Nora - movement disorders simplified Flashcards
Components of the basal ganglia
Striatum
Pallidum
Which structures are functionally related to the basal ganglia?
Subthalamic nucleus
Substantia nigra
What is the function of the basal ganglia?
Not well understood
But know it has a function in controlling movement via the thalamo-cortical projection
What is the thalamo-cortical projection?
Relays the information from the thalamus to the rest of the cortex
Key neurotransmitter of the basal ganglia
Dopamine
Characteristic pathological feature of PD
Asymmetric loss of dopaminergic neurons
What causes the loss of dopaminergic neurons in PD?
Protein accumulation = Lewy bodies
Made from a-synuclein
What structure is shown to be pathological in the F-DOPA scan of PD patients?
Striatum
Since the dopaminergic neurons synapse on this structure
Shows up as less bright
Symptoms of a PD patient
Stiffness of arm
Tremor
Handwriting problems
Progressive slowing down when carrying out repetitive tasks
Signs of PD
Bradykinesia
Cogwheel rigidity
Gait disorder
Rest tremor
What are the disease complications of PD?
Loss of gait and balance
Dementia
What does the Braak hypothesis explain?
Spreading of pathological Lewy Body aggregates
Staging of PD can be correlated to the specific pattern of spreading
Causes of PD
2% - genetic mutations directly linked to the condition (APP, PSEN1/2)
8% - mutations that act as risk factors for developing the condition
90% - idiosyncratic PD
Types of pre-pharmacological treatment
Explanation of diagnosis
SALT
Physio- and occupational therapy
Examples of pharmacological treatment of PD
L-DOPA
Dopamine agonist
COMT inhibtor
MAO-B inhibitor
What is the goal of pharmaceutical therapies in PD?
Raise the dopamine concentrations in the basal ganglia
How is L-DOPA specialised to increase the dopamine in the basal ganglia?
It it can cross the BBB
Given with carbidopa to prevent systemic breakdown of L-DOPA to dopamine which can lead to postural hypotension
What do COMT and MAO-B inhibitors do?
Inhibits the breakdown of dopamine into its products
Increasing its concentration in the synapse
Example of COMT inhibitor
Entacapone
Example of MAO inhibitor
Rasagaline
Example of L-DOPA drug
Carbidopa
Example of Dopamine agonist
Apomorphine
What are prodromal symptoms?
Early symptoms and signs of an illness that precede the characteristic manifestations of the acute, fully developed illness
How many dopaminergic neurons are lost before motor symptoms start to present in PD?
60%
What are the premotor symptoms of PD?
Cognitive -> frontal-executive impairment
Affective -> depression, anxiety
Sleep -> REM behaviour disturbance
Autonomic -> constipation
Special senses -> impaired olfaction
What are 3 other Parkinsonian conditions?
Progressive supranuclear palsy
Multiple system atrophy
Corticobasal degeneration
The two defining characteristics of PSP
Vertical supranuclear gaze palsy
Tendency to fall
Pathological proteins underlying PSP
Tau
Which neurons are degraded in PSP?
Neurons related to walking
Which brain areas are affected by PSP?
Brain stem
Useful clues for PSP diagnosis
No or minimal levodopa response
Little blinking
Frontal dementia -> no problem with memory, but planning and behavioural changes
Age > 40
REM sleep behaviour disturbance
What is the main characteristic of MSA?
Affects the autonomic system
Leads to symptoms like
- urinary incontinence
- postural hypotension
What part of the brain is affected by MSA?
Cerebellum
Protein pathology underlying MSA
A-synuclein aggregates in glial cells
What is the main characteristic of CD?
Caused by atrophy of brain areas, rather than protein aggregate formation
What part of the brain is affected in CD?
Cortex
Basal ganglia
Symptoms of CD
Asymmetric limb stiffness
Action myoclonus
Limb apraxia
Inability to carry out skilled purposeful movement
What distinguishes CD from PD?
CD is very asymmetrical
What helps differentiate between a Parkinson’s diagnosis and diagnosis of other movement disorders?
Scans - F-DOPA uptake
History - peripheral or non-motor symptoms can be conclusive of PD
Treatment - if patients respond to PD therapy, it is conclusive of PD
What is the only way to certainly differentiate between Parkinson’s and other movement disorders?
Post-mortem biopsies
Which pathway has D1 receptors?
Direct
Which pathway has D2 receptors?
Indirect
What is the function of the nigrostriatal pathway?
Dual, antagonistic effects on the direct and indirect pathway
Stimulates the direct pathway through binding to D1
Inhibits the indirect pathway through binding to D2
Overall, allows the production of movement
Where does the nigrostriatal pathway stem from?
Substantia nigra pars compacta
