Parkinsons Disease Flashcards
What symptoms does this give rise to
Diminished facial expression
Lack of arm swing when walking
Movement is difficult to initiate and is slow: bradykinesia
Reduced freq and amp of saccades
Basal ganglia abnormalities in PD
Dopaminergic cells of SN pars compacta are destroyed
Inhibitory outflow from basal ganglia is abnormally high
Timely thalamic activation of UMNs in motor cortex is less likely
4 thpes of PD
Primary/idiopathic (most common)
Secondary/acquired
Hereditory
Parkinson plus syndrome
Epidemiology
1 in 500
Av age of onset 60
Men 1.5 times more likely to get it
White people at greater risk in Uk
Environmental causes?
Toxic agesnts like managanese oxide
Viral encephalitis lethargica
Genetic causes?
Mutations in alpha synuclein gene (autosomal dominant)
Mutation in genes parkin (autosomal recessive)
Anatomical pathology of PD
Cell death on ventral part of compacta region on substantia nigra
70% of cells can be affected
SN shows neuronal loss and presence of Lewy bodies!
Pathophysiology of PD
Loss of nigrostriatal dopaminergic melanised cells
Abnormal accumulation of alpha synuclein bound to ubiquitin. Accumulate and form lewy bodies
Lewy bodies
Concentric eosinophilic cytoplasmic inclusions with peripheral halos and dense cores
Immunoreactive to proteins alpha synuclein and ubiquitin
3 main signs of PD
Resting tremor
Bradykinesia
Hypokinesia (rigidity)
Mechanism for resting tremor
DA neurones diminished so direct pathway less excited and indirect more inhibited - overall inhibitory BG
Pathophys of tremor is unknown, but there are tremor cells in ventrolateral thalamic nuclei that have ca2+ channels that create hyperpolarisation rhythm
Or there is the stn-gpe pacemaker
Bradykinesia
More inhibitroy BG output
No initiation in motor functions
Shuffling steps, monotone voice, akinetic, no facial expression, later stages drool
Rigidity
PD patients have inc muscle tone in flex and extens muscles and resistant to passive movement of limbs
Rigid due to inappropriate sensitivity to muscle stretching and inability to get complete relaxation
Lead pipe rigidity: manipulating limbs feels like lead pipe
Cogwheel rigidity: when leadpipe rigidity is superimposed by resting tremor
Other symptoms of PD
Posture flexed and postural instability Gait slow and shuffling Tendency to fall Freeze when trying to move Handwriting smaller Dpression very common Later stages: memory impairment, confusion, disorientatioon
Testing for PD
CT and MRI generally normal
PET and SPECT can measure dopaminergic function of BG
Levodopa
Naturally ocurring form of LDOPA the precursor for dopamine
Crosses BBB
Broken down by l amino acid decarboxylase
Levodopa cause for nausea
Nausea caused by breakdown of levodopa in the periphery.
Prevented by administering a dopa decarboxylase inhibitor (benserazide or carbidopa)
Other side eeffects of levodopa
Dizziness
Dyskinesias (unwanted movements) subdivided into
- Dystonia: intense and sustained muscle contract
- Chorea: dance like
After using levodopa for a while, complications
After 5yrs treatment 50% will suffer a side effect
- fluctuations in response to ldopa
- ‘on-off’ effect where on is normal movement and off is freezing
- prominent dyskinesias
- changes in sensitivity of da neurones due to the peaks and troughs of medicated ldopa
COMT inhibitors
Entacapone
Give with ldopa as ldopa can be metabolised by COMT in periphery
Ensure longlasting
MAO-B inhibitors
Selegiline
Used with ldopa to reduceep end of dose deterioration
Inhibits enzyme MAO that metabolises dopamine, increasing DA in basal ganglia
Dopamine receptor agonists
Bromocriptine, pergolide, ropinorole
Acts on d1 and d2 receptors
Less effective than ldopa but less later dyskinesias
Use usually if under 65yo
Apomorphine is potent agonist. Fast acting. Injected
Deep brain stimulation
Used to treat resting tremor
Implant brain pacemaker sending impulses to specific parts of brain
Single photon emission computed tomography SPECT
Requires gamma emitting radionucleide to be injected into blood
Binds to ligand and allows ligand conc in areas to be seen by camera
Image gathered from multiple angles - slices and put together to 3D
Gamma radiation measured directly by gamma camera
Used for tumour, infection, thyroid imaging
Pros and cons of SPECT
Cheap and widely avail
Range of tracers
Long lived isotopes
Poor resolution
Limited ligands
Radiation dose
Positron emission tomography PET
Detects gamma rays emitted indirectly by positron emitting radionucleide (usually FDG)
18F FDG is analog of glucose with radioactive fluorine F-18
Uptake is a marker for tissue uptake of glucose needed for metabolism
PET in PD
18f flurodopa is usually used which is fluorinated version of ldopa
Assess presynaptic nigrostriatal da function
Colour meanings
White: high activity
SPECTRUM DOWN TO
Blue: low activity
