Paola Valsasina

San Raffaele Scientific Institute | OSR

Dysregulation of monoaminergic networks might have a role in the pathogenesis of fatigue in multiple sclerosis (MS). We investigated longitudinal changes of resting state (RS) functional connectivity (FC) in monoaminergic networks and their association with the development of fatigue in MS. Eighty-nine MS patients and 49 age- and sex-matched health...

Background In MS, functional connectivity (FC) dynamism may influence disease evolution. Objectives The objective is to assess time-varying functional connectivity (TVFC) changes over time at 2.5-year follow-up in MS patients according to physical and cognitive worsening. Methods We collected 3T magnetic resonance imaging (MRI) for TVFC assessmen...

Monoaminergic network dysfunction is thought to underpin depression in multiple sclerosis (MS) patients. However, longitudinal studies are lacking. Here, we investigated the association between development of depressive symptoms in MS and changes of resting-state functional connectivity (RS FC) within monoaminergic networks. Forty-nine MS patients...

Background: We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. Materials and methods: We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequen...

Background: We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation. Methods: This was a randomized, double-blind, placebo-controlled...

Background Monoaminergic network dysfunction may have a role in multiple sclerosis (MS) fatigue pathogenesis. Objective To investigate modifications of fatigue severity and resting state (RS) functional connectivity (FC) in monoaminergic networks of 45 fatigued MS patients after different symptomatic treatments. Methods Patients were randomly, bl...

Background: The differences in cognitive function between primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) remain unclear. We compared cognitive performance between PPMS and SPMS, and explored the structural and functional MRI correlates of their cognitive functions. Methods: Seventy-five healthy controls and 183 M...

Background Heterogeneous processes may contribute to cognitive impairment in multiple sclerosis (MS). Objective To apply a longitudinal multiparametric MRI approach to identify mechanisms associated with cognitive worsening in MS patients. Methods 3 T brain functional and structural MRI scans were acquired at baseline and after a median follow-up...

Background Altered thalamic volumes and resting state (RS) functional connectivity (FC) might be associated with physical activity (PA) and cardiorespiratory fitness (CRF) in people with progressive multiple sclerosis (PMS). Objectives To assess thalamic structural and functional alterations and investigate their correlations with PA/CRF levels in...

Multiple sclerosis (MS) is a neurological condition characterized by severe structural brain damage and by functional reorganization of the main brain networks that try to limit the clinical consequences of structural burden. Resting‐state (RS) functional connectivity (FC) abnormalities found in this condition were shown to be variable across diffe...

Disruptions to brain networks, measured using either structural (sMRI), diffusion (dMRI), or resting-state functional (rs-fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the importance of damage to regions in the core of the connectome. Here, using a multilayer network approach, we aimed to integrate these three mo...

Background Frontal cortico-subcortical dysfunction may contribute to fatigue and dual-task impairment of walking and cognition in progressive multiple sclerosis (PMS). Purpose To explore the associations among fatigue, dual-task performance and structural and functional abnormalities of frontal cortico-subcortical network in PMS. Methods Brain 3...

The Italian Neuroimaging Network Initiative (INNI) is an expanding repository of brain MRI data from multiple sclerosis (MS) patients recruited at four Italian MRI research sites. We describe the raw data quality of resting-state functional MRI (RS-fMRI) time-series in INNI and the inter-site variability in functional connectivity (FC) features aft...

Objectives To assess the effectiveness of Neuroaspis plp10 nutritional supplement when added to interferon (IFN)-β treatment in patients with relapsing-remitting multiple sclerosis (RRMS). Design A 30-month phase III multicentre, randomised, double-blind, placebo-controlled trial. Randomisation stratified by centre using a computer-generated proce...

Objective: To investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI). Methods: In this prospective study, 213 patients w...

Objectives To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients. Methods Baseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and...

Background and Objectives In multiple sclerosis (MS), functional networks undergo continuous reconfiguration and topography changes over the disease course. Here, we aimed to investigate functional networks topography abnormalities in MS and their association with disease phenotype, clinical and cognitive disability, and structural MRI damage. Met...

Background The precuneus is involved in cognition and depression; static functional connectivity (SFC) abnormalities of this region have been observed in neuromyelitis optica spectrum disorders (NMOSD). Time-varying functional connectivity (TVC) underpins dynamic variations of brain connectivity. Objective The aim of this study was to explore prec...

Multiple sclerosis (MS) is a neurological disorder affecting the central nervous system and features extensive functional brain changes that are poorly understood but relate strongly to clinical impairments. Functional magnetic resonance imaging (fMRI) is a non-invasive, powerful technique able to map activity of brain regions and to assess how suc...

The Papez circuit is central to memory and emotional processes. However, little is known about its involvement in multiple sclerosis (MS). We aimed to investigate abnormalities of resting state (RS) effective connectivity (EC) between regions of the Papez circuit in MS and their relationship with cognitive performances. Sixty-two MS patients and 64...

We aimed to investigate abnormal time-varying functional connectivity (FC) for thalamic sub-regions in multiple sclerosis (MS) and their clinical, cognitive and MRI correlates. Eighty-nine MS patients (49 relapsing-remitting [RR] MS; 40 progressive [P] MS) and 53 matched healthy controls underwent neurological, neuropsychological and resting state...

There is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. Howeve...

Background Altered callosal integrity has been associated with motor deficits in patients with multiple sclerosis (MS), but its contribution to disability has, to the knowledge of the authors, not been investigated by using multiparametric MRI approaches. Purpose To investigate structural and functional interhemispheric MRI substrates of global dis...

Objective To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients’ clinical characteristics and disease progression over the years. Methods Ninety-one patients with episodic migraine and 73 controls underwent interictal r...

Background Spatio-temporal evolution of cord atrophy in multiple sclerosis (MS) has not been investigated yet. Objective To evaluate voxel-wise distribution and 1-year changes of cervical cord atrophy in a multicentre MS cohort. Methods Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluations of 54 healthy controls (HC) and...

Background Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). Purpose To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. Study Typ...

Background Aquaporin-4 (AQP4) water channel is involved in hippocampal plasticity and is the target of neuromyelitis optica spectrum disorders (NMOSD) autoimmunity. We measured volumes of hippocampal subfields and their association with cognitive performance in AQP4-seropositive NMOSD patients. Methods Global and regional hippocampal volumes were...

Background Executive dysfunctions, including difficulties in attention, working memory, planning, and inhibition affect 15%–28% of multiple sclerosis (MS) patients. Objectives To investigate structural and functional magnetic resonance imaging (MRI) abnormalities underlying executive function (EF) in MS patients. Methods A total 116 MS patients a...

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain...

Neuropsychiatric manifestations are highly prevalent in systemic lupus erythematosus (SLE)-patients. We aimed to unravel the substrates of these manifestations by investigating abnormalities of resting state (RS) functional connectivity (FC) and their correlations with neuropsychiatric variables in SLE-patients. Thirty-two SLE-patients and 32 age-...

Objective: In multiple sclerosis (MS), clinical impairment is likely due to both structural damage and abnormal brain function. We assessed the added value of integrating structural and functional network MRI measures to predict 6.4-year MS clinical disability deterioration. Methods: Baseline 3D T1-weighted and resting-state functional MRI scans...

Background: Cognitive impairment frequently affects multiple sclerosis (MS) patients. However, its neuroanatomical correlates still need to be fully explored. We investigated the contribution of structural and functional magnetic resonance imaging (MRI) abnormalities in explaining cognitive impairment in MS. Methods: Brain dual-echo, diffusion t...

Background In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases. Purpose To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones. Methods...

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patie...

This chapter reviews the basic principles, main acquisition, and postprocessing techniques of functional magnetic resonance imaging (fMRI) applied to study multiple sclerosis (MS). First, we describe the blood-oxygenation level dependent (BOLDBlood oxygen level-dependent (BOLD)) effect and the principal analysis techniques used to process fMRIFunct...

Introduction: Dynamic functional connectivity (dFC) allows capturing recurring patterns (states) of interaction among functional networks. Here, we investigated resting state (RS) dFC abnormalities across the different clinical phenotypes of multiple sclerosis (MS) and assessed their correlation with motor and cognitive performances. Methods: RS...

Background: Fatigue in multiple sclerosis (MS) is common and disabling; medication efficacy is still not fully proven. Aim of this study was to investigate four-week modifications of fatigue severity in 45 relapsing-remitting MS patients following different symptomatic treatments, and concomitant resting state (RS) functional connectivity (FC) cha...

Objectives: Grey matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes. Methods: Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 MS patients (34 clinically...

IntroductionThe substrates of cognitive impairment in benign MS (BMS) still need to be identified. We investigated whether cognitive impairment in BMS patients is associated with specific patterns of brain structural and functional abnormalities.Methods Thirty-seven BMS patients (EDSS score ≤ 3.0 and disease duration ≥ 15 years) and 50 healthy cont...

Background and rationale Thalamus atrophy has been linked to cognitive decline in multiple sclerosis (MS) using various segmentation methods. We investigated the consistency of the association between thalamus volume and cognition in MS for two common automated segmentation approaches, as well as fully manual outlining. Methods Standardized neurop...

Background: Hand-motor impairment affects a large proportion of multiple sclerosis (MS) patients; however, its substrates are still poorly understood. Objectives: To investigate the association between global disability, hand-motor impairment, and alterations in motor-relevant structural and functional magnetic resonance imaging (MRI) networks in...

Background The spinal cord is commonly involved in patients with neuromyelitis optica spectrum disorders (NMOSDs). However, the relationship between inflammation and atrophy remains unclear. Purpose To characterize the spatial distribution of T1-hypointense lesions in the spinal cord at MRI, its association with cord atrophy, and its correlation wi...

Background Longitudinal evolution of cortical thickness (CTh) in different MS phenotypes has been rarely studied. Aim To investigate the regional pattern and 1-year progression of cortical thinning in relapsing-remitting (RR) and progressive (P) MS. Methods 3T high-resolution T1-weighted magnetic resonance imaging (MRI) was obtained from 86 patie...

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions...

Resting state (RS) functional connectivity (FC) abnormalities of brain networks involved in pain- and multisensory processing have been disclosed in adult-migraine patients. We explored RS FC of large-scale brain networks in pediatric-migraine patients and their correlation with patients’ clinical characteristics. RS functional MRI data was acquire...

We investigated modifications of resting state dynamic functional network connectivity (dFNC) following a 2-week action observation training (AOT) in 46 right-handed healthy controls (HC) and 41 patients with multiple sclerosis (pwMS) and dominant-hand motor impairment, who were randomized to AOT or control (C) training. PwMS had decreased baseline...

Objective: To characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset. Methods: MRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 second...

Objectives: Spinal cord atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on MRI using segmentation-based methods suffer from measurement variability, especially in multicentre studies. We compared the generalised boundary shift integral (GBSI), a registration-based method, with standard segmentation...

Background Mechanisms associated with cervical spinal cord (CSC) and upper thoracic spinal cord (TSC) atrophy in multiple sclerosis (MS) are poorly understood. Objective To assess the influence of brain, CSC and TSC T2-hyperintense lesions on cord atrophy and disability in MS. Methods Thirty-four MS patients underwent 3T brain, cervical and thora...

Background: Systemic lupus erythematosus (SLE) is an immune-mediated disease that may affect the nervous system. We explored the topographical organization of structural and functional brain connectivity in SLE-patients and its correlation with neuropsychiatric involvement and autoantibody profiles. Methods: Graph theoretical analysis was applie...

Functional magnetic resonance imaging (fMRI) at resting state (RS) has been widely used to characterize the main brain networks. Functional connectivity (FC) has been mostly assessed assuming that FC is static across the whole fMRI examination. However, FC is highly variable at a very fast time-scale, as demonstrated by neurophysiological technique...

Background: Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs). Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correl...