Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis

OBJECTIVES To assess (a) whether the changes in the normal appearing brain tissue (NABT), as revealed by magnetisation transfer (MT) histogram analysis, correlates with cognitive dysfunction in patients with multiple sclerosis and (b) the relative contribution of these changes by comparison with that of multiple sclerosis lesions visible on conventional MRI. METHODS Dual echo, T1 weighted and MT scans of the brain were obtained in 12 patients with multiple sclerosis with cognitive impairment and in seven without cognitive impairment. Lesion loads were assessed from T2 and T1 weighted scans. To create MT histograms of the NABT, multiple sclerosis lesion outlines from dual echo scans were superimposed automatically and nulled out from the coregistered and scalp stripped MTR maps. Average lesion MT ratio (MTR) and brain size were also measured. RESULTS T2 and T1 lesion loads were significantly higher and the average lesion MTR and brain size were significantly lower in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower average MTR and peak location of the NABT histogram. Logistic regression analysis showed that 68% of the total variance was explained by average NABT-MTR alone. A multivariable regression model showed that NABT-MTR was the only factor that significantly correlated with cognitive impairment in these patients (p=0.001). CONCLUSIONS The extent of abnormalities which go undetected when using conventional MRI is relevant in determining cognitive impairment in multiple sclerosis.

[1]  I. Allen,et al.  A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis , 1979, Journal of the Neurological Sciences.

[2]  C. Poser,et al.  Cognitive function in patients with multiple sclerosis. , 1980, Archives of neurology.

[3]  J A Frank,et al.  Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis , 1998, Annals of neurology.

[4]  Massimo Filippi,et al.  Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis , 1995, Journal of the Neurological Sciences.

[5]  C. W. Adams,et al.  Pathology of multiple sclerosis: progression of the lesion. , 1977, British medical bulletin.

[6]  R I Grossman,et al.  Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. , 1995, Radiology.

[7]  A. Thompson,et al.  Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[8]  J. K. Udupa,et al.  Isolated U-fiber involvement in MS , 1998, Neurology.

[9]  C. Pozzilli,et al.  Anterior Corpus Callosum Atrophy and Verbal Fluency in Multiple Sclerosis , 1991, Cortex.

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

[11]  P M Matthews,et al.  Imaging axonal damage of normal-appearing white matter in multiple sclerosis. , 1998, Brain : a journal of neurology.

[12]  F. Fazio,et al.  Functional Basis of Memory Impairment in Multiple Sclerosis: A [18F]FDG PET Study , 1996, NeuroImage.

[13]  G. Comi,et al.  Resolution‐dependent estimates of lesion volumes in magnetic resonance imaging studies of the brain in multiple sclerosis , 1995, Annals of neurology.

[14]  J. Grafman,et al.  Relationship between frontal lobe lesions and Wisconsin Card Sorting Test performance in patients with multiple sclerosis , 1994, Neurology.

[15]  L. Laitinen,et al.  Studies on the pathogenesis of multiple sclerosis. Participation of lysosomes on demyelination in the central nervous system white matter outside plaques. , 1973, European neurology.

[16]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[17]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[18]  I. Moseley,et al.  Signal intensity on MRI of basal ganglia in multiple sclerosis. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[19]  J Foong,et al.  Executive function in multiple sclerosis. The role of frontal lobe pathology. , 1997, Brain : a journal of neurology.

[20]  J Marshall,et al.  Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[21]  M Rovaris,et al.  Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis , 1998, Neurology.

[22]  C P Langlotz,et al.  MR identification of white matter abnormalities in multiple sclerosis: a comparison between 1.5 T and 4 T. , 1998, AJNR. American journal of neuroradiology.

[23]  J. Ridley.  Studies of Interference in Serial Verbal Reactions , 2001 .

[24]  R A Robb,et al.  Analyze: a comprehensive, operator-interactive software package for multidimensional medical image display and analysis. , 1989, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[25]  M Filippi,et al.  A Magnetization Transfer Imaging Study of Normal-Appearing White Matter in Multiple Sclerosis , 1995, Neurology.

[26]  M Filippi,et al.  The role of non-conventional magnetic resonance techniques in monitoring evolution of multiple sclerosis. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[27]  Costanza Papagno,et al.  Dual-task performance in dysexecutive and nondysexecutive patients with a frontal lesion. , 1997 .

[28]  Gerald Q. Maguire,et al.  Comparison and evaluation of retrospective intermodality brain image registration techniques. , 1997, Journal of computer assisted tomography.

[29]  V. Haughton,et al.  Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis , 1989, Neurology.

[30]  F. Barkhof,et al.  Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis , 1996, Annals of neurology.

[31]  I. T. Draper.  MULTIPLE SCLEROSIS: A REAPPRAISAL , 1973, The Medical journal of Australia.

[32]  R I Grossman,et al.  Quantitative volumetric magnetization transfer analysis in multiple sclerosis: Estimation of macroscopic and microscopic disease burden , 1996, Magnetic resonance in medicine.

[33]  P M Matthews,et al.  Axonal dysfunction and disability in a relapse of multiple sclerosis: Longitudinal study of a patient , 1997, Neurology.

[34]  R. Heaton.  Wisconsin Card Sorting Test manual , 1993 .

[35]  E. Weigl,et al.  On the psychology of so-called processes of abstraction. , 1941 .

[36]  Richard A. Robb,et al.  New approach to 3-D registration of multimodality medical images by surface matching , 1992, Other Conferences.

[37]  A. Baddeley,et al.  Dual-task performance in dysexecutive and nondysexecutive patients with a frontal lesion. , 1997, Neuropsychology.

[38]  C Becker,et al.  Quantitative assessment of MRI lesion load in multiple sclerosis. A comparison of conventional spin-echo with fast fluid-attenuated inversion recovery. , 1996, Brain : a journal of neurology.

[39]  R. Knobler,et al.  Neuropsychological and structural brain lesions in multiple sclerosis , 1992, Neurology.

[40]  P. Riekkinen,et al.  Studies on the Pathogenesis of Multiple Sclerosis , 1971 .

[41]  G. Comi,et al.  Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis. , 1998, AJNR. American journal of neuroradiology.

[42]  J K Udupa,et al.  Correlation of volumetric magnetization transfer imaging with clinical data in MS , 1998, Neurology.

[43]  R H Edwards,et al.  Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the "invisible" lesion load. , 1994, Magnetic resonance imaging.

[44]  T. Shallice.  Specific impairments of planning. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[45]  M Filippi,et al.  Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI , 1999, Neurology.

[46]  R I Grossman,et al.  Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. , 1992, Radiology.

[47]  A J Thompson,et al.  Multiple sclerosis lesion detection in the brain: A comparison of fast fluid-attenuated inversion recovery and conventional T2-weighted dual spin echo , 1997, Neurology.

[48]  P M Matthews,et al.  In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis. , 1999, Brain : a journal of neurology.