Neurodenerative Movement Disorders - Ferguson Flashcards
hypokinesia
decreased bodily movement
-associated with diseases of basal ganglia
name a prototypical hypokinetic movement
Parkinson’s disease
Parkinsonisms
diseases which have similar initial presentations to Parkinson’s disease
-but different clinical course and underlying pathology
What part of the brain does Parkinson’s disease impact
substantia nigra neurons die prematurely
- loss of pigmented dopaminergic cells
- accumulation to Lewy bodies and Lewy Neurites
how does a patient get categorized as idiopathic or primary Parkinson’s disease
neurodegeneration in susbtantia nigra and locus coreuleus
what categorizes secondary Parkinson’s disease
some clear cause of the Parkinson’s disease
what infections can cause Parkinson’s disease
epidemic of encephalitis
Von Economo’s Encephalitis
what toxins can cause Parkinson’s disease
carbon monoxide
carbon disulfide
manganese
L-BMAA toxicity
what designer drug can cause Parkinson’s ? what drug was it trying to mimic
MPTP byproduct of meperidine (Demerol)
WHAT DIABETIC GASTROPARESIS HAS MANY FEATURES OF NEUROLEPTICS AND CAUSES SECONDARY PARKINSON’S DISEASE
Metaclopramide ( Reglan)
what type of prescription drugs cause Parkinson
Neuroleptics ( haloperidol/chlorpromazine (throazine))
reserpine ( deplete dopamine)
what is different about acute trauma that induces Parkinsonism
may be reversible
what are the clinical features of Parkinson’s disease
TRAP
tremor, rigidity, akinesia, postural instability
what type of tremor is found in Parkinson’s disease
rest tremor
asymmetric onset
pill rolling or wrist supination/pronation
describe the rigidity of Parkinson’s disease
“cogwheeling” : extension and flexion at elbow and wrist common, ratchet-like feeling
what is akinesia
loss or impairment of the power of voluntary movement.
“freeze”
what are other signs of Parkinson
gait impairment hallucinations (late in disease) REM sleep behavior disorder dementia autonomic dysfunction: constipation, urinary frequency, sweating
what is the gold standard to treat Parkinson
Carbidopa/Levodopa (Sinemet)
MAO of Carbidopa/Levodopa
crosses BBB and converts to dopamine by ALLA-decarboxylase
what are disadvantages Carbidopa/Levodopa
short half life
competes with amino acids in GI and BBB
motor fluctuations
MOA of MAO-B inhibitors
selective inhibition of MAO-B enzyme involved in dopamine metabolism
what are drawbacks for MAO-B inhibitors
tons of drug interactions
very mild anti-Parkinson drug
MOA of dopamine agonists
directly stimulate D2/D1 receptors
compare dopamine agonist to Levodopa and MAO-B and Amantadine
less efficacious then Levodopa
more efficacious then MAO-B and Amantadine
what is drawback for dopamine agonsts
impulsivity
sleep attacks
restless leg syndrome
Amantadine is effective at reducing what
dyskinesia
COMT inhibitors MOA
inhibit COMT
slows dopamine breakdown
what other drug is given with COMT inhibitors and why
levodopa
prolongs half life
when is COMT inhibitor perscribed
advanced PD when patients are experiencing motor flucations
what patients are considered for deep brain stimulator
advanced PD
not demented
symptoms cannot be controlled by medications
what symptoms fail to improve from deep brain stimulator
speech
cognition
postural instability and gait
autonomic symptoms ( constipation)
Lew Body disease
deposition of abnormal tau proteins throughout subcortical white matter
what are clinical motor features of lewy body demenita
Parkinsonian motor features preceding cognitive and psychiatric features
what are psychiatric clinical features of Lewy body
varying levels of alertness and attention
-excessive daytime drowsiness
visual hallucinations
what happens to cognition for lewy body dementia
anterograde memory loss
executive function deficits
visuospatial impairment
Normal pressure hydrocephalus
CSF volume increase results in increase subarachnoid space volume
-disrupts normal blood flow and positioning and function of subcortical white matter
what are motor features of normal pressure hydrocephalus? earliest feature
abnormal gait (earliest feature) shuffling gait
what are cognitive features of normal pressure hydrocephalus
dementia: memory loss
what are other clinical features of normal pressure hydrocephalus
urinary incontinence
name a hyperkinetic movement disorder
Huntington’s disease
what is Huntington’s disease
neurons in caudate nucleus and putamen undergo degeneration
what is the genetic basis for Huntington’s disease
CAG repeat
encodes polyglutamine tract on N-terminus of protein Huntingtin
chromosome 4
worse with generations
what is the motor clinical feature of Huntington’s disease
initially chorea
- then parkinsonian symptoms
- advanced: akinetic-rigid syndrome
chorea
“dance”
writhing type movements
Psychiatric symptoms of Huntington’s disease
depression
obsessive-compulsive
sexual and sleep disorders
changes in personalitly
MOA of Tetrabenazine
dopamine depleting agent
cause choreaform movements
what is a side effect of Tetrabenazine
depression
what should be considered to be first-line therapy for depression in Huntington’s
Selective serotonin reuptake inhibitors SSRI
Is it okay to give antipsychotics to Huntington’s patients
yes
what gender is more likely to get PD
males
what race tends to get PD
Caucasians more than asians and african american
after what age is PD prevelent
65
what are environmental risk factors for PD
heavy metal toxicity
what is the clincial triad for normal pressure hydrocephalus
abnormal gait
urinary incontinence
Dementia
what goes wrong in extraventricular obstructive hyrocephalus
initial event leading to NPH
diminished CSF absorption at the arachnoid villi
how do you diagnose normal pressure hydrocephalus
CT or MRI
lumbar puncture with goal of removing large volume of CSF fluid
what is the morphology of the brain in Huntington’s disease
entire brain atrophy
striking atrophy of caudate nucleus
