Disease Of The Basal Ganglia Flashcards
Motor disorders associated with basal ganglia dysfunction
Parkinson’s Disease
Huntington’s Disease
Dystonia
Gilles de la Tourette syndrome
Psychiatric disorders associated with basal ganglia disorder
OCD
ADHD
Secondary damage associated with basal ganglia dysfunction
Cerebral palsy
Wilson disease
Pathophysiology of Parkinson’s
Not enough dopamine
Detection of Lewy bodies
Pathophysiology of Huntington’s
Too much dopamine
Symptoms of Parkinson’s
Increased muscle tone
Reduced movements
Symptoms of Huntington’s
Decreased muscle tone
Overshooting movements
Formation of dopamine
L-tyrosine —> tyrosine hydroxylase
L-DOPA —> DOPA decarboxylase
Dopamine
Number of dopamine receptors
5
Main area damaged in Parkinson’s
Substantia nigra
How many neurons must a person lose before symptoms of Parkinson’s
2/3
Neuronal cell death in Parkinson’s
About 50% cell death before any symptoms
Main area damaged in Huntington’s
Caudate nucleus/ striatum
Lateral ventricle and Huntington’s
Lateral ventricles are dramatically enlarged as caudate nucleus has shrunk away
Parkinson’s
Less production of dopamine by Substantia nigra so decreases movement
Huntingtons
Reduced production of GABA by striatum so increases movement
Main symptoms of Parkinson’s
Brady/Akinesia
Problems with doing up buttons, keyboard etc
Writing smaller
Walking deteriorated: Small steps, dragging one foot etc
Tremor
= At rest
May be on one side only
Rigidity
Pain
Problems with turning in bed
Most powerful drug for Parkinson’s
L-DOPA (naturally occurring precursor and drug)
- aims to correct dopamine deficit
Drug treatment of Parkinson’s
Drugs mostly aim at correction of dopamine deficit- L-DOPA
But:
More and more cells die
The drugs work shorter and shorter
The longer on treatment, the more likely are the patients to develop side effects, in particular dyskinesias
Dyskinesia
involuntary, erratic, writhing movements of the face, arms, legs or trunk
Deep brain Stimulation
Functional lesions of the Subthalamic nucleus- improvements of Parkinson’s
What does deep brain stimulation target
Subthalamic nucleus
Normal pathway in brain
Cortex - striatum - thalamus - cortex
Regulated. By Substantia nigra and Subthalamic nucleus
Role of Subthalamic nucleus
Inhibit of motor control
Parkinson’s pathway
Lack of dopamine— decreased inhibition of Subthalamic nucleus — increased inhibition of motor movements
How does deep brain stimulation work
Inhibits Subthalamic nucleus— net gain of mivement
Clinical features of Huntington’s
Chorea
Dementia/psychiatric illness
Personality change
Clinical genetics of Huntington’s
Autosomal dominant
Fully penetrant
Chorea
symptom that causes involuntary, irregular or unpredictable muscle movements. It affects your arms, legs and facial muscles
Pharmacological treatment of Huntington’s
Dopamine receptor blockers = neuroleptics
-typically used for psychosis treatment
Genetics of Huntington’s
40 or more triplet CAG repeats of Huntingtin gene- expansion disorder
Normal number of triplet repeats in Huntingtin gene
37
Age of onset and number of CAG repeats - Huntington’s
More repeats - earlier likely to develop disease
Disease-modelling therapy- Huntington’s
Down regulation of mutant Huntingtin protein
