Parkinson's disease Flashcards
(38 cards)
What are the two components of the brain that feed into the upper motor neuron system?
Basal ganglia
Cerebellum
What is Parksinson’s a disease of?
The basal ganglia
Name the components of the basal ganglia system.
Corpus striatum - Caudate nucleus - Putamen Globus pallidus Substantia nigra Thalamus Subthalamic nuclei
Name the loops of the basal ganglia and their function.
Motor - movement
Oculomotor - eye movement control
Lateral orbito-frontal - social behaviour
Dorsolateral prefrontal loop - executive functions and working memory
What is the input and output of posture and voluntary movement control in the basal ganglia?
Input: cortex
Output: cortex and brainstem
Describe the epidemiology of Parkinson’s disease.
180 per 100,000 3men:2women Prevalence increases >60 years Mean duration from diagnosis to death is 15 years Sporadic disorder Monogenic causes (6% of cases)
What are the most common monogenic causes of Parkinson’s?
Mutation in
- LRRK2 protein
- Parkin protein
Describe the pathology of Parkinson’s disease.
Degeneration of dopaminergic neurons within the substantia nigra (dopamine being the main neurotransmitter in substantia nigra)
- dopamine concentrations decrease
- lack of dopamine in the basal ganglia
- biggest loss within the nigrostrial pathway
The surviving neurons accumulate an abnormal type of the protein alpha-synuclein within Lewy bodies
- cytoplasmic inclusion bodies
How do people have Parkinson’s disease for years before symptoms?
The basal ganglia can lose 50-60% of it’s dopamine concentrations before it stops compensating
- then motor symptoms appear
Name some possible mechanisms for Lewy body formation.
Oxidative stress Mitochondrial Excitotoxicity Protein aggregation Interface with DNA transcription Nitric oxide Inflammation Apoptosis Trophin deficiency Infection
Describe the Lewy body staging of Parkinon’s disease.
Stage 1-2
- Lewy bodies first appear in the pons/medulla and olfactory nucleus
- presymptomatic or pre-motor stage (e.g. loss of smell)
Stage 3-4
- Lewy bodies next appear in the midbrain (substantia nigra pars compacta)
- Parkinsonism become evident after extensive nigral damage
Stages 5-6
- Lewy bodies finally involve the neocortex
- development of PD dementia
What are the clinical features of Parkinson’s?
4 main motor symptoms - bradykinesia and at least one of - muscular rigidity - 4-6 Hz rest tremor (quite a slow, asymmetric tremor) - postural instability
What is bradykinesia?
Slowness in initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions (movement becomes slower and smaller)
Name the non-motor symptoms of Parkinson’s disease.
Neuropsychiatric - dementia - depression - anxiety Autonomic - constipation - urinary urgency/nocturia - erectile dysfunction - excessive salivation - postural hypotension Sleep - REM sleep behaviour disorder - restless legs syndrome - daytime somnolence Other - reduced olfactory function - fatigue - pain and sensory sensation
Name some differential diagnosis of Parkinson’s disease.
Benign tremor disorder (e.g. essential tremor)
Dementia with Lewy bodies
Vascular Parkinsonism
Parkinson plus disorders (e.g. progressive supranuclear palsy, multiple system atrophy)
Drug-induced parkinsonism/tremor
- caused by drugs that block dopamine
If you suspect someone has Parkinson’s disease, what investigations would you perform?
Bloods
- if tremor present; thyroid function and copper tests (e.g. Wilson’s disease)
Structural imaging
- CT/MRI brain normal in Parkinson’s disease
- abnormal in vascular parkinsonism and Parkinson plus disorders
Functional imaging
- imaging of presynaptic dopaminergic function using DAT SPECT is abnormal in degenerative Parkinsonism
In a normal DATSCAN, where is the uptake highest?
In the middle slices of the striatum
What happens in a FC-CIT SPEC in Parkinson’s disease?
As dopamine neurons are lost, they can’t take up to DAT SPECT, and the middle part of the striatum glows less
- asymmetric loss
What is the aim of pharmacological treatment of Parkinson’s?
To restore dopamine levels
What is the clinical aim of treating Parkinson’s?
Improve motor symptoms and quality of life
Name the drug classes used to treat Parkinson’s.
L-DOPA
Dopamine agonists
MAO-B inhibitors
COMT-inhibitors
Describe the mechanism of action of L-DOPA.
Absorbed in the stomach and taken in through the BBB
It is taken up by dopaminergic neurons, where it is decarboxylated to dopamine within the presynaptic terminals
What are the two most common preparations of L-DOPA?
L-DOPA and carbidopa = Sinemet
L-DOPA and benserazide = Madopar
It is prescribed with a drug that prevents L-DOPA breakdown before it reaches the BBB
What are the adverse effects of L-DOPA?
Peripheral
- nausea, vomiting and postural hypotension
Central
- confusion and hallucinations
Long term (5 years) - 50% of patients
- fluctuation in motor response
- dyskinesia (chorieform movements at peak dose)
