Locomotor Sensory Organization Test: A Novel Paradigm for the Assessment of Sensory Contributions in Gait

Feedback based balance control requires the integration of visual, proprioceptive and vestibular input to detect the body’s movement within the environment. When the accuracy of sensory signals is compromised, the system reorganizes the relative contributions through a process of sensory recalibration, for upright postural stability to be maintained. Whereas this process has been studied extensively in standing using the Sensory Organization Test (SOT), less is known about these processes in more dynamic tasks such as locomotion. In the present study, ten healthy young adults performed the six conditions of the traditional SOT to quantify standing postural control when exposed to sensory conflict. The same subjects performed these six conditions using a novel experimental paradigm, the Locomotor SOT (LSOT), to study dynamic postural control during walking under similar types of sensory conflict. To quantify postural control during walking, the net Center of Pressure sway variability was used. This corresponds to the Performance Index of the center of pressure trajectory, which is used to quantify postural control during standing. Our results indicate that dynamic balance control during locomotion in healthy individuals is affected by the systematic manipulation of multisensory inputs. The sway variability patterns observed during locomotion reflect similar balance performance with standing posture, indicating that similar feedback processes may be involved. However, the contribution of visual input is significantly increased during locomotion, compared to standing in similar sensory conflict conditions. The increased visual gain in the LSOT conditions reflects the importance of visual input for the control of locomotion. Since balance perturbations tend to occur in dynamic tasks and in response to environmental constraints not present during the SOT, the LSOT may provide additional information for clinical evaluation on healthy and deficient sensory processing

Locomotor Sensory Organization Test: A Novel Paradigm for the Assessment of Sensory Contributions in Gait

Feedback based balance control requires the integration of visual, proprioceptive and vestibular input to detect the body’s movement within the environment. When the accuracy of sensory signals is compromised, the system reorganizes the relative contributions through a process of sensory recalibration, for upright postural stability to be maintained. Whereas this process has been studied extensively in standing using the Sensory Organization Test (SOT), less is known about these processes in more dynamic tasks such as locomotion. In the present study, ten healthy young adults performed the six conditions of the traditional SOT to quantify standing postural control when exposed to sensory conflict. The same subjects performed these six conditions using a novel experimental paradigm, the Locomotor SOT (LSOT), to study dynamic postural control during walking under similar types of sensory conflict. To quantify postural control during walking, the net Center of Pressure sway variability was used. This corresponds to the Performance Index of the center of pressure trajectory, which is used to quantify postural control during standing. Our results indicate that dynamic balance control during locomotion in healthy individuals is affected by the systematic manipulation of multisensory inputs. The sway variability patterns observed during locomotion reflect similar balance performance with standing posture, indicating that similar feedback processes may be involved. However, the contribution of visual input is significantly increased during locomotion, compared to standing in similar sensory conflict conditions. The increased visual gain in the LSOT conditions reflects the importance of visual input for the control of locomotion. Since balance perturbations tend to occur in dynamic tasks and in response to environmental constraints not present during the SOT, the LSOT may provide additional information for clinical evaluation on healthy and deficient sensory processing

Optic flow improves adaptability of spatiotemporal characteristics during split-belt locomotor adaptation with tactile stimulation

Human locomotor adaptation requires feedback and feed-forward control processes to maintain an appropriate walking pattern. Adaptation may require the use of visual and proprioceptive input to decode altered movement dynamics and generate an appropriate response. After a person transfers from an extreme sensory environment and back, as astronauts do when they return from spaceflight, the prolonged period required for re-adaptation can pose a significant burden. In our previous paper, we showed that plantar tactile vibration during a split-belt adaptation task did not interfere with the treadmill adaptation however, larger overground transfer effects with a slower decay resulted. Such effects, in the absence of visual feedback (of motion) and perturbation of tactile feedback, are believed to be due to a higher proprioceptive gain because, in the absence of relevant external dynamic cues such as optic flow, reliance on body-based cues is enhanced during gait tasks through multisensory integration. In this study, we therefore investigated the effect of optic flow on tactile-stimulated split-belt adaptation as a paradigm to facilitate the sensorimotor adaptation process. Twenty healthy young adults, separated into two matched groups, participated in the study. All participants performed an overground walking trial followed by a split-belt treadmill adaptation protocol. The tactile group (TC) received vibratory plantar tactile stimulation only, whereas the virtual reality and tactile group (VRT) received an additional concurrent visual stimulation: a moving virtual corridor, inducing perceived self-motion. A post-treadmill overground trial was performed to determine adaptation transfer. Interlimb coordination of spatiotemporal and kinetic variables was quantified using symmetry indices and analyzed using repeated-measures ANOVA. Marked changes of step length characteristics were observed in both groups during split-belt adaptation. Stance and swing time symmetries were similar in the two groups, suggesting that temporal parameters are not modified by optic flow. However, whereas the TC group displayed significant stance time asymmetries during the post-treadmill session, such aftereffects were absent in the VRT group. The results indicated that the enhanced transfer resulting from exposure to plantar cutaneous vibration during adaptation was alleviated by optic flow information. The presence of visual self-motion information may have reduced proprioceptive gain during learning. Thus, during overground walking, the learned proprioceptive split-belt pattern is more rapidly overridden by visual input due to its increased relative gain. The results suggest that when visual stimulation is provided during adaptive training, the system acquires the novel movement dynamics while maintaining the ability to flexibly adapt to different environments

Plantar tactile perturbations enhance transfer of split-belt locomotor adaptation

Patterns of human locomotion are highly adaptive and flexible and depend on the environmental context. Locomotor adaptation requires the use of multisensory information to perceive altered environmental dynamics and generate an appropriate movement pattern. In this study, we investigated the use of multisensory information during locomotor learning. Proprioceptive perturbations were induced by vibrating tactors, placed bilaterally over the plantar surfaces. Under these altered sensory conditions, participants were asked to perform a split-belt locomotor task representative of motor learning. Twenty healthy young participants were separated into two groups: no-tactors (NT) and tactors (TC). All participants performed an overground walking trial, followed by treadmill walking including 18 min of split-belt adaptation and an overground trial to determine transfer effects. Interlimb coordination was quantified by symmetry indices and analyzed using mixed repeated-measures ANOVAs. Both groups adapted to the locomotor task, indicated by significant reductions in gait symmetry during the split-belt task. No significant group differences in spatiotemporal and kinetic parameters were observed on the treadmill. However, significant group differences were observed overground. Step and swing time asymmetries learned on the split-belt treadmill were retained and decayed more slowly overground in the TC group whereas in NT, asymmetries were rapidly lost. These results suggest that tactile stimulation contributed to increased lower limb proprioceptive gain. High proprioceptive gain allows for more persistent overground after effects, at the cost of reduced adaptability. Such persistence may be utilized in populations displaying pathologic asymmetric gait by retraining a more symmetric pattern

Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis : Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57 years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34(+) cell dose was 4.8 x 10(6)/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70% to 93%), at a median of 21 days (range, 19 to 23). At 2 years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and Ill to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100 days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% 95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion. (C) 2018 American Society for Blood and Marrow Transplantation.Peer reviewe

Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: A study from the Chronic Malignancies Working Party of the EBMT

We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received upfront single (n = 3391) or tandem transplantation (n = 353) between 2005 and 2014 with available data on extramedullary in-volvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n = 682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%) while the majority of 3062 (81.8%) patients had no extramedullary disease. More patients with extramedul-lary organ involvement had multiple involved sites (>/=2;) (p < 0.001). In patients with single sites compared to patients without the disease, upfront transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: p = 0.86, and extramedullary organ: p = 0.88). In single paraskeletal involvement, this translated less clearly into 3-year overall survival (p = 0.07) while single organ involvement was significantly worse (p = 0.001). Multiple organ sites were associated with worse outcome (p < 0.001 and p = 0.01). First line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (p = 0.13, respectively)

Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a study from the Chronic Malignancies Working Party of the EBMT

We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (>= 2; P<0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: P=0.86, and extramedullary organ: P=0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival (P=0.07) while single organ involvement was significantly worse (P=0.001). Multiple organ sites were associated with worse outcome (P<0.001 and P=0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (P=0.13 for both)

Locomotor adaptation to support surface perturbations is characterized by environmental decoupling

Human locomotor adaptation requires control processes driven by sensory feedback to maintain dynamic stability in response to environmental perturbations. Effective postural adaptation is characterized by a decoupling of the environmental perturbation and movements of the trunk. Maladaptive adaptation in conditions of inaccurate sensory input may lead to postural instability. In this study we investigated locomotor adaptation to a continuously rolling treadmill. While walking on the treadmill, 20 participants performed a locomotor adaptation, consisting of baseline, adaptation (sinusoidal roll: ± 5°), catch, retention and transfer trials. Learning was quantified as a decoupling of mediolateral treadmill and trunk roll, computed as the cross-correlation function (XCF) between treadmill and trunk motion. Analysis revealed a trend of decoupling over consecutive trials. Decoupling is primarily observed in the learning phase, indicated by a systematic reduction in XCF in treadmill – trunk (p\u3c0.01) coupling. The learnt sinusoidal roll dynamics transfer to a randomized rolling treadmill (p\u3c0.05). As learning environmental dynamics occurs, over time a stable decoupled state is achieved and maintained. Significant transfer of decoupling behaviour to the random perturbation, suggests sensory reorganization as the driving phenomenon. Increased reliance on visual information to encode physical orientation, as opposed to lower-limb proprioceptive signals allows suprapelvic body segments to be controlled using sensory feedback from more stable sources in the environment. Over time this allows for the minimization of mechanical environmental influences

Age-dependent modulation of sensory reweighting for controlling posture in a dynamic virtual environment.

International audienceOlder adults require more time to reweight sensory information for maintaining balance that could potentially lead to increased incidence of falling in rapidly changing or cognitively demanding environments. In this study, we manipulated the visual surround information during a collision avoidance task in order to investigate how young and elderly adults engage in sensory reweighting under conditions of visual anticipation. Sixteen healthy elderly (age: 71.5 ± 4.9 years; height: 159.3 ± 6.6 cm; mass: 73.3 ± 3.3 kg) and 20 young (age: 22.8 ± 3.3 years; height: 174.4 ± 10.7 cm; mass: 70.1 ± 13.9 kg) participants stood for 240 s on a force platform under two experimental conditions: quiet standing and standing while anticipating randomly approaching virtual objects to be avoided. During both tasks, the visual surround changed every 60 s from a stationary virtual scene (room) to either a moving room or darkness and then back to a stationary scene to evoke sensory reweighting processes. In quiet standing, elderly showed greater sway variability and were more severely affected by the removal or degradation of visual surround information when compared to young participants. During visual anticipation, sway variability was not different between the age groups. In addition, both young and elderly participants were similarly affected by the degradation or removal of the visual surround. These findings suggest that sensory reweighting in a dynamic virtual environment that evokes visual anticipation interacts with postural state anxiety regardless of age. Elderly show less efficient sensory reweighting in quiet standing due to greater visual field dependence possibly associated with fear of falling

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma:An EBMT/CIBMTR Report

Allogeneic hematopoietic cell transplantation (allo-HCT) using siblings and matched donors has the potential for long-term disease control in a subset of high-risk patients with multiple myeloma (MM); however, the data on using haploidentical donors in this disease are limited. We conducted a retrospective analysis to examine the outcomes of patients with MM who underwent haploidentical allo-HCT within European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers. A total of 96 patients underwent haploidentical allo-HCT between 2008 and 2016. With a median follow-up of 24.0 months (range, 13.2 to 24.9 months), 97% (95% confidence interval [CI], 93% to 100%) of patients had neutrophil engraftment by day 28, and 75% (95% CI, 66% to 84%) achieved platelet recovery by day 60. Two-year progression-free survival (PFS) was 17% (95% CI, 8% to 26%), and overall survival (OS) was 48% (95% CI, 36% to 59%). At 2 years, the cumulative risk of relapse/progression was 56% (95% CI, 45% to 67%), and 1-year nonrelapse mortality (NRM) was 21% (95% CI, 13% to 29%). The incidences of acute graft-versus-host-disease (GVHD) grades II-IV by 100 days and chronic GVHD at 2 years were 39% (95% CI, 28% to 49%) and 46% (95% CI, 34% to 59%), respectively. On univariate analysis, use of post-transplantation cyclophosphamide (PT-Cy) (54% [95% CI, 41% to 68%] versus 25% [95% CI, 1% to 48%]; P =.009) and use of bone marrow as source of stem cells (72% [95% CI, 55% to 89%] versus 31% [95% CI, 17% to 46%]; P = .001) were associated with improved OS at 2 years. Disease status, patient sex, intensity of conditioning regimen, recipient/donor sex mismatch, and cytomegalovirus serostatus had no impact on OS, PFS, or NRM. Haploidentical transplantation is feasible for patients with multiply relapsed or high-risk MM, with an encouraging 2-year OS of 48% and an NRM of 21% at 1 year, supporting further investigation of haploidentical allo-HCT in suitable candidates with MM