J Neurol Neurosurg Psychiatry 81:690-695 doi:10.1136/jnnp.2009.188748
  • Research paper

Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis

  1. Jean-Philippe Ranjeva1
  1. 1Centre de Résonance Magnétique Biologique et Médicale, UMR CNRS 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France
  2. 2Pôle de Neurosciences Cliniques, Centre Hospitalier Universitaire Timone, Marseille, France
  1. Correspondence to Dr Bertrand Audoin, CRMBM, UMR CNRS 6612, Faculté de Médecine, 27 boulevard Jean Moulin, Marseille 13386, France; bertrand.audoin{at}
  • Received 13 July 2009
  • Revised 27 November 2009
  • Accepted 22 December 2009
  • Published Online First 14 April 2010


Background The existence of grey matter (GM) atrophy right after the first clinical event suggestive of multiple sclerosis (MS) remains controversial. The aim of this study was therefore to establish whether regional GM atrophy is already present in the earliest stage of MS assessing regional GM atrophy in a large group of patients.

Methods Sixty-two patients with a clinically isolated syndrome (CIS) were examined on a 1.5 T MR imager within 6 months after their first clinical events. A group of 37 matched healthy control subjects were also included in the study. An optimised voxel-based morphometry (VBM) method customised for MS was applied on volumetric T1-weighted images. The functional status of patients was assessed using the Expanded Disability Status Scale (EDSS) and the Brief Repeatable Battery.

Results VBM analysis (p<0.005, familywise error corrected) on patients versus control subjects showed the presence of significant focal GM atrophy in patients involving the bilateral insula, the bilateral orbitofrontal cortices, the bilateral internal and inferior temporal regions, the posterior cingulate cortex, the bilateral thalami, the bilateral caudate nuclei, the bilateral lenticular nuclei and the bilateral cerebellum. EDSS was slightly correlated (ρ=−0.37 p=0.0027) with the atrophy of the right cerebellum. No correlations have been evidenced between the cognitive status of patients and the regional GM atrophy.

Conclusion The present study performed on a large group of CIS patients demonstrated that regional GM atrophy is present right after the first clinical event of multiple sclerosis and mainly affects the deep GM and the limbic system.


  • Funding This research was supported by the CNRS, the Institut Universitaire de France, Bayer-Schering France and The French ‘Association pour la Recherche sur la Sclérose en Plaques’ (ARSEP).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by Timone Hospital, Marseille, France.

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

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