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Research paper
Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease
  1. Knut Busse1,
  2. Robert Heilmann2,
  3. Sabine Kleinschmidt2,
  4. Mazen Abu-Mugheisib2,
  5. Jacqueline Höppner3,
  6. Christian Wunderlich1,
  7. Irene Gemende1,
  8. Lara Kaulitz2,
  9. Alexander Wolters2,
  10. Reiner Benecke2,
  11. Uwe Walter2
  1. 1Parkinson Clinic ‘Waldklinik Bernburg GmbH’, Bernburg, Germany
  2. 2Department of Neurology, University of Rostock, Rostock, Germany
  3. 3Department of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany
  1. Correspondence to Dr Professor U Walter, Department of Neurology, University of Rostock, Gehlsheimer Str 20, D-18147 Rostock, Germany;{at}


Objective Characteristic features of Parkinson's disease (PD) are asymmetric parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on transcranial ultrasound. However, each of these features has limited diagnostic value as they may be present, albeit less frequently, in other parkinsonian disorders. Here, the diagnostic sensitivity and specificity of combined assessment of these three features are evaluated.

Methods 632 patients with parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes, essential tremor and major depressive disorder with motor slowing) were assessed on the Unified Parkinson's disease Rating Scale for motor asymmetry (right–left score difference ≥2), the 12 item Sniffin' Sticks test (SS-12) and transcranial ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects (193 (35) women; age 65.4±9.6 (62.3±10.3) years) of whom 385 (68) had PD and 132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to missing transcranial insonability. Of the validation cohort, all patients had a disease duration ≤2 years and observers were blind to diagnoses.

Results The optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia) and SN echogenic size ≥0.24 cm2 (SN hyperechogenicity). Sensitivity, specificity and positive predictive values for the diagnosis of PD were as follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia 75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present 96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation cohort: two features present 91%, 77% and 85%; three features present 49%, 98% and 97%.

Conclusion The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.

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  • KB and RH contributed equally to this work.

  • Competing interests AW has received speaker honoraria and travel grants from Medtronic Inc, Bayer Pharma, Desitin Pharma and UCB Pharma. RB served on the scientific advisory board for Ipsen Pharma and Merz Pharma, and has received speaker honoraria and travel grants from Ipsen Pharma and Merz Pharma. UW has received speaker honoraria from Bayer Pharma, UCB Pharma, GlaxoSmithKline Pharma and TEVA Pharma.

  • Ethics approval The study was approved by the ethics review board of the medical faculty of the University of Rostock.

  • Provenance and peer review Not commissioned; externally peer reviewed.