CIS II NPH and PSP Flashcards
PSP is due to aggregation of ______
4R tau (3 isoforms that have 4 microtubule binding domains due to alternative splicings of 2,3, & 10 → 6 isoforms
Tau is encoded for by _______ gene.
MAPT
(etiology of PSP)
If MAPT/mRNA includes _____ it is a 4R tau → PSP
E10
(4 microtubule binding domains)
_____ hapylotype on chromo. 17q is over-expressed in patients w/PSP
H1
(this increases 4R tau→ increasing risk of aggregation)
Increase H1 haplotype leads to increased _______ expression.
exon 10 → 4R tau
(PSP)
4R tau increases risk of ______ aggregation
tau
(increased risk of PSP)
Environmental influences in causing PSP
toxins in Annona fruit
(fruit consumed in Caribbean island Guadeloupe)
Annona fruits are toxic due to ______ (2)
- inhibits mitochondrial complex 1
- increase 4R tau mRNA in neurons
Why is tau aggregation bad (2)?
- it can’t stabilize microtubules → impairs axonal transport & metabolism
- activates UPR → apoptosis
(this tau pathology can spread from one neuron to another like prion diz)
The globose neurofibrillary tangles consist of ______, which gives the neurons an oval to round appearance.
whorled filaments composed of aggregated 4R tau
globose neurofibrillary tangles (PSP)
4R tau aggregates in neurons as well as ______
glial cells (i.e. astrocytes)
(leads to globos neurofibrillary tangles)
Tufted astrocytes found in the gray matter are especially characteristic of _______.
PSP
tufted astrocytes
globose neurofibrillary tangles - tau positive
PSP has atrophy of ______ (4).
- midbrain
- globus pallidus
- superior cerebellar peduncles
- cerebral cortex
(degreased pigmentation of substantia nigra & locus coeruleus → parkinsonian sx)
What is a very characteristic feature of PSP (histopathology)
tufted astrocytes
(as well as globus neurofibrillary tangles)
_____% of patients have normal pressure hydrocephalus
1.4% patients > 65 yo
(insidious onset usually > 40)
2 Associated diz w/Normal pressure hydrocephalus
- cerebrovascular diz
- ALZ
Secondary causes of Normal pressure hydrocephalus (3)
- SAH
- TBI
- Meningitis
(in this order)
What other conditions have
0000
______ is NOT attributable ventricular enlargement seen in normal pressure hydrocephalus
cerebral atrophy
Tx for normal pressure hydrocephalus (2)
- shunt
- serial LPs
(ventriculoperitoneal or lumboperitoneal)
Non-communicating hydrocephalus
obstruction of CSF flow through ventricles → CSF pressure increased
(normal pressure hydrocephalus has too much CSF)
3 conditions that cause non-communicatting hydrocephalus
- intraventricular cyst
- tumor
- ependymal granulation
Communicating hydrocephalus is due to _______.
impaired resorption of CSF
(CSF pressure is normal)
_______% of NPH are idiopathic
50
_______ act like one-way valve for CSF
arachnoid villi (aka granulations)
4 secondary causes of NPH
- subarachnoid hemorrhage
- meningitis
- TBI
- CNS tumor
As a subarachnoid hemorrhage heals it can lead to normal pressure hydrocephalus due to
→ fibrosis → obliterates arachnoid granulations → impairs CSF reabsorption
(similar situation w/meningitis & TBI)
hyperproteinarachia
increased protein in CSF
(seen in CNS tumors due to release; this clogs the subarachnoid granulations → NPH)
3 idiopathic NPH causes
- increased central venous pressure
- arteriosclerosis
- congenital hydrocephalus
how does increased central venous pressure lead to idiopathic NPH
central vein pressure increases pressure up to the dural venous sinuses → impaired CSF reabsorption
How does arteriosclerosis lead to NPH?
chronic ischemia of leptomeninges → leptomeningeal fibrosis
4 causes of central venous pressure increase
- OSA
- heart failure
- pulmonary disease
- incompetent internal jugular valves
(increased pressure in the R side of heart)
decompensated congenital hydrocephalus leads to _______ later in life
idiopathic normal pressure hydrocephalus due to cranial sutures not closing
NPH histopathologic findings include (3)
- arteriosclerosis w/scattered micro-infarcts in periventricular white matter
- demyelination in subcortical white matter
- leptomeningeal fibrosis (due to ischemia; aka arachnoid fibrosis)
MC degenerative forms of atypical Parkinsonism
progressive supranuclear palsy (PSP)
Population affected by PSP
Male > 62 yo
(1 in 100,000)
Hallmark sign of progressive supranuclear palsy (PSP)
supranuclear opthalmoparesis: vertical gaze problems
Prognosis of PSP
death w/in 6-12 years
Sx of PSP (5)
(other than hallmark: supranuclear opthalmoparesis - vertical gaze problems)
- dysphagia
- dysarthria
- pseudobulbar palsy
- abnormal postural reflexes
- frontal cognitive abnormalities
PSP treatment
symptom management
(PT/OT, dietician, cognitive therapy)
PSP finding of hummingbird sign indicates ______
midbrain atrophy
How can you tell PSP apart from Parkinson Disease (2)?
(both have rigidity)
- resting tremor rare in PSP
- poor response to L-DOPA
gold standard for diagnosing PSP
neuropathology
Classic triad of normal pressure hydrocephalus
- apraxia (“magnetic gait”)
- urinary incontinence (indifference)
- cognitive problems (frontal & subcortical)
(similar to Parkinson)
both Parkinson disease and normal pressure hydrocephalus have ______ (3 symptoms).
- gait problems
- hypokinesia
- extrapyramidal symptoms
What helps to distinguish between PSP, normal pressure hydrocephalus and Parkinson disease?
L-DOPA only helps Parkinson Disease
Left: Coronal section of normal brain
Right: Coronal section of brain from patient with Normal Pressure Hydrocephalus
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.
