Screening for balance disorders in mildly affected multiple sclerosis patients

Multiple sclerosis (MS) patients often complain about balance problems when Romberg's test and tandem gait are normal. The aim of the study was to determine if measures of trunk sway taken during a battery of stance and gait tasks could be used to detect subclinical balance disorders. We recorded trunk angular sway in the pitch and roll directions from 20 MS patients (EDSS 1.4±0.5) and 20 age- and gender-matched healthy controls (HCs), during 12 stance and gait tasks. We filmed 22 subjects simultaneously. Two neurologists assessed the videos, deciding whether task performance was pathological. Sway measures were significantly different between patients and HCs in eight out of 12 balance tasks. The most significant differences between MS patients and HCs were pitch angle range standing on one leg with eyes open on a firm surface (mean 3.13° vs. 2.09°, p=0.005), and on a foam support surface (mean 6.24° vs. 2.96°, p=0.006), pitch velocity range walking 8m with eyes closed (mean 75.5 vs. 50.2°/s, p<0.001) and pitch velocity range walking 3m on heels (mean 85.37 vs. 60.9°/s, p=0.002). Multivariate analysis revealed a model with three tasks which detected balance disorders in 84% of the MS patients and 90% of the HCs correctly. The neurologists achieved accuracies of 30% for the MS patients and 82% for the HCs. Using trunk sway measures during stance and gait tasks is a sensitive screening method for balance problems in MS patients, and is more accurate than assessment by trained neurologist

Corpus callosum index and long-term disability in multiple sclerosis patients

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume. We investigated medical records and 533 MRI scans at diagnosis and during clinical follow-up of 169 MS patients (mean age 42±11years, 86% relapsing-remitting MS, time since first relapse 11±9years). CCI at diagnosis was 0.345±0.04 and correlated with duration of disease (p=0.002; r=−0.234) and expanded disability status scale (EDSS) score at diagnosis (r=−0.428; p<0.001). Linear regression analyses identified age, duration of disease, relapse rate and EDSS at diagnosis as independent predictors for disability after mean of 7.1years (Nagelkerkes' R:0.56). Annual CCI decrease was 0.01±0.02 (annual tissue loss: 1.3%). In secondary progressive MS patients, CCI decrease was double compared to that in relapsing-remitting MS patients (p=0.04). There was a trend of greater CCI decrease in untreated patients compared to those who received disease modifying drugs (p=0.2). CCI is an easy to use MRI marker for estimating brain atrophy in patients with MS. Brain atrophy as measured with CCI was associated with disability progression but it was not an independent predictor of long-term disabilit

Fatigue and progression of corpus callosum atrophy in multiple sclerosis

Fatigue is one of the most disabling symptoms in multiple sclerosis (MS) patients. There is no or only weak correlation between conventional magnetic resonance imaging (MRI) parameters and level of fatigue. The aim of this study was to investigate the relationship between progression of corpus callosum (CC) atrophy and fatigue in MS patients. This was a cohort study in 70 patients with relapsing form of MS (RRMS) and serial MRIs over a mean follow-up of 4.8years [67% female, mean age 42±11years, mean disease duration 9.7±7.6years, mean Expanded Disability Status Scale (EDSS) 2.8±1.6]. Fatigue was assessed by the Fatigue Severity Scale (FSS). CC size was measured with the CC index (CCI). In total, 40% of the patients suffered from fatigue (mean FSS score 5.3±1.1) and 60% patients had no fatigue (mean FSS score of 2.1±1). Patients with fatigue had higher EDSS scores (p=0.01) and CC atrophy was more pronounced in patients with fatigue (−21.8 vs. −12.1%, p=0.005). FSS correlated with CCI change over time (r=−0.33; p=0.009) and EDSS (p=0.008; r=0.361). The association between annualized CCI change and FSS was independent from EDSS, disease duration, gender and age in a multivariate linear regression analysis (p<0.001). Progression of CC atrophy may play a role in the evolution of MS-related fatigu

Learn to Ignore: Domain Adaptation for Multi-Site MRI Analysis

The limited availability of large image datasets, mainly due to data privacy and differences in acquisition protocols or hardware, is a significant issue in the development of accurate and generalizable machine learning methods in medicine. This is especially the case for Magnetic Resonance (MR) images, where different MR scanners introduce a bias that limits the performance of a machine learning model. We present a novel method that learns to ignore the scanner-related features present in MR images, by introducing specific additional constraints on the latent space. We focus on a real-world classification scenario, where only a small dataset provides images of all classes. Our method \textit{Learn to Ignore (L2I)} outperforms state-of-the-art domain adaptation methods on a multi-site MR dataset for a classification task between multiple sclerosis patients and healthy controls

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter patholog

Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis: A Systematic Review

IMPORTANCE: Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies. OBJECTIVE: To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials. EVIDENCE REVIEW: A literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022. FINDINGS: Of 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult. CONCLUSION AND RELEVANCE: PIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets

Motor network efficiency and disability in multiple sclerosis.

OBJECTIVE: To develop a composite MRI-based measure of motor network integrity, and determine if it explains disability better than conventional MRI measures in patients with multiple sclerosis (MS). METHODS: Tract density imaging and constrained spherical deconvolution tractography were used to identify motor network connections in 22 controls. Fractional anisotropy (FA), magnetization transfer ratio (MTR), and normalized volume were computed in each tract in 71 people with relapse onset MS. Principal component analysis was used to distill the FA, MTR, and tract volume data into a single metric for each tract, which in turn was used to compute a composite measure of motor network efficiency (composite NE) using graph theory. Associations were investigated between the Expanded Disability Status Scale (EDSS) and the following MRI measures: composite motor NE, NE calculated using FA alone, FA averaged in the combined motor network tracts, brain T2 lesion volume, brain parenchymal fraction, normal-appearing white matter MTR, and cervical cord cross-sectional area. RESULTS: In univariable analysis, composite motor NE explained 58% of the variation in EDSS in the whole MS group, more than twice that of the other MRI measures investigated. In a multivariable regression model, only composite NE and disease duration were independently associated with EDSS. CONCLUSIONS: A composite MRI measure of motor NE was able to predict disability substantially better than conventional non-network-based MRI measures

Balance Changes in Patients With Relapsing-Remitting Multiple Sclerosis: A Pilot Study Comparing the Dynamics of the Relapse and Remitting Phases

Aims: To compare balance changes over time during the relapse phase of relapsing-remitting multiple sclerosis (RRMS) with balance control during the remitting phase.Methods: Balance control during stance and gait tasks of 24 remitting-phase patients (mean age 43.7 ± 10.5, 15 women, mean EDSS at baseline 2.45 ± 1.01) was examined every 3 months over 9 months and compared to that of nine relapsing patients (age 42.0 ± 12.7, all women, mean EDSS at relapse onset 3.11 ± 0.96) examined at relapse onset and 3 months later. Balance was also compared to that of 40 healthy controls (HCs) (age 39.7 ± 12.6, 25 women). Balance control was measured as lower-trunk sway angles with body-worn gyroscopes. Expanded Disability Status Scale scores (EDSS) were used to monitor, clinically, disease progression.Results: Remitting-phase patients showed more unstable stance balance control than HCs (p &lt; 0.04) with no worsening over the observation period of 9 months. Gait balance control was normal (p &gt; 0.06). Relapsing patients had stance balance control significantly worse at onset compared to remitting-phase patients and HCs (p &lt; 0.04). Gait tasks showed a significant decrease of gait speed and trunk sway in relapsing patients (p = 0.018) compatible with having increased gait instability at normal speeds. Improvement to levels of remitting patients generally took longer than 3 months. Balance and EDSS scores were correlated for remitting but not for relapse patients.Conclusions: Balance in remitting RRMS patients does not change significantly over 9 months and correlated well with EDSS scores. Our results indicate that balance control is a useful measure to assess recovery after a relapse, particularly in patients with unchanged EDSS scores. Based on our results, balance could be considered as additional measurement to assess recovery after a relapse, particularly in patients with unchanged EDSS

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection