Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuro > Parkinson's > Flashcards

Parkinson's Flashcards

1
Q

typical age of diagnosis

A

over 60

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Young-onset PD

A

symptoms before age 50, 4-10% of PD population, mainly caused by genetics, progression is slower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

which gender and race is more likely to get it?

A

men are more likely, whites are 2x more likely than Black or Asians

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

risk factors

A

increasing age, family history (30% w/PD have a known family history), male, caucasian, personality (intorverted, shy, nervous, strong sense of responsibility), environmental (pesticides, herbicides, heavy metals, well water, repeated head injury)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

primary movement symptoms

A

resting tremor
bradykinesia
rigidity
postural instability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

rigidity

A

inflexibility of the limbs, neck, truck
decreased range of motion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

postural instability

A

later in disease progression
unstable to stand upright
reflexes needed to maintain upright posture are lost
may fall backwards if pushed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what two primary motor symptoms must be present for a diagnosis to be considered

A

bradykinesia and either tremor or rigidity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

resting tremor

A

most common symptom
starts in hand (finger) or foot, sometimes uncommonly in the jaw or face
shaking movement when muscles are relaxed
can be enhanced by stress
starts on 1 side and then spreads to the other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

bradykinesia

A

slow voluntary movement
difficulties with repetitive movements
decrease in facial expressions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

secondary symptoms

A

freezing (differs from rigidity and bradykinesia, during walking, increases risk of falling)
micrographia (shrunken handwriting)
unwanted accelerations ( gait and speech)
reduced sense of small
mask-like expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

secondary symptoms

A

freezing (differs from rigidity and bradykinesia, during walking, increases risk of falling)
micrographia (shrunken handwriting)
unwanted accelerations ( gait and speech)
reduced sense of small
mask-like expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the autonomic NS?

A

part of the peripheral NS that regulates involuntary physiological processes (digestion, respiration, blood pressure, heart rate, etc)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

autonomic dysfunctions

A

constipation
low blood pressure- when changing positions
sweating problems- excessive perspiration even when not hot
urine problems- frequent urination or involuntary urine loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

stage 1

A

symptoms on one side of body
little loss of function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

stage 2

A

symptoms on both sides
balance is normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

stage 3

A

symptoms on both sides
balance impairment
physically independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

stage 4

A

severe impairment in movement and balance
able to walk or stand unassisted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

stage 5

A

severe impairment of movement
wheelchair bound
increase risk of choking, pneumonia and deadly falls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

can we predict disease progression?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how long do symptoms take to progress

A

at least 20 years, or more quickly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the MDS-Unified PD Rating Scale?

A

better measures PD progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the 4 parts to the MDS scale?

A

non-motor aspects of daily living- cognitive impairment, hallucinations, depression, sleep. etc. (13 items)
motor aspects of daily living- speech, swallowing, use of utensils, handwriting, etc. (13 items)
motor examination (18 items) - facial expression, tremor at rest, posture, gait, body bradykinesia, hand movements
motor complications ( 6 items)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

scoring for MDS

A

healthy- 0
severe-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how is PD diagnosed?

A

based on medical history and neurological exam
no blood or lab tests for non-genetic
CT and MRI appear normal but can rule out other diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is Post-encephalitic Parkinsonism

A

unknown causes, but thought to be viral in nature
bradykinesia, rigidity, posture instability, gait disorders with falls, facial masking
present w/ NFTs in hippo and cortical areas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Drug-induced Parkinsonism

A

manganese dust, carbon monoxide
dopamine inhibitors including metoclopramide
MPTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is tardive dyskinesia

A

involuntary, repetitive body movements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is multiple system atrophy w/ predominant Parkinsonism (MSA-P)

A

no known cause
progressive neurodegenerative disorder
nigrostriatal degeneration
alpha synuclein inclusions in neurons and oligodendrocytes (only in neurons In PD and LWD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

symptoms of MSA-P

A

rigid muscles
difficulty bending your arms and legs
bradykinesia
tremors (rare in MSA compared to Parkinsons)
problems w/ posture and balance
autonomic dysfunction
faster rate of symptom progression, more autonomic dysfunction, poorer response to LDOPA treatment than PD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

MSA-P

A

similar to PD (w/ moving slowly, stiffness, and tremor) along w/ more mild problems of balance, coordination, and autonomic NS dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

MSA-C

A

ataxia (problems w/balance and coordination) difficulty swallowing, speech abnormalities, abnormal eye movements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

normal pressure hydrocephalus

A

blockage causes abnormal increase of CSF in ventricles
ventricle enlarge which puts pressure on the brain
problems with walking, general slowing movements and cognitive problems
cognitive problems caused from pressure put on hippo since it is close to ventricles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

corticobasal syndrome (CBS)

A

atrophy of cortex and basal ganglia
rigidity, impaired balance and coordination, dystonia
no treatment
loss of cortical tissue
caused from genetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

LWD

A

build up of leeway bodies in motor and cognitive areas
difficult to diagnosis
loss of memory, confusion, poor attention, muscle stiffness, postural instability
dementia first then motor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

structures involved in motor control

A

cerebral cortex
basal ganglia
cerebellum
thalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Major regions of basal ganglia

A

caudate nucleus
putamen
nucleus accumbent
globus pallidus
subthalamic nucleus
substantia nigra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

region of caudate nucleus

A

head
body
tail

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is the striatum

A

the putamen and caudate nucleus accumbent are collectively referred to as the striatum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what is the substantia nigra

A

black substance
contains neuromelanin synthesized from dopamine
two subregions:
pars compacta- contains dopamine cell bodies
pars reticulate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what are the 4 dopamine system pathways

A

nigrostriatal
mesolimbic
mesocortical
tuberoinfundibulnar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

nigrostriatal

A

where dopamine is vs. axon terminals, regulates movement
-substantia nigra
-striatum- made of caudate and putamen, anterior to midbrain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

mesolimbic

A

in midbrain, addiction pathways (drugs, sex)
-ventral tegmentum
-nucleus accumbens- where axon terminals end

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

mesocortical

A

axons to frontal cortex, regulates decision making, executive functions etc
-ventral tegmentum
-frontal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

tuberoinfundibular

A

hypothalamus
pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

dopamine neurotransmission

A

synthesis
release
receptors (D1-D5)
Uptake (DAT)
Metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what is an auto receptor

A

dopamine binds and auto regulates what is happening in the receptor by increasing or decreasing synthesis and changing dopamine binding in the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what is dopamine transporter(DAT)

A

If dopamine doesn’t bind to receptors, transported recycles it to release it again

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

about how much of the substantia nigra dopamine neurons lost before symptoms occur

A

60-80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

what are lewy bodies

A

aggregates of the protein alpha synuclein protein
found in cell bodies
they are not the cause of PD, there are an outcome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

what are lewy neuritis

A

neuronal processes with alpha synuclein polymers
mainly found in axons and dendrites (extensions of cell bodies)

51
Q

amphipathic N-terminal

A

hydrophobic
interacts with neuronal membrane
found in membrane

52
Q

NAC region

A

non-amyloid component prone to aggregation
imbedded in membrane or hanging off outside membrane
where aggression occurs

53
Q

acidic c-terminal

A

interacts w/ other proteins and metals in neuron

54
Q

why dopamine neurons?

A

dopamine appears to interact w/ alpha synuclein and stabilize oligomers

55
Q

proteosomal

A

gets rid of misfiled proteins

56
Q

oligomers

A

clusters of alpha synuclein, larger structures found in Lewy bodies and neurites

57
Q

what does dopamine do with oligomers

A

dopamine binds to the oligomers and the oligomers stay around longer because they become more stable, dopamine is the only transmitter known to bind to oligomers

58
Q

what do oligomers do?

A

form their own pores by pushing aside phospholipids which allows ions to pass through which changes the ion concentrations and their balance

59
Q

what is the alpha syn cascade hypothesis?

A

the formation of aggregating alpha-syn species precede synaptic dysfunction and subsequent neuronal death
increased levels of differently sized alpha-syn oligomers have been measured in brains w/ Lewy pathology compared to brains from non-diseased individuals
elevated levels of olihpmeric alpha-syn in CSF in PD patients compared to control subjects

60
Q

non-motor symptoms in PD

A

impaired cognition (dopamine, acetylcholine, serotonin, glutamate)
depression (serotonin, glutamate, GABA)
attention dysfunction (dopamine and acetylcholine)
sleep disorders (dopamine, acetylcholine, serotonin, glutamate, GABA)
treated with drugs that target neurotransmitter systems

61
Q

monogenic forms

A

controlled by a single gene
10% of PD cases
highly penetrant, rare gene mutations in families
age of onset tends to be younger

62
Q

idiopathic

A

sporadic
unknown cases
likely multi-factorial, interactions between several genes and environmental

63
Q

penetrance

A

number of people w/ a particular gene that express an associated trait

64
Q

autosomal dominant genes

A

SNCA-alpha synuclein
LRRK2- leucine-rich repeat kinase2

65
Q

autosomal recessive gene

A

PRKN-parkin

66
Q

what were the first genes reported w/ mutations to cause autosomal dominant PD? and characteristics?

A

SNCA-PARK1/PARK4
young onset PD <50 yrs
immediate response to LDOPA
Lewy bodies present at autopsy
rapid progression of motor symptoms
dementia and seizures

67
Q

missense mutations

A

DNA mutation that results in a change in amino acid
likely reduces interaction w/ lipid membrane
lead to increased aggregation of alpha syn

68
Q

what chromosome does duplicate and triplicate SNCA gene repeats of the wild type on?

A

chromosome 4

69
Q

what do triplications lead to?

A

a 10 year earlier age of PD onset and faster progression compared to duplication
increased concentrations of alpha-syn increase likelihood of misfiling
the more copies= the more chances of being diagnosed and faster progression

70
Q

LRRK2-PARK8

A

mutated gene reported to cause autosomal dominant PD
most common, known genetic contributor to PD (1-2% of all cases)
present in dopamine-rich regions
mutations enhance kinase activity
encodes for LRRK2
mutations appear to increase SNCA transcription

71
Q

characteristics of LRRK2-PARK8

A

LO PD >50 yrs
response to LDOPA
inconsistent Lewy bodies presence at autopsy
slow progression of symptoms
dementia is NOT a symptom

72
Q

what can oxidative stress activate?

A

non-mutated LRRK2 in idiopathic PD

73
Q

role of LRRK2 in end-lysosomal trafficking

A

shows how proteins come off membrane and then go back on
If early endoscope gets recycled back to membrane=recycling endosome which then fuses w/ membrane and protein comes back
or earl endoscopes can pair w/ lysosomes which helps degrade proteins on the late end

74
Q

what is an endosome

A

modified vesicle, intracellular so makes protein intracellular

75
Q

what does LRRK2 do?

A

increased activity in protein function
inhibits late endoscope binding to lysosomes
stresses lysosome so the lysosome breaks down

76
Q

what does reactive oxygen species do to LRRK2?

A

increases activity, implications for idiopathic PD
mitochondrial dysfunction can also increase activity

77
Q

what does overactivity of LRRK2 do?

A

increased caspase-dependent apoptosis

78
Q

what is Parkin-PARK2

A

first gene identified causing autosomal recessive PD
protein is part of ubiquitin proteasome system
most common, known cause of young onset PD
if age of first symptoms is <30 years, there is a 25% chance the person has the Parkin mutation
most common cause of juvenile PD <21 yrs
mutated prawn results in protein not being tagged, which causes folded and nonfunctional proteins

79
Q

what do organohalogen industrial contaminants contain?

A

F, Cl, B
electrical insulating coatings, flame-retardant oils, adhesives, plastics
highly stable

80
Q

what are the 2 types of organohalogen contaminants linked to PD?

A

PCBs
PBDEs

81
Q

what are PCBs (polychlorinated biphenyls)

A

209 chemicals
used as fire preventive and insulator in the manufacture of electrical devices because of their ability to withstand exceptionally high temps.

other uses: solvents in paints
hydraulic fluids
window caulking

preferentially accumulate lipid-rich regions of the body

82
Q

how can you be exposed to PCBs?

A

food- bottom feeders and predators b/c PCBs are found in sediment
surface soils- eat or skin exposure (barefoot)
drinking water- not as common, not water soluble
workplace- old fluorescent light transformers that fail, electrical fires, increased incidence of PD in plant workers

83
Q

what are PBDEs (polybrominated biphenyl ethers)?

A

replaced PCBs
commonly used in flame retardants in carpeting, furniture cushions and insulation
lipophilic, resistant to degradation like PCBs (increasing levels in serum and breast milk, penta and exa forms are more frequently detected in humans and wildlife)

84
Q

what are oxygen free radicals?

A

they can damage proteins, lipids, DNA, RNA

85
Q

where is increased PCB desposition?

A

in caudate and substantia nigra

86
Q

Herbicides in PD

A

paraquat- common herbicide in US
maneb- fungicide
ziram- fungicide, widely used on fruits
combined exposure over 25 years increases PD risk
ziram and paraquat exposure increases PD risk by 80%
Agent Orange

87
Q

how does paraquat affect dopamine

A

it can gain access to dopamine neurons by passing through DAT, it then messes with the mitochondrial function

88
Q

what does ziram do

A

prevents misfiled proteins from being broken down

89
Q

how does genes affect paraquat

A

some gene mutations cause more DAT so more paraquat can get in

90
Q

what are dioxins

A

group of chemically related compounds that are environmental pollutants, can cause cancer and increase risk of neurological diseases

91
Q

LDOPA

A

first medication that has proven to treat PD
helps manage motor symptoms
corrects the dopamine deficit
however, it does not reduce the rate of dopaminergic cell loss

92
Q

what is LDOPA given with? and what does it do?

A

carbidopa
inhibits AADC and prevents conversion to DA in periphery
increases the amount of LDOPA that enters brain ( from 1-10%)
product name-sinemet

93
Q

sinemet

A

works for shorter periods of time after years of treatment (2-10 years)
taken 3-8x times a day

94
Q

rasagiline

A

MAO-B inhibitor. FDA approved
taken in early stages, coupled with LDOPA or dopamine agonists to boost effects

95
Q

COMT inhibitors

A

not effective on their own and must be combined with LDOPA

96
Q

stalevo

A

contains LDOPA/carbidopa and entacapone in one pill

97
Q

symptoms unresponsive to LDOPA

A

freezing
posture instability
mental changes (dementia and depression)
speech abnormalities

98
Q

side effects of LDOPA

A

diarrhea, dizziness, drowsiness, dry mouth, increased sweating, loss of appetite, nausea, UTI, vomiting, etc.
LDOPA induced dyskinesias (affects > 50% of patients), after several years of chronic use

99
Q

LDOPA-induced dyskinesia

A

presence of involuntary movements- most commonly observed in uncontrolled movements of the upper body, sometimes In lower body
related to fluctuating LDOPA

100
Q

apokyn (apomorphine)

A

non selective dopamine receptor agonist
helps improve “off” episodes during LDOPA treatment in advanced PD
administered subcutaneously
drug binds to dopamine receptors to mimic dopamine
can work in about 15-20 min
duodenum absorbs it, it enters the bloodstream and is broken down by stomach acid
side effects: nausea and vomiting (may be prescribed Tigamn to suppress)

101
Q

ropinerole (requip) and pramipexole (mirapex)

A

acts at D2, D3, and D4 receptors and some serotonin and norepinephrine receptors
take during LDOPA “off episodes”
more severe side effects: compulsive behaviors, nausea, hypotension, extreme drowsiness
mood disorders: depression, hallucinations, paranoia, and psychosis

102
Q

how does apomorphine, ropinerole, and pramipexole work?

A

act by bypassing the degenerating dopamine neurons and directly stimulate the postsynaptic dopamine receptors in striatum, cortex and other regions

103
Q

depression

A

in 40-70% of patients
tricyclic antidepressants
selective serotonin reuptake inhibitors (SSRIs)-paroxetine (Paxil)

104
Q

dementia

A

estimated in 30-40% of patients
acetylcholinesterase inhibitors; only rivastigmine (Exelon) is FDA approved to treat mild-moderate dementia

105
Q

sleep attacks

A

excessive sleep associated w/ dopamine agonists
can lead to-accidents while driving and falling while standing

106
Q

REM sleep behavior disorder

A

treat w/ clonazepam
acting out of dreams that are vivid

107
Q

psychosis management

A

delusions and hallucinations affect 20-40% of patients
linked to dopamine receptor agonists

108
Q

psychosis treatments

A

pimavanzserin (Nuplazid)- blocks serotonin 2A receptor (FDA approved)
clozapine- causes granulocytes in 1% and requires weekly monitoring of WBC count
quetiapine- no major side effects but may be less effective than clozapine

109
Q

medications in pipeline

A

anle138b- alpha synuclein aggregation inhibitor (MODAG, Pase 1 trial)
immunotherapy (phase 1/2 trials), targets alpha synuclein
DNL201- LRRK2 inhibitor (Denali, Phase 1 trial)
Inosine - precursors of urate, a natural metabolite and major antioxidant in humans (Phase 3 trials)

110
Q

deep brain stimulation

A

most common treatment
electrodes are connected by wires (leads) to a battery (pulse generator, IPG) implanted under the skin below the collarbone
blocks electrical signals from targeted areas of the brain
approved for PD patients who have had PD for at least 4 years and still have motor symptoms
improves stiffness, slowness and tremor
doesn’t work well for imbalance, freezing, or non-motor symptoms
most people can decrease their intake of PD drugs

111
Q

neural transplantation in PD

A

fetal ventral midbrain intrastriatal transplantations (produce dopamine)
humans embryonic dopamine neurons
no signifcant difference in movement
produced non-medication induced dyskinesias in 15% of patients
implanted into nigrostriatal tract

112
Q

early biomarkers

A

about >60% of dopamine neurons lost in striatum before motor symptoms appear
loss of smell appears to occur before motor symptoms in 50-90% of patients (about 4 years before)

113
Q

UPSIT

A

people w/ normal sense of smell can identify about 35 odors correctly
PD patients can only identify 20 or less

114
Q

University of PA Smell Idenifitication Test (UPSIT)

A

original- 40 smells
shorter 12 smell test

115
Q

problems with UPSIT

A

age and allergies can affect performance
females have a better sense of smell
some meds can affect smell
some can’t remember substance names

116
Q

problems with UPSIT

A

age and allergies can affect performance
females have a better sense of smell
some meds can affect smell
some can’t remember substance names

117
Q

purines

A

in DNA and ATP

118
Q

urate (uric acid)

A

antioxidant end product of purine metabolism, eliminated in urine
don’t give as a treatment because it is easily excreted, lots of uric acid can lead to problems

119
Q

why is inosine a better treatment than urate

A

helps create uric acid so the levels of the acid are more controlled and progressive so that way you don’t get a lot at once

120
Q

urate as PD biomarker

A

low levels- linked to higher risk of PD
high levels- lowers risk in men, but not women

121
Q

biomarkers imaging

A

PET and SPECT can be used to monitor changes in DAT levels
PET-expensive
SPECT- used more

122
Q

where is DAT most present

A

on axon terminals in the striatum

123
Q

common DAT ligands

A

123I-beta-CIT (SPECT)
18F-beta-CFT(PET)
18F-FDOPA (PET)

124
Q

why developing alpha syn radiotracers are so difficult

A

18F-ACI-12589= leading contender
increased binding in some patients w/ MSA compared to controls
no differences between PD and controls
they bind in areas that they shouldn’t be binding (lack of specificity)
not FDA approved because 1) needs to cross BBB and be lipiphilic- needs a transporter to pass membrane 2) structure similar to other proteins could be binding to other aggregates (tau and amyloid -not only alpha) 3) we have to get them into neurons to bind to oligomers, Lewy bodies, etc.

Neuro (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions