Mimics of Parkinson’s Disease

A concise guide to common “Parkinson’s mimics,” key differentiators, and practical work-up and treatment notes.

Topic: Movement Disorders Level: Intermediate Tags: parkinsonism, tremor, PSP, MSA, CBS, ET, NPH, drug-induced

Why mimics matter

Not all bradykinesia–rigidity–tremor is idiopathic Parkinson’s disease (PD). Atypical parkinsonian syndromes and other conditions often determine prognosis and treatment response. Early identification guides counseling, selection of symptomatic therapies, and when to avoid potentially harmful interventions.

Classic PD clues

  • Asymmetric onset; rest tremor common but not required
  • Bradykinesia with decrement, rigidity
  • Clear, sustained levodopa responsiveness (motor benefit)
  • Hyposmia, REM behavior disorder, constipation support diagnosis

Red flags for a mimic

  • Early falls or severe postural instability (<1–3 years)
  • Symmetric onset with poor/absent levodopa response
  • Early autonomic failure (orthostatic hypotension, urinary retention)
  • Early gaze palsy, cerebellar signs, pyramidal signs, or cortical signs (apraxia, alien limb)
  • Rapid progression or early dementia/visual hallucinations
  • Stepwise course, vascular risk factors, or prominent lower-body gait disorder

Quick compare

Condition Clues Levodopa Helpful tests
Dementia with Lewy bodies (DLB) Cognitive fluctuations, early visual hallucinations; parkinsonism often mild/early; REM behavior disorder Modest; neuroleptic sensitivity Cognitive screen; consider DaT imaging if tremor dx unclear; review meds
Multiple system atrophy (MSA) Early autonomic failure (orthostasis, urinary); cerebellar or pyramidal signs; stridor Poor/unsustained Orthostatic vitals, urodynamics; brain MRI (putaminal rim, pontine “hot‑cross‑bun”)
Progressive supranuclear palsy (PSP) Vertical gaze slowing/palsy; early falls; axial rigidity; frontal/apathy Poor Ocular exam; MRI midbrain atrophy ("hummingbird")
Corticobasal syndrome (CBS) Asymmetric rigidity/dystonia with cortical signs: apraxia, cortical sensory loss, alien limb Poor Neuropsych testing; MRI/FDG patterns if available
Essential tremor (ET) Action/postural tremor (hands > head/voice), improves with alcohol; no bradykinesia N/A Spiral drawing, weigh cup test; DaT imaging typically normal
Vascular parkinsonism Lower‑body gait disorder, early postural instability, corticospinal signs; stepwise course Poor MRI brain (ischemic burden); vascular risk review
Drug‑induced parkinsonism Dopamine blockers (antipsychotics, metoclopramide), often symmetric onset NA; improves after withdrawal (weeks–months) Medication audit; DaT imaging often normal
Normal‑pressure hydrocephalus (NPH) Gait disturbance (> cognitive > urinary); magnetic gait; parkinsonism may be present Variable MRI ventriculomegaly; large‑volume tap or ELD trial
Stroke/tumor/structural Acute/subacute onset, focal deficits, pyramidal/cerebellar signs out of proportion Poor Urgent MRI/CT as indicated

Lewy body spectrum (DLB)

DLB and PD share α‑synuclein pathology. In DLB, dementia or prominent cognitive fluctuations/visual hallucinations occur before or within a year of parkinsonism (“1‑year rule”). Patients are often neuroleptic sensitive. REM behavior disorder and hyposmia are supportive. Treat parkinsonism gently (low‑dose levodopa); manage hallucinations with cholinesterase inhibitors first‑line; avoid typical antipsychotics; if needed, consider pimavanserin or cautious quetiapine.

Multiple system atrophy (MSA)

Think MSA in early, disproportionate autonomic failure (syncope from orthostasis, urinary retention), stridor, or cerebellar signs. Levodopa response is absent or transient. MRI may show putaminal atrophy/rim and pontine cruciform signal. Focus on non‑pharmacologic and pharmacologic orthostatic management, bladder care, and sleep‑disordered breathing. (See refs 1–2.)

Progressive supranuclear palsy (PSP)

Early falls, axial rigidity, retrocollis, and slowed vertical saccades suggest PSP. Look specifically for impaired downward gaze and square‑wave jerks. MRI midbrain atrophy supports the dx. PT with balance training, prism glasses for downgaze issues, and caregiver education are central; levodopa usually minimal benefit. (See refs 3–4.)

Corticobasal syndrome (CBS)

Marked asymmetry with limb apraxia, cortical sensory loss, myoclonus, or alien limb raises CBS. Levodopa typically ineffective. Occupational therapy for apraxia, botulinum toxin for painful dystonia, and safety planning for severe limb neglect are helpful.

Essential tremor (ET)

Predominantly action/postural tremor of the hands (often bilateral) ± head/voice tremor. No true bradykinesia or rigidity. Handwriting/spiral shows axis‑consistent, regular oscillation; rest tremor absent or minor. Treat with propranolol or primidone; DBS/FUS thalamotomy for refractory cases.

Vascular parkinsonism

Lower‑body predominant gait disorder with early postural instability and corticospinal signs, often with a stepwise history. MRI shows ischemic burden in white matter/basal ganglia. Levodopa usually poor; focus on vascular risk reduction, PT, and assistive devices. (See refs 5–6.)

Drug‑induced parkinsonism

Check for dopamine‑blocking meds (antipsychotics, antiemetics like metoclopramide, some calcium‑channel blockers). Often more symmetric and may include orofacial dyskinesia/akathisia. Management is medication withdrawal/substitution; DaT imaging tends to be normal.

Normal‑pressure hydrocephalus (NPH)

Gait disturbance (“magnetic”), cognitive decline, and urinary symptoms; parkinsonism can coexist. MRI with ventriculomegaly out of proportion to atrophy. Large‑volume tap or short ELD trial can predict shunt response. (See ref 8.)

Stroke/structural mimics

Abrupt or stepwise onset with focal deficits, pyramidal or cerebellar signs suggests stroke, tumor, or other structural causes. Obtain urgent neuroimaging when red flags are present (acute onset, headache, focal weakness, papilledema, cancer history, immunosuppression).

Practical work‑up (clinic checklist)

  1. Clarify the tremor: rest vs action; test spirals and finger‑to‑nose. Look for bradykinesia with decrement and rigidity.
  2. Screen for red flags: early falls, gaze palsy, autonomic failure, cerebellar/pyramidal/cortical signs, early dementia or hallucinations.
  3. Medication audit: antipsychotics, antiemetics, lithium, valproate, flunarizine/cinnarizine, etc.
  4. Orthostatic vitals and focused autonomic review (MSA concern).
  5. MRI brain when atypical features or rapid progression; evaluate for vascular burden, NPH, structural lesions.
  6. Levodopa trial if diagnosis uncertain and no contraindication; document objective response.
  7. DaT imaging (if available) when distinguishing ET/drug‑induced tremor from nigrostriatal degeneration would change management. (See ref 7.)
  8. Consider neuropsych testing for suspected DLB/CBS or early cognitive involvement.

Safety: Avoid typical antipsychotics in DLB/PD psychosis due to severe sensitivity. For orthostatic hypotension, review antihypertensives and diuretics before adding agents.

References

  1. Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372:249–263.
  2. Krismer F, Wenning GK. Multiple system atrophy: advances in pathophysiology, diagnosis and therapy. Lancet Neurol. 2024;23:—.
  3. Boxer AL, Yu J‑T, Golbe LI, et al. Advances in progressive supranuclear palsy. Lancet Neurol. 2017;16:—.
  4. Rowe JB, Rittman T. Progressive supranuclear palsy: diagnosis and management. Pract Neurol. 2021;21:376–383.
  5. Zijlmans JCM, Daniel SE, Hughes AJ, et al. Clinicopathological investigation of vascular parkinsonism. Ann Neurol. 2004;55:—.
  6. Udagedara TB, Jayaweera SMA. Vascular parkinsonism: a review on management updates. Ann Indian Acad Neurol. 2019;22:—.
  7. Bega D, Marotta G, et al. Clinical utility of DaTscan in suspected parkinsonian syndromes: systematic review and meta‑analysis. NPJ Parkinsons Dis. 2021;7:—.
  8. Vibha D, Srivastava AK. Normal‑pressure hydrocephalus: patient evaluation and management. Neurol India. 2021;69:—.

Educational discussion. Not a substitute for clinical judgment. Consider local protocols and individual factors.