Sara Llufriu

• Doctor of Medicine
• Group Leader at Hospital Clínic de Barcelona

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject’s sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the...

People with multiple sclerosis (MS) often present with cognitive deficits that cannot fully be attributed to focal brain alterations. Whole-brain network changes show stronger relations, but MS network insights have mostly focused on either structural or functional (single-layer) networks, while recent work has shown the importance of multilayer fr...

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we in...

Background and objectives The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS). Methods Antibody responses to Epstein–Barr virus (EBV), specifically to...

Background and objectives: The role of the complement system in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is not completely understood, and studies exploring its potential utility for diagnosis and prognosis are lacking. We aimed to investigate the value of complement factors (CFs) as diagnostic and prognostic biomark...

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. Structures affected in MS include the corpus callosum, connecting the hemispheres. Studies have shown that in mammalian brains, structural connectivity is organized according to a conservation principle, an inverse relationship between intra- and interhe...

Background and objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-ag...

Accurate detection of white matter (WM) lesions is essential for diagnosing and monitoring Multiple Sclerosis (MS), but manual lesion identification is challenging and time-consuming. This study employs the “no new U-Net” (nnU-Net) version 2 architecture to enhance the lesion segmentation process. We trained our model with a fine-tuned version of t...

Multiple sclerosis (MS) is a chronic autoimmune disease that predominantly affects the central nervous system (CNS) and is a leading cause of neurological disability among young adults. MS diagnosis heavily relies on clinical symptoms coupled with the detection of demyelinating lesions in the CNS, as depicted in conventional magnetic resonance imag...

Background and Objectives Recovery of vision after acute optic neuritis (AON) is critical to improving the quality of life of people with demyelinating diseases. The objective of the study was to prospectively assess the changes in visual acuity, retinal layer thickness, and cortical visual network in patients with AON to identify the predictors of...

Background and objectives: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. Methods: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MO...

Objectives In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells. Methods CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis a...

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their r...

The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in a...

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new de...

Background and objectives: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this stu...

Background and objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). Methods: Sixty-eight patients with P...

We aimed to compare the ability of diffusion tensor imaging and multi‐compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy‐six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T m...

Objective To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), aquaporin‐4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing–remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions...

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject’s sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the...

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phos...

Background Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. Methods We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseli...

Background We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease. Method We quantified the peripapillary retinal nerve fibre (pRFNL) a...

Background We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). Methods A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in...

Multiple sclerosis is a chronic autoimmune disease that affects the central nervous systems. The detection of new lesions through conventional magnetic resonance imaging is particularly important in the management of people with multiple sclerosis. The advancements in machine learning technology in recent years have significantly transformed the an...

T2-hyperintense lesions are the key imaging marker of multiple sclerosis (MS). Previous studies have shown that the white matter surrounding such lesions is often also affected by MS. Our aim was to develop a new method to visualize and quantify the extent of white matter tissue changes in MS based on relaxometry properties. We applied a fast, mult...

Background and Objective In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or p...

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS...

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. Aim: To synthesise the content presented at the 15th edition of the Pos...

Background We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. Methods Clinical information and brain MRIs were collected from 221 healthy individuals and 823 people wit...

Background. We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. Methods. Clinical information and brain magnetic resonance images were collected from 221 healthy individu...

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 8...

Importance: The value of serum neurofilament light chain (sNfL) levels for predicting long-term disability in patients with multiple sclerosis (MS) remains controversial. Objective: To assess whether high sNfL values are associated with disability worsening in patients who underwent their first demyelinating MS event. Design, setting, and parti...

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from...

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatm...

The relationship between structural connectivity (SC) and functional connectivity (FC) captured from magnetic resonance imaging, as well as its interaction with disability and cognitive impairment, is not well understood in people with multiple sclerosis (pwMS). The Virtual Brain (TVB) is an open-source brain simulator for creating personalized bra...

Background Multiple Sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging, and multimodal biomarkers to define the risk of disease activity. Methods We have analyzed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centers, collecting disability scales at basel...

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...

Multisite machine-learning neuroimaging studies need to remove the differences between sites to avoid effects of the site (EoS) that may either prevent or fraudulently help the creation of prediction models, leading to impoverished or inflated prediction accuracy. However, we have shown earlier that current Methods Aiming to Remove the EoS (MAREoS,...

This study describes the clinical characteristics, diagnostic results, treatment regimens, and clinical course of a cohort of patients with Susac syndrome (SS). It is a retrospective observational study of all patients with the diagnosis of SS evaluated at the Hospital Clinic (Barcelona, Spain) between March 2006 and November 2020. Nine patients we...

The consequences of extremely intense long‐term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose‒response relationship, and mechanisms in a rat model of endurance training. Five‐week‐old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sed...

Background Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive–psychiatric outcomes and could serve as prognostic biomarkers. Methods In this prospect...

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients with the Expan...

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by demyelinating lesions that are often visible on magnetic resonance imaging (MRI). Segmentation of these lesions can provide imaging biomarkers of disease burden that can help monitor disease progression and the imaging response to treatment. Manual delineation of MRI lesions i...

In recent years, research on network analysis applied to MRI data has advanced significantly. However, the majority of the studies are limited to single networks obtained from resting-state fMRI, diffusion MRI, or gray matter probability maps derived from T1 images. Although a limited number of previous studies have combined two of these networks,...

Objective: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. Methods: Eighty MOGAD p...

In multiple sclerosis (MS), cognitive impairment seems highly related to the neurodegenerative component of the disease. It is unknown whether the assessment of the mean upper cervical cord area (MUCCA), a measure highly related to neuroaxonal damage, can help in predicting cognitive decline over the grey matter volume (GMV). Moreover, the value of...

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their sero...

Objective To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). Methods Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in b...

Objective This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). Methods CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified in...

(1) Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who u...

Quadrantanopia caused by inadvertent severing of Meyer's Loop of the optic radiation is a well-recognised complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer's Loop varies considerably between individuals. Quantifying this for individual patients is thus an important step...

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease...

In a companion paper by Cohen-Adad et al . we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 par...

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. Th...

Quantitative diffusion imaging techniques enable the characterization of tissue microstructural properties of the human brain “in vivo”, and are widely used in neuroscientific and clinical contexts. In this review, we present the basic physical principles behind diffusion imaging and provide an overview of the current diffusion techniques, includin...

Background To develop a regression neural network for the reconstruction of lesion probability maps on Magnetic Resonance Fingerprinting using echo-planar imaging (MRF-EPI) in addition to $$T_1$$ T 1 , $${T_2}^*$$ T 2 ∗ , NAWM, and GM- probability maps. Methods We performed MRF-EPI measurements in 42 patients with multiple sclerosis and 6 healthy...

Introduction: For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim: This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 1...

Aim: To evaluate the reliability of synthetic magnetic resonance imaging (SyMRI) for detecting complications associated with subarachnoid haemorrhage (SAH), such as ischaemic lesions, hydrocephalus, or bleeding complications. Materials and methods: Twenty patients with SAH, who underwent a conventional brain MRI and a SyMRI on a 3 T MRI machine....

Introduction: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). Aim: This...

Purpose: Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS). Methods: We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the...

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a surface-based diffusion MRI processing tool to investigate regional modifications of microstructure and volume loss in GM at different time-points of the disease, and their relationship to disability. We studied 54 healthy...

Purpose To develop a regression neural network for the reconstruction of lesion probability maps on Magnetic Resonance Fingerprinting using echo-planar imaging (MRF-EPI) in addition to T 1 , T 2 * , NAWM, and GM- probability maps. Methods We performed MRF-EPI measurements in 42 patients with multiple sclerosis and 6 healthy volunteers along two sit...

Objective To investigate the incidence of coronavirus disease 2019 (COVID-19) in a single-center cohort of patients with MS and to explore the contribution of their comorbidities and therapies to the outcome. Methods A cross-sectional mixed-method study was conducted involving an email-based, self-administered questionnaire sent on May 21, 2020, t...

Background Fractal geometry measures the morphology of the brain and detects CNS damage. We aimed to assess the longitudinal changes on brain’s fractal geometry and its predictive value for disease worsening in patients with Multiple Sclerosis (MS). Methods We prospectively analyzed 146 consecutive patients with relapsing-remitting MS with up to 5...

Purpose To develop an accelerated postprocessing pipeline for reproducible and efficient assessment of white matter lesions using quantitative magnetic resonance fingerprinting (MRF) and deep learning. Methods MRF using echo‐planar imaging (EPI) scans with varying repetition and echo times were acquired for whole brain quantification of T1 and T2∗...

Background Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs). Objective To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes. Methods Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific O...

Background and aim There is increasing interest regarding SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory diseases (AI/IMID) with some discrepancies in different cohorts about their risk and outcomes. The aim was to describe a multidisciplinary cohort of patients with AI/IMID and symptomatic SARS-CoV-2 infection in...

Background: Cognitive reserve (CR) could attenuate the impact of the brain burden on the cognition in people with multiple sclerosis (PwMS). Objective: To explore the relationship between CR and structural brain connectivity and investigate their role on cognition in PwMS cognitively impaired (PwMS-CI) and cognitively preserved (PwMS-CP). Methods:...

Diffusion magnetic resonance imaging can reveal quantitative information about the tissue changes in multiple sclerosis. The recently developed multi-compartment spherical mean technique can map different microscopic properties based only on local diffusion signals, and it may provide specific information on the underlying microstructural modificat...

Understanding of the role of focal inflammation, a treatable feature, on neuro-axonal injury, is paramount to optimize neuroprotective strategy in MS. To quantify the impact of focal inflammatory activity on the rate of neuro-axonal injury over the MS course. We quantified the annualized rates of change in peripapillary retinal nerve fiber layer, g...

Quadrantanopia caused by inadvertent severing of Meyer’s Loop of the optic radiation is a well-recognised complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer’s Loop varies considerably between individuals. Quantifying this for individual patients is thus an important step...

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly...

Although genome‐wide association studies have identified a number of common variants associated with multiple sclerosis (MS) susceptibility, little is known about the relevance of rare variants. Here, we aimed to explore the role of rare variants in fourteen MS risk genes (FCRL1, RGS1, TIMMDC1, HHEX, CXCR5, LTBR, TSFM, GALC, TRAF3, STAT3, TNFSF14,...

Brain structural network modifications in multiple sclerosis (MS) seem to be clinically relevant. The discriminative ability of those changes to identify MS patients or their cognitive status remains unknown. Therefore, this study aimed to investigate connectivity changes in MS patients related to their cognitive status, and to define an automatic...