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Aim: Chronic stroke walking impairment is associated with high healthcare resource utilization (HCRU) costs. InTandem™ is a neurorehabilitation system that autonomously delivers a rhythmic auditory stimulation (RAS)-based intervention for the at-home rehabilitation of walking impairment in adults in the chronic phase of stroke recovery. This study was conducted to estimate the budget impact of InTandem in comparison with currently available intervention strategies for improvement of gait/ambulation in individuals with chronic stroke walking impairment. Methods & materials: A budget impact analysis (BIA) for InTandem was conducted based on a 1-million-member US third-party payer perspective over a 1-year time horizon. Key inputs for the budget impact model were: costs for each intervention strategy (InTandem, physical therapy, self-directed walking and no treatment), HCRU costs for persons with chronic stroke and anticipated HCRU cost offsets due to improvements in gait/ambulatory status as measured by self-selected comfortable walking speed (based on functional ability). In addition to the reference case analysis, a sensitivity analysis was conducted. Results: Based on the reference case, introduction of InTandem was projected to result in overall cost savings of $439,954 in one year. Reduction of HCRU costs (-$2,411,778) resulting from improved walking speeds with InTandem offset an increase in intervention costs (+$1,971,824). Demonstrations of cost savings associated with InTandem were robust and were consistently evident in nearly all scenarios evaluated in the sensitivity analysis (e.g., with increased/decreased patient shares, increased HCRU cost or increased InTandem rental duration). Conclusion: The InTandem system is demonstrated to improve walking and ambulation in adults in the chronic phase of stroke recovery after a five-week intervention period. The BIA predicts that introduction of InTandem will be associated with overall cost savings to the payer.

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BACKGROUND: Walking impairment is one of the most prevalent symptoms in people with multiple sclerosis (pwMS). In this study, we aimed to explore the usefulness of a simple walking test, the Timed 25 Foot Walk (T25FW), in detecting subtle differences in "fully ambulatory" pwMS compared to HC. METHODS: We therefore investigated retrospective data from a clinical real-life cohort of 650 pwMS. We first analyzed the amount of patients showing clinically relevant impairment in the T25FW (T25FW > 6 s) within different levels of disability according to the Expanded Disability Status Scale (EDSS). For detailed analysis in "fully ambulatory" pwMS, we formed four groups according to the respective levels of disability (EDSS 0, EDSS 1, EDSS 1.5-2, EDSS 2.5-3), and compared their walking speed to age- and sex-matched healthy controls (HC). RESULTS: In our cohort, the number of patients showing clinically relevant slowing in the T25FW ranged from 15% in "fully ambulatory" patients (EDSS 0-3) to 69% in patients with moderate (EDSS 3.5-5.5) and 100% in patients with severe impairment (EDSS ≥6). Further analyses in "fully ambulatory" patients revealed that all EDSS-subgroups showed significant slowing compared to HC. The mean difference to walking speed of HC became gradually more pronounced from 0.15 m/s in asymptomatic patients (EDSS 0) to 0.5 m/s in patients with EDSS 2.5-3. CONCLUSION: These findings underline the ability of the T25FW to detect slowing even in patients with minimal disability. While the difference to HC was slightly below clinical relevance in asymptomatic patients (EDSS 0), slowing gradually worsened from EDSS 1 onwards and exceeded published thresholds for clinical meaningfulness.

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Background and Objectives: The Walking Impairment Questionnaire (WIQ) is a short and simple tool to measure walking impairment for patients with peripheral arterial disease requiring no special equipment or trained staff. The aim of this study was to assess the validity and reliability of the culturally adapted Lithuanian WIQ version in patients with intermittent claudication. Materials and Methods: In total, 40 patients with intermittent claudication and ankle-brachial index < 0.90 participated in this study. Reliability and internal consistency of the questionnaire were assessed by the intra-class correlation coefficient (ICC) and Cronbach's alpha (α), respectively. Validity was determined by correlations between the WIQ scores and a subjective test (Quality of Life 5 Dimension Questionnaire 3 Level Version (EQ-5D-3L)) and objective tests (6 min walk test (6MWT), treadmill test, and ankle-brachial index). Results: The test-retest reliability was assessed as excellent with an intraclass correlation coefficient of 0.90. The values of Cronbach's alpha were 0.957 (I time) and 0.948 (II time) and indicated an excellent internal consistency. Statistically significant Spearman correlations were detected between the WIQ and walking distances on the 6MWT (rho 0.514, p < 0.001) and treadmill test (rho 0.515, p < 0.001). Higher WIQ scores were associated with longer walking distances and duration. Moderate negative and low negative correlations were found between the WIQ and EQ-5D-3L scores. Conclusions: The Lithuanian version of culturally adapted WIQ demonstrates reliability and validity for patients with intermittent claudication, supported by two different walking tests showing statistically significant moderate Spearman correlations.

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BACKGROUND: Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions. OBJECTIVES: We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: (1) identify clusters of walking behaviors in people post-stroke and neurotypical controls and (2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants. METHODS: We gathered data from 81 post-stroke participants across 4 research sites and collected data from 31 control participants. Using sparse K-means clustering, we identified walking clusters based on 17 spatiotemporal and force variables. We analyzed the biomechanical features within each cluster to characterize cluster-specific walking behaviors. We also assessed the generalizability of the clusters using a leave-one-out approach. RESULTS: We identified 4 stroke clusters: a fast and asymmetric cluster, a moderate speed and asymmetric cluster, a slow cluster with frontal plane force asymmetries, and a slow and symmetric cluster. We also identified a moderate speed and symmetric gait cluster composed of controls and participants post-stroke. The moderate speed and asymmetric stroke cluster did not generalize across sites. CONCLUSIONS: Although post-stroke walking patterns are heterogenous, these patterns can be systematically classified into distinct clusters based on spatiotemporal and force data. Future interventions could target the key features that characterize each cluster to increase the efficacy of interventions to improve mobility in people post-stroke.

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Background: Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions. Objective: We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: 1) identify clusters of walking behaviors in people post-stroke and neurotypical controls, and 2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants. Methods: We gathered data from 81 post-stroke participants across four research sites and collected data from 31 control participants. Using sparse K-means clustering, we identified walking clusters based on 17 spatiotemporal and force variables. We analyzed the biomechanical features within each cluster to characterize cluster-specific walking behaviors. We also assessed the generalizability of the clusters using a leave-one-out approach. Results: We identified four stroke clusters: a fast and asymmetric cluster, a moderate speed and asymmetric cluster, a slow cluster with frontal plane force asymmetries, and a slow and symmetric cluster. We also identified a moderate speed and symmetric gait cluster composed of controls and participants post-stroke. The moderate speed and asymmetric stroke cluster did not generalize across sites. Conclusions: Although post-stroke walking patterns are heterogenous, these patterns can be systematically classified into distinct clusters based on spatiotemporal and force data. Future interventions could target the key features that characterize each cluster to increase the efficacy of interventions to improve mobility in people post-stroke.

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AIMS: Supervised exercise is a guideline-recommended treatment in intermittent claudication (IC). Hospital-based supervised exercise programmes (SEPs) are underutilized, while home-based structured exercise programmes (HSEPs) have attracted interest. The results from HSEP in IC are inconsistent and may confer no benefit over walk advice (WA) and be less effective than SEP. The aim of the study was to compare the effectiveness of best medical treatment, including Nordic pole WA alone, or WA + SEP or WA + HSEP for patients with IC. METHODS AND RESULTS: This three-armed, multicentre randomized clinical trial enrolled patients with IC; all patients received best medical treatment including walking poles and the advice of regular Nordic pole walking (WA). For HSEP and SEP, additional exercise programmes were provided. The primarily investigated hypothesis was a non-inferiority analysis of SEP vs. HSEP regarding the 6-min walk test (6MWT) maximum distance, with a pre-defined non-inferiority margin of 50 m. Supporting outcomes included muscle endurance tests and the walking impairment questionnaire. Outcomes were assessed at baseline, 3, 6, and 12 months by a blinded evaluator. Altogether 166 patients (mean age 72 years; 59% males) were randomized. In HSEP and SEP, 24 and 26% patients, respectively, were fully exercise adherent. All three groups improved pain-free walking distance over time, but there were no significant intergroup differences. The intergroup 6MWT difference between SEP and HSEP from 0 to 12 months was -11.6 m, 95% confidence interval: -36.4 to 13.0 m (i.e. within the pre-specified non-inferiority margin). CONCLUSION: The HSEP was non-inferior to SEP in patients with IC. There were no significant differences observed between the three groups at 1 year. REGISTRATION: ClinicialTrials.gov: NCT02341716.

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BACKGROUND: Walking impairment, a common health problem among older adults, has been linked to poor vision and mental health. This study aimed to investigate the associations of walking impairment with visual impairment, depression, and cognitive function in older adults. METHODS: A total of 1,489 adults aged 60 years and older who had participated in the National Health and Examination Survey (NHANES) 2013-2014 in the United States were included. Multivariate logistic regression models were used to examine the associations of walking impairment with visual impairment, depression, and four subdomains of cognitive function. Sample weights were used to ensure the generalizability of the results. RESULTS: Among all the participants (median age = 68 years; 53.7% women), 17.5% reported walking impairment. Walking impairment was significantly associated with visual impairment (adjusted odds ratio [aOR] = 2.76; 95% CI: 1.47-5.20) and depression (aOR = 4.66; 95% CI: 3.11-6.99). Walking impairment was only associated with the Digit Symbol Substitution (DSST) subdomain of cognitive function in total participants (aOR = 0.97; 95% CI: 0.95-0.99) and in non-Hispanic white adults (aOR = 0.96; 95% CI: 0.94-0.98). Participants with two or three impairment indicators had a higher OR of walking impairment (aOR = 3.64, 95% CI = 2.46-5.38) than those with 0-1 (reference group) impairment indicator. CONCLUSIONS: Walking impairment was associated with visual impairment, depression, and cognitive impairment in American older adults and also positively associated with the number of impairment indicators. The association between walking impairment and cognitive impairment varied according to race. Evaluations of vision, cognition, and depression should be conducted among older adults with walking impairment, and the needs of older adults should be provided in the evaluations alongside information on the biological aspects of their particular race.

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Background and Research Question: Walking impairment remains a major limitation to functional independence after stroke. Yet, comprehensive and effective strategies to improve walking function after stroke are presently limited. Backward Locomotor Treadmill Training (BLTT) is a promising training approach for improving walking function; however, little is known about its mechanism of effect or the relationship between backward walking training and resulting overground forward walking performance. This study aims to determine the effects of serial BLTT on spatial aspects of backward and forward walking in chronic post-stroke individuals with residual walking impairment. Methods: Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3 × /week) over 2 weeks. Outcome measures included PRE-POST changes in backward and forward walking speeds, paretic and non-paretic step lengths, and single-support center of pressure distances. To determine the association between BLTT and overground walking, correlation analyses comparing training-related changes in these variables were performed. Results: We report an overall improvement in BLTT and overground walking speeds, bilateral step lengths, and single-support center of pressure distances over six training sessions. Further, there were weak positive associations between PRE-POST changes in BLTT speed, BLTT paretic step length, and overground forward walking speed. Conclusion and Significance: Our findings suggest that individuals with chronic post-stroke walking impairment experience improvements in spatial walking measures during BLTT and overground. Therefore, BLTT may be a potential adjunctive training approach for post-stroke walking rehabilitation.

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BACKGROUND: Post-stroke walking impairment is a significant cause of chronic disability worldwide and often leads to loss of life roles for survivors and their caregivers. Walking impairment is traditionally classified into mild (>0.8 m/s), moderate (0.41-0.8 m/s), and severe (≤0.4 m/s), and those categorized as "severe" are more likely to be homebound and at greater risk of falls, fractures, and rehospitalization. In addition, there are minimal effective walking rehabilitation strategies currently available for this subgroup. Backward locomotor treadmill training (BLTT) is a novel and promising training approach that has been demonstrated to be safe and feasible across all levels of impairment; however, its benefits across baseline walking impairment levels (severe (≤0.4 m/s) vs. mild-moderate (>0.4 m/s)) have not been examined. METHODS: Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3×/week) over 2 weeks. Baseline and PRE to POST changes were measured during treadmill training and overground walking. RESULTS: Individuals with baseline severe walking impairment were at a more significant functional disadvantage across all spatiotemporal walking measures at baseline and demonstrated fewer overall gains post-training. However, contrary to our working hypothesis, both groups experienced comparable increases in cadence, bilateral percent single support times, and step lengths. CONCLUSION: BLTT is well tolerated and beneficial across all walking impairment levels, and baseline walking speed (≤0.4 m/s) should serve as a covariate in the design of future walking rehabilitation trials.

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Background: Treadmill walking is the most commonly recommended exercise modality in supervised exercise therapy (SET) for peripheral artery disease (PAD); however, other modalities may be equally effective and more tolerable for patients. The primary aim of this single-blind, randomized pilot study was to compare the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of PAD (i.e., "Stepper Study").. Methods: Participants (n = 19) enrolled in a 12-week SET program and were randomized to either a TM (n = 9) or TBRS (n = 10) exercise group that followed current SET exercise guidelines. Feasibility, safety, and efficacy outcomes were assessed. Results: SET attendance was 86% and 71%, respectively, for TBRS and TM groups (p = 0.07). Session exercise dose (metabolic equivalents of task [MET] minutes) (mean [SD]) for TM was 117.6 [27.4] compared to 144.7 [28.7] in the TBRS group (p = 0.08). Study-related adverse events were nine in 236 training hours and three in 180 training hours for the TBRS and TM groups, respectively. There were no significant differences between groups for improvement in 6-minute walk distance (mean [SD]) (TM: 133.2 ft [53.5] vs TBRS: 154.8 ft [49.8]; p = 0.77) after adjusting for baseline 6-minute walk distance. Conclusion: This is the first randomized study comparing TBRS to TM exercise in SET using current SET guidelines. This pilot study showed that TBRS is a feasible and safe exercise modality in SET. This study provides preliminary efficacy of the use of TBRS exercise in SET programs following current guidelines. Larger studies should be conducted to confirm these findings.

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The functional capacity of patients with peripheral arterial disease (PAD) represents an important indicator of patient health and quality of life. The aim of this prospective study was to investigate the validity of a walking impairment questionnaire (WIQ) compared with walking tests for the estimation of the therapeutic effect of lower limb revascularization. The study included 36 patients with PAD in whom successful percutaneous revascularization of a lower limb was performed due to disabling intermittent claudication. Before the revascularization procedure and 4-6 weeks after successful revascularization, clinical examination, ankle brachial index (ABI) measurement, 6-min walk test, treadmill test, and WIQ were performed. After revascularization, significant improvement in walking capacity was shown by both 6-min walk test and treadmill exercise test as well as with WIQ. However, the increase in ABI was borderline. Significant correlations between improvement of 6-min walk test and treadmill exercise test results and the sum of WIQ points were found. The ABI was significantly correlated with treadmill maximal walking distance only. According to our results, the WIQ correlates well with walking tests and is a reliable indicator of effective revascularization of lower limb arterial occlusions, even in patients with a nonsignificant improvement of the ABI.

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BACKGROUND: Pathological gait patterns are common in neurological and orthopedic patients. These put them at risk of falling and restrict their autonomy and social participation. Novel assistive walking devices are designed to actively support physiological gait patterns by means of motor guidance and mechanical support of the lower limbs. RESEARCH QUESTION: Does a non-electric assistive walking device powered by a cam-spring mechanism (aLQ, Imasen) improve or otherwise affect pathological gait patterns in neurological and orthopedic patients? METHODS: A three-dimensional instrumented gait analysis was conducted on a treadmill (quasar, hp cosmos) using spatiotemporal, kinetic, and kinematic data obtained from synchronized motion capturing (Miqus M3, Qualisys), surface EMG (sEMG; Ultium, Noraxon), and pressure distribution measurements (FMD-T, Zebris). Participants with impaired walking were tested in a randomized repeated measures design (assisted/unassisted; at preferred/fast speed) and analyzed with regard to their medical condition (orthopedic or neurological group, n = 20 each). RESULTS: In both groups, participants showed a significant increase of step length and decrease of cadence during assisted walking compared to baseline. Immediate kinematic effects included enhanced sagittal hip flexion but reduced extension. On the contrary, knee joint angles and muscle activity of M. gastrocnemius and M. rectus femoris seemed to be unaffected by the aLQ device. SIGNIFICANCE: Participants appear to benefit from the assistive walking device regarding gait and movement patterns, which suggests that the tested device may help to improve patients' functional health status and quality of life. Activities of daily living (ADLs) that involve extensive hip flexion like stairs or curb climbing are promising applications. We propose the implementation of an invertible cam-spring that provides an additional resistance training option.

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OBJECTIVES: Progressive pseudorheumatoid dysplasia (PPRD) is a spondyloepiphyseal dysplasia caused by biallelic variants in CCN6. This study aimed to describe the early signs and follow-up findings in 44 Turkish PPRD patients. METHODS: The patients with progressive stiffness of multiple joints, characteristic wide metaphysis of interphalangeal (IP) joints and platyspondyly were clinically diagnosed with PPRD. Fifteen patients who had first symptoms under 3 years of age were grouped as early-onset, while others were grouped as classical. CCN6 sequencing was performed in 43 patients. RESULTS: Thirteen pathogenic/likely pathogenic variants were identified, five were novel. c.156C>A(p.Cys52*) variant was found in 53.3% of the families. The initial symptom in the early-onset group was genu varum deformity, while it was widening of IP joints in the classical group. The median age of onset of symptoms and of diagnosis was 4 and 9.7 years, respectively. The mean follow-up duration was 5.6 years. The median age of onset of IP, elbow, knee and hip stiffness, which became progressive with growth was 5, 9, 9 and 12.2 years, respectively. Waddling gait occurred in 97.7% of the patients. A total of 47.7% lost independent walking ability at the median age of 12 years. In the early-onset group, waddling gait occurred earlier than in classical group (P < 0.001). Two patients had atypical presentation with late-onset and mild or lack of IP involvement. CONCLUSION: We observed that genu varum deformity before the age of 3 years was an early sign for PPRD and almost half of the patients lost walking ability at the median age of 12 years.

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Aim: A better knowledge of the biological consequences in the blood of these exercise-induced ischemic events in lower extremity artery disease (LEAD) may improve the prospects of disease management. We explored the preminus postexercise metabolomic difference in 39 patients with LEAD referred for a treadmill oximetry test [transcutaneous oximetry (TcPO2)]. Methods: Ischemia was estimated through the sum of decrease from rest of oxygen pressure (DROPs) (limb TcPO2 changes minus chest TcPO2 changes) at buttocks, thighs, and calves regions. Targeted metabolomic analyses measuring 188 metabolites were performed on a few microliters blood samples taken at the earlobe at rest and 3 min after exercise. Results: Maximum walking distance (MWD) was 290 m (120-652 m) and ankle brachial index (ABI) was 0.67 ± 0.17. Supervised paired partial least squares discriminant analysis based on 23,345 models showed good predictive performance for test sets with a median area under the receiver operating characteristic (AUROC) curve value of 0.99 and a p-value of 0.00049. The best discriminant metabolites contributing to the model included a subset of 71 (47%) of the 150 accurately measured metabolites in the plasma, comprising 3 acylcarnitines, 3 amino acids, 5 biogenic amines, 9 sphingomyelin, 7 lysophosphatidylcholines, and 44 phosphatidylcholines. In addition, 16 of these metabolites were found to correlate with one or more severity scores of the LEAD. Conclusion: Our results provide new insights into the biological changes that accompany exercise in LEAD and contribute to a better understanding of walking impairment pathophysiology in LEAD, highlighting new candidate biomarkers.

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BACKGROUND: The walking ability of many broilers is characterised by slight or definite defects categorised as gait scores (GS) 1 and 2. The present study aimed to examine potential relationships between GSs and indicators of body morphology, leg pathology, tibia strength and wooden breast in Ross 308 broilers assessed as GS ≤ 2. METHODS: At 38 days of age, GS and live body weight of 179 birds was recorded. Each bird was examined post-mortem for signs of wooden breast, contact dermatitis and a range of leg pathologies. Weights of different body parts and tibia strength were quantified. RESULTS: Within sex, GS increased with increasing live body weight (p = 0.020). There was a tendency for an effect of GS on prevalence of footpad dermatitis (p = 0.086) and dislocated femoral joint cartilage (p = 0.059) where both pathologies increased in frequency with increasing GS. Greater load was required to fracture tibia from GS2 than GS0 birds (p = 0.040). CONCLUSIONS: Within this relatively small data set, no strong relationships between GS ≤ 2 and indicators of body morphology, leg pathology, tibia strength and wooden breast in Ross 308 broilers were found, except for the live terminal body weight. Further studies, involving larger data sets are required for full clarification.

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Exercise therapy and lower extremity revascularization both improve walking performance in symptomatic patients with peripheral artery disease. The combination of therapies provides greater benefit than either alone and may reduce the need for subsequent revascularization procedures, but further trials with longer follow-up are needed for the outcome of subsequent revascularization.

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BACKGROUND: To examine the associations between physical activity (PA) and sedentary behavior (SB) with walking capacity and the effects of reallocating time from SB to PA in patients with symptomatic peripheral artery disease (PAD) using compositional data analysis. METHODS: This cross-sectional study included 178 patients (34% females, mean age = 66 [9] y, body mass index = 27.8 [5.0] kg/m2, and ankle-brachial index = 0.60 [0.18]). Walking capacity was assessed as the total walking distance (TWD) achieved in a 6-minute walk test, while SB, light-intensity PA, and moderate to vigorous-intensity PA (MVPA) were measured by a triaxial accelerometer and conceptualized as a time-use composition. Associations between time reallocation among wake-time behaviors and TWD were determined using compositional isotemporal substitution models. RESULTS: A positive association of MVPA with TWD (relative to remaining behaviors) was found in men (ßilr = 66.9, SE = 21.4, P = .003) and women (ßilr = 56.5, SE = 19.8; P = .005). Reallocating 30 minutes per week from SB to MVPA was associated with higher TWD in men (6.7 m; 95% confidence interval, 2.6-10.9 m) and women (4.5 m; 95% confidence interval, 1.5-7.5 m). CONCLUSIONS: The findings highlight, using a compositional approach, the beneficial and independent association of MVPA with walking capacity in patients with symptomatic PAD, whereas SB and light-intensity PA were not associated.

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Impaired walking ability in terms of slight or definite defects is more common in broiler production than lameness that obviously hinders movement, but it has received limited scientific attention. This study aimed to compare behavior of conventional broilers with impaired walking ability (assessed as gait score (GS) 2) with those walking normally (GS0) and those with only a slight gait defect (GS1). Behavior in the home environment was registered, and an analgesic intervention to quantify changes in time budgets indicating pain relief was applied. The study included 192 Ross 308 broilers. On day 27 of age, the birds were distributed as evenly as possible into birds of GS0 and GS2 of each sex based on obtained gait score. Following this, each experimental bird was housed with 3 companion birds. On days 30 and 32 of age, the behavior in the home pens was recorded. All experimental birds were injected with the NSAID carprofen on one of the 2 d and saline on the other. The statistical analyses used the GS scored on the day of recording as explanatory factor. Compared to GS0 birds, GS2 birds tended to be more inactive (mean (CI): 4,193 (3,971-4416) vs. 4,005 (3,753-4,257) s; P = 0.074), spent more time sitting while feeding (306 (266-353) vs. 213 (180-251) s; P = 0.026), were less likely to perch (probability: 0.78 (0.69-0.85) vs. 0.91 (0.85-0.95); P = 0.012), and spent less time performing comfort behavior (749 (689-814) s vs. 875 (792-967) s; P = 0.043). Compared to GS1 birds, GS2 birds spent more time inactive (GS1: 4,022 (3,818-4225) s; P = 0.027), less time foraging (289 (253-329) vs. 347 (309-388) s; P = 0.047), and were less likely to perch (GS1: 0.90 (0.86-0.93); P = 0.001). For some of these behavioral variables, administration of carprofen led to behavioral changes across the GSs, which may suggest that the behavioral expression of the broilers was limited by pain. These findings are of relevance to animal welfare, but the underlying causes are still not fully clarified.

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Fampridine is the only drug approved for the treatment of walking impairment in multiple sclerosis. Around a third of the patients on treatment obtained an improvement in walking speed during the development phase. The effects are clinically significant, appear soon after the start of the treatment and are long-lasting, but disappear soon after the drug is withdrawn. In the real-world setting, the number of patients with a significant response to the treatment seems to be higher (around 70%). The tolerance is good, with mild to moderate, and transient adverse events. The most commonly reported are insomnia, headache, fatigue, back pain, dizziness, nausea and balance disorders. The main contraindications are a history of seizures, renal impairment and concomitant treatment with OCT2 inhibitors.

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