Expert tips on diagnosing early Parkinson’s disease in the clinic

Making a correct diagnosis of Parkinson’s disease when a patient presents for the first time with bradykinesia with rigidity and/or rest tremor can be challenging, explained Professor Daniela Berg, Kiel, Germany, and Professor Stephen Reich, Baltimore, MD, at MDS 2022. In separate plenaries, they provided tips on how to differentiate early-stage disease from atypical parkinsonism and avoid false-negative and false-positive diagnoses

Diagnosis and differential diagnosis of early Parkinson’s disease

Diagnostic accuracy for early Parkinson’s disease is only 80%1

Only 8 in every 10 patients who present with Parkinson’s disease (PD) are correctly diagnosed,1 said Professor Reich.

Differential diagnoses to consider when a patient presents for the first time with bradykinesia with rigidity and/or rest tremor include atypical parkinsonisms (i.e. multiple system atrophy [MSA], progressive supranuclear palsy [PSP] and corticobasal syndrome [CBS]),2 drug-induced parkinsonism,3 essential tremor,4 normal pressure hydrocephalus,5 gait disorders,6 and vascular parkinsonism.7


Early Parkinson’s disease can only be diagnosed when a patient with parkinsonism has supportive features and no exclusionary features and “red flags” have been scrutinized8

Does the patient have Parkinson’s disease?

A clinical diagnosis of early Parkinson’s disease (PD) can only be made when a patient who presents with parkinsonism (i.e. bradykinesia with rigidity and/or rest tremor) has supportive features and no exclusionary features, and “red flags” have been carefully scrutinized,8 Professor Reich explained.

Supportive features include a positive response to dopamine and olfactory loss.8

Exclusionary features include:

Supportive features include a positive response to dopamine8

  • Cerebellar signs
  • Downward vertical supranuclear gaze palsy or selective slowing of downward vertical saccades
  • Cortical sensory loss, apraxia, or aphasia
  • Treatment with a dopamine receptor blocker or a dopamine-depleting agent in a dose and time-course consistent with drug-induced parkinsonism
  • Normal functional imaging of the presynaptic dopaminergic system8

Absence of the expected non-motor features of Parkinson’s disease suggests that parkinsonism is not due to Parkinson’s disease8 

Red flags include:

  • Rapid progression
  • Early bulbar dysfunction
  • Falls within 3 years of onset
  • Autonomic failure within 5 years of onset
  • Absence of the expected non-motor features of PD — for example, autonomic dysfunction, rapid eye movement sleep behavior disorder, neuropsychiatric features, hyposmia — within 5 years of onset8


Does the patient have an atypical Parkinsonism?

It can be challenging to differentiate atypical Parkinsonism from early PD, said Professor Berg. She presented videos of four patients, one with PD and three with atypical parkinsonism — one MSA, one with PSP, and one with CBS. The videos showed the patients’ lower legs and feet as they walked, and the audience was asked to decide which patient had which disease.

It can be challenging to differentiate atypical Parkinsonism from early Parkinson’s disease

Only one-third of the audience made the correct diagnosis for each patient. Professor Berg explained that she was not surprised at this low level of accuracy because when patients present with early parkinsonism other clinical features are needed to make the diagnosis. For example, the presence of the expected non-motor features of PD supports a diagnosis of PD.9


Causes of false-negative and false-positive Parkinson’s disease diagnoses

Frozen shoulder and young-onset presentations of Parkinson’s disease may lead to a false-negative diagnosis10,11

Professor Reich cautioned that shoulder complaints/frozen shoulder10 and young-onset11 presentations of PD may lead to a false-negative diagnosis. In contrast, diagnoses to consider to avoid making a false-positive diagnosis of PD include:

  • Drug-induced parkinsonism3
  • Essential tremor4
  • Normal pressure hydrocephalus5
  • Neurologic gait disorders in elderly people6
  • Vascular parkinsonism7

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Rizzo G, Copetti M, Arcuti S, et al. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology. 2016;86(6):566–76.
  2. McFarland NR, Hess CW. Recognizing atypical parkinsonisms: "red flags" and therapeutic approaches. Semin Neurol. 2017;37(2):215–27.
  3. Esper CD, Factor SA. Failure of recognition of drug-induced parkinsonism in the elderly. Mov Disord. 2008;23(3):401–4.
  4. Bhatia KP, Bain P, Bajaj N, et al; Tremor Task Force of the International Parkinson and Movement Disorder Society. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018;33(1):75–87.
  5. Espay AJ, Da Prat GA, Dwivedi AK, et al. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol. 2017;82(4):503–13.
  6. Snijders AH, van de Warrenburg BP, Giladi N, Bloem BR. Neurological gait disorders in elderly people: clinical approach and classification. Lancet Neurol. 2007;6(1):63–74.
  7. Vizcarra JA, Lang AE, Sethi KD, Espay AJ. Vascular parkinsonism: deconstructing a syndrome. Mov Disord. 2015;30(7):886–94.
  8. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591–601.
  9. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2015;30(12):1600–11.
  10. Riley D, Lang AE, Blair RD, et al. Frozen shoulder and other shoulder disturbances in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1989;52(1):63–6.
  11. Ruiz-Lopez M, Freitas ME, Oliveira LM, et al. Diagnostic delay in Parkinson's disease caused by PRKN mutations. Parkinsonism Relat Disord. 2019;63:217–220.
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