#7 Parkinsons Disease

Question 1

What is the difference between hypokinetic and hyperkinetic?

Answer 1

Hypokinetic: decreased or slow movement, loss of direct pathway in basal ganglia, loss of dopamine, Parkinsonism

Hyperkinetic: excessive movement, loss of direct pathway in basal ganglia, loss of inhibition in the thalamus, chorea/dystonia

Question 2

What are the two pathways in the basal ganglia? What do they do

Answer 2

Direct pathway: facilitates movement
Indirect pathway: inhibits movement

Question 3

What is the role of the basal ganglia?

Answer 3

Controls voluntary movement
Limbic, visual, oculomotor, motor and frontal cortex, autonomic

Question 4

What is Parkinsonism? What pathway does it disrupt and is it hypo or hyperkinetic?

Answer 4

Hypokinetic, overactive indirect pathway, involves bradykinesia (slow movement), rigidity, and a rest tremor (tremor present when resting and goes away during movement)

Question 5

What are 6 causes of Parkinsonism?

Answer 5

Degenerative (Parkinson’s disease), drugs (neuroleptics that block dopamine), infectious (HIV), toxins (carbon monoxide), and tumors

Question 6

Parkinsons disease involves overactivity of which pathway?

Answer 6

Indirect

Question 7

What are the five criteria for being diagnosed with Parkinsons disease?

Answer 7

Bradykinesia/rigidity/rest tremor, asymmetry of symptoms, absence of autonomic dysfunction/dementia/EOM abnormalities (early), absence of other causes, levodopa response
It is a clinical diagnosis

Question 8

Are investigations (brain imagery) useful for diagnosis? Why are they still used?

Answer 8

They are not useful for diagnosis, but they help rule out other causes of symptoms

Question 9

What is the biggest risk factor for Parkinsons disease?

Answer 9

Aging

Question 10

What are 3 environmental toxins that can cause PD?

Answer 10

Manganese, MPTP (drug), and some agricultural chemicals

Question 11

If you have an early onset of PD, is it more likely that it is a genetic or an environmental cause?

Answer 11

GENETIC for early onset, and ENVIRONMENTAL for late onset

Question 12

The current hypothesis of PD is that it is multifactorial. What does this mean?

Answer 12

There are genetic and environmental risk factors, and genetics may predispose people to environmental toxins. Usually genes play a higher role in younger people with PD.
There are also some neuroprotective measures you can take such as exercise, coffee, nicotine

Question 13

What is the pathology of PD? (cellular mechanism)

Answer 13

Deposition of alpha-synuclein as Lewy bodies (improperly cleared protein)
Degeneration of dopaminergic neurons in pars compacta in the substantia nigra
Degeneration in brainstem of pigmented nuclei, spinal cord, cortex, and gut
Glia cause inflammation to try and clear damaged neurons but this causes more damage, glia not made right
NO deposits of melanin in substantia nigra that is produced by dopamine

Question 14

What is the Braak system?

Answer 14

Stage 1 of PD starts in the olfactory and dorsal motor, then goes up brainstem
Stage 2 goes to the coeruleus, sub-coeruleus complex and leads to dysfunction in sleep and mood
Stage 3 is motor symptoms
Stages 4-6 you get cortical involvement (dementia, etc)

YOU GET MOST OTHER SIGNS BEFORE MOTOR ONES

Question 15

What is levodopa? Why do we not give straight dopamine?

Answer 15

Levodopa is a dopamine precursor that we give to increase PD patients dopamine, and you also give it with an enzyme inhibitor (either COMT or DD) that prevents LD from being broken down before it can work.
We do not give straight dopamine because it cannot cross the blood brain barrier, so once levodopa crosses it it changed into dopamine and can be used

Question 16

What is another class of drug we can give PD patients?

Answer 16

Dopamine agonists which stimulate the dopamine receptor directly (post-synaptically)

Question 17

What are some non-motor problems involved with PD?

Answer 17

Fatigue, apathy, psych disorders (anxiety and depression), sleep disturbances, autonomic nervous system issues (bladder/bowel control, sexual dysfunction, hypotension), and cognitive dysfunction

Question 18

What are other treatments that are not drug related for PD?

Answer 18

Counseling (referral to support groups)
Alternative treatments (exercise, calcium vitamin D)
Neuroprotection (none have been proven)

Question 19

Does the levodopa response last forever?

Answer 19

NO, the receptors degenerate, you can get a long lasting benefit tho, depending on the person, or you can get loss of overall benefit, it can wear off if you miss a dose, or it can wear off during the day and you can get early AM dystonia

Question 20

When do you use surgery as a treatment for PD?

Answer 20

Only in advanced disease, done either in the globus pallidus, subthalamic nucleus, and can be deep brain stimulation or lesioning
Helps with all motor symptoms, and meds can be decreased if deep brain stimulation is used in the subthalamic nucleus

Question 21

How do you treat advanced disease?

Answer 21

Treat the motor symptoms via med adjustment to limit side effects, treat non-motor symptoms like dementia and depression, and plan for care in terms of placement and caregiver burden