Intro to Neuropathology Flashcards
What two things are considered glia?
Astrocytes
Oligodendrocytes
What is selective vulerability?
Neurons don’t necessarily have to be located together so response to insult have many consequences.
- Ex) Neurons can be located in temporal lobe and cerebellum, etc
What happens in the acute neuronal response to injury? (12-24h)
What significant does this have as an indicator?
Red neurons
-Earliest morphologic indicator of acute insult
What are red neurons and how do they come to be? (4)
- Shrinkage of cell body
- Pyknosis
- Loss of nucleolus
- Loss of Nissl substance with intense eosinophilia of cytoplasm
What happens in subacute or chronic neuronal injury (degeneration or progressive disease)?
What significant does this have as an indicator?
- Cell loss & reactive gliosis; apoptosis
- Best indicator of neuronal injury
What is gliosis?
What significant does this have as an indicator?
Essentially “scar tissue” of the brain
- Most important histopathologic indicator of CNS injury, regardless of etiology (pharm, trauma, etc)
- Hypertrophy and hyperplasia of astrocytes
What is an axonal reaction in neuronal injury? What happens?
Inc in protein synthesis a/w axonal sprouting
- Enlarged/rounded cell body
- Periph displacement of nucleus
- Enlarged nucleolus (b/c it’s very active)
- Nissl removed from center of cell to periphery (central chromatolysis)
Side note: Chromatolysis and lipofuscin are normal processes
What are neuronal inclusions in relation to neuronal injury? (2)
- Intracytoplasmic
- Intranuclear
What is an intracytoplasmic inclusion? Rabies Alzheimers Parkinsons CJD
Lipofuscin, proteins, or carbohydrate accumulations
- Rabies: Negri bodies
- Alz: Neurofibrillary tangles
- Parkinson: Lewy bodies
- CJD: Vacuolization of perikaryon & neuronal processes
What is an intranuclear inclusion?
Herpes
CMV
- Herpes: Cowdry body
- CMV: Both intranuclear and cytoplasmic; Owl’s eye inclusions
What are three things that can happen with astrogliosis?
Gliosis, calcifications forming, keratin forming
- Side note: Any tumor that would “spill” contents into or adjacent to brain parenchyma would produce a localized injury and astrogliosis
What are rosenthal fibers?
What are corpora amylacea?
Rosenthal fibers: Thick, elongated, brightly eosinophilic irregular structures occurring w/i astrocytic processes
- Areas of longstanding gliosis; pilocytic astrocytoma
- If we see Rosenthal fibers this is likely a good sign of a slow growing, benign tumor
Corpora amylacea: Round, faintly basophilic, concentrically laminated strictures located adjacent to astrocytic end processes
- PAS +
- Inc with age, represent degenerative change
What are microglia and what are their surface markers?
Macrophages of the CNS
- Surface markers CR3 and CD68 (same as periph macrophages)
- Aggregate around a small foci of necrosis and around cell bodies of dying neurons)
Cerebral edema:
What is vasogenic edema? When and why do we see this?
Inc in extracellular fluid d/t BBB disruption and inc vascular permeability; often follows ischemic injury
- Hard to shift xs fluid out of brain bc no lymphatics
Cerebral edema:
What is cytotoxic edema?
Inc in intracellular fluid secondary to neuronal, glial, or endothelial cell membrane injury
What can a choroid plexus papilloma lead to?
Inc in CSF (d/t xs choroid plexus) leading to hydrocephalus (looks like broccoli)
Pyogenic meningitis:
Where is a typical spot to see exudate in TB or syphilis?
What happens to the meninges and what can this cause?
Base of the brain. Thickened leptomeninges can lead to obstructive hydrocephalus
Name 6 causes of congenital hydrocephalus
- Intrauterine (TORCH) infections
- Agenesis/atresia/stenosis
- AV malformation
- Arnold-Chiari malformations
- Dandy-Walker syndrome
- Cranial defects like achondroplasia or craniostenosis (sutures ossify prematurely)
Name 8 causes of acquired hydrocephalus
- Infections (meningitis, meningoencephalitis, cysticercosis)
- Mass lesions (neoplasms like medulloblastoma, astrocytoma)
- Inflammation (brain abscess)
- Post hemorrhage (IVH, SAH, Injury)
- Choroid plexus papilloma/carcinoma
- Sagittal sinus thrombosis
- Hypervitaminosis A (softening of skull bones in infants and kids)
- Idiopathic
Features of communicating hydrocephalus
- CSF is not properly absorbed at level of dural sinus
- Ventricles are symmetrically dilated
- No single point of obstruction
What is Hydrocephalus Ex-Vacuo? What are some features?
- Shrinkage of brain substance (Atrophy w inc age, stroke or other injury, neurodegenerative process)
- Dilation of ventricles
- CSF Pressure is normal
What is normal pressure hydrocephalus? What are some features?
- Symmetric hydrocephalus
- Occurs in adults, typically over 60yo
- Drainage of CSF is gradually blocked but ventricular system enlarges too so pressure don’t elevate too much
- Can be reversible
- “wet, wacky, wobbly” = incontinence, dementia, magnetic and broad-based gait
What are 3 things that increased ICP are generally due to?
- Generalized brain edema
- Expanding mass lesion (tumor, hemorrhage, abscess, etc)
- Inc CSF volume
What is herniation?
Inc pressure beyond the compensatory ability of the venous system to compress & displace CSF. Tissue herniates past the rigid dural holds (flax & tentorium) or through skull openings
What are 3 types of herniation?
- Subfalcine (cingulate): Cingulate gyrus displaced under the falx
- Transtentorial (Uncinated, Uncal, etc): Medial aspect of the temporal lobe is compressed against tentorium; CNIII compression leads to dilated pupil & impaired eye movement
- Tonsillar: Cerebellar tonsils displaces thru the foramen magnus; this is life threatening d/t compression of the respiratory & cardiac centers
S&S of inc ICP? (Many)
H/A, N/V, lethargy, change in personality, change in pupil reaction esp impaired upward gaze, CNVI palsy, seizures (new adult onset!), ataxia & dec coordination, papilledema
What is Kernohan’s notch phenomenon?
What is a false-localizing sign?
Result of the compression of the opposite side cerebral peduncle against the tentorium cerebelli d/t transtentorial herniation. Produces ipsilateral hemiparesis or hemiplegia.
- Visible notch in the cerebral peduncle
This is considered a false localizing sign because the pressure is on the opposite side of the brain but since the motor fibers cross over, it’s the right side of the body that is affected.
- Right hemisphere herniation cause notch in left cereberal peduncle which results in right-sided motor impairment
With Kernohan’s notch phenomenon, what happens if CNIII is involved with cerebral peduncle?
What may this progress to with time?
Compression of ipsilateral cerebral peduncle (corticospinal tracts) and CNIII leads to contralateral weakness and ipsilateral dilated pupil
Later on is may compress other side against Kernohan’s notch which would lead to ipsilateral weakness and contralateral dilation of pupil
What is a duret hemorrhage?
Progression of transtentorial herniation often accompanied by secondary hemorrhagic lesions in the midbrain and pons
- As mass effect displaces the brain downward, there is a disruption of vessels that leads to herniation along the pons
Hypoxia vs ischemia vs infarct?
Hypoxia: Dec oxygen
Ischemia: Dec blood flow
Infarct: Necrosis from dec blood flow
What kind of necrosis happens in the CNS?
Liquefactive; no architecture remains
What is a hygroma?
Separation of arachnoid from dura d/t contraction of underlying brain parenchyma s/p infarct
What are neural tube defects? What causes them? (general)
Failure of neural tube to close, often d/t folate deficiency before day 28 of conception
Neural tube defects:
What is spina bifida (spinal dysraphism)?
Bony defect, often asymptomatic. Flattened and disorganized segment of cord a/w meningeal pouch
Neural tube defects:
What is a meningocele and myelomeningocele?
What sx can a myelomeningocele lead to?
Meningocele: Protrusion of meninges through a defect in the vertebral column
Myelomeningocele: Protrusion of meninges and CNS tissue through a defect in the vertebral column
- Can lead to motor and sensory defects of the LE including loss of bowel and bladder control, superimposed infections d/t thin covering of the cord
Neural tube defects:
What is an encephalocele? Where is the typical spot for this?
Diverticulum of disorganized brain tissue extending through defect in cranium; usually posterior fossa
Neural tube defects:
What is anencephaly?
Absence of most of the brain and calvarium
Forebrain anomalies:
What is microcephaly d/t and how to rates compare with megacephaly?
Microcephaly more common than mega
- Often d/t fetal alcohol syndrome, HSV-1 acquired in utero, Zika virus
Forebrain anomalies:
What is Lissenencephaly?
Dec number of gyri or agyria
Forebrain anomalies:
What is polymicrogyria?
Small, unusually numerous, irregularly formed convolutions; grey matter <4 layers with entrapment of meningeal tissue
Forebrain anomalies:
What are neuronal heterotopias? What is this commonly a/w?
Collections of neurons in inappropriate places alone the pathway of migration; commonly a/w epilepsy
Forebrain anomalies:
What is holoprosencephaly? What pathway or chromosomal abnormality is it often associated with?
Incomplete separation of cerebral hemispheres across midline
- Can lead to midline facial abnormalities including cyclopia or arrhinenceophaly (absence of olfactory cranial nerves)
- Trisomy 13 and Sonic Hedgehog signaling pathway
Posterior fossa anomalies:
What are Arnold-Chiara malformations?
Both: Small posterior fossa
Type I: Low-lying cerebellar tonsils that extend down vertebral column, often clinically silent but may become symptomatic is the impair CSF flow
Type II: Misshapen cerebellum w downward extension of vermis through foramen magnum, often has hydrocephalus and lumbar myelomeningocele
Posterior fossa anomalies:
What is a Dandy-Walker malformation?
Enlarged posterior fossa, expanded roofless fourth ventricle
- Cerebellar vermis absent or rudimentary, often replaced by a cyst
Posterior fossa anomalies:
What is Joubert syndrome?
Hypoplasia of vermis, elongation of cerebellar peduncles & altered brainstem shape; “molar tooth sign”
Note: OFTEN A DISTRACTOR ON EXAMS
Posterior fossa anomalies:
What is syringmyelia?
Fluid-filled cleft-like cavity in the inner portion of the cord; enlargement of central canal that interrupts fibers that cross through anterior white commissure
- Bilateral isolated loss of pain & temperature in UE; “cape sign”
Perinatal brain injuries:
What is cerebral palsy?
Non-progressive neurologic motor deficit d/t insults during pre/perinatal period
- Spasticity, dystonia, ataxia/athetosis (writhing movements) & paresis
Perinatal brain injuries:
What is intraparenchymal hemorrhage? Starts where and leads to what?
Seen in germinal matrix of premature infants; junction b/w thalamus & caudate nucleus; ventricles then SAH
Perinatal brain injuries:
What is periventricular leukomalacia?
Infarcts in supratentorial white matter
- In premature infants these are chalky yellow plaques (necrosis & calcification)
- Large cystic spaces
Perinatal brain injuries:
Multicystic encephalopathy?
Does it affect white or grey matter?
Extensive ischemia damage of both white and grey matter; large destructive cystic lesions
Perinatal brain injuries:
Ulegyria?
Perinatal ischemia lesions in depths of sulci; thinned out gliotic gyri
Important things to note about skull fractures?
- Later fractures do not extend across previous fracture lines
- Usually: If conscious and fall, you fall backwards. If unconscious and you fall, you fall forwards
What can you see with basilar skull fractures?
Battle signs and racoon eyes, CSF may lead from external auditory canal thru ear or nose
Parenchymal injuries:
Concussion
TBI/CTE
Clinical (not pathological) syndrome; transient and may have LOC or loss of memory surrounding event
- In TBI, brain function is temp or perm impaired; can be d/t a single event
- Chronic traumatic encephalopathy can only be diagnosed after death; progressive loss of brain matter w/ abn buildup of tau protein, neurofibrillary tangles, and depigmentation of substantia nigra
Parenchymal injuries:
Direct parenchymal injury
Contusions or lacerations, caused by transmission of kinetic energy to the brain
- Contusions are often wedge-shaped w broad base at point of impact; may have contre/coup injuries
Parenchymal injuries:
Diffuse axonal injury
What stain can you use?
Axonal swelling +/- focal hemorrhagic lesions; direct action of mechanical forces
- Shaken baby syndrome; child is never normal again
- Silver stain or amyloid precursor protein & alpha synuclein immunostains
Sequelae of brain trauma
Post traumatic hydrocephalus
Chronic traumatic encephalopathy (CTE)
Can happen months to years after brain trauma
- Post-traumatic hydrocephalus: Obstruction of CSF resorption d/t hemorrhage in subarachnoid space
- Chronic traumatic encephalopathy (CTE): Dementing illness that develops after repeated head trauma; atrophy, enlarged ventricles, tau neurofibrillary tangles involving gyral depths & perivascular regions in frontal & temporal lobes
Spinal cord injuries and their levels
Cervical: Quadriplegia
- C4 & Above: Respiratory compromise d/t paralysis of diaphragm
Thoracic: Paraplegia
Micro: Lesion tapers above & below level of injury
- Acute: Hemorrage, necrosis, axonal swlling
- Chronic: Central areas become cystic & gliotic
Patterns of hemorrhage:
Epidural space
Arterial or venous?
Often d/t trauma, usually a/w skull fracture; rapidly evolving neurological symptoms requiring intervention
Arterial
Patterns of hemorrhage:
Subdural space
Arterial or venous?
Often d/t trauma, slowly evolving neurologic symptoms often w/ a delay from the time of injury
Venous
Patterns of hemorrhage:
Trauma (contusions)
Selective involvement of crests of gyri (where brain contacts the skull)
Patterns of hemorrhage:
HTN
Centered in the deep white matter of the brain, thalamus, BG, or brainstem
Characteristics of epidural hematomas? Which vessel is often affected?
- Often a rupture of the middle meningeal artery, usually a/w a skull fracture.
- Stops at suture lines where dura is firmly attached
- Arterial blood
Characteristics of subdural hematomas? Which vessel is often affected?
Damage to bridging veins between brain and superior sagittal sinus
- Venous blood
