Transient Bone Marrow Oedema Syndrome following Dimethyl Fumarate use.

Introduction: Disruptions in functional brain network organization seem to be important underlying mechanisms of cognitive impairment in multiple sclerosis (MS). However, little is known about its longitudinal predictive value and its unique value beyond structural brain pathology. Aim of study: This longitudinal study aimed to investigate the importance of disruptions in functional brain network organization as a predictor of cognitive decline in MS patients, and to explore its unique value irrespective of structural pathology. Methods: Magnetoencephalography (MEG) recordings and magnetic resonance imaging (MRI) were analysed in 100 MS patients at baseline. Neuropsychological assessments were obtained at baseline and after five years. Brain network organization was computed using network properties of the Minimum Spanning Tree (MST; i.e. backbone of the functional brain network). Correlational and regression analyses were performed to relate these measures to cognitive decline, and to explore their effects beyond grey matter and white matter lesion volume. Results: Cognitive decline was best predicted by both a disintegrated network (i.e. a loss of network complexity) in the delta band and a more integrated network (i.e. a larger chance of hub overload) in the beta band at baseline (MEG model: R2=21%). These network measures remained independent predictors of cognitive decline (p< 0.05) when structural brain measures were included (combined MEG and MRI model: R2=27%). Conclusions: In conclusion, disruptions in functional brain network organization can serve as predictive markers of cognitive decline in patients with MS. These disruptions in functional brain network organization may be responsible for cognitive decline irrespective of the accumulation of structural damage.