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1
Q

Pharmacological management of Parkinson’s disease

Name two drugs that can combined with L-DOPA (aka levodopa) that means it doesn’t get metabolised to dopamine outside the BBB [2]

What is their MOA? [1]

A

L-DOPA (levodopa) & carbidopa or benserazide

carbidopa, benserazide are decaboxylase inhibitors: allows L-DOPA to pass BBB where it can then be converted to dopamine

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2
Q

Pharmacological management of Parkinson’s disease

Name 3 dopminergic agonists and describe their MOA

A

Dopamine agonists:
* ropinirole
* pramipexole
* rotigotine (in BB PBL; transdermal patch)

Dopamine agonists act directly on the dopamine receptors and mimic dopamine’s effect

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3
Q

Which of the following dopamine agonists can be used as a transdermal patch?

bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine

A

Which of the following dopamine agonists can be used as a transdermal patch?

bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine

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4
Q

Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?

bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine

A

Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?

bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine

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5
Q

Why are dopamine agonists sometimes an advantage if a patient has difficulty swallowing? [1]

A

Dopamine agonists differ in their pharmacokinetics: longer acting drugs require fewer daily doses and this can be an advantage when there are swallowing difficulties

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6
Q

Pharmacological management of Parkinson’s disease

Name three drugs that are monoamine oxidase inhibitors [3]

Describe their MoA [1]

A
  • rasagiline
  • selegiline (in PBL)
  • safinamide

MAO-B inhibitors stop Monoamine oxidase type B breaking down dopamine into DOPAC or homovanillic acid

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7
Q

What is the MoA of COMT inhibitors? [1]

Explain why [1]

Which drugs are they used in conjunction with? [1]

A

COMT is an enzyme involved in the breakdown of dopamine (DOPAC –> homovanillic acid) and hence may be used as an adjunct to levodopa therapy

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8
Q

Pharmacological management of Parkinson’s disease

Name 2 COMT inhibitors [2]

A

entacapone
tolcapone

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9
Q

Pharmacological management of Parkinson’s disease

Why are anticholinergic (antimuscarininc) compounds used to treat PD? [1]

A

Dopamine loss leads to hyperactivity of cholinergic cells

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10
Q

Pharmacological management of Parkinson’s disease

Name three anticholinergic compounds [3]

Which symtpom are they particularly good for treating? [1]

A

orphenadrine, procyclidine, trihexyphenidyl

Block tremors (as block muscarinic receptors on muscles) but also cause dry mouth and constipation

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11
Q

Pharmacological management of Parkinson’s disease

What is the MoA of Amantadine? [3]

A

inhibits dopamine reuptake, increases dopamine release, also weak antagonist at NMDA glutamate receptors

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12
Q

Pharmacological management of PD:

Other treatment approaches

Name two cell based approaches that can use to treat PD [2]

A
  • Striatal graft of embryonic mesencephalic cells: intrastriatal transplant of foetal nigral cells
  • Systemic administration of mesenchymal stem cells: Improvement following repeated intravenous injection of adipose tissue-derived cells
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13
Q

Surgical approaches in Parkinson’s disease

Describe the surgical approaches to PD treatment [4]

A

Electrode stimulation of the subthalamic nucleus

Thalamotomy

Pallidotomy

deep brain stimulation for people with advanced Parkinson’s disease whose symptoms are not adequately controlled by optimised pharmacological therapy

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14
Q

Name the gene that has associated changes causing Huntingdons disease [1]

What do codon / repeat sequence occurs due to this abnormal gene? [1]

A

Huntingtin gene

Repeats of glutamine (CAG)

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15
Q

Name the mechanisms underlying neurodegeneration of HD [7]

A
  • Excitotoxicity
  • Loss of neurotrophic factors
  • Accumulation of aggregates of mutant huntingtin protein
  • Dysregulation of gene transcription
  • Increased oxidative stress
  • Abnormalities in axonal transport
  • Synaptic abnormalities
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16
Q

Pharmacological management of Huntington’s disease

Name two classes of drugs used to treat HD [2]

A

Vesicular amine transporter inhibitor (Decreases levels of dopamine in dopaminergic terminals)

Antidopaminergic (antipsychotic) drugs

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17
Q

Pharmacological management of Huntington’s disease

Name drugs for that used to treat HD that use following mechanisms:

  • Vesicular amine transporter inhibitor [1]
  • Antidopaminergic (antipsychotic) drugs [2]
A
  • Vesicular amine transporter inhibitor: tetrabenazine
  • Antidopaminergic (antipsychotic) drugs: haloperidol, olanzapine
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18
Q

Pharmacological management of Huntington’s disease

Name three antidepressant drugs used in the management of HD [3]

A

Antidepressant drugs: citalopram, fluoxetine, sertraline

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19
Q

Name an experimental non-pharmacological approach for treatment of HD [1]

A

Striatal fetal grafts

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20
Q

Motor control:

Motor control is a distributed process.

What are the two levels involved in motor control?

A
  1. Central representation of goals and planning of the more abstract components of the movement (what am i going to do / how am i going to do this?)
  2. Production of goal orientated movements (patterns of muscular activation)
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21
Q

The main brain areas involved in motor control:

Name the main areas of the brain involved in:

Decision making & movement planning [2]

Organisation of movement [2]

Movement execution [1]

A

Decision making & movement planning [2]
* Posterior parietal cortex
* Frontopolar cortex

Organisation of movement [2]
* Supplementory motor cortex
* Premotor cortex

Movement execution [1]
* Primary motor cortex

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22
Q

Brain areas involved decision making & movement planning:

Which area of the brain is where conscious intentions are formed and we become aware of motor movement? [1]

Name another key function of this area? [1]

A

The posterior parietal cortex

Also provides a representation of the body and how it is situated in space

Broadmann areas 39 & 40

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23
Q

What is the function of the pre-frontal cortex? [2]

A

Pre-front cortex controls executive function (allows us to use perceptions, knowledge & to bias / choose the from the selection of actions and thoughts from multiple possibilites)

This allows you to overide habitual responses

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24
Q

Pre-frontal cortex:

For successful completion of goal-oriented behaviour, we need to do completee three steps? [3]

A
  1. Develop a plan of action
  2. Monitor our actions
  3. Inhibit habitual response to obtain a goal (e.g. go for a run if trying to get fit instead of sofa)
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25
# Prefrontal cortex: Dorsolateral prefrontal cortex What is this region of the pre-frontal cortex involved with? [3]
**Planning of goal-directed behaviours AND simulating the consequences of plans** **Initiating, inhibiting and swtiching executive behaviour**: input to the basal ganglia about stop / start Involved with: Problem-solving Goal-driven attention Planning Decision making Working memory
26
# dorsolateral prefrontal cortex: Lesions in Brodmann area 46 affects which functions? [1]
Attention and working memory: **affects ability to inhibit a response to a stimulus**
27
What are the regions of the pre-frontal cortex need to know? [3]
- **Dorsolateral pre-frontal cortex** - **Medial prefrontal cortex** - most ventral part: **Orbitofrontal cortex**
28
What is the role of the medial prefrontal cortex ?
**Guide and monitor actions** that are internally guided according to preferences and goals: I.e. it **modulates the degrees of cognitive control** need to keep in behaviour in line with the goal
29
# Prefrontal cortex What is the role of the orbitofrontal cortex? [1]
Representation of **value for rewards and punishers** (what is good for you / bad for you)
30
Lesions to the orbitofrontal cortex lead to what type of behaviours? [1]
**"pseudopsychopathic” behaviours**: * Impulsiveness * Sexual disinhibition * Complete lack of concern for others
31
# Frontal eye fields: Location [1]? Role? [1] Movement of the eyes do they create? [1]
Location: **Broadmann area 9; top of prefrontal cortex** Role: **control of visual attention and eye movements** Movement: **saccadic eye movements** (rapid eye movements designed to shift the fovea to objects of visual interest - ie the eyes/ mouth)
32
Is damage to frontal eye fields a perceptual or motor problem? [1] What is the effect of bilateral FEF lesion? [2] In which direction does the eye move if have a frontal eye field defect? [1]
Frontal eye fields: **motor problem**: Bilateral lesion: causes **oculumotor apraxia** - have to move head horizontally as they c**annot move their eyes** Eye deviates **towards** the side of lesion
33
Name the secondary motor areas involved in motor movement [2]
* The supplementary motor area (SMA) * The premotor cortex
34
label A-C
A: **primary motor cortex** B: **supplementary motor area** C: **premotor cortex**
35
# supplementory motor area: Location: Broadmann area? [1] Lobe? [1] Role? [2]
Location: **medial part of BA 6; frontal cortex** Role: * **Orgnaises actions that are internally guide according to preferences and goals**: choosing objects * Determines response threshold to initiate movement - **the urgency of movement** * Response to **start** or **stop** a **movement** (interconnects to basal ganglia) e.g which object to choose (in alignment with goals) plan sequence of learned actions - e.g. playing piano
36
# Premotor cortex: What is the role of the premotor cortex? [1] Where is the premotor cortex located? [1]
**Lateral** of area 6 Organises **externally sensory guided actions** (catching a ball)
37
Which area of the brain is where conscious intentions are formed and we become aware of motor movement? orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
Which area of the brain is where conscious intentions are formed and we become aware of motor movement? orbitofrontal (pre-frontal) cortex **posterior parietal cortex** medial pre-frontal cortex dorso-lateral pre-frontal cortex
38
Which of the following areas are involved in Initiating, inhibiting and swtiching executive behaviour: input to the basal ganglia about stop / start orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
Which of the following areas are involved in Initiating, inhibiting and swtiching executive behaviour: input to the basal ganglia about stop / start orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex **dorso-lateral pre-frontal cortex**
39
which of the following guides and monitos actions that are internally guided according to preferences and goals orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
which of the following guides and monitos actions that are internally guided according to preferences and goals orbitofrontal (pre-frontal) cortex posterior parietal cortex **medial pre-frontal cortex** dorso-lateral pre-frontal cortex
40
Which of the following modulates the degrees of cognitive control need to keep in behaviour in line with the goal orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
Which of the following modulates the degrees of cognitive control need to keep in behaviour in line with the goal orbitofrontal (pre-frontal) cortex posterior parietal cortex **medial pre-frontal cortex** dorso-lateral pre-frontal cortex
41
Which of the following modulates value for rewards and punishers orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
Which of the following modulates value for rewards and punishers **orbitofrontal (pre-frontal) cortex** posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
42
“pseudopsychopathic” behaviours occurs due to lesions in which of the following brain areas orbitofrontal (pre-frontal) cortex posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
“pseudopsychopathic” behaviours occurs due to lesions in which of the following brain areas **orbitofrontal (pre-frontal) cortex** posterior parietal cortex medial pre-frontal cortex dorso-lateral pre-frontal cortex
43
Label the orange, purple, green and grey barts of the brain
Purple: premotor orange: dorsolateral prefrontal green: orbitofrontal grey: FEF
44
Which region of the brain is responsible for this image? [1]
pre-motor cortex
45
Which region of the brain is responsible for this image? (chosing a food option) [1]
supplementory motor area:
46
How is the the somatosensory cortex involved in motor control?
40% of **corticospinal and corticobulbar tract axons** arise from somatosensory cortex; can **modulate somatosensory input** (e.g. supress nocicpetive pain)
47
Where does the corticospinal tract cross decussate in the body? [1] On the way to the brainstem, which structure does the cortiospinal tract pass through? [1]
Decussates in upper spinal cord: **C1-C5** Goes through the **internal capsule** on way to brainstem
48
The corticobulbar tracts provide innervation to the musculature of which region of the body? Head and neck Upper limbs Lower limbs Neck
The corticobulbar tracts provide innervation to the musculature of which region of the body? **Head and neck** Upper limbs Lower limbs Neck
49
Which part of the body does CST have monosynaptic connections with? [2] Explain why [1] How does the CST control movement in other muscles? [1]
Monosynaptic connections with **thumb and digits** Creates a greater degree of **precision of movement** Other muscles are controlled via CST synapsing on **interneurons**: modulates spinal reflexes
50
Which tract controls the movement of the face? [1]
**Corticobulbar tract**
51
# Extrapyramidal tracts: What is the role of the reticulospinal tract [1]
Responsible for **autonomic control of the sympathetic preganglionic neurons** (eg heart rate, circulation, breathing, respiratory rate) Also provides drive to the **respiration** via the **phrenic** **nerve**)
52
# Extrapyramidal tracts: Desribe the path of the medial and lateral reticulospinal tracts [2]
Medial Reticulospinal Tract (Pontine): **Descends ipsilaterally** Lateral Reticulospinal tracts (Medullary): **Descends bilaterally**
53
# Extrapyramidal tracts: Desribe the path of the medial and lateral reticulospinal tracts [2]
Medial Reticulospinal Tract (Pontine): **Descends ipsilaterally** Lateral Reticulospinal tracts (Medullary): **Descends bilaterally**
54
# Extrapyramidal tracts: Describe the course of the lateral vestibulospinal tract [1] Which type of muscles does it synapse onto? [1]
Fibres descend **ipsilaterally** though the anterior funiculus of the same side of the spinal cord, **synapsing on the extensor antigravity motor neurons**: help maintain upright and balanced posture.
55
# Extrapyramidal tracts: Desribe the function and path of medial vestibulospinal tract
Function: Performs the **synchronization of the movement of the eyes** with the **movement** **of the head** so that **eyes do not lag** behind when the head moves to one side Pathway: Descends **bilaterally in the medial longitudinal fasciculus**. Synapses with the excitatory and inhibitory neurons of the cervical spine
56
Describe the function and path of the rubrospinal tract [2]
Function: **Controls muscle tone in flexor muscle groups; Inhibits extensor tone** Path: - Arises from the red nucleus in the brainstem - crosses at medulla - terminates primarily in the cervical and thoracic portions of the spinal cord
57
Path and function of tectospinal tract? [2]
**Coordinates voluntary head and eye movements** Involved in both auditory and visual cues, **it is primarily understood to orient our eyes and head towards both auditory and visual stimuli.** For example, if you were sitting in a quiet room and all of a sudden heard a noise to your right, you would subconsciously turn your head in that direction and orient your eyes towards the direction of the sound, attempting to find the source. **Path**: Originates in the **superior colliculus** Projects to the contralateral cervical spinal cord to terminate in Rexed laminae VI, VII, and VIII
58
# Clonus Describe the characteristic movements associated with clonus [1] UMN or LMN lesion? [1]
Lots of jerky contractions followed by a suddent stretch of muscle UMN lesion https://www.google.com/search?q=clonus&rlz=1C5CHFA_enGB760GB761&hl=en&sxsrf=AJOqlzUkXZhV4TRE-1FXesUfy9LnZqP-NA:1674751896001&source=lnms&tbm=vid&sa=X&ved=2ahUKEwi-jOT-2OX8AhWuRUEAHcBgBmwQ_AUoAXoECAEQAw&cshid=1674751960915393&biw=714&bih=732&dpr=1#fpstate=ive&vld=cid:596e37d4,vid:4SrhgjGIZ30
59
Describe how rigidity occurs [1]
If have a lesion above the pons occurs, the inhibitory system is lost; **extrapyramidal system becomes hyperactive**
60
Where would damage occur for the following: Decorticate posturing [1] Decerebrate posturing [1]
Decorticate posturing: * Damage to the **corticospinal** tract **above or in midbrain** Decerebrate posturing * Damage to the corticospinal tract at the **level of upper brainstem**, including **corticospinal and rubrospinal tracts**
61
Which of the following ensures that the eyes do not lag behind when the head moves to one side rubrospinal tract reticulospinal tract lateral vestibulospinal tract medial vestibulospinal tract
Which of the following ensures that the eyes do not lag behind when the head moves to one side rubrospinal tract reticulospinal tract lateral vestibulospinal tract **medial vestibulospinal tract**
62
Which of the following controls posture and balance rubrospinal tract reticulospinal tract lateral vestibulospinal tract medial vestibulospinal tract
Which of the following controls posture and balance rubrospinal tract reticulospinal tract **lateral vestibulospinal tract** medial vestibulospinal tract
63
Which of the following controls flexor muscle tone rubrospinal tract reticulospinal tract lateral vestibulospinal tract medial vestibulospinal tract
Which of the following controls flexor muscle tone **rubrospinal tract** reticulospinal tract lateral vestibulospinal tract medial vestibulospinal tract
64
Which extra-pyrimadal tract originates in the superior colliculus? [1]
tectospinal
65
Which of the following synapses on the extensor antigravity motor neurons rubrospinal tract reticulospinal tract lateral vestibulospinal tract medial vestibulospinal tract
Which of the following synapses on the extensor antigravity motor neurons rubrospinal tract reticulospinal tract **lateral vestibulospinal tract** medial vestibulospinal tract

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