Movement Disorders

Question 0

What is the definition of a hypokinetic disorder?

What is an example of a hypokinetic disorder?

Answer 0

A disorder with decreased: 
-initiation 
- speed
-amplitude 
Of normal movements

Parkinson’s disease is an example.

Question 1

In what structure do the direct and indirect pathway of the basal ganglia motor circuits converge?
What are the two signals on this structure?

Answer 1

On the medial globus pallidus-

1. Glutaminergic from the subthalamic nucleus
2. GABA from the D1 neurons of the neostriatum

Question 2

What is the difference between Parkinson Disease and Parkinsonism?

Answer 2

Parkinsonism is a term to describe the constellation of hypokinetic movements associated with Parkinson disease

Parkinsonism is a clinical description, Parkinson disease is the disorder.

Question 3

What is the definition of a hyperkinetic disorder?

What are two examples of hyperkinetic disorders?

Answer 3

Excessive and intrusive abnormal movements

Huntington disease and hemiballism are hyperkinetic

Question 4

What is the abnormal hyperkinetic movement most associated with huntingtons disease?

Answer 4

Chorea

Question 5

What is the abnormal movement associated with hemiballism?

Answer 5

Ballism (flinging limbs)

Question 6

In parkinson disease Is the lack of dopaminergic cells in the pars compacta asymmetrical or symmetrical?
What is the implication of this?
Which side of the body will be show more parkinsonism?

Answer 6

Asymmetrical meaning that the rate of loss is different from the left and right pars compacta.
The side of the body contralateral to the more depleted pars compacta will be more affected.

Question 7

What is the most common cause of Parkinson’s?

Answer 7

Sporadic.

Only 10-15% are genetic.

Question 8

How does the loss of dopamine in Parkinson disease cause Parkinsonism?

Answer 8

Less dopamine will decrease the direct motor circuit because there will be less excitation of D1 and less inhibition on the medial globus pallidus.
Less dopamine will increase the indirect circuit because there will be less inhibition of the D2 neurons, more inhibition of the lateral globus pallidus, less inhibition of the subthalamic nucleus, more excitation of the medial globus pallidus, increased inhibition on the thalamus.

Question 9

What are the five ways that we identify Parkinsonism?

Which symptom is the hallmark (but must present with atleast one other)?

Answer 9

1. Bradykinesia- the hallmark symptom with decreased initiation, speed, and amplitude of movement
2. Rest tremor - not associated with doing a task (4-6Hz)
3. Rigidity- resistance to movement around a joint
4. Stooped posture, decreased speech volume, impaired balance
5. Freezing shuffling gait, falls

Question 10

What non-motor symptoms are associated with Parkinson disease?

Answer 10

Cognitive decline
Autonomic disfunction
Sleep disturbance
Mood disorders

Question 11

What would you see in a pathological sample of someone with Parkinson’s?

Answer 11

1. Decrease neuromelanin in the pars compacta

2. Lewy bodies- abnormal collection of proteins

Question 12

What percent of Parkinson patients develop rest tremors?

Answer 12

70%,

Question 13

What are treatments for Parkinson disease?

Answer 13

1. Levodopa- crosses BBB and gets converted to dopamine
2. D2 receptor agonist
3. Deep brain stimulation surgery (DBS)

Question 14

Why is carbidopa often prescribed with levodopa?

Answer 14

Because it prevents the levodopa from being converted to dopamine in the gut, allowing more to go through the BBB

Question 15

What causes huntingtons disorder?

How many repeats correlates with 100% penetrance?

Answer 15

CAG expansion on chromosome 4 (autosomal dominant disorder)

More than 40 repeats will have 100% penetrance

Question 16

How does huntington disease cause it’s motor symptoms?

Answer 16

It degererates medium spiny neurons in the neostriatum (specifically D2) so there is less inhibition being placed on the lateral globus pallidusv

Question 17

In huntington disease, which motor pathway loses its strength?

Answer 17

The indirect pathway. there is less inhibition of the thalamus, and more motor signals in the cortex. This is what causes the chorea.

Question 18

How does huntingtons disease reduce indirect pathway influence?

Answer 18

Reduced D2 so less inhibition of the lateral globus pallidus, more inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, less inhibition on the thalamus, over excitation of the cortex, hyperkinetic movement

Question 19

What is chorea? How is it different from a tremor?

What disorder is it associated with?

Answer 19

Writing unpredictable flinging, continuous movement.
Chorea is non-rhythmic where a tremor has rhythm.
It is associated with huntingtons disease.

Question 20

What are the non-motor symptoms of huntingtons disease? (4)

Answer 20

Psychiatric and cognitive impairment
Behavior abnormality
Mood disorders
Dementia

Question 21

How do you treat the motor symptoms of huntingtons disease?

Answer 21

1. Block dopamine receptors on the remaining functional D2 neurons using haloperidol
2. Use tetrabenazine to prevent the release of dopamine from the SNc neurons

Question 22

Is hemiballism a disease?

What is the most common cause?

Answer 22

No it’s a brain insult to the subthalamic nucleus

Most commonly caused by a stroke, brain bleed or hyperglycemia

Question 23

What is ballistic movement?

Answer 23

Similar to chorea-
Unpredictable, non-rhythmic, continuous, writhing

Only real difference is that ballism is unilateral

Question 24

Do the following disorders improve or decline with time?

1. Parkinson’s
2. Huntingtons
3. Hemiballism

Answer 24

1. Degenerative (keep losing dopamine)
2. Degenerative (neostriatum continues to atrophy)
3. Non- Progressive (acute insult to STN but it can regain function)

Question 25

How is hemiballism treated?

Answer 25

1. D2 blocker like haloperidol

2. Decrease dopamine release (tetrabenazine)