Structural connectivity in multiple sclerosis and modeling of disconnection

2019 ◽  
Vol 26 (2) ◽  
pp. 220-232 ◽  
Author(s):  
Elisabetta Pagani ◽  
Maria A Rocca ◽  
Ermelinda De Meo ◽  
Mark A Horsfield ◽  
Bruno Colombo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Structural Connectivity ◽  
Progressive Multiple Sclerosis ◽  
Brain Network ◽  
Magnetic Resonance Imaging Mri ◽  
Cortical Regions ◽  
Diffusion Tensors ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Network Metrics ◽  
The Brain

Background: Multiple sclerosis (MS) is characterized by focal white matter damage, and when the brain is modeled as a network, lesions can be treated as disconnection events. Objective: To evaluate whether modeling disconnection caused by lesions helps explain motor and cognitive impairment in MS. Methods: Pathways connecting 116 cortical regions were reconstructed with magnetic resonance imaging (MRI) tractography from diffusion tensors averaged across healthy controls (HCs); maps of pathways were applied to 227 relapse-onset MS patients and 50 HCs to derive structural connectivity. Then, the likelihood of individual connections passing through lesions was used to model disconnection. Patients were grouped according to clinical phenotype (113 relapsing-remitting multiple sclerosis (RRMS), 69 secondary progressive multiple sclerosis (SPMS), 45 benign MS), and then network metrics were compared between groups (analysis of variance (ANOVA)) and correlated with motor and cognitive scores (linear regression). Results: Global metrics differentiated RRMS from SPMS and benign MS patients, but not benign from SPMS patients. Nodal connectivity strength replicated global results. After disconnection, few nodes were significantly different between benign MS and RRMS patients. Correlations revealed nodes pertinent to motor and cognitive dysfunctions; these became slightly stronger after disconnection. Conclusion: Connectivity did not change greatly after modeled disconnection, suggesting that the brain network is robust against damage caused by MS lesions.

scholarly journals Cervical cord myelin abnormality is associated with clinical disability in multiple sclerosis

2021 ◽  
pp. 135245852110017
Author(s):  
Lisa Eunyoung Lee ◽  
Irene M Vavasour ◽  
Adam Dvorak ◽  
Hanwen Liu ◽  
Shawna Abel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Dorsal Column ◽  
Cervical Cord ◽  
In Vivo Measurement ◽  
Subclinical Disease ◽  
Healthy Control ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability. Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability. Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration. Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%, p ⩽ 0.04) and RRMS (between 13% and 26%, p ⩽ 0.02), and ProgMS MHI was associated with EDSS ( r = 0.42–0.52) and 9HPT ( r = 0.45–0.52). Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis

2016 ◽  
Vol 22 (11) ◽  
pp. 1429-1437 ◽  
Author(s):  
Kim A Meijer ◽  
Nils Muhlert ◽  
Mara Cercignani ◽  
Varun Sethi ◽  
Maria A Ron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Domains ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tract Damage

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study (Preprint)

2019 ◽  
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

BACKGROUND Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. OBJECTIVE Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. METHODS This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. RESULTS Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. CONCLUSIONS The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16162

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study

10.2196/16162 ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. e16162
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

Background Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. Objective Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. Methods This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. Results Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. Conclusions The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16162

scholarly journals In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis

2017 ◽  
Vol 24 (8) ◽  
pp. 1029-1038 ◽  
Author(s):  
In-Young Choi ◽  
Phil Lee ◽  
Peter Adany ◽  
Abbey J Hughes ◽  
Scott Belliston ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Disease Status ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). Objective: We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. Methods: GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). Results: Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. Conclusion: Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.

827 Central Sleep Apnea in a patient with Multiple Sclerosis

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A322-A323
Author(s):  
Rahul Dasgupta ◽  
Sonja Schütz ◽  
Tiffany Braley
Keyword(s):  
Multiple Sclerosis ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disordered Breathing ◽  
Central Sleep Apnea ◽  
Progressive Multiple Sclerosis ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Demyelinating Lesions ◽  
The Brain

Abstract Introduction Sleep-disordered breathing is common in persons with multiple sclerosis (PwMS), and may contribute to debilitating fatigue and other chronic MS symptoms. The majority of research to date on SDB in MS has focused on the prevalence and consequences of obstructive sleep apnea; however, PwMS may also be at increased risk for central sleep apnea (CSA), and the utility of methods to assess CSA in PwMS warrant further exploration. We present a patient with secondary progressive multiple sclerosis who was found to have severe central sleep apnea on WatchPAT testing. Report of case(s) A 61 year-old female with a past medical history of secondary progressive multiple sclerosis presented with complaints of fragmented sleep. MRI of the brain, cervical spine, and thoracic spine showed numerous demyelinating lesions in the brain, brainstem, cervical, and thoracic spinal cord. Upon presentation, the patient noted snoring, witnessed apneas, and daytime sleepiness. WatchPAT demonstrated severe sleep apnea, with a pAHI of 63.3, and a minimum oxygen saturation of 90%. The majority of the scored events were non-obstructive in nature (73.1% of all scored events), and occurred intermittently in a periodic fashion. Conclusion The differential diagnosis of fatigue in PwMS should include sleep-disordered breathing, including both obstructive and central forms of sleep apnea. Demyelinating lesions in the brainstem (which may contribute to impairment of motor and sensory networks that control airway patency and respiratory drive), and progressive forms of MS, have been linked to both OSA and CSA. The present data illustrate this relationship in a person with progressive MS, and offer support for the WatchPAT as a cost-effective means to evaluate for both OSA and CSA in PwMS, while reducing patient burden. PwMS may be at increased risk for CSA. Careful clinical consideration should be given to ordering appropriate sleep testing to differentiate central from obstructive sleep apnea in PwMS, particularly for patients with demyelinating lesions in the brainstem. Support (if any) 1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014 Feb 15;10(2):155–62. doi: 10.5664/jcsm.3442. PMID: 24532998; PMCID: PMC3899317.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
Author(s):  
Céline Louapre ◽  
Sindhuja T Govindarajan ◽  
Costanza Giannì ◽  
Nancy Madigan ◽  
Jacob A Sloane ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Focal Lesions ◽  
Thalamic Degeneration ◽  
Relapsing Remitting ◽  
Thalamic Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

At the heart of primary progressive multiple sclerosis: three cases with diffuse MRI abnormalities only

2008 ◽  
Vol 14 (3) ◽  
pp. 428-430 ◽  
Author(s):  
JNP Zwemmer ◽  
JCJ Bot ◽  
B. Jelles ◽  
F. Barkhof ◽  
CH Polman
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Focal Lesions ◽  
Primary Progressive ◽  
Magnetic Resonance Imaging Mri ◽  
Brain And Spinal Cord ◽  
Made In

We present three patients with a clinical course and cerebrospinal fluid findings consistent with a diagnosis of primary progressive multiple sclerosis (PPMS). Extensive and repeated magnetic resonance imaging (MRI) examinations showed only diffuse abnormality in brain and spinal cord, but no focal lesions. We propose that these cases represent the most pure form of PPMS, even though according to currently applied criteria this diagnosis can not be made in the absence of focal lesions on MRI. Multiple Sclerosis 2008; 14: 428—430. http://msj.sagepub.com

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

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