HNN PBL 5

Question 1

What is the most common thing to go wrong in movement disorders?

Answer 1

The basal ganglia

Question 2

What are the roles of the basal ganglia?

Answer 2

• Initiation of voluntary movement
• Maintaining posture
• Eye movement control
• Social behaviour and decision making
• Executive functions – higher function that help in terms of planning etc / working memory

Question 3

Where are the basal ganglia located?

Answer 3

The inferior part of the cerebral hemisphere

Question 4

What are the basal ganglia?

Answer 4

A set of deep nuclear structures that are closely intertwined with lots and lots of pathways between them

Question 5

Is the direct pathway the “stop” or “go” pathway?

Answer 5

GO

Question 6

Is the indirect pathway the “stop” or “go” pathway?

Answer 6

STOP

Question 7

What is linked by the direct pathway?

Answer 7

The striatum and the GPi

Question 8

What does activity in the direct pathway do?

Answer 8

Increases cortical activity

Question 9

What is linked by the indirect pathway?

Answer 9

the striatum and GPi via the GPe (Globus pallidus externa) and the STN (Subthalamic nucleus)

Question 10

What does activity in the indirect pathway do?

Answer 10

Decreases cortical activity

Question 11

Where is the cerebellum located?

Answer 11

the posterior fossa of the cranium

Question 12

What connects the cerebellum to the brainstem?

Answer 12

three cerebellar peduncles (superior, middle, and inferior)

Question 13

What is the Nigrostriatal pathway responsible for?

Answer 13

Movement and sensory stimuli

Question 14

What is the mesolimbic pathway responsible for?

Answer 14

Pleasure and reward seeking behaviours, addiction, emotion, perception

Question 15

What is the Mesocortical pathway responsible for?

Answer 15

Cognition, memory, attention, emotional behaviour and learning

Question 16

What is the Tuberoinfundibular pathway responsible for?

Answer 16

Control of the hypothalamic pituitary endocrine system, inhibition of prolactin secretions

Question 17

What happens to the dopamine producing cells in Parkinson’s disease?

Answer 17

There is a loss of dopaminergic neurones within substantia nigra

Question 18

What is made as a side effect of dopamine production?

Answer 18

Melanin

Question 19

What does less dark staining in the subthalamic nucleus mean?

Answer 19

Less production of melanin –> less dopaminergic stimulation

Question 20

What forms inside the surviving neurones?

Answer 20

Lewy bodies

Question 21

What are Lewy bodies?

Answer 21

Intracytoplasmic inclusion bodies

Question 22

When does Parkinson’s disease begin to manifest clinically?

Answer 22

After approximately 50% of dopaminergic neurones are lost

Question 23

What does the loss of cells within the substantia nigra result in?

Answer 23

Reduced activity in the direct pathway and increased activity in the indirect pathway.
This leads to an overactive STN and GPI which overall inhibits the thalamus.

Question 24

What is the general rule relating to proteins in neurodegenerative disorders?

Answer 24

proteins get misfolded and its these misfolded proteins that accumulate in the cells and can be neurotoxic

Question 25

How many stages are in the Braak staging system?

Answer 25

6 stages

Question 26

What happens in stages 1-2 of the Braak staging system?

Answer 26

virtually confined to the medulla oblongata and often the anterior olfactory nucleus – these were identified in incidental cases without a PD diagnosis. (no symptoms but may have lost their sense of smell)

Question 27

What happens in stages 3-4 of the Braak staging system?

Answer 27

Lewy bodies extend into the mid brain and substantia nigra. Most in stage 3 have a PD diagnosis

Question 28

What happens by the time a patient reaches stage 5-6 of the Braak staging system?

Answer 28

widespread distribution of Lewy bodies and this is consistent with Parkinson’s dementia.

Question 29

What symptoms may a patient with Parkinson's disease have before they present clinically?

Answer 29

Disturbed sleep, bladder issues and constipation

Question 30

What are the key symptoms for a diagnosis of Parkinson's disease?

Answer 30

tremor, rigidity and bradykinesia

Question 31

What symptoms develop as Parkinson's disease progresses?

Answer 31

Patients will get worsening of symptoms at first on one side but it then moves to the other side. They then get balance problems, then cognitive difficulties

Question 32

What is bradykinesia?

Answer 32

slowness in initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions (repeated finger taps or arm movements)

Question 33

What is the pharmacological aim of Parkinson's disease treatment?

Answer 33

To improve motor symptoms/improve quality of life (no evidence for neuroprotection so don’t impact the long term outcome of the disease)

Question 34

What are the classes of drugs used to treat Parkinson's disease?

Answer 34

L-dopa Dopamine agonists MAO-B inhibitors COMT inhibitors

Question 35

What are the ways L-dopa can be prepared?

Answer 35

L-dopa + carbidopa = Sinemet | L-dopa + benserazide = Madopar

Question 36

Why does L-dopa have to be combined with another substance to be administered?

Answer 36

Carbidopa and benserazide both acts to prevent L-dopa being metabolized peripherally and the side effects that would come with that

Question 37

What are the common adverse effects of L-dopa treatment?

Answer 37

- Peripheral: nausea, vomiting, postural hypotension | - Central: confusion, hallucinations

Question 38

What is the half life and efficacy of dopamine agonists like compared to L-dopa?

Answer 38

Longer half-life | less efficacious

Question 39

What are the side effects of dopamine agonists?

Answer 39

Dopaminergic side effects, Daytime somnolence and Impulse control disorders (e.g. pathological gambling, hypersexuality)

Question 40

What are the two types of Enzyme inhibitors used to treat Parkinson's disease?

Answer 40

MAO-B inhibitors e.g. selegiline, rasagiline | COMT inhibitors e.g. Entacapone, Opicapaone

Question 41

When in the progression of Parkinson's disease are MAO-B inhibitors used?

Answer 41

Either in early disease or alongside L-dopa later on.

Question 42

When in the progression of Parkinson's disease are COMT inhibitors used?

Answer 42

Usually prescribed in later disease

Question 43

What are treatment options for advanced PD?

Answer 43

Apomorphine (dopamine agonist subcutaneous needle – gives smooth dopamine profile) pen injections or subcutaneous pump, Intrajejunal duodopa infusion, Deep brain stimulation surgery