Vestibulo-Ocular Reflex Suppression: Clinical Relevance and Assessment in the Digital Age.

Background: Visual acuity and image stability are crucial for daily activities, particularly during head motion. The vestibulo-ocular reflex (VOR) and its suppression (VORS) support stable fixation of objects of interest. The VOR drives a reflexive eye movement to counter retinal slip of a stable target during head motion. In contrast, VORS inhibits this countermovement when the target stimulus is in motion. The VORS allows for object fixation when it aligns with the direction of the head's movement, or when an object within or outside the peripheral vision needs to be focused upon. Summary: Deficits of the VORS have been linked to age-related diseases such as balance deficits associated with an increased fall risk. Therefore, the accurate assessment of the VORS is of particular clinical relevance. However, current clinical assessment methods for VORS are mainly qualitative and not sufficiently standardised. Recent advances in digital health technology, such as smartphone-based videooculography, offer a promising alternative for assessing VORS in a more accessible, efficient, and quantitative manner. Moreover, integrating mobile eye-tracking technology with virtual reality environments allows for the implementation of controlled VORS assessments with different visual inputs. These assessment approaches allow the extraction of novel parameters with potential pathomechanistic and clinical relevance. Key Messages: We argue that researchers and clinicians can obtain a more nuanced understanding of this ocular stabilisation reflex and its associated pathologies by harnessing digital health technology for VORS assessment. Further research is warranted to explore the technologies' full potential and utility in clinical practice.

Postural Sway in Parkinson's Disease and Multiple Sclerosis Patients During Tasks With Different Complexity.

Neurological diseases are associated with static postural instability. Differences in postural sway between neurological diseases could include "conceptual" information about how certain symptoms affect static postural stability. This information might have the potential to become a helpful aid during the process of finding the most appropriate treatment and training program. Therefore, this study investigated static postural sway performance of Parkinson's disease (PD) and multiple sclerosis (MS) patients, as well as of a cohort of healthy adults. Three increasingly difficult static postural tasks were performed, in order to determine whether the postural strategies of the two disease groups differ in response to the increased complexity of the balance task. Participants had to perform three stance tasks (side-by-side, semi-tandem and tandem stance) and maintain these positions for 10 s. Seven static sway parameters were extracted from an inertial measurement unit that participants wore on the lower back. Data of 47 healthy adults, 14 PD patients and 8 MS patients were analyzed. Both healthy adults and MS patients showed a substantial increase in several static sway parameters with increasingly complex stance tasks, whereas PD patients did not. In the MS patients, the observed substantial change was driven by large increases from semi-tandem and tandem stance. This study revealed differences in static sway adaptations between PD and MS patients to increasingly complex stance tasks. Therefore, PD and MS patients might require different training programs to improve their static postural stability. Moreover, this study indicates, at least indirectly, that rigidity/bradykinesia and spasticity lead to different adaptive processes in static sway.

Butyrophilin 3A/CD277-Dependent Activation of Human γδ T Cells: Accessory Cell Capacity of Distinct Leukocyte Populations.

Human Vγ9Vδ2 T cells recognize in a butyrophilin 3A/CD277-dependent way microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) or endogenous pyrophosphates (isopentenyl pyrophosphate [IPP]). Nitrogen-bisphosphonates such as zoledronic acid (ZOL) trigger selective γδ T cell activation because they stimulate IPP production in monocytes by inhibiting the mevalonate pathway downstream of IPP synthesis. We performed a comparative analysis of the capacity of purified monocytes, neutrophils, and CD4 T cells to serve as accessory cells for Vγ9Vδ2 T cell activation in response to three selective but mechanistically distinct stimuli (ZOL, HMBPP, agonistic anti-CD277 mAb). Only monocytes supported γδ T cell expansion in response to all three stimuli, whereas both neutrophils and CD4 T cells presented HMBPP but failed to induce γδ T cell expansion in the presence of ZOL or anti-CD277 mAb. Preincubation of accessory cells with the respective stimuli revealed potent γδ T cell-stimulating activity of ZOL- or anti-CD277 mAb-pretreated monocytes, but not neutrophils. In comparison with monocytes, ZOL-pretreated neutrophils produced little, if any, IPP and expressed much lower levels of farnesyl pyrophosphate synthase. Exogenous IL-18 enhanced the γδ T cell expansion with all three stimuli, remarkably also in response to CD4 T cells and neutrophils preincubated with anti-CD277 mAb or HMBPP. Our study uncovers unexpected differences between monocytes and neutrophils in their accessory function for human γδ T cells and underscores the important role of IL-18 in driving γδ T cell expansion. These results may have implications for the design of γδ T cell-based immunotherapeutic strategies.