@article {Floeter53, author = {Mary Kay Floeter and Laura E Danielian and Laura E Braun and Tianxia Wu}, title = {Longitudinal diffusion imaging across the C9orf72 clinical spectrum}, volume = {89}, number = {1}, pages = {53--60}, year = {2018}, doi = {10.1136/jnnp-2017-316799}, publisher = {BMJ Publishing Group Ltd}, abstract = {Introduction Discrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes.Methods Twenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King{\textquoteright}s college staging system.Results Widespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King{\textquoteright}s stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King{\textquoteright}s stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R.Conclusion Discrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King{\textquoteright}s stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/89/1/53}, eprint = {https://jnnp.bmj.com/content/89/1/53.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }