Parkinson's Disease

Question 1

briefly describe the anatomy of the basal ganglia

Answer 1

1. Striatum
   
   1. cuadate
   2. putamen
2. Globus pallidus
   
   1. internus
   2. externus
3. Substantia nigra
   
   1. compacta
   2. reticularis

Question 2

what is the role of the basal ganglia?

Answer 2

1. Motor control
   
   • initation and execution of movement
   • prevention of unwanted movements through inhibitory control
   • direct and indirect pathways that work together to help create desired movement
2. Eye-movement loop
3. Goal-directed behavior loop
4. Social behavior loop
5. Emotion loop

Question 3

describe the direct pathway of basal ganlia control

Answer 3

1. Thalamus, gone unchecked, sends constant excitatory signals to cortex to elicit movement
2. GP, SN inhibit thalamus to prevent unwanted movement
3. When movement is needed, cortex sends info to striatum, which in turn inhibits GP and SN
   
   • this opens gate for thalamus to resume excitatory projections to cortex to elicit movement

Question 4

describe the indirect pathway of the basal ganglia

Answer 4

1. When movement is NOT needed, cortex has striatum inhibit GPe, losing its usual ability to inhibit subthalamic nuclei
2. Cortex then activates subthalamic nuclei, who’s job is to send excitatory signals to GPi and SN, which strengthens their inhibition of thalamus

Question 5

describe regulation of the direct and indirect loops

Answer 5

1. Substania Nigra pars compacta neurons have connections to the striatum
2. those connections modulate activity of indirect pathway through dopamine release in striatum

Question 6

List important BG neurotransmitter

Answer 6

1. Dopamine
2. Acetylcholine
3. GABA
4. Glutamate

Question 7

where is dopamine made and what does it do?

Answer 7

1. Made in substantia nigra pars compacta
2. SNPC uses it to modulate striatum activity by releasing dopamine to impact both direct/indirect pathways
   
   • excitatory to striatum neurons in direct pathway
   • inhibitory to striatum in indirect pathway
   • dual effect = powerful decrease in suppression of thalamus BG → futher facilitation of movement

Question 8

what is the role of ACh?

Answer 8

1. inhibits dopamine when appropriate
2. can quickly interrupt ongoing motor behavior in response to salient environment stimuli

Question 9

what is the role of GABA and Glutamate?

Answer 9

both are primary NT in direct and indirect pathways

GABA → inhibitory

Glutamate → excitatory

Question 10

List BG dysfunctions/disorders

Answer 10

1. Parkinson’s Disease
   
   • Parkinsonisms
2. Huntington’s Disease
3. Tardive Dyskinesia
4. Dystonia

Question 11

List other causes of BG dysfunction

Answer 11

1. CO poisoning
2. Copper poisoning
3. Drug OD
4. Head injury
5. Infection
6. Liver disease
7. Metabolic problems
8. MS
9. Side effects of certain meds
10. Stroke
11. Tumors

Question 12

List the general S/S of BG dysfunctions

Answer 12

1. Difficulty initiating, continuing or stopping movements
2. Muscle tone abnormalities → rigidity
3. Increased involuntary movements
   
   • Hemiballismus
   • Athetosis
   • Chorea
   • Tremor

Question 13

define hemiballismus

Answer 13

rare hyperkinetic movement disoder (subtype of chorea)

characterized by violent involuntary limb movements, unilaterally

movements are wider and more intense than chorea

Question 14

define athetosis

Answer 14

slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases arms, legs, neck and tongue

Question 15

define chorea

Answer 15

involuntary, irregular unpredictable muscle movements

Question 16

What is Parkinson’s Disease?

Answer 16

idiopathic, slowly progressive degenerative disease with non-motor and motor symptoms

Question 17

List S/S of PD

Answer 17

1. Parkinsonian gait
2. Slowed movement
3. Reduced arm swing
4. Rigidity
5. Freezing
6. Shuffling steps
7. Postural instability
8. Asymmetric resting tremor
9. Mask like face

Question 18

Describe incidence and prevalance of PD

Answer 18

• 1-2% of persons > 60
  
  • incidience increases w/age
• 1 million cases in US, 5-10 million world wide
• Men > women (3:2)
• Mean age of onset: early 60s
  
  • young onset (21-40) PD occurs in 5-10% of cases
• decreased prevalence in black and Asian populations

Question 19

List and describe the 2 etiologic subgroups of PD

Answer 19

1. Primary Parkinsonism (PD) → unknown etiology
   
   • hypothesis - complex interaction of factors
     
     • age, genetics, environment
2. Secondary Parkinsonism
   
   • infectious/postcephalitic, atherosclerosis, toxic, drug-induced

Question 20

describe the pathophysiology of PD

Answer 20

1. degeneration of dopaminergic neurons in BG
   
   • loss of DA stores in substania nigra
2. As disease progresses, numerous other regions of brains involved as well as impaired modulation of other NTs

Question 21

How is PD clinically dx?

Answer 21

1. Clinical exam → dx of exclusion
2. may do a levodopa/carbidopa trial
   
   • most recent guidelines are shifting away from this
3. Some pts will undergo SPECT scan
   
   • dopamine transporter scan (DaTscan)
4. Only definitive way to dx PD is post-mortem exam of the brain

Question 22

List the 4 cardinal PD motor symptoms

Answer 22

1. Bradykinesia, Akinesia, Hypokinesia
2. Rigidity
3. Tremor
4. Postural Instability

Question 23

T/F: motor symptoms appear early on in the disease progression

Answer 23

FALSE

motor symptoms do not appear until - 60% neurodegeneration has already occured in BG

Question 24

describe the motor symptoms of bradykinesia, akinesia, hypokinesia

Answer 24

1. Spontaneous and purposeful movements affected
2. initiation, alteration in direction, stoppage all affected
3. Complex tasks > simple commands

Question 25

what is the difference between bradykinesia, akinesia, hypokinesia?

Answer 25

1. Bradykinesia → slowing/reducing of movement * cardinal feature of all parkinsosim disorders * multifactorial * result of insufficient recruitment of muscle force during movement * BG's perception of how much force it wants to generate decreases 2. Akinesia → complete loss of movement * will see in face * loss of arm swing in gait 3. Hypokinesia → reduced movements * thought to be an issue w/force production * noticeable during writing tasks → letters look small and barely legible * minimal trunk movement during gait

Question 26

T/F: bradykinesia, akinesia, and hypokinesia are often the most disabiling symptom of PD?

Answer 26

TRUE

Question 27

describe the PD motor impairment → rigidity

Answer 27

1. felt uniformly in all directions * asymmetrical early on in disease → eventual whole-body involvement (including trunk) 2. usually seen proximally first 3. leads to increased cognitive load, emotional stress energy expenditure of movements * long-term effects = decreased ROM, contractures, postural deformities 4. Types: * lead pipe → sustained resistance * cogwheel → jerky, ratchet-like (lead pipe + tremor)

Question 28

describe the motor impairment → tremor

Answer 28

1. resting tremor early on (can see kinetic as disease progresses) 2. hands and foot most common, can see in head, neck, jaw or tongue 3. tends to be mild, low frequency 4. 70% of PD pts will experience a tremor at some point in the disease progression 5. progression in 2 ways: * resting to moving tremor * travel to bilateral involvement

Question 29

describe the motor impairment → postural instability

Answer 29

1. abnormal and inflexible postural responses 2. smaller functional LOS 3. difficulties w/self-initiated movements 4. reduced anticipatory postural adjustments and control 5. abnormal patterns of coactivation 6. midline disorientation 7. additional contributing factors: * rigidity * weakness * loss of ROM * freezing * meds AE

Question 30

What are the implications of PD Postural Instability?

Answer 30

1. Pts with PD are 9x more likely to fall 2. Falls become increasingly prevalent as disease progresses to the middle stages * disappear in late stages as pts become immobile

Question 31

what are the biggest overall risk factors for falls in PD pts?

Answer 31

1. postural instability 2. disease severity 3. gait impairments (most notably Freezing of gait) Other: dementia, depression, postural hypotension, involuntary movements from long-term med use

Question 32

List additional motor symptoms of PD (outside of the 4 cardinal symptoms)

Answer 32

1. Weakness * many potential causes: * decrease in torque production at all speeds * dopamine related? * EMG: delayed MU recruitment, asynchronization * disuse weakness common * Fatigue 2. Breakdown of complex motor planning * sequential movements * transitioning between movements