T2 L9 Parkinson's disease

Question 1

What is ballismus?

Answer 1

High amplitude flailing of limbs on one side of the body

Question 2

What is the pathophysiology of ballismus?

Answer 2

Inhibition of STN so no excitatory signals are produced to GPi so GPi does not inhibit thalamus so thalamus excites cortex

Question 3

What is the commonest cause of ballismus?

Answer 3

Stroke

Question 4

What is a tic?

Answer 4

Brief, repetitive stereotypic movements with premonitory urge

Question 5

What are the types of tics?

Answer 5

Simplex: blinding, coughing
Complex: jumping or twirling
Plus: motor disorder
Coprolalia: swearing

Question 6

What can help reduce tics?

Answer 6

Distraction & concentration

Question 7

What can make tics worse?

Answer 7

Anxiety

Fatigue

Question 8

What is Tourette syndrome?

Answer 8

More severe expression on a spectrum of tic disorders

Question 9

What other conditions are associated with tics?

Answer 9

50% have ADHD
33.3% have OCD
≥50% have anxiety

Question 10

What are come causes of tic disorders?

Answer 10

Complex genetic inheritance

Post infectious immune

Question 11

What is chorea?

Answer 11

Jerky, brief, irregular contractions that aren’t repetitive or rhythmic
Appear to flow from one muscle to the next
Patient appears fidgety / restless

Question 12

What is the pathophysiology of chorea?

Answer 12

Inhibition of STN –> no excitation signal produced to GPi so no signal to thalamus which causes it to excite cortex

Question 13

What are some causes of chorea?

Answer 13

Huntington’s disease

Drugs- neuroleptics

Question 14

What is the genetics of Huntington’s disease?

Answer 14

Trinucleotide repeat on chromosome 4
Autosomal dominant with complete penetrance
Longer the repeat sequence the earlier the disease presents
Normal is 10-28 repeats
Disease is 36-121 repeats.

Question 15

What is the clinical presentation of Huntington’s disease?

Answer 15

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

Question 16

What is myoclonus?

Answer 16

Brief movement
Rapid onset & offset
Positive or negative

Question 17

What is the pathophysiology of myoclonus?

Answer 17

Unknown
Possible imbalance between excitatory & inhibitory neurotransmitters as it is treatable with anti epileptic drugs
Perturbations of motor control system leading to brief disequilibrium which explains why it is present at multiple levels

Question 18

What are the causes of myoclonus?

Answer 18

Juvenile myoclonic epilepsy
Brain hypoxia
Prion disease

Question 19

What is dystonia?

Answer 19

Abnormal twisting posture associated with jerky tremor

Often axial, facial, trunk

Question 20

What is the pathophysiology of dystonia?

Answer 20

Unknown
Functional PET studies suggested abnormal activity in motor cortex, supplementary areas, cerebellum & basal ganglia
Abnormal activity in basal ganglia suggested by dystonia being caused by blocking dopamine receptors & some dystonia being levodopa responsive

Question 21

What are the causes of dystonia?

Answer 21

Stroke
Brain injury
Encephalitis
Parkinson's disease
Huntington's disease

Question 22

What is a tremor?

Answer 22

Involuntary, rhythmic, sinusoidal alternating movements of part of the body
Affect different parts of the body
Different occurrence e.g. rest, postural, kinetic

Question 23

What is the pathophysiology of a tremor?

Answer 23

Postulated theory is increased activity in cerebothalamocortical circuit
PD: dopamine dysfunction in pallidum
ET: GABAergic dysfunction in cerebellum

Question 24

What are the types of drug treatment for hyperkinetic movement disorders?

Answer 24

Dopamine (D2) receptor blocking agents
Dopamine depleting agents
Atypical anti-psychotics

Question 25

What are some examples of dopamine receptor blocking agents?

Answer 25

Haloperidol Chlorpromazine Pimozide Risperidone

Question 26

What are some examples of dopamine depleting agents?

Answer 26

Tetrabenazine | Reserpine

Question 27

What are some examples of atypical antipsychotics?

Answer 27

Clozapine Olanzapine Aripiprazole

Question 28

What is an ocylogyric crisis?

Answer 28

Very characteristic acute response to certain drugs Fixed stare, upward deviation of eyes Neck extension Trunk extension Jaw spasms & possible tongue protrusion Acute dystonic reaction

Question 29

What is neuroleptic malignant syndrome?

Answer 29

``` Acute medical emergency due to D2 blocking drugs Rigidity / muscle breakdown - raised CPK Fever Autonomic instability Confusion ```

Question 30

What is Parkinsonism?

Answer 30

Akinetic rigid syndrome | Symptoms: slowness of movement, stiffness, shaking

Question 31

What are the physical signs of Parkinsonism?

Answer 31

Slowness & poverty of movement Voluntary movements are harder to initiate Rigidity Rest tremor

Question 32

What are the non-motor signs of Parkinsonism?

Answer 32

Mood - depression, anxiety Dementia - slowed thought, mental inflexibility Autonomic involvement - postural hypotension, hyper salivation Sleep disturbance - restless legs, REM, parasomnia

Question 33

What are the neurodegenerative causes of Parkinsonism?

Answer 33

Idiopathic - Parkinson's disease Diffuse lewy body disease Atypical parkinsonism Multiple system atrophy, progressive supra nuclear palsy, corticobasal degeneration

Question 34

What are the secondary causes of Parkinsonism?

Answer 34

Drugs - haloperidol, MPTP Cerebrovascular disease Hydrocephalus Toxicity / metal deposition disorders

Question 35

What are the genetic causes of Parkinsonism?

Answer 35

Metabolic - Wilson's disease | Rare familial causes

Question 36

What is the pathophysiology of Parkinsonism?

Answer 36

Decreased dopamine input --> reduced activation of direct pathway & reduced inhibition (higher activity) of indirect pathway. This leads to reduced movements.

Question 37

What is Parkinson's disease?

Answer 37

Neurodegenerative condition primarily affecting dopaminergic cells of substantial nigra

Question 38

What is the histological hallmark of Parkinson's disease?

Answer 38

Lewy bodies

Question 39

What were some early drug therapies for Parkinson's disease?

Answer 39

Amatadine - initially anti flu agent. Glutamate agonist Anticholinergics - procyclidine, benzhexol. Limited by side effects Mono-amine oxidase inhibitors

Question 40

What are monoamine oxidase inhibitors?

Answer 40

Prevent breakdown of monoamine chemical transmitters | 2 isoforms: MAO-type A (serotonin, adrenaline, noradrenaline, dopamine). MAO-type B (dopamine)

Question 41

What is non selective MAO-I used for?

Answer 41

Depression (moclobemide) Rarely used due to problems metabolising dietary amines / tryptophan leading to risk of hypertensive crisis from cheese, red wine & marmite

Question 42

What is more selective MAO-IB used for?

Answer 42

Parkinson's disease Selegiline, rasagiline No dietary restrictions

Question 43

What is entacapone / tolcapone used for?

Answer 43

Reduced peripheral metabolism of L-DOPA. Also reduces central but to a lower extent

Question 44

What are the pros & cons of entacapone / tolcapone?

Answer 44

Pros: increases duration & efficacy of action of L-Dopa Good for wearing off with L-Dopa inbetween doses Cons: makes dyskinesia worse, diarrhoea Liver disease with tolcapone

Question 45

Where is L-DOPA absorbed?

Answer 45

Duodenum

Question 46

What affects L-DOPA absorption?

Answer 46

Poor gastric motility / constipation & diet / protein load

Question 47

What do dopamine agonists do?

Answer 47

Bypass degenerating nigrostriatal neurons Directly activate dopamine receptors No need for enzymatic conversion More stable & longer acting

Question 48

What are the pros of amorphine?

Answer 48

Very instant effect as given by s/c infusion | Reduces dyskinesia by allowing continuous dopaminergic stimulation

Question 49

What are the cons of amorphine?

Answer 49

Only for right patients | Skin nodules

Question 50

What is the favoured target for deep brain stimulation?

Answer 50

Subthalamic nucleus for Parkinson's disease Pallidum for dystonia Thalamus for tremor

Question 51

What is the future for non-drug therapies?

Answer 51

Neurorestorative (stem cells) | Neuroprotective (growth factors)