Improving Spasticity by Using Botulin Toxin: An Overview Focusing on Combined Approaches.

Spasticity is a very common sign in the neurological field. It can be defined as "a motor disorder marked by a velocity-dependent increase in muscle tone or tonic stretch reflexes" associated with hypertonia. It leads to a high risk of limb deformities and pain that prejudices residual motor function, impairing quality of life". The treatment of spasticity depends on its severity and its location and, in general, it is based on rehabilitation, oral therapies (the gamma-aminobutyric acid b agonist baclofen) and injectable medications (i.e., botulin toxins, acting on polysynaptic reflex mechanisms). The botulin toxin type A (BoNT-A) injection has been effectively used to improve different types of spasticity. However, when BoNT-A is not sufficient, a combination of nonpharmacological approaches could be attempted. Therefore, additional intervention, such as conventional physical therapy by itself or further combined with robotic gait training, may be needed. Indeed, it has been shown that combination of BoNT-A and robotics has a positive effect on activity level and upper limb function in patients with stroke, including those in the chronic phase. The aim of this review is to evaluate the efficacy of pharmacological or nonpharmacological treatment in combination with BoNT-A injections on spasticity. The combined therapy of BoNT with conventional or adjunct activities or robot-assisted training, especially with end-effectors, is a valid tool to improve patients' performance and outcomes. The combined strategies might rise the toxin's effect, lowering its dosages of botulinum and reducing side effects and costs.

The Role of Muscle Biomarkers in Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the predominant orthopedic disorder in children, affecting 1-3% of the global population. Research in this field has tried to delineate the genetic factors behind scoliosis and its association with heredity since AIS is considered a polygenic disease and has different genetic and epigenetic factors. The current study conducted a narrative review of the literature, focusing on biomarkers in the pathophysiology of muscle in AIS patients. Articles were collected from Scopus, Pubmed, and Web of Science. The key screening parameters were scoliosis classification, sampling, and the biomarkers evaluated. This review emphasizes potential key mechanisms and molecular regulators in muscle tissue. While there has been limited focus on the proteins contributing to muscle changes in AIS, significant attention has been given to genomic studies of single-nucleotide polymorphisms, particularly in LBX1. Despite these efforts, the exact causes of AIS remain elusive, with several theories suggesting genetic and hormonal factors. This review identified critical protein biomarkers such as Gi-protein alpha subunits, fibrillin-1 and -2, and various differentially expressed proteins, which may be linked to muscle alterations in AIS. This field of research is still limited due to a lack of homogeneity in the distinction of patients by groups and curve severity. Although the pathophysiology of AIS is still unclear, molecular research is important to guide the treatment of AIS before achieving skeletal maturity, thus avoiding serious problems associated with posture changes and low quality of life. In the future, a more comprehensive synergy between orthopedic and molecular research might ameliorate the diagnosis and treatment of AIS patients.

Do Individuals with Spinal Cord Injury Benefit from Semi-Immersive Virtual Reality Cognitive Training? Preliminary Results from an Exploratory Study on an Underestimated Problem.

A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations in specific domains can also occur. The aim of this study was to evaluate the effects of semi-immersive virtual reality (VR) cognitive training (using the BTS Nirvana, Italy) in promoting global functional recovery in patients with SCI. Forty-two SCI patients were included in this retrospective case-control study, and the analysis was carried out using an electronic data retrieval system. The enrolled patients were divided into two groups with the same demographic and medical characteristics: the control group (CG: 21 patients) participated in traditional therapy, whereas the experimental group (EG: 21 patients) received training using semi-immersive VR. In both groups, there were patients with A- or B-grade impairments according to the American Spinal Injury Association (ASIA) scale. Both study groups underwent the same amount of cognitive training (but using a different type of training: conventional vs. innovative), consisting of three weekly sessions for eight weeks (24 sessions in total), each session lasting approximately sixty minutes, as well as the same amount of physiotherapy. The effect of the two treatments (EG/CG) was significantly different in global cognitive functioning (MOCA: p = 0.001), mood (BDI: p = 0.006), and overall quality of life (SF12 Total: p < 0.001), especially in physical perception (SF12-Physics: p = 0.004). Our results suggest that SCI patients could benefit from cognitive training using semi-immersive VR. Indeed, the integration of cognitive exercises that require movement and provide increased feedback could allow for better motor and cognitive recovery in people with SCI.

Gait Recovery in Spinal Cord Injury: A Systematic Review with Metanalysis Involving New Rehabilitative Technologies.

Gait recovery is a fundamental goal in patients with spinal cord injury to attain greater autonomy and quality of life. Robotics is becoming a valid tool in improving motor, balance, and gait function in this patient population. Moreover, other innovative approaches are leading to promising results. The aim of this study was to investigate new rehabilitative methods for gait recovery in people who have suffered spinal cord injuries. A systematic review of the last 10 years of the literature was performed in three databases (PubMed, PEDro, andCochrane). We followed this PICO of the review: P: adults with non-progressive spinal cord injury; I: new rehabilitative methods; C: new methods vs. conventional methods; and O: improvement of gait parameters. When feasible, a comparison through ES forest plots was performed. A total of 18 RCTs of the 599 results obtained were included. The studies investigated robotic rehabilitation (n = 10), intermittent hypoxia (N = 3) and external stimulation (N = 5). Six studies of the first group (robotic rehabilitation) were compared using a forest plot for 10MWT, LEMS, WISCI-II, and SCIM-3. The other clinical trials were analyzed through a narrative review of the results. We found weak evidence for the claim that robotic devices lead to better outcomes in gait independence compared to conventional rehabilitation methods. External stimulation and intermittent hypoxia seem to improve gait parameters associated with other rehabilitation methods. Research investigating the role of innovative technologies in improving gait and balance is needed since walking ability is a fundamental issue in patients with SCI.

Finding the Way to Improve Motor Recovery of Patients with Spinal Cord Lesions: A Case-Control Pilot Study on a Novel Neuromodulation Approach.

Robot-assisted rehabilitation (RAR) and non-invasive brain stimulation (NIBS) are interventions that, both individually and combined, can significantly enhance motor performance after spinal cord injury (SCI). We sought to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with active transvertebral direct current stimulation (tvDCS) (namely, NIBS) in association with RAR (RAR + NIBS) improves lower extremity motor function more than RAR alone in subjects with motor incomplete SCI (iSCI). Fifteen adults with iSCI received one daily session of RAR+NIBS in the early afternoon, six sessions weekly, for eight consecutive weeks. Outcome measures included the 6 min walk test (6MWT), the 10 m walk test (10MWT), the timed up and go (TUG) to test mobility and balance, the Walking Index for Spinal Cord Injury (WISCI II), the Functional Independence Measure-Locomotion (FIM-L), the manual muscle testing for lower extremity motor score (LEMS), the modified Ashworth scale for lower limbs (MAS), and the visual analog scale (VAS) for pain. The data of these subjects were compared with those of 20 individuals matched for clinical and demographic features who previously received the same amount or RAR without NIBS (RAR - NIBS). All patients completed the trial, and none reported any side effects either during or following the training. The 10MWT improved in both groups, but the increase was significantly greater following RAR + NIBS than RAR - NIBS. The same occurred for the FIM-L, LEMS, and WISCI II. No significant differences were appreciable concerning the 6MWT and TUG. Conversely, RAR - NIBS outperformed RAR + NIBS regarding the MAS and VAS. Pairing tvDCS with rTMS during RAR can improve lower extremity motor function more than RAR alone can do. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.

Pain characteristics in Italian people with spinal cord injury: a multicentre study.

STUDY DESIGN: Multicentre cross-sectional study. OBJECTIVE: The objective of this study is to evaluate prevalence, location and characteristics of pain in hospital inpatients people with spinal cord injury (SCI). SETTING: Ten Italian rehabilitation centres specialized in spinal injury care, where inpatients are admitted both after the acute lesion and for late complications (time since injury, median [IQR]: 0.8 [0.2-8.2] years). METHODS: All the persons were submitted to AIS scale assessment [1] and modified Ashworth scale [2]; personal data and anamnesis were recorded; any pain within 1 week was investigated and the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) Italian version [3] was administered by physicians expert in type of pain definition. RESULTS: Of 385 included persons, 275 (72%) suffered pain, with the score value median [IQR]: 6 [4-8]. The worst pain of the person was nociceptive in 52% and neuropathic in 48% of the cases; 46% of nociceptive pain was located in the neck-shoulder region, whereas 67% of neuropathic pain was located in the sublesional part of the body. In 48% of the whole population, spasticity was observed but only 74% of them had pain. Being old and female are associated with high pain development, OR (95% CI): 1.24 (1.01-1.04) and 1.83 (1.05-3.20), respectively. CONCLUSIONS: A high prevalence of pain is confirmed in persons with SCI, with both nociceptive and neuropathic pain characteristics. Only old age and female sex resulted as variables highly associated with pain.

Changes in gut microbiota in the acute phase after spinal cord injury correlate with severity of the lesion.

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Effects of Functional Electrical Stimulation Cycling of Different Duration on Viscoelastic and Electromyographic Properties of the Knee in Patients with Spinal Cord Injury.

The benefits of functional electrical stimulation during cycling (FES-cycling) have been ascertained following spinal cord injury. The instrumented pendulum test was applied to chronic paraplegic patients to investigate the effects of FES-cycling of different duration (20-min vs. 40-min) on biomechanical and electromyographic characterization of knee mobility. Seven adults with post-traumatic paraplegia attended two FES-cycling sessions, a 20-min and a 40-min one, in a random order. Knee angular excursion, stiffness and viscosity were measured using the pendulum test before and after each session. Surface electromyographic activity was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles. FES-cycling led to reduced excursion (p < 0.001) and increased stiffness (p = 0.005) of the knee, which was more evident after the 20-min than 40-min session. Noteworthy, biomechanical changes were associated with an increase of muscle activity and changes in latency of muscle activity only for 20-min, with anticipated response times for RF (p < 0.001) and delayed responses for BF (p = 0.033). These results indicate that significant functional changes in knee mobility can be achieved by FES-cycling for 20 min, as evaluated by the pendulum test in patients with chronic paraplegia. The observed muscle behaviour suggests modulatory effects of exercise on spinal network aimed to partially restore automatic neuronal processes.