Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Real-World Adherence to OnabotulinumtoxinA Treatment for Spasticity: Insights From the ASPIRE Study.

OBJECTIVE: To identify baseline characteristics and treatment-related variables that affect adherence to onabotulinumtoxinA treatment from the Adult Spasticity International Registry (ASPIRE) study. DESIGN: Prospective, observational registry (NCT01930786). SETTING: International clinical sites. PARTICIPANTS: Adults with spasticity (N=730). INTERVENTIONS: OnabotulinumtoxinA at clinician's discretion. MAIN OUTCOME MEASURES: Clinically meaningful thresholds used for treatment adherent (≥3 treatment sessions during 2-year study) and nonadherent (≤2 sessions). Data analyzed using logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Treatment-related variables assessed at sessions 1 and 2 only. RESULTS: Of the total population, 523 patients (71.6%) were treatment adherent with 5.3±1.6 sessions and 207 (28.4%) were nonadherent with 1.5±0.5 sessions. In the final model (n=626/730), 522 patients (83.4%) were treatment adherent and 104 (16.6%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=1.84; CI, 1.06-3.21; P=.030) and use of orthotics (OR=1.88; CI, 1.15-3.08; P=.012). Baseline characteristics associated with nonadherence: history of diplopia (OR=0.28; CI, 0.09-0.89; P=.031) and use of assistive devices (OR=0.51; CI, 0.29-0.90; P=.021). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.43; CI, 0.26-0.72; P=.001) and clinician dissatisfaction with onabotulinumtoxinA to manage pain (OR=0.18; CI, 0.05-0.69; P=.012). Of the population with stroke (n=411), 288 patients (70.1%) were treatment adherent with 5.3±1.6 sessions and 123 (29.9%) were nonadherent with 1.5±0.5 session. In the final stroke model (n=346/411), 288 patients (83.2%) were treatment adherent and 58 (16.8%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=2.99; CI, 1.39-6.44; P=.005) and use of orthotics (OR=3.18; CI, 1.57-6.45; P=.001). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.42; CI, 0.21-0.83; P=.013) and moderate/severe disability on upper limb Disability Assessment Scale pain subscale (OR=0.40; CI, 0.19-0.83; P=.015). CONCLUSIONS: These ASPIRE analyses demonstrate real-world patient and clinical variables that affect adherence to onabotulinumtoxinA and provide insights to help optimize management strategies to improve patient care.

Myostatin as a potential biomarker to monitor sarcopenia in hip fracture patients undergoing a multidisciplinary rehabilitation and nutritional treatment: a preliminary study.

Hip fractures are the most common osteoporotic fractures related to disability in older adults, requiring surgery and a subsequent rehabilitation treatment. Sarcopenia is currently considered as a predictive of worse outcome in hip fracture patients and myostatin has been recently proposed a potential biomarker of this condition. Twenty hip fracture patients after total hip replacement (mean aged 75.9 ± 2.4 years) were randomly divided into two groups of ten subjects (groups A and B). Both groups performed a rehabilitation program (5 sessions of 40 min/week for 2 weeks, followed by home-based exercise protocol). Group A received also 2-month amino acid supplementation. Serum myostatin levels significantly decreased after 2 months in both group A (p = 0.01) and group B (p = 0.03) in sarcopenic patients only in group A (p = 0.04). These results suggest that myostatin might be considered a promising biomarker of sarcopenia in hip fracture older adults' patients undergoing rehabilitation and amino acid supplementation.

Falls, fractures and bone density in Parkinson's disease - a cross-sectional study.

AIM: Evidence suggests that falls and associated bone fractures are more frequent in patients suffering from Parkinson's disease (PD) than in the general population. In this cross-sectional study we evaluated the clinical and biochemical characteristics that are associated to falls, fractures and bone health in a population of PD subjects. MATERIALS AND METHODS: Forty-two consecutive subjects suffering from idiopathic PD (mild-to-moderate severity) with/without falls in the previous year were included. They were characterized as regards functional independence, balance, fear of falling, bone density (ultrasound densitometry) and plasma levels of vitamin D. Twenty-one age- and sex-matched healthy subjects were evaluated as controls. RESULTS: We detected a greater degree of osteoporosis in PD subjects as compared to controls, more pronounced in males than in females (Z-score: M -3.8 ± 1.6, F -2.28 ± 0.92, p = 0.0006). A positive correlation was found between independence levels and bone density or vitamin D levels. Twenty seven patients (64%) reported falls in the previous year. These were associated to post-traumatic fractures in 16 subjects (59% of fallers). Women fell more than men (fallers: 20 F/7 M; non fallers: 4 F/11 M, χ² test p = 0.02), although the occurrence of post-traumatic fractures among fallers did not differ between sexes (F 11/9, M 5/2, χ² test p > 0.05). Fallers with post-traumatic fractures showed higher degrees of motor impairment. CONCLUSIONS: These findings confirm that falls and osteoporosis represent major health issues in PD, already in the middle stages of disease.

High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis.

We retrospectively evaluated the efficacy and safety of high doses of onabotulinumtoxinA (from 600 to 800 units) in 26 patients affected by upper and/or lower limb post-stroke spasticity. They were assessed before, 30 and 90 days after treatment. We observed a significant muscle tone reduction and a significant functional improvement (assessed with the Disability Assessment Scale). No adverse events were reported. In our retrospective analysis the treatment with high doses of onabotulinumtoxinA showed to be effective and safe.

May Spasticity-Related Unpleasant Sensations Interfere with Daily Activities in People with Stroke and Traumatic Brain Injury? Secondary Analysis from the CORTOX Study.

Background/Objectives: This study examined the impact of spasticity-related unpleasant sensations (pain, heaviness, stiffness) on various domains of the International Classification of Functioning, Disability, and Health (ICF) and psychosocial well-being in individuals affected by stroke or traumatic brain injury (TBI). The primary aim is to explore how these sensations affect daily activities, participation, and overall quality of life, guided by the comprehensive framework of the ICF. Methods: Utilizing a secondary analysis of data from a cohort undergoing Botulinum toxin type-A treatment for spasticity post-stroke or TBI, we developed and administered an ad-hoc questionnaire focusing on ICF domains such as body function, activities and participation, and psychosocial aspects such as mood, relationship, social life, motivation, and sleep quality. Spearman rho correlation was applied to assess the relationship between unpleasant sensations and functional as well as psychosocial outcomes among 151 participants. Results: This study identified significant correlations between the severity of unpleasant sensations and limitations in daily functioning, particularly in activities of daily living and mobility. Furthermore, an impactful association was identified between increased unpleasant sensations and deterioration in psychosocial well-being, notably in mood and sleep quality. Conclusions: These findings advocate for a person-centered approach in spasticity management, emphasizing the integration of sensory impairment strategies into rehabilitation to enhance functional outcomes and quality of life. Such an approach aims to improve functional outcomes and enhance the quality of life for individuals experiencing spasticity post-stroke or TBI. Future directions include targeted interventions to alleviate these sensations, support better rehabilitation results and improve patient experiences.

Botulinum Toxin for Pain Relief in Cancer Patients: A Systematic Review of Randomized Controlled Trials.

Cancer pain is one of the most disabling symptoms complained by cancer patients, with a crucial impact on physical and psychological well-being. Botulinum neurotoxins (BoNTs) type A and B have emerged as potential interventions for chronic pain; however, their role in these patients is still debated. Thus, this systematic review of randomized controlled trials aimed at assessing the effects of BoNT treatment for cancer pain to guide physicians in an evidence-based approach integrating BoNT in cancer care. Out of 5824 records, 10 RCTs satisfied our eligibility criteria and were included in the present work for a total of 413 subjects with several cancer types (breast, head and neck, esophageal, and thoracic/gastric cancers). While some studies demonstrated significant pain reduction and improved quality of life post-BoNT-A injections, outcomes across different cancer types were inconclusive. Additionally, several effects were observed in functioning, dysphagia, salivary outcomes, esophageal strictures, gastric emptying, and expansions. This review emphasizes the need for further standardized research to conclusively establish the efficacy of BoNT in comprehensive cancer pain management.

The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis.

Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence of keywords. Our search yielded 1489 publications. Analysis revealed a consistent annual increase in research output. The United States, United Kingdom, and Italy were the leading contributors. The top institution in this research was Assistance Publique Hopitaux, Paris. The journal containing the highest number of relevant publications was Toxins. Key frequently occurring keywords were 'stroke', 'cerebral palsy', 'adult spasticity', and 'upper extremity'. This study identified 12 clusters of keywords and 15 clusters of co-cited references, indicating the main focus areas and emerging themes in this field. This study comprehensively analyzed and summarized trends in BoNT-A research in the field of spasticity over the past 22 years.

Post-stroke spasticity: follow-up and functional implications of chronic long-term treatment with botulinum toxin.

BACKGROUND: Around 40% of stroke survivor develop spasticity. Plantar flexors (PF) muscles are often affected, with severe functional impairment. The treatment of choice is botulinum toxin type A (BoNT-A) combined with adjuvant treatments. The temporary pharmacological effect implies periodic reassessment and reinjection. These long-term chronic programs require monitoring the functional impact of each cycle and the clinical evolution in relation to aging and repeated interventions. AIM: Evaluating changes of functional level in patients with post-stroke spasticity treated with BoNT-A by assessing the long-term maintenance of the therapeutic efficacy. DESIGN: Retrospective longitudinal observational study. SETTING: Outpatients. POPULATION: Chronic stroke survivors undergoing BoNT-A treatment and subsequent intensive rehabilitation (10 sessions in a day-hospital regime). METHODS: Medical records of the enrolled patients were consulted. The primary endpoint was the change in PF spasticity by at least 1 point on the Modified Ashworth Scale (MAS) at each cycle. Secondary endpoints were the assessment of possible trends in gait parameters (Six Minute Walking Test [6MWT]; Timed Up and Go [TUG], and 10 Meters Walking Test [10mWT]) pre- and post-injection and at each cycle. RESULTS: Thirty-six patients were enrolled. A reduction of at least one MAS point for PF was recorded after each cycle in all subjects. A time-dependent reduction in the proportion of patients reporting an improvement higher than the minimal clinically important difference (MCID) in 6MWT and 10mWT was observed. In the case of TUG, this data kept stable at all cycles. A one-point increase in the basal functional ambulation classification (FAC) score resulted in a reduction in the probability of having a TUG improvement greater than the MCID. The opposite correlation was found for 6MWT and 10mWT. CONCLUSIONS: With the proposed treatment, the clinical significance TUG improvement remains constant throughout repeated cycles and the proportion of patients with improvement in 6MWT and 10mWT tends to decline over time. The predictive value of basal FAC on the functional variables expected improvement may provide a potential treatment targeting tool. CLINICAL REHABILITATION IMPACT: These results may deliver prognostic indication allowing an optimized integration of different post-BoNT-A rehabilitation approaches, agreeing with current evidence. Adequate monitoring and treatment protocols are crucial for the stability of functional level and may prevent excessive fluctuations.

Pain, disability, and quality of life in participants after concurrent onabotulinumtoxinA treatment of upper and lower limb spasticity: Observational results from the ASPIRE study.

INTRODUCTION: Upper and lower limb spasticity is commonly associated with central nervous system disorders including stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and spinal cord injury, but little is known about the concurrent treatment of upper and lower limb spasticity with botulinum toxins. OBJECTIVE: To evaluate onabotulinumtoxinA (onabotA) utilization and to determine if concurrent onabotA treatment of the upper and lower limbs has supported improvements in participants with spasticity. DESIGN: Sub-analysis of a 2-year, international, prospective, observational registry (ASPIRE, NCT01930786). SETTING: International clinic sites (54). PARTICIPANTS: Adult spasticity participants across etiologies, who received ≥1 concurrent onabotA treatment of the upper and lower limbs during the study. INTERVENTION: Participants were treated with onabotA at the clinician's discretion. OUTCOMES: Baseline characteristics and outcomes of disability (Disability Assessment Scale [DAS]), pain (Numeric Pain Rating Scale [NPRS]), participant satisfaction, physician satisfaction, and quality of life (QoL; Spasticity Impact Assessment [SIA]) were evaluated. Adverse events were monitored throughout the study. RESULTS: Of 744 participants enrolled, 730 received ≥1 dose of onabotA; 275 participants received treatment with onabotA in both upper and lower limbs during ≥1 session; 39.3% of participants were naïve to onabotA for spasticity. The mean (SD) total dose per treatment session ranged from 421.2 (195.3) to 499.6 (188.6) U. The most common baseline upper limb presentation was clenched fist (n = 194, 70.5%); lower limb was equinovarus foot (n = 219, 66.9%). High physician and participant satisfaction and improvements in pain, disability and QoL were reported after most treatments. Nine participants (3.3%) reported nine treatment-related adverse events; two participants (0.7%) reported three serious treatment-related severe adverse events. No new safety signals were identified. CONCLUSION: More than a third of enrolled participants received at least one concurrent onabotA treatment of the upper and lower limbs, with reduced pain, disability, and improved QoL after treatment, consistent with the established safety profile of onabotA for the treatment of spasticity.

Role of Diagnostic Nerve Blocks in the Goal-Oriented Treatment of Spasticity with Botulinum Toxin Type A: A Case-Control Study.

The goal-setting process is pivotal in managing patients with disabling spasticity. This case-control study assessed the role of diagnostic nerve blocks in guiding the goal-setting process within goal-targeted treatment of spasticity with botulinum neurotoxin-A. In this case-control study, patients with disabling spasticity underwent either a goal-setting process based on the patient's needs and clinical evaluation (control group) or additional diagnostic nerve block procedures (case group). All enrolled patients underwent a focal treatment with botulinum neurotoxin-A injection and a 1-month follow-up evaluation during which goal achievement was quantified using the goal attainment scaling-light score system. Data showed a higher goal achievement rate in the case group (70%) than in the control group (40%). In conclusion, diagnostic nerve blocks may help guide the goal-setting process within goal-targeted treatment of spasticity with botulinum neurotoxin-A towards more realistic and achievable goals, thereby improving the outcomes of botulinum neurotoxin-A injection. Future studies should better explore the role of diagnostic nerve blocks to further personalize botulinum neurotoxin-A according to individual patients' preferences and requirements.

Does altering inclination alter effectiveness of treadmill training for gait impairment after stroke? A randomized controlled trial.

OBJECTIVE: To assess whether a downhill walking training programme is more effective than the same amount of training applied uphill in chronic stroke survivors. DESIGN: Randomized, single-blind study. SETTING: Outpatient rehabilitation service. METHODS: Thirty-eight adults with hemiplegia from stroke lasting more than three months were randomly allocated to one of the two groups: 'UP' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% ascending slope; and 'DOWN' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% descending slope. Both groups were treated 5 times a week for six weeks. Patients were evaluated before treatment, at the end of treatment and after three months. OUTCOME MEASURES: Primary outcome measure was the number of patients showing an improvement in 6-minute walking test (6MWT) greater than 50 m. Secondary outcome measures were: (1) number of patients showing a clinically relevant improvement of gait speed during 10-m walking test (10mWT); (2) number of patients showing an improvement in timed up and go (TUG) greater than minimal detectable change. RESULTS: Both groups had a significant improvement after treatment and at follow-up. At the end of treatment, compared to UP group, more patients in the DOWN group showed clinically significant improvements in primary and secondary outcomes (16/19 patients for 6MWT, 11/19 patients for 10mWT and 9/19 patients for TUG compared with 3/19, 4/19 and 2/19 patients, respectively, P < 0.01). At follow-up, results were similar except for 10mWT. CONCLUSIONS: In chronic stroke patients, downhill treadmill training produces a bigger effect than uphill training.

Sensor based assessment of turning during instrumented Timed Up and Go Test for quantifying mobility in chronic stroke patients.

BACKGROUND: Turning may be particularly challenging for stroke patients leading to decreased mobility and increased functional restriction. Timed up and go instrumentation using a simple technology in the clinical context could allow for the collection of both traditional and potentially more discriminatory variables in turning ability. AIM: Determine whether the speed turning metrics obtained by a single inertial sensor are suitable for differentiating between stroke patients with varying levels of mobility and disability. DESIGN: Cross-sectional study. SETTING: Outpatients setting. POPULATION: Chronic stroke patients. METHODS: A total of 48 chronic stroke patients and 23 healthy controls were included. Stroke patients were divided in two groups based on the total iTUG score: an impaired mobility (> 20 seconds) and an available mobility (<20 seconds) group. All subjects performed an instrumented Timed Up and Go (iTUG) wearing a single IMU sensor on the lower back. Time of subcomponents of the timed up and go test and kinematic parameters of turning were quantified. Other clinical outcomes were: 10 meters walk test, Functional Ambulation Categories Scale (FAC), the Rivermead Mobility Index (RMI), Modified Rankin Scale and the Saltin-Grimby Physical Activity Level Scale (SGPALS). RESULTS: There were significant differences (P<0.01) in iTUG phases and turning speeds among groups. Low to strong significant correlations were found between measures derived from the turning speeds and clinical measures. The area under the curve (AUC) of Receiver Operating Characteristic (ROC) turning speeds was demonstrated to be able to discriminate (AUC: 0.742-0.912) from available to impaired stroke patients. CONCLUSIONS: This study provides evidence that turning speeds during timed up and go test are accurate measures of mobility and capable of discriminating stroke patients with impaired mobility from those with normal mobility. CLINICAL REHABILITATION IMPACT: The turning metrics are related to impairment and mobility in chronic stroke patients; hence they are important to include during clinical evaluation and may assist in creating a customized strategy, assess potential treatments, and effectively organize recovery.

Tolerability, Safety and Efficacy of a Specific Rehabilitation Treatment Protocol for Axillary Web Syndrome: An Observational Retrospective Study.

Axillary web syndrome (AWS) is a highly prevalent surgical complication affecting BC survivors. It presents as a subcutaneous cording that limits the upper limb range of motion (ROM) and causes pain. Its etiology is still debated, and its treatment is not well defined. Therefore, we aimed to investigate the safety, tolerability and efficacy of our specific AWS rehabilitative treatment protocol. We conducted an observational retrospective study on a cohort of 92 AWS patients referred to the oncological outpatient service of a university hospital. We collected data from medical records before (T0) and after (T1) the treatment. The studied protocol was composed of 60-min sessions, carried out 3 times/week by specialized physiotherapists, until the clinical resolution of AWS. We found that a mean of 8.74 ± 2.12 rehabilitative sessions were needed, and only one patient stopped early. At T1, shoulder ROM was complete in both abduction and flexion in 98% of patients; AWS was no longer detectable in 64% of them, and pain significantly decreased compared to T0. In conclusion, our protocol proved to be safe, well-tolerated and seemed to be effective in treating AWS.

Short-wave diathermy for spastic equinus foot in chronic stroke patients: a proof-of-concept pilot study.

BACKGROUND: Physical modalities may be useful to manage poststroke spasticity. Shortwave diathermy has been demonstrated to improve extensibility of the myotendinous tissue. Spasticity may alter morphology of the muscle and its elastic properties. Our main aim was to evaluate the effects of shortwave diathermy on spastic equinus foot in stroke patients. METHODS: Ten chronic stroke patients with spastic equinus foot received 10 shortwave diathermy sessions, 5 days/week for 2 consecutive weeks to the spastic calf muscles. Clinical (modified Ashworth Scale and ankle dorsiflexion passive range of motion) and ultrasound (spastic gastrocnemius muscle echo intensity and hardness percentage measured by sonoelastography) evaluation was done before, after treatment, and at two weeks of follow-up. RESULTS: A significant difference in calf muscle spasticity (P=0.004), ankle passive range of motion (P=0.014), and spastic gastrocnemius muscle hardness percentage (P=0.004) was found after treatment. A significant difference in calf muscle spasticity (P=0.004) was found also at the follow-up evaluation. CONCLUSIONS: Our preliminary findings support the hypothesis that shortwave diathermy might improve calf muscle tone, ankle passive range of motion, and gastrocnemius muscle elasticity in chronic stroke patients with spastic equinus. This might be due to the deep thermal effects coupled with the rheological direct action of shortwave diathermy on spastic muscles.

A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature.

Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release factor (PTRF) gene. It encodes for a cytoplasmatic protein called caveolae-associated protein 1 (Cavin-1), which, together with caveolin 1, is responsible for the biogenesis of caveolae, being a master regulator of adipose tissue expandability. Cavin-1 is expressed in several tissues, including muscles, thus resulting, when dysfunctional, in a clinical phenotype characterized by the absence of adipose tissue and muscular dystrophy. We herein describe the clinical phenotypes of two siblings in their early childhood, with a phenotype characterized by a generalized reduction of subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, and atlantoaxial instability. One of the siblings developed paroxysmal supraventricular tachycardia leading to cardiac arrest at 3 months of age. Height and BMI were normal. Blood tests showed elevated CK, a mild increase in liver enzymes and triglycerides levels, and undetectable leptin and adiponectin concentrations. Fasting glucose and HbA1c were normal, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was mildly elevated. Both patients were hyperphagic and had cravings for foods rich in fats and sugars. Genetic testing revealed a novel pathogenic mutation of the CAVIN1/PTRF gene (NM_012232 exon1:c T21A:p.Y7X) at the homozygous state. The diagnosis of lipodystrophy can be challenging, often requiring a multidisciplinary approach, given the pleiotropic effect, involving several tissues. The coexistence of generalized lack of fat, myopathy with elevated CK levels, arrhythmias, gastrointestinal dysmotility, and skeletal abnormalities should prompt the suspicion for the diagnosis of CGL4, although phenotypic variability may occur.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Long-Term Spasticity Management in Post-Stroke Patients: Issues and Possible Actions-A Systematic Review with an Italian Expert Opinion.

Spasticity is a well-known motor dysfunction occurring after a stroke. A group of Italian physicians' experts in treating post-stroke spasticity (PSS) reviewed the current scientific evidence concerning the state-of-the-art clinical management of PSS management and the appropriate use of botulinum toxin, aiming to identify issues, possible actions, and effective management of the patient affected by spasticity. The participants were clinicians specifically selected to cover the range of multidisciplinary clinical and research expertise needed to diagnose and manage PSS. When evidence was not available, the panel discussed and agreed on the best way to manage and treat PSS. To address the barriers identified, the panel provides a series of consensus recommendations. This systematic review provides a focused guide in the evaluation and management of patients with PSS and its complications. The recommendations reached by this panel of experts should be used by less-experienced doctors in real life and should be used as a guide on how to best use botulinum toxin injection in treating spasticity after a stroke.

Ageing, functioning patterns and their environmental determinants in the spinal cord injury (SCI) population: A comparative analysis across eleven European countries implementing the International Spinal Cord Injury Community Survey.

BACKGROUND: As the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning. METHODS: Data from 6'635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants. RESULTS: In countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning. CONCLUSIONS: Functioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.