Neuropathology Flashcards
1
Q
Neuropathology
A
Subspecialty within Pathology (and Neurology) which involves study of:
- Brain (biopsies and at autopsy)
- Spinal Cord
- Peripheral Nerves and Ganglia
- Pituitary gland
- Coverings of Nervous system (skull, meninges)
- Skeletal Muscle
2
Q
Key Anatomic/Physiologic Features
A
- Skull and spinal canal ⇒ rigid barrier to prevent external injuries
- Brain and spinal cord float on a cushion of CSF ⇒ further cushioning vs shock
- Blood-brain barrier regulates transport of fluids, ions, and macromolecules between vascular space and brain
- No lymphatics in the CNS ⇒ immunologically privileged, but prone to edema
3
Q
Neurons and axons visualized using…
A
Bodian Stain
4
Q
Neuronal Reaction to Injury
A
Axonal Injury shows up in the cell body (Chromatolysis) and in the axon (Wallerian Degeneration):
- Chromatolysis ⇒ swelling, nuclear eccentricity, and dispersal of the Nissl substance to the periphery of the cell
-
Wallerian Degeneration ⇒ axon degenerates distal to the point of injury and macrophages ingest the debris
- Sometimes, esp. in the PNS, axons regenerate
5
Q
Hypoxic Change
A
See changes similar to that seen in other cells/tissues:
-
Acute neuronal injury (red neuron)
- With H&E: shrunken, hyper-eosinophilic cell body with nuclear pyknosis and disappearance of nucleolus within 12-24 hours after irreversible hypoxic/ischemic insult
-
Subacute and chronic neuronal injury
- Seen in slowly evolving disease (e.g. ALS) with resulting cell loss and associated reactive gliosis
6
Q
Transsynaptic Degeneration
A
- Occurs when a destructive process interrupts the majority of the afferent input to a group of neurons
- Ex. degeneration of sets of lateral geniculate neurons after eye enucleation
- See shrinkage and degeneration of cell bodies
7
Q
Neuroglia
A
Outnumber neurons 10:1
8
Q
Astrocytes
Overview
A
- Supporting cells of CNS
- Seen on H&E as small nuclei
- Can only see cell processes on special stain (GFAP)
9
Q
Astrocyte
Reaction to Injury
A
-
Gliosis
- Reaction to tissue destruction in CNS
- See prominent nuclei and lots of bright pink cytoplasm packed with intermediate filaments
- Stain with GFAP (known as a gemistocytic astrocyte)
-
Rosenthal Fibers
- Chronically reactive astrocytic process have lots of brightly eosinophilic proteins
-
Corpora amylacea
- Elaboration of astrocytic processes seen in normal aging human brains, contain glucose polymers
-
Alzheimer Type II Astrocyte
- Large, comma-shaped vacuolated nuclei
- Seen in hepatic encephalopathy
- Reaction to circulating toxins from liver failure
- Note: Unrelated to Alzheimer disease
10
Q
Oligodendroglia
Overview
A
- Myelin producing cells
- Small dark nuclei on H&E
- Don’t be fooled by a normal finding ⇒ ‘satellitosis’
- Normal clustering of up to 5-6 oligodendrocytes around neuronal cell bodies
11
Q
Oligodendrocyte
Response to Injury
A
Limited response
Involute when injured and their myelin wraps are lost ⇒ replaced by glial scars
12
Q
Ependymal Cells
Overview
A
Single layer of ciliated columnar cells that line ventricles
13
Q
Ependymal Cells
Response to Injury
A
Can see ependymal ‘granulations’ as an astrocytic response to ependymal damage in encephalitis or meningitis
14
Q
Microglia
Overview
A
- Derived from monocytes
- Hard to see on H&E
- Small elongated nuclei
15
Q
Microglia
Response to Injury
A
-
Transform into macrophages (gitter cells)
- Look brown on H&E due to release of lipid from CNS damage
- Can form microglial nodules in encephalitis
- Seen as clusters around infected neurons as part of a ‘cleanup’ process ‘neuronophagia’
-
Rod cells
- Another form of microglial proliferation in response to injury
- See elongated nuclei
16
Q
Neuronal Inclusions
A
- Subcellular alterations of in the neuronal organelles and cytoskeleton
- Seen in many different cell types and in many different conditions
- Ex. viral infections and accumulation of metabolic intermediates
17
Q
Cerebral Edema
Mechanisms
A
-
Vasogenic
- Involves direct damage to the blood-brain barrier
- ↑ capillary permeability and ↑ extracellular fluid
- Can be localized or generalized
- Most commonly seen with primary and metastatic tumor and with abscesses
- May respond to treatment with steroids
-
Cytotoxic
- Involves damage to the metabolism of neurons and glia that disrupts maintenance of fluid and electrolyte homeostasis
- Results in intracellular accumulation of fluid
- Seen most commonly in brain infarction
- No effective treatment exists
18
Q
Cerebral Edema
Morphology
A
- Brain is boggy and heavy, with flattened gyri in affected areas
- On cut section, see blurring of gray matter-white matter junction
- Microscopically, see poor staining of tissue with lucent haloes around the nuclei
19
Q
Cerebral Edema
Consequences
A
Can lead to increased intracranial pressure, which can lead to herniation.
20
Q
Subfalcine (Cingulate Gyrus)
Herniation
A
- Results from mass lesion in one hemisphere forcing the cingulate gyrus across the midline under the falx
- The anterior cerebral artery can be caught under the falx and its territory infarcted
21
Q
Transtentorial (Uncal)
Herniation
A
- Displacement of the medial temporal lobe (uncus) between the brain stem and the tentorium
- Results from mass lesion in one of the hemispheres
-
Consequences
- Compression of the adjacent third cranial nerve ⇒ fixed, dilated pupil
- Displacement of the midbrain to the opposite side with compression of the contralateral cerebral peduncle against the falx ⇒ hemiparesis ipsilateral to the side of the lesion
- Change in brain known as Kernohan’s notch
22
Q
Cerebellar Tonsillar
Herniation
A
- Results from mass lesion serious enough to cause rostrocaudal movement in the posterior fossa
- Usually fatal due to medullary compression and consequent cardiorespiratory arrest
- Downward displacement ⇒ rupture of penetrating arteries in the brainstem ⇒ Duret hemorrhages in the brainstem and pons
23
Q
Hydrocephalus
Overview
A
-
Refers to accumulation of CSF with ventricular enlargement
- Reflects an imbalance between production and resorption
- If it occurs before closure of cranial sutures ⇒ increase in head circumference
- If later ⇒ increased intracranial pressure since the head can’t expand
-
Pathogenesis
- Obstruction
- Loss of cerebral tissue
- Overproduction of CSF
-
Treatment
- Shunting
24
Q
Obstructive Hydrocephalus
A
-
Within the ventricular system ⇒ ‘non-communicating hydrocephalus’
- Causes include mass lesions, aqueductal stenosis, obstruction of 4th ventricle
-
Outside the ventricular system ⇒ ‘communicating hydrocephalus’
- Tends to follow subarachnoid hemorrhage or meningitis with secondary meningeal scarring
25
Q
Loss of Cerebral Tissue
Hydrocephalus
A
- Refers to the fact that as there is less brain tissue, there is a compensatory enlargement of the ventricles
- Called ‘hydrocephalus ex vacuo’
26
Q
Overproduction of CSF
Hydrocephalus
A
Rare, seen with choroid plexus tumors (Papilloma)
CSF production exceeds capacity of resorptive mechanisms
27
Q
Skull Fractures
A
-
Displaced skull fracture
- Bone is displaced into the cranial cavity by a distance thicker than the bone thickness
- Bone thickness varies throughout the skull
- Frontal impact from a fall suggests loss of consciousness before fall
- Orbital or mastoid hematomas suggest a basal skull fracture resulting from impact to occiput or side of head
- CSF may leak from nose or ear
- Risk for infection and subsequent meningitis
-
Diastatic fracture
- One that crosses a suture line
28
Q
Concussion
A
Direct parenchymal injury
-
Clinical syndrome of altered consciousness secondary to head injury
- Usually due to change in momentum of the head i.e., moving head hits rigid surface
-
See immediate onset of transient neurologic dysfunction
- Likely due to dysregulation of the reticular activating system in the brainstem
- Can include:
- Loss of consciousness
- Temporary respiratory arrest
- Loss of reflexes
- Neurological recovery is complete but may have amnesia for the event
29
Q
Post-Concussive Neuropsychiatric Syndromes
A
- Learning more about these
- Usually associated with repetitive injuries
- Can see cognitive impairment
- Chronic traumatic encephalopathy can be diagnosed microscopically
- NFL, NHL, brain banks, etc.
30
Q
Contusion
A
Direct parenchymal injury
- Caused by blunt trauma
-
See tissue displacement, disruption of vessels and subsequent hemorrhage tissue injury and edema
- Crests of gyri are most susceptible to hemorrhage ⇒ receive the direct force
- Contusions seen most often in frontal lobes, along orbital ridges and temporal lobes
-
Gross exam of acute contusion: wedge shape, base along point of impact, see hemorrhage and edema
- Later, blood extravasates into tissue
- Microscopic evidence of neuronal injury takes about 24 hours to appear, then see usual sequence
31
Q
Old Trauma Lesion
A
- See ‘plaque jaune’
- Yellowish depressed area grossly
- Contains gliosis and hemosiderin laden macrophages; if large enough, can cavitate
- These can eventually become a seizure focus
32
Q
Brain
Laceration
A
Penetrating object that tears tissue
33
Q
Coup vs Contrecoup
Injury
A
-
Coup Injury
- If head is immobile at time of injury
- Tissue damage at site of injury
-
Contrecoup Injury
- Head is mobile, seen along with coup
- Due to brain striking opposing inner surface of skull
- Impact causing violent posterior or lateral hyperextension of neck can avulse pons from medulla or medulla from spinal cord
- Instant death
34
Q
Diffuse Axonal Injury
A
-
Below the surface
- Deep white matter, cerebral peduncles and many other areas affected
- See axonal swelling
- Estimated to occur in up to 50% of people who develop coma shortly after trauma, even without cerebral contusions
- Axons injured by direct action of mechanical forces, alters axoplasmic flow; can even be caused by angular acceleration without impact
- Later see increased microglia in damaged areas with degeneration of involved fiber tracts
35
Q
Traumatic Vascular Injury
A
- Hemorrhage can occur in the epidural, subdural, subarachnoid and/or intraparenchymal compartments
- Epidural and subdural hemorrhages rarely occur without trauma
- With coagulopathy or cerebral atrophy ⇒ very minor trauma ⇒ tearing of vessels ⇒ subdural hemorrhage
36
Q
Epidural Hematoma
A
-
Dural arteries, esp. middle meningeal artery, vulnerable to injury
- Temporal skull fracture line that crosses this artery can tear it
- Blood extravasates under arterial pressure ⇒ separates dura from the inner surface of the skull
- Hematoma compresses brain surface
- Clinically, see a lucid interval followed within hour(s) by neurologic signs and symptoms
- Neurosurgical emergency
37
Q
Subdural Hematoma
A
-
Bridging veins tear
- Brain atrophy increases likelihood of tear due to stretching of the bridging veins; seen more in the elderly
- In infants, thin-walled bridging veins are the risk factor
-
Bleeding separates layers of the dura ⇒ creates a ‘subdural space’ where blood accumulates ⇒ acute subdural hematoma
- Eventually clot lyses and fibroblasts grow in from dura to organize the hematoma
- Can get recurrent bleeding with subsequent chronic subdural hematoma
- See neurologic signs later
38
Q
Sequelae of Brain Trauma
A
- Post-traumatic hydrocephalus
- Chronic traumatic encephalopathy (previously called dementia pugilistica)
- Dementing illness from repeated head trauma
39
Q
Spinal Cord Injury
A
Most damage from injury is due to transient or permanent displacement of the vertebral column.
Level of injury determines clinical sequelae.
40
Q
Neural Tube Defects
A
Anencephaly
- Absence of a major portion of the brain, skull, and scalp that occurs during embryonic development
- Occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception
Encephalocele
- Sac-like protrusions of the brain and meninges through openings in the skull
- Caused by failure of the neural tube to close completely during fetal development
Spinal dysraphism (spina bifida)
- Broad group of malformations affecting the spine and/or surrounding structures in the dorsum of the embryo
- Results when the neural plate does not fuse completely in its lower section
-
Open spinal dysraphism (formerly spina bifida aperta or cystica): occurs when the cord and its covering communicate with the outside
-
Myelomeningocele
- Spinal cord and nerves develop outside of the body
- Contained in a fluid-filled sac that is visible outside of the back area
-
Myelomeningocele
-
Closed spinal dysraphism (formerly spina bifida occulta): occurs when the cord is covered by other normal mesenchymal elements
-
Meningocele
- Sac protruding from the spinal column containing spinal fluid but neural tissue
- May be covered with skin or with meninges
-
Meningocele
41
Q
Forebrain Anomalies
A
-
Polymicrogyria
- Brain develops too many folds
-
Megaloencephaly
- Brain is abnormally large (>2.5x normal)
-
Microencephaly
- Head is too small
-
Lissencephaly (agyria)
- Smooth brain
- Caused by defective neuronal migration
-
Holoprosencephaly
- Prosencephalon fails to develop into two hemispheres
-
Agenesis of the Corpus Callosum
- Partial or complete absence (agenesis) of the corpus callosum that connects the two cerebral hemispheres
42
Q
Posterior Fossa Abnormalities
A
-
Arnold-Chiari Malformation
- Cerebellum pushes through foramen magnum into spinal canal
-
Dandy-Walker Malformation
- Absence of the cerebellum
43
Q
Spinal Abnormalities
A
-
Syringomyelia
- Fluid-filled cyst forms within the spinal cord
-
Hydromyelia
- Abnormal widening of the central canal of the spinal cord that creates a cavity in which CSF can accumulate
