Inflammation in multiple sclerosis: consequences for remyelination and disease progression

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(5), P. 305 - 320

Published: April 14, 2023

Language: Английский

---

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Annals of Neurology, Journal Year: 2023, Volume and Issue: 94(1), P. 182 - 195

Published: March 27, 2023

Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear.This retrospective study included 2 prospective 3.0-T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients indications for lumbar puncture underwent 3-dimensional T1-weighted sequence (3D-T1) before at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). 2, WMH were enrolled from the CIRCLE had median follow-up time 1.4 years. CP lateral ventricles automatically segmented on T2 fluid-attenuated inversion recovery (FLAIR) 3D-T1, respectively. volume was expressed as ratio intracranial volume. Glymphatic measured signal percentage change baseline 8 brain locations based MRI first cohort, or noninvasive diffusion tensor image analysis along perivascular space (DTI-ALPS) index DTI second cohort.In total 52 included. Higher correlated slower rate all locations. 197 Baseline positively associated growth. Furthermore, DTI-ALPS partially mediated both load growth.Enlarged could be an indicator larger growth WMH, potentially involving impaired function. The exploration may provide novel perspective clarify mechanism pathogenesis, well other glymphatic-related disorders. ANN NEUROL 2023;94:182-195.

Language: Английский

---

Neurodegeneration and demyelination in multiple sclerosis

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

---

Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis

Brain, Journal Year: 2024, Volume and Issue: 147(4), P. 1331 - 1343

Published: Jan. 24, 2024

Abstract Cortical myelin loss and repair in multiple sclerosis (MS) have been explored neuropathological studies, but the impact of these processes on neurodegeneration irreversible clinical progression disease remains unknown. Here, we evaluated vivo cortical demyelination remyelination a large cohort people with all phenotypes MS followed up for 5 years using magnetization transfer imaging (MTI), technique that has shown to be sensitive content changes cortex. We investigated 140 (37 clinically isolated syndrome, 71 relapsing-MS, 32 progressive-MS), who were assessed at baseline after and, along 84 healthy controls, underwent 3 T-MRI protocol including MTI 1 year. Changes volume over radiological follow-up computed Jacobian integration method. Magnetization ratio was employed calculate each patient an index dynamic period. The three indices change heterogeneous across patients did not significantly differ or treatment groups. remyelination, which tended fail regions closer CSF (−11%, P < 0.001), extensive half occurred independently age, duration phenotype. Higher (β = 0.23, 0.024) lower −0.18, 0.03) associated greater atrophy year, age While extent predicted higher probability entire [odds (OR) 1.2; 0.043], reducing risk accumulating disability significant only subgroup shorter limited (OR 0.86, 0.015, area under curve 0.93). In this subgroup, 30% increase nearly halved years, relapses. Overall, our results highlight critical role dynamics cascade events leading subsequent accumulation MS. Our findings suggest early-stage compensating potential prevent neuro-axonal its long-term consequences

Language: Английский

---

Remyelination protects neurons from DLK-mediated neurodegeneration

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 23, 2024

Chronic demyelination and oligodendrocyte loss deprive neurons of crucial support. It is the degeneration their connections that drives progressive disability in demyelinating disease. However, whether chronic triggers neurodegeneration how it may do so remain unclear. We characterize two genetic mouse models inducible demyelination, one distinguished by effective remyelination other failure demyelination. While both lines feature axonal damage, mice with blocked have elevated neuronal apoptosis altered microglial inflammation, whereas efficient not improved functional recovery. Remyelination incapable show increased activation kinases downstream dual leucine zipper kinase (DLK) phosphorylation c-Jun nuclei. Pharmacological inhibition or disruption DLK block demyelinated neurons. Together, we demonstrate associated neuroprotection identify as protective strategy for chronically

Language: Английский

---

A Fully Automatic Method to Segment Choroid Plexuses in Multiple Sclerosis Using Conventional MRI Sequences

Journal of Magnetic Resonance Imaging, Journal Year: 2023, Volume and Issue: 59(5), P. 1643 - 1652

Published: Aug. 2, 2023

Background Choroid plexus (CP) volume has been recently proposed as a proxy for brain neuroinflammation in multiple sclerosis (MS). Purpose To develop and validate fast automatic method to segment CP using routinely acquired T1‐weighted FLAIR MRI. Study Type Retrospective. Population Fifty‐five MS patients (33 relapsing–remitting, 22 progressive; mean age = 46.8 ± 10.2 years; 31 women) 60 healthy controls (HC; 36.1 12.6 years, 33 women). Field Strength/Sequence 3D T2‐weighted gradient echo sequences at 3.0 T. Assessment Brain tissues were segmented on Gaussian Mixture Model (GMM) was fitted image intensities obtained from the ventricle masks of SIENAX. A second GMM then applied thresholded filtered mask. volumes automatically determined compared with those manual segmentation by two raters (with 3 10 years' experience; reference standard). previously published methods (freely available Freesurfer [FS] FS‐GMM) also standard. Expanded Disability Status Scale (EDSS) score assessed within days Computational time each technique segmentation. Statistical Tests Comparisons standard evaluated Bland Altman analysis. Dice similarity coefficients (DSC) computed assess segmentations. Volume differences between HC t‐tests correlations EDSS Pearson's correlation ( R ). P value <0.05 considered statistically significant. Results Compared segmentation, had highest accuracy (mean DSC 0.65 0.06) FS 0.37 0.08) FS‐GMM (0.58 0.06). The percentage relative −0.1% 0.23, 4.6% 2.5, −0.48% 2 method, FS, FS‐GMM, respectively. manually 0.70, 0.54, 0.56 significant found pipeline 0.2), 0.3) 0.4). (32 minutes) similar (20 5 but <25% (120 15 (125 methods. Data Conclusion This study developed an accurate easily implementable Evidence Level 1 Technical Efficacy Stage 4

Language: Английский

---

Remyelination in the Central Nervous System

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(3), P. a041371 - a041371

Published: Feb. 5, 2024

Robin J.M. Franklin1, Benedetta Bodini2,3 and Steven A. Goldman4,5 1Altos Labs Cambridge Institute of Science, CB21 6GH, United Kingdom 2Sorbonne Université, Paris Brain Institute, CNRS, INSERM, 75013, France 3Saint-Antoine Hospital, APHP, 75012, 4Center for Translational Neuromedicine, University Rochester Medical Center, Rochester, New York 14642, USA 5University Copenhagen Faculty Medicine, 2200, Denmark Correspondence: rfranklin{at}altoslabs.com

Language: Английский

---

Longitudinal enlargement of choroid plexus is associated with chronic lesion expansion and neurodegeneration in RRMS patients

Multiple Sclerosis Journal, Journal Year: 2024, Volume and Issue: 30(4-5), P. 496 - 504

Published: Feb. 6, 2024

Background and Objective: We explored dynamic changes in the choroid plexus (CP) patients with relapsing-remitting multiple sclerosis (RRMS) assessed its relationship chronic lesion expansion atrophy various brain compartments. Methods: Fifty-seven RRMS were annually for a minimum of 48 months 3D FLAIR, pre- post-contrast T1 diffusion-weighted magnetic resonance imaging (MRI). The CP was manually segmented at baseline last follow-up. Results: volume significantly increased by 1.4% annually. However, extent enlargement varied considerably among individuals (ranging from −3.6 to 150.8 mm 3 or −0.2% 6.3%). magnitude correlated central ( r = 0.70, p < 0.001) total −0.57, 0.001), white −0.61, deep grey matter −0.60, 0.001). Progressive associated 0.60, but not number new lesions. Conclusion: This study provides evidence progressive RRMS. Our findings also demonstrate that is linked lesions neurodegeneration periventricular patients.

Language: Английский

---

Multiple sclerosis: 2023 update.

PubMed, Journal Year: 2023, Volume and Issue: 4

Published: Jan. 1, 2023

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of Central Nervous System (CNS). Significant progress has been made during recent years in preventing relapses by using systemic immunomodulatory or immunosuppressive therapies. However, limited effectiveness such therapies for controlling progressive course indicates there a continuous progression independent relapse activity which may start very early course. Dissecting underlying mechanisms developing stopping this represent, currently, biggest challenges field MS. Here, we summarize publications 2022 provide insight into susceptibility to MS, basis features relatively recently recognized distinct forms inflammatory/demyelinating disorders CNS, as myelin oligodendrocyte glycoprotein antibody-associated (MOGAD).

Language: Английский

---

Lateral Ventricular Enlargement and Asymmetry and Myelin Content Imbalance in Individuals With Bipolar and Depressive Disorders: Clinical and Research Implications

Bipolar Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

ABSTRACT Background The link between ventricular enlargement and asymmetry with other indices of brain structure remains underexplored in individuals bipolar (BD) depressive (DD) disorders. Our study compared the lateral size, asymmetry, cortical myelin content BD versus those DD healthy controls (HC). Methods We obtained T1w T2w images from 149 (age = 27.7 (SD 6.1) years, 78% female, 38, 57, HC 54) using Magnetic Resonance Imaging (MRI). group consisted Type I ( n 11) II 27), while major disorder (MDD, 38) persistent (PDD, 19) Cortical was calculated T1w/T2w ratio. Elastic net regularized regression identified regions whose associated size asymmetry. A post hoc linear examined how participants' diagnosis, illness duration, current level depression moderated relationship ventricles levels selected regions. Results Individuals had larger than HC. Larger lower were observed who longer lifetime duration more severe symptoms. greater left participants p < 0.01). revealed that both altered cingulate, frontal, sensorimotor cortices. In BD, but not groups, related to right insular Conclusions Lateral are linked imbalance, thus potentially leading emotional cognitive dysfunction mood

Language: Английский

---