Demyelinating, Degenerative, Genetic, Toxic, Eye Disease Flashcards
1
Q
What are examples of demyelinating diseases?
A
Multiple Sclerosis (MS)
Neuromyelitis Optica/Devic Disease
Acute Disseminated Encephalomyelitis (ADEM)
Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)
Central Pontine Myelinolysis
2
Q
What are examples of degenerative diseases?
A
Alzheimer’s
Frontotemporal Dementias
--> Pick's
--> Progressive
Supranuclear Palsy
--> Vascular Dementia
Parkinson's
Huntington’s
Amyotrophic Lateral Sclerosis (ALS)
3
Q
Are demyelinating diseases inherited or acquired?
A
acquired
4
Q
Describe demyelinating disorders
A
preferentially damage myelin
relative preservation of axons (c/t ischemia where neurons die so axons disappear)
limited capacity for CNS to replenish myelin
5
Q
Are demyelinating leukodystrophies immunologic or inherited?
A
inherited
6
Q
Define multiple sclerosis (MS)
A
distinct episodes of neuro deficits separated in time d/t white matter lesions separated in space
–> 1 sx at a time, caused by lesions in diff parts of brain (or brain and spinal cord)
7
Q
Is MS autoimmune?
A
YES
autoimmune demyelinating disorder
8
Q
Describe the duration of MS
A
relapsing and remitting episodes of variable duration (wk-mon-yrs)
Neuro def–> gradual partial recovery
9
Q
What happens to MS patients as they age?
A
frequency of relapses decline, but neuro deterioration continues to be steady
little sx but still progressing
10
Q
What is the frequent initial presentation for MS?
A
unilateral visual impairment (optic neuritis, retrobulbar neuritis)
(also can be urinary d/t loss of bladder control)
11
Q
10-50% of patients with this disease develop MS, thus need careful f/u.
A
optic neuritis
12
Q
What are common brainstem MS sx?
A
ATAXIA NYSTAGMUS CN signs Intranuclear ophthalmoplegia ----> can't adduct eye
13
Q
What are common spinal cord MS sx?
A
Motor and sensory impairment of trunk and limbs
spasticity
difficulty with voluntary control of bladder
14
Q
Are women or men more affected by MS?
A
Women, temperate zones
15
Q
What are the genetic factors that predispose to MS?
A
15x if 1st degree relative (mother-daughter)
150x if mono twin affected
16
Q
What genes are implicated in MS?
A
DR2 (MS susceptibility)
IL-2 and 7 receptor genes
17
Q
When is it rare to get MS?
A
childhood
over 50
18
Q
Describe the pathway of chronic inflammation in MS
A
CD4+ Th 1 and 17 cells react against SELF-MYELIN Ag and secrete cytokiens
Th1–> IFN gamma–> + macrophages
Th17–> recruit leukocytes
19
Q
What are in plaque infiltrates in MS?
A
T cells (mainly CD4 but some CD8 and macrophages)
20
Q
Is MS a disease of the white or gray matter?
A
white (myelin)
21
Q
What is the gross appearance of MS?
A
multiple well circumscribed, slightly depressed, glassy, gray-tan irregular shaped PLAQUES
with gliosis d/t inflammation–> sclerosis of plaques that make it firmer than surrounding white matter
usually around lateral ventricles with sharp borders
22
Q
What should be your first thought if you see multiple periventricular plaques on MRI?
A
MS
23
Q
What structures are affected in MS?
A
optic nerves and chiasm
brainstem
ascending and descending fiber tracts
cerebellum
spinal cord
24
Q
Are axons preserved in MS?
A
YES–> demyelinating disorder
25
What is the general progression of plaques in MS?
- ongoing myelin breakdown
- abundant macrophages (lipid rich, PAS + debris from myelin)
- perivascular lymphocytes at outer edge of plaque with relative preservation of axons and depletion of oligodendrocytes
-->
quiescent, inflammation disappears, gliosis and astrocyte prolif
-->
not sharply circumscribed, resolving
26
CSF findings in MS
mildly elevated protein
moderate pleocytosis (increased WBC)
increased IgG
Oligoclonal IgG bands
27
Define neuromyelitis optica
BL optic neuritis and spinal cord demyelination AT SAME TIME (spares brain)
considered variant of MS
28
CSF of neuromyelitis optica
Neutrophils, increased opening pressure, turbid (cloudy)
*****looks like CSF of bacterial meningitis, but doesn't have decrease in glucose
29
Neuromyelitis optica Ab
antibodies to aquaporins (NMO) that maintain astrocyte foot processes (and also BBB)
30
Neuromyelitis optica tmt
steroid and plasmapheresis to remove Ab
immunosuppression
31
Define Acute Disseminated Encephalomyelitis (ADEM)
perivenous encephalomyelitis
diffuse monophasic demyelinating disease that FOLLOW VIRAL infection or immunization
32
Describe sx onset of Acute Disseminated Encephalomyelitis (ADEM)
1-2 weeks after infection
HA
lethargy
coma
33
What is the prognosis of Acute Disseminated Encephalomyelitis (ADEM)?
20% die
| 80% recover completely
34
Morphology of Acute Disseminated Encephalomyelitis (ADEM)
grayish discoloration around white matter vessels
myelin loss with axon preservation
PMN or lymphocytes
accumulation of lipid-laden macrophages from myelin breakdown
35
What cells are seen early in Acute Disseminated Encephalomyelitis (ADEM)?
PMNs (neutrophils)
36
What cells are seen late in Acute Disseminated Encephalomyelitis (ADEM)?
Mononuclear (lymphocytes)
37
What is Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)?
sudden onset of CNS demyelination in YOUNG ADULTS and CHILDREN
38
What is the prognosis of Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)?
most often fatal
if survive--> significant defects
39
What causes Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)?
recent URI (virus)
40
Is Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE) common?
No, rare
often distractor
41
What is Central Pontine Myelinolysis?
loss of myelin with neuro sx d/t overcorrection of sodium
42
What would you see on CT if a patient had Central Pontine Myelinolysis?
demyelination in the center of the pons
43
What are the sx of Central Pontine Myelinolysis?
```
acute paralysis
dysphagia
dysarthria
diplopia
LOC
```
all occur very quickly
44
What causes Central Pontine Myelinolysis?
severe electrolyte/osmolar imbalance
| --> overcorrection of sodium when hyponatremic
45
What is the tmt for Central Pontine Myelinolysis?
liver transplant
46
Describe the histology/morphology of Central Pontine Myelinolysis
Symmetric loss of myelin in basis pontis and portions of pontine tegmentum
no inflammation
neurons and axons preserved
47
What is the difference between demyelinating and degenerative diseases?
demyelinating--> lose myelin, so WHITE matter
degenerating--> lose neurons first, GRAY matter
48
Describe degenerative diseases
Gray matter
progressive loss of neurons
protein aggregates/inclusions hallmark of diseases
---> CAG, tau, amyloid, etc
49
How do proteins accumulate in degenerative disease?
resistant to degradation through ubiquitin-proteasome system
50
Protein aggregate/inclusion in Huntington disease
```
polyglutamine repeats (CAG)
--> mutated protein
```
51
Protein aggregate/inclusion in Alzhemier's disease
amyloid beta
| --> peptide derived from larger precursor protein
52
Protein aggregate/inclusion in Parkinson's disease
alpha-synuclein
| --> unexplained alteration of normal cellular protein
53
Define dementia
progressive loss of cognitive function
54
Is dementia a normal part of aging?
NO!!!! always pathologic
55
What is the most common cause of dementia in the elderly?
Alzheimer's
56
Describe Alzheimer's disease
insidious impairment of higher intellectual function, alterations in mood and behavior
57
What is the timeline for Alzheimer's disease?
early: impairment of higher intellectual function, mood and behavior changes
late: progressive disorientation, memory loss, aphasia (demonstrates severe cortical dysfunction)
within 5-10 years of sx: profound disability, mute, immobile
58
Is Alzheimer's symptomatic before age 50?
not typically
if before 50, usually familial form with rapid decline
59
What is the correlation between age and Alzheimer's?
incidence rises with age
doubles every 5 years
60
Are most cases of Alzheimer's disease sporadic or familial?
sporadic
5-10% familial
61
What is necessary to diagnose Alzheimer's?
examine brain (after death)
62
Describe the atrophy progression in Alzheimer's disease
GLOBAL cortical atrophy with widened sulci
first starts in frontal and temporal lobes, then progresses to parietal and ends with occipital
63
What hydrocephalus is associated with Alzheimer's and why?
ex vacuo
cortical atrophy in brain--> less mass--> shrinks--> brain compensates with excess fluid--> ventricular enlargement
64
What general histology do you see in Alzheimer's?
plaques and neurofibrillary tangles
65
What types of plaque exist in Alzheimer's and what's the main difference between them?
Neuritic (senile)--> amyloid core
Diffuse--> no amyloid core
66
Where do you find neuritic plaque in AD?
hippocampus, amygdala, neocortex
reactive astrocytes and microglia in periphery
67
What stain do you use to identify the amyloid core in neuritis plaques of AD?
Congo red
derived from amyloid precursor protein (APP)
68
Where do you find diffuse plaque in AD?
superficial cortex, basal ganglia, cerebellum
early stage of neuritic plaque development
69
What condition has early onset AD?
Down syndrome
70
What is the location of plaque vs tangles in AD?
plaques outside of cells
tangles inside cells
71
Describe neurofibrillary tangle shape
bundles of filaments in cytoplasm of neuron
pyramidal neurons--> flame d/t displaced nucleus
globose or basket weave of fibers around nucleus (d/t tangles encircle nucleus)
72
What is an abnormally hyperphosphorylated, axonal microtubule-associated protein that enhances assembly and is implicated in AD?
tau
--> MAP2 and ubiquitin proteins
73
What stain is used to identify neurofibrillary tangles?
Bielschowsky stain (silver stain)
74
When would you see ghost or tombstone neurofibrillary tangles?
when they are resistant to clearance in vivo and the neuron is dead--> just see outline made by tangles
75
What is highly associated with severe cognitive dysfunction?
large number of plaques and tangles
76
Do tangles or plaques correlate better with degree of dementia?
tangles
77
What are hirano bodies?
elongated, glassy, eosinophilic bodies
ACTIN major component
hippocampal pyramidal cells
seen in AD
78
What is granulovacuolar degeneration?
small, clear intraneuronal cytoplasmic vacuoles (lose definition)
normal aging to have few
AD have lots
79
What is cerebral amyloid angiopathy (CAA)?
thick vessel walls with the same amyloid protein as AD
use Congo red stain
accompanies Alzheimer's disease
80
What is the significance of Congo red stain?
when polarized--> apple green birefringence
means there is amyloid
81
What is the connection between CAA and AD?
if you have Alzheimer's, you have CAA
if you have CAA, doesn't mean you have Alzheimer's
82
Describe frontotemporal dementias
share clinical features of progressive behavior and language changes
with tau: pick, progressive supranuclear palsy
without tau: vascular dementia (HTN related)
83
Describe sx of Pick disease
EARLY ONSET of behavior changes, then language changes
first goes to frontal lobe (behavior changes) then temporal lobe (language disturbances)
84
Describe gross/histo appearance of brain in Pick disease
asymmetric atrophy of frontal and temporal lobes
spares posterior 2/3 superior temporal gyrus, occipital and parietal lobes (like someone drew line where atrophy stops)
KNIFE-EDGE thin gyri
-->really wide sulci
Pick cells and bodies (cytoplasmic inclusions, basophilic and stain silver)
85
What is Pick disease?
rare, distinct, progressive dementia
most sporadic forms
86
What is the main difference between Pick and AD when looking at the brain?
Pick affects frontal and temporal
AD is global atrophy
87
Define progressive supranuclear palsy
truncal rigidity in 50-70 Men
fatal within 5-7 years of onset
widespread neuronal loss
globose tangles
tau protein
88
Describe vascular dementia
if d/t vasculitis--> dementia improves with treatment
if d/t progressive cognitive disorder a/w vascular injury (HTN): widespread infarction, diffuse white matter injury
89
Degenerative diseases of basal ganglia and brainstem are associated with ______________
movement disorders
rigidity, abnormal posturing, chorea (dancing, unpredictable involuntary muscle movements)
90
What pathway is implicated in Parkinson's disease?
nigrostriatal pathway
91
What are sx of Parkinson's disease?
Pill rolling movement of hand
persistent tremors that go away when reaching for something
shuffling gait, small steps that accelerate, hunched over (festinating gait)
slowness of voluntary movement
rigidity
diminished facial expressions
92
What disease is misdiagnosed as Parkinson's early on?
Huntington's disease
93
Rest tremor vs intention tremor
Parkinson vs cerebellar lesion (MS, stroke)
94
Damage to the nigrostriatal dopaminergic system can cause what diseases?
Parkinson Disease
Multiple System Atrophy
Postencephalitis Parkinsonism
95
What are sx of Parkinson's that respond to L-Dopa?
tremor
rigidity
bradykinesia
96
What is the inheritance pattern for Parkinson's?
AD
alpha-synuclein on Chr 4
97
What is the protein involved in juvenile AR Parkinson's?
parkin
98
What happens to the substantia nigra in Parkinson's and why?
loses pigment (black to white)
lewy bodies push pigment out to rim of neuron--> when neurons die, lose pigment
99
Describe Parkinson's disease morphology
Pallor of substantia nigra and locus ceruleus
lewy bodies (eosinophilic, dense core of alpha-synuclein and pale halo)
100
Describe dementia with lewy bodies
Parkinson disease with cognitive dysfunction
--> 10-15% parkinson patients develop dementia, increases with age
HALLUCINATIONS
lewy neurites contain alpha-synuclein aggregated protein
depigmentation of substantia nigra and locus ceruleus
--> preservation of cortex, hippocampus and amygdala
101
Describe Multiple System Atrophy
sporadic disorder, alpha-synuclein in oligodendrocytes with 3 involved systems:
1. striatonigral circuit--> parkinsonism
2. ataxia
3. autonomic dysfunction (ex: orthostatic hypotension)
102
What happens to brain morphology in Huntington disease?
Normally, caudate and putamen are round
HD: they become very flat with wide sulci (atrophy)
103
What is unique about Huntington disease?
one of few AD lethal diseases
104
Describe Huntington disease
progressive movement disorder and dementia
degeneration of striatal neurons
105
Sx of HD
jerky, hyperkinetic movements-->chorea (dancing)
106
What is the outlook on HD?
death after 15 years
progressive
107
What can you develop in the later stages of HD?
Parkinsonism with bradykinesia and rigidity
108
What protein is involved in HD?
Huntingtin (toxic gain of fxn)
--> form intranuclear inclusions
CAG repeats on Chr 4p16.3
109
What is anticipation?
repeat expansions of CAG during spermatogenesis--> juvenile form HD
110
What is the relationship between HD and CAG repeats?
lower number, less likely to get HD or older when have sx
40-50 (adult); over 60 (juvenile)
111
What is the pathology of HD?
loss of medium spiny striatal neurons--> dysregulation of basal ganglia circuit that normally dampen motor output
112
Why do you have cognitive changes in HD?
neuronal loss from cortex
113
Describe gross brain appearance in HD
Striking atrophy of caudate nucleus, then putamen
globus pallidus atrophy
atrophy in frontal lobes
severe loss of striatal neurons, most in caudate nucleus
severity of sx= degree of degeneration
114
What are spinocerebellar ataxias?
characterized by sx of cerebellum (progressive ataxia), brainstem, spinal cord and peripheral nerves
neuronal loss from affected area + secondary degeneration of white-matter tracts
115
What are 2 forms of spinocerebellar ataxias?
Friedreich Ataxia
Ataxia-Telangiectasia
116
What protein and inheritance type is Friedreich Ataxia?
AR
GAA repeat on Chr 9
FRATAXIN protein
also mitochondrial disorder
117
When do you first see Friedreich Ataxia symptomology?
First 10 years with gait ataxia
--> hand clumsiness, dysarthria
118
What are reflex grades in Friedreich Ataxia?
DTR depressed or absent
extensor plantar reflex + (babinski normally resolves at 24 months)
119
What is a hallmark sx of Friedreich Ataxia?
Cardiac arrhythmias and CHF
pes cavus and kyphoscoliosis
loss of pain, temp, sensation, light touch
DM
wheelchair after 5 years
120
What is the COD in Friedreich Ataxia?
intercurrent pulmonary infections and cardiac disease
d/t kyphoscoliosis and cardiac issues
121
What is the inheritance and protein in Ataxia-Telangiectasia?
AR
ATM gene on Chr 11q22-q23
--> DNA breaks, fails to remove cells with DNA damage
122
When do sx of Ataxia-Telangiectasia first appear?
early chilhood
die in 20s
123
What are sx of Ataxia-Telangiectasia?
telangiectasis of CNS, conjunctiva, skin of neck, face and arms
lymphoid neoplasms, gliomas, sarcomas
IMMUNODEFICIENCY with recurrent sinopulmonary infections
124
What is unique about Amyotrophic Lateral Sclerosis (ALS)?
have both LMN and UMN loss of neurons
125
When does Amyotrophic Lateral Sclerosis (ALS) appear?
50+
126
What is the inheritance and protein involved in Amyotrophic Lateral Sclerosis (ALS)?
AD (10% familial)
Superoxide Dismutase (SOD1 on Chr 21)
127
Describe anterior spinal cord roots in Amyotrophic Lateral Sclerosis (ALS)
thin
decreased number of anterior horn neurons throughout SC
128
Describe gross brain and muscles in Amyotrophic Lateral Sclerosis (ALS)
precentral gyrus atrophic
neurogenic atrophy of skeletal muscles
loss of UMN--> degeneration of corticospinal tracts
129
What inclusions are found in Amyotrophic Lateral Sclerosis (ALS)?
bunina bodies
| --> PAS+ cytoplasmic inclusions in neurons
130
What are classic sx of Amyotrophic Lateral Sclerosis (ALS)?
dropping objects
cramping of arms and legs
speaking and swallowing issues
131
What are progressive sx of Amyotrophic Lateral Sclerosis (ALS)?
muscular atrophy
bulbar palsy (degen of lower brainstem-->speaking and swallowing issues)
132
What is the prognosis of Amyotrophic Lateral Sclerosis (ALS)?
Half die within 2 years of dx
133
What other sx are involved in Amyotrophic Lateral Sclerosis (ALS)?
respiratory infections d/t respiratory muscle involvement
fasciculations d/t involuntary muscle contractions
muscles waste away d/t lack of input
134
What diseases involve alpha-synuclein?
Parkinson disease
Multiple System Atrophy
135
What diseases involve Tau?
Alzheimer's
Frontotemporal lobar degeneration
Progressive supranuclear palsy
Corticobasilar Degeneration
136
When would you start to suspect a genetic metabolic disease that affects the nervous system?
when kids miss developmental milestones
137
What inheritance are neuronal storage diseases?
AR
138
What are general sx of neuronal storage diseases when they involve the cortex?
cognitive dysfunction and seizures
139
How do neuronal storage diseases work?
defect in catabolism of sphingolipids, mucopolysaccharides or mucolipids--> accumulation of substrate of enzymes in lysosomes--> neuronal death
140
Are leukodystrophies white or gray matter?
white matter
141
Are mitochondrial encephalomyopathies white or gray matter?
gray matter
also skeletal muscle
142
What is the inheritance pattern for leukodystrophies?
most AR
exception is adrenoleukodystrophy: X linked
143
Describe sx of leukodystrophies
deterioration of motor skills
spasticity
hypotonia
ataxia
144
What causes sx of leukodystrophies?
myelin abnormalities
lack neuronal storage defects but have lysosomal or peroxisomal enzymes
145
What causes mitochondrial encephalomyopathies?
oxidative phosphorylation disorders
mutations in mito genome
affects muscle first, then CNS
146
What enzyme is involved in Tay-Sachs?
hexosaminidase A
Chr 15
147
What accumulates in neurons in Tay-Sachs?
GM2 gangliosides
148
What is the prognosis of Tay-Sachs?
fine until 1 year old--> mental and physical deterioration
death around 2-3
149
Hallmark of Tay-Sachs
cherry red spots in maculae
normal choroid against swollen, pale, ganglioside-stuffed retina
150
Define MELAS
Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes
151
What is the most common neuro syndrome caused by mitochondrial abnormalities?
MELAS
152
What is the mutation that causes MELAS?
tRNAs
153
What are sx of MELAS?
muscle weakness with lactic acidosis
stroke-like episodes with reversible defects that don't correspond well to specific vascular territories
154
Define MERRF
Myoclonic Epilepsy + Ragged Red Fibers
155
What is the mutation that causes MERRF?
tRNA distinct from MELAS
some overlap between the two
156
What are the sx of MERRF?
Myoclonus
Seizure disorder
Myopathy
Ataxia (neuronal loss from cerebellum)
see ragged red fibers on stain
157
Describe dysfunction behind Kearn-Sayre syndrome
large mitochondrial DNA deletion/rearrangement
158
What are sx of Kearn-Sayre syndrome?
PROGRESSIVE inability to move eyes and eyebrows
ataxia
ophthalmoplegia
pigmentary retinopathy
cardiac conduction defects
spongiform change in gray and white matter--> neuronal loss most in cerebellum
159
Describe Leigh Syndrome
AKA subacute necrotizing encephalopathy
dark areas of degeneration of neural tissue around aqueduct
nuclear and mitochondrial DNA mutations
lactic acidemia, seizures, hypotonia in early childhood--> DEATH within 2 years
160
Describe general outcomes of Vit B12 deficiency
macrocytic, megaloblastic anemia
numbness, tingling, slight ataxia, weakness of extremities
161
Describe neuro sx of Vit B12 deficiency
within a few weeks: numbness, tingling, slight ataxia in LE
rapid progression to spastic weakness of LE
end result is complete paraplegia
162
Can neuro sx of Vit B12 be reduced?
replacement can reverse sx UNTIL complete paraplegia has occurred
163
Describe histology of Vit B12 deficiency
swelling of myelin layers (vacuoles) progress up and down SC via ascending posterior columns and descending pyramidal tracts
--> subacute combined degeneration of SPC (how you get paraplegia)
164
What deficiency causes Wernicke and Korsakoff syndromes?
Thiamine (Vit B1)
165
Describe Wernicke encephalopathy
acute psychotic sx
ophthalmoplegia (weak eye muscles or paralysis)
166
Is Wernicke reversible?
can with thiamine
167
Describe Korsakoff syndrome
memory disturbance and confabulation
168
Is Korsakoff reversible?
no
169
What is a consequence of Beriberi, an what causes it?
cardiac failure
thiamine (B1) deficiency
170
Chronic alcoholism causes a deficiency in ______
thiamine (B1)
--> carcinoma, chronic gastritis, persistent vomiting
171
What is classic histo for Wernicke encephalopathy?
hemorrhage and necrosis of mamillary bodies and walls of 3rd and 4th ventricles
172
Classic gross presentation of hypoglycemia
Pseudolaminar necrosis of large pyramidal neurons in cerebral cortex
affects pyramidal neurons of Sommer's sector of hippocampus and purkinje cells of cerebellum
173
CNS presentation of hyperglycemia
confusion
stupor
coma
174
What cells are found in the CNS with hepatic encephalopathy
Alz type 2
175
Describe gross appearance of brain in carbon monoxide poisoning
RED layers 3 and 4 of cortex, sommer's sector and purkinje cells
BL necrosis of globus pallidi
176
Describe methanol poisoning
selective BL putamenal necrosis
retinal ganglion cell degeneration--> blindness
177
Describe ethanol poisoning
chronic alcoholics (1%)--> truncal ataxia, unsteady gait, nystagmus
atrophy of anterior vermis
Bergmann gliosis
178
What can radiation induce?
tumors--> sarcoma, glioma, meningioma
179
What histo is seen with radiation?
coagulative necrosis, thickened walls with intramural fibrin-like material
180
What is the most common malignant tumor of skin around the eye?
basal cell carcinoma
181
What are hallmarks of basal cell carcinoma around the eye?
```
pearly nodules
telangiectatic vessels
central/rodent ulcer
rolled edged
peripheral palisading nuclei
```
182
Describe sebaceous carcinoma
masquerade syndrome (unilateral keratoconjunctivitis unresponsive to therapy)
necrotic centrally
oil red o fat stain
mets to LN, lung, liver, brain, skull
15% mortality
183
Pinguecula vs Pterygium
Pinguecula: benign adjacent to cornea
Pterygium: on cornea and disrupts vision, often removed
184
What is the most common primary intraocular tumor in adults?
uveal melanoma
185
What oncogenes are mutated in uveal melanoma?
GNAQ and GNA11
although nevi with these genes rarely transform into melanoma
186
Describe morphology of uveal melanoma
epithelioid--> worse prognosis
large nuclei, prominent nucleoli, infiltrating plasma cells and lymphs
187
Where do uveal melanomas spread to first?
liver
188
Survival rates of uveal melanoma
80% 5 year
| 40% 10 year
189
Why are corneal transplants unique?
lack blood vessels and lymphatics--> no rejection
190
What are cataracts?
lenticular opacities that may be congenital or acquired
191
What are risk factors for cataracts?
```
DM
wilson disease
atopic dermatitis
drugs
radiation
trauma
```
192
What is nuclear sclerosis?
age-related cataracts that result from opacification of lens nucleus
193
What is a posterior subcapsular cataract?
migration of the lens epithelium posterior to the lens equator
194
What is a morgagnian hypermature cataract?
lens cortex liquefies
195
What is phacolysis?
proteins from liquefied lens cortex leaks through lens capsule, clogs meshwork and increases intraocular pressure (--> phacolytic glaucoma)
196
What is glaucoma?
collection of diseases with distinct changes in visual field and cup of optic nerve
197
What is most glaucoma associated with?
increased intraocular pressure
198
Describe open-angle glaucoma
complete open access to trabecular meshwork
increased resistance to aqueous outflow--> increased intraocular pressure
199
What is the most common form of glaucoma and what mutations can be involved?
primary open angle glaucoma
MYOC in juveniles
200
Describe the most common form of secondary open angle glaucoma and mutations involved
pseudoexfoliation
LOX1 gene
201
What is angle-closure glaucoma?
peripheral zone of iris adheres to trabecular meshwork and physically impedes outflow of fluid
202
What is the most common primary intraocular malignancy of childhood?
retinoblastoma
neuroblastic origin from retina
Chr 13 long arm, RB gene (nml suppresses development of retinoblastoma)
203
What is the most common sx of retinoblastoma?
leukocoria (white pupillary reflex--> one shines white, the affected one doesn't)
204
Describe pseudohypopyon found in retinoblasoma
cells shed into anterior chamber--> aggregate and form nodules on iris or settle inferiorly
205
Where does retinoblastoma metastasize to?
skull bones, distal bones, brain, spinal cord, LN, abdominal viscera
206
What is the most common route of escape for retinoblastomas?
optic nerve--> brain
poor prognosis when invades optic nerve
207
Histology of retinoblastoma
small round blue cells
Flexner-wintersteiner characteristic
Homer wright rosette
Fleurette rosette
