Week 7- Basal Ganglia Disorders (Parkinson's) Flashcards
PART 1: NEUROANATOMY REVIEW
PART 1: NEUROANATOMY REVIEW
What are the (4) parts of the basal ganglia?
- Caudate
- Putamen
- Globus Pallidus (internus and externus)
- Substantia Nigra (compacta and reticularis)
- What are the caudate and putamen typically referred to?
- Virtually all inputs to the basal ganglia arrive via the ______ and _______.
- Outgoing information leaves the basal ganglia via the ___________ and _________.
- Striatum
- caudate and putamen
- globus pallidus and substantia nigra
The globus pallidus and substantia nigra send information out from the basal ganglia back up to the cortex via the _________, but also send projections down to important structures in our brain stem including our _________ ________.
- thalamus
- reticular formation
The basal ganglia has ______ and ________ function.
motor (control) and nonmotor
Basal Ganglia Motor Control:
- _______ and ________ of movement.
- Prevention of unwanted movements through _________ control.
- Direct and Indirect pathways that work together to help create ________ movement.
- INITIATION and EXECUTION
- inhibitory
- desired
What are some additional roles of the basal ganglia?
- Eye movement loop
- Goal-directed behavior loop
- Social behavior loop
- Emotion loop
Does the basal ganglia directly equate to movement?
No, modulates incoming info from the cortex and then sends it back up to help regulate things like muscle contraction, muscle force, multi-joint movements and sequencing of movements.
- What is initiation?
- What is execution?
- “I want to move, I move.”
- How well we move, how forcefully we move.
Our goal-directed and social behavior loops are often combined into the __________ loop that involves the ___________ _________ cortex.
- prefrontal
- dorsolateral prefrontal cortex
Our emotion loop is often referred to as the __________ loop which involves the anterior cingulate and orbital frontal cortex.
-limbic
Direct (GO) Pathway of Basal Ganglia Control:
- ) Thalamus, gone unchecked, sends constant __________ signals to cortex to elicit movement.
- ) _____, _____ inhibit thalamus to prevent unwanted movement.
- ) When a movement is needed, cortex sends information to striatum, which in turns ________ GP & SN. In turn, opens gate for thalamus to resume excitatory projections to cortex to elicit movement.
- excitatory
- Globus pallidus internus (GPi) and Substantia nigra pars reticularis (SNpr).
- inhibits
What inhibitory NT is sent to the thalamus via the GP and SN to prevent unwanted movement?
GABA
What excitatory NT is sent to the striatum via the cortex to cause the striatum to send GABA to the GP and SN to turn off its inhibitory function?
Glutamate
The ____________ pathway is what happens when we want to move.
Direct (GO)
- Normally the globus pallidus externus (GPe) acts by ___________ the subthalamic nuclei.
- When the indirect pathway is activated, the cortex will send an excitatory message to the striatum, and instead of talking to the GPi and SNpr, it sends _________ information to the GPe.
- This means the GPe can no longer inhibit the subthalamic nuclei, then the cortex starts directly sending excitatory information to the __________ _________.
- The subthalmic nuclei then sends excitatory information to the ______ and ______ causing movement to stop.
- inhibiting
- inhibitory
- subthalamic nuclei
- GPi and SNpr
The ___________ pathway is what happens when we don’t want movement.
-Indirect (NO GO)
- What structure is watching over both the Direct (GO) and Indirect (NO GO) pathway by modulating loops?
- It has connections directly to the _________.
- These connections modulate activity of indirect pathway through ________ release in striatum.
- Substantia Nigra pars compacta (SNpc)
- striatum
- dopamine
What are the main BG neurotransmitters?
- Dopamine
- Acetylcholine (ACh)
- GABA, Glutamate
Dopamine:
- Made in _________, which modulates striatum activity through dopamine release to impact Direct and Indirect pathways.
- Excitatory to striatum neurons in _______ pathway, inhibitory to striatum neurons in ________ pathway.
- Dual effect = powerful ________ in suppression of thalamus by BG, which leads to further facilitation of movement.
- SNpc
- direct, indirect
- DECREASE
Acetylcholine:
- Inhibits _________ when appropriate.
- Can quickly interrupt ongoing ________ behavior in response to salient environmental stimuli.
- dopamine
- motor
________ and _________ are the primary NTs in direct and indirect pathways.
GABA and Glutamate
PART 2: INTRO TO PARKINSON’S DISEASE
PART 2: INTRO TO PARKINSON’S DISEASE
What are some general SxS of BG dysfunction? (3)
- Difficulty initiating, continuing, or stopping movement.
- Muscle tone abnormalities (rigidity).
- Increased involuntary movements (hemiballismus, athetosis, chorea, tremor),
- What is the most common disorder associated with BG dysfunction?
- It is an ________, _______ progressive degenerative disease.
- Does it have motor or non-motor symptoms?
- Parkinson’s Disease
- idiopathic, slowly progressive
- both motor and non-motor
Parkinson’s Incidence and Prevalence:
- Incidence ________ with age.
- ________ cases in US
- Does it affect men or women more?
- What is the mean age of onset?
- _______ prevalence in black and Asian populations?
- increases
- 1 million
- Men>Women (3:2)
- early 60s
- decreased
- Parkinson’s Disease can also be called _________ ___________.
- What is the cause?
- Primary Parkinsonism
- Unknown, hypothesis is a complex interaction of factors (age, genetics, environment)
What are some causes of Secondary Parkinsonism?
- Infections/postencephalitic
- atherosclerosis
- toxic
- drug-induced
Parkinson’s Disease Pathophysiology:
-Degeneration of ___________ neurons in the BG
(Loss of DA stores in substantia nigra).
-As disease progresses, numerous other regions of brains involved as well as impaired modulation of other _____________.
- dopaminergic
- neurotransmitters
What are 3 ways we may diagnose Parkinson’s Disease?
- clinical examination
- levadopa/carbidopa trial (recent guidelines shifting away)
- SPECT scan (DaTscan)
What is the only definitive way to diagnose Parkinson’s?
post-mortem examination of brain
PART 3: PARKINSON’S DISEASE MOTOR SYMPTOMS
PART 3: PARKINSON’S DISEASE MOTOR SYMPTOMS
Motor symptoms do not appear until ~___% of neurodegeneration has already occurred in the basal ganglia.
~60%
What are the 4 cardinal motor symptoms of Parkinson’s Disease?
- Bradykinesia***
- Akinesia
- Hypokinesia
- Rigidity
Bradykinesia, Akinesia, Hypokinesia:
- __________ and ___________ movements affected.
- Initiation, alteration in direction, stoppage all affected
- _________ tasks > _______ commands
- spontaneous and purposeful
- complex tasks > simple commands
- What is bradykinesia?
- What is akinesia?
- What is hypokinesia?
- Bradykinesia = Reduction (slowing) of movement.
- Akinesia = Loss of spontaneous movement.
- Hypokinesia = Decreased amplitude or range of movement.
- __________ is present in all types and subtypes of Parkinson’s.
- It is a result of insufficient recruitment of muscle ______ during movement due to dopamine depletion.
- Bradykinesia
- force
Where will we see akinesia over bradykinesia in Parkinson’s Disease?
- In the face, patients will present with masked, blunted, resting facial features.
- Loss of arm movement during gait.
- Hypokinesia, like bradykinesia, is thought to be an issue of ______ production.
- Where will we easily find hypokinesia in Parkinson’s?
-force
- When asking patient to write something down. (small and squished letters)
- Very minimal trunk movement when walking.
What are often the most disabling symptoms of Parkinson’s?
Kinesias
Rigidity:
- Felt _________ in all directions. (asymmetrical early → eventual whole-body involvement)
- Is it usually seen proximally or distal first?
- Leads to increased ________ load, emotional stress, energy expenditure of movement. (long-term effects are decresed ROM, contractures, postural deformities).
- Presents as _____ _____ or _________ rigidity.
- uniformly
- proximal
- cognitive load
- lead pipe or cogwheel rigidity
What is the difference between lead pipe and cogwheel?
- Lead pipe: sustained resistance
- Cogwheel: jerky, ratchet-like (lead pipe + tremor)
What are 2 other cardinal motor symptoms seen with Parkinson’s?
- Tremor
- Postural Instability
Tremor:
-________ tremor early on (can see kinetic as disease progresses).
-______ and _______ most common, can see in head, neck, jaw or tongue.
Tends to be ______, _____ frequency.
- resting
- Hand and foot
- mild, low frequency
What is a good piece of education to give to patients regarding tremor?
Tremors are often exacerbated by stress, emotional strain, or excitement. Relaxation techniques can be used to help.
Postural Instability:
- Abnormal and inflexible postural responses.
- Smaller functional limits of _________.
- Difficulties with ____-________ movements.
- Reduced ___________ postural adjustments and control.
- Abnormal patterns of ____________.
- _______ disorientation.
- Additional contributing factors: rigidity, weakness, loss of ROM, freezing, medication side effects.
- stability
- self-initiated
- anticipatory
- coactivation
- midline
The most frequent presentation of midline disorientation in Parkinson’s is __________.
retropulsion
The Implications of PD Parkinson’s Instability:
- Patients with PD are __x more likely to fall.
- Falls become increasingly prevalent as disease progresses to the ________ stages. (Disappear in late stages as patients become immobile)
- ___% of patients with PD fall each year.
- ___% of patients with PD report recurrent falls.
- ___% of those that fall experience injury.
- ___% of patients experience a hip fracture within 10 years of diagnosis.
- 9x
- middle
- 70%
- 50%
- 40%
- 25%
- What are the 3 biggest risk factors for falls in PD patients?
- What are some other risk factors for falls?
- Postural Instability
- Disease Severity
- Gait Impairments (most notable in freezing gait)
-dementia, depression, postural hypotension, involuntary movements from long-term medication use
Do we see weakness with Parkinson’s patients? Why?
Yes
- Decrease in torque production at all speeds
- Dopamine related?
- EMG: Delayed MU recruitment, asynchronization
- Disuse weakness common
- Fatigue
Parkinson’s patients also present with a breakdown of complex motor _________. This involves sequential movements and transitioning between movements.
planning
PART 4: GAIT DISTURBANCES AND NON-MOTOR IMPAIRMENTS
PART 4: GAIT DISTURBANCES AND NON-MOTOR IMPAIRMENTS
Gait characteristics of Parkinson’s are broken into what 2 characteristics? What are they?
- Continuous (typically seen whenever they get up and around)
- Episodic (what happens occasionally)
Continuous Characteristics:
- Overall ___________ presentation (smaller steps/reduced arm swing/minimal trunk rotation, LE regidity/axial rigidity).
- Increased __________ and ____________.
- Poor __________ control (achieving, maintaining, and restoring balance impacted)
As Disease Progresses:
- _________ gait pattern emerges (“festinating gait” becomes more continuous)
- Increased tendency for _____/_______pulsion.
- hypokinetic
- variability and asymmetry
- postural
- shuffling
- retropulsion/anteropulsion
What are the 4 main episodic gait characteristics seen with PD?
- Festinating Gait Pattern
- Midline Disorientation
- En Bloc Turning
- Freezing of Gait
Episodic gait characteristics of PD are seen in the _____/_______ stages of PD.
early/middle
- What is festinating gait pattern?
- How is a festinating gait pattern different from shuffling gait?
- Unintentionally quick, shuffled steps that worsens as gait progresses.
- They start to take increasingly shorter and faster steps as they are walking. (shuffle gait doesn’t change with time)
- Common types of midline disorientation?
- Why can midline disorientation be episodic?
- retropulsion/anteropulsion
- Tends to be mild but present, might not impact someone performing easier tasks such as flat surface but will when put on incline. (specific tasks)
What is en bloc turning?
Strategy to overcome significant difficulty with turning.
En Bloc Turning:
- ___ rotations of head, trunk, pelvis to complete turns.
- ___ instabilities observed during turns.
- Reduced ______, more steps to complete turns.
- Can be further impacted by ___ postural tone, axial rigidity, and/or loss of flexibility.
- ↓
- ↑
- speed
- ↑
What is “freezing of gait”?
“Brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk.”
Freezing of Gait:
- How long does it typically last?
- Leads to significant ____ risk.
- What is the mechanism of FoG?
- When is it most often seen?
- Can be exacerbated by _______/______/_______.
- Does it worsen with disease progression?
- Typically last a few seconds but can occasionally exceed up to 30s, and even can be entirely unable to generate steps for several minutes until compensatory or manual interventions are applied.
- fall risk
- not well understood
- When it involves a confrontation of competing afferent stimuli (walking through doorways, turning, variable surfaces).
- stress/fatigue/distractions
- Yes
List non-motor symptoms of PD and %.
- Loss of smell (90%)
- Sleep disturbances (90%)
- Constipation (20%–79%)
- Pain and Paraesthesias (76%)
- Visual impairments (75%)
- Orthostatic hypotension (may or may not be symptomatic) (60%)
- Fatigue (58%)
- Urinary symptoms (25%–50%)
- Apathy (40%)
- Early mild cognitive impairment (25%)
- Dementia (80% late stage)
- Depression (22%)
Pain:
- Pain is common with PD and is present in __-__% of patients as an early symptom. (MSK, dystonic, neuropathic, central, akathisia)
- What is akathisia?
- Central pain though to be due to abnormal modulation of pain caused by _________ deficiency.
- What are common areas of pain?
- ___________ common.
- 60-80%
- Inner restlessness, inability to remain still.
- dopamine
- lower back, legs, shoulders, face
- hypersensitivities
PART 5: CLASSIFICATION, MEDICAL MANAGEMENT, AND PROGNOSIS
PART 5: CLASSIFICATION, MEDICAL MANAGEMENT, AND PROGNOSIS
What are the 2 ways we classify PD?
- Symptoms
- Where in progression disease pattern is at.
What are the 2 main subtypes (phenotypes) of PD?
- Postural Instability Gait Disorder phenotype
- Tremor-Dominant phenotype
Patients will be identified as part of phenotypes based off of what?
Most early and dominant symptoms.
Postural Instability Gait Disorder:
- ___% of all PD cases.
- What are the dominant symptoms?
- More _________ disease course.
- 25%
- postural instability and gait disturbances
- significant
Tremor-Dominant:
- Typically demonstrate ________ problems with bradykinesia or postural instability.
- Lower prevalence of ____-_______ symptoms.
- Less likely to develop _________ and other _______ deficits.
- fewer
- non-motor
- dementia and other cognitive deficits
- What scale is used for staging of PD?
- How many stages are there?
- It primarily considers ______ impairments.
- What 3 things does it look at?
- Hoehn and Yahr Scale for Staging of PD
- 5 Stages
- motor
- unilateral vs bilateral, impact balance, impact function
Describe each stage of PD.
Stage 1
-Unilateral involvement only usually with minimal or no functional disability.
Stage 2
-Bilateral or midline involvement without impairment of balance.
Stage 3
-Bilateral disease: mild-to-moderate disability with impaired postural reflexes; physically independent.
Stage 4
-Severely disabling disease; still able to walk or stand unassisted.
Stage 5
-Confinement to bed or wheelchair unless aided.
At which stage do we see the classic PD flexed position?
Stage 3
At which stage do we start to see akinesias over bradykinesias?
Stage 4
What is the primary mode of medical management for PD?
Medication
What are some drugs used to manage PD?
- Carbidopa and Levodopa (Sinamet)
- Dopamine agonists
- Catechol-O-methyltransferase (COMT) inhibitors
- Monoamine oxidase-B (MOA-B) inhibitors
- Anticholinergics
PD symptoms can be reduced by trying to elevate depleted _________ or reducing _________ effects.
- dopamine
- acetylcholine
- What is the primary drug (first line of defense) that will be prescribed to PD patients?
- This drug is a _________ replacement drug.
- __________ converts into dopamine; _________ facilitates the process and minimizes the side effects.
- Sinamet
- dopamine
- levodopa, carbidopa
What drugs mimic effects of dopamine by stimulating dopamine receptors? They can be used to delay the need for C/L, but often is used in combination with it.
Dopamine agonists
What drugs increase the availability of dopamine by blocking disruptive enzymes? They must be used with C/L to be effective.
COMT inhibitors
What drugs function mimics that of COMT inhibitors but is often used as monotherapy in early stages or in combination with C/L later on?
MAO-B inhibitors
What drugs combat the reciprocal increase of ACh that is seen in response to dopamine depletion and is primarily used to treat tremors in early stages of disease?
Anticholinergics
Early initiation of pharmaceuticals are shown to help with progression of disease long-term, but prolonged treatment can lead to ___________.
dyskinesias
Describe ON/OFF times of PD medications.
- Sinamet and other PD drugs have half lives that often lead to times in which effects of medications have worn off (“OFF times”)
- Patients’ function and capabilities can look significantly different when comparing ON and OFF times.
- With disease progression, see more fluctuations and increased frequencies during the day of OFF times.
Does levadopa improve all Parkinson’s symptoms?
No
Levadopa:
- Does not improve _____ rigidity.
- Typically worsens _________ responses to external perturbations.
- Shown to improve hypokinetic gait in the early stages of PD but tends to be less effective at improving gait as the disease progresses.
- Generally improves freezing of gait in the “___” state but not during the “___” state.
- axial
- postural
- “OFF”, “ON”
What is the common surgical option used for PD?
Deep Brain Stimulation
Deep Brain Stimulation:
-Typically reserved for bradykinesia, rigidity and tremor in patients who no longer respond to __________ in a predictable manner or who suffer medication-induced dyskinesias.
Can increase ____ periods, reduce frequency of _____ periods, and lead to a reduction in many PD symptoms.
- medication
- ON, OFF
Symptoms not responsive to medication _____ responsive to surgery.
are not
Prognosis:
- Symptoms of PD vary widely and disease can progress very quickly or can go several decades with _____ limitations.
- Typically does not lead directly to mortality. Life expectancy often just slightly less than average. What are some common secondary sequalae that can lead to death?
- mild
- CHF and Pneumonia
List some negative prognostic factors of PD.
- Degree of symmetry of symptoms
- Postural Instability Gait Disorder (PIGD) phenotype
- Higher baseline UPDRS motor scores
- Age at onset
- Early cognitive decline or baseline cognitive impairment
- Smoking history
- Male gender
PART 6: OUTCOME MEASURES
PART 6: OUTCOME MEASURES
List some PD outcome measures.
- PDQ-39
- MDS-UPDRS
- Montreal Cognitive Assessment (MoCA)
- Parkinson’s Fatigue Scale
- Freezing of Gait Questionnaire
PDQ-39:
- Evaluates Parkinson’s Disease-specific health-related quality of life over the last _______.
- What are the 8 domains assessed?
- Closely correlates with ____, better construct validity than generic measures.
- month
- Mobility, ADLs, emotional well-being, stigma, social support, cognition, communication, bodily discomfort
- H and Y scale
MDS-UPDRS:
- ______________ assessment designed to monitor the burden and extend of PD across the longitudinal disease course.
- What are the 4 parts of MDS-UPDRS?
-comprehensive (33 pages)
- Part I: Non-motor experiences of daily living (Cognition, emotions, hallucinations, depression, anxiety, apathy, etc)
- Part II: Motor experiences of daily living (Speech, saliva/drooling, chewing/swallowing, eating, dressing, hygiene, tremor, transferring, walking, etc)
- Part III: Motor examination
- Part IV: Motor complications (Functional impact of dyskinesias, OFF states, functional impact of dystonia, etc)
MoCA:
- Rapid screen of __________ abilities designed to detect dysfunction.
- Common component of OT evaluation.
- What is the cut-off score for normal cognitive function?
- Is it specific to Parkinson’s disease?
- cognitive
- > /=26 points considered normal cognitive function
- No, but is recommended.
Parkinson’s Fatigue Scale:
- Reflection of _________ aspects of fatigue; measures presence of fatigue and impact on daily function.
- Excludes _________ and __________ features of fatigue.
- Excludes _________ and ___________ of fatigue symptoms.
-physical
-cognitive and emotional
severity and frequency
Freezing of Gait Questionnaire:
- Assess FOG severity unrelated to _______ in patients with PD.
- 6-item questionnaire with 4 questions on FOG _____________ and 2 questions on disturbances in ______.
- Correlates well with _______ stage.
- falls
- frequency, gait
- H and Y
