Muscle Hypotrophy Research Articles

Classification of paravertebral muscle trophism and its correlation with thoraco-lumbar fascia thickening in patients with chronic low back pain.

The aim of this work is to demonstrate how the chronicity of low back pain can modify the trophism of the paraspinal muscles, by performing an ultrasound and MRI evaluation of the paraspinal muscles in the lumbar spine and correlating it to the time of onset of low back pain. An ultrasound evaluation was carried out in the lumbar area with a 5-17MHz linear probe of the paraspinal muscles of the lumbar region, compared with the MRI of the lumbar spine, in patients presented to our attention for chronic low back pain (> 6months), from January 2021 to January 2023. In each patient, two series of images were analyzed, in the coronal and sagittal planes. Between January 2021 and January 2023, a total of 79 patients were retrospectively evaluated by ultrasound for chronic low back pain. The patients, including 46 men and 33 women, had an average age of 51.6years (min 24-max 74). In the evaluation of the profile of the paravertebral muscles, 22 patients (27.8%) showed hypotrophy of the paravertebral muscles with a concave profile, while the measurement of the thickness of the fascia showed an average thickness of 2.19mm with a range between 1, 3 and 3.2mm and an interquartile range of 1.7-2.65mm. 77.2% of patients with a concave profile showed a thickness of the FTL > 2.5mm, and an average duration of symptoms of approximately 15.3months, to demonstrate a correlation between muscle hypotrophy, thickness of the FTL and duration of onset of symptoms. In the evaluation of chronic low back pain carried out with MRI and ultrasound, the paravertebral musculature profile and the thickness of the thoracolumbar fascia are two instrumental data which, associated with the proposed classification and correlated to the clinical picture, allow to determine the chronicity of the pathological picture.

Post-traumatic patellar tendon ossification in children: a case series

Background. Fractures of the bones that form the knee joint in children are quite rare, accounting for up to 6% of all bone fractures. These include avulsion fractures of the patellar apex as well as tibial tuberosity avulsion fractures, which may result in patellar tendon ossification. Based on literature, the ossification may also occur in cases of primary or chronic (complete or partial) patellar tendon tears. Such a complication is quite rare in pediatric traumatology; it requires differential diagnosis and various surgical tactics. The aim of the study is to present a clinical and radiological picture of post-traumatic patellar tendon ossification in children and its surgical treatment outcomes using a case series as an example. Methods. We present a monocenter retrospective series of 4 male patients. Anamnestic, clinical, radiological and histological data were analyzed. Results. The patients’ mean age was 14 (range, 11-16) years. In all cases, there was a history of trauma. Initially, after getting injured, the patients were treated for a knee injury. In one patient, as a result of his falling on 2 limbs, a bilateral pathology was observed; in other three cases, the pathology was unilateral. Flexion contracture and pain syndrome prevailed in the clinical picture. All patients underwent surgery ranging from excision of ossifications to excision of ossifications with reconstruction of tendon defects and refixation of the tibial tuberosity with osteosynthesis. In all cases, knee joint contracture was eliminated and the volume of movement was fully restored. Histology showed fragments of mature bone tissue represented by thinned bone beams with focal osteoclastic reaction and areas of endochondral ossification. Conclusions. The clinical picture of pediatric patients with patellar tendon ossification manifests in the form of a chronic cascade of symptoms and functional and topographic disorders: patellar tendon ossification, patella alta, anterior knee pain, flexion contracture and rectus femoris muscle hypotrophy. X-ray and MRI data determine a formation of bone density with uneven clear contours in the projection of the patellar tendon, along with patella alta and the Caton-Deschamps index increasing more than 1.3. The primary treatment method of the developed complication is the surgical one, which leads to the restoration of the full amplitude of movements in the knee joint.

The androgen receptor in mesenchymal progenitors regulates skeletal muscle mass via Igf1 expression in male mice

Androgens exert their effects primarily by binding to the androgen receptor (AR), a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skeletal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via nonmyofiber cells. In this context, the cellular and molecular mechanisms of AR in mesenchymal progenitors, which play a crucial role in maintaining skeletal muscle homeostasis, remain largely unknown. In this study, we demonstrated expression of AR in mesenchymal progenitors and found that targeted AR ablation in mesenchymal progenitors reduced limb muscle mass in mature adult, but not young or aged, male mice, although fatty infiltration of muscle was not affected. The absence of AR in mesenchymal progenitors led to remarkable perineal muscle hypotrophy, regardless of age, due to abnormal regulation of transcripts associated with cell death and extracellular matrix organization. Additionally, we revealed that AR in mesenchymal progenitors regulates the expression of insulin-like growth factor 1 (Igf1) and that IGF1 administration prevents perineal muscle atrophy in a paracrine manner. These findings indicate that the anabolic effects of androgens regulate skeletal muscle mass via, at least in part, AR signaling in mesenchymal progenitors.

Abstract B008: Twist1 drives pancreatic ductal adenocarcinoma-mediated muscle cachexia

Abstract Cancer cachexia is a debilitating syndrome that affects the survival and quality of life of cancer patients. Up to 95% of pancreatic ductal adenocarcinoma (PDAC) patients experience muscle cachexia, yet the underlying mechanisms remain poorly understood. The transcription factor Twist1 plays essential roles in mesenchymal stem cell fate determination, and its deregulation contributes to cancer progression and metastasis. In this study, we report on the serendipitous finding that Twist1 functions in PDAC to drive muscle cachexia. We found that conditional overexpression of Twist1 in the pancreatic epithelium (pTwist1) during early development resulted in severe growth retardation, which was mainly characterized by muscle hypotrophy. This intriguing observation prompted us to inquire whether pTwist1 could function in the pancreatic epithelium to regulate muscle mass, and if so, whether this has any implication as it relates to PDAC-mediated muscle cachexia. We found that enforced expression of pTwist1 in healthy adult animals was sufficient to elicit the cardinal features of muscle cachexia, including progressive decline in body weight, physical activity, muscle force, and muscle mass. In the context of PDAC, enforced expression of pTwist1 in a KrasG12D background led to a dramatic acceleration of tumor progression, and this was associated with severe muscle cachexia. To the best of our knowledge, these findings provide the first evidence that the pro-malignant transcription factor Twist1 functions in PDAC to drive muscle cachexia, thus revealing new insights into the underlying mechanisms of muscle that could be harnessed to curb this debilitating syndrome. Citation Format: Parash Parajuli, Azeddine Atfi. Twist1 drives pancreatic ductal adenocarcinoma-mediated muscle cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B008.

The Differential Diagnosis between Cushing's Disease and Pseudocushing Syndrome in a Pre-agonic Patient.

The pseudo-Cushing's encompass several disorders that can occur in high-stress situations and that show biochemical features like those of Cushing's syndrome. We present a case with difficult differential diagnosis for overlapping laboratory findings. A 74-year-old man was admitted to our hospital for worsening dyspnoea for a month, 15 kilograms of weight loss in the previous months, asthenia, hypotonia, and muscle hypotrophy. Moreover, due to the onset of acute hypoxic-hypercapnic respiratory failure, the patient was treated with non-invasive ventilation and then admitted to the intensive care unit, for pneumonia and respiratory failure due to Meticillin-sensitive Staphylococcus aureus and Klebsiella Aerogenes. Antibiotic therapy was started. During the treatment in the ICU, the patient underwent endotracheal intubation for the worsening of respiratory function, and inotropic drug therapy was introduced for the development of septic shock. Hormones were tested, showing an ACTH-dependent hypercortisolism. The results of Nugent, Liddle, and the dexamethasone- suppressed CRH stimulation tests suggested a not-neoplastic ACTH-dependent hypercortisolism. The pituitary contrasted magnetic resonance image showed gland hypertrophy, and the abdominal computed tomography ruled out adrenal lesions. Unfortunately, the patient developed a multi-organ failure and died. The autopsy finding confirmed the absence of pituitary and other neuroendocrine tumors and showed bilateral adrenal hypotrophy. Our clinical case described a patient with pseudo-Cushing's syndrome during sepsis and pre-agonist phase, with a difficult differential diagnosis, in which the combination of the low-dose dexamethasone suppression test and the CRH test allowed a conclusive and correct diagnostic orientation.

Long-term patient outcome is affected by deep venous thrombosis after Achilles tendon rupture repair.

The aim of the study was to examine the impact of a deep venous thrombosis (DVT) on patient outcomes 3 years after Achilles tendon rupture (ATR) repair and if there were continued improvements between 1 and 3 years after surgery. A secondary aim was to determine risk factors associated with impaired patient outcomes in the long term. This cohort study consisted of 181 ATR-repaired patients, from two large randomized clinical trials, who attended a 3-year follow-up evaluation. Patients were postoperatively randomized to two different weight-bearing interventions compared with immobilization in a below-knee plaster cast for 2 weeks. During immobilization, screening for DVT was performed with Doppler ultrasound. At 1 and 3 years postoperatively, functional- and patient-reported outcomes were evaluated by the validated heel-rise test and self-reported questionnaire, Achilles tendon Total Rupture Score (ATRS). In total, 76 out of 181 (42%) patients exhibited a DVT at the 2- or 6-week screening after ATR surgery. Suffering from a DVT during immobilization resulted at 3 years in a worse limb symmetry index (LSI) of heel-rise total work compared to patients without DVT, adjusted for age (DVT mean LSI 68% vs. no DVT 78%, p = 0.027). At 3 years, patients with a DVT during immobilization displayed lower ATRS (DVT median 88 vs. no DVT 93, p = 0.046), which was not significant after adjustment for age. However, patients with DVT exhibited an improvement in ATRS, LSI total work, and LSI maximum height between 1 and 3 years, which was not seen among patients without DVT. Independent risk factors for reduced patient functional outcomes at 3 years were older age, greater calf muscle hypotrophy, and suffering a DVT. DVT during immobilization affects patients' long-term functional outcomes 3 years after ATR repair. Clinicians should adequately address risk factors contributing to impaired patient outcomes in the long term, including calf muscle hypotrophy, DVT, and older age. Level Ⅲ.

Horizontal running inside circular walls of Moon settlements: a comprehensive countermeasure for low-gravity deconditioning?

Long-lasting exposure to low gravity, such as in lunar settlements planned by the ongoing Artemis Program, elicits muscle hypotrophy, bone demineralization, cardio-respiratory and neuro-control deconditioning, against which optimal countermeasures are still to be designed. Rather than training selected muscle groups only, 'whole-body' activities such as locomotion seem better candidates, but at Moon gravity both 'pendular' walking and bouncing gaits like running exhibit abnormal dynamics at faster speeds. We theoretically and experimentally show that much greater self-generated artificial gravities can be experienced on the Moon by running horizontally inside a static 4.7 m radius cylinder (motorcyclists' 'Wall of Death' of amusement parks) at speeds preventing downward skidding. To emulate lunar gravity, 83% of body weight was unloaded by pre-tensed (36 m) bungee jumping bands. Participants unprecedentedly maintained horizontal fast running (5.4-6.5 m s-1) for a few circular laps, with intense metabolism (estimated as 54-74 mlO2 kg-1 min-1) and peak forces during foot contact, inferred by motion analysis, of 2-3 Earth body weight (corresponding to terrestrial running at 3-4 m s-1), high enough to prevent bone calcium resorption. A training regime of a few laps a day promises to be a viable countermeasure for astronauts to quickly combat whole-body deconditioning, for further missions and home return.

Visual disturbances in a 12-year-old male patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome

Abstract: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare condition. Here, we present a case of a male patient with a very unique combination of symptoms that started at the age of 12. Transient symptoms manifested after 4 days of high fever and included lethargy, a loss of appetite, and an inability to recognize faces. After that, the patient was symptom-free for 4 years before he was hospitalized again with a working diagnosis of acute disseminated encephalomyelitis. The ophthalmic symptoms at this stage were photophobia and discrete horizontal nystagmus. One year later, the patient had another seizure and during hospitalization, predominantly displayed cerebral symptoms such as dystaxia, dysmetria, generalized muscle hypotrophy, and absent myotonic reflexes. Like before, an ophthalmic examination demonstrated a best-corrected visual acuity of 1.0 and a normal anterior segment. A fundus examination revealed a slightly rarefied retina, along with areas of perifoveal and parapapillary atrophy, in addition to increased vascular tortuosity. Optical coherence tomography scans of the macula and the optic disc depicted a mild thinning of the retinal layers. Visual field testing showed an isopter contraction with a predominant loss of the temporal visual field in both eyes. A genetic serum analysis was positive for mitochondrial mutation m.3243A>G, and a diagnosis of MELAS was confirmed. The treatment included anticonvulsive drugs and dietary precautions. Patients with MELAS syndrome can manifest a wide range of visual disturbances, meaning that a detailed ophthalmic examination is required.

REFERRED MUSCLE PAIN, SOME CONSIDERATIONS OF ITS SIGNIFICANCE IN PRACTICE

Muscle pain is a common symptom in many musculoskeletal disorders. When it is local as a result of a muscle injury, correct diagnosis does not appear difficult. Referred muscle pain is a symptom associated with diagnostic and therapeutic challenges. It can be a consequence of an injury that develops elsewhere in the body: a skeletal muscle in another area or joint, or it can often be associated with a visceral injury (in this case we have referred muscle pain or secondary muscle pain). The aim of this article is to make a review of the available literature studying the nature, diagnosis, and treatment of referred pain and its relevance to clinical practice. Materials and Methods: In this review, the available scientific articles concerning the field of reflected pain are reviewed: Google Scholar, Pubmed, Science Direct Web of Science, Scopus, and scientific articles in Cyrillic) databases were reviewed. The search results included keywords that define the current problem: muscle pain, referred muscle pain, nociceptive pain, neuropathic pain, radicular pain, somatic, viscera, visceral pain, hyperalgesia, central sensitization, spinal sensitization, visceral hyperalgesia; viscerosomatic convergence; descending modulation, muscle contraction, muscle hypotrophy. Results: When searching for topical scientific results, not many publications have been found. Some of them were older, in some possible mechanisms of pathogenetic manifestation of referred muscle pain were discussed. One article suggested the existence of another possible mechanism besides the generally described ones. Several hypotheses concerning the occurrence of this secondary pain were found to exist, without giving priority to any theory. Most articles described different localizations of symptoms of referred pain and their relationship to other body structures (muscle or joint in a distant region) or internal organ dysfunction or disease. Most of the authors emphasized on the need of better knowledge of this type of pain and the distinction between local, nociceptive, radicular, and neuropathic pain that has a precise clinical characteristic and evidence of a specific injury to an underlying body structure. Conclusion: Knowledge and diagnosing of referred muscle pain is important for clinical practice. Differentiation from primary skeletal muscle pain is still a challenge, but a good knowledge of the problem can provide solutions, although the pathogenetic mechanisms of its occurrence remain unclear. It is likely that the totality of central-nervous mechanisms, the convergence of information from different somatic areas in the dorsal horn and/or its facilitation in it as well as at the level of the thalamus, and the phenomenon of hyperexcitability are essential, although the notion that referred muscle pain has a peripheral origin should not be ignored. Knowledge and targeted search for referred secondary pain could prevent some diagnostic problems and at the same time treat it with appropriate treatments, including the means of physiotherapy.

Congenital Myasthenic Syndromes

Congenital myasthenic syndromes (CMS) are characterized by congenital defects in the neuromuscular signal transmission and are caused by pathogenic variants in 36 genes. Recently identified forms of CMS include TOR1AIP1-CMS, CHD8-CMS, PURA-CMS, and TEFM-CMS. Most forms of CMS are caused by autosomal recessive variants, whereas four forms of CMS are caused by autosomal dominant variants, in which adult-onset cases are not rare. As myasthenic features are not always observed and muscle hypotrophy is sometimes observed, CMS should be considered in differential diagnosis of congenital myopathies and other neuromuscular diseases. Low- and high-frequency repetitive nerve stimulation is essential to diagnose CMS for patients who develop muscle weakness at less than 2 years of age. Tubular aggregates are observed in muscle biopsy in four forms of CMS, and serum CK levels are elevated in some forms of CMS. As rational therapies are available for most forms of CMS, identification of causative gene variants by genetic analysis is required.

A new family with a case of severe early-onset muscle fatigue and a peculiar maternally inherited painful swelling in chewing muscles associated with homoplasmic m.15992A>T mutation in mitochondrial tRNAPro

A 16-year-old boy was evaluated for a history of exercise-induced fatigability associated with nausea even after minimal effort, lower limbs muscle hypotrophy, and swelling of the masseter muscles after chewing. Laboratory tests were remarkable for hyperlactatemia and metabolic acidosis after short physical activity. The muscle biopsy showed non-specific mitochondrial alterations and an increase in intrafibral lipids. Biochemical analysis showed reduced activity of the respiratory chain complexes. Mitochondrial DNA sequencing revealed the presence of a homoplasmic variant m.15992A>T in the MT-TP gene, coding for the mt-tRNAPro in the patient, in his mother and in his brother. Pathogenic or likely pathogenic variants in MT-TP gene are rare. They are responsible for different clinical presentation, almost ever involving the muscle tissue. We report the first family with exercise-induced muscle weakness and swelling of the chewing muscles due to m.15992A>T variant in absence of J1c10 haplogroup, confirming its pathogenicity.

Neurological disorders imitating spinal stenosis in elderly patients. Series of clinical observations

Spinal stenosis is a pathological narrowing of the central spinal canal, lateral pocket, or intervertebral foramen due to age‑related changes, including pathology of the discs, facet joints, ligament hypertrophy, osteophyte formation and destruction of the arches. Clinically, the disease can manifest itself with pain, as well as numbness, or weakness in the arms or legs. The complexity of differential diagnosis is due to the lack of correlation between the degree of stenosis according to neuroimaging data and the severity of clinical manifestations. Spinal stenosis among 21 % of people may have an asymptomatic course.Spinal stenosis has to be differentiated from atherosclerosis of the vessels of the lower extremities, rheumatoid arthritis, piriformis syndrome, sacroiliitis, spondylitis/spondylodiscitis, amyotrophic lateral sclerosis, Guillain–Barré syndrome and other polyneuropathies. Isolated weakness should be of a particular concern in the clinical picture. Muscle hypotrophy, brisk tendon reflexes, the presence of pyramidal signs, muscle fasciculations, as well as patients’ complaints of simultaneous weakness in both the upper and lower extremities accompany them.We present and discuss three clinical cases of patients with a presumptive diagnosis of spinal stenosis. Two of them were held surgical treatment, which did not produce the expected result. Subsequently, it was found that the cause of progressive muscle weakness in the limbs was amyotrophic lateral sclerosis in two patients and the third one had Guillain–Barré syndrome, a form of acute demyelinating polyneuropathy.

Description of Twenty-Nine Animal Hoarding Cases in Italy: The Impact on Animal Welfare.

The hoarding of animals is a psychiatric disease, characterized by a compulsive collection of animals, with a relevant impact upon the care and welfare of animals, as well as on human society. In Italy, there are neither substantial reports nor information shared about such a phenomenon, making it difficult to draw a clear picture of the hoarder profile. Therefore, in the present work, we sought to detail 29 cases of animal accumulators in Italy, who lived within two areas of the Lazio region, and accumulated a total of 1080 animals from 2019 to 2022. In line with other international studies, we observed a prevalence of middle-aged (in their fifties) women, who lived mainly alone in a high level of social and health degradation. Most of the hoarded animals exhibited severe signs of dehydration and malnutrition, muscle hypotrophy, dermatological injuries, and behavioral disorders. Animal hoarding is not yet fully understood nor recognized as a psychosocial disorder, although it produces a deep suffering for the hoarder themselves, as well as corresponding family members, and the animals accumulated. Therefore, given the crucial impact of animal hoarding upon human and animal welfare, cross-cultural networks aimed at properly raising awareness of the problem could be established.

DNM2 levels normalization improves muscle phenotypes of a novel mouse model for moderate centronuclear myopathy

Dynamin 2 (DNM2) is a ubiquitously expressed GTPase regulating membrane trafficking and cytoskeleton dynamics. Heterozygous dominant mutations in DNM2 cause centronuclear myopathy (CNM), associated with muscle weakness and atrophy and histopathological hallmarks as fiber hypotrophy and organelles mis-position. Different severities range from the severe neonatal onset form to the moderate form with childhood onset and to the mild adult onset form. No therapy is approved for CNM. Here we aimed to validate and rescue a mouse model for the moderate form of DNM2-CNM harboring the common DNM2 R369W missense mutation. Dnm2R369W/+ mice presented with increased DNM2 protein level in muscle and moderate CNM-like phenotypes with force deficit, muscle and fiber hypotrophy, impaired mTOR signaling, and progressive mitochondria and nuclei mis-position with age. Molecular analyses revealed a fiber type switch toward oxidative metabolism correlating with decreased force and alteration of mitophagy markers paralleling mitochondria structural defects. Normalization of DNM2 levels through intramuscular injection of AAV-shDnm2 targeting Dnm2 mRNA significantly improved histopathology and muscle and myofiber hypotrophy. These results showed that the Dnm2R369W/+ mouse is a faithful model for the moderate form of DNM2-CNM and revealed that DNM2 normalization after a short 4-week treatment is sufficient to improve the CNM phenotypes.

Cardiac magnetic resonance findings and prognosis in type 1 myotonic dystrophy.

Cardiac involvement is a major determinant of prognosis in type 1 myotonic dystrophy (DM1), but limited information is available about myocardial remodeling and tissue changes. The aim of the study was to investigate cardiac magnetic resonance (CMR) findings and their prognostic significance in DM1. We retrospectively identified all DM1 patients referred from a neurology unit to our CMR laboratory from 2009 to 2020. Thirty-four patients were included (aged 45 ± 12, 62% male individuals) and compared with 68 age-matched and gender-matched healthy volunteers (43 male individuals, age 48 ± 15 years). At CMR, biventricular and biatrial volumes were significantly smaller (all P < 0.05), as was left ventricular mass (P < 0.001); left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were significantly lower (all P < 0.01). Five (15%) patients had a LVEF less than 50% and four (12%) a RVEF less than 50%. Nine patients (26%) showed mid-wall late gadolinium enhancement (LGE; 5 ± 2% of LVM), and 14 (41%) fatty infiltration. Native T1 in the interventricular septum (1041 ± 53 ms) was higher than for healthy controls (1017 ± 28 ms) and approached the upper reference limit (1089 ms); the extracellular volume was slightly increased (33 ± 2%, reference <30%). Over 3.7 years (2.0-5.0), 6 (18%) patients died of extracardiac causes, 5 (15%) underwent device implantation; 5 of 21 (24%) developed repetitive ventricular ectopic beats (VEBs) on Holter monitoring. LGE mass was associated with the occurrence of repetitive VEBs (P = 0.002). Lower LV stroke volume (P = 0.017), lower RVEF (P = 0.016), a higher LVMi/LVEDVI ratio (P = 0.016), fatty infiltration (P = 0.04), and LGE extent (P < 0.001) were associated with death. DM1 patients display structural and functional cardiac abnormalities, with variable degrees of cardiac muscle hypotrophy, fibrosis, and fatty infiltration. Such changes, as evaluated by CMR, seem to be associated with the development of ventricular arrhythmias and a worse outcome.

The association between the skeletal muscle state, lipid metabolism disorders and the development of insulin resistance in children with type 1 diabetes mellitus

The aim of the study. To establish a possible association between the skeletal muscles state, changes in lipid metabolism and the development of insulin resistance in children with type I diabetes mellitus. Materials and methods. 98 children with type 1 diabetes, aged from 11 to 17 years, were examined. Children were divided into 3 groups depending on the state of skeletal muscles: the first group – 22 children without disorders of the muscular system; the second group – 42 children with dynapenia; the third group – 34 patients with diabetic myopathy. The control group – 30 conditionally healthy children. The groups were representative by age, sex, and body mass index. Children were subjected to examinations of skeletal muscle mass and fat mass, followed by calculation of the skeletal muscle index and body fat percentage, sonomyography of the anterior group of thigh muscles with their thickness determination, measurements of the degree and coefficient of muscle hypotrophy, fasting blood glucose level, serum cholesterol, triglycerides and triglyceride-glucose (TyG) index. Insulin resistance was diagnosed when the TyG index was higher than 4.33 c. u. Results. It was found that the development of diabetic myopathy, in addition to a decrease in muscle mass, was characterized by a redistribution of the body component composition due an increase in the fat mass proportion. These changes were accompanied by a disturbance of lipid metabolism in the form of increase in serum cholesterol level, triglycerides and TyG index, which was 4.33 c. u. higher in 32.4 % of children with diabetic myopathy, and in 9.5 % of children with dynapenia, while among patients with normal state of the muscular system, the TyG index exceeded the threshold value in no case. Comparison of clinical and laboratory indicators depending on the TyG index level found an increase in the fat mass proportion, a violation of glycemic control, an increase in the daily dose of insulin, appearance of combined hyperlipidemia and the dawn phenomenon in children with an indicator that was higher than 4.33 c. u. All these were indicative of the insulin resistance development. Conclusions. Skeletal muscle dysfunction in children with type 1 diabetes is a causal risk factor for the development of insulin resistance, a sensitive marker of which is the TyG index. The simplicity of calculating this indicator allows it to be used in daily clinical practice.

Subacute polyneuropathy of a patient under treatment with disulfiram, suffering from alcohol use disorder

Abstract Disulfiram is a drug commonly used in the treatment of chronic alcohol use disorder. It works by inhibiting the enzyme acetaldehyde dehydrogenase, causing highly unpleasant symptoms upon alcohol intake, which supports abstinence by deterring alcohol consumption. We present the case of a 31-year-old male with a long history of alcohol dependence, since the age of 14. The patient had no other comorbidities. His addiction problem determined him to pursue alcohol withdrawal and psychiatric treatment. He had been on disulfiram therapy for one year. The onset of his symptoms started three months prior to admission to our clinic; he developed progressive, symmetric lower limb weakness, which notably worsened during the two weeks prior to hospitalization. According to collateral history, this exacerbation coincided with significant alcohol consumption while on disulfiram treatment. Neurological Examination Findings revealed: no meningeal signs, right-sided hearing loss, stepping gait achievable only with partial assistance, flaccid paraparesis (MRC grade 4 in the lower limbs muscle groups), tongue tremor, upper limb postural tremor, and palpebral myoclonus, symmetrical deep tendon reflexes, decreased in the lower limbs, no pyramidal signs, pallhypesthesia of the legs with reduced vibratory sense in the distal lower limbs, lower limb muscle hypotrophy, no sphincter or erectile dysfunction, preserved coordination and orientation in time and space. Electromyography and electroneurography revealed bilateral active denervation in the lower limb muscles, consistent with progressive poly(radiculo)neuropathy. Laboratory tests, cranial CT, spinal MRI, and cerebrospinal fluid analysis showed no other pathological findings to explain the neuropathy. Disulfiram therapy was discontinued, and the patient was treated with neurotrophic medications and physical therapy, leading to a gradual resolution of his symptoms. Although peripheral neuropathy due to disulfiram is rarely reported in the literature, in this case, the combination of disulfiram treatment with concurrent alcohol use likely contributed to the acute exacerbation of peripheral nerve damage.

Bridging the Gap: Gene Therapy in a Patient With Spinal Muscular Atrophy Type 1.

Molecular therapies exploit the understanding of pathogenic mechanisms to reconstitute impaired gene function or manipulate flawed RNA expression. These therapies include (1) RNA interference by antisense oligonucleotides, (2) mRNA modification using small molecules, and (3) gene replacement therapy, the viral-mediated intracellular delivery of exogenous nucleic acids to reverse a genetic defect. Several molecular therapies are approved for treating spinal muscular atrophy (SMA), a recessive genetic disorder caused by survival motor neuron (SMN)1 gene alterations. SMA involves degeneration of lower motor neurons, which leads to progressive muscle weakness, hypotonia, and hypotrophy. Onasemnogene abeparvovec is a gene replacement therapy for SMA that uses adeno-associated virus delivery of functional SMN1 cDNA to motor neurons. Two other molecular therapies modulate SMN2 transcription: nusinersen, an antisense oligonucleotide, and risdiplam, a small molecule designed to modify faulty mRNA expression. The most suitable individualized treatment for SMA is not established. Here, we describe remarkable clinical improvement in a 4-month-old patient with SMA type 1 who received onasemnogene abeparvovec therapy. This case represents an explanatory bridge from bench to bedside with regard to therapeutic approaches for genetic disorders in neurology. Knowledge of the detailed mechanisms underlying genetic neurologic disorders, particularly monogenic conditions, is paramount for developing tailored therapies. When multiple disease-modifying therapies are available, early genetic diagnosis is crucial for appropriate therapy selection, highlighting the importance of early identification and intervention. A combination of drugs, each targeting unique genetic pathomechanisms, may provide additional clinical benefits.

Role of psoas muscle area as an indicator of adverse outcomes after transcatheter aortic valve implantation

Introduction. Patient frailty, having muscle hypotrophy as the main component, is important in determining the treatment tactics of cardiovascular diseases due to a decrease in the physiological reserve. An objective assessment of dystrophic changes level in the total muscle mass is possible by measurig the cross-sectional area of the psoas muscle (PMA). Аim was to determine if the psoas muscle area (PMA) could predict adverse outcomes and to investigate its utility in patients after transcatheter aortic valve implantation (TAVI). Materials and methods. The study included 51 patients with critical symptomatic aortic stenosis and high risk factors according to EuroScore II and STS. The study is a retrospective, single-centre analysis of the association of PMA from preoperative multislice computed tomography with adverse outcomes after TAVI. PMA was calculated as the average area of the left and right psoas. PMA measurements were then normalized to the patient’s body surface area (m2) and showed as psoas muscle index (iPMA; cm2/m2). Results. The mean age of the patients was 78.2±9.3 years, where 29 (56.9 %) were women. Since iPMA was not normally distributed, median values were analyzed: median iPMA for men 4.35 cm2/m2 and for women 3.55 cm2/m2. In our study, we found that iPMA was lower in patients with an early adverse outcome than in patients without an early adverse outcome (3.21±0.42 vs 5.47±0.43 cm2/m2; p=0.017). Patients with low iPMA (62.8 %) required longterm hospitalization, and low iPMA can be considered a predictor of higher hospital resource costs (p=0.056). Conclusion. Our study demonstrated that computed tomography-calculated iPMA is a simple and objective predictor of early postoperative complications and prolonged hospital stay after TAVI, and consequently higher hospital resource costs.

Long-term patient rehabilitation and quality of life after oncological endoprosthesis of long bones and joints

Background. Currently, endoprosthesis of large bones and joints is the standard of treatment for patients with tumors in the bones and joints of the upper and lower limbs and pelvis. However, the problem of integrated medical rehabilitation of these patients remains unsolved. In the postoperative period, patients frequently experience such functional abnormalities as limited mobility in the operated joint, pain, deceased locomotor activity in the joints due to prolonged bedrest leading to muscle hypotrophy. These abnormalities interfere with return to full social life affecting patients’ quality of life and making rehabilitation very important. Aim. To evaluate the effect of rehabilitation on patients’ quality of life and social adaptation after oncological endoprosthesis. Materials and methods. The study included 57 patients: 27 (47 %) males and 30 (53 %) females. Mean age was 46 years (19–71 years). In 10 patients, tumors were localized in the bones of the upper limb; in 6 patients, in the pelvic bones; in 41 patients, in the bones of the lower limb. Tumor volume varied between 24 and 3,783 cm3 (median 631 cm3 ). Pathological fractures were observed in 13 (24.5 %) patients, their risk – in 13 (24.5 %) patients. Patient activization was started at day 1–14 after surgery, passive working out of the operated limb on day 2–14. For quality of life evaluation, The Short Form-36 (SF-36) was used allowing to determine patients’ health. Functional results were analyzed using the Musculoskeletal Tumour Society score (MSTS), rehabilitation potential using the Tampa Scale of Kinesiophobia covering both physical and psychological components. Social status was evaluated based on patient’s occupation and social adaptation. Results. Performance of active rehabilitation activities after onco-orthopedic intervention allows 72 % of patients to achieve good and excellent functional results per the MSTS scale (60–97 %) under condition of protective regimen observation, as well as positively affects physical and psychological parts of quality of life. Use of Tampa Scale of Kinesiophobia allows to correct psychological and/or physical parts of kinesiophobia in a timely fashion. Adequately performed rehabilitation allows 46 % of patients to remain socially active, continue working. Conclusion. Scale of surgical intervention, presence of pathological fracture, as well as postoperative complications, affect both functional results and quality of life of patients which in this period in most observations is higher than prior to onco-orthopedic treatment. Tampa Scale of Kinesiophobia allows to evaluate patient motivation towards postoperative recovery and provide psychological help in a timely manner which decreases rehabilitation time.