Parkinson's Disease Flashcards
Briefly: what is the pathophysiology of Parkinson’s disease?
The basal ganglia are a group of structures situated in the middle of the brain. They is responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine.
Parkinson’s disease:
M>F
or
F>M
M>F
Explain the TRAP mnemonic of Parkinson’s features.
- Tremor (resting): unilateral/asymmetrical + worse on walking or distracted
- Rigidity: asymmetrical tonicity/stiffness, limbs heavy and feel weak/fatigued
- Akinesia (but really bradykinesia): slowed movement, loss of kinetic versatility
- Postural instability: falls/balance difficulties
Which feature of Parkinson’s is the most important?
BRADYKINESIA!
- you CANNOT diagnose it without this.
- lack of initiation of movement
- difficulty with repetitive movements
- can demonstrate with finger tapping
Outline the typical presentation of Parkinson’s disease
- The typical patient is an older aged man around the age of 70.
- Stooped posture
- Forward tilt
- Facial masking
- Reduced arm-swing
- Shuffled gait
- Unilateral tremor “pill-rolling” 4-6 Hz
- Cogwheel rigidity
- Others: depression/sleep disturbance/anosmia/postural instability/cognitive impairment or memory problems
Compare and contrast a Parkinson’s tremor with an essential tremor
Outline some other clinical features of PD.
- Motor abnormalities
- Non-motor abnormalities
- Cognitive impairments
- Autonomic dysfunction
- Neuropsychiatric problems
Outline non-motor symptoms of PD.
- Hyposmia (specific to alpha-synuclein)
- Psychochosis (visual hallucinations) - alpha-syn
- REM sleep behaviour disorder - alpha-syn
- Mood disorder (frontal lobe involvement) - act out dreams
- Apathy
- Constipation
- Autonomic - orthostatic hypertension/bladder/bowels/erectile dysfunction
Outline the autonomic features of PD.
Orthostatic hypertension/bladder/bowels/erectile dysfunction = bad prognosis
Non-motor symptoms + motor abnormalities =
Parkinson’s disease
Non-motor symptoms + motor abnormalities + autonomic dysfunction =
Multi-system atrophy
What modality is used to DIAGNOSE Parkinson’s disease?
DAT scan
What finding on DAT scan indicates Parkinson’s?
- Full stop
- Comma is normal
Give some differential diagnoses of Parkinson’s disease.
• Essential Tremor
• Cerebro-vascular Disease – lower body
parkinsonism
• Parkinson Plus Syndrome – PSP, MSA, CBD
• Drug Induced Parkinsonism
• Dementia – AD, VD, FTD, LBD
• Gait Disorder – NPH / CJD
What are the treatment options for Parkinson’s disease?
- Increase Dopamine Concentration
- Dopamine Agonists
- Manipulate other Transmitters
- Manage Specific Symptoms
Outline Levodopa in managing Parkinson’s disease
- Synthetic dopamin given orally
- Combined with other drugs to stop levodopa being broken down before reaching brain
- Peripheral decarboxylase inhibitors e.g. carbidopa (co-careldopa) and benserazide (co-benyldopa)
- Most effective treatment for symptoms but less effective over time (often referred for when other treatments are not managing to control symptoms)
What are the main side-effects of Levodopa?
The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:
- Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
- Chorea: These are abnormal involuntary movements that can be jerking and random.
- Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
Outline COMT inhibitors
The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.
Outline dopamine agonists
These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use is pulmonary fibrosis.
Examples are:
- Bromocryptine
- Pergolide
- Carbergoline
Outline MAOB Inhibitors
Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose.
Examples are:
- Selegiline
- Rasagiline
What is punding?
Repetitive/Mindless behaviours triggered by dopaminergic therapy:
• Cleaning / tidying
• DIY / Gardening
• Collecting / sorting
• Assembling / dismantling
• X’s Computer Usage
- Associated:
- Impulsive personality
- Obsessive / Compulsive
- Young age of onset
- Disease severity
- Higher non-dopa med
What is dopamine dysregulation syndrome?
- Dopamine-dysregulation syndrome (DDS) is an uncommon complication of the treatment of Parkinson’s disease, characterised by addictive behaviour and excessive use of dopamine medication. Patients may develop prominent dyskinesias, cyclothymia, psychosis and significant functional decline.
- • Compulsive increase in tabs
• Altering pump settings
• Dismantling objects ++
• Scratch Cards ++++
What is hedonistic dopamine dysregulation syndrome?
- Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction.
- Obsessive compulsive behaviour (punding/walkabout)
- Risk behaviour
- Grandiose business plans
- Appetite alterations
- Weight loss
- Food cravings
- Hypomania/psychosis
- Gambling
- Shopping sprees
- Betting (online)/scratch cards/poker
- Hypersexuality
- Increased libido
- Exhibitionism
- Prostitution
What other management options are available?
- Neurosurgery
- Deep brain stimulation
- Duodenal infusion
