Neurology Flashcards
Pathology of Parkinson’s disease
Dopaminergic neurones in the substantia migrans degenerate.
Progressive, adult onset movement disorder.
What are the two parts of the substantia nigra and which is affected in Parkinson’s disease?
Pars reticulata
Pars compacta - affected area
Which neuro pathway is affected in Parkinson’s disease and what is its function?
Nigrostriatal pathway - helps to stimulate the cerebral cortex and initiate movement
What are the cardinal motor signs of Parkinson’s disease?
- Bradykinesia
- Resting tremor
- Rigidity
- Postural instability
What does bradykinesia look like in a patient?
- Slow to initiate movement
- Actions slow and decrease in amplitude with repetition
- Gait is shuffling, pitched forward
- Decreased arm swing and freezing at obstacles or doors (due to poor simultaneous motor and cognitive function)
- Expressionless face
Is Parkinson’s disease unilateral or bilateral?
Symptoms often begin on one side of the body or even in one limb on one side of the body. As the disease progresses, it eventually affects both sides. However, the symptoms may still be more severe on one side than on the other.
Non motor symptoms of Parkinson’s disease
- Reduced sense of smell (can lose sense of smell years before motor symptoms)
- Sleep disturbances
- Autonomic dysfunction
- postural hypotension
- constipation
- urinary symptoms
- dribbling of saliva
- Neuropsychiatric complications
- depression
- dementia
- psychosis
Does Parkinson’s disease have a treatment that will stop the progressive neurodegeneration?
No - treatments only aim to control symptoms and will not affect the underlying disease
What are the pharmacological treatments for Parkinson’s disease?
- Levodopa
- Dopamine agonists
- MAO-B inhibitors
- COMT inhibitors
- Anticholinergics
Why is levodopa (precursor to dopamine) given instead of dopamine?
Levodopa can cross the blood brain barrier while dopamine cannot.
What is levodopa combined with and why?
Levodopa is administered with carbidopa - a dopa decarboxylase inhibitor that isn’t able to cross the blood brain barrier
- Levodopa is converted to dopamine by dopa decarboxylase (within nigrostriatal neurones and by peripheral dopa decarboxylase)
- Periperal dopa decarboxylase can metabolise levodopa into dopamine before it gets to the blood brain barrier. Dopamine can be further metabolised into other catecholamines such as epinephrine which can have side effects such as arrhythmias
When should levodopa be started?
Efficacy of this therapy reduces over time, requiring larger and more frequent dosing, with worsening side effects and response fluctuations.
It may be wise to start levodopa late eg >70 years or when symptoms seriously interfere with life.
Side effects of levodopa
- Compulsive gambling, hypersexuality, binge eating, or obsessive shopping (can develop in patient on any dopaminergic therapy)
- Dyskinesia - involuntary movements
- Wearing off - the effects of the drug wear off before the next dose
Why should levodopa not be withdrawn suddenly?
It risks acute akinesia and neuroleptic malignant syndrome
How do anticholinergics work? Who should they be used for?
They balance acetylcholine with dopamine
They cause confusion in the elderly and have multiple side effects - limit use to younger patients