Parkinson's disease and movement disorders Flashcards
What is Parkinson’s disease?
A degenerative, progressive movement disorder caused by a reduction in dopamine in the substantia nigra with characteristic motor symptoms of tremor, bradykinesia, and postural instability
What is the difference between parkinsonism and Parkinson’s disease?
Parkinsonism is a collection of symptoms that are similar to those of Parkinson’s without the degenerative changes of Parkinson’s
How common is Parkinson’s?
Increasing prevalence with age
Peak age of onset 55-65
More common in men
What can cause Parkinson’s disease?
Idiopathic
Combination of…
- Environmental factors - pesticides, methylphenyl tetrahydropyridine found in illegal opiates
- Parkinson genes - mutation in Parkins gene and alpha synuclein gene
- Oxidative stress and mitochondrial dysfunction
What can cause Parkinsonism?
Drugs - neuroleptics, anti-emetics
Normal pressure hydrocephalus
Vascular Parkinsonism
Parkinson’s plus eg multiple system atrophy
What can increase your risk of Parkinson’s disease?
Male
Increasing age
FHx
Non-smoker
What is the pathology of Parkinson’s disease?
Mitochondrial dysfunction and oxidative stress
Results from progressive degeneration of dopaminergic neurons from pars compacta of SN in midbrain that projects to striatum of basal ganglia
Reduced striatal dopamine levels due to loss of dopaminergic neurons
Less dopamine so thalamus inhibited decreasing movement
Neuronal inclusions - Lewy bodies present in Parkinson’s and becomes gradually more widespread as disease progresses, spreading from lower brainstem to midbrain and then cortex
Degeneration in other basal ganglia nuclei
What makes up the basal ganglia?
Striatum
Globus pallidus
Substantia nigra
Subthalamic nucleus
What makes up the striatum?
Putamen and caudate nucleus
What makes up the globus pallidus?
External and internal
How does dopaminergic cell loss correlate to degree of akinesia?
Increased cell loss = increased akinesia
What is akinesia?
Muscle rigidity
Stiffness
Lack of responsiveness
How does Parkinson’s present (motor symptoms)?
Onset gradual and often presents with impaired dexterity
Asymmetrical
Tremor 70% (4Hz slow resting pill rolling)
Rigidity - cogwheel
Bradykinesia/hypokinesia
Gait problems - festinance, freezing, reduced arm swing)
Expressionless face (hypomimesis)
Cramping
Difficulty with fine movements eg problems doing up buttons
Micrographa
What pre-symptomatic symptoms can you get with Parkinson’s?
Anosmia Depression/anxiety Aches and pains REM sleep disorders Urinary urgency Hypotension Constipation
What is tremor in Parkinson’s like?
Worse at rest
Asymmetrical
Most obvious in hands
Improved with voluntary movements and made worse by anxiety
4-6 cycles/sec
Issue with repetitive hand movements with worsening rhythm longer attempted
What is rigidity like in Parkinson’s?
Increased tone in limbs and trunk
Limbs resist passive extension throughout movement
Rigidity over entire radius of joint movement
Can cause pain and problems with turning in bed
What does bradykinesia look like in Parkinson’s?
Slow to imitate movements
Reduced blink rate, monotonous hypophonic speech
Micrographia
What does gait look like in Parkinson’s?
Reduced asymmetrical arm swing
Narrow gait
Narrow base
Stooped posture and small steps
Festinance - shuffling steps, maybe dragging foot with flexed trunk
Difficulty initiating movement and turning
Poor balance
How does Parkinson’s present (non-motor symptoms)?
Drooling of saliva and swallowing difficulty late feature (aspiration pneumonia as a terminal event) Mood disturbance - depression 40% Sleep disturbance Cognitive disorders Pain Impulse control disorders Autonomic dysfunction Anxiety Psychotic symptoms Dopamine dysregulation syndrome
What sleep disturbance might you get in Parkinson’s?
REM sleep behaviour disturbance Insomnia (due to one/more of lack of muscle and mental relaxation, stiffness, restlessness, difficulty moving into comfortable positions, tremor bothersome, medications wearing off, driving/work implications) Daytime sleepiness Sleep disruptions Restless leg syndrome
What autonomic dysfunction might you get in Parkinson’s?
Orthostatic hypotension Constipation Heat intolerance Urinary frequency and incontinence and urgency Nocturia Sweating Hypersalivation Drooling Sexual dysfunction N&V
What are the phases of Parkinson’s treatment?
Early honeymoon period - quite easy to treat, still have buffer of axons in SN - medication seems to last for longer as dopamine released in brain in response to medication
Middle period wearing off - medication doesn’t last as long, loss of buffer
Later period dyskinesia’s (drug induced chorea), fluctuations between chorea and stiffness, cognitive impairment
What is a differential diagnosis for Parkinson’s?
Benign essential tremor - worse on movement and rare whilst at rest Multiple cerebral infarcts Lewy-body dementia Drug-induced Wilson's disease Trauma All dopamine antagonists
How is Parkinson’s diagnosed?
Clinical - based on Hx and examination
Confirmed by response to L-dopa
MRI head - initially normal but slowly atrophies, used to exclude tumours or normal pressure hydrocephalus
Lack of - incontinence, symmetry, early falls
U&E, LFT, TFT, Ca (rule out differentials)
Diagnose using UK PD society brain bank criteria - cannot diagnose without bradykinesia
Review diagnosis every 6-12 months
Document discussion of risk impulse control disorder, sleep attacks, hallucinations
Consider DAT scan in atypical tremors
PET and SPECT - look at metabolic activity of dopamine transporters in basal ganglia measured with PET and SPECT
How might normal pressure hydrocephalus present?
Forget how to walk
Enlarged ventricles
Dementia
How benign essential tremor treated?
50% respond to medication
Treat with propranolol, primidone, gabapentin
How does benign essential tremor present?
Intention tremor
What is the role of the GP in Parkinson’s diagnosis?
Refer to specialist untreated
Refer to specialist if any problems arise
What do you need to put in place for a patient with Parkinson’s?
Oral and written communication to patient and family Care plan Point of contact to specialist services Access to PT, OT, SALT, and dietician Advise vit D supplementation
What medication can you prescribe in Parkinson’s?
Co-careldopa/co-beneldopa - controlled release/dispersible for resuce/morning
COMT - catechol-O-methyltransferase inhibitor - prevents breakdown of levodopa in brain and periphery
Dopamine agonists - non-ergot/ergot
MAO inhibitors
Apomorphine
Amantadine
New - safinamide, opicapone
Name a non-ergot dopamine agonist
Ropinirole
Pramipexole
Rotigontine
Name an ergot dopamine agonist
Bromocriptine
Pergolide
Cabergoline
Name a disadvantage of ergot dopamine agonists
Can cause fibrosis all around body
Name an advantage of dopamine agonists
Less dyskinesia than levo-dopa
Longer acting
Name a disadvantage of dopamine agonists
Risk of hallucinations Compulsive behaviour Postural hypotension Daytime sleepiness S/E
Name a MAO inhibitor
Selegiline
Rasagiline
How can you prescribe selegiline?
5-10mg PO
1.25mg sublingual
How can you prescribe rasagiline?
1mg OD
What is possibly special about rasagiline?
Possibly neuroprotective
What should you be careful with when prescribing MAO inhibitors?
Prescribing with SSRIs/tricyclics - serotonin syndrome
CI - tramadol, pethidine
Rasagiline SSRI best avoided - citalopram relatively safe, tricyclics - nortryptilline
Selegiline - avoid antidepressants
What is apomorphine?
Water soluble dopamine agonist
Rescue treatment in pen form/continuous daytime infusion
Helps smooth out motor fluctuations, less hallucinogenic than other dopamine agonists
What is amatadine used for?
Dyskinesia
How can you treat cognitive disorders in Parkinson’s?
Cholinesterase inhibitors
Memantine if cholinesterase inhibitors not tolerated
How do you treat orthostatic hypotension?
Stop any medications that may be causing it - anti-hypertensives, midodrine, fludrocortisone, ephedrine
How can you treat urinary symptoms?
Anticholinergics
Tropsium
How can you treat hypersalivation?
Glycopyrrolate
Botulinum
How can you treat N&V?
Anti-emetics
How can you treat depression and anxiety?
Treat as non-PD
How do you treat psychotic symptoms?
Refer onto neurologists
Low dose anti-psychotics - quetiapine or clozapine
What motor effects can you get with long term L-dopa usage?
Reduced efficacy over time even if dose increased
On-dyskinesias
Off-dykinesias
Freezing
Doesn’t alter disease progression, just offers symptoms relief
What else can you do to treat Parkinson’s?
Deep brain stimulation
If not dopamine responsive
When should you refer someone with a tremor?
All new tremors that aren’t essential
If diagnostic uncertainty
Essential tremor requiring further management
Tremor with other neurological symptom - ataxia, cerebellar signs, Parkinsonism
What is Huntington’s disease?
An inherited neurodegenerative disease characterised by chorea, dystonia, incoordination, cognitive decline and behavioural difficulties
What is chorea?
Continuous flow of jerky, semi-purposeful movements, flitting from one part of the body to another, may interfere with voluntary movements, cease during sleep
What is the inheritance pattern of Huntington’s disease?
Autosomal dominant condition with full penetrance - all gene carriers with develop disease
How common is Huntington’s disease?
Very rare
Prevalence worldwide 5 per 100,000
What causes Huntington’s disease?
Mutation on chromosome 4 resulting in repeated expression of CAG sequence - encodes huntingtin protein
CAG trinucleotide repeat expansion accumulates in brain cells causing damage
What is the risk of a child of a someone with Huntington’s also having Huntington’s?
50%
What is the pathology of Huntington’s disease?
Repeated expression of CAG sequence leads to translation of expanded polyglutamine repeated sequence in huntingtin gene expressed throughout body
Protein gene product function is unclear but thought to be toxic gain of function mutation
The more CAG repeats present the earlier symptoms onset
- Most adult onset 36-55 repeats
- Early onset from childhood over 60 repeats
Progressive cerebral atrophy with marked loss of neurons in caudate nucleus and putamen of basal ganglia - specifically loss of corpus striatum gaba-nergic and cholinergic neurons
Results in decreased Ach and GABA synthesis in striatum
GABA main inhibitory neurotransmitter, loss of this will result in decreased inhibition of dopamine release and therefore results in excessive thalamic stimulation and thus excessive movements - chorea
What is the course of Huntington’s disease?
Initially tends to present in middle age with prodromal phase of mild symptoms then progressing to psychiatric and cognitive symptoms
What are the symptoms of the prodromal phase in Huntington’s disease?
Mild psychotic and behavioural symptoms
What is chorea like?
Relentlessly progressive, jerky, explosive, rigidity, involuntary movements - cease with sleep
Can’t sit still
May begin as general restlessness, unintentionally initiated movements and lack of co-ordination
What symptoms might you get in Huntington’s disease?
Chorea Dysarthria Dysphagia Abnormal eye movements Psychiatric problems Dementia - impaired cognitive abilities and memory Associated with seizures Eventually death
What psychiatric problems can you get with Huntington’s?
Behavioural change - aggression, addictive behaviour, apathy, self-neglect
Depression/anxiety
What could be a differential diagnosis of Huntington’s disease?
Sydenham's chorea (rheumatic fever) Creutzfeldt-Jacob disease (prion) Wilson's disease SLE Stroke of basal ganglia
How is Huntington’s diagnosed?
Mainly clinical diagnosis
Genetic testing/DNA analysis - extensive genetic counselling required due to impact positive diagnosis will have - inevitable terrible death
CT/MRI - shows caudate nucleus atrophy and increased size of frontal horns of lateral ventricles (signs of brain matter destruction)
How is Huntington’s disease treated?
No disease-modifying treatment available
Treatment for symptoms
Counselling to patient and family, genetic counselling to any children of patients
Symptomatic management of chorea
- Benzodiazepines
- Sulpiride - neuroleptic - depresses nerve function
- Tetradenzaine - dopamine depleting agent
Anti-depressants such as SSRI
Antipsychotic medications
Aggression treatment - risperidone
What is the prognosis of Huntington’s disease?
Death within 15-20 years of diagnosis
