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
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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
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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
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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
Loss of Cerebral Tissue
Hydrocephalus
* Refers to the fact that as there is less brain tissue, there is a compensatory enlargement of the ventricles
* Called **‘hydrocephalus ex vacuo’**
26
Overproduction of CSF
Hydrocephalus
Rare, seen with **choroid plexus tumors** (Papilloma)
CSF production exceeds capacity of resorptive mechanisms
27
Skull Fractures
* **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
Concussion
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:
* L**oss of consciousness**
* **Temporary respiratory arrest**
* **Loss of reflexes**
* Neurological recovery is complete but may have amnesia for the event
29
Post-Concussive Neuropsychiatric Syndromes
* Learning more about these
* **Usually associated with repetitive injuries**
* Can see c**ognitive impairment**
* **Chronic traumatic encephalopathy** can be diagnosed microscopically
* NFL, NHL, brain banks, etc.
30
Contusion
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
Old Trauma Lesion
* 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
Brain
Laceration
**Penetrating object that tears tissue**
33
Coup vs Contrecoup
Injury
* **_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
Diffuse Axonal Injury
* **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
Traumatic Vascular Injury
* **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
Epidural Hematoma
* **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
Subdural Hematoma
* **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
Sequelae of Brain Trauma
* **Post-traumatic hydrocephalus**
* **Chronic traumatic encephalopathy** (previously called dementia pugilistica)
* **Dementing illness** from repeated head trauma
39
Spinal Cord Injury
Most damage from injury is due to **transient or permanent displacement of the vertebral column**.
Level of injury determines clinical sequelae.
40
Neural Tube Defects
**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
* _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
41
Forebrain Anomalies
* **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
Posterior Fossa Abnormalities
* **Arnold-Chiari Malformation**
* Cerebellum pushes through foramen magnum into spinal canal
* **Dandy-Walker Malformation**
* Absence of the cerebellum
43
Spinal Abnormalities
* **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
