B7-037 Parkinsons Disease Flashcards
[…] control systems have no direct output
motor
(modulate outputs through cerebellum and basal ganglia via thalamus)
responsible for automatic movements (habits)
basal ganglia
responsible for feed forward systems (accuracy)
cerebellum
akinetic rigid syndrome is characterized by [3]
slowness of movement (bradykinesia)
velocity independent increased tone (rigidity)
postural instability
move too little
akinetic-rigid syndrome
parkinsonism
hypo-kinetic movement disorders
(all synonyms)
move too much
abnormal involuntary movements
hyper-kinetic movement disorders
primary clinical signs of parkinsonism [3]
bradykinesia/akinesia
rigidity
postural instability
most common cause of parkinsonism
parkinson’s
what two structures make up the striatum of the basal ganglia?
caudate
putamen
what two structures make up the lenticular nucleus of the basal ganglia?
putamen
globus pallidus
parts of the basal ganglia [5]
caudate
putamen
globus pallidus
subthalamic nucleus
substantia nigra
integrate multimodal cortical information in the context of motivational information to facilitate automatic and stereotyped behaviors
basal ganglia
(habits: walking, driving, etc)
major inputs to basal ganglia system
cortico-striate
major output of the basal ganglia
globus pallidus internus
the output from the globus pallidus internus is […] to the thalamus
inhibitory
the output from the globus pallidus internus is inhibitory to the thalamus, which decreases […]
magnitude of movement
excess activity in the globus pallidus interna will result in
akinetic rigid syndrome
increased activity of the direct pathway gives […] output of GPi and […] movement
less
increased
increased activity of the indirect pathway gives […] output of GPi and […] movement
more
decreased
the inhibitory neurotransmitter in the basal ganglia system is
GABA
the excitatory neurotransmitter in the basal ganglia system is
glutamate
the direct and indirect inputs of the basal ganglia fire […]
simultaneously
(and both can both increase and decrease movement)
dopaminergic modulation of the basal ganglia system occurs through
substantia nigra
more dopaminergic activity […] output from GPi, […] movement
less
more
via substantia nigra
less dopaminergic activity […] output from GPi, […] movement
more
less
via substantia nigra
direct pathway […] movement
facilitates
indirect pathway […] movement
inhibits
there are […] neurons within the striatum that also modulate the basal ganglia system
ACh
hypokinetic movement disorders result from […] activity of GPi
too much (more inhibition)
hyperkinetic movement disorders result from […] activity of GPi
too little (less inhibition)
when a patient has akinetic rigid syndrome that is bilateral and mildly asymmetric with no other systems affected, the pathology is affecting the
substantia nigra
parkinson’s disease is caused by idiopathic neurodegeneration of the
substantia nigra
in Parkinson’s, there is […] dopaminergic input to the striatum, and […] output from GPi resulting in […] inhibition of thalamus
in Parkinson’s, there is [less] dopaminergic input to the striatum, and [more] output from GPi resulting in [more] inhibition of thalamus
the basal ganglia is also associated with parts of limbic system which can cause […] in Parkinson’s patients
apathy (amotivational)
the basal ganglia is also associated with parts of prefrontal cortex which can cause […] in Parkinson’s patients
dysexecutive symptoms
the basal ganglia is associated with parts of frontal eye fields which can cause […] in Parkinson’s patients
hypometric saccades
the basal ganglia is associated with the motor and premotor cortex which causes […] in Parkinson’s patients
akinesia
decreased output from the GPi can cause what affect on the limbic system?
hypermotivation (addiction)
decreased output from the GPi can cause what affect on the prefrontal cortex?
excessive planning (obsessive complex disorder)
symptomatic treatment of Parkinson’s focuses on [2]
repair of dopamine deficiency
modulation of basal ganglia circuits with DBS
can dopamine cross the BBB?
no, but levodopa can (precursor, converted once crosses)
most effective agent for the treatment of Parkinson’s
levodopa
what patients with Parkinson’s will have a significant benefit from levodopa?
all of them
(however, wears off after 10 years)
blocks dopamine decarboxylase in the blood
carbidopa
blocks comethyltransferase in the blood and brain
tolcapone
COMT inhibitor
blocks monoamine oxidase B in the brain [2]
selegiline
rasagiline
Sinemet is what combination of drugs?
carbidopa/levodopa
dopamine agonists [2]
pramipexole
ropinirole
(not as effective for motor symptoms as LDOPA, but have longer half life)
long term complications of LDOPA
wearing off-phenomenon
dyskinesias (chorea, dystonia)
what is the cause of long term complications of LDOPA [2]
short half life
decreasing ability of nigral neurons to store dopamine
deep brain stimulation is only effective in PD patients responsive to
LDOPA
targets of DBS [2]
GPi
subthalamic nucleus (can adversely affect speech)
primary feature suggesting a patient with akinetic rigid syndrome does not have Parkinson’s
poor response to LDOPA
other causes of akinetic rigid syndrome (not Parkinsons)
encephalitis
multi-system atrophy
vascular
toxins
drug induced
the pathology in multiple system atrophy is in the […]
striatum
parkinsonian features
early postural instability
early speech difficulty
peripheral neuropathy
cerebellar signs
pyramidal tract signs
multiple system atrophy
caused by ischemia to the striatum
history of HTN and strokes
MRI white matter changes
vascular parkinsonism
dopamine antagonists can cause
drug induced Parkinsonism
dopamine antagonists [3]
phenothiazines
metoclopramide
thioxanthenes
drug induced Parkinsonism can take up to […] to reverse
6 months
in […] postural tremor is greater than resting tremor
drug induced Parkinsonism
rhythmic abnormal involuntary movement
tremor
most common tremor
essential
treatment of tremor [3]
primidone
propanolol
focused US targeting thalamus
abnormal involuntary movement that the patient can voluntarily suppress but still have an urge to move
tic
common diseases causing tics [2]
Tourette’s
adult-onset Tic disorder
treatment of tic
neuroleptics
pimozide
cognitive behavioral therapy
sustained abnormal involuntary movements
dystonia
common diseases causing focal dystonia
torticollis
writer’s cramp
treatment of dystonia
botulinum toxin (focal)
anticholinergics (generalized, hard to treat)
non-sustained, arrhythmic ballistic movement
chorea
involves an agonist, antagonist, agonist
ballistic movement
hemi-ballismus can result from […] stroke
subthalamic
chorea is seen in […] disease
Huntington’s
treatment of chorea
dopamine antagonists
contralateral hemiballismus indicates lesion in the
subthalamic nucleus
brief, shock like movement of simulatenous agonist/antagonist
myoclonus
common diseases causing myoclonus
primary generalized epilepsy
post anoxic
treatment of myoclonus
valproic acid
long-acting benzos
abnormal involuntary movements after the use of a dopamine blocking unit
(often an antipsychotic)
tardive dyskinesia
dystonia and chorea of the tongue, mouth, and mandible are commonly seen in
tardive dyskinesia
[…] prevent tardive dyskinesia
anticholinergics
treatment of tardive dyskinesia
valbenazine
akinetic rigid syndrome is a synonym for
Parkinsons/parkinsonism
if a patient with akinetic rigid syndrome does not respond to levodopa, what diagnosis do they have?
Parkinsonism
cause of Parkinson’s disease
degeneration of the substantia nigra
cardinal features of akinetic rigid syndrome [3]
bradykinesia
rigidity
postural instability
velocity independent increased tone
rigidity
MOA-B inhibitors prevent the breakdown of
dopamine
carbidopa prevents the breakdown of
L-DOPA
the major output of the basal ganglia is via the
globus pallidus interna
the GPi inhibits the
ventral lateral thalamus
decreasing the activity of the GPi would […] the ventrolateral thalamus
disinhibit
do basal ganglia have direct motor outputs?
no,
they modulate the output of the corticospinal and corticobulbar
precursor to dopamine
L-DOPA
inhibits the peripheral metabolism of levodopa
carbidopa
[…]inhibitors prevent the breakdown of dopamine [2]
MOA inhibitors
COMT inhibitors
damage to the […] results in decreased inhibitory output from the basal ganglia to the motor thalamus
subthalamic nucleus
atrophy of the globus pallidus would result in
dystonia
non-sustained arrhythmic ballistic movements affecting one extremity
hemiballismus
(i.e. arm flings out uncontrollably, striking people or objects)
classically hemiballismus is related to damage in the
subthalamic nucleus
(but can be any part of the basal ganglia)