Parkinson's Disease (Low Dopamine)

Question 1

Definition

Answer 1

neurodegenerative disorder characterised by loss of dopaminergic neurones within the substantia nigra pars compacta (SNPC) of the basal ganglia (nigrostriatal pathway).

Question 2

Epidemiology and Risk Factors

Answer 2

Age: 60-70, 80+
Males
Family history
Smoking protective?

Question 3

Pathophysiology

Answer 3

To initiate movement: nigrostriatal pathways signals striatum to stop firing to substantia nigra pars compacta leading to stop movement inhibition.
Degeneration of SNPC = harder to initiate movement
Ultimately, the result is a loss of transmission between the basal ganglia, thalamus, and motor cortex, resulting in impaired control of voluntary movements.

Question 4

Histological hallmark for Parkinson’s

Answer 4

Eosinophilic inclusion bodies consisting of misfolded α-synuclein in the dopaminergic neurones of the SNPC called Lewy bodies.

Question 5

Aetiology

Answer 5

Idiopathic and unknown

Question 6

Non-motor symptoms

Answer 6

Anosmia (early signs)
Sleep disturbances
- REM sleep impaired
Psychiatric symptoms
- Depression
- Anxiety
- Dementia: usually develops after motor symptoms, unlike in Lewy-body dementia
Constipation

Question 7

Motor symptoms

Answer 7

PD symptoms usually start unilaterally and then become bilateral later in the disease course
Bradykinesia
- slow movements
- shuffling gait with reduced arm swing and turning en bloc
Tremor
- Resting ‘pill rolling’ tremor
Rigidity
- Cogwheel rigidity occurs due to a tremor superimposed on a rigid movement
- Lead-pipe rigidity describes stiffness throughout the entire movement
Other features
- Micrographia
- Hypomimia

Question 8

CARDINAL SIGNS - TRAP

Answer 8

Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability

Question 9

Investigations

Answer 9

Clinical diagnosis
MRI
SPECT (DaT scan): single-photon emission computed tomography will show reduced dopamine uptake in the basal ganglia

Question 10

Treatment

Answer 10

FIRST LINE:
- Motor symptoms affecting QoL: LDOPA + decarboxylase inhibitor = CO-BENELDOPA
- Motor symptoms not affecting QoL:
= Dopamine agonist (Pramipexole)
= Monoamine oxidase B inhibitor (selegriline, rasagiline)
= Levodopa + decarboxylase inhibitor
SECOND LINE:
- COMT inhibitor (ENTACAPONE)
- AMANTADINE

Question 11

Problems with LDOPA

Answer 11

Initially works very well BUT soon body becomes resistant to it, effects wear off therefore dont give it too early when symptoms are mild
“on-off” fluctuations = well controlled periods with sudden decline following

Question 12

DDx

Answer 12

Lewy body dementia (assosciated with parkinsonism)
Parkinson symptoms THEN dementia = Parkinson dementia
Parkinson symptoms AFTER dementia = Lewy body dementia with parkinsonism

Question 13

Complications

Answer 13

Motor complications:
Motor fluctuations: symptoms are initially well-controlled (on period) but then re-emerge prior to the next dose (off period)
The off period gets longer and more unpredictable as PD advances
Freezing: sudden stoppage of movement
Dyskinesia: excessive involuntary movements related to levodopa use

Non-motor complications:
Psychiatric: impulse control disorders, depression, anxiety, dementia
Autonomic: postural hypotension, constipation

Question 14

How does a decarboxylase inhibitor work?

Answer 14

Prevents peripheral conversion of L-DOPA to dopamine