04b: Path

Question 1

Main 3 causes of brain (parenchymal) hemorrhage:

Answer 1

1. HT
2. Trauma
3. Cerebral amyloid angiopathy

Question 2

(X) hemorrhage results from rupture of parenchymal arterioles that have become less
compliant/weakened due to
replacement of (Y) tissue by (Z) tissue.

Answer 2

X = HT brain (parenchymal) hemorrhage
Y = smooth muscle
Z = fibrocollagenous

(Arteriosclerosis due to chronic HT)

Question 3

List some main causes of weakened vessels, leading to spontaneous SAH.

Answer 3

1. Berry (saccular) aneurysm***
2. Infective aneurysms
3. AV malformations
4. Cerebral amyloid angiopathy

Question 4

(X) hemorrhage usually results from trauma (rapid acceleration/deceleration). Why does this motion cause injury?

Answer 4

X = Subdural (acute)

Causes traction/tearing of the bridging veins between brain and dura

Question 5

(X) hemorrhage is due to cycles of organization and re-bleeding, due to the formation of densely vascular granulation
tissue around the original hematoma.

Answer 5

X = Subdural (chronic)

Question 6

(X) hemorrhage: momentary loss of consciousness, followed by asymptomatic
period (1-48 hrs), followed by the (Y) symptom. If not treated with surgery, patient will die.

Answer 6

X = epidural
Y = high ICP

Question 7

(X) hemorrhage often results
from a skull fracture that
produces tearing of the
(Y) artery.

Answer 7

X = epidural
Y = middle meningeal

Question 8

Epidural hemorrhage: Most common in the (X) fossa in adults and in (Y) fossa in children

Answer 8

X = temporal
Y = posterior

Question 9

(CD4/CD8) lymphocytes predominate in active MS lesions. And (CD4/CD8) in less active lesions.

Answer 9

CD4; CD8

Question 10

T/F: Macrophages present in MS plaque.

Answer 10

True

Question 11

T/F: Axonal bodies are damaged in MS.

Answer 11

False - preserved

Question 12

Presence of reactive (X) is seen in MS plaque.

Answer 12

X = astrocytes

Question 13

(X) Myopathy: Subsarcolemmal and/or intermyofibrillary aggregates that appear reddish (Y) stain.

Answer 13

X = mitochondrial
Y = Gomori Trichrome

Question 14

Soleus has Type (I/II) muscle fibers.

Answer 14

I (one slow fat red ox)

Question 15

(X) myopathies characterized by “ragged red fibers”.

Answer 15

X = mitochondrial

Question 16

Muscular dystrophy: marked by (acquired/inherited) abnormality, (acute/chronic) weakness and elevated serum (X).

Answer 16

Inherited (genetic);
Chronic/progressive;
X = CK

Question 17

Duchenne muscular dystrophy: (X) inheritance pattern with which mutated protein?

Answer 17

X = X-linked

Cytoskeletal protein dystrophin

Question 18

(X) myopathy characterized by perifascicular atrophy of muscle fibers and lymphocytic infiltrates

Answer 18

X = DERMATOMYOSITIS (an inflammatory myopathy)

Question 19

Group atrophy of muscles is indicative of (nerve/muscle) pathology.

Answer 19

Nerve (denervation)

Question 20

Neuronopathy: is a category of (myelin/axon) neuropathy where the primary abnormality is in the (X), with synchronous injury to the (Y). Is regeneration possible?

Answer 20

Axon;
X = cell body
Y = axon

No

Question 21

Repeated episodes of (X) results in “schwannian onion-bulb proliferation”.

Answer 21

X = segmental demyelination and remyelination

Question 22

MCI (mild cognitive impairment) definition

Answer 22

Subjective and objective decline in cognitive abilities that is not severe enough to cause obvious functional impairment

Question 23

T/F: MCI can revert to normal

cognition.

Answer 23

True

Question 24

Most dementia syndromes are either due to (X) or (Y) or some combination of these two.

Answer 24

X = neurodegenerative disorders
Y = vascular brain
injury

Question 25

AD: neurofibrillary tangles consist of (X), a(n) (Y) protein that is critical for axonal transport.

Answer 25

``` X = hyperphosphorylated tau Y = MT-associated ```

Question 26

AD: the severity of dementia (Braak stages) is quantified based on...

Answer 26

How many tangles (density) and where in the cortex they are found (distribution)

Question 27

AD: Initiating event is (X) pathology.

Answer 27

X = amyloid (abnormal generation/clearance)

Question 28

AD: The amyloid cascade involved inappropriate cleavage of (X), a transmembrane protein normally encoded on chromosome (Y).

Answer 28

``` X = APP (amyloid precursor protein) Y = 21 ```

Question 29

AD: Cleavage of APP by a (X), followed by a (Y) leads to the formation of Aβ amyloid fragments.

Answer 29

``` X = beta secretase Y = gamma secretase ```

Question 30

An important clearance pathway Aβ fragments are poorly understood but an important pathway is the (X) system, most active during (Y) sleep.

Answer 30

``` X = perivascular glymphatic Y = slow wave ```

Question 31

T/F: In evaluating dementia, it's most important to focus on current cognitive abilities/tests.

Answer 31

False - HISTORY; focus on changes in cognitive abilities, | usual activities and interests and behaviors in the past 1-5 years

Question 32

T/F: In evaluating dementia patient, important to talk with all available caregivers/child/spouse, preferably as a group.

Answer 32

False - preferably alone (Different family | members may differ in their perceptions of whether something is abnormal and if so what)

Question 33

The general neurological exam will usually be affected in (early/late) dementia.

Answer 33

Late

Question 34

Diagnosis of "definite" AD requires:

Answer 34

BOTH pathological confirmation as well as | documentation of the clinical picture

Question 35

T/F: Diagnosis of "probable" AD can be made in most cases based on the clinical presentation

Answer 35

True

Question 36

(MRI/CT) is preferred for dementia/AD patients. Why are some reasons the other imaging is used?

Answer 36

MRI; CT may be used because: faster, easier to obtain, lower cost, pacemakers ok

Question 37

AD: CSF has (increased/decreased) tau and P-tau levels, (increased/decreased) beta-amyloid.

Answer 37

Increased; decreased | more Aβ is deposited in brain, less reaches CSF

Question 38

AD: med Rx regimen starts with...

Answer 38

discontinuing medications that could be causing confusion or poor cognition (ex: anticholinergics, sedatives)

Question 39

AD: to enhance cognition, patients with (mild/severe) AD should be started on (X) drug type and be continued until..

Answer 39

Mild/early; X = cholinesterase inhibitors Indefinitely or until the disease is so severe that there seems to be little function left

Question 40

List main cholinesterase inhibitor used in AD.

Answer 40

Donepezil

Question 41

Combination of a (X) and (Y) is typically used in moderate AD

Answer 41

``` X = cholinesterase inhibitor Y = Memantine ```

Question 42

Memantine, used for (X) disease, MOA:

Answer 42

X = AD (in combo with cholinesterase) 1. Uncompetitive antagonist at the NMDA glutamate R 2. Dopamine agonist

Question 43

Lewy Body dementia: where do the lewy bodies accumulate?

Answer 43

Substantia nigra

Question 44

Lewy Body dementia Sx:

Answer 44

1. Atypical Parkinsonism 2. Episodic confusion 3. Early prominent/vivid visual hallucinations of animals/people 4. REM-sleep behavior disorder (don't lose muscle tone during REM; attack/violent in sleep)

Question 45

Lewy Body dementia patients: brain shows (amyloid plaques/hyperphosphorylated tau).

Answer 45

Amyloid plaques; no tau/tangles

Question 46

T/F: Lewy Body dementia responds as to levodopa as PD.

Answer 46

False - may have modest response, but LB patients more likely to experience side effects or increased hallucinations and worsening confusion

Question 47

Pick bodies are a type of (X) seen in (Y) disorder.

Answer 47

``` X = inclusion bodies (that stain for either tau or ubiquitin) Y = FTD (fronto-temporal dementia) ```

Question 48

T/F: Like AD, cholinesterase is helpful in patients with FTD.

Answer 48

False

Question 49

Mixed Dementia consists of:

Answer 49

Vascular + Alzheimer's

Question 50

Which dementia accounts for most clinical cases?

Answer 50

Mixed

Question 51

Some AD Genes not expressed in neurons, only in (X) cells, indicating they're important in pathology of AD.

Answer 51

X = microglia

Question 52

Which NT abnormalities seen in AD?

Answer 52

Decrease ACh | Increased Glu

Question 53

Lewy Body dementia has (tau/amyloid) and (X) pathology

Answer 53

Amyloid; | X = Synuclein

Question 54

Fronto-temporal dementia has (tau/amyloid) and (X) pathology

Answer 54

Tau | X = ubiquitin

Question 55

Prominent and severe language impairment is a key clinical sign of (X) dementia.

Answer 55

X = fronto-temporal