Lecture 22 - Introduction to Movement Disorders Flashcards
What are movement disorders?
Clinical disorders associated with basal ganglia disease.
What can movement disorders be sub-divided into?
Too little movement (hypo kinetic disorders)
Too much movement (hyperkinetic disorders)
What is Parkinson’s disease?
A degeneration disease characterised by a group of cardinal features that include rigidity, resting tremor, slowness in movement (bradykinesia) and balance problems.
Why is Parkinson’s and Lewy body dementia linked?
The main proteins involved in both are alpha-synuclein deposits in the brain.
LBD patients eventually get PD and PD patients sometimes get LBD.
Why do PD patients lose their smell and taste?
Basal monoamines in the brainstem are affected.
What does the basal ganglia contain?
Putamen
External globus pallidus (GPe)
Internal globus pallidus (GPi)
Substantia nigra
Subthalamic nucleus (STN)
Thalamus
Caudate nucleus
Where is the basal ganglia located in the brain?
Cerebrum
Describe the loops in the basal ganglia.
Four largely segregated cortical loops that have some cross talk.
Links the basal ganglia to the limbic system so movement selection can be informed by emotional and motivational state.
Links to the frontal lobe so that it is receiving proprioceptive feedback of ongoing motor activity.
Describe the direct pathway in the basal ganglia.
Striatum to GPi directly.
Activation = GPi inhibition > thalamic disinhibition > cortical activation.
Describe the indirect pathway in the basal ganglia.
Striatum to GPi indirectly via GPI and STN. GPi activation > thalamic inhibition > cortical inhibition.
What does the direct pathway in the basal ganglia facilitate?
The activation of desired movement pathways.
What does the indirect pathway in the basal ganglia facilitate?
The activation of inappropriate/conflicting movement pathways.
What is overactivity of the GPi predicted to cause?
A reduced activation of desired movements - bradykinesia.
What is under activity of the GPi predicted to cause?
Excessive activation of undesired movements - chorea.
What are the causes of Parkinson’s symptoms?
Parkinson’s disease
Drugs such as anti-dopaminergics
Cerebrovascular disease
Structural lesion in the basal ganglia.
What are the 4 main clinical signs of PD?
Tremor
Bradykinesia
Problems with initiating movements
Postural instability
What are the 2 separate groups of tremors?
Rest
Postural
Describe the pathophysiology of bradykinesia.
Normally dopaminergic fibres stimulate the direct pathway via D1 receptors and inhibit the indirect pathway via D2 receptors.
In bradykinesia the direct (activating) pathway becomes underactive and the indirect pathway (inhibitory) pathway becomes overactive leading to an overactive GPi.
The overactive GPi inhibits the motor thalamus and cortex leading to reduced cortical activity > bradykinesia.
Describe the relationship between bradykinesia and abnormal oscillatory basal ganglia activity.
Excessive beta band oscillations seen in LFPs of PD patients.
The strong, extensive synchronisation in beta bands prevents neurons coding information in time and space.
The pathological oscillations cause distributed cortical activation that degrades movements.
Describe levodopa as a treatment for Parkinson’s.
Dopamine is the key drug as it is the main chemical that is dropped in PD, but high doses of dopamine can’t be given as it is involved in too many other things.
So, the dopamine precursor levodopa (LDOPA) is given as it can cross the BBB and be taken up into nigral neurons, decarboxylates into dopamine, released into the synaptic cleft to activate post stratal dopamine receptors.
Describe deep brain stimulation (DBS) as a treatment for PD.
DBS can block the output of the STN or GPi and reduces the level of inhibition and improves bradykinesia.
Stimulation frequency and amplitude titrated against clinical impairment.
The stimulating electrode blocks the firing of neurons in its vicinity.
DBS of the striatum and GPi is effective in treating advanced pD.
Describe hyperkinetic disorders.
A heterogenous group of diseases that are characterised by the presence of excessive involuntary movements with a range of different clinical manifestations.
Characteristic of a tic is that it can be suppressed to a certain extent.
What is Huntington’s disease?
Autosomal dominant genetic condition with excess Huntington gene (Chr4p) causing there to be excess Huntington protein which causes excessive movement.
What are the clinical features of Huntington’s disease?
Chorea
Dementia
Anxiety
Depression
