9 Parkinson's Disease Flashcards
Basal ganglia components
Caudate Putamen Globus pallidus (internus and externus) Subthalamic nucleus Substantia nigra (pars compacta and pars reticulata)
Striatum
Caudate and putamen
Lentiform nucleus
Globus pallidus and putamen
Basal ganglia function
Regulates movement via control of sequencing, muscle tone, muscle force
Communicates through thalamus to cortex
To lower motor neurons via pedunculopontine nucleus of midbrain
Basal ganglia neurotransmitters
GABA (inhibitory)
Glutamate (excitatory)
Dopamine (both)
Function of direct pathway in BG
Facilitates movement
Nigrostriatal impact in the direct pathway
Dopamine acts as an excitatory NT by binding to D1 receptors, further exciting stratum leading to dis-inhibition of thalamus and increased motor activity
Function of indirect pathway in BG
Suppresses unwanted movement
Nigrostriatal impact in the indirect pathway
Dopamine acts as an inhibitory NT by binding to D2 receptors, inhibiting striatum leading to reduced inhibition of thalamus and increased motor activity
Parkinson’s disease definition
Chronic, progressive CNS disorder that results from death of dopamine-producing cells in substantia nigra
Direct pathway effect in PD
Less dopamine results in decreased facilitation of motor output
Indirect pathway effect in PD
Less dopamine results in increased inhibition of (decreased) motor output- less output occurs because there is more movement suppression
Cellular mechanisms of PD
Oxidative stress Accumulation of toxic proteins Mitochondrial malfunction Inadequate neurotrophic factors (GDNF) Inflammatory glia
Environmental/dietary factors in PD
Pesticides and herbicides, heavy metals
Smoking, caffeine, possibly alcohol protect
Antioxidants, dairy/milk, iron possible positive association
PD from genetic cause
Younger onset, dystonia, early dementia
Cardinal signs of PD
Tremor (70%, begins unilaterally)
Rigidity (cogwheel or leadpipe- proximal, extends distal)
Akinesia/bradykinesia
Postural instability
Other motor signs and symptoms of PD
Freezing of gait Forward flexed posture Incoordination (gross and fine) Hypomimia (facial expression) Dystonia Dysarthria
Non-motor signs and symptoms of PD
Loss of smell Sleep disturbances Mood disorders Dysautonomia Constipation Depression Dysphagia Hypophonia Micrographia Sialorrhea Cognitive dysfunction
Dementia with Lewy bodies
Misfolded alpha-synuclein proteins (Lewy bodies) are hallmark of PD
Progressive dementia- deficits in attention and executive function
Fluctuating cognition
Visual hallucinations
Primary Parkinsonism
85% of all PD cases
Unilateral onset, slow progression
Tremor dominant- more favorable prognosis, relative preservation of mental status, earlier age of onset
Postural instability/ gait disturbance- more rapid progression, severe cog dysfunction, two variants (postural instability with falling and freezing of gait)
Diagnostic criteria for primary Parkinsonism
Clinical diagnosis
Presence of at least 2/4 cardinal signs
Positive levodopa response
Other causes ruled out
Types of secondary Parkinsonism
Vascular
Drug-induced
Infection
Toxins
Vascular Parkinsonism
One or more small strokes
LE and gait more affected
Rest tremor uncommon
Scarce response to levodopa
Drug-induced Parkinsonism
From neuroleptic/anti-psychotic meds
Symmetrical presentation
Orolingual dyskinesia, tardive dyskinesia, or akathisia may be present
Ceasing meds can reverse symptoms, can take up to 2 years
Infection-induced Parkinsonism
Encephalitis
Influenza
HIV
Meningitis
Toxin-induced Parkinsonism
Carbon monoxide Heavy metals (manganese, copper, lead) Mercury (tremor) MPTP Toluene (paint thinners, adhesives)
Parkinson-plus syndromes
Progressive supranuclear palsy
Multiple system atrophy
Corticobasalganglionic degeneration
Progressive supranuclear palsy
Early postural instability and falls
Vertical gaze paresis
Difficulty controlling eyelids (PSP stare)
5.3 year survival
Multiple system atrophy
PD-symptoms, plus autonomic dysfunction and cerebellar dysfunction
8.5 year survival
Corticobasalganglionic degeneration
Focal rigidity Marked dystonia (usually one arm) Limb apraxia Alien hand syndrome PD-symptoms 6-8 year survival
Modified Hoehn and Yahr Scale
0- no disease
1- unilateral
1.5- unilateral and axial
2- bilateral, no balance impairment
2.5- mild bilateral disease with recovery on pull test
3- balance impairment. mild-mod disease. independent.
4- severe disability, but can stand and walk unassisted
5- needs wheelchair or bedridden unless assisted
MDS-UPDRS Motor
Items 0-4 (normal to severe impairment)
Speech, facial expression, tremor, rigidity, coordination, transfers, posture, gait, postural stability, bradykinesia
Sinemet facts
Levodopa- precursor to dopamine that can cross blood-brain barrier
Carbidopa- prevents levodopa from converting in periphery
Side effects- nausea, drowsiness, orthostatic hypotension, dyskinesia, motor fluctuations, hallucinations
Protein can slow absorption
On-off times effect
Dyskinesia- at peak dose
Off- no symptom management between doses
Other PD meds
Dopamine agonists COMT inhibitors MAO type-B inhibitors Anticholinergics Amantadine
Dopamine agonists
Initial or adjunct therapy- delay or reduce motor fluctuations and dyskinesia
Longer half-life than Sinemet but not as effective
Mirapex, Requip, Neupro
COMT inhibitors
Prevent peripheral degradation of levodopa
May decrease “off” time or dosage
Comtan, Tasmar
MAO type-B inhibitors
Block breakdown of dopamine in brain
Selegiline, Rasagiline
Anticholinergics
Inhibit dopamine reuptake in striatum
Mainly for tremors and rigidity
Artane, Cogentin
Amantadine
Dopamine agonist and dopamine reuptake inhibitor
Often used to treat dyskinesia
Symmetrel, Kemadrin
Symptoms unresponsive to meds
Postural instability
Freezing
Mental changes
ANS dysfunction
Deep brain stimulation
Electrodes in brain connected to implantable pulse generator in chest
Minimize “off” times and dyskinesia, lower dosage of meds
Results no better than “on” time
For idiopathic PD only
Intact cog function, good dopamine response
Target sites for DBS
Thalamus- reduces tremor, no other symptoms
Globus pallidus internus or subthalamic nucleus- reduces tremor, rigidity, bradykinesia, dyskinesia
STN DBS- better ADLs in “off” times, greater med reduction
Dopamine’s effect on limbic functions
Low- depression, apathy, anhedonia, anxiety
High- euphoria/ mania, impulsivity, pleasure-seeking/risk-taking behavior
Depression in PD
Most common psychiatric symptom in PD- 40%
Depressed mood, diminished interest/pleasure, fatigue, sleep changes, poor concentration, change in appetite
Exercise effects in PD
May delay or prevent PD in healthy individuals
May slow disease progression and motor deterioration in early PD
High-intensity exercise for PD
More normal corticomotor excitability
Lengthened cortical silent period (more normal corticomotor excitability)
Forced use cycling effects
Improvement in UPDRS-motor, bimanual dexterity, rigidity, bradykinesia
Greater reliance on feedforward vs feedback processes- shifts central motor control processes
Forced exercise has similar effects on symptoms as meds do
Individual vs group treatment for PD
Individual- best for balance and function improvements
Group- best for gait
Treadmill training for PD
Improved gait parameters
Improved balance and motor performance
Improved QOL
Reduced fatigue
Boxing for PD
Improved balance, gait, disability, QOL
Mild-mod PD
Dancing for PD
Tango slightly superior
Partnered dancers more compliant
Mild-mod PD
Tai chi for PD
Improve postural stability, reduce falls, improve motor function, improve QOL
Inconsistent effects on gait
Dual-task training for PD
Best for mild-mod PD
Improves gait and balance in dual task, and in single-task gait
How strategies work
Bypass basal ganglia via cortical, cerebellar, or brainstem pathways to normalize movement
Shifts to explicit learning vs implicit
BESTest
36-item balance assessment Biomechanical constraints, stability constraints Anticipatory postural adjustments Reactive postural responses Sensory orientation Stability in gait Score 0-3 (severe to normal) Max score 108, converted to percentage Cut-off <69% for fall risk
Mini-BESTest
14-item scale 0-2 (severe to normal) Max 28 Use AD lowers each item by 1 point Score of 0 if needs assistance <23/28 is fall risk
Freezing of gait questionnaire
6-item, to be given during “on” state
0 (no symptoms) to 4 (most severe)
Total 0-24 (high score is severe freezing)
Based on past week or overall presence of FOG throughout day
Parkinson’s disease questionnaire-39
Self-report, QOL
Experience over past month
Mobility, ADLs, emotional well-being, stigma, cognition, communication, bodily discomfort
0 (never) to 4 (always)
Treatment of freezing of gait
Improve weight shifting
External cueing
Exercise in small spaces
Dual task training
Trail-making test involves
Attention shifting
