week 5- diseases Flashcards
Red flags for PD diagnosis
name something that would be decreased in the CSF of Parkinsons Its
Decreased HVA (hemovanillic acid- dopamine metabolite) in CSF
What is the Back hypothesis
GI sending toxins to the brain (vagus nerve innervates GI and it does bring stuff to the medulla brain starts in medulla (dorsal medulla CN X, XI) and makes its way up rostrally Can find lewy bodies to PD PTs early on,….smell lost first because olfactory neurons sensitive to toxins from the GI
what is the Parkinsons staging
starts in medulla (dorsal medulla CN X, XI) and makes its way up rostrally • Presymptomatic 1-2, symptomatic – 3-4 with lost dopamine, advanced 5-6 with dementia
what are the predisposing factors for Parkinsons disease
Age (incidence increases rapidly over 60y, mean age of dx 70.5y)
Males
Genetics: SNCA , LRRK2, GBA
Pesticide exposure
Europe, North American, South American have higher prevalence
what is the classical clinical presentation of parkinsons
Classic presentation TRAP – tremor, cogwheel rigidity, akinesia (bradykinesia, hypokinesia) and postural instability
May also see: masked faces, orthostatic hypotension, constipation prior to manifestation, festinating gait, freezing, micrographia, microphonia
clinically–> see less heel to toe tapping
what sign is always consistent for PD
Cogwheel rigidity classic for parkinsons
what is the Tx for PD
COMT –> MOA –> agonist –> L dopa
L-DOPA (levadopa) + carbidopa–>
Moderate to severe
DA agonists (e.g. pramipexole) –>
Can be used for moderate symptoms in <65 yo over levodopa b/c less likely to cause dyskinesias and once/day dosing
MAO-B inhibitors (e.g. rasagiline, selegiline)
Because dopamine can be converted into this
mild symptoms
COMT inhibitors (e.g. entacapone)
Because dopamine can be converted into this
Amantadine (antiviral)
(mech of action in PD is unknown. It may cause NE release; may block NMDA receptors)
Anticholinergics (mAChR antagonists)
where would you target a DBS for PD
rigidity and bradykinesia–> STN and GPI
tremor target thalamus
what is the mechanism of astrocyte modulation as a potential PD therapeutic
increase endocannabinoids and excite the direct pathway or inhibit the indirect
how do you distinguish between lewy body dementia and PD
PD- if dementia is more than a year after motor symptoms
How do you manage psychosis and hallucinations in PD PTs
1st: lower PD drugs (usually due to amantadine, MAO-Is, dopamine agonists or COMT….levodopa least likely to cause)
2nd: low-dose antipsychotic: quetiapine or Pimavanserin (only approved drug for PD psychosis)
what do PD PTs usually die of
malnutrition and aspiration pneumonia is the leading cause of death in PD
what is the prognosis of PD
80% severely disabled or dead within 10-14 years of diagnosis
From disease impairment to disability occurred between 3-7 years after the onset of PD
what are some associated conditions of PD
Akinetic crisis (stiffness, hyperthermia) - can occur as a result of unintended dopamine withdrawal in patients on dopamine therapy
What is the pathophysiology of HD
Hyperkinetic disorder
loss of medium spiny neurons in striatum will see shrinking putamen and expansion of Lateral ventricles
- Since medium spiny neurons are impacted it ill hit indirect path first = early presentation of hyperkinesia (chorea)
- Loss of cortical and subcortical cells
- decreased neurotrophins
- excitotoxicity
- astrocyte loss/ activation/ microglia activation
- ROS
Eventual damage to both the direct (bradykinesia, rigidity and dystonia)
what is wilsons disease, clinical presentation and how do you Tx it
Genetic Disorder of copper metabolism affecting the brain and the liver with a hallmark of Kayser-Fleischer ring (around cornea)
Presents as a movement disorder: dystonia, tremor, chorea, rigidity & additional BG-related signs
Tx = chelate the Cu++
what is Tardive dyskinesia
Induced by anti-psychotics
Antipsychotics block D2 = activation of the indirect pathway ( aka block the inhibitor of indirect pathway )= increase inhibition = hypokinesia BUTTTTTT
Cortico-striatal path compensates by upregulation the blocked receptors = hyperkinesia
what are other non hyperkinetic causes that you would differentiate from tremor
Asterixis, Chorea/athetosis, Clonus, Dyskinesias, Dystonia, Myoclonus, Seizure
differentiate between the frequency of tremors
faster is usually least pathologic
physiologic tremor fastest, the intentional tremor and PD are the slowest
parkinsonian tremor
characteristics
location
frequency
associated conditions
pathophysiology
postural tremor
characteristics
location
frequency
associated conditions
pathophysiology
Intentional/Cerebellar
characteristics
location
frequency
associated conditions
pathophysiology
ID some of the parkinsonisms
drug induced, supranuclear palsy, Multiple system atrophy, vascular, lewy body dementia, corticobasal degeneration
how do you differentiate drug induced from PD
drug induced usually symetrical, does not respond to Tx and improves with stopping of drug
how do you differentiate supranuclear palsy from PD
they have more falls and they have eye involvement
how do you differentoiate MSA from PD
MSA involves ANS dysfunction ad does not respond to levadopa
how do you differentiate CBD from PD
CBD will have myoclonus, RIGIDITY and lack of limb control
how do you differetiate vascular PD from PD
vascular PD will usually have lower limb involvement
YOU CAN DIFFERENTIATE THIS FROM CBD BY LACK OF MYOCLONUS AND RIGIDITY
