Parkinsons Disease

Question 0

What symptoms does this give rise to

Answer 0

Diminished facial expression
Lack of arm swing when walking
Movement is difficult to initiate and is slow: bradykinesia
Reduced freq and amp of saccades

Question 1

Basal ganglia abnormalities in PD

Answer 1

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

Question 2

4 thpes of PD

Answer 2

Primary/idiopathic (most common)
Secondary/acquired
Hereditory
Parkinson plus syndrome

Question 3

Epidemiology

Answer 3

1 in 500
Av age of onset 60
Men 1.5 times more likely to get it
White people at greater risk in Uk

Question 4

Environmental causes?

Answer 4

Toxic agesnts like managanese oxide

Viral encephalitis lethargica

Question 5

Genetic causes?

Answer 5

Mutations in alpha synuclein gene (autosomal dominant)

Mutation in genes parkin (autosomal recessive)

Question 6

Anatomical pathology of PD

Answer 6

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!

Question 7

Pathophysiology of PD

Answer 7

Loss of nigrostriatal dopaminergic melanised cells

Abnormal accumulation of alpha synuclein bound to ubiquitin. Accumulate and form lewy bodies

Question 8

Lewy bodies

Answer 8

Concentric eosinophilic cytoplasmic inclusions with peripheral halos and dense cores
Immunoreactive to proteins alpha synuclein and ubiquitin

Question 9

3 main signs of PD

Answer 9

Resting tremor
Bradykinesia
Hypokinesia (rigidity)

Question 10

Mechanism for resting tremor

Answer 10

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

Question 11

Bradykinesia

Answer 11

More inhibitroy BG output
No initiation in motor functions
Shuffling steps, monotone voice, akinetic, no facial expression, later stages drool

Question 12

Rigidity

Answer 12

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

Question 13

Other symptoms of PD

Answer 13

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

Question 14

Testing for PD

Answer 14

CT and MRI generally normal

PET and SPECT can measure dopaminergic function of BG

Question 15

Levodopa

Answer 15

Naturally ocurring form of LDOPA the precursor for dopamine
Crosses BBB
Broken down by l amino acid decarboxylase

Question 16

Levodopa cause for nausea

Answer 16

Nausea caused by breakdown of levodopa in the periphery.

Prevented by administering a dopa decarboxylase inhibitor (benserazide or carbidopa)

Question 17

Other side eeffects of levodopa

Answer 17

Dizziness
Dyskinesias (unwanted movements) subdivided into
- Dystonia: intense and sustained muscle contract
- Chorea: dance like

Question 18

After using levodopa for a while, complications

Answer 18

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

Question 19

COMT inhibitors

Answer 19

Entacapone
Give with ldopa as ldopa can be metabolised by COMT in periphery
Ensure longlasting

Question 20

MAO-B inhibitors

Answer 20

Selegiline
Used with ldopa to reduceep end of dose deterioration
Inhibits enzyme MAO that metabolises dopamine, increasing DA in basal ganglia

Question 21

Dopamine receptor agonists

Answer 21

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

Question 22

Deep brain stimulation

Answer 22

Used to treat resting tremor

Implant brain pacemaker sending impulses to specific parts of brain

Question 23

Single photon emission computed tomography SPECT

Answer 23

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

Question 24

Pros and cons of SPECT

Answer 24

Cheap and widely avail
Range of tracers
Long lived isotopes

Poor resolution
Limited ligands
Radiation dose

Question 25

Positron emission tomography PET

Answer 25

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

Question 26

PET in PD

Answer 26

18f flurodopa is usually used which is fluorinated version of ldopa
Assess presynaptic nigrostriatal da function

Question 27

Colour meanings

Answer 27

White: high activity
SPECTRUM DOWN TO
Blue: low activity