Parkinson’s Disease And Drug Therapy

Question 1

Disturbance of planning?

Answer 1

Apraxia

Question 2

Ballismus?

Answer 2

High amplitude flailing of the limbs on one side of the body

Question 3

Hemiballismus pathophysiology?

Answer 3

Disruption of indirect pathway at STN

Question 4

What causes hemiballismus?

Answer 4

Stroke

Question 5

Tic disorder?

Answer 5

Brief repetitive stereotype movements with a premonitory urge (uncomfortable feeling)

Question 6

Coprolalia?

Answer 6

Swearing

Question 7

Chorea?

Answer 7

Jerky, brief, not repetitive, flowing contracting

Question 8

Chorea pathophysiology?

Answer 8

problem in STN in indirect pathway

Question 9

What causes chorea?

Answer 9

Huntington’s and neuroleptics

Question 10

Huntington’s chorea genetics?

Answer 10

Trinucleotide repeat chromosome 4

Autosomal dominant

Longer the repeat sequence the earlier the disease presents

Question 11

Myoclonus?

Answer 11

Brief movement, rapid onset and offset. Positive and negative

Question 12

Causes of myoclonus

Answer 12

Prion
Juvenile myoclonus epilepsy
Brain hypoxia

Question 13

Dystonia?

Answer 13

Abnormal twisting posture, may be associated with jerking movement

Question 14

Possible pathophysiology for dystonia?

Answer 14

Abnormal dopaminergic activity in basal ganglia: blocking dopamine receptors and treatment with levodopa

Question 15

Dystonia causes?

Answer 15

Huntington’s, Parkinson’s, encephalitis, stroke, brain injury

Question 16

Kinetic tremor?

Answer 16

Nose finger

Question 17

Essential tremors

Answer 17

Predominantly postural

Question 18

Essential tremor is due to?

Answer 18

Gabaergic dysfunction in cerebellum

Question 19

Problems with dopamine blocking agents?

Answer 19

Oculogyric crisis (spasmodic movements of eye usually upwards), neuroleptic malignant syndrome

Subacute: drug induced Parkinsonism

Long term: tardive dyskinesia

Question 20

Parkinsonism triad of symptoms?

Answer 20

Bradykinesia, rigidity and shaking (resting tremor)

Question 21

Parkinson’s: REM parasomnia?

Answer 21

Sleep disorders, unusual movement, emotion, behaviour and dreams between different stages of sleep

Question 22

Pathophysiology of PD?

Answer 22

Lack of dopamine from substantia nigra

Question 23

Percentage cell loss of dopaminergic cells of substantia nigra?

Answer 23

70%

Question 24

Causes of Parkinsonism?

Answer 24

Idiopathic over 80, diffuse levy body, drugs, hydrocephalus, Wilson’s disease, rare familial, cerebri vascular disease

Question 25

Break-down of levodopa?

Answer 25

Dopa decarboxylase

Question 26

MAO inhibitors: type A and B:

Answer 26

A: serotonin, adrenaline, noradrenaline and dopamine B: dopamine We use B because selective e.g selegiline and rasagiline

Question 27

COMT inhibitor?

Answer 27

Entacapone/tolcapone. Makes dyskinesia worse, diarrhoea, liver disease

Question 28

Dopamine agonists?

Answer 28

Work on dopamine receptors Cons, Dopamine dysregulation syndrome E.g apomorphine s/c infusion but skin nodules

Question 29

Disturbance of coordination is called?

Answer 29

Ataxia

Question 30

Example of tic disorders?

Answer 30

Simple- coughing blinking Complex- twirling jumping Plus motor disorder and coprolalia

Question 31

How do you reduce tic disorder?

Answer 31

Distraction and concentration

Question 32

What is the more sever expression of spectrum of tic disorders?

Answer 32

Tourette syndrome

Question 33

Tic disorder causes?

Answer 33

``` Complex genetic inheritance Post infectious immune Often associate with other co-morbid conditions 50%- ADHD 33.3% - OCD And up to 50% with anxiety ```

Question 34

What is the clinical presentation of Huntington’s?

Answer 34

Cognitive- inability to make decisions multitask and slowness of thought Behavioural- irritability, depression apathy anxiety delusions Physical- chorea, motor persistence dystonia and eye movements

Question 35

What can myoclonus be treated by?

Answer 35

Antiepilieptics

Question 36

What is th pathophysiology of tremor?

Answer 36

Increased activity in the cerebellothalamocortical circuit

Question 37

PD is due to?

Answer 37

Dopamine dysfunction in the pallidus

Question 38

Drugs to treat hyperkinetic movement disorders?

Answer 38

Dopamine receptor blocking agents (eg haloperidol, chlorpromazine, pimozide, risperidone) Dopamine depleting agents (eg Tetrabenazine, Reserpine) Atypical anti-psychotics (eg Clozapine, Olanzapine, Aripiprazole)

Question 39

Oculogyric crisis?

Answer 39

``` Very characteristic acute response to certain drugs Fixed stare, upward deviation of eyes Neck extension Trunk extension Jaw spasms +/- tongue protrusion ‘Acute dystonic’ reaction ```

Question 40

Neuroleptic malignant syndrome?

Answer 40

Rigidity/ muscle breakdown – raised CPK. ●Fever ●Autonomic instability (volatile BP/PR) ●Confusion

Question 41

Tardive dyskinesia?

Answer 41

Choreic oral-facial movements (video), dystonic trunk posturing ●Exact mechanism unclear – likely dopamine supersensitvity of basal ganglia –ie secondary receptor/ plastic changes ●Treatment -gradual withdrawal of offending agent, substitution with an atypical anti-psychotic ; use of a dopamine depleting agent (tetrabenazine); use of a benzodiazepine (clonazepam) if distressing

Question 42

No motor symptoms of Parkinson’s?

Answer 42

``` Depression anxiety Dementia: slowed thoughts Postural hypotension, hypersalivation Restless legs rem parasomnia Reduced sense of smell ```

Question 43

PD pathophysiology?

Answer 43

Decreased dopamine input leads to reduced activation of direct pathway and reduced inhibition of indirect pathway, leading to reduced movements

Question 44

What else do you find in Parkinson’s?

Answer 44

Lewy bodies and intraneuronal protein inclusion

Question 45

Early drug therapies for Parkinson’s?

Answer 45

Amantadine – Initially anti-flu agent Glutamate agonist Anti-cholinergics – Procyclidine, Benzhexol May help with tremor Limited by side effects (confusion, urinary retention, dry mouth…) Mono-amine oxidase inhibitors

Question 46

Non drug therapies?

Answer 46

Not clear how it works (but it does!) Probably high freq stimulation causing ‘jamming’(inhibition of neurons by depolarising block) Also disrupts abnormally synchronous basal ganglia rhythms ``` Favoured target subthalamic nucleus (STN) for PD Also pallidum (for dystonia) and thalamus (for tremor) ``` ``` Disease will still progress and no effect on non-motor -dementia, -dysautonomia, -postural instability….. ``` - Future – neurorestorative (stem cells) - Neuroprotective (growth factors)