Skeletal muscle symptoms and quantitative MRI in females with dystrophinopathy.

INTRODUCTION/AIMS: The dystrophinopathies primarily affect males; however, female carriers of pathogenic dystrophin variants can develop skeletal muscle symptoms. This study aimed to evaluate muscle involvement and symptoms in females with dystrophinopathy using quantitative magnetic resonance imaging (MRI), functional assessments, and patient-reported outcomes. METHODS: Controls and females with dystrophinopathy with muscle symptoms of pain, weakness, fatigue, or excessive tightness were enrolled in this cross-sectional study. Participants underwent lower extremity MRI to quantify muscle inflammation, replacement by fat, and disease asymmetry. Cardiac MRI, functional ability, muscle symptoms, and serum creatine kinase levels were also evaluated. RESULTS: Six pediatric females with dystrophinopathy (mean age: 11.7 years), 11 adult females with dystrophinopathy (mean age: 41.3 years), and seven controls enrolled. The mean fat fraction was increased in females with dystrophinopathy compared to controls in the soleus (0.11 vs. 0.03, p = .0272) and vastus lateralis (0.16 vs. 0.03, p = .004). Magnetic resonance spectroscopy water T2, indicative of muscle inflammation, was elevated in the soleus and/or vastus lateralis in 11 of 17 individuals. North Star Ambulatory Assessment score was lower in the dystrophinopathy group compared to controls (29 vs. 34 points, p = .0428). From cardiac MRI, left ventricle T1 relaxation times were elevated in females with dystrophinopathy compared to controls (1311 ± 55 vs. 1263 ± 25 ms, p < .05), but ejection fraction and circumferential strain did not differ. DISCUSSION: Symptomatic females with dystrophinopathy quantitatively demonstrate muscle replacement by fat and inflammation, along with impairments in functional ability and cardiac function. Additional research is needed to evaluate how symptoms and muscle involvement change longitudinally.

Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec.

OBJECTIVE: We describe outcomes following onasemnogene abeparvovec monotherapy for patients with ≥four survival motor neuron 2 (SMN2) gene copies in RESTORE, a noninterventional spinal muscular atrophy patient registry. METHODS: We evaluated baseline characteristics, motor milestone achievement, post-treatment motor function, use of ventilatory/nutritional support, and adverse events as of December 22, 2022. RESULTS: At data cutoff, 19 patients in RESTORE had ≥four SMN2 copies and were treated with onasemnogene abeparvovec monotherapy (n=12 [63.2%] four copies; n=7 [36.8%] >four copies). All patients were identified by newborn screening and were reported as asymptomatic at diagnosis. Median age at onasemnogene abeparvovec administration was 3.0 months. Median time from treatment to last recorded visit was 15.4 months, with a range of post-treatment follow-up of 0.03-39.4 months. All 12 children who were assessed for motor development achieved new milestones, including standing alone (n=2) and walking alone (n=5). Five children reported one or more treatment-emergent adverse events (one Grade 3 or greater). No deaths or use of ventilatory/nutritional support were reported. CONCLUSIONS: Real-world findings from the RESTORE registry indicate that patients with ≥four SMN2 gene copies treated with onasemnogene abeparvovec monotherapy demonstrated improvements in motor function. Adverse events experienced by these patients were consistent with previously reported findings.

Bazi Bushen mitigates age-related muscular atrophy by alleviating cellular senescence of skeletal muscle.

Background and aim: Muscular atrophy is one of the most common age-related conditions characterized by the deterioration of skeletal muscle structures and impaired functions. It is associated with cellular senescence and chronic inflammation, which impair the function of muscle stem cells. Bazi Bushen (BZBS) is a patent compound Chinese medicine that has been shown to have anti-aging effects in various animal models. In this study, we investigated the effects and mechanisms of BZBS on muscular atrophy in naturally aged mice. Experimental procedure: A muscular atrophy model of naturally aged mice (18 months) was employed with administration of BZBS (2 g/kg/d, 1 g/kg/d) and nicotinamide mononucleotide (NMN, 200 mg/kg/d). After six months of drug administration, muscle weight loss, muscle function and muscle histopathology were measured to evaluate the therapeutic effect of BZBS. The expression of cellular senescence, inflammatory and satellite cell-related factors were used to assess the effects of BZBS in inhibiting cellular senescence, reducing inflammation and improving muscle atrophy. Results and conclusion: Compared with age matched natural aging mice, we found that BZBS improved muscle strength, mass, and morphology by reducing senescent cells, inflammatory cytokines, and intermyofiber fibrosis in aged muscle tissues. We also found that BZBS prevented the reduction of Pax7 positive stem cells and stimulated the activation and differentiation into myocytes. Our results suggest that BZBS might be a promising intervention in senile muscular atrophy.

DENV-1 infection with rhabdomyolysis in an adolescent: A case report and review of challenge in early diagnosis and treatment.

Dengue infection is a well-known tropical disease that has become a global health issue. The clinical characteristics of dengue range from asymptomatic to severe, which can involve multiple organs and challenge management. Rhabdomyolysis in dengue infection is a rare condition described in children and adolescents. Herein, we present the case of a young adolescent with autism spectrum disorder who had a dengue virus serotype 1 infection complicated by rhabdomyolysis, which was not detected based on its typical manifestations. Rhabdomyolysis is recognized as one of the manifestations of expanded dengue syndrome and is associated with significant morbidity and mortality, especially if acute kidney injury develops. These coexisting conditions should be carefully considered, particularly in patients with underlying medical issues that may contribute to a worse prognosis. The early diagnosis and management of patients with dengue complicated by rhabdomyolysis is challenging and should be widely acknowledged. The detection of potential complications and appropriate fluid balance are essential to achieve a better prognosis.

Evaluation of fatigue and fatigability in people with Duchenne muscular dystrophy using a dynamic arm support - a pilot study.

BACKGROUND: Due to progressive muscle wasting and weakness in patients with Duchenne Muscular Dystrophy (DMD), physical fatigability increases, upper extremity function reduces, which negatively impacts quality of life. Assistive technology such as dynamic arm supports (DAS) may help reduce this fatigability. This study aims to assess whether the novel Yumen 'EXone' DAS can reduce upper extremity fatigue and fatigability in DMD patients and healthy controls (HC), both with and without the DAS. Additionally, longitudinal changes in DMD patients were evaluated. METHODS: Five DMD patients from the Yumen Bionics pioneer program and five HCs participated. Two submaximal tests simulating drinking and reaching were performed for two minutes, each with and without DAS. DMD participants completed these tests twice, at baseline (T0) and after 6-9 months (T1), while HCs completed them once. Physical fatigability was measured by the number of repetitions and changes in surface electromyography (sEMG) amplitude. Subjective fatigue was assessed using the Borg Scale (6-20) Rate of Perceived Exertion (RPE). RESULTS: DMD participants generally performed more repetitions with the DAS than without. HCs showed similar or increased repetitions with the DAS. Assessing fatigability with sEMG was difficult due to the compensatory mechanisms used for the tests. Subjective fatigue scores on the Borg Scale were lower with the DAS for both DMD patients and HCs. CONCLUSION: The Yumen 'EXone' DAS effectively reduces both fatigue and fatigability in DMD patients and healthy controls. Despite the methodological shortcomings, this research is one of the first studies investigating the impact of DAS on fatigue and fatigability.

This study is one of the pioneering studies investigating the impact of a dynamic arm support on fatigue and fatigability in Duchenne Muscular Dystrophy.Both, physical fatigability and experienced fatigue, decrease when using a dynamic arm support.Using sEMG to assess fatigability in DMD is difficult due to the compensatory mechanisms used for daily life task performance.Reduced fatigue and fatigability when using a dynamic arm support could be a significant reason for its use, alongside enhanced arm functionality.

Walker-Warburg syndrome: A case report of congenital muscular dystrophy with hydrocephalus.

Walker-Warburg Syndrome is a genetically heterogeneous disease with autosomal recessive inheritance characterized by brain and eye deformities, profound mental retardation, congenital muscular dystrophy, and early death. This case study demonstrates a mutation on chromosome 12q14 in the TMEM5 gene (RXYLT1; 605862), which encodes a transmembrane protein with glycosyltransferase function. We present a case of a full-term male baby delivered by Cesarean section due to macrocephaly. At birth, the newborn had hypotonia and respiratory distress, requiring mechanical ventilation. On examination the patient was found to have macrocephaly, generalized hypotonia, hyporeflexia, and retinal degeneration. Genetic testing revealed a homozygous variant in the RXYLT1 gene, consistent with the diagnosis of autosomal recessive muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A10. The patient underwent a ventriculoperitoneal shunt and received supportive management. WWS is a fatal disease, and most affected children do not survive beyond the age of 3. Prenatal screening, ultrasonography and magnetic resonance imaging can aid in the detection and confirmation of abnormal brain development in WWS cases.

Thrombospondin-4 as potential cerebrospinal fluid biomarker for therapy response in pediatric spinal muscular atrophy.

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) as the second most common neurodegenerative disorder in childhood is characterized by the deficiency of survival of motor neuron (SMN) protein leading predominantly to degeneration of alpha motor neurons and consequently to progressive muscle weakness and atrophy. Besides some biomarkers like SMN2 copy number therapeutic biomarkers for SMA with known relevance for neuromuscular transmission are lacking. Here, we examined the potential of Thrombospondin-4 (TSP4) to serve as a cerebrospinal fluid (CSF) biomarker, which may also indicate treatment response. METHODS: We used untargeted proteomic analyses to determine biomarkers in CSF samples derived from pediatric pre-symptomatic (n = 6) and symptomatic (n = 4) SMA patients. The identified biomarker TSP4 was then validated in additional 68 CSF samples (9 adult and 24 pediatric SMA patients, 5 adult and 13 pediatric non-disease controls in addition to 17 pediatric disease controls) by enzyme-linked immunosorbent assay (ELISA) as an additional analytical approach. RESULTS: Untargeted proteomic analyses of CSF identified a dysregulation of TSP4 and revealed a difference between pre-symptomatic SMA patients and patients identified after the onset of first symptoms. Subsequent ELISA-analyses showed that TSP4 is decreased in pediatric but not adult SMA patients. CSF of pediatric patients with other neurological disorders demonstrated no alteration of TSP4 levels. Furthermore, CSF TSP4 levels of pediatric SMA patients increased after first dose of Nusinersen. CONCLUSIONS: We found that TSP4 levels are exclusively reduced in CSF of pediatric SMA patients and increase after treatment, leading us to the hypothesis that TSP4 could serve as a CSF biomarker with the potential to monitor treatment response in pediatric SMA patients. Moreover, TSP4 enable to distinguish pre-symptomatic and symptomatic patients suggesting a potential to serve as a stratification marker.

Ultrasound assisted versus landmark based intrathecal administration of nusinersen in adults with spinal muscular atrophy disease: A randomized trial.

INTRODUCTION/AIMS: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)-assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients. METHODS: Fifty-eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US-assisted technique) or Group 2 (nusinersen infusion with landmark-based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t-test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi-square test or Fisher's exact test in case of expected frequencies <5. The p-values <.05 were considered statistically significant. RESULTS: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark-based group (p < .05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US-group versus landmark-based group (p < .05). DISCUSSION: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion.

Cataloging health state utility estimates for Duchenne muscular dystrophy and related conditions.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic disease resulting in progressive muscle weakness, loss of ambulation, and cardiorespiratory complications. Direct estimation of health-related quality of life for patients with DMD is challenging, highlighting the need for proxy measures. This study aims to catalog and compare existing published health state utility estimates for DMD and related conditions. METHODS: Using two search strategies, relevant utilities were extracted from the Tufts Cost-Effectiveness Analysis Registry, including health states, utility estimates, and study and patient characteristics. Analysis One identified health states with comparable utility estimates to a set of published US patient population utility estimates for DMD. A minimal clinically important difference of ± 0.03 was applied to each DMD utility estimate to establish a range, and the registry was searched to identify other health states with associated utilities that fell within each range. Analysis Two used pre-defined search terms to identify health states clinically similar to DMD. Mapping was based on the degree of clinical similarity. RESULTS: Analysis One identified 4,308 unique utilities across 2,322 cost-effectiveness publications. The health states captured a wide range of acute and chronic conditions; 34% of utility records were extrapolated for US populations (n = 1,451); 1% were related to pediatric populations (n = 61). Analysis Two identified 153 utilities with health states clinically similar to DMD. The median utility estimates varied among identified health states. Health states similar to the early non-ambulatory DMD phase exhibited the greatest difference between the median estimate of the sample (0.39) and the existing estimate from published literature (0.21). CONCLUSIONS: When available estimates are limited, using novel search strategies to identify utilities of clinically similar conditions could be an approach for overcoming the information gap. However, it requires careful evaluation of the utility instruments, tariffs, and raters (proxy or self).

Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids.

BACKGROUND AND PURPOSE: Treatment with glucocorticoids (GCs) is part of the standard of care in Duchenne muscular dystrophy, but excess weight gain and height stunting are common side-effects. It is still unclear how these growth-related side-effects affect motor function. METHODS: This retrospective cohort study utilized 2228 observations from 648 participants in the UK NorthStar database who had growth and ambulation data recorded between 2006 and 2020. Joint modelling was used to analyse the effect of longitudinal growth centiles on loss of ambulation with respect to GC type and regimen. RESULTS: Loss of ambulation was observed in 113 patients. National estimates of loss of ambulation age were updated by GC group and showed no significant association between loss of ambulation risk and absolute growth centile. However, yearly drift in weight and/or height centile had an associated risk effect on loss of ambulation. Over a 2-year period, a yearly drift in weight from the 50th to the 75th, 75th to the 90th and 90th to the 95th centile was associated with 138%, 118% and 64% increased risk of loss of ambulation, respectively. Conversely, a 2-year drift in height from the 50th to the 25th, 25th to the 10th and 10th to the 5th centile was associated with 53%, 49% and 35% decreased risk of loss of ambulation, respectively. CONCLUSIONS: Our results suggest a complex relationship between growth and loss of ambulation in Duchenne muscular dystrophy boys on chronic GCs, the first step in understanding the effects of drugs which also affect growth patterns.

Efficacy and safety of different doses of vamorolone in boys with Duchenne muscular dystrophy: a systematic review and network meta-analysis.

Background and objectives: Several recent clinical studies have indicated that vamorolone is comparable in effectiveness to glucocorticosteroids for treating Duchenne muscular dystrophy (DMD). However, there is a lack of extensive data regarding the efficacy and safety of various doses of vamorolone. We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD. Methods: We performed systematic searches of the PubMed, Embase, and Cochrane Library databases for vamorolone, glucocorticosteroids, prednisone or deflazacort in boys with DMD. We assessed statistical heterogeneity across trials based on the Newcastle Ottawa scale (NOS) tool test and I2 values, and mean differences were pooled using the random-effects model. We used traditional meta-analysis to evaluate efficacy and safety of vamorolone 6.0 mg/kg/d vs. vamorolone 2.0 mg/kg/d and vamorolone vs. prednisone. A network meta-analysis was applied to estimated the safety of vamorolone in comparison to glucocorticosteroids, prednisone and deflazacort. Our meta-analysis were performed using Revman 5.4 software, and our network meta-analysis were performed using Stata/MP 18.0. Results: In the meta-analysis, a total of 193 patients were analyzed across four clinical trials (97 patients receiving vamorolone 2 mg/kg per day; 96 patients receiving vamorolone 2 mg/kg per day). We observed that there were statistically significant differences in boys with DMD between vamorolone 6.0 mg/kg/d and vamorolone 2.0 mg/kg/d in TTSTANDV (MD = 0.03, 95%CI = 0.00-0.06, p = 0.04), TTRWV (MD = 0.13, 95%CI = 0.08-0.19, p < 0.01), 6MWT (MD = 24.54, 95%CI = 4.46-44.82, p = 0.02), TTCLIMBV (MD = 0.04, 95%CI = 0.01-0.06, p = 0.009), no significant difference in BMI z score (MD = 0.09, 95%CI = -0.03-0.20, p = 0.13). Indirect comparisons derived from network meta-analysis did not show significant differences among vamorolone, glucocorticosteroids, prednisone and deflazacort in BMI z score. Conclusion: Our findings implied that boys with DMD who took vamorolone 6 mg/kg daily instead of 2 mg/kg daily may be safer and have superior motor function. However, more large sample randomized controlled trials are needed to confirm our results. Systematic Review Registration: This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916).

Clinical application of a modified wiltse approach in middle and lower thoracic vertebrae: a case-control study of thoracic fracture patients.

BACKGROUND: The Wiltse approach has been extensively employed in thoracolumbar surgeries due to its minimal muscle damage. However, in the middle and lower thoracic spine, the conventional Wiltse approach necessitates the severance of the latissimus dorsi and trapezius muscles, potentially leading to muscular injury. Consequently, we propose a modified Wiltse approach for the middle and lower thoracic vertebrae, which may further mitigate muscular damage. METHODS: From May 2018 to April 2022, 60 patients with spinal fractures in the middle and lower thoracic vertebrae (T5-12) were enrolled in this study. Thirty patients underwent surgery using the modified Wiltse approach (Group A), while the remaining 30 patients received traditional posterior surgery (Group B). The observation indices included operation time, intraoperative blood loss, incision length, number of C-arm exposures, postoperative drainage, postoperative ambulation time, discharge time, as well as preoperative and postoperative Cobb's angle, percentage of anterior vertebral body height (PAVBH), visual analog scale (VAS) Score, and Oswestry disability index (ODI). RESULTS: Compared to the traditional posterior approach, the modified Wiltse approach demonstrated significant advantages in operation time, intraoperative blood loss, length of incision, postoperative ambulation time, postoperative drainage, and discharge time, as well as postoperative VAS and ODI scores. No significant differences were observed between the two groups in terms of number of C-arm exposures, postoperative Cobb's angle, or postoperative PAVBH. CONCLUSION: We propose a modification of the Wiltse approach for the middle and lower thoracic vertebral regions, which may further minimize muscular damage and facilitate the recovery of patients who have undergone surgery in the middle and lower thoracic vertebrae.

Sensory dysfunction in SMA type 2 and 3 - adaptive mechanism or concomitant target of damage?

BACKGROUND: The motor neuron survival protein performs numerous cellular functions; hence, spinal muscular atrophy (SMA) is considered to be a multi-organ disease with possible sensory system damage. The controversy surrounding the presence of sensory disturbances, prompted us to conduct standard electrophysiological studies and assess the sensory thresholds for different modalities in adults with SMA types 2 and 3. The study group consisted of 44 adult SMA patients (types 2 and 3). All patients underwent neurological examination using the Hammersmith Functional Motor Scale - Expanded (HFMSE). Standard sensory electrophysiological studies in the ulnar nerve and the estimation of vibratory, temperature, and warm- and cold-induced pain thresholds with temperature dispersion assessment were performed using quantitative sensory testing (QST). RESULTS: The most repeatable result was the high amplitude of the sensory nerve action potentials (SNAP) in SMA patients compared to controls. This was higher in type 2 patients compared to type 3a and 3b patients and patients with low HFSME scores. Patients with SMA, especially type 3b presented a longer sensory latency and slower conduction velocity than did controls. Cold pain threshold was higher and warm dispersion larger in SMA. The vibratory limit was higher in patients with high HFSME scores. CONCLUSIONS: A high SNAP amplitude suggests sensory fibre hyperactivity, which may be based on overactivation of metabolic pathways as an adaptive mechanism in response to SMN protein deficiency with additionally coexisting small C- and A-delta fibre damage. SMA patients seem to have a concomitant, mild demyelinating process present at the early SMA stage.

The Vectorcardiogram Characteristic and Its Predictive Value for Reduced Left Ventricular Ejection Fraction of Children with Duchenne Muscular Dystrophy.

Background: The prognosis of Duchenne muscular dystrophy (DMD) is poor once it develops to the stage of cardiac impairment. Recent studies have demonstrated that electrocardiogram (ECG), which consists of general ECG and vectorcardiogram (VCG), retains an extremely powerful role in the assessment of patients with reduced left ventricular (LV) systolic dysfunction. However, data regarding VCG recordings in DMD and its prognostic value for reduced left ventricular ejection fraction (LVEF) of DMD have never been reported. This study aims to describe the characteristics of VCG in children with DMD and to explore the predictive value of VCG for reduced LVEF in children with DMD. Methods: A total of 306 patients with a known diagnosis of DMD confirmed by the genetic test were retrospectively enrolled at our hospital between August 2018 and August 2022. This resulted in a total study group of 486 VCG recordings. Among them, 75 DMD patients who underwent cardiac magnetic resonance (CMR) later after one year follow-up were prospectively enrolled. The trend of VCG parameters of DMD patients across the different age span were compared with age-matched normal children. Concordance statistic analysis was further performed to assess the validity of VCG parameters in predicting the occurrence of reduced LVEF in patients with DMD. Results: DMD patients have a significantly higher heart rate, R waves in V1, QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) than normal children. Concordance statistic (C-statistic) showed an area under the curve of quadrant IV in the sagittal plane of baseline was 0.704. The receiver operating characteristic (ROC) curve shows that quadrant IV in the sagittal plane of 7.57% was the optimal cutoff with a sensitivity of 53.3% and a specificity of 88.3% for predicting reduced LVEF in DMD patients. Conclusions: Our study firstly showed that QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) could be abnormal in DMD boys as early as before 5 years old. Evaluation of the myocardium by VCG in the early age to predict possible cardiac systolic dysfunction may have important implications for the ongoing management of DMD boys.

Cobblestone lissencephaly (Type II), clinical, and neuroimaging: A case report and literature review.

Cobblestone lissencephaly (C-LIS) (TYPE II) is a rare and severe neuronal migration disorder characterized by a smooth brain surface with overmigrated neurons and abnormal formation of cerebral convolutions or gyri during fetal development, resulting in a cobblestone appearance. C-LIS is associated with eye anomalies and muscular dystrophy. This case report presents a detailed clinical and neuroimaging analysis of a patient diagnosed with cobblestone lissencephaly (Type II). It reviews pertinent literature to enhance our understanding of this complex condition. We report a case of a 6-year-old female child with cobblestone lissencephaly (C-LIS) (Type II) severe developmental delays, hypotonia, and recurrent intractable seizures. Magnetic resonance imaging (MRI) revealed a characteristic cobblestone appearance on the brain surface, indicative of abnormal neuronal migration. In addition to the classic findings of Type II Cobblestone lissencephaly, the patient displayed ventriculomegaly and cerebellar hypoplasia, contributing to the overall neurological impairment observed. The literature review highlights the genetic basis of cobblestone lissencephaly, emphasizing the involvement of genes associated with glycosylation processes and basement membrane integrity. Neuroimaging findings, including MRI and computed tomography scans, are crucial for accurate diagnosis and prognostication. Early identification of cobblestone lissencephaly allows for appropriate counseling and management strategies. However, the prognosis remains guarded, and interventions primarily focus on supportive care and seizure management. This case report contributes to the knowledge of cobblestone lissencephaly, shedding light on the clinical spectrum and neuroimaging features associated with this rare disorder. To clarify the underlying genetic mechanisms and possible therapeutic pathways for better patient outcomes, more investigation is necessary.

Clinical decision making around commercial use of gene and genetic therapies for spinal muscular atrophy.

Spinal muscular atrophy is no longer a leading cause of inherited infant death in the United States. Since 2016, three genetic therapies have been approved for the treatment of spinal muscular atrophy. Each therapy has been well studied with robust data for both safety and efficacy. However, there are no head-to-head comparator studies to inform clinical decision making. Thus, treatment selection, timing, and combination therapy is largely up to clinician preference and insurance policies. As the natural history of spinal muscular atrophy continues to change, more data is needed to assist in evidence-based and cost-effective clinical decision making.

Trans-Abdominal Pre-Peritoneal (TAPP) Approach for Anatomical Repair of Direct Inguinal Hernia in Children, Could it Be the New Standardized Approach?

BACKGROUND: The incidence of direct inguinal hernia in the pediatric population is relatively low and is usually discovered intraoperatively, rendering it unfamiliar to most pediatric surgeons. The traditional approach involves directly addressing the peritoneal defect, which includes dissecting the sac and repairing the peritoneum, reinforced with the umbilical ligament. In this paper, we present our experience with a novel approach to anatomical repair utilizing a non-mesh transabdominal preperitoneal (TAPP) approach. METHODS: This a retrospective case series of direct inguinal hernia that were operated laparoscopically using the novel approach of repair from January 2018 to January 2024. Data were analyzed for demographics, presentation, type of defect, operative time, complications, and recurrence. The new approach utilizes the pre-peritoneal approach to delineate the exact facial defect then, primary anatomical repair is established using 2/0 non-absorbable braided sutures. Finally, closure of the peritoneum was performed using running 4/0 absorbable sutures. This is a retrospective case series of direct inguinal hernias that were operated on laparoscopically using the novel repair approach from January 2018 to January 2024. Data were analyzed for demographics, presentation, type of defect, operative time, complications, and recurrence. The new approach employs the pre-peritoneal approach to accurately delineate the fascial defect, followed by primary anatomical repair using 2/0 non-absorbable braided sutures. Finally, the peritoneum is closed using running 4/0 absorbable sutures. RESULTS: Data from nine cases were included. Six cases were on right side, and three cases were on left side. Patients were predominantly boys (8 boys and 1 girl). The mean age at operation was 25.1 months (range:11 month to 5 years). Four patients had previous indirect inguinal hernia repair on the same side. The mean operative time was 34 ± 9 min. No intraoperative complications occurred. The median follow up period was 24 months with no recurrence was detected in any of the cases. CONCLUSION: The non-mesh TAPP approach offers excellent exposure of the fascial structures, facilitating accurate identification and repair of the defect. Despite being technically demanding, it allows for the establishment of a robust anatomical repair. No recurrences occurred in the study group; however, a longer follow up and a larger sample are needed to provide more reliable evaluation. LEVEL OF EVIDENCE: III.

Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.

Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.