Parkinson Disease Differential Diagnoses

Updated: Jun 04, 2020
  • Author: Robert A Hauser, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
  • Print

Diagnostic Considerations

The most common tremor disorders are Parkinson disease and essential tremor. When a patient presents with tremor, the clinician should pay particular attention to the body parts involved, positions/conditions in which the tremor occurs (ie, resting, postural, kinetic, intention), and the frequency of the tremor. It is also critical to look for potential associated signs. The patient should be examined for evidence of parkinsonism (bradykinesia, rigidity, postural instability), dystonia, and other neurologic signs.

An 8-12 Hz action (postural/kinetic) tremor of the upper extremities that is temporarily relieved by drinking alcohol is characteristic of essential tremor, whereas the presence of a pill-rolling rest tremor, bradykinesia, and rigidity is consistent with Parkinson disease and argues against essential tremor.

In patients with parkinsonism, careful attention to the history is necessary to exclude secondary causes such as medications, toxins, or trauma. Medications that block striatal dopamine receptors, such as metoclopramide and neuroleptics, can cause drug-induced parkinsonism. Certain toxins such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and manganese (at high levels of exposure) can also cause parkinsonism.

Consider evaluating patients with parkinsonism for osteoporosis and osteopenia. In a meta-analysis of 23 studies, Tornsey and colleagues found evidence that individuals with Parkinson disease have an increased risk for osteoporosis and osteopenia. [35, 36] A pooled analysis of 2 of the studies, for example, indicated that in patients with Parkinson disease, the odds ratio for developing osteoporosis, when compared with healthy controls, was 2.61, although the increase was lower in men than in women.

Analysis of 14 studies found bone mineral densities in patients with Parkinson disease to be significantly lower at the hip, lumbar spine, and femoral neck, whereas, after an examination of 9 studies, the investigators estimated that bone fracture risk is doubled in Parkinson patients. [35, 36]

Early clinical features that suggest an atypical parkinsonism rather than Parkinson disease include the following [22] :

  • Falls at presentation or early in the disease

  • Poor response to levodopa

  • Symmetry at disease onset

  • Rapid disease progression

  • No tremor

  • Dysautonomia (eg, urinary incontinence, fecal incontinence, catheterization for urinary retention, persistent erectile failure, prominent symptomatic orthostatic hypotension)

The atypical parkinsonisms are usually associated with little or no tremor, relatively early speech and balance difficulty, and little or no response to dopaminergic medications. Multiple system atrophy (MSA) is relatively symmetric and characterized by parkinsonism, often with some combination of autonomic, corticospinal, and cerebellar dysfunction. Progressive supranuclear palsy (PSP) is relatively symmetric and characterized by parkinsonism with early falls (often in the first year) and a supranuclear gaze palsy in which the patient has difficulty with voluntary down-gaze. Corticobasal ganglionic degeneration (CBD) is typically very asymmetric and characterized by both cortical (difficulty identifying objects, apraxias) and basal ganglionic (usually marked rigidity in an arm) features.

Lewy body disease is characterized by substantial cognitive dysfunction within 1 year of onset of parkinsonism. Hallucinations are common.

Patients with onset of parkinsonism before age 40 years should be tested for Wilson disease, starting with serum ceruloplasmin measurement and ophthalmologic evaluation for Kayser-Fleischer rings.

Differential Diagnoses