Extensive white matter dysfunction in cognitively impaired patients with secondary-progressive MS

In this study, the association between cognitive impairment and white matter (WM) dysfunction in secondary-progressive multiple sclerosis was investigated using DTI.

The authors hypothesized that patients with secondary progressive multiple sclerosis (SPMS) with impairment spanning multiple cognitive domains should exhibit extensive WM dysfunction not restricted to tracts implicated in cognition, such as the cingulum and corpus callosum (CC).

Patients with SPMS were prospectively recruited. A standard MS cognitive battery, consisting of seven neuropsychological tests, was administered: Paced Auditory Serial Addition Test (working memory), Symbol Digit Modalities Test (processing speed), California Verbal Learning Test, 2nd Edition (verbal memory), Brief Visuospatial Memory Test, Revised (visuospatial memory), Delis-Kaplan Executive Function System (executive function), Controlled Word Association Test (verbal fluency), and Judgement of Line Orientation (visuospatial perception).

Patients with two or more test impairments were designated as having cognitive impairment. Beck Depression Inventory scores were also obtained because of the association between depression and cognitive impairment in patients with MS. MR imaging scanning was performed on a 3T scanner and the following sequences were acquired: 1) T1-3D; 2) proton density/T2; 3) DTI. Of 45 patients with SPMS prospectively recruited, 25 (55.6%) were classified as being cognitively impaired. Impaired patients displayed significantly reduced normalized global GM volume, significantly lower normalized global WM volume, significantly higher normalized T2-weighted WML volume, significantly greater normalized T1-weighted WM lesion volume, and significantly lower WM skeleton FA than patients without cognitive impairment.

Patients with cognitive dysfunction had significantly lower FA values in over 50% of the voxels within every major WM tract compared with those without . The most extensively affected WM tracts were the left posterior thalamic radiation (100.0%), CC (97.8%), right sagittal stratum (97.5%), right posterior thalamic radiation (96.1%), and left sagittal stratum (95.4%). Only one other region (right medial lemniscus) had greater than 90% alteration (90.8%).

These findings illustrate that, although WM dysfunction is predominantly generalized with respect to cognitive status, preferential involvement of specific WM tracts was apparent. No WM voxels had significantly higher FA in patients with cognitive impairment compared with their non impaired counterparts. Multivariate analysis of factors predicting cognitive status demonstrated that only WM skeleton FA was significant.

The study demonstrated that, in advanced MS disease characterized by SPMS, multiple domain cognitive dysfunction is the result of diffuse WM injury with regional predilections present in the CC, posterior thalamic radiation, and sagittal stratum. Of these three regions, only the CC is traditionally associated with cognition, but thalamic radiations are implicated in a wide range of cognitive tasks.

Authors: Francis PL, Chia TL
Source: AJNR Am J Neuroradiol. 2014 May 15. [Epub ahead of print]
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