Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis

Background/Objectives: The objective of this study was to investigate associations between the spatial distribution of brain lesions and clinical outcomes in a cohort of people followed up 20 years after presentation with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated from 74 people who underwent magnetic resonance imaging (MRI) and clinical assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics were used to compare LPMs between the following groups: clinically definite (CD) MS and those who remained with CIS, with an abnormal MRI; people with MS and an Expanded Disability Status Scale (EDSS) ≤3 and >3; people with relapsing–remitting (RR) and secondary progressive (SP) MS. The probability of each voxel being lesional was analysed adjusting for age and gender using a multiple linear regression model. Results: People with CDMS were significantly more likely than those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions in the corona radiata, optic radiation, and splenium of the corpus callosum (periventricularly) and T2 lesions in the right fronto-occipital fasciculus. People with MS EDSS >3, compared with those with EDSS ≤3, were more likely to have optic radiation and left internal capsule T2 lesions. No significant difference in lesion distribution was noted between RRMS and SPMS. Conclusion: This work demonstrates that lesion location characteristics are associated with CDMS and disability after long-term follow-up following a CIS. The lack of lesion spatial distribution differences between RRMS and SPMS suggests focal pathology affects similar regions in both subgroups.

[1]  A Achiron,et al.  Cognitive impairment in probable multiple sclerosis , 2003, Journal of neurology, neurosurgery, and psychiatry.

[2]  H. Moser,et al.  Magnetic resonance imaging detection of lesion progression in adult patients with X-linked adrenoleukodystrophy. , 2007, Archives of neurology.

[3]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[4]  M. Battaglini,et al.  Voxel-based assessment of differences in damage and distribution of white matter lesions between patients with primary progressive and relapsing-remitting multiple sclerosis. , 2008, Archives of neurology.

[5]  C. Polman,et al.  Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. , 2004, Archives of neurology.

[6]  S. Reingold,et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” , 2005, Annals of neurology.

[7]  Frederik Barkhof,et al.  Patterns of Brain Magnetic Resonance Abnormalities on T2-Weighted Spin Echo Images in Clinical Subgroups of Multiple Sclerosis: A Large Cross-Sectional Study , 1998, European Neurology.

[8]  I. Moseley,et al.  Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination , 1998, Journal of neurology, neurosurgery, and psychiatry.

[9]  B. Mädler,et al.  Is diffusion anisotropy an accurate monitor of myelination? Correlation of multicomponent T2 relaxation and diffusion tensor anisotropy in human brain. , 2008, Magnetic resonance imaging.

[10]  A. Thompson,et al.  Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. , 2008, Brain : a journal of neurology.

[11]  F. Barkhof,et al.  Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study , 2011, American Journal of Neuroradiology.

[12]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[13]  D.L. Plummer,et al.  DispImage: Un mezzo di analisi e presentazione per iconografia medica , 1992 .

[14]  A. Janssens,et al.  Callosal lesion predicts future attacks after clinically isolated syndrome , 2009, Neurology.

[15]  C. Svarer,et al.  Correlations of brain MRI parameters to disability in multiple sclerosis , 2001, Acta neurologica Scandinavica.

[16]  P M Matthews,et al.  Axonal injury or loss in the internal capsule and motor impairment in multiple sclerosis. , 2000, Archives of neurology.

[17]  J. Bodensteiner,et al.  Serial MRI and CT findings in infantile Krabbe disease. , 1992, Pediatric neurology.

[18]  K. J. Kim,et al.  MR of childhood metachromatic leukodystrophy. , 1997, AJNR. American journal of neuroradiology.

[19]  A. Achiron,et al.  Walking while talking--difficulties incurred during the initial stages of multiple sclerosis disease process. , 2010, Gait & posture.

[20]  Jeffrey A. Cohen,et al.  Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria , 2011, Annals of neurology.

[21]  F. Barkhof,et al.  Clinical correlations of brain lesion distribution in multiple sclerosis , 2009, Journal of magnetic resonance imaging : JMRI.

[22]  P. Szeszko,et al.  MRI atlas of human white matter , 2006 .

[23]  M. Filippi,et al.  A 3‐year magnetic resonance imaging study of cortical lesions in relapse‐onset multiple sclerosis , 2009, Annals of neurology.

[24]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[25]  Lublin Fd,et al.  Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. , 1996 .

[26]  M. Battaglini,et al.  T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis , 2010, Journal of Neurology, Neurosurgery & Psychiatry.