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Abstract
Objective: To assess the correlation between cognitive impairment and overall vs regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI tractography in multiple sclerosis (MS).
Methods: Brain dual-echo, T1-weighted, and DT MRI data were acquired from 82 patients with MS. DT tractography was used to produce maps of white matter (WM) tracts involved in cognition. The sensory thalamocortical projections and optic radiations were studied as “control” WM tracts. The contribution of global brain damage (T2 lesion volume, normalized brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal-appearing WM and GM damage) and damage to selected WM tracts to overall cognitive impairment and to impairment at individual neuropsychological tests was assessed using a random forest (RF) analysis.
Results: Thirty-three patients had cognitive impairment. The majority of MRI measures differed significantly between cognitively impaired and cognitively preserved (CP) patients. Significant correlations were found between performance in the majority of neuropsychological tests and global or regional brain damage (r ranging from −0.60 to 0.57). The RF analysis showed a high performance in classifying cognitively impaired vs CP patients, with a classification (C)–index = 76.8, as well as in classifying patients' impairment in individual neuropsychological tests (C-index between 75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather than measures of normal-appearing WM damage in the same tracts or global brain/WM/GM damage, resulted in the highest classification accuracy.
Conclusions: Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.
GLOSSARY
- %C-index =
- classification index;
- CC =
- corpus callosum;
- CII =
- cognitive impairment index;
- CP =
- cognitively preserved;
- DT =
- diffusion tensor;
- EDSS =
- Expanded Disability Status Scale;
- FA =
- fractional anisotropy;
- GM =
- gray matter;
- LL =
- lesion load;
- MCP =
- middle cerebellar peduncle;
- MD =
- mean diffusivity;
- MPRAGE =
- magnetization prepared rapid acquisition gradient echo;
- MS =
- multiple sclerosis;
- NAWM =
- normal-appearing white matter;
- PASAT =
- Paced Auditory Serial Addition Test;
- RF =
- random forest;
- SCP =
- superior cerebellar peduncle;
- SDMT =
- Symbol Digit Modalities Test;
- SRT =
- Selective Reminding Test;
- sTCP =
- sensory thalamocortical projections;
- UF =
- uncinate fasciculus;
- WM =
- white matter
Footnotes
Study funding: This study was partially supported by a grant from the Ministry of Science, Republic of Serbia (project number: 175031).
Supplemental data at www.neurology.org
- Received May 3, 2011.
- Accepted September 13, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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