Parkinson's Disease Flashcards
Define Parkinson’s disease.
A neurodegenerative disorder. The cardinal features include resting tremor, rigidity, bradykinesia, and postural instability.
What is the aetiology of Parkinson’s disease?
- Loss of dopaminergic neurons in the substantia nigra, associated with Lewy bodies in the basal ganglia, brainstem, and cortex.
- Most cases are sporadic, though multiple genetic loci have been identified in familial cases.
- Mean age at onset is 60yrs
Describe the pathophysiology of Parkinson’s disease.
- Severe loss of dopaminergic projection cells in SNc (of the nigrostriatal pathway –> movement disorder symptoms)
- Lewy bodies & neurites seen in neuronal cell bodies & axons respectively. Associated with neurodegeneration at molecular level.
- Consist of abnormally phosphorylated neurofilaments, ubiquitin & alpha-synuclein
Describe the clinical presentation of PD.
- Motor symptoms –> resting tremor, bradykinesia, rigidity, postural instability (cardinal symptoms)
- Autonomic nervous system effects(first) –> olfactory deficits, orthostatic hypotension, constipation
- Neuropsychiatric(last) –> sleep disorders, memory deficits, depression, irritability
What percentage of PD is inherited?
- 5% -→ earlier onset
What are the non-motor features of Parkinson’s disease?
- Autonomic dysfunction (postural hypotension, constipation, urinary frequency/urgency, dribbling of saliva)
- Sleep disturbance,
- Reduced sense of smell.
- Neuropsychiatric complications e.g. depression, dementia, and psychosis
What is the extrapyramidal triad of Parkinsonism?
- Tremor. Worse at rest; often ‘pill-rolling’ of thumb over fingers.
- Hypertonia. Rigidity + tremor gives ‘cogwheel rigidity’, felt by the examiner during rapid pronation/supination.
- Bradykinesia. Slow to initiate movement; actions slow and decrease in amplitude with repetition, eg ↓ blink rate, micrographia. Gait is festinant (shuffling, pitched forward) with ↓ arm-swing and freezing at obstacles or doors (due to poor simultaneous motor and cognitive function). Expressionless face.
What is the difference between lead pipe and cogwheel rigidity?
Cogwheel vs lead pipe
- Cogwheel is a tremor on top of rigidity
- Lead pipe rigidity – feels very stiff when moving the arm
Why do you not get spasticity in PD?
Parkinson’s mainly affects the extrapyramidal tract
NB: Pyramidal and corticospinal tract lesions would cause more clasp/knife rigidity (only initially rigid) and spasticity.
What investigations would you do for PD? What should you exclude?
Clinical diagnosis
- Cerebellar disease and frontotemporal dementia should be excluded
- Clinical response to dopaminergic therapy is supportive
- Signs should be WORSE on ONE SIDE
MRI - if other causes suspected
DaTscan, PET (functional neuroimaging) - may show reduced uptake in the substantia niagra.
What are the 2 major ways of treating Parkinson’s disease.?
- Dopamine increase = levodopa, carbidopa, MAOBi and COMTi.
- Receptor activation = dopamine receptor agonists, ropinirole, bromocriptine.
What is the likely diagnosis?
- Parkinson’s disease
- Alzheimer’s disease
- Age-related dementia
- Depression
- Sub-dural haematoma
He has classical symptoms of Parkinson’s disease with a syndrome of tremors, rigidity and bradykinesia. Alzheimer’s disease and multi-infarct dementia would present with forgetfulness predominantly. Sub-dural haematomata are more common in elderly people and are often incidentally found. They may present with features of dementia or epilepsy.
Parkinson’s
Neuroanatomically, which one of these brain areas contains the cells which are primarily affected by Parkinson’s disease?
- Frontal lobes
- Caudate nucleus
- Substantia nigra
- Sub-thalamic nuclei
- Temporal lobes
Substantia niagra
Degenerative changes taking place in the dopaminergic neurons in the substantia nigra have been implicated as the causal factor in the development of Parkinson’s disease. The frontal lobes are associated with the thought and analytical process, temporal lobes with auditory functions and association, the sub-thalamic nuclei with kinetic movement and pain relay centre.
Which of the following toxins can cause Parkinsonism in young people?
- Nicotine
- Heroin
- Cannabis
- Amphetamines
- Ecstasy
Heroin
MPTP found in use with heroin abuse is known to ‘chemically’ destroy neurons in substantia nigra and produce the same disease pattern.
If a patient with PD were to develop vertical gaze palsies in addition to his parkinsonian symptoms, what would be the diagnosis?
- Progressive supranuclear palsy (PSP)
- Cortical-basal ganglionic degeneration (CBD)
- Midbrain stroke
- Diffuse Lewy body disease
- Multiple system atrophy (MSA)
PSP – Axial dystonia in extension with supranuclear opthalmoplegia are the characteristic signs that define this condition in addition to the parkinsonian features.
Cortical-basal ganglionic degeneration may be mistaken for Parkinson’s disease, but intellectual decline, aphasia, apraxia and sensory neglect predominate and give the diagnosis.
Midbrain stroke can present with internuclear ophthalmoplegia and loss of conjugate eye movements.
In Diffuse Lewy body disease, parkinsonism is joined with a conspicuous dementia with evidence of widespread neurologic involvement.
Shy-Drager syndrome is a Parkinson + syndrome associated with autonomic neuropathy.
Which of the following are used in the treatment of Parkinson’s disease? Select one or more answers.’
- L-dopa with Carbidopa
- Ropinirole
- Entacapone
- Bromocriptine
- Prochlorperazine
- All except p_rochlorperazine -_ a neuroleptic agent that can cause Parkinsonian symptoms; not treat it.
- Entacapone is a COMT inhibitor that increases ‘on’ time when on-off phenomenon is a problem.
- Bromocriptine is a dopamine receptor agonist that improves symptoms with tremors.
- Ropinirole is a newer generation dopamine agonist with selective action on D2 receptor licensed for use as monotherapy.
Which three of the following are plausible causes, to be considered in the differential diagnosis?
- Anxiety-induced tremor
- Drug-induced tremor
- Essential tremor
- Huntington’s disease
- Parkinson’s disease
The history is typical for essential tremor. Anxiety often causes tremor and we have not asked him about this. It would be an unusual history for Parkinson’s disease, but in this age group it must be ruled out. His drugs do not cause tremor; salbutamol occasionally can, but he takes this infrequently and the tremor is persistent. Huntington’s disease does not present like this.
Anxiety-induced tremor, essential tremor, Parkinson’ disease
Which four features in the history are typical for essential tremor?
- Gradual onset over five years
- No other associated symptoms
- No relevant family history
- Symmetrical
- Worse when lifting a cup
All the symptoms are typical for essential tremor, except that about half of patients with ET have a family history.
- Gradual onset over five years
- No other associated symptoms
- Symmetrical
- Worse when lifting a cup - i.e. ET causes an action or intention tremor*
NB: Typical PD tremor is a resting tremor.
Both drug-induced parkinsonism (DIP) and PD would normally have a gradual onset and could easily cause postural instability.
PD usually shows some symptomatic benefit from levodopa, drug-induced usually not.
The typical coarse rest tremor of PD is less common in drug-induced parkinsonism.
Dyskinesia (chorea, in other words) is common as a side-effect of levodopa in PD patients but is not caused by PD alone, while (tardive) dyskinesia is common in long-term antidopaminergic drug use.
- Dyskinesia
- Levodopa improves symptoms
- Unilateral rest tremor
What are the advantages and disadvantages of COMT inhibitors?
COMT = catechol-O-methyl-transferase inhibitors (prevent peripheral degradation of levodopa)
Advantages:
- Improvement in motor symptoms
- Improvement in activities of daily living
- Lower risk of hallucination
Disadvantages:
- Off-time reduction
- More adverse events
