The Basal Ganglia Flashcards
Neostriatum
(caudate nucleus & putamen)
Substantia nigra
- Filled with melanin
- Pars reticulata (GABAergic)
• Pars compacta (dopaminergic)
Functions of Basal Ganglia
- Smooth movement
- Switching behaviour
- Reward systems
- Closely linked to thalamus, cortex and limbic system
Direct pathway
– Cortical excitation of neostriatum leads to
disinhibition of thalamic nuclei
– Movement follows activation of putamen by cortical areas
Indirect pathway
– Cortical excitation of neostriatum leads to inhibition of inhibitory input to Subthalamus
– Activation of indirect pathway leads to inhibition of cortical areas
Activation of the dopamine pathway leads to
activation of direct and inhibition of indirect pathways
Parkinson’s disease
(substantia nigra pars compacta deficit)
– Hypokinetic, bradykinesia, hypertonia
Bradykinesia, akinesia, rigidity
• Degeneration of dopaminergic neurons of substantia nigra pars compacta
Huntington’s disease
chorea (caudate deficit) – Hyperkinetic, hypotonia
- Autosomal dominant
- CAG triplet repeat disease (>40 repeats)
- Mutant huntingtin protein accumulates, toxic
- Chorea, behavioural disorders, dementia
- Caudate nucleus wasting
- Hyperkinesia, dyskinesia
- Characterised by inappropriate or repetitive execution of movement patterns
- Degeneration of caudate, putamen & globus pallidus
Hemiballism
(subthalamic deficit)
– Hyperkinetic
– Violent, involuntary movements
Wilson’s disease
(lenticular)
– Associated with copper deposition
– Involuntary movements
- Autosomal recessive
- Abnormal copper accumulation
- Hepato-lenticular degeneration (liver & brain)
- Dystonia, ataxia, subcortical dementia
- Copper transport protein abnormality
- Low serum copper and caeruloplasmin
- Kayser-Fleisher rings (see arrow)
- Teatment - Penicillamine
Clinical Features of Parkinson’s Disease
- Tremor at rest
- Rigidity – cogwheel, limbs>axial
- Bradykinesia
- Asymmetry
- Loss righting reflex
- 30% cognitive decline
- Hypomimia (lack facial expression)
- Glabellar tap
- Quiet Speech
- Micrographia
treatment for Parkinson’s disease
Dopa decarboxylase (DDC)
• Catechol-O-methyl transferase
(COMT)
• Monoamine oxidase B (MAO-B)
Levodopa
- First line treatment for PD and combined with a dopa decarboxylase inhibitor (carbidopa or benserazide).
- This combination lowers the dose needed and reduces peripheral system side effects (e.g. nausea, hypotension).
Long Term Side Effects of levodopa
- Involuntary writhing movements (dyskinesia) which may appear within 2 years. Affect 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.
