HNN PBL 5 Flashcards
What is the most common thing to go wrong in movement disorders?
The basal ganglia
What are the roles of the basal ganglia?
- Initiation of voluntary movement
- Maintaining posture
- Eye movement control
- Social behaviour and decision making
- Executive functions – higher function that help in terms of planning etc / working memory
Where are the basal ganglia located?
The inferior part of the cerebral hemisphere
What are the basal ganglia?
A set of deep nuclear structures that are closely intertwined with lots and lots of pathways between them
Is the direct pathway the “stop” or “go” pathway?
GO
Is the indirect pathway the “stop” or “go” pathway?
STOP
What is linked by the direct pathway?
The striatum and the GPi
What does activity in the direct pathway do?
Increases cortical activity
What is linked by the indirect pathway?
the striatum and GPi via the GPe (Globus pallidus externa) and the STN (Subthalamic nucleus)
What does activity in the indirect pathway do?
Decreases cortical activity
Where is the cerebellum located?
the posterior fossa of the cranium
What connects the cerebellum to the brainstem?
three cerebellar peduncles (superior, middle, and inferior)
What is the Nigrostriatal pathway responsible for?
Movement and sensory stimuli
What is the mesolimbic pathway responsible for?
Pleasure and reward seeking behaviours, addiction, emotion, perception
What is the Mesocortical pathway responsible for?
Cognition, memory, attention, emotional behaviour and learning
What is the Tuberoinfundibular pathway responsible for?
Control of the hypothalamic pituitary endocrine system, inhibition of prolactin secretions
What happens to the dopamine producing cells in Parkinson’s disease?
There is a loss of dopaminergic neurones within substantia nigra
What is made as a side effect of dopamine production?
Melanin
What does less dark staining in the subthalamic nucleus mean?
Less production of melanin –> less dopaminergic stimulation
What forms inside the surviving neurones?
Lewy bodies
What are Lewy bodies?
Intracytoplasmic inclusion bodies
When does Parkinson’s disease begin to manifest clinically?
After approximately 50% of dopaminergic neurones are lost
What does the loss of cells within the substantia nigra result in?
Reduced activity in the direct pathway and increased activity in the indirect pathway.
This leads to an overactive STN and GPI which overall inhibits the thalamus.
What is the general rule relating to proteins in neurodegenerative disorders?
proteins get misfolded and its these misfolded proteins that accumulate in the cells and can be neurotoxic
How many stages are in the Braak staging system?
6 stages
What happens in stages 1-2 of the Braak staging system?
virtually confined to the medulla oblongata and often the anterior olfactory nucleus – these were identified in incidental cases without a PD diagnosis. (no symptoms but may have lost their sense of smell)
What happens in stages 3-4 of the Braak staging system?
Lewy bodies extend into the mid brain and substantia nigra. Most in stage 3 have a PD diagnosis
What happens by the time a patient reaches stage 5-6 of the Braak staging system?
widespread distribution of Lewy bodies and this is consistent with Parkinson’s dementia.
What symptoms may a patient with Parkinson’s disease have before they present clinically?
Disturbed sleep, bladder issues and constipation
What are the key symptoms for a diagnosis of Parkinson’s disease?
tremor, rigidity and bradykinesia
What symptoms develop as Parkinson’s disease progresses?
Patients will get worsening of symptoms at first on one side but it then moves to the other side. They then get balance problems, then cognitive difficulties
What is bradykinesia?
slowness in initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions (repeated finger taps or arm movements)
What is the pharmacological aim of Parkinson’s disease treatment?
To improve motor symptoms/improve quality of life (no evidence for neuroprotection so don’t impact the long term outcome of the disease)
What are the classes of drugs used to treat Parkinson’s disease?
L-dopa
Dopamine agonists
MAO-B inhibitors
COMT inhibitors
What are the ways L-dopa can be prepared?
L-dopa + carbidopa = Sinemet
L-dopa + benserazide = Madopar
Why does L-dopa have to be combined with another substance to be administered?
Carbidopa and benserazide both acts to prevent L-dopa being metabolized peripherally and the side effects that would come with that
What are the common adverse effects of L-dopa treatment?
- Peripheral: nausea, vomiting, postural hypotension
- Central: confusion, hallucinations
What is the half life and efficacy of dopamine agonists like compared to L-dopa?
Longer half-life
less efficacious
What are the side effects of dopamine agonists?
Dopaminergic side effects, Daytime somnolence and Impulse control disorders (e.g. pathological gambling, hypersexuality)
What are the two types of Enzyme inhibitors used to treat Parkinson’s disease?
MAO-B inhibitors e.g. selegiline, rasagiline
COMT inhibitors e.g. Entacapone, Opicapaone
When in the progression of Parkinson’s disease are MAO-B inhibitors used?
Either in early disease or alongside L-dopa later on.
When in the progression of Parkinson’s disease are COMT inhibitors used?
Usually prescribed in later disease
What are treatment options for advanced PD?
Apomorphine (dopamine agonist subcutaneous needle – gives smooth dopamine profile) pen injections or subcutaneous pump, Intrajejunal duodopa infusion, Deep brain stimulation surgery
