Parkinson's Disease Flashcards
1
Q
Describe the concept of exercise is medicine
A
- Skilled exercise that entails perceptual & a higher level cognitive processyngtarget prefrontal & associated cortical circuits for executive function
- Aerobic exercise: brood increase in cerebral blood flow including brain circuits in the BG and cerebellum
- Global factors activated: reduced oxidative stress, reduced neuro-inflammation, increased expression of neurotrophic factors
2
Q
Incidence of Parkinson’s
A
- 2nd most common neurodegenerative disorder after Alzhiemer’s
- Global data indicate that PD will become a pandemic
3
Q
Risk factors for PD
A
- Risk increases with age: prevalence rises sharply after 50 y/o
- White Americans & europeans > black africans
- Family history: autosomal dominant Parkinsonism (synuclein, UCHL1, NURR1, LRRK2) and autosomal recessive disease (DJ1, PINK1, parkin)
- Toxic exposures: carbon monoxide, Manganese, Cyanide, Methanol, MPTP, Neuroleptics, Pesticides/Herbicides
- Infection exposures: Measles, Rubella, Herpes simplex 1 & 2
- Men 1.5x more than women
- More years of formal education increases risk
- Smoking may decrease risk
- High levels of physical exercise may lower one’s risk
4
Q
Parts of the basal ganglia
A
- Striatum: caudate nucleus, putamen, & nucleus accumbent
- Lentiform nucleus: putamen & globus pallidus
- Globus pallidus: external and internal segments
- Substantia nigra: pars compacta & pars reticulata
- Subthalamic nucleus (STN)
5
Q
What is the main input and output region of the basal ganglia (BG)
A
- Input: striatum
- Output: globus pallidus internal & substantia nigra reticulata
6
Q
What does the Striatum, Globus pallidus internal, and Substantial nigra reticulata do
A
- Striatum: receives afferents from the cerebral cortex including motor & premotor, cingulate, & prefrontal cortices, & the intralaminar nuclei of the thalamus
- GPi & SNr: project to the thalamus modulating activity of cortical regions & to the brainstem
7
Q
Describe goal directed behavior done by the BG
A
- Caudate head participates in evaluating the full context of potential actions and selects the appropriate action to take
8
Q
Describe social behavior done by the BG
A
- Head of the caudate is part of the circuit that recognizes social cues, regulates self-control, and parses out relevant from irrelevant information
9
Q
Describe emotional/motivation done by the BG
A
- Ventral striatum (also called the nucleus accumbens) and the ventral putamen involved in seeking rewards, an essential aspect of motivation
- Is involved in predictions when the outcome is unknown
10
Q
What is the oculomotor function of the BG
A
- Patients with basal ganglia pathology demonstrate impaired saccadic eye movements
11
Q
Describe the cortico-BG-thamalic motor circuit
A
- Hyperdirect pathway: “Stop”; stops ongoing movements
- Direct pathway: “Go”; facilitates desired movement
- Indirect pathway: “No-Go”; suppresses unwanted movements
12
Q
Describe the Nigrostriatal pathway in the BG
A
- Composed of dopaminergic neurons whose cell bodies are located in the substantial nigra pars compacta
- Project to the BG and synapse in the striatum
- Parkinson’s: the nigrostriatal pathway degenerates = marked loss of dopaminergic neurons that project to the putamen; more modest loss of those that project to the caudate
13
Q
Describe normal function of the basal ganglia (BG)
A
- Target 1: The inhibition of the motor thalamus contributes to a normal level of activity in the corticospinal tracts. This induces these tracts to provide a normal level of facilitation to the lower motor neurons that innervate voluntary muscles.
- Target 2: The IGP inhibits the PPN. Then the PPN inhibits the reticulospinal tracts, which in turn provide the normal level of facilitation to lower motor neurons that innervate postural and girdle muscles, thus controlling muscle tone.
- Target 3: The IGP inhibits the midbrain locomotor region. The midbrain locomotor region stimulates reticulospinal neurons that activate stepping pattern generators, facilitating walking or running.
14
Q
What does an overactive globus pallidus internus excessively inhibit and result in
A
- Motor thalamus
- Pedunculopontine nucleus (PPN)
- Midbrain motor region
- Results in: inadequate facilitation of voluntary movement, overactivity of postural & girdle muscles (rigidity), inadequate facilitation of stepping pattern generators for walking
15
Q
Parkinson’s versus Parkinsonism
A
- Parkinsonism is a general term that refers to a group of neurological disorders that cause movement problems similar to those seen in Parkinson’s disease such as tremors, slow movement and stiffness.
16
Q
What disorders fall under Parkinsonism
A
- Progressive Supranuclear Palsy (PSP)
- Multiple System Atrophy (MSA) aka - - – - Shy-Drager Syndrome
- Vascular Parkinsonism (e.g. basal ganglia strokes)
- Dementia with Lewy Bodies
- Corticobasal Degeneration
- Drug Induced Parkinsonism (anti-psychotics, amphetamines, cocaine)
17
Q
What is the 1st essential criterion for diagnosing Parkinson’s
A
- Parkinsonism, which is defined as bradykinesia in combination with at least 1 of either rest tremor or rigidity
18
Q
Supportive criteria for diagnosis of Parkinson’s disease
A
1) Clear & dramatic beneficial response to dopaminergic therapy
2) Presence of levodopa-induced dyskinesia
3) Rest tremor of a limb documented in clinical exam
4) The presence of either olfactory loss or cardiac sympathetic denervation on MIBG scintigraphy
19
Q
Absolute exclusion criteria for Parkinson’s (presence of any one of these features rules out PD)
A
- Unequivocal cerebellar abnormalities, such as cerebellar gait, limb ataxia, or cerebellar oculomotor abnormalities (eg, sustained gaze evoked nystagmus, macro square wave jerks, hypermetric saccades)
- Downward vertical supranuclear gaze palsy, or selective slowing of downward vertical saccades
- Diagnosis of probable behavioral variant frontotemporal dementia or primary progressive aphasia, defined according to consensus criteria within the first 5 yrs of disease
- Parkinsonian features restricted to the lower limbs for more than 3 yrs
- Treatment with a dopamine receptor blocker or a dopamine-depleting agent in a dose and time-course consistent with drug-induced parkinsonism
- Absence of observable response to high-dose levodopa despite at least moderate severity of disease
- Unequivocal cortical sensory loss (ie, graphesthesia, stereognosis with intact primary sensory modalities), clear limb ideomotor apraxia, or progressive aphasia
- Normal functional neuroimaging of the presynaptic dopaminergic system
- Documentation of an alternative condition known to produce parkinsonism and plausibly connected to the patient’s symptoms, or, the expert evaluating physician, based on the full diagnostic assessment feels that an alternative syndrome is more likely than PD
20
Q
Red flags/indicators that PD is less likely
A
- Rapid progression of gait impairment requiring w/c within 5yrs of onset
- Absence of progression of motor symptoms over ≥5yrs
- Early bulbar dysfunction
- Inspiratory respiratory dysfunction
- Severe autonomic failure in first 5yrs of disease
- Recurrent falls bc of impaired balance within 3yrs of onset
- Disproportionate anterocollis (dystonic)
- Absence of any of the common non-motor features of disease despite 5yrs duration
- Pyramidal weakness or clear pathologic hyperreflexia
- Bilateral symmetric Parkinsonism
21
Q
When is it timely to know a Parkinson’s diagnosis
A
- Earlier the better: early/asymptomatic: some people will want to know their risk
- Depends on availability of neuroprotective strategies: will only want to know if something can be done to alter risk/asymptommatic disease
- Some will only want to know when symptomatic
- Some may never want to know
22
Q
Ideas that support early diagnosis of Parkinson’s
A
- Individual’s right to know
- Highlight opportunities for health improvement & potential disease modification
- Early access to support services
- Opportunity to interact with research
- Provide reason/understanding for symptoms
- Targeted treatment
- Wider window of opportunity to initiate dopamine replacement therapy
23
Q
Ideas that support against early diagnosis of Parkinson’s
A
- Individual’s right to not know
- Limited access to specialist services for existing pts
- Impact on insurance/driving restrictions
- Lack of proven disease modifying treatment
- Risk of causing social/psychological harm
- Risk of over medicalization of aging & over diagnosis
- Stigma associated with diagnosis of PD
24
Q
Subtypes of Parkinson’s Disease
A
- PIGD (postural instability gait difficulty): late onset PD, faster rate of cognitive decline & a higher incidence of dementia, rapid disease progression more common
- Tremor dominant: young onset PD, good prognosis with slow progression, often initially misdiagnosed as essential tremor
- Mixed Parkinson’s Disease
25
Q
Staging of the Hoehn and Lahr classification of disability for Parkinson’s
A
- Stage I: minimal or absent, unilateral if present
- Stage II: minimal bilateral or midline involvement, balance not impaired
- Stage III: impaired righting reflexes, unsteadiness when turning or rising from chair, some activities limited but pt can live independently & continue some forms of employment
- Stage IV: all symptoms present & severe, standing & walking possible only with assistance
- Stage V: confined to bed or wheelchair
26
Q
Common movement disorders in people with Parkinson’s Disease
A
- Bradykinesia: slowness of movement that is ongoing
- Akinesia: indicates failure of voluntary/spontaneous/associated movement
- Episodes of freezing
- Impaired balance & postural control
- Dyskinesia
- Tremor
- Rigidity
- Adaptive responses
27
Q
Cardinal signs of Parkinson’s Disease
A
- Bradykinesia: slow movement
- Rigidity
- Resting tremor
- Postural instability
28
Q
Describe bradykinesia
A
- General reduction of spontaneous movement; appears as abnormal stillness & decrease in facial expressivity (hypomimia=masked facies)
- Causes reduction in speed & amplitude of repetitive movements (finger tapping, walking)
29
Q
Define hypokinesia
A
- Refers to movements that are smaller than desired in particular with repetitive movements
30
Q
Define sequence effect
A
- Refers to amplitude reduction during movement repetition (reduction of hand writing = micrographia)
31
Q
Although both speed and movement amplitude are affected in PD
A
- Speed is usually disproportionally more affected in off state and less normalized by levodopa than the movement amplitude, suggesting that they may be associated with partially separate mechanisms
32
Q
What do ALL people with bradykinesia experience
A
- Difficulty in performing repetitive or sequential movements of the limbs
- Movement size progressively decreases during sequential actions
- When a person with PD stop a movement sequence to rest & begin again the movement size & speed start close to normal and begin to reduce as they continue the sequence
33
Q
Describe rigidity
A
- Stiffness & inflexibility of the limbs, neck, and trunk
- Muscle (increased) tone of an affected limb is always stiff & does not relax sometimes contributing to a decreased ROM
- May manifest as: reduced arm swing, decreased trunk rotation, decreased dissociation of shoulder/hips, rolling/turning, reduced joint ROM during postural transitions & gait
34
Q
Is rigidity more marked in flexor or extensor muscles
A
- More marked in flexor muscles
35
Q
Is rigidity more remarkable during slow or fast stretching
A
- More remarkable during slow stretching
- Help differentiate PD rigidity from spasticity which is worse during fast displacement
36
Q
Define Cogwheel phenomenon
A
- Result of coexisting rigidity and tremor
