CIS II NPH and PSP

Question 1

PSP is due to aggregation of ______

Answer 1

4R tau (3 isoforms that have 4 microtubule binding domains due to alternative splicings of 2,3, & 10 → 6 isoforms

Question 2

Tau is encoded for by _______ gene.

Answer 2

MAPT

(etiology of PSP)

Question 3

If MAPT/mRNA includes _____ it is a 4R tau → PSP

Answer 3

E10

(4 microtubule binding domains)

Question 4

_____ hapylotype on chromo. 17q is over-expressed in patients w/PSP

Answer 4

H1

(this increases 4R tau→ increasing risk of aggregation)

Question 5

Increase H1 haplotype leads to increased _______ expression.

Answer 5

exon 10 → 4R tau

(PSP)

Question 6

4R tau increases risk of ______ aggregation

Answer 6

tau

(increased risk of PSP)

Question 7

Environmental influences in causing PSP

Answer 7

toxins in Annona fruit

(fruit consumed in Caribbean island Guadeloupe)

Question 8

Annona fruits are toxic due to ______ (2)

Answer 8

1. inhibits mitochondrial complex 1
2. increase 4R tau mRNA in neurons

Question 9

Why is tau aggregation bad (2)?

Answer 9

1. it can’t stabilize microtubules → impairs axonal transport & metabolism
2. activates UPR → apoptosis

(this tau pathology can spread from one neuron to another like prion diz)

Question 10

The globose neurofibrillary tangles consist of ______, which gives the neurons an oval to round appearance.

Answer 10

whorled filaments composed of aggregated 4R tau

Question 11

Answer 11

globose neurofibrillary tangles (PSP)

Question 12

4R tau aggregates in neurons as well as ______

Answer 12

glial cells (i.e. astrocytes)

(leads to globos neurofibrillary tangles)

Question 13

Tufted astrocytes found in the gray matter are especially characteristic of _______.

Answer 13

PSP

Question 14

Answer 14

tufted astrocytes

Question 15

Answer 15

globose neurofibrillary tangles - tau positive

Question 16

PSP has atrophy of ______ (4).

Answer 16

1. midbrain
2. globus pallidus
3. superior cerebellar peduncles
4. cerebral cortex

(degreased pigmentation of substantia nigra & locus coeruleus → parkinsonian sx)

Question 17

What is a very characteristic feature of PSP (histopathology)

Answer 17

tufted astrocytes

(as well as globus neurofibrillary tangles)

Question 18

_____% of patients have normal pressure hydrocephalus

Answer 18

1.4% patients > 65 yo

(insidious onset usually > 40)

Question 19

2 Associated diz w/Normal pressure hydrocephalus

Answer 19

1. cerebrovascular diz
2. ALZ

Question 20

Secondary causes of Normal pressure hydrocephalus (3)

Answer 20

1. SAH
2. TBI
3. Meningitis

(in this order)

Question 21

What other conditions have

Answer 21

0000

Question 22

______ is NOT attributable ventricular enlargement seen in normal pressure hydrocephalus

Answer 22

cerebral atrophy

Question 23

Tx for normal pressure hydrocephalus (2)

Answer 23

1. shunt
2. serial LPs

(ventriculoperitoneal or lumboperitoneal)

Question 24

Non-communicating hydrocephalus

Answer 24

obstruction of CSF flow through ventricles → CSF pressure increased

(normal pressure hydrocephalus has too much CSF)

Question 25

3 conditions that cause non-communicatting hydrocephalus

Answer 25

1. intraventricular cyst 2. tumor 3. ependymal granulation

Question 26

Communicating hydrocephalus is due to \_\_\_\_\_\_\_.

Answer 26

impaired resorption of CSF ***_(CSF pressure is normal)_***

Question 27

\_\_\_\_\_\_\_% of NPH are idiopathic

Answer 27

50

Question 28

\_\_\_\_\_\_\_ act like one-way valve for CSF

Answer 28

arachnoid villi (aka granulations)

Question 29

4 secondary causes of NPH

Answer 29

1. subarachnoid hemorrhage 2. meningitis 3. TBI 4. CNS tumor

Question 30

As a subarachnoid hemorrhage heals it can lead to normal pressure hydrocephalus due to

Answer 30

→ fibrosis → obliterates arachnoid granulations → impairs CSF reabsorption (similar situation w/meningitis & TBI)

Question 31

hyperproteinarachia

Answer 31

increased protein in CSF (seen in CNS tumors due to release; this clogs the subarachnoid granulations → NPH)

Question 32

3 idiopathic NPH causes

Answer 32

1. increased central venous pressure 2. arteriosclerosis 3. congenital hydrocephalus

Question 33

how does increased central venous pressure lead to idiopathic NPH

Answer 33

central vein pressure increases pressure up to the dural venous sinuses → impaired CSF reabsorption

Question 34

How does arteriosclerosis lead to NPH?

Answer 34

chronic ischemia of leptomeninges → leptomeningeal fibrosis

Question 35

4 causes of central venous pressure increase

Answer 35

1. OSA 2. heart failure 3. pulmonary disease 4. incompetent internal jugular valves (increased pressure in the R side of heart)

Question 36

decompensated congenital hydrocephalus leads to _______ later in life

Answer 36

idiopathic normal pressure hydrocephalus due to cranial sutures not closing

Question 37

NPH histopathologic findings include (3)

Answer 37

1. arteriosclerosis w/scattered micro-infarcts in periventricular white matter 2. demyelination in subcortical white matter 3. leptomeningeal fibrosis (due to ischemia; aka arachnoid fibrosis)

Question 38

MC degenerative forms of atypical Parkinsonism

Answer 38

progressive supranuclear palsy (PSP)

Question 39

Population affected by PSP

Answer 39

Male \> 62 yo | (1 in 100,000)

Question 40

Hallmark sign of progressive supranuclear palsy (PSP)

Answer 40

supranuclear opthalmoparesis: vertical gaze problems

Question 41

Prognosis of PSP

Answer 41

death w/in 6-12 years

Question 42

Sx of PSP (5) (other than hallmark: supranuclear opthalmoparesis - vertical gaze problems)

Answer 42

1. dysphagia 2. dysarthria 3. pseudobulbar palsy 4. abnormal postural reflexes 5. frontal cognitive abnormalities

Question 43

PSP treatment

Answer 43

symptom management | (PT/OT, dietician, cognitive therapy)

Question 44

PSP finding of hummingbird sign indicates \_\_\_\_\_\_

Answer 44

midbrain atrophy

Question 45

How can you tell PSP apart from Parkinson Disease (2)? (both have rigidity)

Answer 45

1. resting tremor rare in PSP 2. poor response to L-DOPA

Question 46

gold standard for diagnosing PSP

Answer 46

neuropathology

Question 47

Classic triad of normal pressure hydrocephalus

Answer 47

1. apraxia ("magnetic gait") 2. urinary incontinence (indifference) 3. cognitive problems (frontal & subcortical) (similar to Parkinson)

Question 48

both Parkinson disease and normal pressure hydrocephalus have ______ (3 symptoms).

Answer 48

1. gait problems 2. hypokinesia 3. extrapyramidal symptoms

Question 49

What helps to distinguish between PSP, normal pressure hydrocephalus and Parkinson disease?

Answer 49

L-DOPA only helps Parkinson Disease

Question 50

Answer 50

**Left:** Coronal section of normal brain **Right:** Coronal section of brain from patient with Normal Pressure Hydrocephalus

Question 51

Answer 51

**Left:** Section of brain showing normal leptomeninges (arrow) and underlying cerebral cortex. **Right:** Leptomeningeal fibrosis: thickening of the pia-arachnoid (arrow), exhibiting dense fibrosis with a scattering of lymphocytes. The subarachnoid space has been obliterated. Immediately beneath the pia is a broad band of glial fibers (\*), and the underlying molecular layer shows reactive gliosis.