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Alzheimer -etiology
- AMYLOID PRECURSOR PROTEIN IS ABNORMALLY CLEAVED
- Normal cleavage : Abeta 40 --> cannot aggregate
- Abnormal cleavage: Abeta 42 --> senile plaque
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Genes associated with Alzheimers
Amyloid precursor protein (APP)
Presenilin 1, presenilin 2 (early onset)
E4 allele of apolipoprotein E
- Genetic or acquired defects in APP processing result in accumulation of amyloid
- containing A4Beta.
- ? Amyloid is a primary or secondary event.
- Amyloid plaques and cerebral amyloid angiopathy.
Neurofibrillary tangles- Paired helical filaments with hyperphosphorylated tau in neurons.
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In Alzheimer, Genetic or acquired defects in APP processing result in
accumulation of amyloid containing A4Beta.
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In Alzheimer, Paired helical filaments with hyperphosphorylated tau in neurons.
Neurofibrillary tangles
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Alzheimer's 4 features
Plaques
Neurofibrillary tangles (***correlate best with disease)
- Congophilic amyloid angiopathy
- (cerebral amyloid angiopathy, CAA)
Granulovacuolar Degeneration of Simchowicz
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ALZHEIMER DISEASE - what is it, its etiology, its microscopic presentation, cause of death
SLOWLY EVOLVING DEMENTIA
PLAQUES AND AMYLOID ANGIOPATHY CONTAIN A4-Beta
NEUROFIBRILLARY TANGLES CONTAIN TAU PROTEIN
TANGLES CORRELATE WITH DZ
DEATH FROM PNEUMONIA, SEPSIS
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Amyotrophic Lateral Sclerosis
- Rapidly progressive, fatal disorder that attacks neurons (brain, spinal) controlling
- voluntary muscles
Causes wasting of muscle resulting in respiratory failure
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ALS- results in
denervation atrophy
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ALS - genetic component
SOD1- antioxidant functions implicated in some familial forms. TDP43 in sporadic ALS.
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True or false
Elevated glutamate (neurotransmitter toxicity) may mediate ALS
True
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True or False
In ASL, the disease affects both muscle and sensory fxn because of the demylination
false
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Definition of Stroke
Rapidly progressive
Irreversible
Non-convulsive neurologic deficit >24 hr
- 70-80% from infarcts and 20-30% from
- hemorrhages in Western world
Includes cerebral infarcts and hemorrhages
- Cerebral infarcts (localized injury related to ischemia/hypoxia) include thrombotic,
- embolic, and hemorrhagic reperfusion injuries
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Stroke: TIA
This is a transient ischemic attack in which neurologic symptoms are from transient vascular obstruction. < 24 hrs
1/3 of TIA patients will have significant infarcts in 5 years
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Stroke: F.A.S.T.
F= FACE Ask them to smile. Does one side droop?
- A= ARMS Ask to raise both arms. Does
- one arm drift downward?
S= SPEECH Ask the person to repeat a simple phrase. Does the speech sound strange or slurred?
T= TIME See any of these signs. Time to CALL 911.
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Stroke: INFARCTS
Local interruption of blood flow
Risk factors: 70 yo, male, atherosclerosis (hypertension, diabetes, smoking)
Thrombosis in atherosclerotic vessels
Emboli from heart or atherosclerotic vessels
Extensive vascular anastomoses in the Circle of Willis may mitigate a stroke
Edema maximal at 3-4 days
Cystic and liquified by 6 months
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Stroke: Hemorrhages
Hypertension/Atherosclerosis
Coagulopathies (Blood thinners, liver failure, defective coagulation factors)
Saccular Aneurysms
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STROKE - risk factor
Atherosclerosis, hypertension, and coagulopathies are important risk factors
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Stroke - causes
Hemorrhage and infarct
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BRAIN TUMORS
Prevalence: 360,000 primary brain tumors
Most common intraaxial/intrinsic brain tumor is glioblastoma
Most common extraaxial/meninges-based tumor is meningioma
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Glioblastoma
MEDIAN SURVIVAL: 1 year
AGGRESSIVE INFILTRATIVE INTRAXIAL (PARENCHYMAL) TUMOR
HIGH GRADE
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Extraaxial Tumors
Most common is meningioma
A tumor derived from arachnoidal cells
Mostare benign- slow growing. Grade I can recur. Some are aggressive and can metastasize distantly.
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Brain tumor morphology
- FALCINE
- Convexity
- WHORLS ARE TYPICAL OF MENINGIOMA
- Can be fibrous with much collagen
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Intraaxial vs extraaxial: which one is better to cure
extraaxial
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BRAIN TUMOR's intraaxial
Glioblastoma- malignent -
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Brain tumor - extraaxial
Menigioma - often beign
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In Multiple Sclerosis, The neurologic symptom progress
Waxing and waning
Sharply demarcated demyelinated plaques are typical (Axons are intact)
Dawson’s fingers
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Multiple Sclerosis is probably caused by
- autoimmune and Sharply
- demarcated demyelinated plaques are typical (Axons are intact
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MS's brain scan presentation
Dawson finger
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