Constantinescu_EU Neurology 09/03/2010 13:33 Page 73
Magnetic Resonance Imaging and Cognitive Impairment in Multiple Sclerosis
of mapping voxels belonging to specific tracts.
35
It has recently been Second, the tests of cognitive function vary considerably between
suggested by Lin et al.
36
that relating pathology in specific tracts to studies. Some studies use an extensive battery of tests, usually with a
relevant measures of function may improve correlations; this score summarising the results. Often the summary score does not
approach was named importance sampling. In that study the voxels correlate with dysfunction, yet some of the many individual test scores
within the CC were identified in 29 RR MS patients. Within the CC do; in these cases there is danger of type 1 statistical error, so results
diffusion metrics and lesion volumes were measured and related to need to be repeated to confirm the correlation. In some studies only a
cognitive function assessed using the PASAT. It was found that while single score of cognitive function is available, such as the PASAT or the
lesion volumes did not correlate with cognitive function, the mean mental score from the EDSS. While this reduces the risk associated with
diffusivity did. The same group performed a similar study on 36 RR MS multiple statistical tests, a single test will probably not encompass the
patients, this time measuring the MTR within the CC as well as mean whole domain of cognitive function.
diffusivity; CC area measured on a mid-sagittal slice and LV within the
CC were also estimated. Both MTR and mean diffusivity within the CC Another major limitation of the conventional MRI studies is the
and the area of the CC correlated with PASAT scores, but again the unknown contribution of the NABT to dysfunction, although it is
within-CC LV did not. probably included to some extent within studies of brain volume.
Quantitative MRI is now feasible on clinical scanners, and can be
Another analysis method specific to DTI is Tract-Based Spatial used to measure changes due to pathology, even within the NABT.
Statistics (TBSS).
37
This uses the quantitative anisotropy measure Several studies have now shown that changes within the NABT do
derived from the DTI to identify a skeleton image of the white-matter correlate with cognitive dysfunction; indeed, some studies indicate
tracts. Using such images, tract-specific group comparisons and that these changes are more important than the lesion burden.
correlation between tract-specific measures and clinical measures Inclusion of quantitative imaging therefore seems necessary in future
are possible. Recently, Dineen et al.
38
utilised this method to studies. However, even with the inclusion of quantitative imaging, the
investigate disconnection as a mechanism for cognitive dysfunction resulting picture may still be incomplete. Recent evidence from
in 37 MS patients with mild impairment. Regional reduction in functional MRI studies suggests that cognitive function can be
anisotropy was significantly associated with tests of sustained maintained by cortical plasticity.
39,40
This may complicate the
attention, working memory and processing speed, visual working relationship between cognitive function and pathology assessed by
memory and verbal learning and recall. Statistically significant MRI and, ultimately, limit the correlations. n
localisations were found in tracts interconnecting cortical regions
thought to be involved in processing in these cognitive domains, or
Christopher R Tench is a Research Fellow in the Division of Clinical Neurology, School
involved possible compensatory processing pathways.
of Clinical Sciences at the University of Nottingham. His current primary research
interest is medical image processing. Dr Tench obtained a PhD in neuroimaging from
Summary
the University of Nottingham as a staff candidate in 2003. This followed several years
of research in theoretical physics and then working as a research fellow in clinical
Conventional MRI has been used to study the relationship between
neurology at the same institution. Dr Tench obtained a BSc (Hons) in physics from
cognitive impairment and LV and/or brain volume (reflecting atrophy). Manchester University in 1996.
In general, MS-related cognitive dysfunction is shown to relate to lesion
burden and tissue loss. Furthermore, it has been demonstrated in
Cris S Constantinescu is a Professor of Neurology in the Division of Clinical Neurology,
School of Clinical Sciences at the University of Nottingham. His clinical and research
longitudinal studies that cognitive decline might be related to changes
interests are the immunology and imaging of neuroinflammatory disease, in particular
on MRI. However, results have not always been consistent, and there multiple sclerosis. He held posts in neurology and neurobiology in Basel prior to
are several possible explanations for this. First, the cohort of patients
moving to Nottingham. He was a member of the junior faculty at the University of
Pennsylvania, where he completed a PhD in immunology and was a recipient of the
varies in terms of disease course between studies. The heterogeneous
National Institutes of Health Physician Scientist Award. Professor Constantinescu
cohort in some studies might promote correlation compared with those completed neurology training and a fellowship in neuroimmunology at the University
using homogeneous cohorts, due to known differences in MRI
of Pennsylvania after graduating from Boston University Medical School.
measures and in impairment between the different disease courses.
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EUROPEAN NEUROLOGICAL REVIEW 73
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