Movement Disorders Flashcards
What are the 4 cardinal features of Parkinsons?
a progressive, neurodegenerative disorder
1) resting tremor
2) bradykinesia
3) rigidity
4) gait instability
*all due to nigrostriatal dopamine neruons
Parkinsons Pathology
degeneration of pigmented brainstem neurons (in substantia nigra etc)
Lewy bodies = accumulation of alpha-synuclein (thus anti-synuclein Abs can be used in histology)
Reduced dopamine in striatum (aka caudate + putamen)
What is the biochemical pathway to make endogenous dopamine?
tyrosine —> L-DOPA (via tyrosine hydroxylase **rate-limiting step)
L-DOPA —> Dopamine (via dopamine de-carboxylase)
Dopamine into vesicle (via vesicular monoamine transporter) into synapse
what are the non-motor features of PD?
1) olfactory dysfunction
2) constipation
3) autonomic dysfunction
4) REM sleep behavior disorder
-these all occur well before the motor problems present
Some important Parkinsons epidemiology facts
- 2nd most common neuroDegen disorders
- cumulative risk = 2.7%
- slightly more common in men
- 90-95% are sporadic (aka not inherited)
risk factors include:
- severe head trauma (comatose for at least a day)
- pesticides, well water, rural living
- Low Uric acid
Carbidopa-Levodopa
Carbidopa = de-carboxylase inihibitor that prevents L-DOPA being converted to dopamine (with cannot cross the BBB as well as L-DOPA)
Levodopa = given to skip the rate-limiting tyrosine hydroxylase step
ALWAYS give together
Levodopa is an Amino Acid, thus it will compete with dietary amino acids for absorption if taken with food resulting in much LESS absorption… thus NEVER take with food/milk
entacapone
Catechol-O-methyltransferase Inhibitor (COMT inhibitor)
prevents the breakdown of Dopamine in the synapse also prevents breakdown of dopa in periphery
Name 2 dopamine agonists used to treat parkinsons and what dopamine receptor is targeted?
1) Parmipexole
2) ropinirole
D2 receptors are most targeted
Name 2 monoamine oxidase inhibitors to treat parkinsons
1) selegiline (irreversible)
2) rasagiline
Pros and Cons of dopamine agonists
pros: reduce long-term risk of motor complications, have a longer duration of action than levodopa
cons: hallucinations, dyskinesias, nausea, sleepiness, leg edema ***compulsive disorders in 15% like gambling, sex etc. probably due to binding of D3/D4 receptors
what is the biggest myth in treating parkinsons?
Levodopa does NOT accelerate parkinsons progression (its a myth)
there is NO benefit to delaying treatment
What is the biggest challenge to treating parkinsons with medication?
There is a response threshold, and then a dyskinesia threshold sometimes with a small therapeutic window in between
dyskinesias don’t always bother the patient (may not need to treat)… if they do want it treated, amantidine can help (NMDA antagonist with some D2 agonism)
What are some red flags that tell you it is NOT parkinsons?
1) supranuclear gaze
2) dementia, hallucinations (early dementia)
3) prominent dysautonomia
4) acute changes
5) very early onset (less than 40)
6) poor response to L-DOPA
Differential diagnosis of Parkinsons
- secondary parkinsonism (normal pressure hydrocephalus aka wet wobbly wacky)
- progressive supranuclear palsy
- multiple system atrophy
- corticobasal degeneration
- wilsons disease
- huntingtons
Progressive supranuclear palsy
early falls
down-gaze paresis
axial rigidity
wide-eyed unblinking face
Path = accumulation of hyper-phosphorylated “tau” protein in neurons
Multiple systems atrophy
prominent early disautonomia
nocturnal stridor (crazy-ass yell during bedtime)
Path = alpha-synuclein inclusions in glial cells
3 types of multiple systems atrophy and there cardinal sign
1) Striatonigral Degeneration (SND) - levodopa unresponsive parkinsonism
2) Olivopontocerebellar atrophy - cerebellar features predominate
3) Shy-Drager Syndrome - severe dysautonomia and prominent early orthostatic hypotension
Corticobasal Degeneration
Progressive asymmetric rigidity
levodopa unresponsive
alien limb fixed extensor/flexor muscles in one hand… asymmetry is important feature as well
Parkinsonism in dementia
30% with alzheimers have signs of Parkinsonism
vascular parkinsonism and dementia
normal pressure hydrocephalus (wet wobbly wacky) AKA urinary incontinence, gait ataxia, and dementia
Wilsons Disease
auto recessive deficient copper excretion
copper deposits in basal ganglia result in akinetic-rigid, wing-beating tremor, dystoria, and chorea
kayser-fleischer ring copper deposits in eye
VERY rare disease but actually curable!
name the 6 hyperkinetic movement disorders and one important hypokinetic one
1) tremor
2) chorea
3) myoclonus
4) dystonia
5) tics
6) hemiballismus
*Parkinsons is hypokinetic
Tremor
repititive, rhythmic, alternating contractions of agonist and antagonist muscle
Rest tremor
parkinsonism, associated with rigidity and bradykinesia
terminal tremor
cerebellar disease associated with dysmetria, dysarthria, nystagmus
seen as hand moves distally
