Mind the gap: from neurons to networks to outcomes in multiple sclerosis

Abstract

Jaume Sastre-Garriga reports in the last 36 months grants and personal fees from Genzyme, personal fees from Biogen, personal fees from Merck, personal fees from Almirall, personal fees from Novartis, personal fees from Roche, personal fees from TEVA, personal fees from Celgene, personal fees from Bial; J Sastre-Garriga is Director of Revista de Neurologia for which he does not receive any compensation, and serves as member of the Editorial Board of Multiple Sclerosis Journal, for which he receives a compensation.Menno M. Schoonheim serves on the editorial board of Frontiers of Neurology, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen.Betty Tijms received funding from the ZonMW Memorabel grant programme #73305056.Carmen Tur has received a post-doctoral research ECTRIMS fellowship (2015). She has also received honoraria and support for travelling from Merck Serono, Sanofi, Roche, TEVA Pharmaceuticals, Novartis, Biogen, Bayer, Ismar Healthcare. She also provides consultancy services to Roche.

Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

“…New imaging methods incorporating the different characteristics of lesions and diffuse pathology in the normal appearing white matter could also potentially benefit this approach by more sensitive lesion characteristics. 54 In conclusion, by providing evidence for an association between imaging-based brain disconnectome mapping and a peripheral biomarker reflecting axonal damage in patients with multiple sclerosis, these findings establish a neuropathological correlate of brain white matter…”

Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study

“…Accumulating evidence has demonstrated abnormal patterns of brain functional connectivity (FC) in MS patients as compared to healthy controls (HCs). 4,[6][7][8][9][10][11][12] While extensive evidence shows that FC abnormalities are associated with clinical disability in MS, 4,[6][7][8][9][10]12 there is a complex pattern of increased and decreased connectivity, both between brain regions directly affected by lesions, as well as putative secondary cascade effects in distal brain regions. 4 In addition, the heterogeneity across patients in lesions location is likely to further contribute to individual differences in FC aberrations in MS. 4,13 The complex interplay between FC dysregulation and clinical impairment cannot be reduced to the effects of local FC increase or decrease in a cross-sectional setting.…”

“…4,[6][7][8][9][10][11][12] While extensive evidence shows that FC abnormalities are associated with clinical disability in MS, 4,[6][7][8][9][10]12 there is a complex pattern of increased and decreased connectivity, both between brain regions directly affected by lesions, as well as putative secondary cascade effects in distal brain regions. 4 In addition, the heterogeneity across patients in lesions location is likely to further contribute to individual differences in FC aberrations in MS. 4,13 The complex interplay between FC dysregulation and clinical impairment cannot be reduced to the effects of local FC increase or decrease in a cross-sectional setting. 4,13 A longitudinal, individual-based and connectome-wide approach that accounts for FC stability Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study following structural damage is warranted to better understand the complex interplay between brain lesions, disease progression and heterogeneous FC aberrations in MS. 4,[13][14][15] This can be conceptualized as connectome stability, where the instability could refer to both compensatory 'good' changes, and aberrant connectivity caused by lesions giving rise to disorganization in FC (like maladaptation).…”

Coupling structure and function in early MS: How a less diverse repertoire of brain function could lead to clinical progression

“…Multiple sclerosis (MS) is characterized by extensive tissue damage in the central nervous system (CNS), which affects both the structural and functional brain network and its individual connections. Recent evidence has shown that network abnormalities in MS play an important role in complex symptoms such as cognitive impairment, 1 although interpreting these findings has been difficult. For instance, increased functional connectivity has been described as beneficial, maladaptive or both at the same time.…”

“…For instance, increased functional connectivity has been described as beneficial, maladaptive or both at the same time. 1 To address this problem, the field has since moved towards more advanced network techniques, indicating that clinical progression is related to a sudden loss of network efficiency, the so-called network collapse. 2 However, these studies have mostly been performed in relatively late MS stages, leaving behind a crucial lack of knowledge on early MS. Taken together, we are currently unable to predict which patient is most at risk for the network collapse and why.…”