scholarly journals Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis

2019 ◽  
Vol 12 ◽  
pp. 175628641983867 ◽  
Author(s):  
Vinzenz Fleischer ◽  
Nabin Koirala ◽  
Amgad Droby ◽  
René-Maxime Gracien ◽  
Ralf Deichmann ◽  
...  
Keyword(s):  
Disease Activity ◽  
Gray Matter ◽  
Network Dynamics ◽  
Network Connectivity ◽  
Clustering Coefficient ◽  
Local Network ◽  
Cortical Atrophy ◽  
Disease Manifestation ◽  
Local Efficiency ◽  
Relapsing Remitting

Background: Network science provides powerful access to essential organizational principles of the brain. The aim of this study was to investigate longitudinal evolution of gray matter networks in early relapsing–remitting MS (RRMS) compared with healthy controls (HCs) and contrast network dynamics with conventional atrophy measurements. Methods: For our longitudinal study, we investigated structural cortical networks over 1 year derived from 3T MRI in 203 individuals (92 early RRMS patients with mean disease duration of 12.1 ± 14.5 months and 101 HCs). Brain networks were computed based on cortical thickness inter-regional correlations and fed into graph theoretical analysis. Network connectivity measures (modularity, clustering coefficient, local efficiency, and transitivity) were compared between patients and HCs, and between patients with and without disease activity. Moreover, we calculated longitudinal brain volume changes and cortical atrophy patterns. Results: Our analyses revealed strengthening of local network properties shown by increased modularity, clustering coefficient, local efficiency, and transitivity over time. These network dynamics were not detectable in the cortex of HCs over the same period and occurred independently of patients’ disease activity. Most notably, the described network reorganization was evident beyond detectable atrophy as characterized by conventional morphometric methods. Conclusion: In conclusion, our findings provide evidence for gray matter network reorganization subsequent to clinical disease manifestation in patients with early RRMS. An adaptive cortical response with increased local network characteristics favoring network segregation could play a primordial role for maintaining brain function in response to neuroinflammation.

scholarly journals White matter microstructure and network-connectivity in emerging adults with subclinical psychotic experiences

2019 ◽  
Vol 14 (5) ◽  
pp. 1876-1888
Author(s):  
Stijn Michielse ◽  
Iris Lange ◽  
Jindra Bakker ◽  
Liesbet Goossens ◽  
Simone Verhagen ◽  
...  
Keyword(s):  
White Matter ◽  
Emerging Adults ◽  
Rating Scale ◽  
Mean Diffusivity ◽  
Network Connectivity ◽  
Clustering Coefficient ◽  
Positive Symptom ◽  
Psychotic Experiences ◽  
Local Efficiency ◽  
White Matter Microstructure

AbstractGroup comparisons of individuals with psychotic disorder and controls have shown alterations in white matter microstructure. Whether white matter microstructure and network connectivity is altered in adolescents with subclinical psychotic experiences (PE) at the lowest end of the psychosis severity spectrum is less clear. DWI scan were acquired in 48 individuals with PE and 43 healthy controls (HC). Traditional tensor-derived indices: Fractional Anisotropy, Axial Diffusivity, Mean Diffusivity and Radial Diffusivity, as well as network connectivity measures (global/local efficiency and clustering coefficient) were compared between the groups. Subclinical psychopathology was assessed with the Community Assessment of Psychic Experiences (CAPE) and Montgomery–Åsberg Depression Rating Scale (MADRS) questionnaires and, in order to capture momentary subclinical expression of psychosis, the Experience Sampling Method (ESM) questionnaires. Within the PE-group, interactions between subclinical (momentary) symptoms and brain regions in the model of tensor-derived indices and network connectivity measures were investigated in a hypothesis-generating fashion. Whole brain analyses showed no group differences in tensor-derived indices and network connectivity measures. In the PE-group, a higher positive symptom distress score was associated with both higher local efficiency and clustering coefficient in the right middle temporal pole. The findings indicate absence of microstructural white matter differences between emerging adults with subclinical PE and controls. In the PE-group, attenuated symptoms were positively associated with network efficiency/cohesion, which requires replication and may indicate network alterations in emerging mild psychopathology.

scholarly journals Voxel-based correlation of 18F-THK5351 accumulation with gray matter structural networks in cognitively normal older adults

2020 ◽  
Author(s):  
Yoko Shigemoto ◽  
Daichi Sone ◽  
Norihide Maikusa ◽  
Yukio Kimura ◽  
Fumio Suzuki ◽  
...  
Keyword(s):  
Older Adults ◽  
Gray Matter ◽  
Clustering Coefficient ◽  
Local Network ◽  
Single Subject ◽  
Characteristic Path Length ◽  
Cognitively Normal ◽  
Network Measures ◽  
Positron Emission ◽  
Gray Matter Network

Abstract Background No previous studies have examined the correlations between tau and gray matter network alterations in cognitively normal (CN) older adults. Here, we investigated the correlations between 18F-THK5351 and local network measures at the voxel level. Material and methods We recruited 47 amyloid-negative CN older adults (65.0 ± 7.9 years, 55% women). All participants underwent structural magnetic resonance imaging (MRI) and 11C-Pittsburgh compound-B and 18F-THK5351 positron emission tomography (PET) scans. Single-subject gray matter networks extracted from T1-weighted MRI data based on cortical similarities were analyzed using the graph theoretical approach. The 18F-THK5351 PET and four local network measures (betweenness centrality, clustering coefficient, characteristic path length, and degree) were evaluated to calculate voxel-wise correlations among the imaging modalities. Result Significant positive correlations between 18F-THK5351 and local network measures were detected in the bilateral caudate. Conclusion Our findings suggest that tau and neuroinflammation in CN older adults may influence local gray matter network in the caudate.

scholarly journals Discontinuation and dose reduction of rituximab in relapsing–remitting multiple sclerosis

2021 ◽  
Author(s):  
Malin Boremalm ◽  
Peter Sundström ◽  
Jonatan Salzer
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Dose Reduction ◽  
Inflammatory Disease ◽  
University Hospital ◽  
Full Dose ◽  
Reduced Dose ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

scholarly journals α4-integrin receptor desaturation and disease activity return after natalizumab cessation

2017 ◽  
Vol 4 (5) ◽  
pp. e388 ◽  
Author(s):  
Tobias Derfuss ◽  
John M. Kovarik ◽  
Ludwig Kappos ◽  
Marina Savelieva ◽  
Richa Chhabra ◽  
...  
Keyword(s):  
Disease Activity ◽  
Time Course ◽  
Receptor Occupancy ◽  
Lesion Volume ◽  
Integrin Receptor ◽  
Parallel Group ◽  
Increased Risk ◽  
Relapsing Remitting ◽  
First Relapse ◽  
Study Support

Objective:To describe the time course of α4-integrin receptor desaturation and disease activity return in patients with relapsing-remitting MS who discontinued natalizumab and to investigate baseline and on-study predictors for the recurrence of disease activity.Methods:In the course of TOFINGO, a 32-week, patient- and rater-blinded multicenter, parallel-group study, we performed MRI, counted relapses, and measured α4-integrin receptor occupancy (RO) at baseline and 8, 12, 16, 20, and 24 weeks. The relationship between RO and total number of new T1 gadolinium-enhancing (Gd+) lesions was modeled using Poisson linear regression.Results:Patients (N = 142) were randomized (1:1:1) to 8-, 12-, or 16-week washout (WO) groups. At randomization, the median RO in the 8-, 12-, and 16-week WO groups was 94.5%, 92.4%, and 90.9%, which declined to 79.8%, 30.7%, and 8.7% after 8, 12, and 16 weeks of WO, respectively. The percentage of patients with new T1 Gd+ lesions increased with longer WO period before commencing fingolimod: 2.1% (8 weeks), 9.1% (12 weeks), and 50.0% (16 weeks). Overall, 71% of patients with first relapse between weeks 6 and 18 had RO values below the time-matched population median. Higher T2 lesion volume (LV) at baseline predicted a higher number of new T1 Gd+ lesions.Conclusions:A faster decline in natalizumab RO, longer WO period, and higher T2 LV at baseline were associated with an increased risk for return of inflammatory disease activity. These results provide a mechanistic rationale and, together with the main outcomes of the TOFINGO study, support initiation of fingolimod within 8 weeks of natalizumab discontinuation.ClinicalTrials.gov identifier:NCT01499667.

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