Background: Mutations in the GBA gene that encodes the lysosomal enzyme acid β‐glucocerebrosidase cause Gaucher disease (GD), the most common lysosomal storage disorder. Most of the mutations are missense/nonsense, however, a few splicing mutations within or close to conserved consensus donor or acceptor splice sites have also been described. The aim of the study was to identify the mutation(s) in a Cypriot patient with type I GD.Methods: The genomic DNA of the proband was screened for nine common mutations using Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. All exons and exon‐intron boundaries, and the 5’UTR and 3’UTR regions of the GBA gene, were investigated by Sanger sequencing. RNA analysis was performed using standard procedures, and the abnormal transcript was further cloned into pGEM‐T‐Easy plasmid vector and sequenced. The relevant intronic region was further sequenced by the Sanger method to identify the genetic variant.Results: A novel point mutation, g.12599C > A (c.999 + 242C > A), was detected deep in intron 7 of the GBA gene. This type of mutation has been previously described for other diseases but this is the first time, as far as we know, that it is described for GD. This mutation creates a new donor splice site leading to aberrant splicing and resulting in the insertion of the first 239nt of intron 7 as a pseudoexon in the mRNA, creating a premature stop codon.Conclusion: This study expands the mutation spectrum of GD and highlights the importance of RNA sequencing for the molecular diagnosis of patients bearing mutations in nonexonic regions.

Restoring mobility and rehabilitation of gait are high priorities for post-stroke rehabilitation. Cueing using metronomic rhythmic sensory stimulation has been shown to improve gait, but most versions of this approach have used auditory and visual cues. In contrast, we developed a prototype wearable system for rhythmic cueing based on haptics, which was shown to be highly effective in an early pilot study. In this paper we describe a follow-up study with four stroke survivors to inform design, and to identify issues and requirements for such devices to be used in home-based or out-door settings. To this end, we present a blended user-centred design study of a wearable haptic gait rehabilitation system. This study draws on the combined views of physiotherapists, nurses, interaction designers and stroke survivors. Many of the findings were unanticipated, identifying issues outside the scope of initial designs, with important implications for future design and appropriate use

Wearable technologies, in the form of small, light and inconspicuous devices, can be designed to help individuals suffering from neurological conditions carry out regular rehabilitation exercises. Current research has shown that walking to a rhythm can lead to significant improvements in various aspects of gait. Our primary aim is to provide a suitable, technology based intervention to enhance gait rehabilitation of people with chronic and degenerative neurological health conditions (such as stroke). This intervention will be in the form of small, lightweight, wireless, wearable devices the user can take out of the clinic, extending their rehabilitation to their own home setting. The devices can deliver a series of vibrations at a steady rhythm giving the patient a more stable and symmetric pace of walking. The simplest version of this approach typically comprise of a very small network of just two nodes and a central controller. The existing prototypes (called the Haptic Bracelets) capture and analyse motion data in real time to provide adaptive haptic (through vibrations) cueing. In the future and after more refinement, the system could allow a single therapist to monitor and advise groups of stroke survivors undergoing therapy sessions.

Background: Huntington disease (HD) is an inherited genetic disorder that results in the death of brain cells. HD symptoms generally start with subtle changes in mood and mental abilities; they then degenerate progressively, ensuing a general lack of coordination and an unsteady gait, ultimately resulting in death. There is currently no cure for HD. Walking cued by an external, usually auditory, rhythm has been shown to steady gait and help with movement coordination in other neurological conditions. More recently, work with other neurological conditions has demonstrated that haptic (ie, tactile) rhythmic cues, as opposed to audio cues, offer similar improvements when walking. An added benefit is that less intrusive, more private cues are delivered by a wearable device that leaves the ears free for conversation, situation awareness, and safety. This paper presents a case study where rhythmic haptic cueing (RHC) was applied to one person with HD. The case study has two elements: the gait data we collected from our wearable devices and the comments we received from a group of highly trained expert physiotherapists and specialists in HD. Objective: The objective of this case study was to investigate whether RHC can be applied to improve gait coordination and limb control in people living with HD. While not offering a cure, therapeutic outcomes may delay the onset or severity of symptoms, with the potential to improve and prolong quality of life. Methods: The approach adopted for this study includes two elements, one quantitative and one qualitative. The first is a repeated-measures design with three conditions: before haptic rhythm (ie, baseline), with haptic rhythm, and after exposure to haptic rhythm. The second element is an in-depth interview with physiotherapists observing the session. Results: In comparison to the baseline, the physiotherapists noted a number of improvements to the participant’s kinematics during her walk with the haptic cues. These improvements continued in the after-cue condition, indicating some lasting effects. The quantitative data obtained support the physiotherapists’ observations. Conclusions: The findings from this small case study, with a single participant, suggest that a haptic metronomic rhythm may have immediate, potentially therapeutic benefits for the walking kinematics of people living with HD and warrants further investigation.

Background: Rhythm, brain, and body are closely linked. Humans can synchronize their movement to auditory rhythms in ways that can improve the regularity of movement while reducing perceived effort. However, the ability to perform rhythmic movement may be disrupted by various neurological conditions. Many such conditions impair mechanisms that control movement, such as gait, but typically without rhythmic perception being affected. This paper focuses on hemiparetic stroke, a neurological condition that affects one side of the body. Hemiparetic stroke can cause severe asymmetries in gait, leading to numerous physical problems ranging from muscle degeneration to bone fractures. Movement synchronization via entrainment to auditory metronomes is known to improve asymmetry and related gait problems; this paper presents the first systematic study of entrainment for gait rehabilitation via the haptic modality. Objective: This paper explores the gait rehabilitation of people with hemiparesis following a stroke or brain injury, by a process of haptic entrainment to rhythmic cues. Various objective measures, such as stride length and stride time, are considered. Methods: This study is a quantitative gait study combining temporal and spatial data on haptically cued participants with hemiparetic stroke and brain injury. We designed wearable devices to deliver the haptic rhythm, called Haptic Bracelets, which were placed on the leg near the knee. Spatial data were recorded using a Qualisys optical motion capturing system, consisting of 8 optoelectronic cameras, and 20 markers placed on anatomical lower limb landmarks and 4 additional tracking clusters placed on the right and left shank and thigh. Gait characteristics were measured before, during, and after cueing. Results: All 11 successfully screened participants were able to synchronize their steps to a haptically presented rhythm. Specifically, 6 participants demonstrated immediate improvements regarding their temporal gait characteristics, and 3 of the 6 improved their gait in terms of spatial characteristics. Conclusions: Considering the great variability between survivors of stroke and brain injury and the limited number of available participants in our study, there is no claim of statistical evidence that supports a formal experimental result of improved gait. However, viewing this empirical gait investigation as a set of 11 case studies, more modest empirical claims can be made. All participants were able to synchronize their steps to a haptically presented rhythm. For a substantial proportion of participants, an immediate (though not necessarily lasting) improvement of temporal gait characteristics was found during cueing. Some improvements over baseline occurred immediately after, rather than during, haptic cueing. Design issues and trade-offs are identified, and interactions between perception, sensory deficit, attention, memory, cognitive load, and haptic entrainment are noted.