Intro to Neuropathology Flashcards
1
Q
True or False: neurons have a centrally-located nucleus
A
True; if it’s not in the center, look for inclusions that could indicate some kind of pathologic process
2
Q
What type of cell looks like a “fried egg” on H and E stains?
A
-oligodendrocytes that produce the myelin; they are usually located right near neurons
3
Q
What type of stain shows astrocytes well?
A
Glial Fibrillary Acidic Protein
4
Q
What is the neuronal response to acute injury (12-24 hrs) such as hypoxia, hypoglycemia, and trauma?
A
“Red Neurons”
- cell body shrinks
- pyknosis (chromatin condenses)
- loss of nucleolus, blurring of cellular features
- loss of Nissl substance w/ intense eosinophilia
5
Q
What is the neuronal response to subacute and chronic injury such as degeneration and progressive disease (ex: ALS, Alzheimer)?
A
- -loss of functionally-related groups of neurons
- -neuron death by apoptosis
- -reactive gliosis (best indicator)
- –hypertrophy and hyperplasia of astrocytes
- –areas of gliosis are more firm to the touch
6
Q
Describe axonal reaction, a change in the cell body during regeneration of the axon.
A
- increased protein synthesis
- enlarged and rounded cell body, enlarged nucleolus
-peripheral displacement of nucleus and Nissl substance (central chromatolysis)
7
Q
What are some examples of intracytoplasmic neuronal inclusions?
A
- -lipofuscin (wear and tear pigment, gold-ish)
- -negri bodies in rabies (eosinophilic)
- -neurofibrillary tangles in Alzheimer (teardrop shape)
- -Lewy bodies in Parkinson
8
Q
What are some examples of intranuclear neuronal inclusions?
A
–Cowdry bodies in HSV (acidophilic)
–CMV has basophilic owl’s eye nuclear inclusions as well as cytoplasmic inclusions
9
Q
What is the most important histopathologic indicator of CNS injury?
A
Gliosis (hypertrophy and hyperplasia of astrocytes)
10
Q
What is the role of astrocytes?
A
- metabolic buffers and detoxifiers in the brain
- foot processes contribute to the blood brain barrier
11
Q
Describe what happens to astrocytes in the process of gliosis.
A
- nuclei enlarge and develop prominent nucleoli
- nuclei become vesicular
- cytoplasm expands and becomes bright pink
- nuclei is displaced from the center of the cell
- these types of cells are called gemistocytes
12
Q
What are Alzheimer Type II Astrocytes that form during gliosis?
A
- nucleus 2-3x larger
- pale central chromatin
- intranuclear glycogen droplet
- prominent nuclear membrane and nucleolus
13
Q
What types of diseases are commonly associated with Alzheimer Type II Astrocytes?
A
- hyperammonemia (chronic liver dz)
- Wilson Disease
- hereditary metabolic disorders of the urea cycle
14
Q
What is a craniopharyngioma?
A
- -slow-growing tumor located above the sella turcica
- -remnant of Rathke’s pouch
- -contains keratin b/c it’s derived from epithelium
- -children (5 to 15yrs), and adults > 65yrs
- -hemorrhage, calcification, “machine oil” fluid cysts
15
Q
What are Rosenthal Fibers?
A
–thick, elongated, eosinophilic, irregular structures that occur within astrocytic processes in areas of long-standing gliosis
–contain alphaB-crystalline and HSP27
16
Q
What tumor is characteristically associated with Rosenthal Fibers?
A
- pilocytic astrocytoma
- -seen in younger people
- also Alexander Disease
- -leukodystrophy w/ mutation of gene encoding GFAP
17
Q
What is Corpora Amylacea?
A
- result of injury, increase w/ age and degeneration
- PAS+ polyglucosan bodies
- concentrically lamellated structures
- subpial and perivascular locations
- consist of glycosaminoglycan polymers and HSP’s
18
Q
What are microglia?
A
- -macrophages of the CNS, mesoderm-derived
- -surface markers CR3 and CD68 (
19
Q
How do microglia respond to CNS injury?
A
- proliferate
- elongate their nuclei (rod cells in neurosyphilis)
- microglial nodules (aggregate around foci of necrosis)
- neuronophagia (congregate around dying neurons)
20
Q
What are characteristics of oligodendrocytes in response to CNS injury and examples of diseases where oligodendrocytes are injured?
A
-apoptosis in acquired demyelinating disorders and leukodystrophies
- PML (progressive multifocal leukoencephalopathy)
- -viral intranuclear inclusions
- MSA (multiple system atrophy)
- -glial cytoplasmic inclusions of alpha-synuclein
21
Q
How are ependymal cells (ciliated columnar cells that line the ventricles) affected by CNS injury?
A
- subependymal astrocytes proliferate and cause ependymal granulations (small irregularities on the ventricular surface)
- CMV causes viral inclusions in ependymal cells
22
Q
In regards to cerebral edema, what is vasogenic edema?
A
–increased EXTRAcellular fluid (shift from intravascular compartment to intercellular spaces)
–due to blood-brain-barrier disruption and increased vascular permeability (ex: caused by ischemia - damaged vessel walls are leakier)
23
Q
In regards to cerebral edema, what is cytotoxic edema?
A
-increased INTRAcellular fluid (secondary to cell membrane injury)
24
Q
Why is excess extracellular fluid, as seen in vasogenic edema, difficult to resorb?
A
-there aren’t many lymphatics in the brain
25
What is the gross appearance of cerebral edema?
- flattened gyri
- narrow sulci
- compressed ventricles
- can lead to herniation
26
What is Hydrocephalus Ex Vacuo?
- compensatory increase in ventricular volume due to a loss of brain parenchyma, but CSF pressure is normal
- ventricles "inflate" to push the brain back out to decrease tension on subarachnoid bridging vessels
27
What are the physical changes in response to increased cerebral spinal fluid in the setting of hydrocephalus?
- Papilledema (d/t increased intracranial pressure)
- enlargement of the 3rd ventricle downward
- stretching and perforation of the septum pellucidum
- thinning of the cerebral mantle
- elevation of the corpus callosum
28
What are possible obstructive causes of hydrocephalus?
- blockage of the interventricular foramina d/t exudates, tumors, infection, hemorrhage or clots
- congenital aqueduct stenosis or atresia of foramina
29
What is a possible cause of hydrocephalus due to overproduction of CSF?
- choroid plexus papilloma (rare)
- -has a thick fibrous core/stalk
- -picture in the lecture looked like broccoli
30
Describe how pyogenic meningitis is an obstructive cause of hydrocephalus.
- suppurative exudate covers the brainstem and cerebellum (most often seen in TB)
- leptomeninges is thickened
31
What are congenital causes of hydrocephalus?
- TORCH infections
- AV malformations
- Arnold Chiari malformations
- Dandy Walker Syndrome
- Cranial defects (achondroplasia, craniostenosis)
32
What are acquired causes of hydrocephalus?
- meningitis, cysticercosis (T. solium), or brain abscesses
- neoplasms (medulloblastoma, astrocytoma)
- choroid plexus papilloma/carcinoma
- sagittal sinus thrombus
- hypervitaminosis A (softens skull, fontanelles bulge)
33
True or False: ventricles are enlarged symmetrically in communicating hydrocephalus.
True, the ventricular system is in communication with the subarachnoid space where absorption happens and the entire ventricular system is enlarged
34
What is Normal Pressure Hydrocephalus?
- symmetric hydrocephalus in patients usually over the age of 60 that has developed slowly due to gradual blocking of the drainage of CSF; normally idiopathic
- ventricles slowly enlarge so fluid pressure is normal
35
What are the symptoms of Normal Pressure Hydrocephalus?
- dementia
- gait disturbance ("magnetic gait")
- urinary incontinence
-"wet, wacky, wobbly" mnemonic
36
Is Normal Pressure Hydrocephalus reversible or irreversible?
Reversible
37
What is a subfalcine herniation?
- when the cingulate gyrus is displaced below the falx
| - aka "cingulate herniation"
38
What is a transtentorial (aka uncinated or uncal) herniation?
- when the medial aspect of the temporal lobe (the uncus on the parahippocampal gyrus) is compressed against the tentorium
- CN3 defects (dilated pupil or impaired eye mvmt)
39
What is a tonsillar herniation?
-when the cerebellar tonsils are displaced through the foramen magnum
--can be life-threatening d/t compression of the respiratory and cardiac centers
40
What is Kernohan's Notch Phenomenon?
- when a transtentorial herniation is severe enough to push the cerebral peduncle to the opposite side and compress it, causing ipsilateral hemiparesis since the peduncle contains motor fibers that cross the body
- a false localizing sign
41
What are Duret Hemorrhages?
-when a transtentorial herniation progresses and causes hemorrhagic lesions in the midbrain and pons
--linear or flame-shaped lesions in the midline or paramedian, d/t distortion/tearing of vessels supplying upper brainstem
42
What neurons are most sensitive to hypoxia?
-neurons in the pyramidal cell layer of the hippocampus, especially area C1 (aka Sommer Sector)
- cerebellar Purkinje cells
- pyramidal neurons in the cerebral cortex
43
What type of necrosis occurs in the CNS?
Liquefactive Necrosis
- denaturation of intracellular proteins
- enzymes from the lysosomes of the dying cell digest it
- tissue becomes a viscous mass
- no architectural remains
44
True or False: in regards to malformations and developmental disorders, the earlier the malformation occurs, the more severe the phenotype
True
45
What is the most common type of malformation?
- neural tube defects d/t folate deficiency
| - neural tube normally closes by Day 28 of gestation
46
What is spina bifida occulta?
- neural tube defect that's only a bony defect
- asymptomatic
- a dimple or a tuft of hair over the region may exist
47
Describe the more severe presentation of spina bifida.
- flattened, disorganized segment of spinal cord
| - associated w/ an overlying meningeal pouch
48
What is an encephalocele?
--diverticulum of disorganized BRAIN tissue extending through a cranial defect (usually posterior fossa)
--called a "nasal glioma" (kind-of a misnomer) when the tissue extends through the cribriform plate
49
What is anencephaly?
- malformation of the anterior end of the neural tube
| - absence of most of the brain and calvarium d/t disruption of forebrain development around 28 days gestation
50
What is the Area Cerebrovasculosa?
- only thing present in anencephaly
- flattened remnant of disorganized brain tissue admixed w/ ependymal, choroid plexus, and meningothelial cells (posterior fossa may be spared)
51
What is Lissencephaly?
- a forebrain anomaly
- reduction in the number of gyri
- agyria = NO gyri
52
What is Microgyria?
- small, unusually numerous, irregularly formed cerebral convolutions
- grey matter has four or fewer layers w/ meningeal tissue trapped at points of fusion that would normally be cortical surface
53
What is hydranencephaly?
- brain defect where cerebral hemispheres are mostly absent, and the cranial cavity is filled with a cystic sac
- only remnants of the basal ganglia and posterior lobe are present
54
What is a dermal sinus?
-indentation or opening between the cutaneous ectoderm and the neuroectoderm, usually over lumbosacral region
55
What is a meningocele?
-extrusion of the meninges through a defect in the vertebral column
56
What is a myelomeningocele?
- expansion of CNS tissue through a defect in the vertebral column; accompanied by motor and sensory deficits in the lower extremities, as well as disturbances in bowel and bladder control
- often complicated by infections that extend into the spinal cord from the thin, overlying skin
57
What is an Arnold-Chiari malformation?
- small posterior fossa
- misshapen midline cerebellum
- extension of vermis through foramen magnum
-almost always includes hydrocephalus and lumbar myelomeningocele
58
What causes forebrain anomalies?
-abnormalities in the generation and migration of neurons
59
What are characteristics of microcephaly?
-decrease in the number of neurons in the neocortex, resulting in simplification of gyral folding
- usually associated w/ small head circumference
- more common than megalocephaly
-d/t chromosome abnormality, fetal alcohol syndrome, HIV-1 acquired in utero, Zika virus
60
What are neuronal heterotopias?
- group of disorders caused by the presence of collections of neurons in inappropriate locations along the path of migration
- associated w/ epilepsy
61
What are two examples of neuronal heterotopias?
--mutations in the gene for filamin A, an actin-binding protein (on X chromosome); lethal in males
-DCX gene mutation (on X chromosome); lissencephaly in males, subcortical band heterotopias in females
62
What is holoprosencephaly?
- incomplete separation of cerebral hemispheres
- midline facial abnormality, causing cyclopia
- can have arrhinencephaly, absent olfactory CN's
- associated w/ Trisomy 13
- can be d/t mutations in SHH pathway
63
What are the characteristics of agenesis of the corpus callosum?
-absence of the white matter bundles that carry cortical projections between hemispheres
- "batwing deformity" of lateral ventricles
- mental retardation common, but not always present
64
What is Dandy Walker Malformation?
- enlarged posterior fossa
- expanded roofless 4th ventricle
- absent or rudimentary cerebellar vermis
- -instead, replaced by cyst w/ ependymal lining that is contiguous w/ the leptomeninges on its outer surface
65
What is Joubert Syndrome?
- hyperplasia of the cerebellar vermis
- elongation of the cerebral peduncle
- altered brainstem shape
- "molar tooth sign" on imaging
66
What is Syringomyelia?
- -fluid-filled cavity in inner portion of spinal cord
- -generally manifests in teens and 20's
--classic symptom: cape-like distribution of pain and temperature sensation loss of upper extremities
67
What is Hydromyelia?
--expansion of ependymal-lined central canal of the spinal cord; same symptoms as Syringomyelia
68
What are the symptoms of Dandy Walker?
- slow motor development; lack of muscle coordination
- irritability
- vomiting
- convulsions; unsteadiness
- bulging at the back of the skull; heart malformations
69
What is Cerebral Palsy?
- -non-progressive neurologic motor deficit
- -attributed to prenatal and postnatal insults
--symptoms: spasticity, dystonia, ataxia, athetosis (abnormal muscle ctx causing writhing mvmts), paresis
70
What are intraparenchymal hemorrhages?
- seen in the germinal matrix of premies, near the junction b/w the thalamus and the caudate nucleus
- can lead to hydrocephalus d/t subarachnoid hemorrhage if the hemorrhage spreads into ventricles
71
What is periventricular leukomalacia?
- infarct of supratentorial periventricular white matter
- chalky yellow plaques, necrosis, calcification
- occurs in premies
72
What is multicystic encephalopathy?
- when both grey and white matter are damaged due to severe ischemia
- large destructive cystic lesions develop throughout the hemispheres
73
What is ulegyria?
- perinatal ischemic damage to the cerebral cortex
- the depths of the sulci suffer the most
- result in thinned, gliotic gyri
74
Where are head impacts common during falls while conscious versus falls during a loss of consciousness?
Awake: occipital impact
LOC: frontal impact
75
What is a diastatic fracture?
-fracture that crosses a suture
76
True or False: subsequent skull fractures can cross previous fracture lines
False; later fractures do NOT extend across previous fracture lines
77
What is a displaced/depressed skull fracture?
-fracture where the bone is displaced into the cranial cavity by a distance greater than the thickness of the bone
78
What are the characteristics of a basilar skull fracture?
- orbital and/or mastoid hematomas
- CSF drainage from the nose or ear
- "raccoon" eyes
79
What is a TBI?
-damage to brain resulting from external mechanical force
- diminished/altered state of consciousness
- temporary or permanent impairment of brain function
80
True or False: head injury and TBI are synonymous
False
81
What is Chronic Traumatic Encephalopathy?
- brain disease linked with repeated blows to the head
- can only be Dx by examining postmortem brain
- progressive loss of normal brain matter
- abnormal buildup of tau protein
- combat veterans and contact sports athletes at risk
82
What are symptoms of Chronic Traumatic Encephalopathy?
- behavioral and mood changes
- memory loss
- cognitive impairment
- dementia
83
What is a coup contusion?
-contusion at the point of impact
84
What is a contrecoup contusion?
- diametrically opposed contusion from point of injury
- occurs when the head is mobile at the time of injury
- occurs during sudden deceleration
85
What is Plaque Jaune?
- old traumatic lesions
- depressed, yellow patches on gyral crests
- can become epileptic foci
- most common at sites of contrecoup injuries
- -inferior frontal cortex, temporal and occipital poles
86
What are the characteristics of Diffuse Axonal Injury?
- axonal swelling and focal hemorrhagic lesions
- can occur d/t angular acceleration alone, w/o impact
-best seen with silver stain, or amyloid precursor protein and alpha synuclein immunostains
87
True or False: about half of post-trauma coma patients have diffuse axonal injury, even w/o cerebral contusions
True
88
What types of injuries might appear in a shaken baby?
- diffuse axonal injury
- cerebral edema
- subdural hematomas (venous)
- retinal hemorrhages
- sometimes microscopic iron from old bleeding
89
What are characteristics of trauma to the epidural space?
- usually associated w/ a skull fracture in adults
- rapid neurologic symptoms
- arterial blood
90
What are the characteristics of trauma to the subdural space?
- level of trauma may be only mild
- slow neurologic symptoms, often delayed from injury
- venous blood
91
What are characteristics of trauma to the subarachnoid space?
- sudden onset of severe headache
- rapid neurologic deterioration
- secondary injury may arise d/t vasospasm
92
What is the artery most commonly insulted in the brain?
-middle meningeal artery
