Diffusion tensor imaging to stratify a clinically heterogeneous multi-system cerebral neurodegenerative syndrome

The unmistakeable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a common clinical endpoint for an expanding range of upstream cellular pathway derangements.1 Clinical, genetic and molecular signatures shared with frontotemporal dementia (FTD) have rendered the brain axiomatic to ALS pathology2 ; a core feature of what is a motor and paramotor multisystem degeneration, rather than a secondary afterthought overshadowed by the more visible consequences of peripheral lower motor neuron loss. For the emerging era of therapy for neurodegenerative disorders to flourish, tools that can assess pathology at the system as well as cellular level are essential. Floeter et al 3 demonstrate the potential of advanced structural MRI of the brain in this respect, exploring the relationship of white matter tract integrity using diffusion tensor imaging (DTI) to clinical parameters in a genetically homogeneous but clinically heterogeneous group of individuals carrying the C9orf72 repeat expansion. 

Underlying nearly one in every 10 cases of ALS and FTD is a hexanucleotide GGGGCC repeat expansion in C9orf72. This genetic variant may be associated with cases of both ‘pure’ …