What is parkinsonism?
Umbrella term that describes many conditions which share some of the symptoms of Parkinson’s. The main symptoms of Parkinson’s – tremor, rigidity and bradykinesia – are also the main symptoms of a number of conditions that are grouped together under the term parkinsonism
What are causes of parkinsonism?
- Idiopathic Parkinson's disease
- Parkinson's plus syndromes
- Drug/toxin induced - antipsychotics
- Degenerative Parkinsonism - alzheimers
- Genetic disorders - wilson's, huntington's
How does parkinson's disease develop?
Arises from the death of dopaminergic in the pars compacta of the substantia nigra. This leads to striatal actvitiy increasing due to lack of inhibitory influence of the substantia nigra.
Striatal activity exerts inhibitory affect on pallidum. As substantia nigra is no longer exerting excitatory effect on striatum, it reduces it's inhibitory effect on the pallidum, which in turn grossly inhibits the thalamus. This prevents excitatory signals being sent to the motor cortex, resulting in difficulty initiating movement
What are the characteristic features of the resting tremor in parkinson's disease?
- 4-6 cycles per second
- Pill rolling - thumb over finger
- Disappears with voluntary movement
- Unilateral at presentation, progresses to bilateral
What are the characteristic features of rigidity in parkinsonism?
- Lead-pipe rigidity
- Cogwheel rigidity - series of catches/stalls when rapid movement performed by examiner
What are the features of bradykinesia/hypokinesia seen in parkinsonism?
Slow to initiate movement
- Problems with fine motor tasks: writing, sewing or getting dressed.
- Decreased blink rate (abnormal glabellar reflex)
- Monotonous hypophonic speech
- Dead pan face
- Decreased arm swing
- Shuffling steps
What are the core features of parkinson's disease?
Bradykinesia/hypokinesia, plus one of:
- Resting tremor
- Postural instability
What is characteristic about the shuffling gait seen in parkinson's disease?
Shuffling steps with reduced arm swing and flexed trunk, as if chasing one's centre of gravity. Have difficulty turning on the spot, taking many steps
What are non-motor symptoms of parkinson's disease?
- Reduced sense of smell
- Visual hallucinations
- Dribbling of saliva
Bradyphrenia - slowed process of thought
- Autonomic symptoms
What is the typical age of onset of parkinson's disease?
65 yrs old
What would be a diffirential diagnosis for tremor and bradykinesia?
- Idiopathic parkinsons disease
- Drug induced parkinsonism
- Vascular parkinsonism
- Essential tremor
- Normal pressure hydrocephalus
- Dementia with lewy bodies
What are parkinson's plus syndromes?
- Progressive supranuclear palsy
- Multiple system atrophy
- Corticobasal degeneration
What are causes of secondary parkinsonism?
- Drug induced
How would you investigate someone with parkinsonism?
- Clinical examination - cardinal signs, positive pull test
- Toxicology screen
What would a resting tremor potentially indicate?
What could cause a tremor that occurs on maintaining a posture or with movement?
- Essential tremor
- Exaggerated physiological tremor
- Dystonic tremor
How does levodopa work?
Levadopa is a natural precursor of dopamine. To prevent levodopa from being broken down peripherally, it is given in combination with a dopa-decarboxylase (carbidopa), which increases the amount available to the basal gnaglia
What would you be thinking of if someone had the following tremor (improves during the action of reaching a target but is worse on reaching the target)?
Cerebellar dysfunction - intention tremor - The amplitude of an intention tremor increases as an extremity approaches the endpoint of deliberate and visually guided movement
How do dopamine agonists work?
Bind to dopaminergic post-synaptic receptors in the CNS and thereby increase dopaminergic neurotransmission
What is essential tremor?
Postural or kinetic tremor in the frequency range of 4 to 12 Hz (usually at the lower end of the range in older patients) is generally the only manifestation in patients with essential tremor. Occasionally, when severe, rest tremor and mild abnormalities of tone and gait may also occur.
How do MOA-B inhibitors work?
Protects dopamine from being degraded within neurones
What would indicate that someone had an essential tremor?
Reduces/disappears after consuming alcohol
How would you manage someone with parkinson's disease?
- MDT involvement
- Levodopa + Carbidopa - early disease
- Dopamine agonists - early disease
- MAO-B inhibitors - early disease
- Anticholinergic drugs
- COMT inhibitors
- Neuropsychiatric conditions
- Respite care
- Deep brain stimulation
What are side effects of levodopa?
- Psychiatric symptoms - hallucinations, delusions, nightmares, confusion
- Unpredictable on/off switching
- Hypotension and syncope
What are the side effects of Dopamine agonists?
- Nausea, vomiting
- Psychiatric symptoms - hallucinations, delusions, nightmares
- Sleep disturbance and sudden onset of sleep
- Impulse control disorders - compulsive sexual activity, overeating, gambling
How do COMT inhibitors work?
Block the enzyme breakdown of dopamine and the drug levodopa and thereby reduces 'off' times. Because these medications affect levodopa levels directly the dose commonly needs to be reduced.
In early parkinson's disease, what is important to think about in terms of pharmacological intervention?
The decision of when to begin treatment can be a difficult one, particularly as levodopa is associated with more adverse effects the longer it is used
What drugs would you use in early parkinson's disease?
- Levodopa + dopa decarboxylase inhibitor
- Dopamine Receptor Agonists
- Monoamine oxidase B inhibitors