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Human Brain Mapping Jun 2024Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS)...
Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.
Topics: Humans; Female; Male; Adult; Middle Aged; Brain; Multiple Sclerosis; Diffusion Magnetic Resonance Imaging; Water; Cognitive Dysfunction; Parenchymal Tissue; White Matter; Gray Matter; Processing Speed
PubMed: 38895882
DOI: 10.1002/hbm.26761 -
Sensors (Basel, Switzerland) May 2024Robotic devices are known to provide pivotal parameters to assess motor functions in Multiple Sclerosis (MS) as dynamic balance. However, there is still a lack of...
BACKGROUND
Robotic devices are known to provide pivotal parameters to assess motor functions in Multiple Sclerosis (MS) as dynamic balance. However, there is still a lack of validation studies comparing innovative technologies with standard solutions. Thus, this study's aim was to compare the postural assessment of fifty people with MS (PwMS) during dynamic tasks performed with the gold standard EquiTest and the robotic platform hunova, using Center of Pressure (COP)-related parameters and global balance indexes.
METHODS
Pearson's ρ correlations were run for each COP-related measure and the global balance index was computed from EquiTest and hunova in both open (EO) and closed-eyes (EC) conditions.
RESULTS
Considering COP-related parameters, all correlations were significant in both EO (0.337 ≤ ρ ≤ 0.653) and EC (0.344 ≤ ρ ≤ 0.668). Furthermore, Pearson's analysis of global balance indexes revealed relatively strong for visual and vestibular, and strong for somatosensory system associations (ρ = 0.573; ρ = 0.494; ρ = 0.710, respectively).
CONCLUSIONS
Findings confirm the use of hunova as a valid device for dynamic balance assessment in MS, suggesting that such a robotic platform could allow for a more sensitive assessment of balance over time, and thus a better evaluation of the effectiveness of personalized treatment, thereby improving evidence-based clinical practice.
Topics: Humans; Multiple Sclerosis; Postural Balance; Male; Robotics; Female; Adult; Middle Aged; Self-Help Devices
PubMed: 38894116
DOI: 10.3390/s24113325 -
Nutrients Jun 2024Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology...
Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology remains elusive. Both genetic and environmental factors contribute to MS susceptibility; however, the link between diet and MS lacks substantial evidence due to limited large-scale studies. We exploited the UK Biobank resources to explore the nexus between diet, lifestyle, and MS risk. The dietary and lifestyle habits of MS incident cases, derived from a general food frequency questionnaire (FFQ) completed by all participants at study enrollment, were compared to those of subjects who did not develop MS during the follow-up. Our findings suggest the protective role of moderate oily fish consumption and weekly alcohol intake. Furthermore, by analyzing food intake data obtained through 24 h recall, completed by a subset of participants, we found a protective, though non-significant, trend of an increased adherence to the Mediterranean diet (MD). These findings, derived from the analysis of the UK Biobank and representing an unprecedented approach for this inquiry, warrant further exploration and integration in future research.
Topics: Humans; Multiple Sclerosis; United Kingdom; Male; Female; Prospective Studies; Biological Specimen Banks; Diet, Mediterranean; Middle Aged; Diet; Adult; Life Style; Alcohol Drinking; Risk Factors; Feeding Behavior; Surveys and Questionnaires; UK Biobank
PubMed: 38892680
DOI: 10.3390/nu16111746 -
International Journal of Molecular... May 2024We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35-55 (OM-MOG35-55) in vivo (EAE mouse model) and in vitro (human...
We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35-55 (OM-MOG35-55) in vivo (EAE mouse model) and in vitro (human peripheral blood) and demonstrated that OM-MOG35-55 suppresses antigen-specific T cell responses associated with autoimmune demyelination. Based on these results, we developed different types of dendritic cells (DCs) from the peripheral blood monocytes of patients with multiple sclerosis (MS) or healthy controls presenting OM-MOG35-55 or MOG-35-55 to autologous T cells to investigate the tolerogenic potential of OM-MOG35-55 for its possible use in MS therapy. To this end, monocytes were differentiated into different DC types in the presence of IL-4+GM-CSF ± dexamethasone (DEXA) ± vitamin D3 (VITD3). At the end of their differentiation, the DCs were loaded with peptides and co-cultured with T cells +IL-2 for 4 antigen presentation cycles. The phenotypes of the DC and T cell populations were analyzed using flow cytometry and the secreted cytokines using flow cytometry or ELISA. On day 8, the monocytes had converted into DCs expressing the typical markers of mature or immature phenotypes. Co-culture of T cells with all DC types for 4 antigen presentation cycles resulted in an increase in memory CD4+ T cells compared to memory CD8+ T cells and a suppressive shift in secreted cytokines, mainly due to increased TGF-β1 levels. The best tolerogenic effect was obtained when patient CD4+ T cells were co-cultured with VITD3-DCs presenting OM-MOG35-55, resulting in the highest levels of CD4+PD-1+ T cells and CD4+CD25+Foxp3+ Τ cells. In conclusion, the tolerance induction protocols presented in this work demonstrate that OM-MOG35-55 could form the basis for the development of personalized therapeutic vaccines or immunomodulatory treatments for MS.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Dendritic Cells; Multiple Sclerosis; Immune Tolerance; Peptide Fragments; Adult; Female; Mannans; Male; Cell Differentiation; Monocytes; T-Lymphocytes; Cells, Cultured; Middle Aged; CD4-Positive T-Lymphocytes; Cytokines
PubMed: 38892275
DOI: 10.3390/ijms25116092 -
International Journal of Molecular... May 2024Neuroinflammatory conditions in the central nervous system (CNS) are implicated in the pathogenesis of several neuroimmune disorders such as acquired demyelinating...
Neuroinflammatory conditions in the central nervous system (CNS) are implicated in the pathogenesis of several neuroimmune disorders such as acquired demyelinating syndromes, autoimmune encephalopathies, acute or chronic bacterial and viral CNS infections as well as multiple sclerosis (MS) [...].
Topics: Humans; Neuroinflammatory Diseases; Animals; Multiple Sclerosis; Central Nervous System; Inflammation
PubMed: 38892158
DOI: 10.3390/ijms25115973 -
International Journal of Molecular... May 2024Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model,...
Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of and in the hypothalamus does not change, except for and , while at the pituitary level the , and genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated and expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Female; Rats; Growth Hormone; Insulin-Like Growth Factor I; Hypothalamus; Pituitary Gland; Receptors, Somatotropin; Receptors, Pituitary Hormone-Regulating Hormone; Multiple Sclerosis; Growth Hormone-Releasing Hormone; Liver; Disease Models, Animal
PubMed: 38892024
DOI: 10.3390/ijms25115837 -
Journal of Neuroengineering and... Jun 2024Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed...
BACKGROUND
Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases.
METHODS
We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal.
RESULTS
We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3-13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8-39] ms) and 26 ms (IQR [12-50] ms).
CONCLUSIONS
Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability.
Topics: Humans; Male; Female; Multiple Sclerosis; Adult; Middle Aged; Gait Disorders, Neurologic; Gait Analysis; Gait; Aged; Stroke; Accelerometry; Young Adult
PubMed: 38890696
DOI: 10.1186/s12984-024-01405-x -
Scientific Reports Jun 2024Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult... (Observational Study)
Observational Study
Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.
Topics: Humans; Female; Mindfulness; Pilot Projects; Male; Stress, Psychological; Middle Aged; Adult; Multiple Sclerosis; Magnetic Resonance Imaging; Neuroimaging; Inflammation; Prospective Studies; Hydrocortisone; Quality of Life
PubMed: 38890336
DOI: 10.1038/s41598-024-62960-w -
Neurology(R) Neuroimmunology &... Jul 2024Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD)....
BACKGROUND AND OBJECTIVES
Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10.
METHODS
Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19 IgD, CD27) and plasmablasts (PBs; CD19, CD27, CD38). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab.
RESULTS
DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200 PBs produced more IL-10 than CD200 PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200 PBs than patients during the acute attacks.
DISCUSSION
Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200 PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.
Topics: Humans; Neuromyelitis Optica; Female; Adult; Male; Middle Aged; Interleukin-6; Receptors, Interleukin-6; Plasma Cells; Interleukin-10; Signal Transduction
PubMed: 38889374
DOI: 10.1212/NXI.0000000000200266 -
Neurology Research International 2024Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study...
BACKGROUND
Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity.
METHODS
CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated.
RESULTS
Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels.
CONCLUSIONS
CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP.
PubMed: 38887668
DOI: 10.1155/2024/7229216