Parkinsons ☺️ Flashcards
Epidemiology
Aetiology
Pathophysiology
Key triad
Men, 65+
Most idiopathic
Genetic - PARK1 gene overexpressed
Environmental = unclear
Degeneration of dopaminergic neurons in substancia nigra
Formation of Lewy bodies
Bradykinesia, tremor, rigidity
Describe the clinical progression of PD
-symptoms and presentation
Prediagnosis
- constipation
- autonomic dysfunction => OH, urogenital dysfunction
- anosmia, visual changes
- REM behaviour disorder
- depression+anxiety
- face-like mask
- micrographia
Early stages - classic unilateral triad
- bradykinesia - shuffling, difficulty initating mv, reduced arm swing
- cogwheel rigidity
- pillrolling resting tremor - worse when stressed/tired, improves with voluntary mv
Advanced stages - on off dyskinesias
- flexed posture, dystonias, freezing
- gait instability, falls
- dysarthria, dysphagia
- dementia
- psychosis, hallucinations
Describe the basal ganglia thalamocortical loop
D1 => promotes movement via direct pathway
D2 => inhibits movement via indirect pathway
Cortex => basal ganglia => thalamus => cortex
Glutamate activates the direct pathway
Dopamine activates direct pathway via D1
Dopamine deactivates indirect pathway via D2
Imbalance between the amount of stimulation => dyskinesia or akinesia because thalamocortical feedback falls
- direct pathway becomes under active
- indirect pathway becomes overactive
- increased ACH linked to tremor
Describe the Braak PD staging
-what is the significance of this
Symptoms ascend upwards
1 amygdala, brainstem, olfactory
2 medulla, pons (NA in locus coerulus, 5HT in raphe nucleus)
3 substancia nigra (Ach in basal forebrain)
4 cortical involvement
5 temporal, parietal, frontal lobes
6 motor and sensory regions affected
Diagnosis
Usually clinical
DATSCAN used to differentiate between essential tremor and PD - SPECT imaging of dopamine transporters in caudate and putamen
What are the differentials for Parkinsonism (rigidity, resting tremor, bradykinesia, gait issues)
-how would you classify them
Degenerative
- PD
- multiple system atrophy
- progressive supranuclear palsy
Non degenerative
- drug induced (antipsychotics, metoclopramide
- vascular => from stroke
- head trauma
- CO
- viral encephalitis
- Wilsons disease
Management
- 1st line for QoL disruptive motor symptoms
- adjuncts in levadopa induced dyskinesia
- SE and problems associated with levadopa
-1st line for motor symptoms not affecting QoL
Levodopa + carbidopa/benserazide (decarboxylase inh)
-reduced efficacy with progression
Levadopa induced dyskinesia
Off - freezing
On - chorea, dystonias
Postural hypotension, palpitations
Psychosis, confusion
Dry mouth, anorexia
Adjuncts - dopamine agonist/MAOBinh/COMTinh
1st line for motor symptoms not affected QoL - Dopamine agonist/levodopa/MAOBinh
How might you address the problems associated with pulsatile stimulation
Transdermal rotigotine (patch)
SC apomorphine infusion
Intrajejunal levodopa infusion
Deep brain stimulation
Anticholinergics
- when would you use this
- examples
- SE
Procyclidine, Benzhexol, benzatropine
Now used more to treat drug induced parkinsonism
-address tremor and rigidity
SE =>
- confusion, mood changes
- can’t see, can’t shit, can’t pee, can’t think, too dry
Amantadine
- mechanism of action
- SE
NMDA antagonist
- increase dopamine release
- inhibits uptake
Ataxia
Slurred speech
Confusion
Dizziness
Surgical approaches to PD
-When would you use this
Medically refractory patients or uncontrolled LID
Neuroablative surgery
- irreversible
- other areas may be damaged
DBS = silence increased inhibitory signal to thalamus
-reversible but gives the patient control via a brain pacemaker
What are the common causes of drug induced Parkinsonism
Rapid bilateral development of motor signs (months)
- antipsychotics (haloperidol)
- antiemetics (prochlormethazine, promethazine, metoclopramide)
For nausea+vomiting
- drugs to use
- drugs to avoid
Why do we get this
Ok to use
- Domperidone
- Ondasetron
Dopamine antagonists
- Metoclopramide
- Prochlorperazine
Peripheral activation of dopamine => nausea
For hallucinations/confusion
-drugs to avoid
Why
Typical or atypical antipsychotics
- haloperidol
- zine
- apine
- idone
Reduce dopamine
How to differentiate between drug induced Parkinsonism and actual PD
Motor symptoms - rapid onset and bilateral
Rigidity and resting tremor uncommon
