Parkinsons - 1a/b PD Flashcards
1
Q
what nuclei is the basal ganglia composed of
A
3 nuclei at base of cerebral cortex
- caudate nucleus
- putamen
- globus pallidus
2 brainstem (midbrain) nuclei
- substantia nigra
- subthalamic nucleus
2
Q
what is the normal function of the basal ganglia
A
initiation and continuation/fluidity of mvmt as well as inhibition of undesired mvmts
3
Q
how does the basal ganglia influence and control mvmts
A
controls the production of mvmt
- timely running of complex mvmt patterns via direct and indirect loops in the cerebrum
“on off” switch for selected motor programs
- communication to cortex to either initiate and continue or inhibit mvmts
4
Q
is parkinsons considered a mvmt or motor disorder and why
A
mvmt disorder
extrapyramidal system disorder, no pathology in motor corticospinal tracts bc no direct connections to alpha or gamma motor neurons
5
Q
what does the basal ganglia communicate with
A
communicates w motor cortex via thalamus along indirect and direct loops
6
Q
what are the 2 loops that compose the basal ganglia’s corticothalamic loops
A
direct
indirect
7
Q
what is the pathway of the basal ganglia’s direct loop
A
cortex -> putamen -> globus pallidus -> thalamus
8
Q
what is the pathway of the basal ganglia’s indirect loop
A
cortex -> putamen -> globus pallidus -> subthalamic nucleus -> thalamus
9
Q
describe how the basal ganglia’s corticothalamic loops works
A
cortex determines voluntary mvmt needed
-> BG selects & presents motor programs to motor cortex via thalamus
- appropriate motor program facilitated by direct pathway/loop
- competing motor programs inhibited by indirect pathway/loop
10
Q
direct vs indirect pathway functions
A
direct pathway
- voluntary mvmt produced
indirect pathway
- suppress unwanted mvmts
11
Q
what are the 3 neurotransmitters associated w the BG and what is the main one
A
**dopamine **
acetylcholine (ACh)
gamma-aminobutyric acid (GABBA)
12
Q
where is dopamine produced
A
substantia nigra
13
Q
what are dopamines functions & impact on BG
A
excitatory to neurons in direct loop
inhibitory to neurons in indirect
has greatest impacts on pathways out of neurotransmitters
14
Q
where is ACh found
A
caudate and putamen
15
Q
what is the function of ACh & impact on BG
A
inhibitory to action of dopamine
- changes BG’s pathways indirectly
16
Q
what is GABBA’s function & impact on BG
A
overall inhibitory neuro transmitter found throughout brain
- changes BG’s pathwq]ays indirectly
17
Q
what is the neuropathology of PD
A
degenerative neurologic condition bc of progressive death of dopamine-producing cells in substantia nigra
-> alterations of neural activity or signaling in corticothalamic loops (both indirect and direct loops)
18
Q
how does the neuropathology of PD impact the direct loops’s function
A
impaired function produces:
- bradykinesia (slow mvmts)
- akinesia (paucity/loss of mvmt)
19
Q
how does the neuropathology of PD impact the indirect loops’s function
A
impaired function produces:
- tremors (resting tremors)
- chorea (unwanted, extraneous mvmts)
20
Q
what are 3 possible etiologies of PD and what is the most common
A
idiopathic* - majority
neurotoxins
genetic factors
21
Q
what are some examples of idiopathic etiologic factors (5)
A
- proteinopathy
- failure of construction of protein cells that lead to dysfunction - mitochondrial dysfunction
-> interferes w cellular energy produciton - oxidative stress
- accumulation of free radicals and other toxins -> excitoxicity - excitotoxicity
- inflammatory markers
22
Q
what is hard to differentiate w idiopathic etiologic factors and why
A
hard to know if idiopathic etiologies are causes or s/sx of PD
by time dx, substantial loss of cells in substantia nigra already
23
Q
what are 3 ex of neurotoxin etiologies
A
pesticides
heavy metals - factories, water/air
agent orange - vietnam war
24
Q
what are genetic factors as an etiology linked to
A
linked to earlier onset, more rapid progression of motor sx and cog changes
25
how does a genetic predisposition impact the risk of developing PD
many people w a genetic predisposition don't have PD
likely that an exposure to an environmental factor triggers the dz
26
parkinsons vs parkinsonisms vs PPS
parkinsons = idiopathic
parkinsonisms = can attribute sx to another cause
PPS = distinct health conditions that have overlapping parkinsons features, but have distinct hallmarks/features that can be determined as a different health condition when doing a differential dx
27
what are common parkinsonisms (6)
head trauma (ie boxing)
toxins, pesticides, metabolic d/o
antipsych, antidep, and HTN meds
viral infections, tumors
alzheimer's dz
normal pressure hydrocephalus
28
how can head trauma lead to a parkinsonism
damage nuclei
29
how can hydrocephalus lead to a parkinsonism
compress basal ganglia
-> interfere w communication loops
---> cause sx similar to parkinsons
30
what are 4 parkinson-plus syndromes
multiple system atrophy (MSA)
progressive supranuclear palsy (PSP)
corticobasal ganglionic degen (CBD)
dementia w lewy body (DLB)
31
what is the single largest risk factor for PD
age
32
what is the epidemiology for PD
2nd most common neurodegen d/o
fastest growing neuro condition worldwide
33
what is the average age of onset for PD
50-60yo
34
at what age is considered early onset PD
<40yo
35
at what age is considered juvenile onset PD
<21yo
36
what are common characteristics of the onset of PD
unilateral and asymmetrical
37
what are the hallmarks of PD and what is the significance of these
bradykinesia
tremor
rigidity
2 out of 3 required for dx
38
what is the significance of seeing postural instability in PD
later manifestation not required for a dx, but also a hallmark of PD
39
s/sx of PD (4 hallmarks + 3)
hypokinesia
akinesia
bradykinesia
tremor
postural instability
rigidity
dyskinesia
40
what type of dx is PD
clinical dx
41
when is dyskinesia seen
secondary to gold standard meds for PD
42
what is hypokinesia and what are 4 ways this can manifest
reduced amplitude of mvmt
1. lack of arm swing and trunk rotation in gait
2. lack of facial expression ("masked faces")
3. micrographia - small handwriting
4. hypokinetic dysarthria & dysphagia
43
what is akinesia and how does this commonly manifest
freezing episodes, lack of mvmt
common in gait "fog"
- can't turn on mvmt or initiate
44
what is bradykinesia and what are 2 ways this can manifest
slow mvmts and delayed reaction times
1. difficulty performing simultaneous or sequential mvmts
2. difficulty w transitional mvmt, direction changes
45
resting tremors: where can this be seen, aggravating and relieving factors
extremities, trunk, jaw, tongue
- pill rolling hand tremor is common
- unilateral initially
worsen w stress
stop when moving and sleep
46
dyskinesia: what is it, when is this commonly seen, what can this result in
random and purposeless mvmts affecting limbs, trunk, face, or tongue
side effect of PD med (levodopa)
result in: ms pain, embarrassment, self-limiting behaviors
47
what is posturography
sequence of activation is intact but speed and amplitude of firing is impaired
48
what are 3 common characteristics of postural instability and what can postural instability lead to
1. ineffective responses to external perturbations
2. posturography
3. dec anticipatory/feed forward postural adjustments
leads to inc episodes of falling
49
what is are good tests to assess postural instability
push test
pull test - give post perturbation at shoulder girdle (abnormal >2steps to regain balance)
50
what is rigidity and what are 2 phenotypes
inc resistance to passive elongation in agonist and antagonists
1. cogwheel - tremor superimposed on rigidity, catch and release
2. lead pipe - sustained resistance
51
what ms are affected by rigidity and how
prox ms often affected first
- forward flex/kyphotic posture
asymmetrical early in dz process
52
what secondary things can rigidity lead to
inc energy demands and leads to fatigue
secondary adaptive ms shortening and disuse weakness
53
what are 2 common gait d/o are seen in PD
festinating gait
freezing of gait (FOG)
54
what is a festinating gait and when might this patient have difficulty
progressive inc in speed and shortening of stride
- inc cadence, dec in step length
loss of heel toe progression -> shuffles
dec ability to step over obstacles or walk on uneven surfaces
55
what is freezing of gait (FOG) and when is this especially a problem for pts
gait ignition failure, akinetic gait
obstacle clearance and negotiating doorways are especially problematic
56
what are some common non-motor sx (7)
attentional and cog deficits
sensory impairments
sleep disturbances
mental health issues
autonomic dysfunction
anosmia & sialorrhea
fatigue and CV issues
57
what might be one of the earliest signs of PD
anosmia
sleep disturbances also may be seen before mvmt sx
58
what are some attentional and cognitive deficits (4)
1. inability to shift attention, dual tasks
2. inability to quickly access "working memory" & manipulating memory
3. difficulty w visuospatial perception and discrimination, learning
4. subcortical dementia**
59
what sensory impairments are seen (3)
paresthesia
pain
proprioception/kinesthesia
60
what sleep disturbances are seen in PD (4)
REM sleep behavior d/o
insomnia
daytime sleepiness
nocturia
61
what autonomic dysfunction is seen in PD (4)
thermoregulation, sweating
seborrhea
GI disorders, constipation, UI
OH, altered HR and BP
62
what mental health issues have a high co-morbid rate
anxiety and depression
63
what is sialorrhea and why is this commonly seen w PD
drooling
- lack of ms activity needed for swallowing and needed for secretions management
64
how can PD impact CV function
inc trunk tone & rigidity
- > develop flex kyphotic posture --> dec vital capacity -> inc difficulty swallowing --> aspiration -> bronchopneumonia
fatigue and dec CV can lead to multifactorial and secondary impairments
65
what is the significance of secondary impairments to PT
secondary impairments are where PT really need to intervene bc can perpetuate health problems
66
what are prodromal symptoms
non-motor sx that may precede motor sx by up to 2 decades
67
at what point is there finally an onset of motor sx
when 50% or more of dopaminergic neurons have died
68
what are the most common prodromal sx (4)
autonomic changes (orthostasis)
anosmia or phantom smells
sleep disturbances
constipation
69
what are the common complaints that lead to people seeking out an MD (2) and what is the significance when these pts usually get referred to PT
stiffness in one hand/limb
shoulder/back pain
PTs have to be aware of & perform additional tests
- ask about common non-motor prodromal signs
70
if a PT suspects a person has parkinsons, what should our referral be
back to MD
neurologist or preferably a mvmt disorder clinic
- these lead to best outcomes
71
what is the process for diagnosing PD
clinical dx based on 2/3 hallmarks
- no definitive dx tests
must exclude parkinsonisms and parkinson-plus syndromes in differential dx
72
what is a DaTSCAN, what is a positive, and what are its 2 main limitations
nuclear medicine study
(+) = dec and asymmetrical uptake of pre-synaptic dopamine transporters
doesn't differentiate PD from parkinsonisms
antidepressant meds may confound results
73
what and how can neuroimaging be utilized in PD
MRI/CT scans
- show cell death in SN in late stages only (usually dark -> get lighter as die off)
fMRI
- detect low levels of activity in BG early stages
- but not widely available, mostly used in research centers
74
what are the 2 main clinical subgroups/phenotypes of PD
1. postural instability and gait disorder (PIGD)
2. tremor dominate (TD)
75
PIGD vs TD phenotypes
PIGD
- more rapid rate of progression
- neurobehavioral sx & depression
TD
- less bradykinesia & postural control deficits
- typically more benign course, esp if younger age at onset
76
what is the typical clinical course of PD
onset of motor sx usually unilateral and asymmetrical
progressive condition - tends to then affect all limbs
77
what is the common cause of death in PD and why is this significant
CV dz, pneumonia
significance of secondary intervention and aerobic activity
78
how does levodopa therapy impact the clinical course of PD and when does it stop being effective
can prolong lifespan
doesn't cure dz or stop progression
- masks sx
doesn't have same effectiveness once native dopamine depleted
79
what is the gold standard for pharmacological management of PD
levodopa/carbidopa (Sinemet)
80
how does levodopa work
dopamine precursor is converted after crossing BBB
alleviates bradykinesia & rigidity
- but not tremor
81
what are 2 major difficulties of levodopa therapy
1. therapeutic window and dosing is problematic
- difficult to determine when person should start therapy
- will dec effectiveness after 10-15yrs
- want to optimize mvmt as long as possible
2. difficult to get pts to stay compliant and take right doses at right time
82
how long optimal benefit of levodopa last
wears off after 4-6yrs
- will dec effectiveness after 10-15yrs
83
what are side effects of levodopa and what is the major one to remember (10)
**dyskinesia
dystonia
visual hallucinations
delusions
paranoia
depression
hypotension
dizziness
arrhythmias
insomnia
84
what are 4 types of pharmacologic management
levodopa (Sinemet)
dopamine agonist
anticholinergic
neuroprotective agents
85
how do dopamine agonists work
meds to mimic dopamine
- bind to and activate striatal dopamine receptors
alleviates rigidity and bradykinesia, motor fluctuations
86
why might a pt be on both a dopamine agonist and sinemet
can be used to reduce the Sinemet dose
87
what are the side effects of dopamine agonists and what is the major one
same SE as levodopa
**impulse control disorder**
- risky behaviors like gambling, overtly sexual
88
what are anticholinergics used for
managing tremors, dystonia, sialorrhea
89
what is the danger of taking anticholinergic meds at wrong times
linked to cog impacts of dz you see
90
what are adverse effects of anticholinergics (4)
blurred vision
dry mouth
dizziness
urinary retention
91
what are 4 signs of anticholinergic toxicity and what should be done if suspected
impaired memory
confusion
hallucinations
delusions
emergency management is needed
92
how do neuroprotective agents work
MAO B inhibitors
prevent degradation of native dopamine
93
when/why are neuroprotective agents typically used
early treatment and/or later to reduce levels of levodopa needed
94
what are adverse effects of neuroprotective agents (5)
nausea
orthostasis
confusion
hallucinations
insomnia
95
when/why is a dose response trial used (3)
1. determines response to med
2. assist in dx process (no response in PPS)
3. ensure pt isn't over or under medicated
96
what is the PT's role in a dose response trial
work w neurologist and do battery of tests
- doc response of specific mvmt disorder to meds
97
what are the 2 main options for surgical management
neuroablation (lesioning)
deep brain stim (DBS)
98
what is the goal of a neuroablation (lesioning) and how does this work
permanently blocking signals from BG
thermacoagulation and neural tissue death achieved by transmitting high frequency radiowaves stereotacticallly thru small electrode
- targeting globus pallidus (palidotomy) or parts of thalamus (thalamotomy) most frequently
99
what sx is neuro ablation effective in treating
reducing tremor, bradykinesia, rigidity
100
pros/cons of neuroablation vs deep brain stim
neuroablation
- not highly invasive
- permanent
deep brain stim
- reversible
- higher cost
- risk of infection
101
what is the goal of deep brain stim and how does it work
"jam" abnormal signals from BG loops
microelectrode implanted in BG
delivers high frequency electrical discharge via impulse generator implanted under clavicle
creates depolarizing block to jam signals
102
what are 2 contraindications for DBS
cog impairments
- have to interrogate it
- go for follow ups
parkinsonisms
- not as effective
103
what are the 2 growing areas of research searching for a cure to PD
stem cells
exercise
104
how does stem cell regeneration med research work as a cure for PD
extract cells from adult thru cartilage in nose or bone marrow in iliac crest
- process in lab and bring back to pluripotent state
- can be implanted in areas where there are deficiencies, loss of native cells
= differentiate into midbrain dopaminergic neurons
105
what are 4 considerations of stem cell regen
immunogenicity
proliferation
timing in dz progression
measuring effects & outcomes
106
what are limitations in stem cell research
having trouble getting them to start producing dopamine
- also problems w getting them to stop proliferating and reproducing once implanted -> become tumors
107
what benefits does exercise may have for PD
modify disease & slow progression
- may also dec risk of developing PD
108
what type of exercise does research suggest may slow PD progression
early intense, large amplitude aerobic activity that includes complex/whole body mvmt
- LSVT Loud
109
how can exercise dec risk of PD
exercising mod intense aerobic 3-4x/wk and get GDNF production which has neuroprotective effects
110
what is the key for utilizing exercise to slow PD progression
early referral to quickly start exercise
111
what is thought to be the mechanism that exercise uses to slow PD progression
activates release of neurotrophic factors and promotes angiogenesis
neuroprotective mechanisms d/t PA (read the following over)
- inc production of superoxide dimutase, endothelial nitric oxide synthase, brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factor, vascular endothelial growth factor, and reduction in production of free radicals
limits alteration in dopaminergic neurons in SN and contributes to optimal functioning in BG
