Movement disorders + laughing Flashcards
What is the major neurotransmitter within the striatum and pallidum
GABA / inhibitory
What is the main output structure of the basal ganglia projecting to the thalamus?
GPi
What is GPi main role
It receives info from striatum via direct/indirect pathway AND its job is to INHIBIT the THALMAUS
What is dopamine effect on movement?
Dopamine facilitates movement
possible enzyme deficits in dopa-responsive dystonia
- tyrosine hydroxylase
2. GTP cyclohydrolase 1
What are the ways the striatum influences the Globus pallidus (2 paths)
- Directly to the GPi (excitatory D1) which inhibits thalamus
- via GPe (inhibitory D2) then STN then GPi
Diagnostic screening tests in Wilson’s dz?
screening: high 24 hr urine copper and low serum ceruloplasmin
child or young adult with twisted foot, gait abnormality, juvenile parkinsonism
may be dopa-responsive dystonia which is treatable with low dose l-dopa!
Red flags (3) you aren’t dealing with pure parkinsonism
- ataxia
- weakness
- spasticity
toxicity in Welders that may lead to parkinsonism
manganese
Top 3 dx to consider instead of Parkinson disease in the young
- Wilson’s
- Dopa responsive dystonia
- huntington’s can have no chorea and more PD sx in young
Autosomal dominant mutation w/ successive generations of PD with normal onset age 50-70
LRRK2 mutation
more rare cause of dominant inheritance of PD with younger onset?
SNCA alpha synuclein (PARK-1)
most common cause of young onset PD that is not present in successive families’
- tends to have dystonia, and diurnal variations with improvement with sleep
- response to tx?
Parkin gene, good l-dopa response, absence of Lewy bodies
(Autosomal recessive)
(PARK 2: wen teen goes Parkin looking for sex: Chr 6)
what are Lewy bodies made up of?
alpha synuclein
ubiquitin
neurofilament protein
dose of levodopa considered a fair trial?
at least 900-1000mg/day (300 TID)
3 nonmotor sx in PD that may precede motor sx
- REM behavior disorder
- anosmia
- autonomic dysfunction
early severe presentation of autonomic dysfunction suggests what?
MSA: Multiple system atrophy
REM behavior disorder in isolation is highly predictive of what?
an alpha synucleinopathy
Deep brain stimulation improves what (4) and has no effect on what (1)
DBS good for:
- improving dyskinesias to best dyskinesia-free ON state on meds alone
- reduced med requirements
- improved ON time
- reduced OFF time
Does not effect postural reflexes
Contraindications for Deep brain stim for PD?
severe psych disease, cognitive impairment, postural instability (may worsen it)
Most effective and best tolerated med for PD and how does it work
levodopa with carbidopa which prevents it from getting broken down before it gets to the brain
What are ropinirole, pramipexole, and apomorphine?
What is the role? Benefits / disadvantages
dopamine agonists
they are less effective and have more s/e than ldopa for pd BUT they have less dyskinesias particularly in young patients who are at more risk for dyskinesias with levodopa
5 main med categories for PD
- Levodopa
- DA agonist
- Anticholinergics
- MAO-B inhibitors
- Amantadine
med that is rarely used but can prolong duration of effect of levodopa
entacapone (COMT inhibitor)
major side effects of levodopa
dyskinesias, vivid dreams/illusions/hallucinations (esp in older cognitively impaired pts), dizziness, hypotension, somnolence
major s/e of Dopamine agonists
worse hallucinations/nausea
sleep attacks
compulsive behaviors
when do dyskinesias usually occur with PD med treatment / levodopa
at peak of ON
order of options in patient on multimedications for PD and who are having cognitive / psych side effects (3)
- get off anticholinergics –> amantadine –> MAOB–>DA agonist –> levodopa (keep the ones with best efficacy and least s/e)
- add Rivastigmine which is a cholinesterase inhibitor approved for PD dementia
- lastly add antipsychotic but be very careful (black box warning)
Best two antipsychotics in PD least likely to worsen PD
Quetiapine and clozapine
Tao or alpha synuclein?
Multiple system atrophy
alpha synuclein
Tao or alpha synuclein?
Progressive Supranuclear Palsy
Tao
Corticobasal degeneration
Tao or alpha synuclein?
Tao
Tau or alpha synuclein?
PD
Parkinson disease - alpha synuclein
Tau or alpha synuclein?
Lewy Body dementia?
Alpha synuclein
Parkinsonism with very early falls?
supranuclear vertical palsy