Neurology: Idiopathic Parkinson’s Disease and Parkinsonism Flashcards
What is the clinical course of Parkinson’s Disease?
- Parkinson’s disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra. There are non-motor symptoms and motor symptoms.
- The symptoms of Parkinson’s disease are characteristically asymmetrical. It is around twice as common in men and has mean age of diagnosis is 65 years
- There is a presence of Lewy bodies in substantia nigra. Tremor in 75%.
Which part of the brain is affected by Parkinson’s Disease?
Basal Ganglia Circuit
- Loss of dopaminergic neurone in substantia nigra results in reduced inhibition in neostriatum
- Loss of inhibition of neostriatum allows increased production of acetylcholine (excitatory)
- Chain of abnormal signalling leads to impaired mobility
Which genes are affected in Parkinson’s Disease?
At least 75% sporadic. Genetic determination in younger patients. Genes are:
- Alpha synuclein – Autosomal Dominant
- Parkin – Autosomal Recessive
What are the motor symptoms of Parkinson’s Disease?
-
Tremor: low dopamine and disturbance in other neurotransmitter levels
- Most marked at rest, 3-5 Hz
- Worse when stressed or tired, improves with voluntary movement
- Typically ‘pill-rolling’, i.e. in the thumb and index finger
-
Rigidity: low dopamine and disturbance in other neurotransmitter levels
- lead pipe
- cogwheel: due to superimposed tremor
-
Bradykinesia: low dopamine
- Poverty of movement also seen, sometimes referred to as hypokinesia
- Short, shuffling steps with reduced arm swinging
- Difficulty in initiating movement
- Postural instability
What are non-motor symptoms of Parkinson’s Disease?
- Pain
- Cognitive changes
- Sweating
- Salivation
- Sphincter problems: urinary symptoms
- Olfactory problems
- Mask-like face
- Flexed posture
- Micrographia
- Drooling of saliva
- Psychiatric features: depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances may also occur (REM)
- Fatigue
- Autonomic dysfunction: Postural hypotension
What are other causes of Parkinsonism?
- Paralysis agitans (IPD)
- Drugs
- Other neurodegenerative disorders: MSA, PSP, CBD.
- Vascular pseudo-parkinsonism
- Infection - encephalitis lethargica
- Metabolic - Wilson’s
- Toxins - MPTP, Mn, CO
What are diagnostic criteria for Parkinson’s Disease?
Step 1:
- Diagnosis of Parkinsonian Syndrome requires
- Bradykinesia
- At least one of the following
- Muscular rigidity
- 4-6 Hz rest tremor
- Postural instability not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction
Step 2:
- Exclusion of other causes of parkinsonism
Step 3:
- Supportive prospective positive criteria for Parkinson’s disease. Three or more required for diagnosis of definite Parkinson’s disease in combination with step one
- Unilateral onset
- Rest tremor present
- Progressive disorder
- Persistent asymmetry affecting side of onset most
- Excellent response (70-100%) to levodopa
- Severe levodopa-induced chorea
- Levodopa response for 5 years or more
- Clinical course of ten years or more
What is the purpose of a DAT scan?
- Uses labelled tracer that is taken up pre-synaptically. Abnormal in Parkinson’s disease but this is not diagnostic
What is the prognosis for those with Parkinson’s Disease?
- Dyskinesia - 94%
- Falls - 81%
- Cognitive decline (50% hallucinations) - 84%
- Somnolence - 80%
- Swallowing difficulty - 50%
- Severe speech problems - 27%
What is the drug treatment for Parkinson’s Disease?
Drug Types are: Levodopa, Dopamine Receptor agonists, MAOI inhibitors, COMT inhibitors, Anticholinergics, Others
-
For first-line treatment:
- if the motor symptoms are affecting the patient’s quality of life: levodopa
- if the motor symptoms are not affecting the patient’s quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor
What are the treatment options for motor fluctuations that occur despite treatment?
- Modify oral therapies
- Apomorphine
- Stereotactic neurosurgery
- Duodopa
What are the risk to the patient if medication is not taken/absorbed?
Risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a ‘drug holiday’ for the same reason.
When are impulse control disorders common?
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
- Dopamine agonist therapy
- History of previous impulsive behaviours
- History of alcohol consumption and/or smoking
What should happen in the cases of orthostatic hypotension, excessive daytime sleepiness and drooling?
If excessive daytime sleepiness:
- Develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.
If orthostatic hypotension:
- Develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.
If Droooling:
- Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson’s disease.
How does drug-induced parkinsonism present slightly differently?
- Motor symptoms are generally rapid onset and bilateral
- Rigidity and rest tremor are uncommon
