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Theme 2: Sensory input and motor outputs > Parkinson's disease and drug therapy of basal ganglia disorders > Flashcards

Parkinson's disease and drug therapy of basal ganglia disorders Flashcards

1
Q

Hyperkinetic movements

A

Hyperkinesis

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2
Q

Jerky movements

A

Hemiballismus

Tics

Chorea

Myoclonus

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3
Q

Non-jerky movements

A

Dystonia

Tremor

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4
Q

Hypokinetic movements

A

Hypokinesis

Parkinsonian conditions

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5
Q

Disturbance of co-ordination

A

Ataxia

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6
Q

Disturbance of planning

A

Apraxia

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7
Q

Ballismus

A

High amplitude flailing of the limbs on one side

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8
Q

Hemiballismus

A

Commonest cause is a stroke

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9
Q

Tic disorders

A

Brief repetitive stereotype movements with prmonitory urge

Reduced by distraction and concentration

Worse with anxiety or fatigue

Tourettes is more severe expression

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10
Q

Tics

A

Simple: blinking and coughing

Complex: jumping or twirling

Plus: motor disorder

Coprolia: swearing (rare)

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11
Q

Tic disorder causes

A

Often associated with other co-morbid conditions

  • 50% have ADHD
  • 33.3% have OCD
  • up to 50% have anxiety

Complex genetic inheritance

Post infectious immune

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12
Q

Chorea

A

Jerky, brief, irregular contractions that are not repetitive or rhythmic

Patient appears fidgety, restless

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13
Q

Chorea causes

A

Common causes include

  • degenerative- huntington’s disease
  • drugs- neuropletics
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14
Q

Huntington’s chorea genetics

A

Trinucleotide repeat on chromosome 4

Autosomal dominant with complete penetrance

Longer the repeat sequence, earlier the disease presents

Repeat sequence unstable and tends to enlarge ‘anticipate’ with each generation

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15
Q

Huntington’s clinical presentation

A

Cognitive
- inability to make decisions, multitasking, slowness of thought

Behavioural
- irritability, depression, apathy, anxiety, delusions

Physical
- chorea, motor persistence, dystonia, eye movements

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16
Q

Myoclonus

A

Brief movement

Rapid onset and offset

Positive (muscular contractions) or negative (muscular inhibitions)

17
Q

Myoclonus pathophysiology

A

Unknown

Possible an imbalance between excitatory and inhibitory neurotransmitters

Perturbations of motor control system leading to brief equilibrium

18
Q

Myoclonus causes

A

Juvenile myoclonic epilepsy

Brain hypoxia

Prion disease

19
Q

Dystonia

A

Abnormal twisting posture

Often axial/ facial/ truncal

May be associated with jerky tremor

20
Q

Dystonia pathophysiology

A

Not fully understood

Functional PET studies suggest abnormal activity in motor cortex, supplementary motor areas, cerebellum and basal ganglia

21
Q

Dystonia causes

A

Stroke

Brain injury

Encephalitis

Parkinson’s disease

Huntington’s disease

22
Q

Tremor

A

Involuntary, rhythmic, sinusoidal alternating movements of part of the body

Affect different parts of the body

Movement of occurence

23
Q

Tremor pathophysiology

A

Postulated theory: increased activity in the cerebellothalamocortical circuit

PD: dopamine dysfunction in the pallidum results in this

ET: GABAergic dysfunction in the cerebellum causes this

24
Q

Drug treatment of hyperkintetic movement disorders

A

Tics/ chorea/ ballismus

Dopamine (D2) receptor blockers

  • haloperidol
  • chlorpromazine

Dopamine depleting agents

  • tetrabenazine
  • reserpine

Atypical anti-psychotics

  • clozapine
  • olanzapine
25
Q

Response of basal ganglia to dopamine blocking agents

A

Neuropletics and other D2 blockers can cause acute problems

  • oculogyric crisis
  • neuroleptic malignant syndrome

Subacute problems
- drug induced parkinsoniusm

Or long term dyskinesias

26
Q

Oculogyric crisis

A

Very characteristic acute response to certain drugs

Fixed stare, upward deviation of eyes

Neck extension

Trunk extension

Jaw spasms and tongue protrusion

27
Q

Neuroleptic malignant syndrome

A

Acute medical emergency developing over hours/ days in response to D2 blockers

Rigidity/ muscle breakdown

Fever

Autonomic instability

Confusion

28
Q

Tardive dyskinesia

A

Choreic oral facial movements

Exact mechanism unclear

Treatment

  • gradual withdrawal of offending agent
  • substitution with atypical anti-psychotic
  • use of dopamine depleting agent
29
Q

Parkinsonism

A 
Slowness of movement
Stiffness
Shaking
Rigidity
Rest tremor
30
Q

Non motor symptoms of parkinsonism

A

Mood: depression, anxiety

Dementia: slowed thought, mental inflexibility

Autonomic involvement
- postural hypotension, hypersalivation

Sleep disturnace
- restless legs, REM parasomnia

Reduced sense of smell

31
Q

What is Parkinson’s disease?

A

Neurodegenerative condition, primarily affecting dopaminergic cells of substantia nigra

32
Q

Causes of parkinsonism

A

Neurodegenerative

  • parkinson’s disease >80%
  • diffuse lewy body disease
  • atypical parkinsonism

Secondary

  • drugs
  • cerebrovascular disease
  • hydrocephalus
  • toxicity/ metal deposition disorders

Genetic

  • metabolic- wilson’s disease
  • rare familial causes
33
Q

Parkinson’s disease early drug therapies

A

Amantadine

  • initially anti flu agent
  • glutamate agonist

Anti-cholinergics (procyclidine, benzhexol)

  • may help with tremor
  • limite by side effects

Mono-amine oxidase inhibitors

34
Q

Acetyl choline/ dopamine balance in basal ganglia

A

Striatum is rich in acetylcholine as well as dopamine

Reduction of dopamine in Parkinson’s disease leads to functional excess of acetylcholine

Compensation can be achieved by reducing acetylcholine effect

35
Q

Monoamine oxidase inhibitors

A

Prevent breakdown of monoamine chemical neurotransmitters

Type A: serotonine, adrenaline, dopamine

Type B: dopamine

Non selective for depression

More selective for Parkinson’s disease

36
Q

L-dopa

A

Available in several formulations

Always combined with dopa decarboxylase inhibitor

Commercial preparations

37
Q

Entacapone/ tolcapone

A

Reduced peripheral metabolism of L-dopa

Pros: increases duration of action of L-dopa, increases efficacy of L-dopa, good for wearing off with L-dopa between doses

Cons: makes dyskinesis worse, diarrhoea, liver disease (tolcapone)

38
Q

Apomorphine s/c infusion

A

Dopamine agonist

Pros: very effective, instant effect, reduced dyskinesis

Cons: only for the right patient, skin nodules

Theme 2: Sensory input and motor outputs (11 decks)

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