Basal Ganglia and Parkinson's Disease Flashcards
Striatum =
Dorsal striatum and ventral striatum
Dorsal striatum =
caudate and lentiform
Neostriatum =
caudate nucleus and putamen
Ventral striatum =
nucleus accumbens and olfactory tubercle
Lentiform/Lenticular =
putamen and globus pallidus
What are the basal ganglia? And name the main components
- Neostriatum (caudate nucleus and putamen)
- Paleostriatum (globus pallidus)
- Subthalamic nucleus
- Substantia nigra
What are the main functions of the basal ganglia?
- Smooth movement
- Switching behaviour
- Reward systems
- Closely linked to thalamus, cortex and limbic system
What sort of patterns do the basal ganglia generate?
- Basal ganglia thought to generate basic patterns of movement (motor programs)
Where do all parts of the cerebral cortex project to?
- All parts of cerebral cortex project to corpus striatum, basal ganglia project to thalamus, thalamus projects to cerebral cortex (the motor loop)
What does cortical activation of the putamen lead to?
- Cortical activation of putamen leads to excitation of supplementary motor area (SMAO by ventrolateral nuclei (VLN) of thalamus
Draw a diagram of the direct pathway of the basal ganglia system
- Cortical excitation of neostriatum leads to distribution of thalamic nuclei
- Movement follows activation of putamen by cortical areas
Draw a diagram of the indirect pathway of the basal ganglia components
- Cortical excitation of neostriatum leads to inhibition of inhibitory input to subthalamus
What leads to activation of the direct pathway and inhibition of the indirect pathway
Activation of the dopamine pathway
What is the MAIN function of the basal ganglia?
remove the inhibition on the thalamus
**The thamalus allows information to travel to the cortex and trigger movement with inhibitory signal removed
What are the major clinical problems associated with the basal ganglia? And where does the defect occur
- Parkinson’s disease (substantia nigra deficit)
- Huntington’s disease (caudate deficit)
- Hemiballismus (subthalamic deficit)
- Wilson’s disease (lenticular)
What are the clinical features of Parkinson’s Disease?
- Hypokinetic - decreased bodily movement
- Tremor at rest
- Rigidity – cogwheel, limbs > axial
- Bradykinesia
- Asymmetry
- Loss righting reflex
- 30% cognitive decline
- Hypomimia (lack of facial expression)
- Glabellar tap
- Quiet speech
- Micrographia
What is the pathogenesis of Parkinson’s Disease?
- Bradykinesia, akinesia, rigidity
- Degeneration of dopaminergic neurons on substantia nigra
Describe the features of Huntington’s disease
- Hyperkinetic - increased bodily movements
- Autosomal dominant
- CAG triple repeat disease (>40 repeats)
- Mutant huntingtin accumulates, toxic
- Chorea, behavioural disorders, dementia
- Caudate nucleus wasting
What is the pathophysiology of the basal ganglia in Huntington’s Disease?
- Degeneration of caudate, putamen and globus pallidus
What are the clinical features of Huntington’s disease?
- Hyperkinesia, dyskinesia
- Characterised by inappropriate or repetitive execution of movement patterns
What type of genetic disorder is Wilson’s disease?
- Autosomal recessive
What are the clinical features of Wilson’s Disease?
- Abnormal copper accumulation
- Hepato-lenticular degeneration (liver and brain)
- Dystonia, ataxia, subcortical dementia
- Copper transport, protein abnormality
- Low serum copper and caeruloplasmin
- Kayser-Fleisher rings
What is the main treatment of Wilson’s Disease?
- Treatment = Penicillamine
What is the main stratgey in the treatment of Parkinson’s Disease?
counteract the deficiency in dopamine in the basal ganglia
What are the 5 main drugs used in the treatment of Parkinson’s?
- Levodopa (in combination with carbidopa or benserazide)
- Dopamine agonists (e.g. pramipexole, ropinirole and bromocriptine)
- Monoamine oxidases B (MAO-B) inhibitors (e.g. selegiline and rasagiline)
- Amantadine – releases dopamine
- Muscarinic Acetylcholine Antagonist (trihexyphenidyl (benzhexol))
What are the main sites of action of drugs used in Parkinson’s?
What is the first line treatment for Parkinson’s?
- First line treatment for PD combined with a dopa decarboxylase inhibitor (cabidopa or benserazide)
- This combination lowers the dose needed and reduces peripheral system side effects (e.g. nausea, hypotension)
Why is there a limited time effectiveness of levodopa?
- Limited effectiveness with time as the neurodegeneration progresses
What are the long term side effects of levadopa
- Involuntary writhing movements (dyskinesia) which may appear within 2 years. After face and limbs mainly. Occurs at peak therapeutic effect
- Rapid fluctuations in clinical state. Hypokinesia and rigidity may suddenly worsen and then improve again. This on-off effect not seen in untreated PD patients or with other PD drugs. Reflects fluctuating receptor dynamics
What are the main dopamin agonists that work on the D1 and D2 receptors? And what are their side effects?
Bromocriptine, cabergoline and pergolide (ergots) are orally active drugs that work on D1 and D2 receptors.
They have limiting side effects – fibrotic reactions.
Name the D2/3 selective dopamine receptor agaonists
Pramipexole and roprinole
What are the amin MAO inibitiors and why are they used in combination?
- Selegiline & Rasagiline are a selective MAO-B which lacks the unwanted peripheral effects of non-selective MAO inhibitors.
- Inhibition of MAO-B protects dopamine from extra neuronal degradation.
- Combination with levodopa is more effective in relieving symptoms and prolonging life.
What is amantadine and how does it work?
- Antiviral drug discovered to be beneficial in PD.
- Increased dopamine release is primarily responsible for its therapeutic effect.
- Less effective than levodopa or bromocriptine and action declines with time.
What are the main acetylcholine anatgonists?
- Muscarinic acetylcholine receptors exert an inhibitory effect on dopaminergic nerves suppression of which compensates for a lack of dopamine.
- Benzhexol, Orphenadrine and procyclidine can all be used, with usual anti- cholinergic side effects.
