Parkinsonism

Background

• Parkinsonism describes a neurologic syndrome characterized by tremor at rest (usually 4-6 hertz [Hz]), rigidity, akinesia (bradykinesia), and postural instability.
• Common causes of parkinsonism include:
  • Parkinson disease (accounts for about 40%-70% of patients with parkinsonism)
  • drug-induced parkinsonism (accounts for up to 20% of patients with parkinsonism)
  • vascular parkinsonism (characterized by lower body parkinsonism primarily gait impairment)
  • progressive supranuclear palsy (characterized by eye movement abnormalities and gait instability)
  • dementia with Lewy bodies (characterized by cognitive impairment with features of parkinsonism and hallucinations)
  • multiple system atrophy (characterized by dysautonomia and parkinsonism)
  • corticobasal degeneration (characterized by apraxia and prominent asymmetry of parkinsonism)

Evaluation

• Initial evaluation should include medication history and physical exam including an evaluation for resting tremor, bradykinesia, rigidity, and gait abnormalities.
• To determine whether a patient has Parkinson disease or atypical parkinsonism consider:
  • the presence of clinical signs or symptoms suggestive of atypical parkinsonism such as:
    • rapid progression (significant worsening in < 3 years)
    • early cognitive symptoms, hallucinations, or dementia
    • early imbalance or falling
    • accompanying neurological findings such as ataxia, significant dysautonomia, or ophthalmoplegia
    • symmetric findings of rigidity and bradykinesia
    • lack of significant tremor
    • limited response to dopaminergic therapy
  • an adequate trial of carbidopa/levodopa as improvement of motor features in response to medication is consistent with Parkinson disease. Non-motor symptoms of Parkinson disease and tremor are typically poorly responsive to levodopa.
  • magnetic resonance imaging (MRI) (may show vascular disease or selective atrophy suggestive of atypical disorder)
  • other testing as needed such as cognitive testing, neurophysiologic testing, or autonomic testing. Consider testing for genetic causes of parkinsonism, such as Wilson’s disease, for patients < 40 years old presenting with parkinsonism. Genetic testing is not clinically routine, but can be considered in patients with young onset symptoms or family history of Parkinson disease.

Management

• Carbidopa/levodopa is the mainstay of treatment for Parkinson disease. Levodopa doses of up to 800-1,000 mg/day may be necessary for treatment of refractory symptoms.
• Sustained and predictable response to levodopa is consistent with idiopathic Parkinson disease, whereas atypical parkinsonism disorders may have no response or respond initially, but progress quickly with refractory symptoms.
• Levodopa can cause long-term motor fluctuations such as dyskinesias and wearing “off” phenomenon. Adjunct medications such as dopamine agonists, amantadine, anticholinergics, catechol-O-methyl transferase inhibitors (COMT inhibitors) and monoamine oxidase B inhibitors (MAO-b inhibitors) may also be used.
• Referral to a specialist is recommended for diagnostic uncertainty or management complications.
• For drug-induced parkinsonism
  • Subacute exposure to antipsychotics (typical and atypical) and antiemetics, such as metoclopramide, domperidone and prochlorperazine are the most common cause.
  • Discontinue causative medication, if possible, instead of treating with dopaminergic therapy.
  • Consider trial of amantadine or anticholinergic medication.
  • Tardive parkinsonism may take months to resolve following discontinuation of antidopaminergic agents. If symptoms do not completely resolve, consider the possibility of medication “unmasking” latent idiopathic Parkinson disease.