broad at point of impacts
What is a coup?
- Contusion at point of impact
What is a contrecoup?
- Diametrically opposed to coup
- Contusion opposite point of impact due to rebound
What are plaque jaune?
- Depressed, retracted, yellowish brown patches involving crests of gyri
What causes plaque jaune?
- Old trauma lesions –> often countercoup inferior frontal cortex, temporal and occipital lobes
What is diffuse axonal injury?
- Axonal swelling +/- focal hemorrhagic lesions
When does diffuse axonal injury present?
- Typically within hours and will persist much longer
What stain is used to help identify diffuse axonal injury?
- Silver stain
- Amyloid precursor protein (APP)
- Alpha synuclein immunostains
What can cause diffuse axonal injury?
- Direct action of mechanical forces
- Angular acceleration alone can produce even in the absence of impact
Why is shaking a baby bad?
- Brains are very soft and not fully developed
- Shaking them causes brain damage but does not kill them
How does several occasions of shaking a baby kill them?
- Is like second concussion syndrome
- Don’t die instantly but after hours of brain swelling and DAI
How is shaken impact syndrome recognized?
- DAI/Cerebral edema
- Subdural hematomas
- Retinal hemorrhages
- Sometimes, subgaleal hemorrhages
- Sometimes, microscopic iron
What is post-traumatic hydrocephalus?
- Obstruction of CSF resorption due to hemorrhage in subarachnoid space
What is chronic traumatic encephalopathy?
- Dementing illness developed from repeated head trauma?
What is seen in CTE?
- Atrophy
- Enlarged ventricles
- Tau neurofibrillary tangles involving gyral depths
- Perivascular regions in frontal and temporal lobes (characteristic pattern)
What is a traumatic brain injury (TBI)? What is it associated with?
- Some level of damage to the brain due to external mechanical force
- Generally associated with diminished or altered state of consciousness
What are some major features of CTE?
- Neurofibrillary tangles/amyloid and tau depositions (similar to Alzheimer’s)
- Depigmentation of substantia nigra (similar to parkinsons)
What kind of paresis is seen in a spinal cord injury in the thoracic region?
- Paraplegia (just legs)
What kind of paresis is seen in a spinal cord injury in the cervical region?
- Quadriplegia (all limbs)
What kind of paresis is seen in a spinal cord injury in C4 or above?
- Respiratory compromise and paralysis of diaphragm
What do acute lesions of the spinal cord look like?
- Hemorrhage
- Necrosis
- Axonal swelling
What do chronic lesions of the spinal cord look like?
- Central areas become cystic and gliotic
What is the most likely cause of an epidural hematoma?
- Rupture of the meningeal artery –> usually due to skull fracture
What is the most likely cause of a subdural hematoma?
- Rupture of bridging veins between the brain and superior sagittal sinus
