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Research paper
Using atypical symptoms and red flags to identify non-demyelinating disease
  1. Siobhan B Kelly1,
  2. Elijah Chaila1,
  3. Katie Kinsella1,
  4. Marguerite Duggan1,
  5. Cathal Walsh2,
  6. Niall Tubridy1,
  7. Michael Hutchinson1
  1. 1Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland
  2. 2Department of Statistics, Trinity College, Dublin, Ireland
  1. Correspondence to Professor Michael Hutchinson, Consultant Neurologist, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; mhutchin{at}


Background Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. The aim of this study was to establish the predictive value of red flags and the typicality/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS.

Methods All patients referred with suspected MS over a 3-year period were assessed by the typicality of the clinical presentation and the occurrence of red flags in relation to the eventual diagnosis. The extent of agreement of trainee and consultant neurologists as to typicality of clinical presentations was determined.

Results Of 244 patients referred, 119 (49%) had MS/CIS and 125 (51%) did not. 41 patients were referred because of an abnormal MRI. Of 203 with clinical symptoms, 96 patients had atypical symptoms of whom, 81 (84%) did not have MS and 15 (16%) had MS/CIS. Typical symptoms occurred in 107 patients; 10% did not have MS/CIS. Atypical symptoms had a sensitivity of 84%, specificity of 90% and positive likelihood ratio (PLR) of 8.4, whereas red flags had a sensitivity of 47%, specificity of 88% and PLR of 3.9 for the exclusion of MS/CIS. Mean percentage agreement between consultants and trainees was 73% with a range of 32–96%.

Conclusions Atypical features at presentation are more sensitive, specific and have a higher PLR than red flags to refute a diagnosis of MS/CIS.

  • Multiple sclerosis
  • red flags
  • medically unexplained symptoms
  • other neurological disease
  • diagnosis

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  • Competing interests N Tubridy receives a grant support from Bayer Schering and the Health Research Board of Ireland and MS Ireland. M Hutchinson serves on a medical advisory board [BG00012] for Biogen-Idec; serves on the editorial boards of the Multiple Sclerosis journal and the International MS journal and receives research support from Dystonia Ireland and the Health Research Board of Ireland.

  • Ethics approval The study was approved by the Medical Research Ethics Committee of St. Vincent's University Hospital, Dublin.

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