Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram

BackgroundQuantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group.MethodsTwenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram.ResultsFor both cohorts, all criteria showed moderate to very high test–retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria.ConclusionsThe proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS

Data_Sheet_1_Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram.PDF

BackgroundQuantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group.MethodsTwenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram.ResultsFor both cohorts, all criteria showed moderate to very high test–retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria.ConclusionsThe proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS.</p

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field