Lecture 13: Parkinsons Disease Flashcards
parkinson disease is a
highly prevalent neurodegenerative disorder (~1% over age 60)
parkinsons is characterised by
motor dysfunction AND non-motor dysfunction symptoms
pathology of parkinsons:
DEGENERATION of dopamine neutrons in the substantia nigra (and other areas; olfactory)
% of people >40 yrs
0.4%
% of people >/= 65 years
1%
% of people >/= 80 years
10%
mean age at onset of parkinsons is about
57 years. As we live longer as a society potentially a huge healthcare burden
parkinsons is a neurodegenerative disease meaning its the _____ specifically..
- dysfunction + death of neutrons.
- specifically - Nigrastriatal neutrons of the basal ganglia
in normal basal ganglia
- cells of the Substantia nigra (SN) produce and release dopamine
- dopamine from SN neutrons affects other centres
- main centres affect = dorsal striatum (caudate nucleus & putamen)
- dorsal striatum involved in motor function
what does dopamine do?
- transmits signals between the areas in the brain that, when working normally, coordinate smooth and balanced muscle movement
- may also control functions related to mood
dopamine precursors are
medications the brain converts to dopamine
what do antagonists do:
directly stimulate nerves in the brain that are not naturally being stimulated by dopamine
what two drugs have been prescribed to patients with Parkinsons’ and shown some effect
- Dopamine precursors
- antagonists
what goes wrong gin Parkinson’s disease?
- Cells of substantia nigra degenerate
- these cells can no longer produce adequate amounts dopamine
- neurons of striatum, etc. are no longer well regulated, thus do not behave in normal manner
- results in loss of control of movements- symptoms characteristic of Parkinson’s
Basal ganglia: anatomy
- middle of brain
- Globus pallidus in middle
- hearing aid like shape, putamen surrounds GP
- caudate head to left
- caudate body above
- caudate tail right
- thalamus in-between caudate and putamen
- nucleus accumbent front bottom left
the basal ganglia circuitry
- cortex leads to caudate & putamen (substantial nigra pars compacta [in &out])
- Caudate & Putamen leads to Globus pallidus. leads out to Subthalamic nucleus, back to Substantia nigra Pars reticulata
- leads to thalamus –> loops back to cortex
DRAW IT
in parkinson’s disease, the inputs provided by the ____ ____ are diminished, meaning
- Substantia nigra
- its more difficult generate the transient inhibition form the caudate & putamen
The result of this change is the tonic inhibition from the globus pallidus is sustained to
the thalamus.
This REDUCES the thalamic excitation of the motor cortex
characteristic symptoms: cardinal (motor) features
- Slowness of movement.
- Decreased spontaneous movements, eg eye blinking.
- Tremors
- Muscle rigidity
- Postural change Gait disorders
- slow, short steps
non-motor symptoms
- bowing of shoulders
- swelling of feet
- depression
- sleep disorders
- weight loss
- excessice salivation
- respiratory problems
- orthostatic hypotension
- increases sweating
- constipation
A lewy body is composed of
alpha-synuclein, ubiquitin, neurofilament, alpha B crystallin
stages & symptoms:
1+2 = non-motor signs 3 = motor signs 4,5+6 = cognition, emotion
conventional treatments:2 types
medication + surgery
medical treatment: Levodopa
- (L-DOPA)
- Precursor to dopamine, can be converted by neutrons to dopamine
- can cross blood-brain barrier (dopamine can’t)
- can be prescribed with carbidopa (inhibits dopamine metabolism)
- can produce dyskinesias = uncontrolled movements among other side effects
medical treatment: dopamine agonists
- not metabolised into but act like dopamine
- usually used with L_DOPA in round papers
- side effects: similar to L-DOPA but less involuntary movements but can cause hallucinations
