Clinical Features & Phenotypes

1. The Motor Features in Detail

The motor syndrome of PD is built on the four cardinal features (TRAP, see Part I) but expresses them through a constellation of bedside signs:

Bradykinesia — the obligatory feature

• Finger taps — thumb-to-index, full amplitude, fast as possible. Look for: slowness, decrement (the “sequence effect” that distinguishes PD bradykinesia from cerebellar slowness), hesitations / arrests.
• Hand opening/closing and pronation-supination — same principles.
• Foot tapping and leg agility (heel raise) — lower-limb correlates.
• Hypomimia — reduced facial expression; spontaneous blink rate falls from ~17/min to ~5–10/min.
• Hypophonia & monotonic dysarthria — reduced volume, prosody, articulatory precision (the basis of LSVT-LOUD therapy).
• Micrographia — handwriting that progressively shrinks across a sentence.
• Reduced arm swing on the affected side; often the earliest and longest-asymmetric sign.

Tremor — the most recognisable feature

• Rest tremor — 4–6 Hz, asymmetric, “pill-rolling”; suppressed by movement, exacerbated by mental load (“count back from 100 by 7”).
• Re-emergent tremor — tremor recurs after a few seconds in a sustained posture (e.g., outstretched arms). Highly specific for PD vs essential tremor (which is action tremor).
• Jaw, tongue, leg, chin tremor — supportive features.
• ~30% of PD never develops tremor (the non-tremor / PIGD phenotype).

Rigidity

• Lead-pipe (constant) or cogwheel (with superimposed tremor); through full range; both flexors and extensors.
• Activated by Froment’s manoeuvre (have the patient open/close the contralateral fist).
• Distinguishes from spasticity (velocity-dependent, clasp-knife, UMN signs).

Postural instability

• Pull test: brisk backward pull at the shoulders; abnormal >2 corrective steps or fall.
• Late feature in idiopathic PD; early postural instability suggests PSP (or vascular parkinsonism, NPH).

2. Gait, Freezing, and Festination

The PD gait is a syndrome in itself:

• Stooped posture with flexed hips/knees and trunk.
• Reduced arm swing (often unilateral early).
• Short, shuffling, en-bloc steps with reduced foot clearance.
• En-bloc turning — whole-body turn rather than axial rotation.
• Freezing of gait (FOG) — a sudden, episodic inability to initiate or continue locomotion despite intact intention. Most often at gait initiation (start hesitation), in tight spaces (door thresholds), or when turning. Triggered by dual-tasking and stress.
• Festination — involuntary acceleration of step cadence as the patient leans forward, with progressive loss of balance.

FOG and festination disproportionately impact quality of life and predict falls. They are characteristic of advanced PD and of the PIGD phenotype, and respond poorly to dopaminergic medication (the “OFF-medication freezer” vs the dopamine-resistant ON-medication freezer who illustrates non-dopaminergic substrates — pedunculopontine nucleus, midline cerebellar pathways).

3. Non-Motor Features — The Iceberg Below

The clinical face of PD has shifted dramatically in the last 20 years. The landmark recognition: PD is a multisystem proteinopathy whose non-motor features (NMS) precede, accompany, and outlive its motor ones. Chaudhuri and colleagues built the modern NMS framework (Lancet Neurol 2006) and the NMSS / NMSQuest scoring instruments. Categories:

Non-motor symptom burden — not motor severity — is the dominant driver of quality of life in advanced PD. The implications for management are substantial: every modern movement-disorders clinic now screens NMS routinely, and dedicated treatment of constipation, RBD, depression, and orthostatic hypotension dwarfs incremental dopaminergic optimisation in patient impact.

4. Sleep — RBD and Excess Daytime Sleepiness

REM-sleep behaviour disorder (RBD) is characterised by loss of normal REM atonia, allowing the patient to enact dreams with vocalisations and complex motor behaviour, often violent. It is the most specific premotor marker of synucleinopathy: ~80% of polysomnography-confirmed RBD patients develop PD, DLB, or MSA within 10–15 years (Postuma et al., Brain 2019). RBD precedes motor PD by a median ~10 years.

Pathophysiologically, RBD reflects degeneration of the sublaterodorsal nucleus in the pontine tegmentum and its descending projection through the magnocellular reticular formation to the spinal cord — a Braak stage-2 territory. RBD is therefore the clinical readout of pontine pathology that is upstream of motor onset, and is the cornerstone of prodromal-PD criteria (Berg et al., Mov Disord 2015).

Other sleep features: excessive daytime sleepiness (often dopaminergic side effect), insomnia, restless legs syndrome, sleep-disordered breathing, and circadian rhythm fragmentation. The RBD-PD-MSA-DLB pipeline has produced major cohorts (NAPS, RBDStudyGroup) for prevention-trial design.

5. Autonomic Dysfunction

Synuclein pathology in the dorsal motor nucleus of the vagus, the intermediolateral column of the spinal cord, the cardiac sympathetic plexus, and the enteric nervous system produces a wide autonomic syndrome:

• Constipation — ~70%; can precede motor onset by >20 years; predicts PD risk in long-term cohorts (Honolulu Asia Aging Study).
• Orthostatic hypotension (OH) — postural systolic drop ≥20 mmHg or diastolic ≥10 mmHg; reflects cardiac sympathetic denervation, which can be visualised on ¹²³I-MIBG scintigraphy. Severe early OH suggests MSA.
• Urinary urgency / nocturia — detrusor overactivity from loss of basal ganglia inhibition.
• Erectile dysfunction — very common, often early.
• Hyperhidrosis / sialorrhoea — salivary pooling from impaired swallowing rather than over-production.
• Thermoregulatory dysfunction.

MIBG cardiac scintigraphy — a measure of cardiac sympathetic innervation — is reduced in PD and DLB but preserved in MSA, and is one of the most useful PD-vs-MSA discriminators where available (Treglia et al., Mov Disord 2012; covered in Part VI).

6. Neuropsychiatric Features

• Depression — ~30–50%; partly intrinsic to PD biology (raphe and limbic synucleinopathy), partly reactive. Treat with SSRIs, SNRIs (avoid the very strong anticholinergic TCAs in elderly PD), pramipexole has antidepressant effect.
• Anxiety — ~40%; often fluctuates with motor OFF state.
• Apathy — common, distinct from depression; mesolimbic dopamine territory.
• Psychosis (PDP) — visual hallucinations, often well-formed (people, animals, intruders), with retained insight early. Up to 50% in advanced PD. Triggered or worsened by all dopaminergic medication; managed by reducing offending drugs (anticholinergic, amantadine, agonist, then COMT, then MAO-B, then levodopa) and adding pimavanserin (5-HT2A inverse agonist; FDA 2016) or quetiapine. Avoid haloperidol — will precipitate severe parkinsonism.
• Impulse-control disorders (ICDs) — pathological gambling, hypersexuality, compulsive shopping, binge eating. ~17% of PD on dopamine agonists (DOMINION study, Weintraub et al., Arch Neurol 2010); risk is class effect of agonists, not levodopa, and reflects mesolimbic D3-receptor stimulation. Always ask, often missed, frequently devastating financially and socially.
• Dopamine dysregulation syndrome (DDS) — compulsive overuse of dopaminergic medication, often associated with punding (stereotyped purposeless behaviour). Younger-onset, male predominant.

7. Cognitive Decline & PD Dementia

Cognitive impairment in PD spans a continuum:

• PD-MCI — ~30% at the time of motor diagnosis; primarily executive and visuospatial deficits. MDS-Task-Force criteria (Litvan et al., Mov Disord 2012).
• PD dementia (PDD) — clinical dementia >1 year after motor onset; ~25–40% prevalence in cross-sectional cohorts; ~80% lifetime risk in 20-year follow-up (Sydney Multicenter Study).
• Dementia with Lewy bodies (DLB) — cognitive decline preceding motor parkinsonism by >1 year, with the “1-year rule” (McKeith et al., Neurology 2017) distinguishing DLB from PDD. Same molecular biology, different clinical timing.

The cognitive profile in PDD/DLB is dysexecutive and visuospatial, with relatively preserved naming and recognition memory early — distinct from the amnestic, hippocampal pattern of typical AD. Cortical Lewy pathology, cholinergic deficit (from nucleus basalis Ch4 degeneration), and frequent co-existing AD pathology (~50% have meaningful Aβ plaques) all contribute.

Risk factors for PDD: older age at PD onset, longer disease duration, PIGD phenotype, RBD, hyposmia, GBA carrier status, MAPT H1 haplotype, and posterior cognitive deficits (visuospatial, semantic-fluency) at baseline. Cholinesterase inhibitors (rivastigmine; EXPRESS trial, NEJM 2004) provide modest cognitive benefit. Memantine effect is small.

8. Clinical Phenotypes — TD, PIGD, and Mixed

PD has long been clinically subdivided by Jankovic and colleagues (Neurology 1990) into:

Phenotype assignment uses the ratio of mean tremor score to mean PIGD score on MDS-UPDRS subscales (Stebbins et al., Mov Disord 2013).

9. The MDS-UPDRS

The Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (Goetz et al., Mov Disord 2008) is the workhorse clinical scale of modern PD trials and clinics. Four parts:

Each item scored 0–4. The motor exam (Part III) is the section every neurologist learns: finger taps, hand movements, pronation-supination, foot taps, leg agility, rising from a chair, gait, freezing, postural stability, rigidity at neck and limbs, rest tremor, postural and kinetic tremor, bradykinesia constancy, speech, facial expression. Reliability is high among trained raters (ICC ~0.9).

Clinically meaningful change on UPDRS-III is ~3–5 points. Disease-modifying trials typically use change in UPDRS or the time to a clinical milestone (Hoehn-Yahr 3, dementia, falls) as primary endpoints, often combined with imaging biomarkers (DaTscan, tau-PET).

10. Atypical Parkinsonism — The Differential

~10–20% of patients presenting with parkinsonism do not have idiopathic PD. The four classical atypical (or “Parkinson-plus”) syndromes are important to recognise because their prognosis, management, and (for some) molecular biology differ:

Red flags that argue againstidiopathic PD (Postuma et al., MDS Criteria 2015):

• Rapid progression to wheelchair within 5 years
• Complete absence of motor progression over 5 years
• Early bulbar dysfunction (severe dysphagia, dysarthria, dysphonia within 5 years)
• Inspiratory stridor (suggests MSA)
• Severe autonomic failure within 5 years (suggests MSA or PAF)
• Recurrent falls due to balance impairment within 3 years
• Anterocollis or pisa syndrome
• Absence of any non-motor features after 5 years
• Otherwise unexplained pyramidal signs
• Bilateral symmetric parkinsonism throughout course

The full diagnostic apparatus — MDS criteria, DaTscan, MRI red flags, autonomic testing, MIBG, genetic testing, and the new SAA assays — is detailed in Part VI.