What are the causes of parkinsonism?

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Last updated: September 18, 2026 • View editorial policy

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Causes of Parkinsonism

Parkinsonism has multiple etiologies beyond idiopathic Parkinson's disease, including neurodegenerative "Parkinson-plus" syndromes (progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration), vascular parkinsonism, drug-induced parkinsonism, and various secondary causes that must be systematically excluded. 1

Primary Neurodegenerative Causes

Idiopathic Parkinson's Disease (Most Common)

  • Accounts for the majority of parkinsonian syndromes with an annual incidence of 10-18 per 100,000 population 1
  • Peak onset between 60-70 years of age
  • A synucleinopathy characterized by Lewy body deposition and progressive dopaminergic neuron loss in the substantia nigra
  • Symptoms appear after approximately 40-50% of dopaminergic neurons are lost (roughly 5 years after initial neuronal degeneration) 1

Atypical Parkinsonism ("Parkinson-Plus" Syndromes)

These conditions present with classic parkinsonian features plus additional distinguishing clinical features 1:

  • Progressive Supranuclear Palsy (PSP): A tauopathy with tau protein accumulation
  • Multiple System Atrophy (MSA): A synucleinopathy with three subtypes:
    • MSA-P (striatonigral degeneration) - extrapyramidal features predominate
    • MSA-C (olivopontocerebellar atrophy) - cerebellar ataxia predominates
    • MSA-A (Shy-Drager syndrome) - autonomic dysfunction predominates
  • Corticobasal Degeneration (CBD): Another tauopathy distinct from MSA and PD

Secondary Causes (Critical Not to Miss)

Drug-Induced Parkinsonism

The most common cause of secondary parkinsonism 2:

  • Neuroleptics (antipsychotics)
  • Calcium channel blockers
  • Other medications can cause or worsen parkinsonian symptoms

Vascular Parkinsonism

  • Second most common secondary cause
  • Results from cerebrovascular lesions affecting basal ganglia circuits 2

Infectious Etiologies

  • Viral infections (including post-encephalitic parkinsonism from historical pandemics and emerging concerns with COVID-19) 3
  • Prion-like diseases
  • Other infectious processes 2

Autoimmune and Paraneoplastic Causes

  • Systemic lupus erythematosus (SLE)
  • Sjögren syndrome
  • Paraneoplastic syndromes
  • Immune checkpoint inhibitor-related parkinsonism (increasingly recognized with cancer immunotherapy) 3

Toxin-Induced Parkinsonism

Multiple environmental and occupational toxins cause dopaminergic neuron damage 4:

  • Heavy metals (manganese, mercury)
  • MPTP (contaminant in synthetic heroin)
  • Pesticides (organochlorines, organophosphates, paraquat, rotenone)
  • Agent Orange

Structural Lesions

  • Brain tumors (rare but important) 2
  • Normal pressure hydrocephalus 5
  • Chronic traumatic encephalopathy 2

Genetic Causes (Particularly in Early-Onset)

In patients under age 50, genetic etiologies become increasingly important 6:

  • Wilson's disease (treatable - must not miss)
  • Cerebrotendinous xanthomatosis (treatable - must not miss)
  • Spinocerebellar ataxias (SCA2, SCA3) - can present with levodopa-responsive parkinsonism indistinguishable from idiopathic PD
  • Various PARK genes and non-PARK genetic disorders

Diagnostic Approach

Initial Imaging Strategy

MRI brain without contrast is the optimal initial imaging modality to evaluate parkinsonian syndromes 1. The goals are:

  1. Identify patterns of atrophy or parenchymal abnormality specific to different neurodegenerative conditions
  2. Exclude secondary causes:
    • Structural lesions (tumors, vascular lesions)
    • Hydrocephalus
    • Inflammatory/infectious processes
    • Drug/medication toxicity effects

Key Clinical Pitfalls

Critical treatable causes that must be excluded 6:

  • Wilson's disease in patients under 50
  • Cerebrotendinous xanthomatosis
  • Drug-induced parkinsonism (medication review is mandatory)
  • Normal pressure hydrocephalus
  • Autoimmune/inflammatory conditions

Response to levodopa does not confirm idiopathic PD - some genetic conditions (SCA2, SCA3) and even atypical parkinsonisms may show levodopa responsiveness 6.

When to Consider Genetic Testing

Strongly consider genetic evaluation in 6, 7:

  • Early-onset parkinsonism (age <50 years)
  • Family history of parkinsonism
  • Atypical features suggesting specific genetic syndromes
  • Lack of response to standard dopaminergic therapy

The updated understanding recognizes that PD encompasses a broader spectrum than previously thought, including both idiopathic and hereditary forms, requiring a comprehensive diagnostic framework 7.

References

1
Guideline

acr appropriateness criteria® movement disorders and neurodegenerative diseases.

Journal of the American College of Radiology, 2020

3
Research

Parkinsonism in viral, paraneoplastic, and autoimmune diseases.

Journal of the neurological sciences, 2022

4
Research

Toxin-Induced Parkinsonism.

Neurologic clinics, 2020

5
Research

The etiopathogenetic and pathophysiological spectrum of parkinsonism.

Journal of the neurological sciences, 2022

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.