Parkinson Disease

What You'll Learn

MDS Criteria: bradykinesia + rest tremor OR rigidity; asymmetric onset is typical and strongly supportive (symmetric onset is a red flag but does not by itself exclude PD)
Braak Staging: α-synuclein pathology begins in olfactory bulb/dorsal motor nucleus of vagus → non-motor symptoms precede motor by years
Levodopa response: robust, sustained response is the strongest supportive criterion; poor response is a red flag
Non-motor prodrome: RBD, anosmia, constipation appear 10–20 years before motor onset; RBD converts to α-synucleinopathy in >80%
DBS: indicated for motor fluctuations/dyskinesias refractory to medical optimization; STN vs. GPi both effective
PDD vs. DLB: 1-year rule — dementia within 1 year of parkinsonism = DLB; ≥1 year after = PDD
Genetics: LRRK2 (AD, most common genetic cause), GBA (most common risk factor), PARK2/Parkin (AR, young-onset)

HighYield Pearls

Asymmetric onset + sustained levodopa response: hallmark of idiopathic PD; absent levodopa response despite high dose is an absolute exclusion
Bradykinesia is mandatory (MDS 2015): must show decrement in speed AND amplitude on repetitive tapping — not just slowness
Postural instability is NO LONGER a core feature — early falls/postural instability is a red flag for PSP/MSA
RBD + parkinsonism = α-synucleinopathy (PD, DLB, MSA); >80% of isolated RBD converts within ~14 yr
1-year rule (DLB vs PDD): dementia within 1 yr of motor onset → DLB; ≥1 yr after → PDD
DaTscan: abnormal in PD/MSA/PSP/CBD/DLB; normal in essential tremor, drug-induced, dystonic, functional tremor — cannot separate PD from atypical
Hallucinations: first reduce DA agonists/anticholinergics → pimavanserin (5HT2A inverse agonist) or quetiapine; AVOID typical antipsychotics + risperidone/olanzapine
DA agonist red flags: impulse control disorders (gambling, hypersexuality, shopping, binge eating); pergolide/cabergoline → valvulopathy (off-market)
DBS candidacy: robust levodopa response + motor fluctuations/dyskinesias; contraindicated if cognitive impairment, severe axial/gait-freezing, or no levodopa response
LRRK2 = most common monogenic (AD, Ashkenazi + North African Berber); GBA = strongest risk factor, faster cognitive decline + earlier dementia; PARK2/Parkin = juvenile AR

🔍 Quick ReferenceClinical · Imaging / biomarkers · Genetics / pathology

Clinical phenotype

Asymmetric pill-rolling rest tremor (4–6 Hz), re-emergent on posture → Parkinson disease
Bradykinesia with decrement/sequence effect on finger tapping → PD (mandatory feature)
Cogwheel rigidity, enhanced by Froment maneuver → PD
Masked facies, hypomimia, hypophonia, micrographia → PD
Festinating gait, retropulsion, freezing of gait (late) → PD (PIGD subtype)
RBD, hyposmia, constipation, depression years before motor onset → PD non-motor prodrome (α-synucleinopathy)
Sialorrhea, orthostatic hypotension (late), urinary urgency → PD autonomic features
Impulse control disorder (gambling/hypersexuality) on new dopamine agonist → DA agonist side effect
Visual hallucinations + parkinsonism + fluctuating cognition (early) → DLB (1-yr rule)

Imaging / biomarkers

Normal structural MRI → typical PD (vs structural mimics)
DaTscan: asymmetric reduced putaminal uptake (posterior > anterior) → PD
Normal DaTscan → essential tremor, drug-induced, dystonic, or functional tremor (NOT PD)
Reduced MIBG cardiac scintigraphy (postganglionic) → PD (preserved in MSA — preganglionic)
Skin biopsy phosphorylated α-synuclein → emerging adjunctive biomarker for α-synucleinopathy (not a core board criterion)
CSF α-synuclein seed amplification (RT-QuIC/SAA) → emerging adjunctive biomarker for α-synucleinopathy (not a standalone diagnostic criterion)
Neuromelanin loss in substantia nigra pars compacta on imaging/pathology → PD

Genetics / pathology / treatment pearls

Brainstem Lewy bodies with α-synuclein neuronal inclusions in SN → Parkinson disease
LRRK2 (PARK8), autosomal dominant, Ashkenazi Jewish + North African Berber → most common monogenic PD (resembles sporadic)
GBA mutation, Gaucher heterozygote, 5–10× PD risk → faster cognitive decline + earlier dementia
SNCA (PARK1/4) duplication or triplication → familial PD (gene dosage effect)
PARK2/Parkin, PINK1, DJ-1 — autosomal recessive, juvenile onset → young-onset PD
Pimavanserin (5HT2A inverse agonist, no D2 block) → PD psychosis (doesn’t worsen motor)
DBS STN > GPi for medication reduction; GPi better for axial/dyskinesia → advanced PD with fluctuations
Levodopa-carbidopa intestinal gel (Duopa) → advanced PD wearing-off
Apomorphine subcutaneous → rescue therapy for sudden off periods
Amantadine → levodopa-induced dyskinesias
Pergolide / cabergoline (ergot DA agonists) → cardiac valvulopathy — AVOID

Diagnosis & MDS Clinical Diagnostic Criteria

Core Diagnostic Features

Parkinsonism: bradykinesia (progressive reduction in speed AND amplitude of repetitive movements) PLUS at least one of:
- Rest tremor (4–6 Hz)
- Rigidity (lead-pipe or cogwheel)
Parkinsonism is the entry criterion; bradykinesia is mandatory

MDS Criteria: Clinically Established PD

Category	Criteria
Supportive Criteria	Clear, dramatic beneficial response to dopaminergic therapy; levodopa-induced dyskinesias; rest tremor of a limb; olfactory loss or cardiac sympathetic denervation on MIBG
Absolute Exclusion	Cerebellar signs; downward vertical gaze palsy; behavioral variant FTD or primary progressive aphasia within 5 yr; parkinsonism restricted to lower limbs >3 yr; dopamine-receptor blocker exposure consistent with drug-induced; absent response to high-dose levodopa despite moderate severity; cortical sensory loss, limb apraxia, or progressive aphasia; normal functional neuroimaging of the presynaptic dopaminergic system (normal DaTscan)
Red Flags	Rapid gait impairment (wheelchair ≤5 yr); no progression over 5 yr; early bulbar dysfunction; inspiratory stridor; severe early autonomic failure within the first 5 years; early recurrent (>1/yr) falls from balance impairment within 3 years of onset; anterocollis; absent non-motor features despite 5 yr; unexplained pyramidal signs; bilateral symmetric throughout

Clinically established PD: absence of absolute exclusion criteria; ≥2 supportive criteria; no red flags
Clinically probable PD: absence of absolute exclusion criteria; up to 2 red flags, each counterbalanced by ≥1 supportive criterion

DaTscan (Ioflupane SPECT)

Binds dopamine transporter (DAT) in presynaptic striatal terminals
Abnormal (reduced uptake): PD, MSA, PSP, CBD, DLB — all presynaptic dopaminergic degenerations
Normal: essential tremor, drug-induced parkinsonism, dystonic tremor, functional tremor
Cannot distinguish PD from other parkinsonian syndromes (MSA, PSP, CBD)
Asymmetric putaminal loss (posterior > anterior) is characteristic of PD

💎 Board Pearl

DaTscan differentiates degenerative parkinsonism from non-degenerative (ET, drug-induced, functional) but does NOT distinguish PD from MSA/PSP/CBD
Absent response to high-dose levodopa despite moderate severity is an absolute exclusion for PD

Motor Features

Cardinal Motor Features (TRAP)

Feature	Key Characteristics	Board-Relevant Details
Tremor	4–6 Hz rest tremor; "pill-rolling"; re-emergent on posture	Asymmetric onset; suppressed by voluntary movement; worse with distraction (mental subtraction); absent during sleep
Rigidity	Lead-pipe; cogwheel (rigidity + superimposed tremor)	Velocity-independent (vs. spasticity = velocity-dependent); enhanced by contralateral activation (Froment maneuver)
Akinesia / Bradykinesia	Progressive reduction in speed AND amplitude; decrement pattern	Must show decrement (not just slowness); test: finger tapping, hand opening/closing, toe tapping; most strongly correlated with striatal dopamine loss; mandatory feature for diagnosis
Postural Instability (no longer a core feature)	Impaired postural reflexes; retropulsion	Under MDS 2015, postural instability is NO LONGER a core diagnostic feature (it was in UKPDS Brain Bank criteria); early postural instability is now a RED FLAG suggesting PSP/MSA; tested with pull test

PD Motor Subtypes

Subtype	Features	Prognosis
Tremor-dominant	Prominent rest tremor; relatively preserved gait/balance early	Slower progression; less cognitive decline
Akinetic-rigid	Bradykinesia and rigidity dominate; less prominent tremor	Intermediate progression
PIGD (Postural Instability/Gait Disorder)	Predominant gait dysfunction, postural instability, freezing	Fastest progression; worst cognitive outcomes; more falls; higher PDD risk

Other Motor Signs

Freezing of gait (FOG): transient inability to initiate or continue stepping; triggered by doorways, turns, dual-tasking; occurs in advanced disease
Micrographia: progressively smaller handwriting; decrement pattern mirrors bradykinesia
Hypomimia: masked facies; reduced blink rate
Hypophonia: soft, monotone voice; loss of prosody
Festinating gait: short, shuffling steps with forward flexed posture
Asymmetric onset: typical and strongly supportive of PD; symmetric onset from the start is a red flag but does not by itself exclude PD

Clinical Pearl

Cogwheel rigidity = lead-pipe rigidity + tremor superimposed on the resistance; rigidity alone (without tremor) is lead-pipe only
Bradykinesia requires progressive decrement in amplitude AND speed — simply slow movement alone is not bradykinesia

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