Parkinson's Disease Flashcards
What is Parkinson’s disease?
Neurodegeneration of the dopaminergic neurones of the substantia nigra
What is the pathophysiology of PD?
Degeneration of dopaminergic neurones in the pars compacta (substantial nigra)
Pars compacta connects the substantia nigra to the striatum (caudate + putamen). This dopamine pathway is called the NIGROSTRIATAL PATHWAY.
This pathway is needed to initiate movement and stimulate the thalamus/ motor cortex
What is thought to be the mechanism of degeneration
It is thought mitochondrial DNA dysfunction causes degeneration of dopaminergic neurones in the substantia nigra pars compacta as this is associated with Lewy bodies.
- Lewy bodies are found within the neuronal cell bodies
- The bodies consist of abnormally phosphorylated neurofilaments- alpha-synuclein and ubiquitin
What are the causes of PD?
Usually sporadic/ idiopathic.
Has genetic mutation links- PINK 1
- could also occur as a result of the following:
- Drugs like neuroleptics, metoclopramide, prochlorperazine
- MPPP toxicity (synthetic opioid)
- Wilson’s disease
- Repeated head injury (trauma)
- Vascular insults (stroke)- this is vascular parkinson’s disease!! (not the same thing)
What are the risk factors for PD?
- Family history
- Frequent head trauma/ previous head injuries
- Pesticide exposure
- Xs caffeine/ nicotine
Describe the prevalence of HD
- 6% at 60-64 years
- 5% at 85-89 years
Typical age of onset= 65
Describe the symptoms/ presentation of PD
*usually very sudden
- Noticeable tremor at rest (noticeably worse on one side)
- Feeling stiff and slow movements
- Might feel a little unbalanced- from history patient may have had a few falls
- Mood changes
- Micrographic (smaller handwriting)
- Insomnia and mental slowness (bradyphenia)
- Constipation
- Reduced sense of smell
- Drooling of saliva
Describe some of the signs of PD
- Tremor is a pill-rolling tremor- will be decreased on action or in a flexed posture. Tremor will be asymmetrical.
- Cogwheel rigidity- felt during rapid pronation and supination
- Bradykinesia/ hypokinesia
- Gait- Stooped posture, shuffling, reduced arm swinging. FESTINANT GAIT
- Unstable and falls over easily
- Expressionless face- serpentine stare, soft monotonous voice
- Dementia- note strange dreams, psychosis and hallucinations
there is no muscle weakness as it doesn’t affect the motor cortex
what is the Levodopa + carbidopa management?
Lifestyle management- pt needs to be told it is incurable. Ask them to do postural exercises and weight-lifting
Levodopa + carbidopa (peripheral DOPA decarboxylase inhibitor)
DOPA decarboxylase converts levodopa into dopamine. Carbidopa inhibits the action of DOPA decarboxylase to prevent the conversion in the periphery. It cannot cross BBB so conversion can occur in the brain.
efficacy reduces with time and will require larger doses
SE: dyskinesia, dystonia, psychosis, visual hallucinations
Name some other medications that can be used
DA receptor agonists; bromocriptine, pergolide
- Increases stimulation of postsynaptic receptors of dopaminergic neurons
- SE: nausea, vomiting, postural hypotension, impulse control disorder; pathological gambling and hypersexuality
Anticholinergics; benzhexol and orphenadrine
Help with tremor SE: confusion, dizziness, poor vision, increased pulse
MAO-B inhibitors; Selegilline
Will decrease the action time of DA. Limited by the cheese reaction (tyramine).
COMT inhibitors; entacapone and tolacapone
Increases concentration of dopamine. Lessens the off time in those with end dose wearing off.
SSRIs could be given for depression
What are some of the potential surgical treatments
- Stereotactic thalamotomy
- Pallidotomy
- Deep brain stimulation
- Surgical ablation of overactive basal ganglia circuits
