Progressive neurodegenerative movement disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to the classic triad of bradykinesia, resting tremor, and rigidity. Pathologically characterized by Lewy bodies (aggregates of α-synuclein) in affected neurons.
Most common form of parkinsonism (~80% of cases) and a major cause of disability in the elderly. Affects ~1% of people over age 60. Frequently tested on boards, especially distinguishing idiopathic PD from atypical Parkinson-plus syndromes and secondary causes.
Typically an older adult (>55) with insidious, asymmetric onset of a resting "pill-rolling" tremor, progressive bradykinesia (slowed movements, shuffling gait, micrographia), and cogwheel rigidity. Facial expression becomes masked and speech soft. Non-motor features are common (e.g., anosmia, constipation, REM sleep behavior disorder). Postural instability (balance impairment) emerges later in idiopathic PD (early falls are a red flag for atypical parkinsonism).
Parkinson-plus (atypical) syndromes present with parkinsonism plus early additional features. Progressive supranuclear palsy (PSP) – early loss of balance (frequent backward falls) and impaired vertical gaze (cannot look down), with axial rigidity. Multiple system atrophy (MSA) – early autonomic dysfunction (severe orthostatic hypotension, urinary incontinence, erectile dysfunction) and often cerebellar ataxia; may have neck tilt (anterocollis) or vocal cord paralysis. Both PSP and MSA typically show minimal response to levodopa.
Corticobasal degeneration (CBD) – markedly asymmetric Parkinsonism with cortical features like limb apraxia, alien limb phenomenon, cortical sensory deficits, and focal dystonia (usually poor medication response). Dementia with Lewy bodies (DLB) – parkinsonian motor signs coupled with early dementia (within 1 year of motor symptoms) and persistent visual hallucinations (fluctuating cognition).
Secondary causes of parkinsonism: Drug-induced (dopamine-blocking agents like antipsychotics or metoclopramide) cause subacute, symmetric parkinsonian symptoms (often lacking tremor) that gradually improve after stopping the offending drug. Vascular parkinsonism (multiple small infarcts) presents with lower-body predominant bradykinetic gait and falls, with poor levodopa response. Rarely, other disorders (e.g., normal pressure hydrocephalus, Wilson disease) can mimic PD.
First, confirm true parkinsonism (bradykinesia plus rest tremor and/or rigidity) and exclude secondary causes. Review medications (e.g., antipsychotics, antiemetics) that could induce parkinsonian symptoms; also look for signs of stroke or hydrocephalus that might suggest an alternate diagnosis.
A dramatic improvement in symptoms with a levodopa trial strongly supports idiopathic PD.
Assess for atypical features ("red flags" such as early falls, early autonomic impairment, symmetrical onset, gaze palsy, or rapid progression) that point to a Parkinson-plus syndrome rather than idiopathic PD.
Neuroimaging is not required in classic PD, but brain MRI should be considered if atypical features are present or diagnosis is uncertain (to exclude strokes, tumors, normal pressure hydrocephalus, etc.). A dopamine transporter scan (DaT-SPECT) can distinguish degenerative parkinsonism (abnormal scan) from benign tremor syndromes (normal scan).
In young-onset cases (<50 years), test for Wilson disease (e.g., ceruloplasmin) since it is a reversible cause of parkinsonism.
early dementia and hallucinations (within 1 year of parkinsonian motor symptoms)
Levodopa (with carbidopa) is the most effective treatment for motor symptoms. In younger patients, dopamine agonists (pramipexole, ropinirole) or MAO-B inhibitors (selegiline, rasagiline) may be used first to delay levodopa; anticholinergics (trihexyphenidyl) can help tremor in young patients. Long-term levodopa use often leads to motor fluctuations ("wearing off") and dyskinesias.
Manage advanced PD: add COMT inhibitors (entacapone) to extend levodopa duration; consider deep brain stimulation (subthalamic nucleus or GPi) for medication-refractory tremor or severe on/off fluctuations. Encourage regular exercise and therapy (physical therapy for gait/balance, speech therapy for hypophonia). Treat non-motor symptoms: e.g., melatonin or clonazepam for REM sleep behavior disorder, or low-dose atypical antipsychotics (quetiapine) for hallucinations.
Atypical Parkinsonism generally responds poorly to PD medications, so management is largely supportive. For MSA, treat autonomic failure (midodrine or fludrocortisone for orthostatic hypotension, intermittent catheterization for bladder dysfunction). For PSP/CBD, provide fall precautions and symptomatic care (e.g., botulinum toxin for dystonia). Drug-induced parkinsonism usually reverses after stopping the culprit drug; short-term use of anticholinergics (e.g., benztropine) can help symptoms in the meantime.
Mnemonic: TRAP for PD's motor features – Tremor (resting, "pill-rolling"), Rigidity (cogwheel), Akinesia (bradykinesia), Postural instability.
Parkinson tremor vs essential tremor: PD classically has a rest tremor (at rest, improves with action) in one hand, whereas essential tremor is an action tremor (during posture or movement) typically affecting both hands and head, often improving transiently with alcohol.
Lewy bodies (intracellular eosinophilic inclusions of aggregated α-synuclein) are the pathologic hallmark of Parkinson disease.
Early falls (within first 1–2 years of symptoms), especially backward falls, or early ocular motility problems (difficulty looking up or down) → suggest PSP (atypical) rather than PD.
Early autonomic dysfunction – e.g., severe orthostatic hypotension, early urinary retention/incontinence – out of proportion to motor symptoms → think MSA (Shy-Drager syndrome).
Symmetric onset of parkinsonian symptoms, absence of tremor, and poor response to high-dose levodopa are red flags for atypical or secondary parkinsonism.
Early dementia or prominent visual hallucinations in a parkinsonian patient (especially if cognitive symptoms begin at the same time or within a year of motor onset) → suggests dementia with Lewy bodies rather than idiopathic PD.
Check for offending drugs (antipsychotics, metoclopramide, etc.) or other causes (stroke, hydrocephalus) → if found, address those causes first.
If idiopathic PD is likely (no red flags for atypical), initiate therapy based on age and symptom severity (e.g., older patients: carbidopa-levodopa; younger patients: consider dopamine agonist or MAO-B inhibitor).
If atypical features are present, evaluate for Parkinson-plus syndromes (PSP, MSA, etc.) and consider brain MRI to exclude structural lesions. A trial of levodopa can be done to gauge response (poor response suggests atypical).
Provide multidisciplinary care (neurologist, physical therapy, occupational therapy). Monitor for motor complications and adjust medications. In advanced PD, consider referral for DBS evaluation.
An older man with a unilateral resting hand tremor, shuffling gait, stooped posture, and cogwheel rigidity that significantly improve with levodopa → Idiopathic Parkinson disease.
A patient with parkinsonian symptoms plus early frequent falls and inability to look down (vertical gaze palsy) → Progressive supranuclear palsy (an atypical Parkinsonism).
Case 1
A 65‑year‑old man presents with a one-year history of tremor and slowness.
Histology of the substantia nigra showing a Lewy body (Parkinson disease).
