Equinovarus foot is one of the most commonly spasticity related conditions in stroke survivors, leading to an impaired gait and poor functional performances. Notably, spastic muscles undergo a dynamic evolution following typical pathophysiological patterns. Botulinum Neurotoxin Type A (BoNT-A) is the gold standard for focal spasticity treatment, and ultrasound (US) imaging is widely recommended to guide injections and monitor muscle evolution. The role of BoNT-A in influencing muscle fibroadipose degeneration is still unclear. In this study, we analyzed medial gastrocnemius (MG) and soleus (SOL) US characteristics (cross-sectional area, muscle thickness, pennation angle, and mean echo intensity) in 53 patients. MG and SOL alterations, compared to the unaffected side, depend on the spasticity only and not on the BoNT-A treatment. In functionally preserved patients (functional ambulation classification, FAC > 3; modified Ashworth scale, MAS ≤ 2), the ultrasonographic changes of MG compared to ipsilateral SOL observed in the paretic limb alone seems to be due to histological, anatomical, pathophysiological, and biomechanical differences between the two muscles. In subjects with poor walking capability and more severe spasticity, such ipsilateral difference was found in both calves. In conclusion, BoNT-A does not seem to influence muscle degeneration. Similar muscles undergo different evolution depending on the grade of walking deficit and spasticity.

Primary sarcopenia is considered to be age-related when no other cause is evident, other than aging itself. Secondary sarcopenia should be considered when one or more other causes are evident, such as multiple chronic conditions. Previous studies have reported that low muscle strength and impaired physical performance can be found in chronic diseases, including metabolic disease (diabetes, hypertension, and obesity), arthritis, osteoporosis, cancer, chronic kidney disease, chronic obstructive pulmonary disease, neuromuscular disease, and chronic infection. The development of preventive and therapeutic strategies against secondary sarcopenia and wasting disorders in general is an epidemiological need. The planning of a complex rehabilitation program in sarcopenia associated to chronic conditions, in the context of a comprehensive treatment, is made up of a nutritional support, exercise, correction of lifestyles, and the use of advanced physical energies. Therefore, for the purposes of the optimal management, it is essential to identify the pathogenesis and clinical characteristics that can affect the different rehabilitative treatment.

In stroke survivors, rectus femoris (RF) spasticity is often implicated in gait pattern alterations such as stiff knee gait (SKG). Botulinum toxin type A (BoNT-A) is considered the gold standard for focal spasticity treatment. However—even if the accuracy of injection is crucial for BoNT-A efficacy—instrumented guidance for BoNT-A injection is not routinely applied in clinical settings. In order to investigate the possible implications of an inadequate BoNT-A injection on patients’ clinical outcome, we evaluated the ultrasound-derived RF characteristics (muscle depth, muscle thickness, cross-sectional area and mean echo intensity) in 47 stroke survivors. In our sample, we observed wide variability of RF depth in both hemiparetic and unaffected side of included patients (0.44 and 3.54 cm and between 0.25 and 3.16 cm, respectively). Moreover, our analysis did not show significant differences between treated and non-treated RF in stroke survivors. These results suggest that considering the inter-individual variability in RF muscle depth and thickness, injection guidance should be considered for BoNT-A treatment in order to optimize the clinical outcome of treated patients. In particular, ultrasound guidance may help the clinicians in the long-term follow-up of muscle quality.

Inflammation is an immediate response to damage; in acute phase, it is a form of defense for body and it aims to restitutio ad integrum, in the chronic form itself becomes disease. This mechanism determines inflammatory diseases that are a group of clinical disorders which are characterized by abnormal inflammatory responses such as osteoarthritis, in myalgic syndromes (like fibromyalgia or miofascial sindrome), in some forms of headache, in peripheral vascular disease, in many malignancies. In Physical and Rehabilitation Medicine, the use of analgesic drugs (including NSAIDs) is a crucial resource inside a complex bioprogressive rehabilitative project. A part of the classic use per os is characterized by a serious and systemic side effect and there is also a possibility to administer drugs through other routes. Antalgic and rehabilitative mesotherapy (ARM) is a minimally invasive technique consisting of subcutaneous injections of bioactive substances. Other alternatives are represented by iontophoresis, phonophoresis, phytotherapy, and topical application. The purpose of this chapter is to give an overview about the state of the art regarding the use of NSAIDs in physical medicine and rehabilitation.

Shoulder pain is a common problem and it is responsible for a high proportion of patients presenting to general practice, causing work absenteeism and claims for sickness. A lot of factors and conditions can contribute to shoulder pain. The most prevalent cause is rotator cuff tendinitis; its relevance is correlated not only to its high prevalence rate but also to the fact that is disabling, causing high direct and indirect cost in industrialized country. Other causes of shoulder pain are shoulder impingement syndrome, calcific tendonitis, frozen shoulder, etc. In this context, physical medicine and rehabilitation plays a fundamental role. The conservative approach consists of several interventions. The aim is to decrease shoulder pain and to regain shoulder function, with the goal to reduce the degree of impingement, decreasing swelling and inflammation, and to minimize the risk of further injuries. The purpose of this chapter is to give an overview about shoulder disorders and their conservative treatment by means of physical therapy.

Introduction The β-thalassemias are due to autosomal mutations of the β-globin gene, inducing absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that high production of fetal hemoglobin (HbF) is beneficial for β-thalassemia patients. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus found to be a strong HbF inducer in vitro and in vivo. In this study, we report biochemical, molecular and clinical results of the sirolimus-based NCT03877809 clinical trial (A Personalized Medicine Approach for β-thalassemia Transfusion Dependent Patients: Testing sirolimus in a First Pilot Clinical Trial: Sirthalaclin). Methods Accumulation of γ-globin mRNA was analyzed by reverse-transcription-quantitative PCR and the hemoglobin pattern by HPLC. The immunophenotype was analyzed by FACS using antibodies against CD3, CD4, CD8, CD14, CD19, CD25. Results The results were obtained in 8 patients with β+/β+ and β+/β0 genotypes, treated with a starting dosage of 1 mg/day sirolimus for 24-48 weeks. The first finding of the study was that expression of γ-globin mRNA was increased in blood and erythroid precursor cells isolated from β-thalassemia patients treated with low-dose sirolimus. A second important conclusion of our trial was that sirolimus influences erythropoiesis and reduces biochemical markers associated to ineffective erythropoiesis (I.E.) (excess of free α-globin chains, bilirubin, soluble transferrin receptor and ferritin). In most (7/8) of the patients a decrease of the transfusion demand index was observed. The drug was well tolerated with minor effects on immunophenotype, the only side effect being frequently occurring stomatitis. Conclusions The data obtained indicate that sirolimus given at low doses modifies hematopoiesis and induces increased expression of γ-globin genes in a sub-set of β-thalassemia patients. Further clinical trials are warranted, considering the possibility to test the drug in patients with less severe forms of the disease and exploring combination therapies.