A static posturography guide to implementing time-to-boundary.

The emergence of time-to-boundary provides an advanced representation of the spatiotemporal characteristics of postural control through the estimation of the time required for the center of pressure to reach the boundary of the base of support. Time-to-boundary has demonstrated its utility in several healthy and clinical adoptions; however, unknown inconsistencies among studies exist. Text and graphical representations understandably highlight idealistic standards, but new investigators to this measure are forced to wade through the same potential pitfalls that others have addressed, but the field has neglected to concatenate. The purpose of this communication is to share recent methodological advancements made to enhance time-to-boundary and describe the components of the time-to-boundary code that is being made publicly accessible for the first time. We anticipate future researchers who wish to apply this methodology to their data processing toolbox could utilize our script in full, with any deviations in potential future developments noted in clear fashion. Historically, researchers (including ourselves) have had to interpret text-based descriptions of the existing literature into quantitative steps in a computational mathematics script. In contrast to fixed process measures that do not require investigator input (e.g., path length), time-to-boundary poses two distinct but connected challenges to investigators. The coding process itself can be a hurdle for novices or practitioners. Second, transferring logical considerations such as robust, objective event detection routines must be defended in the review process. This comprehensive guide to time-to-boundary, as used in our applications, should enhance adoption and advance the comprehension of postural control.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest.

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Distinct spatial landscapes in clear-cell renal cell carcinoma as revealed by whole transcriptome analysis.

Background: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of renal cancer and a paradigm of inter- and intratumor heterogeneity. We carried out an exploratory digital spatial profiling of the tumor interior and periphery of two ccRCC tumor specimens and mapped spatially the molecular and cellular composition of their tumor microenvironment and ecosystem. Materials and methods: Digital spatial profiling of the whole transcriptome of 19 regions of interest (ROIs) was carried out from two selected highly immunogenic stage pT3a/grade 3 (G3) and stage pT3a/grade 4 (G4) ccRCC. A total of 9-10 ROIs were selected from distinct areas from each tumor, including tumor interior and tumor periphery, and differences in gene expression were analyzed by RNA sequencing, pathway enrichment analysis, and cell deconvolution. Results: The distinct areas from the two locally advanced tumors displayed unique gene expression spatial patterns defining distinct biological pathways. Dimensional reduction analysis showed that the G3 ccRCC, compared to the G4 ccRCC, correlated with more variability between regions from the tumor interior and tumor periphery. Cell deconvolution analysis illustrated higher abundance of immune cells, including macrophages, myeloid dendritic cells, and CD4 T cells, and lower abundance of regulatory T cells in the tumor periphery compared to the tumor interior. Conclusions: Transcriptome spatial profiling revealed high inter- and intratumor heterogeneity in the analyzed tumors and provided information with potential clinical utility. This included the finding of less intratumor heterogeneity and more tumor-infiltrated T cells in the ccRCC tumor specimen with a higher grade.

Good times, bad times? An evaluation of event detection strategies in time to boundary postural assessments.

Time-to-boundary (TtB) is a popular balance metric that identifies minimum reaction times available to correct balance challenges during quiet standing. Minimum event criteria is a critical methodological consideration to determine physiologically relevant TtB outcomes yet selection methodology appears inconsistent and/or vaguely defined across studies. This study aimed to identify a robust, objective methodology to select meaningful TtB outcomes. Ninety-seven healthy adults stood quietly on a force platform with eyes open and feet together. Anterior-posterior (AP) and medial-lateral (ML) center-of-pressure data from 150 s were utilized to compute a TtB series. The MATLAB findpeaks function identified minima with and without a time delay following selected events and/or a vertical axis threshold. An individualized time delay excluded excessively large values that hold no clinically relevant information, and this effect was enhanced by a vertical threshold at 22 s. The absolute minimum TtB was unaffected by any findpeaks criteria. The recommendations implicated by these results will help improve clarity and consistency among TtB studies, thereby enhancing the applicability of clinical findings.

Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain-wide glymphatic function.

The glymphatic system is a brain-wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium-based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium-based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region-of-interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium-based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k-means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium-based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium-based contrast agent in healthy human participants.

IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action.

The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics.

Characterization of trial duration in traditional and emerging postural control measures.

Researchers may select from varied technological and practical options when evaluating balance. Methodological choices inform the quantitative outcomes observed and allow practitioners to diagnose balance abnormalities. Past investigations have differed widely on sampling duration, and these discrepancies hinder comparisons among studies and confidence in outcomes where trials were excessively short. This study aimed to identify necessary trial lengths for common and emerging center of pressure-based measures. We hypothesized that dependent variables would fluctuate over time but eventually reach a stable magnitude. Ninety-seven apparently healthy adults performed quiet standing for 180-seconds (s) with eyes (A) open and (B) closed on a force platform. Anterior-posterior and medial-lateral elements of the center of pressure were used to calculate velocity, time-to-boundary, and Hurst exponents using 15, 30, 90, 120, 150, and 180 s of data. Two-way repeated measures ANOVAs were used to differentiate postural measures over time and between vision conditions. Outcomes were considered stable when significant changes in the measure were no longer observed in the time factor. Dependent measures stabilized for velocity between 60 and 120 s, time-to-boundary between 120 and 150 s, and the Hurst exponent between 30 and 120 s. Velocity measures stabilized quicker with eyes open, whereas vision had no effect or the eyes closed condition was faster to stabilize in time-to-boundary and detrended fluctuation analysis measures. We conclude that 150 s of standing data is sufficient to capture a broad range of postural stability outcomes regardless of vision condition.

Neurological soft signs are associated with reduced medial-lateral postural control in adolescent athletes.

INTRODUCTION: Neurological soft signs (NSS) are minor deviations from the norm in motor performance that are commonly assessed using neurological examinations. NSS may be of clinical relevance for evaluating the developmental status of adolescents. Here we investigate whether quantitative force plate measures may add relevant information to observer-based neurological examinations. METHODS: Male adolescent athletes (n = 141) aged 13-16 years from three European sites underwent a neurological examination including 28 tests grouped into six functional clusters. The performance of tests and functional clusters was rated as optimal/non-optimal resulting in NSS+/NSS- groups and a continuous total NSS score. Participants performed a postural control task on a Balance Tracking System measured as path length, root mean square and sway area. ANCOVAs were applied to test for group differences in postural control between the NSS+ and NSS- group, and between optimal/non-optimal performance on a cluster- and test-level. Moreover, we tested for correlations between the total NSS score and postural control variables. RESULTS: There was no significant overall difference between the NSS+ and NSS- group in postural control. However, non-optimal performing participants in the diadochokinesis test swayed significantly more in the medial-lateral direction than optimal performing participants. Moreover, a lower total NSS score was associated with reduced postural control in the medial-lateral direction. CONCLUSION: Our findings demonstrate that NSS are related to postural control in adolescent athletes. Thus, force plate measures may add a quantitative, objective measurement of postural control to observer-based qualitative assessments, and thus, may complement clinical testing.

Eosinophilic Asthma Secondary to Adjuvant Anti-PD-1 Immune Checkpoint Inhibitor Treatment in a Melanoma Patient.

Background: Adjuvant immune checkpoint inhibitors are a new standard of care in melanoma. However, the immune related toxicity associated with these agents can be serious, and the long-term implications are yet to be defined especially in the adjuvant setting. We report, to our knowledge, the first case of anti-PD-1-induced eosinophilic asthma in a melanoma patient treated with adjuvant pembrolizumab. Case Presentation. A 72-year-old man commenced pembrolizumab in the adjuvant setting after resection of a stage IIIB cutaneous melanoma. The patient experienced episodes of breathlessness 4 weeks after cycle 1. These episodes were nocturnal and caused acute respiratory distress and cough, occasionally waking him up. The episodes progressed, and he was admitted after cycle 2 with a productive cough, wheeze, and breathlessness. Observations showed saturations on air of 94% and a respiratory rate of 19/min. The only laboratory abnormality was a raised eosinophil count of 1.1 × 109. Spirometry showed a FEV1 of 2.57 (91% predicted), FVC of 4.04 (108% predicted), and ratio of 64%. Peak expiratory flow rate was 94% predicted, and corrected gas transfer was 6.29 (78% predicted) with KCO 1.18 (93% predicted). FeNO was raised at 129 indicating inflammation of his airways, and peak flow was 422 l/min. CT of the chest did not show pneumonitis or other lung pathology. A diagnosis of acute eosinophilic asthma was made. Treatment with steroids and beclometasone dipropionate and formoterol inhaler produced rapid resolution of symptoms and normalisation of the eosinophil count. Pembrolizumab was safely recommenced once steroids had discontinued and symptoms had resolved. Conclusions: Specialist respiratory input was needed for optimal patient management and is ongoing. Although a safe rechallenge with pembrolizumab was possible, treatment in the adjuvant setting is curative in intent and long-term safety follow-up is required to assess for delayed toxicity and long-term health implications. This is likely to require large regional/national/international databases to detect, monitor, and educate the wider medical community as these patients are followed up in primary care following initial specialist follow-up.

Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spaceflight.

Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T1-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p < 0.001). In addition, we found high reliability for four of five PVS metrics across the two pre-flight time points and across the four control time points (ICC(3,k) > 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60-0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

Bursting TENS increases walking endurance more than continuous TENS in middle-aged adults.

The application of transcutaneous electrical nerve stimulation (TENS) can improve motor performance in both healthy individuals and those who present with clinically detectable sensory impairments. The purpose of our study was to compare the influence of continuous and intermittent TENS applied to the anterior thigh and tibialis anterior muscles on walking endurance and kinematics in healthy, middle-aged adults. Twenty-seven participants completed 4 trials of the 6-min walk test: Baseline, Continuous TENS (0.2 ms pulses at 50 Hz), Fast burst TENS (seven 0.15 ms pulses in 5 Hz bursts), and Slow burst TENS (seven 0.15 ms pulses in 0.5 Hz bursts). Linear mixed-effects models revealed that participants walked further (p ≤ 0.046) during all three TENS trials compared with Baseline (560 ± 76 m) and that they walked even further during both burst TENS trials (576 ± 83 m and 576 ± 83 m) compared with Continuous TENS (566 ± 79 m). Increases in walking speed were predicted by increases in stride length (p < 0.001) and stride frequency (p < 0.001) with toe-off angle being the only significant predictor (p ≤ 0.013) of both kinematic variables for the increase in walking speed. Bursting TENS was more effective than Continuous TENS at improving walking endurance in middle-aged, healthy adults.

Bridging the callosal gap in gait: corpus callosum white matter integrity's role in lower limb coordination.

Bilateral coordination of the lower extremities is an essential component of mobility. The corpus callosum bridges the two hemispheres of the brain and is integral for the coordination of such complex movements. The aim of this project was to assess structural integrity of the transcallosal sensorimotor fiber tracts and identify their associations with gait coordination using novel methods of ecologically valid mobility assessments in persons with multiple sclerosis and age-/gender-matched neurotypical adults. Neurotypical adults (n = 29) and persons with multiple sclerosis (n = 27) underwent gait and diffusion tensor imaging assessments; the lower limb coordination via Phase Coordination Index, and radial diffusivity, an indirect marker of myelination, were applied as the primary outcome measures. Persons with multiple sclerosis possessed poorer transcallosal white matter microstructural integrity of sensorimotor fiber tracts compared to the neurotypical adults. Further, persons with multiple sclerosis demonstrated significantly poorer bilateral coordination of the lower limbs during over-ground walking in comparison to an age and gender-matched neurotypical cohort. Finally, bilateral coordination of the lower limbs was significantly associated with white matter microstructural integrity of the dorsal premotor and primary motor fiber bundles in persons with multiple sclerosis, but not in neurotypical adults. This analysis revealed that persons with multiple sclerosis exhibit poorer transcallosal microstructural integrity than neurotypical peers. Furthermore, these structural deficits were correlated to poorer consistency and accuracy of gait in those with multiple sclerosis. Together, these results, emphasize the importance of transcallosal communication for gait coordination in those with multiple sclerosis.

The effect of shoe cushioning on gait and balance in females with multiple sclerosis.

Gait and balance deficits are significant concerns for people with multiple sclerosis (MS). Shoe cushioning can influence mobility and balance, but its effect on walking and balance remains unknown in MS. This study aimed to determine how shoe cushioning affects gait and balance in females with MS (FwMS). We hypothesized that extra cushioning would improve gait but reduce balance performance. FwMS performed gait (n = 18) and balance (n = 17) assessments instrumented using inertial sensors in two different shoe conditions: a standard-cushioned and an extra-cushioned shoe. Care was taken to ensure minimal differences between shoe types other than midsole cushioning, but shoe construction was not identical between conditions. Spatiotemporal gait parameters were assessed during a 2-min walk test, while postural sway measures were evaluated using the modified Clinical Test of Sensory Interaction and Balance. In the extra-cushioned shoe, FwMS spent less time in the double support and stance phase with more time in the single support and swing phase. No differences in stride length, gait speed, or elevation at midswing were observed between shoe conditions. Decreased path length, RMS sway, and sway velocity were observed in the extra-cushioned shoe. No differences were observed in the gait cycle's spatial composition between shoe conditions, but FwMS demonstrated improvements in the gait cycle's temporal parameters and postural sway in the extra-cushioned shoe. This may suggest a less cautious walking strategy and improved balance when wearing a shoe with extra cushioning.

The assessment of center of mass and center of pressure during quiet stance: Current applications and future directions.

This perspective article provides a brief review of our understanding of how center of pressure (CoP) and center of mass (CoM) are traditionally utilized to measure quiet standing and how technological advancements are allowing for measurements to be derived outside the confines of a laboratory setting. Furthermore, this viewpoint provides descriptions of what CoP and CoM outcomes may reflect, a discussion of recent developments in selected balance outcomes, the importance of measuring instantaneous balance outcomes, and directions for future questions/research. Considering the enormous number and cost of falls annually, conclusions drawn from this perspective underscore the need for more cohesive efforts to advance our understanding of balance performance. As we refine the technology and algorithms used to portably assess postural stability, the question of which measurement (i.e. CoP or CoM) to utilize seems to be highly dependent on the question being asked. Further, the complexity of the question appears to span multiple disciplines and cultivate exploration of the intrinsic mechanisms of stability. Recently developed multi-dimensional methods for assessing balance performance may provide additional insight into balance, improving our ability to predict balance impairments and falls outside the laboratory and in the clinic. However, additional work will be necessary to understand the clinical significance and predictive capacity of these outcomes in various fall-prone populations.

Middle-age people with multiple sclerosis demonstrate similar mobility characteristics to neurotypical older adults.

BACKGROUND: Clinical trials often report significant mobility differences between neurotypical and atypical groups, however, these analyses often do not determine which measures are capable of discriminating between groups. Additionally, indirect evidence supports the notion that some mobility impaired populations demonstrate similar mobility deficits. Thus, the current study aimed to provide a comprehensive analysis of three distinct aspects of mobility (walking, turning, and balance) to determine which variables were significantly different and were also able to discriminate between neurotypical older adults (OA) and middle-aged people with multiple sclerosis (PwMS), and between middle-aged neurotypical adults and PwMS. METHODS: This study recruited 21 neurotypical OA, 19 middle-aged neurotypical adults, and 30 people with relapsing remitting MS. Participants came into the laboratory on two separate occasions to complete mobility testing while wearing wireless inertial sensors. Testing included a self-selected pace two-minute walk, a series of 180˚ and 360˚ turns, and a clinical balance test capturing a total of 99 distinct mobility characteristics. We determined significant differences for gait and turning measures through univariate analyses and a series of repeated measures analysis of variance in determining significance for balance conditions and measures. In determining discrimination between groups, the Area Under the Curve (AUC) was calculated for all individual mobility measures with a threshold of 0.80, denoting excellent discrimination. Additionally, a stepwise regression of the top five AUC producing variables was performed to determine whether a combination of variables could enhance discrimination while accounting for multicollinearity. RESULTS: The results between neurotypical OA and middle-aged PwMS demonstrated significant differences for three gait and one turning variable, with no variable or combination of variables able to provide excellent discrimination between groups. Between middle-age neurotypical adults and PwMS a variety of mean and variability gait measures demonstrated significant differences between groups; however, no variable or combination of variables met discriminatory threshold. For turning, five 360˚ turn variables demonstrated significant differences and furthermore, the combination of 360˚ mean turn duration and variability of peak turn velocity were able to discriminate between groups. Finally, the majority of postural sway measures demonstrated significant group differences and the ability to discriminate between groups, particularly during more challenging balance conditions where participants stood on a compliant surface. CONCLUSION: These results offer a comprehensive analysis of mobility differences and measures capable of discriminating between middle-age neurotypical adults and PwMS. Additionally, these results provide evidence that OA and middle-age PwMS display similar movement characteristics and thus a potential indicator of advanced aging from a mobility perspective.

White Matter Microstructure of the Cerebellar Peduncles Is Associated with Balance Performance during Sensory Re-Weighting in People with Multiple Sclerosis.

People with multiple sclerosis (PwMS) exhibit impaired balance during different sensory environments and poor cerebellar peduncle microstructure. We aimed to examine associations between microstructures of the superior, middle and inferior cerebellar peduncles (CP) with visual, vestibular, and proprioceptive-based balance in PwMS. Twenty-seven PwMS and twenty-nine healthy controls (HC) underwent MRI and balance assessments. We assessed CP microstructure with radial diffusivity (RD) and fractional anisotropy (FA) and balance with center of pressure-derived measures of path length and root mean square of sway during proprioceptive (C2), visual (C3), and vestibular (C4) balance conditions of the modified clinical test of sensory integration on balance (mCTSIB). PwMS exhibited significantly lower FA (p < 0.001) and greater RD (p < 0.001) across all CP and greater path length (p < 0.05) in the mCTSIB compared with HC. In PwMS, significant associations were detected between inferior CP white matter microstructure and proprioceptive-based balance control (rho = -0.43, p < 0.05) and middle CP white matter microstructure and visual-based balance control (rho = 0.39, p < 0.05). PwMS may rely more on cerebellar-regulated proprioceptive- and visual-based balance control than HC.

Advanced characterization of static postural control dysfunction in persons with multiple sclerosis and associated neural mechanisms.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune-based chronic inflammatory disease characterized by the neurodegeneration of the central nervous system and produces postural dysfunction. Quiet or static standing is a complex task carried out through afferent sensory inputs and efferent postural corrective outputs. Currently the mechanisms underlying these outputs remain largely unknown. RESEARCH QUESTION: Assess the relationship between multi-dimensional measures of postural control and microstructural integrity of the cortical sensorimotor pathway (CSP) in persons with MS (PwMS) and neurotypical adults. METHODS: Postural control performance was assessed by both overall and directional time-to-boundary measures across four manipulated sensory stance conditions (eyes open/closed; stance firm/foam) in twenty-nine neurotypical and twenty-seven PwMS. These postural outcomes were evaluated with mixed-model repeated measures analysis of variance across group (MS and control) and stance condition. Postural performance was also correlated with magnetic resonance imaging diffusion tensor-derived measures of microstructural integrity of the CSP. RESULTS: PwMS displayed significantly (p = 0.026) worse anterior-posterior postural control compared to their neurotypical counterparts across sensory testing conditions and poorer CSP microstructural integrity in comparison to neurotypical adults (p = 0.008). Additionally, PwMS displayed a significant association (2D (rho = -0.384, p = 0.048), AP (rho = -0.355, p = 0.035), and ML (rho = -0.365, p = 0.030) between integrity of the CSP and postural control performance during proprioceptive-based balance, such that those with worse cortical structure had poorer balance control. SIGNIFICANCE: This is the first study to establish connections between the microstructural integrity of the CSP and multi-dimensional postural control performance. Results indicate that a reduction in the CSP microstructural integrity is associated with poorer postural control in PwMS. These outcomes identify neural underpinnings of postural control dysfunction in PwMS and provide new avenues for evaluating the efficacy of postural rehabilitation strategies in PwMS that express proprioceptive-based postural deficits.

A temporal analysis of bilateral gait coordination in people with multiple sclerosis.

BACKGROUND: Gait performance often dictates an individual's ability to navigate the dynamic environments of everyday living. With each stride, the lower extremities move through phases of stance, swing, and double support. Coordinating these motions with high accuracy and consistency is imperative to constraining the center of mass within the base of support, thereby maintaining balance. Gait abnormalities accompany neurodegeneration, impeding stride to stride cohesion and increasing the likelihood of a fall. This study sought to identify the temporal actions underlying bilateral coordination in people with multiple sclerosis (PwMS) and furthermore, how bilateral coordination is affected by gait speed augmentation in these individuals. METHODS: The Phase Coordination Index (PCI), a temporal analysis of left-right step pattern generations throughout the gait cycle was used to quantify bilateral coordination in twenty-nine neurotypical (21 females and 8 males) and twenty-seven PwMS (20 females and 7 males). PCI was acquired with inertial monitoring units while performing two-minute over ground gait trials while walking at a self-selected pace and at a fast pace. RESULTS: PwMS displayed significantly worse bilateral coordination compared to neurotypical adults regardless of gait speed. The poorer left-right stepping patterns generated by PwMS were derived from significant decreases in both phase (step) generation accuracy and consistency. In addition to demonstrating poorer bilateral coordination, PwMS walked more slowly than their neurotypical peers during each walking condition. CONCLUSION: PwMS exhibited poorer left-right coordinated stepping patterns during gait compared to neurotypical peers across walking conditions. Beyond the novelty of this examination, this assessment highlights PCI as a potential target for future rehabilitative interventions for PwMS and individualized rehabilitation strategies aimed at improving the health span and overall quality of life for PwMS.

Virtual time-to-contact identifies balance deficits better than traditional metrics in people with multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease that negatively affects the quality of electrical signaling throughout the central nervous system. Although impaired postural control is one of the most common symptoms in people with MS (PwMS), commonly reported metrics such as center of pressure (CoP) path length and velocity have not been great predictors of fall risk. A relatively new metric, known as virtual time-to-contact (VTC), is a measurement that uses the instantaneous position, velocity and acceleration of the CoP, to predict how long it would take the CoP to reach the boundary of the base of support for every data point in a trial. While the VTC metric has shown promising results in PwMS, there are still inconsistencies in how VTC is reported. Thus, the purpose of this work was to compare VTC to commonly reported measures of postural balance control to identify the most appropriate metric(s) for assessing balance impairments unique to PwMS. A group of patients with MS and a group of neurologically healthy controls performed a static balance task with both eyes open and eyes closed. The VTC minimum values (minima) were the best at detecting balance performance differences between conditions and between study groups. In addition, VTC minima was the best at detecting proprioceptive weaknesses in PwMS, assessed via the Romberg ratio. These results suggest that the VTC minima may be better than traditional metrics at detecting balance impairments unique to PwMS as well as proprioceptive deficits within this population.