TY - JOUR T1 - Widespread structural brain involvement in ALS is not limited to the <em>C9orf72</em> repeat expansion JF - Journal of Neurology, Neurosurgery &amp; Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1354 LP - 1360 DO - 10.1136/jnnp-2016-313959 VL - 87 IS - 12 AU - Henk-Jan Westeneng AU - Renée Walhout AU - Milou Straathof AU - Ruben Schmidt AU - Jeroen Hendrikse AU - Jan H Veldink AU - Martijn P van den Heuvel AU - Leonard H van den Berg Y1 - 2016/12/01 UR - http://jnnp.bmj.com/content/87/12/1354.abstract N2 - Background In patients with a C9orf72 repeat expansion (C9+), a neuroimaging phenotype with widespread structural cerebral changes has been found. We aimed to investigate the specificity of this neuroimaging phenotype in patients with amyotrophic lateral sclerosis (ALS).Methods 156 C9− and 14 C9+ patients with ALS underwent high-resolution T1-weighted MRI; a subset (n=126) underwent diffusion-weighted imaging. Cortical thickness, subcortical volumes and white matter integrity were compared between C9+ and C9− patients. Using elastic net logistic regression, a model defining the neuroimaging phenotype of C9+ was determined and applied to C9− patients with ALS.Results C9+ patients showed cortical thinning outside the precentral gyrus, extending to the bilateral pars opercularis, fusiform, lingual, isthmus-cingulate and superior parietal cortex, and smaller volumes of the right hippocampus and bilateral thalamus, and reduced white matter integrity of the inferior and superior longitudinal fasciculus compared with C9− patients (p&lt;0.05). Among 128 C9− patients, we detected a subgroup of 27 (21%) with a neuroimaging phenotype congruent to C9+ patients, while 101 (79%) C9− patients showed cortical thinning restricted to the primary motor cortex. C9− patients with a ‘C9+’ neuroimaging phenotype had lower performance on the frontal assessment battery, compared with other C9− patients with ALS (p=0.004).Conclusions This study shows that widespread structural brain involvement is not limited to C9+ patients, but also presents in a subgroup of C9− patients with ALS and relates to cognitive deficits. Our neuroimaging findings reveal an intermediate phenotype that may provide insight into the complex relationship between genetic factors and clinical characteristics. ER -