Disease Of The Basal Ganglia

Question 1

Motor disorders associated with basal ganglia dysfunction

Answer 1

Parkinson’s Disease
Huntington’s Disease
Dystonia
Gilles de la Tourette syndrome

Question 2

Psychiatric disorders associated with basal ganglia disorder

Answer 2

OCD
ADHD

Question 3

Secondary damage associated with basal ganglia dysfunction

Answer 3

Cerebral palsy
Wilson disease

Question 4

Pathophysiology of Parkinson’s

Answer 4

Not enough dopamine
Detection of Lewy bodies

Question 5

Pathophysiology of Huntington’s

Answer 5

Too much dopamine

Question 6

Symptoms of Parkinson’s

Answer 6

Increased muscle tone
Reduced movements

Question 7

Symptoms of Huntington’s

Answer 7

Decreased muscle tone
Overshooting movements

Question 8

Formation of dopamine

Answer 8

L-tyrosine —> tyrosine hydroxylase
L-DOPA —> DOPA decarboxylase
Dopamine

Question 9

Number of dopamine receptors

Answer 9

5

Question 10

Main area damaged in Parkinson’s

Answer 10

Substantia nigra

Question 11

How many neurons must a person lose before symptoms of Parkinson’s

Answer 11

2/3

Question 12

Neuronal cell death in Parkinson’s

Answer 12

About 50% cell death before any symptoms

Question 13

Main area damaged in Huntington’s

Answer 13

Caudate nucleus/ striatum

Question 14

Lateral ventricle and Huntington’s

Answer 14

Lateral ventricles are dramatically enlarged as caudate nucleus has shrunk away

Question 15

Parkinson’s

Answer 15

Less production of dopamine by Substantia nigra so decreases movement

Question 16

Huntingtons

Answer 16

Reduced production of GABA by striatum so increases movement

Question 17

Main symptoms of Parkinson’s

Answer 17

Brady/Akinesia
Problems with doing up buttons, keyboard etc
Writing smaller
Walking deteriorated: Small steps, dragging one foot etc

Tremor
= At rest
May be on one side only

Rigidity
Pain
Problems with turning in bed

Question 18

Most powerful drug for Parkinson’s

Answer 18

L-DOPA (naturally occurring precursor and drug)
- aims to correct dopamine deficit

Question 19

Drug treatment of Parkinson’s

Answer 19

Drugs mostly aim at correction of dopamine deficit- L-DOPA

But:
More and more cells die
The drugs work shorter and shorter
The longer on treatment, the more likely are the patients to develop side effects, in particular dyskinesias

Question 20

Dyskinesia

Answer 20

involuntary, erratic, writhing movements of the face, arms, legs or trunk

Question 21

Deep brain Stimulation

Answer 21

Functional lesions of the Subthalamic nucleus- improvements of Parkinson’s

Question 22

What does deep brain stimulation target

Answer 22

Subthalamic nucleus

Question 23

Normal pathway in brain

Answer 23

Cortex - striatum - thalamus - cortex

Regulated. By Substantia nigra and Subthalamic nucleus

Question 24

Role of Subthalamic nucleus

Answer 24

Inhibit of motor control

Question 25

Parkinson’s pathway

Answer 25

Lack of dopamine— decreased inhibition of Subthalamic nucleus — increased inhibition of motor movements

Question 26

How does deep brain stimulation work

Answer 26

Inhibits Subthalamic nucleus— net gain of mivement

Question 27

Clinical features of Huntington’s

Answer 27

Chorea Dementia/psychiatric illness Personality change

Question 28

Clinical genetics of Huntington’s

Answer 28

Autosomal dominant Fully penetrant

Question 29

Chorea

Answer 29

symptom that causes involuntary, irregular or unpredictable muscle movements. It affects your arms, legs and facial muscles

Question 30

Pharmacological treatment of Huntington’s

Answer 30

Dopamine receptor blockers = neuroleptics -typically used for psychosis treatment

Question 31

Genetics of Huntington’s

Answer 31

40 or more triplet CAG repeats of Huntingtin gene- expansion disorder

Question 32

Normal number of triplet repeats in Huntingtin gene

Answer 32

37

Question 33

Age of onset and number of CAG repeats - Huntington’s

Answer 33

More repeats - earlier likely to develop disease

Question 34

Disease-modelling therapy- Huntington’s

Answer 34

Down regulation of mutant Huntingtin protein