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TRAP Cardinal Features
- Tremor (rest, asymmetric, 4-6 Hz)
- Rigidity (cogwheel)
- Akinesia/bradykinesia
- Postural instability (later)
Pathology
- α-synuclein aggregation (Lewy bodies)
- Loss of dopaminergic neurons SNpc
Braak Staging
- Lower brainstem â SN â cortex
Non-Motor Features
- REM behavior disorder (prodromal â 80% develop)
- Hyposmia (very early)
- Constipation
- Orthostatic hypotension
- Cognitive impairment (PD-MCI â PDD)
- Depression, anxiety
- ICDs (with DA agonists)
MDS Diagnostic Criteria
- Bradykinesia + (rest tremor OR rigidity)
- Plus supportive
- No exclusions
- No red flags
Red Flags for Atypical Parkinsonism
- Rapid progression
- Early falls (< 1 year)
- Severe autonomic failure
- Severe bulbar dysfunction
- Inspiratory stridor
- Cerebellar signs
- Supranuclear gaze palsy
- Symmetric onset
- Poor levodopa response
DaT-SCAN
- Distinguishes PD/parkinsonism from essential tremor, vascular, drug-induced, psychogenic
Levodopa Side Effects
- Nausea, hypotension (early)
- Motor fluctuations + dyskinesias (after years)
- Behavioral
- Pulmonary (rare with infusion)
Dopamine Agonist Side Effects
- ICDs (impulse control disorders) â gambling, hypersexuality, eating, shopping â counsel!
- Sleep attacks
- Edema
- Hallucinations
- Orthostatic
MAO-B Inhibitors
- Selegiline, rasagiline, safinamide
- Mild benefit
- Tyramine reaction risk minimal at low doses
COMT Inhibitors
- Entacapone (with each levodopa)
- Opicapone (once daily)
- Reduce wearing off
- Dyskinesias, urine discoloration
Amantadine
- Reduces dyskinesias
- Gocovri ER FDA-approved
Pimavanserin
- Selective 5HT-2A inverse agonist
- FDA for PD psychosis
- No dopaminergic blockade
Rivastigmine
- FDA for PD dementia
- Cholinesterase inhibitor
DBS Targets
- STN (most common)
- GPi
- Vim (tremor)
Advanced Therapies
- DBS
- LCIG (Duopa)
- Foslevodopa-foscarbidopa SC (Vyalev) FDA 2024
- Apomorphine
- Focused ultrasound (thalamotomy, pallidotomy)
Genetic PD
- LRRK2 (most common AD)
- GBA (risk allele, also Gaucher)
- PARKIN, PINK1, DJ-1 (AR, young-onset)
- SNCA (rare AD)
Specific Treatment Pitfalls
Levodopa Wearing-Off
- Predictable
- Treatment: more frequent dosing, COMT inhibitor, ER formulations, DA agonist, MAO-B
Levodopa Dyskinesias
- Peak-dose typically
- Treatment: amantadine, reduce levodopa, DA agonist substitution, DBS
Freezing of Gait
- Difficult
- Cueing strategies, levodopa response variable
Falls
- Multifactorial
- PT, home modifications, treat OH
Psychosis Management
- Reduce dopaminergic if possible
- Pimavanserin
- Quetiapine, clozapine (avoid typical antipsychotics)