Parkinsons disease & drug therapy basal ganglia disorders Flashcards
Broadly speaking there are 4 types of disorders of movement. State them
- Hyperkinetic movement disorders
- Hypokinetic movement disorders
- Disturbance of coordination
- Disturbance of planning
Ballismus is an example of a hyperkinetic movement disorder.
What is Hemiballismus?
How does it arise?
Cause?
A high amplitude flailing of the limbs on one side of the body
Pathophysiology: blocks indirect pathway
Cortex –> GPe
BLOCKADE BETWEEN GPe AND STN
So GPi is less stimulated and so thalamus remains stimulated
Commonest cause: Stroke
Tic disorders are an exampled of hyperkinesis.
What are they are?
What alleviates their presentation? What exacerbates their presentation?
What is tourettes?
What is it associated with/caused by?
Brief repetitive stereotypical movements with a premonitory urge.
- Simple: blinking, coughing
- Complex: jumping, swirling
- Plus: Motor disorder
- Coprolaila: Swearing- RARE
Reduced by distractions and concentration
Worsened by anxiety/fatigue
TOURETTE syndrome is a more severe expression of a spectrum of tic disorders. Associated with motor basal ganglia loop
Associations/causes:
- Comorbid conditions: Morethan 50% have anxiety, 1/3 have OCD, 50% have ADHD
- Complex genetic inheritance
- Post infectious immune
- Associated with motor basal ganglia loop
What type of movement disorder is chorea?
What is its pathophysiology?
Causes?
HYPERKINETIC
Jerky, brief irregular contractions that are NOT repetitive or rhythmic but appear to flow from 1 muscle to next. Patient appears fidgety or restless
Same pathophysiology as Tics and Ballismus. (Blockade between GPe and STN in indirect pathway)
Causes:
- Degenerative- Huntingtons
- Drugs- Neuroleptics
Consider Chorea caused by Huntingtons. What is known about the genetics?
How is its presentation, consider cognitive? Behavioural?
Physical?
Trinucleotide repeat on chromosome 4
Autosomal dominant with complete penetrance
Longer the sequence, the earlier the disease presents
-Repeat sequence is unstable and tends to enlarge ‘anticipate’ with each generation
Cognitive- inability to make decisions, multitasking, slowness of thought
Behavioural-irritability, depression, apathy, anxiety, delusions
Physical- chorea, motor persistence, dystonia, eye movements
What type of movement disorder is Myoclonus?
What is its pathophysiology?
Causes?
Hyperkinetic
Brief movement, rapid onset and offset. Positive- muscular contractions or Negative- muscular inhibitions
Pathophysiology:
- Unknown
- Imbalanace between excitatory and inhibitory neurotransmitters. Pertubations of the motor control system–> brief disequilibrium
Causes:
- Juvenile myoclonic epilepsy
- Brain hypoxia
- Prion disease
What type of movement disorder is Dystonia?
What is its pathophysiology?
Causes?
Hyperkinetic
Abnormal twisting posture, often axial/facial truncal, may be associated with jerky tremor
Pathophysiology:
- Idiopathic
- Abnormal activity in the motor cortex, supplementary motor areas, cerebellum, and basal ganglia?
- Abnormal dopaminergic activity in basal ganglia?
Causes:
- Stroke
- Brain injury
- Encephalitis
- Parkinsons
- Huntingtons
What type of movement disorder is Tremor?
What is its pathophysiology?
Causes?
Hyperkinetic
Involuntary, rhythmic, sinusoidal alternating movements of parts of the body. Affect limbs, head, chin, soft palate
Movements of occurrence: rest, postural, kinetic, essential tremor
PATHOPHYSIOLOGY
- Increased activity in the cerebellothalamocortical circuit
- Dopamine dysfunction in pallidum (postural)
- GABAergic dysfunction in the cerebellum (essential t)
Which drug treatments exist for hyperkinetic movement disorders? Give example
D2 receptor blocking agents- haloperidol, chlorpromazine, pimozide, risperidone
Dopamine-depleting agents- Tetrabenazine, Reserpine
Atypical anti-psychotics- Clozapine, Olanzapine, Aripiprazole
What are the acute responses of basal ganglia to dopamine blocking agents
ACUTE PROBLEMS
- Oculogyric crisis(days/weeks)
- fixed state, upward deviation
- neck and trunk extension
- jaw spasms and/or tongue protrusions
- acute dystonic reaction - Neuroleptic malignant syndrome (days/weeks)
- rigidity/muscle breakdown - increased CPK
- fever
- autonomic instability
- confusion
What is the sub-acute response of basal ganglia to dopamine blocking agents
SUBACUTE PROBLEMS
- Over weeks/months
Drug induced Parkinsons
Consider the long-term response of basal ganglia to dopamine blocking agents
Treatment?
LONG TERM
- Over months/years
Tardive dyskinesias
- Choreic oral facial movements
Treatment: Gradually withdraw offending agents
What type of movement disorder is Parkinsonsism?
What are the physical signs?
What are the non-motor signs?
Hypokinetic movement disorder
Parkinsonism =Akinetic-rigid syndrome
** A neurodegenerative disease primarily affecting dopaminergic cells of the substantia nigra
Physical signs: bradykinesia (slowness of movement) eg loss of facial expression and arm swing, difficulty with fine movement and rigidity, rest tremor
Non-motor signs:
- Mood: depression, anxiety
- Dementia: slowness of thought, mental inflexibility
- Autonomic: postural hypotension, hypersalivation
- Sleep: restless legs, REM parasomnia
- Reduced sense of smell
What are the causes of Parkinsonism?
Neurodegenrative
- Idiopathic Parkinsons disease (>80%)
- Diffuse Lewy body disease
- Atypical parkinsonism (MSA, PSP, CBD)
Secondary
- Drugs (e.g. haloperidol, MPTP)
- CV disease
- Hydrocephalus
- Toxicity/metal deposition disorders
Genetic
Metabolic- Wilsons disease (copper deposition)
Rare familial causes (both dominant and recessive)
Parkinsonism may be caused by Levodopa breakdown. What are the breakdown products of Levodopa?
Dopamine (via DOPAdecarboxylase)
or COMT (via 3-O-methyldopa)
