title: Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease.
abstract: 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 cm(2) (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%.
  
  
  CONCLUSIONS
  The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.
authors.affiliation: Parkinson Clinic ‘WaldklinikBernburg GmbH’, Bernburg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Busse
authors.forename: Robert
authors.initials: R
authors.lastname: Heilmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Kleinschmidt
authors.forename: Mazen
authors.initials: M
authors.lastname: Abu-Mugheisib
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Höppner
authors.forename: Christian
authors.initials: C
authors.lastname: Wunderlich
authors.forename: Irene
authors.initials: I
authors.lastname: Gemende
authors.forename: Lara
authors.initials: L
authors.lastname: Kaulitz
authors.forename: Alexander
authors.initials: A
authors.lastname: Wolters
authors.forename: Reiner
authors.initials: R
authors.lastname: Benecke
authors.forename: Uwe
authors.initials: U
authors.lastname: Walter
mesh_terms: D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D015897:Comorbidity; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis / Q000453:epidemiology*; D000857:Olfaction Disorders / Q000175:diagnosis / Q000453:epidemiology*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D012189:Retrospective Studies; D013378:Substantia Nigra / Q000000981:diagnostic imaging; D017585:Ultrasonography, Doppler, Transcranial