scholarly journals Functional network dynamics in progressive multiple sclerosis

2020 ◽  
Author(s):  
Giulia Bommarito ◽  
Anjali Tarun ◽  
Younes Farouj ◽  
Maria Giulia Preti ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Large Scale ◽  
Dynamic Properties ◽  
Progressive Multiple Sclerosis ◽  
Default Mode ◽  
Functional Reorganization ◽  
Functional Dynamics ◽  
One Year ◽  
Progressive Stage

AbstractFunctional reorganization at the progressive stage of multiple sclerosis has received limited attention, despite the fact that functional changes are known to occur. Characterizing large-scale network dynamics at rest has the potential to provide new insights into the complexity of such functional alterations. In this case-control study, we explored the dynamic properties of large-scale functional networks during rest in 25 healthy controls and 32 patients with progressive multiple sclerosis, using the innovation-driven co-activation patterns. Thirty-five subjects also underwent a one-year follow-up examination. Partial least squares correlation analysis was applied to explore the relationship between functional dynamics and clinical disability. We observed a reduced dynamic engagement of the anterior default mode network and its coupling with the executive-control network in patients with progressive multiple sclerosis compared to controls, at baseline and follow-up. The global and motor disabilities were related to functional dynamics of subcortical, sensory-motor and posterior default mode network, while the cognitive disability was associated to the altered dynamics of anterior default mode, visual and temporal networks. These findings reveal that the anterior default mode functional recruitment and its interaction with other networks play a major role in the functional reorganization occurring during the progressive stage of multiple sclerosis. Also, the dynamic properties of large-scale functional networks are steady over one year and unveil the intricate relationship between brain function and clinical disability.

scholarly journals Multiple challenges for people after transitioning to secondary progressive multiple sclerosis: a qualitative study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e026421 ◽  
Author(s):  
Angeliki Bogosian ◽  
Myfanwy Morgan ◽  
Rona Moss-Morris
Keyword(s):  
Multiple Sclerosis ◽  
Qualitative Interviews ◽  
Healthcare Services ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Multiple Challenges ◽  
Physical Challenges ◽  
Progressive Stage

ObjectivesTransitioning to secondary progressive multiple sclerosis (SPMS) is demanding for both patients and healthcare professionals. The particular challenges and the ways patients cope are poorly understood. The present study examines what challenges people face when diagnosed with SPMS by exploring experiences of people who have transitioned recently (up to 5 years).DesignSemistructured qualitative interviews at two time points a year apart. Interviews were analysed using inductive thematic analysis.SettingUK.ParticipantsWe interviewed 21 people at baseline and 17 participated in the follow-up interviews.ResultsThe majority of participants reported expecting to transition to SPMS, and the diagnosis did not make much difference to them. Participants described increasing emotional and physical challenges after transitioning to SPMS and between the first and second interviews. Planning, using distractions and maintaining social roles helped participants cope with the increased challenges. The same coping strategies were used between the two interviews. Participants felt there was not much left to do regarding the management of their symptoms. A key theme was the sense of abandonment from healthcare services after transitioning to SPMS.ConclusionsAfter transitioning to SPMS, people are faced with multiple challenges. Participants described a lack of directions for symptoms management and lack of support from the healthcare system. An integrated multidisciplinary healthcare approach is crucial at the progressive stage of the disease to alleviate feelings of helplessness and promote symptom management.

scholarly journals CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Jeppe Romme Christensen ◽  
Lars Börnsen ◽  
Mohsen Khademi ◽  
Tomas Olsson ◽  
Poul Erik Jensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Underlying Disease ◽  
Progressive Multiple Sclerosis ◽  
Axonal Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Relapsing Remitting ◽  
One Year

Background: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. Objectives: To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS. Methods: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing–remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. Results: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased. Conclusion: CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.

scholarly journals Altered anterior default mode network dynamics in progressive multiple sclerosis

2021 ◽  
pp. 135245852110181
Author(s):  
Giulia Bommarito ◽  
Anjali Tarun ◽  
Younes Farouj ◽  
Maria Giulia Preti ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Default Mode Network ◽  
Dynamic Properties ◽  
Brain Activity ◽  
Progressive Multiple Sclerosis ◽  
Functional Networks ◽  
Cognitive Disability ◽  
Dynamic Activity ◽  
Default Mode ◽  
Motor Network

Background: Modifications in brain function remain relatively unexplored in progressive multiple sclerosis (PMS), despite their potential to provide new insights into the pathophysiology of the disease at this stage. Objectives: To characterize the dynamics of functional networks at rest in patients with PMS, and the relation with clinical disability. Methods: Thirty-two patients with PMS underwent clinical and cognitive assessment. The dynamic properties of functional networks, retrieved from transient brain activity, were obtained from patients and 25 healthy controls (HCs). Sixteen HCs and 19 patients underwent a 1-year follow-up (FU) clinical and imaging assessment. Differences in the dynamic metrics between groups, their longitudinal changes, and the correlation with clinical disability were explored. Results: PMS patients, compared to HCs, showed a reduced dynamic functional activation of the anterior default mode network (aDMN) and a decrease in its opposite-signed co-activation with the executive control network (ECN), at baseline and FU. Processing speed and visuo-spatial memory negatively correlated to aDMN dynamic activity. The anti-couplings between aDMN and auditory/sensory-motor network, temporal-pole/amygdala, or salience networks were differently associated with separate cognitive domains. Conclusion: Patients with PMS presented an altered aDMN functional recruitment and anti-correlation with ECN. The aDMN dynamic functional activity and interaction with other networks explained cognitive disability.

scholarly journals Cyclophosphamide Versus Rituximab in Progressive Forms of Multiple Sclerosis

2020 ◽  
Author(s):  
Masoud Etemadifar ◽  
Shadi Ghourchian ◽  
Nazanin Mahinparvar ◽  
Mehri Salari ◽  
Fatemeh Etemadifar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
The Other ◽  
Medical Sciences ◽  
Mri Findings ◽  
Disability Score ◽  
Radiologic Findings ◽  
Spss Software ◽  
And Gender

This study aimed to compare the efficacy of rituximab versus Cyclophosphamide on active secondary progressive multiple sclerosis (SPMS). The randomized clinical trial was performed from 2015 to 2017 in multiple sclerosis (MS) clinics affiliated to Isfahan MS society (IMSS). Patients were randomized to two groups, and one of them received Rituximab that was repeated every six months in case of medical indication. The other one received a monthly pulse of methylprednisolone plus cyclophosphamide (Endoxan, Baxter, UK) until two years. Expanded disabilities status scale (EDSS), clinical, and MRI findings were assessed every six months. Statistical analysis was performed using SPSS software. 39 patients in the Rituximab group and 30 in the Cyclophosphamide group with similar age and gender distribution were entered for analysis. At baseline, the mean number of attacks in the Rituximab group was significantly more than the Cyclophosphamide group (P=0.0001). After 6, 12, and 18 months of treatment, the rate of attacks was similar between groups although it increased significantly in the Rituximab group (P=0.030) after 24 months of treatment. EDSS was increased in the Rituximab group more than the other group at the end of the study. Both drugs were well-tolerated by patients. The EDSS was increased in the Rituximab group but the disability score did not worsen in the Cyclophosphamide group. Both therapies were associated with a reduction in disease attacks and improvement in radiologic findings in a two-year period of follow-up. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(8):484-491.

scholarly journals Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain

2021 ◽  
Vol 11 ◽  
Author(s):  
Angel P. Sempere ◽  
Leticia Berenguer-Ruiz ◽  
Ines Borrego-Soriano ◽  
Amparo Burgos-San Jose ◽  
Luis Concepcion-Aramendia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Real World ◽  
Median Number ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Clinical Practice Setting ◽  
Number Of Treatment ◽  
Relapsing Multiple Sclerosis

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting.Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded.Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4–6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious.Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

scholarly journals Improved relapse recovery in paediatric compared to adult multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2733-2741
Author(s):  
Tanuja Chitnis ◽  
Greg Aaen ◽  
Anita Belman ◽  
Leslie Benson ◽  
Mark Gorman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional System ◽  
Progressive Multiple Sclerosis ◽  
Age Related ◽  
Younger Age ◽  
Disability Status ◽  
The Us ◽  
The Difference ◽  
Effect Of Age

Abstract Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.

482Direct oral anticoagulant rivaroxaban in very old and frail patients: A one-year prospective follow-up of a large-scale cohort (SAFIR-AC)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Hanon ◽  
J Vidal ◽  
E Chaussade ◽  
J P David ◽  
N Boulloche ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Major Bleeding ◽  
Large Scale ◽  
Bleeding Risk ◽  
Geriatric Population ◽  
Very Old ◽  
The Mean ◽  
One Year ◽  
The One

Abstract Background/Introduction Age is one of the strongest predictors/risk factors for ischemic stroke in subjects with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) have been shown to be effective in the prevention of this condition; however, clinical evidence on bleeding risk with this therapeutic strategy in very old and frail geriatric patients is poor. Purpose To assess bleeding risk in French geriatric patients aged ≥80 years and diagnosed with AF newly treated with rivaroxaban. Methods Subjects, presenting to one of 33 geriatric centers, with non-valvular AF and recent initiation of a treatment with rivaroxaban were enrolled in the study and followed-up every 3 months for 12 months. Clinical and routine laboratory data and evaluation scores, such as HAS-BLED, HEMORR2HAGES, ATRIA, and CHA2DS2-VASc, as well as comprehensive geriatric evaluation were reported. Major bleeding, as defined in ROCKET AF study, was reported at each visit, and this primary outcome was adjudicated by an independent committee. Results of this cohort were compared with findings from a similar cohort treated with vitamin K antagonists (VKAs) from the same centers (n=924). Results A total of 1045 subjects were enrolled in the study of whom 995 (95%) had a one-year follow-up (analyzed population). The mean (standard deviation (SD)) age was 86.0 (4.3) years, with the majority of patients being female (61%), 23% aged 90 years or older, and 48% having an estimated glomerular filtration rate (eGFR) <50 mL/min. The main comorbidities were hypertension in 77% of subjects, malnutrition 49%, anemia 43%, dementia 39%, heart failure 36%, and falls 27%. The mean (SD) score for CHA2DS2-VASc was 4.8 (1.4), HAS-BLED 2.4 (0.9), Mini-Mental State Examination (MMSE) 21.5 (6.9), Activities of Daily Living (ADL) 4.4 (1.9), and Charlson Comorbidity Index 6.7 (2.0). The one-year rate of major bleeding events was 6.4% of which 0.8% were fatal and 1.1% intracranial hemorrhages (ICH), whereas the one-year rate of ischemic stroke was 1.4% and all-cause mortality 17.9%. Computed with VKA cohort findings and adjusted for age, gender, eGFR and Charlson score, this would result in a hazard ratio of 0.54 (95% confidence interval [CI], 0.38 to 0.78) for major bleeding, 0.36 (0.17 to 0.76) for ICH, 0.62 (0.29 to 1.33) for ischemic stroke, and 0.82 (0.65 to 1.02) for all-cause mortality, in favor of rivaroxaban. Conclusions This is the first large-scale prospective study in geriatric population in AF subjects treated with DOAC (rivaroxaban) Major bleeding risk appeared higher in very old than younger population, however major bleeding and ICH rates were significantly lower with rivaroxaban than with VKAs when used in the same geriatric population. This study indicates that Rivaroxaban can be used in very old and frail patients for the treatment of non-valvular AF. Acknowledgement/Funding Unrestricted grant from Bayer

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

2004 ◽  
Vol 10 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Emmanuelle Cassol ◽  
Jean-Philippe Ranjeva ◽  
Danielle Ibarrola ◽  
Claude Mékies ◽  
Claude Manelfe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Lesion Load ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
One Year ◽  
Diffusion Tensor Imaging Dti

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

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