CKS Parkinson's disease Flashcards
What is Parkinson’s disease?
Chronic progressive neurodegenerative condition resulting from loss of dopamine-containing cells of substantia nigra
Resulting dopamine deficiency within basal ganglia leads to movement disorder with classical parkinsonian motor symptoms (not clinically apparent until 50% dopaminergic cell activity lost)
What is parkinsonism?
Umbrella term for clinical syndrome involving bradykinesia plus at least one of
- Tremor
- Rigidity
- Postural instability
What causes parkinsonism?
Most common cause is idiopathic PD Also -drug induced parkinsonism -Lewy body dementia -cerebrovascular disease -multiple system atrophy -progressive subnuclear palsy
What causes Parkinson’s disease?
Cause unknown (but interplay of genetics and environment) Some FHx (20%) 24 gene loci with significant association (PARK1-9)
How prevalent is Parkinson’s disease?
137,000 living with PD
Increases with age
M>F
Lifetime risk 2.7%
What effect does PD have on life expectancy?
Reduced (mortality rate in 70-89y increased 2-5 times)
Risk of dementia is 2-6 times higher in PD
Slowly progressive
What effect does age of onset have on long term outcomes in PD?
Older age at onset/longer disease duration = higher prevalence of motor and non-motor complications
Early onset/short duration = lower prevalence of complications
What complications are associated with PD?
Motor complications (related to use of anti-parkinsonian medication)
Non-motor complications (usually onset later)
-Mental health
-Autonomic dysfunction
-Other
What are the motor complications of PD?
Deteriorating function (immobility, slowness, withdrawal from activities, communication difficulty)
Loss of drug effect
Motor fluctuations (end of dose fading e.g. from levodopa, typically predictable; on-off phenomenon, fluctuating response to levodopa classically after years of use; dose failure to provide symptomatic relief)
Dyskinesia (Choreiform - quick fidgety movements and Dystonic - slow distorted movements/postures)
Freezing of gait (initiation, inability to lift foot)
Falls (multifactorial e.g. think drugs, postural instability , cognitive impairment, orthostatic hypotension; early onset falls may indicate progressive supranuclear palsy)
What are the mental health conditions associated with PD?
Depression, anxiety and apathy (up to 50%) Dementia and cognitive impairment (affects up to 1/3 e.g. visuospatial impairment, visual hallucinations and delusions, impaired concentration) Impulse control disorders (adverse effect of dopaminergic medication, increased risk if history of impulsive behaviour/previous dopamine agonist therapy/history of heavy alcohol or smoking use) Dopamine dysregulation syndrome (rare, compulsive overuse of dopaminergic drugs, associations with gambling/hypersexuality) Psychotic symptoms (delusions and hallucinations, normally visual; psychosis may be caused by dementia or depression)
What autonomic dysfunction can occur in PD?
Constipation (30%, LB degeneration in myenteric plexus of colon slows transit times, overflow incontinence may occur around impaction, role of medication) Orthostatic hypotension (fatigue/pre-syncope/syncope/falls/gradual LOC, >20mmHg systolic decrease or >10mmHg diastolic decrease, likely cause Lewy body degeneration of hypothalamus/brainstem/peripheral nervous system, symptoms may be exaggerated by anti-Parkinson medication/other drugs) Dysphagia (95%, increases risk of pneumonia, asphyxia etc) and weight loss (causes: dyskinesia, dysphagia, depression, malnutrition; also consider malignancy and endocrine conditions) Excessive salivation and sweating (70-80%, sweating with end of dose 'off' phenomenon) Bladder (75%, OAB) and sexual problems (ED, premature ejaculation, dopaminergic drugs induce hypersexuality, anorgasmia in women)
What additional complications can occur in PD?
Nausea (esp after medications) and vomiting
Pain (MSK, dystonic, radicular neuropathic, primary or central neuropathic pain, akathisia-related pain)
Sleep disturbance and daytime sleepiness (degeneration of sleep centres of brainstem/thalamocortical pathway, restless legs syndrome, psychotic disturbance)
Aspiration pneumonia (leading cause of mortality)
Pressure sores
What are the likely signs of PD?
Progressive symptoms of
-Bradykinesia (slow initiation of movement, finger/foot tapping)
-Hypokinesia (poverty of movement e.g. reduced facial expression, arm swing, blinking, micrographia, difficulty dressing, festinant gait)
In addition
-Stiffness/rigidity affecting side of onset (lead-pipe rigidity, cogwheel rigidity)
-Rest tremor (improves on movement, pill rolling)
-Balance problems and/or gait disorders (pull test diagnostic)
Other features
-Depression, anxiety, fatigue
-Reduced sense of smell
-Cognitive impairment
-Sleep disturbance
-Constipation
What can cause drug-induced parkinsonism?
Antipsychotics
-First generation (haloperidol, chlorpromazine) > second generation
Anti-emetics
-Prochlorperazine
-Metoclopramide
Other drugs more rarely cause parkinsonism
What else may be responsible for a tremor other than PD?
Essential tremor Physiological Dystonic tremor (more common in young adults) Intention tremor (cerebellar) Drugs
What other differentials should be considered with PD?
CVA e.g. repeated strokes Non-parkinsons dementia Neurodegenerative parkinsonism (progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration) Wilson's disease Repeated head injury
How should suspected PD be managed?
Referral urgently and untreated to a specialist
If drug-induced parkinsonism, stop drug suspected (and refer to specialist)
What should be done on routine review of confirmed PD in GP?
Comprehensive review every 6-12m, regular medication review
Support (leaflets)
Advise informing DVLA of decision
Consider MDT involvement e.g. SALT, physio, OT
Advise Vit D supplements
Ask about motor and non-motor complications caused by disease or anti-parkinsonian meds
What first line treatments are available for PD?
Levodopa
-Early stages
-More improvement, fewer side effects (but can cause more motor complications vs other drug classes)
Oral MAO-B inhibitors (selegiline, rasagiline, safinamide)
-Fewer side effects but less effective control of
Oral dopamine agonists (pramipexole, ropinirole) or transdermal dopamine agonist (rotigotine)
-Ergot-derived dopamine agonists (cabergoline and pergolide) should not be used as first line due to risk of cardiac fibrosis
What side effects are commonly associated with first line treatments for PD?
Excessive sleepiness
Hallucination
Impulse control disorder
What adjuvant therapy can be used in the management of PD?
Oral COMT inhibitors (entacapone)
-Often given with levodopa, carbodopa, entacapone to improve compliance
-Reduce fluctuations in motor symptoms
-May cause excessive sleepiness/impulse control disorders but less associated with hallucination
Oral amantadine
-Used in poor control of dyskinesia
Subcutaneous apomorphine (dopamine agonist)
-Advanced PD
Duodopa (entral delivery)
Deep brain stimulation (DBS) of subthalamic nucleus
-Advanced PD
-Insertion of electrodes (bilaterally) into deep nuclei; generator in chest wall (transcutaneous charge)
How is constipation in PD managed?
Conservative -Inc dietary fibre and fluid intake -Exercise (within capacity) Medical -Consider laxatives -Enemas if laxatives fail
How is nausea and vomiting managed in PD?
Increase levodopa/dopamine agonist
Persistent N&V
-Do not use metoclopramide/prochlorperazine (exacerbate parkinsonism)
-Consider low dose domperidone (many interactions e.g. apomorphine + D causes prolonged QT, associated risk of ventricular tachyarrhythmia and sudden cardiac death)
How is pain managed in PD?
Review with appropriate team (e.g. for dystonic/primary or central neuropathic/akathisia-related pain
Simple analgesia (e.g. NSAIDs) and exercise for MSK pain
For radicular neuropathic pain use analgesia and exercise, relevant drugs if necessary
