1. Corpus Callosum Damage Predicts Disability Progression and Cognitive Dysfunction in Primary-Progressive MS After Five Years

2. MRI Techniques Fractional anisotropy (FA) –A diffusion tensor imaging-derived measure used to quantify the integrity of white matter (WM) tracts – FA indicates demyelination and axonal loss – FA at onset of MS predicts rate of disability progression (physical and cognitive) –Correlates significantly with cognitive scores in MS and predicts motor impairment in relapsing-remitting MS Gray matter (GM) volume –Commonly used measure to assess GM integrity using T1-weighted images – GM volume indicates clinically relevant, irreversible tissue loss/atrophy Tract based spatial statistics (TBSS) and voxel-based morphometry (VBM) –TBSS identifies WM regions with reduced FA, VBM identifies areas of GM atrophy –Both localize specific regions of damage/loss by searching across the whole brain, thus avoiding the need for an a priori hypothesis Bodini B, et al. Hum Brain Mapp. 2012, Feb 13 [Epub ahead of print].

3. Physical and Cognitive Disability and Corpus Callosum (CC) Abbreviations: FA, fractional anisotropy; EDSS, Expanded Disability Status Scale Bodini B, et al. Hum Brain Mapp. 2012, Feb 13 [Epub ahead of print]. Damage to the CC predicts physical and cognitive disability Physical –Lower baseline FA in the splenium of the CC was associated with greater progression of disability over 5 years as measured by the EDSS step-change (P<.05) Cognitive –Strongest and most consistent association between lower baseline FA and worse cognition at 5 years found in the CC –Damage to different regions of CC affects different cognitive tasks

4. Cognitive Dysfunction and the Corpus Callosum (CC) FA in the splenium and genu of the CC associated with worse immediate verbal memory on the immediate SRT (P =.003) FA in the splenium, body, and genu of the CC (with extension into the right thalamic radiation) associated with worse delayed verbal memory on the delayed SRT (P =.003) FA in the body and splenium of the CC associated with worse attention and speed of information processing on the SDMT (P <.05) FA in the genu and body of the CC (and in the bilateral corona radiata) associated with worse executive functions on the HSCT (P =.003) Abbreviations: HSCT, Hayling Sentence Completion Task; SDMT, symbol digit modalities test; SRT, story recall test. Bodini B, et al. Hum Brain Mapp. 2012, Feb 13 [Epub ahead of print].

5. Cognitive Dysfunction and the Corpus Callosum (CC) Analysis adjusted for total lesion load – Significant association between FA in the genu and body of the CC and the HSCT executive functions at 5 years (P <.05) Analysis adjusted for CC lesion load –Significant association between FA of the splenium of the CC at study entry and a worse performance on immediate and delayed verbal memory tests (SRT; P < 0.05) –Significant association between FA of the body of the CC and a poorer performance on a test of executive function at five years (HSCT; P <.05) Both lesion load and corpus callosum damage contribute to cognitive impairment in MS Abbreviations: HSCT, Hayling Sentence Completion Task; SRT, story recall test. Bodini B, et al. Hum Brain Mapp. 2012, Feb 13 [Epub ahead of print].

6. CC ensures effective communication between motor and cognitive networks in the two hemispheres If a clinician sees a patient with an atrophic brain and/or atrophic CC, it is likely that this patient will have greater cognitive dysfunction in 5 years than a patient with less brain atrophy or thicker CC Bodini B, et al. Hum Brain Mapp. 2012, Feb 13 [Epub ahead of print]. Practice Implications for MS Patients