Dataset Information

Reduced rich-club connectivity is related to disability in primary progressive MS.

ABSTRACT:

Objective

To investigate whether the structural connectivity of the brain's rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures.

Methods

We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were reconstructed based on diffusion-weighted imaging data using probabilistic tractography and analyzed with graph theory.

Results

We observed the same topological organization of brain networks in patients and controls. Consistent with the originally defined rich-club regions, we identified superior frontal, precuneus, superior parietal, and insular cortex in both hemispheres as rich-club nodes. Connectivity within the rich club was significantly reduced in patients with MS (p = 0.039). The extent of reduced rich-club connectivity correlated with clinical measurements of mobility (Kendall rank correlation coefficient ? = -0.20, p = 0.047), hand function (? = -0.26, p = 0.014), and information processing speed (? = -0.20, p = 0.049).

Conclusions

In patients with primary progressive MS, the fundamental organization of the structural connectome in rich-club and peripheral nodes was preserved and did not differ from healthy controls. The proportion of rich-club connections was altered and correlated with disability measures. Thus, the rich-club organization of the brain may be a promising network phenotype for understanding the patterns and mechanisms of neurodegeneration in MS.

SUBMITTER: Stellmann JP

PROVIDER: S-EPMC5532749 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Reduced rich-club connectivity is related to disability in primary progressive MS.

Stellmann Jan-Patrick JP Hodecker Sibylle S Cheng Bastian B Wanke Nadine N Young Kim Lea KL Hilgetag Claus C Gerloff Christian C Heesen Christoph C Thomalla Götz G Siemonsen Susanne S

Neurology(R) neuroimmunology & neuroinflammation 20170727 5

<h4>Objective</h4>To investigate whether the structural connectivity of the brain's rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures.<h4>Methods</h4>We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were reconstructed based on diffusion-weighted imaging data using probabilistic tractograp ...[more]

PMID: 28804744

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Project description:BackgroundMultiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder of the central nervous system (CNS). While current MS therapies target the inflammatory processes, no treatment explicitly targets mitochondrial dysfunction and resulting axonal loss. Therefore, the aim of this study was to determine whether idebenone inhibits mitochondrial dysfunction and accumulation of disability in primary progressive MS (PPMS) and to enhance understanding of pathogenic mechanisms of PPMS progression using cerebrospinal fluid (CSF) biomarkers.MethodsThe double-blind, placebo-controlled Phase I/II clinical trial of Idebenone in patients with Primary Progressive MS (IPPoMS; NCT00950248) was an adaptively designed, baseline-versus-treatment, placebo-controlled, CSF-biomarker-supported trial. Based on interim analysis of the 1-year pre-treatment data, change in the area under the curve of Combinatorial Weight-Adjusted Disability Score (CombiWISE) became the primary outcome, with >80% power to detect ≥40% efficacy with 28 patients/arm treated for 2 years in baseline versus treatment paradigm. Changes in traditional disability scales and in brain ventricular volume were secondary outcomes. Exploratory outcomes included CSF biomarkers of mitochondrial dysfunction (Growth/differentiation factor 15 [GDF15] and lactate), axonal damage (neurofilament light chain [NFL]), innate immunity (sCD14), blood brain barrier leakage (albumin quotient) and retinal nerve fiber layer thinning.ResultsIdebenone was well tolerated but did not inhibit disability progression or CNS tissue destruction. Concentrations of GDF15, secreted predominantly by astrocytes and choroid plexus epithelium in vitro, increased after exposure to mitochondrial toxin rotenone, validating the ability of this biomarker to measure intrathecal mitochondrial damage. CSF GDF15 levels correlated strongly with age and MS patients had CSF levels of GDF15 significantly above age-adjusted healthy volunteers, with highest levels measured in PPMS. Idebenone did not change CSF GDF15 levels.ConclusionMitochondrial dysfunction exceeding normal aging reflected by age-adjusted CSF GDF15 is present in the majority of PPMS patients, but it is not inhibited by idebenone.

Dataset Information

Reduced rich-club connectivity is related to disability in primary progressive MS.

Objective

Methods

Results

Conclusions

Publications

Reduced rich-club connectivity is related to disability in primary progressive MS.

Similar Datasets

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