Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study

Background: Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function. Objective: The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS. Methods: Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer. Results: Disease duration spanned five decades (1.6–46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT (r = 0.793, p < 0.001) and moderately correlated with EDSS (r = −0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong. Conclusions: The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.

[1]  Fernando Faria Andrade Figueira,et al.  Corpus callosum index: a practical method for long-term follow-up in multiple sclerosis. , 2007, Arquivos de neuro-psiquiatria.

[2]  Martola Juha,et al.  Progression of non-age-related callosal brain atrophy in multiple sclerosis: a 9-year longitudinal MRI study representing four decades of disease development , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[3]  Jan Hillert,et al.  Progression of non-age-related callosal brain atrophy in multiple sclerosis: a 9-year longitudinal MRI study representing four decades of disease development. , 2007, Journal of neurology, neurosurgery, and psychiatry.

[4]  Bernhard Hemmer,et al.  An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis , 2012, NeuroImage.

[5]  Bruce Fischl,et al.  Within-subject template estimation for unbiased longitudinal image analysis , 2012, NeuroImage.

[6]  A. Gass,et al.  The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients , 2014, Multiple sclerosis.

[7]  Emilio Portaccio,et al.  Multiple sclerosis-related cognitive changes: A review of cross-sectional and longitudinal studies , 2006, Journal of the Neurological Sciences.

[8]  Wolfgang Brück,et al.  Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. , 2002, Brain : a journal of neurology.

[9]  R. Bakshi,et al.  Corpus Callosum Atrophy Correlates with Gray Matter Atrophy in Patients with Multiple Sclerosis , 2015, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[10]  Edith V. Sullivan,et al.  Sex differences in corpus callosum size: relationship to age and intracranial size , 2001, Neurobiology of Aging.

[11]  Massimo Filippi,et al.  MR imaging of multiple sclerosis. , 2011, Radiology.

[12]  Rohit Bakshi,et al.  MRI in multiple sclerosis: current status and future prospects , 2008, The Lancet Neurology.

[13]  Rohit Bakshi,et al.  The measurement and clinical relevance of brain atrophy in multiple sclerosis , 2006, The Lancet Neurology.

[14]  H. Hartung,et al.  Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) , 2012, Multiple sclerosis.

[15]  L. Lemieux,et al.  Reliable callosal measurement: population normative data confirm sex-related differences. , 2003, AJNR. American journal of neuroradiology.

[16]  P. Morgan,et al.  Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[17]  O. Almkvist,et al.  Callosal atrophy in multiple sclerosis is related to cognitive speed , 2013, Acta neurologica Scandinavica.

[18]  E. Havrdová,et al.  Corpus Callosum Atrophy – A Simple Predictor of Multiple Sclerosis Progression: A Longitudinal 9-Year Study , 2012, European Neurology.

[19]  L. Jäncke,et al.  Brain size, sex, and the aging brain , 2015, Human brain mapping.

[20]  A. Nieto,et al.  Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing–remitting multiple sclerosis , 2008, European journal of neurology.

[21]  J. Valk,et al.  Functional correlates of callosal atrophy in relapsing-remitting multiple sclerosis patients. A preliminary MRI study , 1998, Journal of Neurology.

[22]  E. Mooshagian,et al.  Anatomy of the Corpus Callosum Reveals Its Function , 2008, The Journal of Neuroscience.

[23]  P. Matthews,et al.  Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. , 2000, Brain : a journal of neurology.

[24]  A. Gass,et al.  Corpus callosum index and long-term disability in multiple sclerosis patients , 2010, Journal of Neurology.