Psychometric Properties of LUN-MS: A New Questionnaire to Identify the Unmet Needs of People With Multiple Sclerosis.

Background: We developed a 29-item Questionnaire, Long-term Unmet Needs in MS (LUN-MS) to identify the unmet needs of people with multiple sclerosis (pwMS). Objective: To assess acceptability, test-retest reliability, internal consistency, and validity of the LUN-MS. Methods: Participants completed the LUN-MS and MSIS-29 twice, four weeks apart. Acceptability was assessed by looking at the response rate in each time point. Reliability was calculated by comparing the response during the two time points using Cohen's weighted kappa. Using principal component analysis, the dimensionality of the questionnaire's items was reduced, to five domains and the internal consistency of each domain was assessed using Cronbach's alpha. Concurrent validity was tested by comparing the total LUN-MS score against MSIS-29 and EQ-5D-3L using Pearson's product-moment correlation coefficient. Results: Among 88 participants, rate of completion at time points-1 and 2 was 96 and 80% respectively. Test-retest reliability for individual items was between fair to near-perfect (weighted Cohen's kappa 0.39-0.81). The unmet needs could be divided into five internally consistent domains (Cronbach's alpha 0.83-0.74): neuropsychological, ambulation, physical, interpersonal relationship and informational. Concurrent validity with MSIS-29 (r = 0.705, P < .001) and EQ-5D-3L (r = 0.617, P < .001) were good. Conclusion: LUN-MS is a reliable, valid, and acceptable tool to identify the unmet needs of pwMS.

Cognition and Quality of Life of People with Spinal Cord Injury.

Objectives: The aim of this study was to assess the cognitive abilities of people with spinal cord injury (SCI) using the Edinburgh Cognitive and Behavior Amyotrophic Lateral Sclerosis Screen (ECAS), a tool designed for testing cognition in individuals with limited hand motor function. The impact of cognitive dysfunction on quality of life was also assessed. Methods: Forty-one patients with SCI were assessed using ECAS, the brief version of the World Health Organisation Quality of Life questionnaire (WHOQOL-BREF), and the Spinal Cord Independence Measure. Results: Overall, 28 of the 41 participants scored below the cut-off threshold for normal population in ECAS. The domains affected were language, 63%; memory, 51%; executive function, 44%; verbal fluency, 44%; and visuospatial skills, 24%. On multiple regression analysis, the ECAS total score moderately strongly explained the variance in the WHOQOL-BREF psychological (ß = 0.428, t = 2.958, P = 0.005) and environmental (ß = 0.411, t = 2.819, P = 0.008) domains. ECAS memory scores independently influenced WHOQOL-BREF physical (ß = 0.398, t = 2.67, P = 0.011) and environmental (ß = 0.37, t = 2.697, P = 0.010) domains. WHOQOL-BREF psychological scores were significantly influenced by ECAS executive scores (ß = 0.415, t = 2.85, P = 0.007), whereas the social domain was not significantly influenced by ECAS scores. Conclusions: It was feasible to use ECAS in individuals with SCI. Cognitive ability influenced the quality of life of people with SCI.

Usability engineering in practice: developing an intervention for post-stroke therapy during a global pandemic.

This paper provides an overview of the usability engineering process and relevant standards informing the development of medical devices, together with adaptations to accommodate situations such as global pandemics where use of traditional face-to-face methods is restricted. To highlight some of those adaptations, a case study of a project developing a novel electronic rehabilitation device is referenced, which commenced in November 2020 amidst the COVID-19 pandemic. The Sheffield Adaptive Patterned Electrical Stimulation (SHAPES) project, led by Sheffield Teaching Hospitals NHS Foundation Trust (STH), aimed to design, manufacture and trial an intervention for use to treat upper arm spasticity after stroke. Presented is an outline and discussion of the challenges experienced in developing the SHAPES health technology intended for at-home use by stroke survivors and in implementing usability engineering approaches. Also highlighted, are the benefits that arose, which can offer easier involvement of vulnerable users and add flexibility in the ways that user feedback is sought. Challenges included: restricted travel; access to usual prototyping facilities; social distancing; infection prevention and control; availability of components; and changing work pressures and demands. Whereas benefits include: less travel; less time commitment; and greater scope for participants with restricted mobility to participate in the process. The paper advocates a more flexible approach to usability engineering and outlines the onward path for development and trialling of the SHAPES technology.

The Effectiveness of Physiotherapy Interventions for Mobility in Severe Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: People with Multiple Sclerosis (pwMS) prioritise gait as the most valuable function to be affected by MS. Physiotherapy plays a key role in managing gait impairment in MS. There is little evidence on the effectiveness of physiotherapy for severe MS. Objective: To undertake a systematic review and meta-analysis of the literature to identify evidence for the effectiveness of physiotherapy for gait impairment in severe MS. Methods. The available literature was systematically searched, using a predetermined protocol, to identify research studies investigating a physiotherapy intervention for mobility in people with severe MS (EDSS ≥ 6.0). Data on mobility related endpoints was extracted. Meta-analysis was performed where a given mobility end point was reported in at least 3 studies. Results: 37 relevant papers were identified, which included 788 pwMS. Seven mobility-related endpoints were meta-analysed. Robot-Assisted Gait Training (RAGT) was found to improve performance on the 6-minute walk test, 10-metre walk test, fatigue severity scale, and Berg Balance Scale. Neither body weight supported training nor conventional walking training significantly improved any mobility-related outcomes. Conclusion: Physiotherapy interventions are feasible for mobility in severe MS. There is some evidence for the effectiveness of RAGT.

Fatigue in multiple sclerosis: A UK MS-register based study.

BACKGROUND: Fatigue is a widely experienced, incapacitating symptom of MS. It hinders daily functioning and has deleterious effects on quality of life. The UK MS Register is an online registry of over 20,000 participants with MS. The aim of this study was to estimate the prevalence, predictors, and impact of fatigue on people with MS using data from the UKMS register. METHODS: All participants who completed the Fatigue Severity Scale (FSS), WebEDSS, Hospital Anxiety and Depression Scale (HADS) within 28 days of each other were selected from the UK MS Register. Data on age, gender, duration and type of MS, use of disease modifying drugs and comorbidities were obtained from the UKMS register. We categorised people with FSS score of 5 or more as with fatigue and those with scores of 4 or less as without fatigue. Descriptive statistics and logistical and multiple regressions were used to explore predictors of fatigue and the effect of fatigue on mobility (MS Walking Scale), physical and psychological aspects of life (MS Impact Scale) and quality of life (European Quality of Life 5D-3 L). RESULTS: Amongst the 20,946 participants of the UK MS registry, 4620 completed FSS. Out of these, 775 (mean age= 54.71 years, SD= 10.90; mean duration of MS diagnosis =13.21 years, SD=9.75) had completed the FSS, Web EDSS and Hospital Anxiety and Depression Scale within 28 days of each other. 427 (55.1%) of pwMS had a FSS score >5 consistent with clinical fatigue. Logistic regression analysis showed that depression (p=<0.001), duration of MS (p = 0.017), secondary progressive MS (p = 0.001) and EDSS (p=<0.001) predicted fatigue. FSS scores had a significant negative impact on both psychological (p > 0.001) and physical (p > 0.001) domains of the MS Impact scale, MS walking scale (p = 0.003) and EQoL (p = 0.005). CONCLUSIONS: Fatigue was a common symptom amongst people with MS. Depression, longer duration of MS, secondary progressive MS, and high EDSS predicted fatigue. Fatigue had an adverse effect on physical activities, mobility, psychological wellbeing, and quality of life of people with MS.

Remote ischaemic conditioning for stroke: unanswered questions and future directions.

Remote ischaemic conditioning (RIC) refers to a process whereby periods of intermittent ischaemia, typically via the cyclical application of a blood pressure cuff to a limb at above systolic pressure, confers systemic protection against ischaemia in spatially distinct vascular territories. The mechanisms underlying this have not been characterised fully but have been shown to involve neural, hormonal and systemic inflammatory signalling cascades. Preclinical and early clinical studies have been promising and suggest beneficial effects of RIC in acute ischaemic stroke, symptomatic intracranial stenosis and vascular cognitive impairment. Through systematic searches of several clinical trials databases we identified 48 active clinical trials of RIC in ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage. We summarise the different RIC protocols and outcome measures studied in ongoing clinical trials and highlight which studies are most likely to elucidate the underlying biological mechanisms of RIC and characterise its efficacy in the near future. We discuss the uncertainties of RIC including the optimal frequency and duration of therapy, target patient groups, cost-effectiveness, the confounding impact of medications and the absence of a clinically meaningful biomarker of the conditioning response. With several large clinical trials of RIC expected to report their outcomes within the next 2 years, this review aims to highlight the most important studies and unanswered questions that will need to be addressed before this potentially widely accessible and low-cost intervention can be used in clinical practice.

A Multifactorial Model of Multiple Sclerosis Gait and Its Changes Across Different Disability Levels.

OBJECTIVE: Mobility assessment is critical in the clinical management of people with Multiple Sclerosis (pwMS). Instrumented gait analysis provides a plethora of metrics for quantifying concurrent factors contributing to gait deterioration. However, a gait model discriminating underlying features contributing to this deterioration is lacking in pwMS. This study aimed at developing and validating such a model. METHODS: The gait of 24 healthy controls and 114 pwMS with mild, moderate, or severe disability was measured with inertial sensors on the shanks and lower trunk while walking for 6 minutes along a hospital corridor. Twenty out of thirty-six initially explored metrics computed from the sensor data met the quality criteria for exploratory factor analysis. This analysis provided the sought model, which underwent a confirmatory factor analysis before being used to characterize gait impairment across the three disability groups. RESULTS: A gait model consisting of five domains (rhythm/variability, pace, asymmetry, and forward and lateral dynamic balance) was revealed by the factor analysis, which was able to highlight gait abnormalities across the disability groups: significant alterations in rhythm/variability-, asymmetry-, and pace-based features were present in the mild group, but these were more profound in the moderate and severe groups. Deterioration in dynamic balance-based features was only noted in pwMS with a moderate and severe disability. CONCLUSION: A conceptual model of gait for disease-specific mobility assessment in pwMS was successfully developed and tested. SIGNIFICANCE: The new model, built with metrics that represent gait impairment in pwMS, highlighted clinically relevant changes across different disability levels, including those with no clinically observable walking disability. This shows the clear potential as a monitoring biomarker in pwMS.

Survival following the placement of gastrostomy tube in patients with multiple sclerosis.

BACKGROUND: Around a third of people with multiple sclerosis (MS) experience dysphagia. There is a need for disease-specific information on survival following placement of gastrostomy tube in people with MS. OBJECTIVE: We aimed to study survival following gastrostomy in patients with MS. METHODS: We reviewed medical records, home enteral feeding database and death certificates of people with MS who had gastrostomy from 2005 to 2017. Cox regression analysis was performed to identify independent predictors associated with mortality after gastrostomy. RESULTS: Median survival of 53 patients with MS after gastrostomy was 21.73 months. Median duration of hospital stay after gastrostomy was 14 days (IQR 5.25, 51.5). Survival at 30 days, 3 months, 1, 2, 5 and 10 years were 100% (53/53), 98.1% (52/53), 81.1% (43/53), 54.7% (29/53), 22.4% (11/49) and 6.8% (3/44), respectively. Of 53 patients, 24 died due to respiratory tract infection. Patients who had gastrostomy tube before 50 years of age survived longer (median 28.48 months) compared with those who had the gastrostomy after age 50 years (median 17.51 months) (p = 0.040). CONCLUSION: Around 54% of patients with MS survived two or more years following gastrostomy. Younger patients had better survival. The most frequent cause of death was respiratory infection.

Is a Wearable Sensor-Based Characterisation of Gait Robust Enough to Overcome Differences Between Measurement Protocols? A Multi-Centric Pragmatic Study in Patients with Multiple Sclerosis.

Inertial measurement units (IMUs) allow accurate quantification of gait impairment of people with multiple sclerosis (pwMS). Nonetheless, it is not clear how IMU-based metrics might be influenced by pragmatic aspects associated with clinical translation of this approach, such as data collection settings and gait protocols. In this study, we hypothesised that these aspects do not significantly alter those characteristics of gait that are more related to quality and energetic efficiency and are quantifiable via acceleration related metrics, such as intensity, smoothness, stability, symmetry, and regularity. To test this hypothesis, we compared 33 IMU-based metrics extracted from data, retrospectively collected by two independent centres on two matched cohorts of pwMS. As a worst-case scenario, a walking test was performed in the two centres at a different speed along corridors of different lengths, using different IMU systems, which were also positioned differently. The results showed that the majority of the temporal metrics (9 out of 12) exhibited significant between-centre differences. Conversely, the between-centre differences in the gait quality metrics were small and comparable to those associated with a test-retest analysis under equivalent conditions. Therefore, the gait quality metrics are promising candidates for reliable multi-centric studies aiming at assessing rehabilitation interventions within a routine clinical context.

Reliability and acceptability of the Multiple Sclerosis Quality of Life-29 questionnaire in an English-speaking cohort.

BACKGROUND: Multiple Sclerosis Quality-of-Life Questionnaire-54 (MSQoL-54) is a disease-specific instrument for assessing health-related quality of life (HRQoL). Due to the number of items, the time taken to complete it is long. A shorter 29-item version, Multiple Sclerosis Quality-of-Life Questionnaire-29 (MSQoL-29) is yet to be evaluated in English. OBJECTIVE: To assess reliability and acceptability of English version of MSQoL-29. METHODS: Among 100 participants with MS who first completed both MSQoL-54 and MSQoL-29, 91 completed MSQoL-29 after 4-8 weeks. We looked for internal consistency (Cronbach's alpha), acceptability, reliability (intraclass correlation coefficients (ICCs)) and agreement (Bland-Altman plots). RESULTS: ICCs were strongly positive between MSQoL-54 and MSQoL-29 (Physical Health Composite (PHC) -ICC = 0.914, confidence interval (CI) = 0.872-0.942; Mental Health Composite (MHC) - ICC = 0.875, CI = 0.814-0.916) and between the two MSQoL-29 (PHC - ICC = 0.970, CI = 0.955-0.980; MHC - ICC = 0.937, CI = 0.904-0.958). On Bland-Altman plots, the MSQoL-29 scores of 95% of participants during two visits were within the limits of agreement (LOAs). Time taken to complete MSQoL-29 was 7.2 ± 2.9 minutes and MSQoL-54 was 19.79 ± 5.4 minutes (p = 0.0001). CONCLUSION: MSQoL-29 has good test-retest reliability in English-speaking population and was quicker to complete.

Intermittent theta-burst stimulation for upper-limb dysfunction and spasticity in spinal cord injury: a single-blind randomized feasibility study.

STUDY DESIGN: Single-blind, sham-controlled, crossover randomized feasibility study OBJECTIVES: (1) Assess the feasibility of a full-scale trial of intermittent theta-burst stimulation (iTBS) for upper-limb sensorimotor dysfunction following spinal cord injury (SCI). (2) Determine the safety and tolerability of iTBS over primary motor cortex on upper-limb function in people with spinal cord injury (SCI). SETTING: Large Tertiary Spinal Injuries Centre METHODS: Participants with incomplete SCI, suffering with upper-limb spasticity were recruited and randomized to receive active/sham iTBS over the hand representation of the primary motor cortex. The intervention was delivered in 10 sessions over a 2-week period, followed by a 2-week washout, before being crossed over to receive the alternative intervention for the same number of sessions. Feasibility was assessed by pre-specified criteria which included recruitment rate of 3 participants per month, 10 completed interventions and 10 complete data sets for 15 recruited participants with no serious adverse events. Secondary outcomes included preliminary data collection for spasticity, pain and sensorimotor function. RESULTS: Twelve participants were recruited over 10 weeks (i.e., 4.8 per month), with 11 randomized and 10 completing the intervention protocol with no serious adverse events. Eight complete data sets were obtained as two participants failed to attend follow-up. Data from 10 participants were analyzed, with one early dropout due to an unrelated adverse event. CONCLUSIONS: It is safe and feasible to conduct a full-scale trial. Whilst iTBS has shown promising results, further research optimizing the intervention is required to improve anticipated clinical efficacy.

Sensory Barrage Stimulation in the Treatment of Elbow Spasticity: A Crossover Double Blind Randomized Pilot Trial.

OBJECTIVE: To assess the feasibility of using a novel form of multichannel electrical stimulation, termed Sensory Barrage Stimulation (SBS) for the treatment of spasticity affecting the elbow flexor muscles and to compare this with conventional single-channel TENS stimulation. MATERIALS AND METHODS: Altogether ten participants with spasticity of the flexor muscles of the elbow of Grade 2 or above on the Modified Ashworth Scale (MAS) were recruited to this crossover double blind randomized trial. The participants received two intervention sessions (SBS and TENS), one week apart in a randomized order. Both interventions were applied over the triceps brachii on the affected arm for a duration of 60 minutes. Spasticity was measured using the MAS. Secondary outcome measures were self-reported change in spasticity, measured on a visual analog scale (VAS, 0-100), and therapist-rated strength of elbow extension and strength of elbow flexion. Measurements were taken immediately before each intervention was applied, immediately after the intervention, and one hour after the intervention. RESULTS: Immediately after stimulation spasticity showed a significant reduction for both TENS and SBS groups assessed by MAS -0.9 ± 0.2 vs. -1.1 ± 0.2 and by VAS -15 ± 3 vs. -31 ± 8. For SBS this improvement in MAS was still present at one hour after the stimulation, but not for TENS. Altogether seven SBS responders and four TENS responders were identified. CONCLUSIONS: This study demonstrates the feasibility and practicality of applying the new concept of SBS. Promising results indicate it causes a reduction in spasticity.

Spasticity: pathophysiology, evaluation and management.

Spasticity is common in many neurological disorders, such as stroke and multiple sclerosis. It is part of the upper motor neurone syndrome manifesting as increased tone, clonus, spasms, spastic dystonia and co-contractions. The impact of spasticity varies from it being a subtle neurological sign to severe spasticity causing pain and contractures. Existing spasticity can be worsened by external factors such as constipation, urinary tract infections or pressure ulcers. Its management involves identification and elimination of triggers; neurophysiotherapy; oral medications such as baclofen, tizanidine and dantrolene; focal injection of botulinum toxin, alcohol or phenol, or baclofen delivered intrathecally through a pump; and surgical resection of selected dorsal roots of the spinal cord. This article reviews the current understanding of pathophysiology, clinical features and management of spasticity.

Tics after traumatic brain injury.

BACKGROUND: Tics are involuntary non-rhythmic, stereotyped muscle contractions which can be suppressed temporarily. Tics usually start during childhood as part of Tourette syndrome. Adult onset tics are infrequent. This study reports on an adult man who developed tics 1 year after severe traumatic brain injury (TBI). METHODS: Case report and review of literature. RESULTS: A 19-year-old man sustained TBI following a road traffic accident. He did not have tics or features of obsessive compulsive disorder before the brain injury. A year after injury he developed motor and vocal tics. Magnetic resonance image of the brain showed lesions in the basal ganglia. A search of databases Medline, EMBASE and CINHAL found only four publications on tics in adults with TBI. None of these reported cases had lesions in the basal ganglia. CONCLUSION: Tics are a rare complication of TBI. People with early onset post-traumatic tics may have had a previously unrecognized, mild tic disorder or a genetic predisposition for tics, which was unmasked by the TBI. In contrast, late post-traumatic tics could be due to delayed effects of injury on neural circuits connecting the frontal cortex and basal ganglia.