J Neurol Neurosurg Psychiatry 82:72-77 doi:10.1136/jnnp.2009.201574
  • Research paper

T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis

Open Access
  1. O Ciccarelli1
  1. 1Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, London, UK
  2. 2Department of Neurological Sciences, University of Rome “La Sapienza”, Rome, Italy
  3. 3Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy
  4. 4Department of Radiology and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
  5. 5Department of Neuroinflammation, Institute of Neurology, University College London, London, UK
  6. 6Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy
  7. 7Unitat de Neuroimmunologia Clinica and Magnetic Resonance Unit, Hospital Universitario Vall d'Hebron, Barcelona, Spain
  8. 8Multiple Sclerosis Center, Scientific Institute Santa Maria Nascente, Fondazione Don Gnocchi, Milan, Italy
  1. Correspondence to Dr O Ciccarelli, Department of Brain Repair and Rehabilitation, Institute of Neurology, Queen Square, London WC1N 3BG, UK; o.ciccarelli{at}
  • Received 30 November 2009
  • Revised 18 February 2010
  • Accepted 21 March 2010
  • Published Online First 13 July 2010


Objectives Prediction of long term clinical outcome in patients with primary progressive multiple sclerosis (PPMS) using imaging has important clinical implications, but remains challenging. We aimed to determine whether spatial location of T2 and T1 brain lesions predicts clinical progression during a 10-year follow-up in PPMS.

Methods Lesion probability maps of the T2 and T1 brain lesions were generated using the baseline scans of 80 patients with PPMS who were clinically assessed at baseline and then after 1, 2, 5 and 10 years. For each patient, the time (in years) taken before bilateral support was required to walk (time to event (TTE)) was used as a measure of progression rate. The probability of each voxel being ‘lesional’ was correlated with TTE, adjusting for age, gender, disease duration, centre and spinal cord cross sectional area, using a multiple linear regression model. To identify the best, independent predictor of progression, a Cox regression model was used.

Results A significant correlation between a shorter TTE and a higher probability of a voxel being lesional on T2 scans was found in the bilateral corticospinal tract and superior longitudinal fasciculus, and in the right inferior fronto-occipital fasciculus (p<0.05). The best predictor of progression rate was the T2 lesion load measured along the right inferior fronto-occipital fasciculus (p=0.016, hazard ratio 1.00652, 95% CI 1.00121 to 1.01186).

Conclusion Our results suggest that the location of T2 brain lesions in the motor and associative tracts is an important contributor to the progression of disability in PPMS, and is independent of spinal cord involvement.


  • Funding BB is funded by FISM (Fondazione Italiana Sclerosi Multipla - 2007/B/01). OC is a Wellcome Trust Advanced Fellow. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  • Competing interests None.

  • Ethics approval This study was approved by the local ethics committees in each one of the participating centres (Amsterdam, Barcelona, Bordeaux, London and Milan).

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

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

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