Parkinson's disease Flashcards
What is the epidemiology of Parkinson’s?
Age of onset – 45-65
2nd most common neurodegenerative disease (after Alzheimer’s)
What is the aetiology of Parkinson’s?
Most commonly caused by idiopathic Parkinson’s disease
Others: Can be other rare genetic syndromes Certain drugs – neuroleptics, metoclopramide, prochlorperazine Trauma/boxing Encephalopathy post flu Manganese/copper toxicity – Wilsons HIV
What is the pathophysiology of Parkinson’s?
Result of a loss of domaminergic neruons in the basal ganglia (substantia nigra)
Surviving neurons contain aggregations of protein (α-synuclein) called Lewy bodies
Sometimes these present throughout the brain and in such instances, Lewy Body dementia often co-occurs (whether its classified as dementia with Parkinson’s or Parkinson’s with dementia depends on which presents first)
Symptoms are exhibited once neuron levels are 20-40% of the normal
The degree of cell loss and akinesia are strongly correlated
There is no obvious cause for the loss in neurons
The disease progresses slowly and without remission
What is the classic triad of symptoms in Parkinson’s?
Tremor – usually of the hands ‘pill-rolling’ , 4-7Hz, disappears with deliberate activity/worse at rest
Rigidity – increased resistance to passive movement that is equal throughout the range of movement (unlike spasticity which is velocity dependent); equal in extensors and flexors; power remains normal and there is no sensory loss
Bradykinesia – slow movements, especially exaggerated in fine movements – touch finger to thumb
What are some other symptoms of Parkinson’s?
Posture + gait – slow shuffling steps, often stooped with reduced arm swinging
Speech – may be slow and monotonous; may be slurred or absent in late stage
Plain/blank face – exaggerated by low blink rate
Depression, Dementia
Constipation, frequency/urgency
Hallucinations
Poor decoding of emotional content of speech
REM sleep disorders
Reduced sense of smell
Micrographia
How do you diagnose Parkinson’s?
Usually completely clinical
Can do ioflupane SPECT scan = DaTSCAN:
Looking at dopaminergic neurons in substantia nigra can be used to identify degeneration
SN usually look like comas – in degeneration will look like dots or much reduced
What is the mainstay of Parkinson’s treatment?
L-DOPA:
Dopamine cannot cross BBB but precursor L-DOPA can → converted to dopamine in brain → increases levels
Often given with other agents i.e. dopa-decarboxylase inhibitors, used to prolong its short half-life and extend its effects = Co-beneldopa, co-careldopa
What is important to note when treating with L-DOPA?
Therapeutic window = narrow:
Can easily give too much and get side effects (e.g. hypotension, nausea, psychotic symptoms) or too little and under treat
This leads to an ‘on-off effect’:
From the fluctuating plasma concentration
Window narrows further over 10-15yrs of treatment as efficacy decreases too (hence given with dopa-decarboxylase inhibitors), delay treatment until necessary
Do not stop suddenly as can precipitate neuroleptic malignant syndrome
What are some other agents given in Parkinson’s?
Ropinirole and Pramipexole:
i) Selective D3 agonists
ii) Often used as adjuncts to L-DOPA
Bromocriptine and amantadine:
i) Dopamine agonists
ii) Rotigotine – available as patch and useful for NBM
Selegilene:
i) MAO-B inhibitors
ii) Useful adjunct
Catechol-O-methyl transferase (COMT) inhibitors:
i) Inhibit breakdown of levodopa, increase its half life and so helps with end of dose titrations
What other management is required in Parkinson’s?
Detailed review of care and Dx every 6-12/12 - tackle any new features properly (i.e. DLB)
Medicines reviews frequently
Written info - disease + drugs (e.g. Parkinsons.org.uk)
Advise them to inform DVLA
Advance directives + LPA
Vit D supplementation (due to seditary life and increased falls risk)
MDT specialist care - SALT, PT, OT, dietetics, social care, community nursing, continence + urology, psychology - as required
Carer support
Atypical antipsychotics (if necessary) - olanzapine
What conditions are associated with PD?
Parkinson plus syndromes:
Progressive Supranuclear Palsy:
Early postural instability and falls, vertical gaze palsy, rigidity of trunk>limbs, no tremor
(PD + gaze palsy = PSP)
Multiple System Atrophy:
Early/simultaneous autonomic features (postural hypotension, bladder dysfunction, ED) and cerebellar signs
(PD + autonomic features at same time = MSA)
Hot cross bun sign = cross shape on pons
DLB:
Cognitive decline, fluctuating cognitive impairment and hallucinations - before/very early in PD progression
Poor responses to levodopa, generally pretty sad
