Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's. The pathology — alpha-synuclein aggregates (Lewy bodies) and progressive loss of substantia nigra dopaminergic neurons — produces a progressive disorder with motor and non-motor features. Diagnosis remains clinical despite advances in imaging.
The cardinal motor triad:
Bradykinesia — slowness of movement, the diagnostic anchor. Reduced amplitude and frequency of repetitive movements (finger tap testing). Without bradykinesia, the diagnosis is not Parkinson's.
Rigidity — increased resistance to passive movement, often with cogwheel quality. Asymmetric typically.
Resting tremor — 4-6 Hz tremor at rest, often pill-rolling quality. Asymmetric onset typical. Suppressed with movement (distinguishing from essential tremor).
Postural instability emerges later — not part of the initial diagnostic criteria.
Plus the famous Parkinsonian phenomenology: masked face (reduced facial expression), shuffling gait with reduced arm swing, micrographia (small handwriting), stooped posture, hypophonia (soft voice). Asymmetric onset is typical and helps distinguish PD from atypical parkinsonian syndromes.
Non-motor symptoms are often more disabling than motor symptoms and often precede motor symptoms by years:
Prodromal: hyposmia (loss of smell — present in most PD patients well before motor onset), REM sleep behavior disorder (dream enactment — strongest known prodromal marker), constipation (years to decades before motor symptoms), depression and anxiety.
Concurrent: orthostatic hypotension, urinary urgency, sialorrhea, sleep disturbance, dementia (often emerges later — PDD).
Diagnosis: primarily clinical. Bradykinesia plus rigidity or rest tremor, with supportive features and absence of red flags (early severe autonomic dysfunction or dementia suggesting atypical parkinsonian syndrome; rapid progression suggesting MSA, PSP, CBD). DAT-SPECT imaging can distinguish PD from essential tremor when uncertain. MRI to rule out structural causes.
Treatment evolution across disease:
Early disease: levodopa-carbidopa often the most effective. Some clinicians start with MAO-B inhibitor (selegiline, rasagiline) or dopamine agonist (pramipexole, ropinirole) in younger patients to delay levodopa-related motor complications.
Moderate disease: levodopa with adjuncts (COMT inhibitors — entacapone — to extend levodopa half-life; amantadine for dyskinesias and tremor). Pramipexole and ropinirole add dopaminergic support but carry impulse control disorder risk.
Advanced disease: motor fluctuations and dyskinesias dominate. Deep brain stimulation (DBS) of subthalamic nucleus or globus pallidus internus for selected patients with levodopa-responsive symptoms but motor complications. Levodopa-carbidopa intestinal gel (Duopa) for severe fluctuations. Apomorphine pump for rescue dosing.
Non-motor treatment: address depression (SSRI), anxiety, psychosis (pimavanserin, low-dose quetiapine), constipation, sleep, orthostatic hypotension. Often these have larger impact on quality of life than incremental motor improvements.
When you encounter a Parkinson's patient, comprehensive care addresses both motor and non-motor domains. Coordinate with movement disorder neurology for complex cases. The motor symptoms respond well to dopaminergic therapy initially; the non-motor and late motor complications shape long-term trajectory.