Parkinson's Flashcards
1
Q
Motor symptoms
A
- cogwheel rigidity
- pin rolling
2
Q
A
PIGD
Tremor dominant
Akinetic syndrome
3
Q
Abbrv.
PIGD
A
Postural Instability Gait Disorder
4
Q
Characteristic features
PIGD
A
Worst prognosis
5
Q
What is the difference between a patient being ‘on’ vs being ‘off’
A
On - medication
Off- no medication
6
Q
Resting tremor
Cardinal parkinson’s feature
A
7
Q
Action tremor
A
E.g. essential tremor present when doing actions (not a feature of PD)
8
Q
Clinical features
What are the clinical features of PD?
A
Reduced arm swing
Face (still)
Micrographia (small handwriting and spiral drawing)
Anosmia
Constipation
Shuffling gait
Freezing extremities
Poor coordination
9
Q
Spirals
A
Parkinson’s resting tremor - micrographia - small spiral
Essential tremor - worse on action, shaky spiral
10
Q
Hoehn & Yahr scale
A
A five stage scale for PD
11
Q
What are three common features of parkinsons seen in young female patients
A
- Dystonia
- Lower limb clonus
- Dyskinesia
12
Q
Define
Dystonia
A
Abnormal writhing or twisting movements of disortions of the body and limbs
13
Q
Management
Levodopa (L-dopa)
A
14
Q
Mx evalaution
L-dopa
A
Therapeutic window decreased after prolonged use resulting in dyskinesia
15
Q
Clinical ax
A
postural instability (pulling back)
16
Q
Postural instability
A
Progressive parkinson’s in tremor dominant or akinetic syndrome?
presenting feature in PIGD
17
Q
A
18
Q
Staging descriptions
Hoehn & Yahr Scale Stage 1
A
- Unilateral tremor only
- No to minimal functional disability
19
Q
Staging descriptions
Hoehn & Yahr Scale Stage 2
A
- Bilateral or midline involvement (tremor).
- Balance isn’t impaired.
20
Q
Staging descriptions
Hoehn & Yahr Scale Stage 3
A
- Bilateral symptoms.
- Mild to moderate disability/
- Impaired postural relfexes
- Physically independent
21
Q
Staging descriptions
Hoehn & Yahr Scale Stage 4
A
- Severe disability.
- Able to walk or stand unassisted.
22
Q
Staging descriptions
Hoehn & Yahr Scale Stage 5
A
- Bed or wheelchair bound.
- Fully dependent on carer for activities of daily living.
23
Q
Freezing
A
Vision
Hearing (vestibulocochlear)
Motor learning
Metronome
Step over the line
24
Q
Non motor symptoms in Parkinson’s
A
- constipation
- speech
- swallowing difficulties
- panic attacks
- hyposmia
- lack of facial expression
- hypotension
- impulse control disorder
- delusionsal behaviour
- sleep
- constitution
- pain
- mood
- gastric reflux
- hallucinations
- sweating
- dementia
These can occur 20 years before diagnosis!
25
Non motor symptoms in Parkinson's
- constipation
- speech
- swallowing difficulties
- panic attacks
| *These can occur 20 years before diagnosis!*
26
Motor symptoms of Parkinson's
- Tremor
- Rigidity
- Akinesia/ Bradykinesia
- Postural disturbance
- poverty of movement
27
Most common non motor symptoms
- nocturia
- urgency
- constipation
- insomnia
- difficulties concentrating
- anxiety
- restless leg syndrome
- sialorrea
- altered libido
- altered sexual capacity
- EDS
- diploplia
28
# True or false
Non-motor symptoms have a greater overall burden on quality of life than motor symptoms
True
29
which other neurochemical pathways are associated with PD symptoms?
* dopamine
* norepinephrine
* serotonin
* acetylcholine
30
How do you assess nonmotor symptoms in Parkinson's?
Parkinsons disease nonmotor symptoms questionnaire
| *Chaudhuri et al. 2006
31
How do you assess motor symptoms in Parkinson's
* Unified parkinsons disease rating scale (UPDRS)
* PKG (parkinsons kinetigraph: wrist worn device)
32
how do you assess non motor symptoms in PD?
non motor symptoms questionnaire (NMSQuest)
| 0: no NMS to more than 14: very severe NMS
33
What is the risk of developing Parkinson's in patients with RBD?
70%
34
Predicting Parkinson's
Skin biopsy and saliva sampling for alpha synuclein
35
Common prodromal features of Parkinson's
Loss of smell
RBD
36
Pathophysiology of Parkinson's
Loss of dopaminergic neurons in the substnatia nigra (basal ganglia). This is seen as a loss of the classic 'comma' nad hypointentisty on MRI.
Lewy bodies in substantia nigra and extranigral regions.
| *Substantia nigra = dopamine and voluntary movement!*
37
Direct vs indirect pathway
In PD the direct pathway is reduced more given intracellular pathology in the dopaminergic neurons particularly with D1 receptors.
Treatments currently work less effectively on D1 receptors than D2 receptors
38
# What are
Lewy bodies
Intracellular aggregates of misfolded alpha-synuclein.
39
Lewy bodies
Collection of alpha synuclein (proteins)
40
# Braak Stages (1-6)
what are the premotor features of braak stages 1 and 2
autonomic and olfactroy disturbances
41
what are the clinical features of braak stages 3 and 4?
sleep and motor disturbances
42
what are the clinical features of braak stages 5 and 6
emotional and cognitive disturbances
43
# Imaging
DaTSCAN
lightning commas (clearly defined in normal brain)
numerical measure of dopamine loss
44
what does a DaTSCAN do?
detects degeneration of dopaminergic nigrostriatal pathway i.e. caudate and putamen
45
what is one disadvantage of DaTSCAN?
aysmmetrical dopamine uptake cannot distinguish PD from other presynaptic parkinsonisms
46
what does a normal DaTSCAN show?
commas
47
what does an abnormal DaTSCAN show?
retreating commas and full stops
48
SWEPL
scan without evidence of dopamine loss
49
Progression - preclinical, orodronmal etc.
50
Gut-brain hypothesis
Suggests the loss of good microbiota/ inlfmmatory reponse/ diet... vagus nerve... alphasynuclein travels up the vagus nerve to the brain
51
What is the evidence supporting the gut-brain hypothesis?
Early lewy body pathology in the enteric nervous system.
Early PD symptoms can include constipation (decades before dx), olfactory loss and RBD.
This suggests prodromal PD (stage 0) symptoms occur outside of the CNS (Brain)
52
What is the enteric nervous system
A complex network of neurons in the walls of the digestive tract (the second brain)
53
# variants
Olfactory dysfunction
Late onset hyposmia
Anosmia
54
# Risk factors that *increase* risk
Environmental risk factors
55
# Risk factors that *decrease* risk
Environmental risk factors
- pesticide exposure
- head injury
56
# Risk factors that *increase* risk
Genetic risk factors
GBA (increases risk by 50%)
PARKIN-1 (increases risk by 2%)
57
# Risk factors that *decrease* risk
Genetic risk factors
58
what are the degenerative differential diagnosis of parkinsonism and tremor disorders
parkinsons or atypical parkinsonism
59
what are the non degenerative differentials for parkinsonism and tremor disorders?
* drug induced
* vascular
* structural
* toxins
* infections
* metabolic
60
61
Parkinson*ism*
Tremor (resting or postural)
Muscular rigidity
Bradykinesia
Postural instability/ gait difficulty (postural abnormailty)
62
what are the features of tremor disorders
* essential tremor
* dystonic tremor
* tremor may be resting or postural
63
what are the atypical parkinsonisms
MSA
PSP
CBS
64
# Positive Parkinson's diagnosis
Which features are needed to support a diagnosis of Parkinson's
Unilateral to bilateral progression of motor symptoms
Positive response to L-dopa
Supportive imaging (CT/ MRI)
65
MSA
* Parkinsonism with autonomic dysfunction
* Positive (abnormal) MIBG scan (dopamine uptake in the heart when blocker is given).
* In Parkinson's dopamine is not taken up by the heart when blocker is given i.e., blocker blocks
* Midbrain atrophy
66
PSP
Postural instability
Downward gaze palsy
Unresponsive to levodopa
Falling backwards
67
CBS
Unilateral parkinsonism
Poor response to levodpa
68
MIBG (metaiodobenzylguanidine) scan
a cardiac imaging test that can be used to help diagnose and differentiate Parkinson's disease (PD) from other parkinsonian syndromes by measuring dopamine uptake in the heart
69
What is the result of the MIBG in brain first PD?
Normal
70
What is the result of the MIBG in body first PD?
Abnormal. Dopamine uptake is **reduced **
71
PDD vs LBD
TIME
PPD - parkinsonism with cognitive decline over a number of years
LBD presenting problem is cogntive decline
72
# Mx - pharmacological
Dopamine replacement therapy
Risagilin (MAO-B inhibitor) working on indo- and exogenous dopamine
73
# MX - non pharmacological
74
# Important
What is the role of Dopamine?
*Dopamine regulates...*
- movement
- cortical excitation of striatal neurons
- excitability of the striatum
- plasticity (LTP)
*When these processes are dysregulated we get the motor symptoms which are characteristc in Parkinson's disease.*
75
# Environmental (geographic) features
Which environmental features affect PD symptomps?
* Warmer weather and more exercise (easier to get out and exercise when it is warmer which improves symptoms and increases mobility/ decreases rigidty)
* Thermoregulation
* Light/ dark sleep-wake cycles
* Diet
* Geography (lower incidence in mediterranean countries)
76
# Genes
Which was the first gene to be identified in PD/ parkinsonism?
Alpha-synuclein on chromosome 4
77
# Clinical features
Tremor
- Presenting feature in 75% of cases
- Tremor frequency 4-6 Hz
- Present at rest
- Absent during sleep
- Decreases during voluntary movement
- Worsend by sleep, anxiety and fatigue
78
# Pathophysiology - *other explanations*
What is the Braak hypothesis?
This is the hypothesis that PD pathology begins in non dopaminergic areas such as the dorsal motor nucleas of the vagus nerve, the enteric nervous sytemem and olfactory bulb. *What has become evident is that there are other pathways involded
79
# Pathophysiology - *other explanations*
What is the staging system?
The staging system hypothesis proposes that progression ascends from the brainstem to the midbrain and then the cortex (rather than from cortex down).
80
Cogwheel rigidity
Slight jerking movements of the arms as you passively move them towards the patients body
81
What are the typical physical features of parkinson's?
* rigidity and trembling of the head and extremities
* rigidity and shuffling gait with short steps
* reduced arm swing
* forward tilt of the trunk
* resting tremor
* passive rigidity
* bradykinesia
* hypokinesia (poverty of movement)
82
Epidemiology of parkinsons disease
* the second most common neurodegenerative disorder
* approximately 6 million diagnosed worlwide
* 1.2 million affected in Europe
83
What is the incidence of parkinsons?
1-2 per 1,000 population
84
# *define*
incidence
A measure of new cases arising in a population over a period of time. Typically, incidence is measured as the
number of people diagnosed per year.
85
# *define*
prevalence
A measure of all individuals affected by the disease at a particular time
86
Is there a higher incidence in males or females?
Males ♂
| *Males aare 1.5 times more likely to get PD than females*
87
What is the mean age of onset?
65
88
What is the excitatory neurotransmitter that stimulates the striatum
Glutamate
89
What are the two inhibitory neurotransmitters implicated in the indirect pathway
dopamine and GABA
90
which receptors are associated with the direct pathway
D1
91
which receptors are associated with the indirect pathway
D2
92
Which brain areas make up the direct pathway?
1. motor cortex
1. substantia nigra pars compactum (SNc)
1. striatum
1. internal globus pallidus/ substantia nigra pars reticulata complex (GPi/SNr)
1. thalamus
93
which brain areas make up the indirect pathway?
1. motor cortex
1. substantia nigra pars compactum (SNc)
1. external globus pallidus (GNe)
1. subthalamic nucleus
1. internal globus pallidus/ substantia nigra pars reticulata complex (GPi/SNr)
1. thalamus
94
body first PD starts with alphasynuclein spatio-temporal propagation where?
intestine
95
brain first PD starts with alphasynuclein spatio-temporal propagation where?
amygdala
96
what are some pharmacological treatments for PD?
tyrosine
levodopa
MAOB inhibtors-safinamide
COMT inhibitors
amantadine (dopamine release)
rotigotine (d1 and d2 recptors)
apomorphine (d1 and d2 receptors)
ropinirole (d2 and d3-5 receptors)
pramipexole (d2 and d2-3 receptors)
97
which two key factors interact in the development of motor complications
**progressive degeneration** and **pulsatile stimulation**
