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Research paper
Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score
  1. Nina A Hilkens1,
  2. Charlotte J J van Asch2,3,
  3. David J Werring4,
  4. Duncan Wilson4,
  5. Gabriël J E Rinkel2,
  6. Ale Algra1,2,
  7. Birgitta K Velthuis5,
  8. Gérard A P de Kort5,
  9. Theo D Witkamp5,
  10. Koen M van Nieuwenhuizen2,
  11. Frank-Erik de Leeuw6,
  12. Wouter J Schonewille7,
  13. Paul L M de Kort8,
  14. Diederik W J Dippel9,
  15. Theodora W M Raaymakers10,
  16. Jeannette Hofmeijer11,
  17. Marieke J H Wermer12,
  18. Henk Kerkhoff13,
  19. Korné Jellema14,
  20. Irene M Bronner15,
  21. Michel J M Remmers16,
  22. Henri Paul Bienfait17,
  23. Ron J G M Witjes18,
  24. H Rolf Jäger19,
  25. Jacoba P Greving1,
  26. Catharina J M Klijn2,6
  27. the DIAGRAM study group
    1. 1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
    2. 2 Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
    3. 3 Kempenhaeghe, Academic Centre for Epileptology, Heeze, The Netherlands
    4. 4 Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
    5. 5 Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
    6. 6 Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
    7. 7 Department of Neurology, St Antonius Hospital, Nieuwegein, The Netherlands
    8. 8 Department of Neurology, St Elisabeth Hospital, Tilburg, The Netherlands
    9. 9 Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
    10. 10 Department of Neurology, Meander Medical Center, Amersfoort, The Netherlands
    11. 11 Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands
    12. 12 Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
    13. 13 Department of Neurology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
    14. 14 Department of Neurology, MCH Westeinde, The Hague, The Netherlands
    15. 15 Department of Neurology, Flevo Hospital, Almere, The Netherlands
    16. 16 Department of Neurology, Amphia Hospital, Breda, The Netherlands
    17. 17 Department of Neurology, Gelre Hospital, Apeldoorn, The Netherlands
    18. 18 Department of Neurology, Tergooi Hospitals, Blaricum, The Netherlands
    19. 19 Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
    1. Correspondence to Professor Catharina J M Klijn, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Karin.Klijn{at}radboudumc.nl

    Abstract

    Objective A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH.

    Methods The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%).

    Results Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51–70 years with deep ICH and SVD, to more than 50% in patients aged 18–50 years with lobar or posterior fossa ICH without SVD.

    Conclusion The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA.

    • intracerebral haemorrhage
    • CT angiography
    • digital subtraction angiography
    • arteriovenous malformation

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    Footnotes

    • NAH, CJJA and DJW contributed equally.

    • Contributors CJMK, BKV, GJER and AA designed the study. BKV, GAPdK, TDW and HRJ assessed brain images. CJJvA, KMvN, FEdL, WJS, PLMdK, DWJD, TR, JH, MJHW, HK, KJ, IMB, MJMR, HPB, RJGMW, CJMK, DJW and DW collected data. NAH, CJJvA and JPG conducted the statistical analyses. NAH drafted the paper and all authors reviewed and commented on the report. CJMK is the guarantor.

    • Funding This study was supported by a Dutch Heart Foundation grant (no 2007B048 to CJMK). CJMK is also supported by a clinical established investigator grant from the Dutch Heart Foundation (no 2012T077), and an Aspasia grant from the Netherlands Organisation for Health Research and Development, ZonMw (015008048). JPG and NAH are supported by a grant from the Dutch Heart Foundation (no 2013T128 to JPG).

    • Competing interests None declared.

    • Ethics approval The DIAGRAM study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, the Netherlands, and local approval was obtained from all participating hospitals. Data collection for the validation cohort was approved by the Clinical Governance Committee of the National Hospital and the UCL Institute of Neurology and National Hospital Joint Research Ethics Committee.

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

    • Data sharing statement Requests for data sharing should be sent to the senior author (Karin.klijn@radboudumc.nl) and will be considered on approval by the DIAGRAM investigators.

    • Collaborators FE de Leeuw, HB Boogaarts and EJ van Dijk (Radboud University Nijmegen Medical Center, Nijmegen; 27 patients enrolled); WJ Schonewille, WMJ Pellikaan and C Puppels-de Waard (St Antonius Hospital, Nieuwegein; 22); PLM de Kort, JP Peluso and JH van Tuijl (St Elisabeth Hospital Tilburg; 20); J Hofmeijer, FBM Joosten (Rijnstate Hospital, Arnhem; 16); DW Dippel, L Khajeh (Erasmus MC University Medical Center, Rotterdam; 16); TWM Raaijmakers (Meander Medical Center, Amersfoort; 16); MJ Wermer and MA van Walderveen (Leiden University Medical Center, Leiden; 14); H Kerkhoff, E Zock (Albert Schweitzer Hospital, Dordrecht; 14); K Jellema, GJ Lycklama à Nijeholt (Medical Center Haaglanden, The Hague; 12); IM Bronner (Flevo Hospital, Almere; 12); MJM Remmers (Amphia Hospital, Breda; 9); RJGM Witjes (Tergooi Hospital, Blaricum; 8); HP Bienfait, KE Droogh-Greve (Gelre Hospital, Apeldoorn; 8); RCJM Donders (Diakonessen Hospital, Utrecht; 6); VIH Kwa (now: Onze Lieve Vrouwe Gasthuis, Slotervaart Hospital, Amsterdam; 4); TH Schreuder and CL Franke (Atrium Medisch Centrum, Heerlen; 4); JS Straver (Hofpoort Hospital, Woerden; 2); C Jansen (Gelderse Vallei Hospital, Ede; 1); SLM Bakker and CC Pleiter (Sint Franciscus Gasthuis, Rotterdam; 1); MC Visser (Free University Medical Center, Amsterdam; 1); and CJJ van Asch, BK Velthuis, GJE Rinkel, KM van Nieuwenhuizen, CJM Klijn (University Medical Center Utrecht; 90).

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