Unraveling disease burden in familial ALS due to SOD1 mutation through the combination of brain and cervical cord MRI (P5.074)

Objective: To explore structural and functional changes of the brain and cervical cord in patients with familial amyotrophic lateral sclerosis (FALS) due to mutation in superoxide dismutase ( SOD1 ) gene. Background: Approximately 20% of FALS cases show mutations in the SOD1 gene. Although these patients show a clinical phenotype similar to sporadic ALS (SALS), their survival is generally longer for undetermined reasons. To our knowledge, this is the first study investigating both brain and cervical cord magnetic resonance imaging (MRI) alterations in SOD1 + FALS patients. Design/Methods: 20 SOD1 + FALS patients, 11 SALS patients and 33 healthy controls underwent clinical evaluation and a comprehensive MRI protocol assessing brain structural and functional alterations using T1-weighted, diffusion tensor and resting-state (RS) functional MRI. Cortical thickness, tractography of the corticospinal tracts (CST), and RS functional connectivity analyses were performed. Patients also underwent cervical cord MRI to evaluate cord atrophy and magnetization transfer ratio (MTR). Results: SOD1 + FALS patients showed a longer disease duration (p vs controls), with a trend toward a greater damage in SALS relative to FALS (p=0.06 bilaterally). Functional hyperconnectivity of the right motor cortex in the sensorimotor network was observed in SALS patients only. Conversely, FALS patients showed greater cervical cord atrophy at all included myelomeres relative to SALS (p Conclusions: SOD1 + FALS subjects showed cervical cord atrophy relative to SALS, despite a similar cord MTR and the relative preservation of brain motor networks. Our results suggest that pathological burden accumulated through presymptomatic stages and longer disease duration in SOD1 + cases might selectively affect the cervical cord. Disclosure: Dr. Spinelli has nothing to disclose. Ms. Agosta has received personal compensation for activities with EXCEMED - Excellence in Medical Education as a speaker. Dr. Marjanovic has nothing to disclose. Dr. Stevic has nothing to disclose. Dr. Pagani has nothing to disclose. Dr. Valsasina has nothing to disclose. Dr. Lavrnic has nothing to disclose. Dr. Kostic has received personal compensation for activities with Novartis, Boehringer Ingelheim Pharmaceuticals, Merck & Co., Inc., Lundbeck Research USA, Inc., GlaxoSmithKline, Hoffman-La Roche, Alkaloid, and Dr. Filippi has received personal compensation for activities with Biogen Idec, Excemed, Novartis, and Teva as a consultant and/or speaker.