Myogenic Changes Research Articles

Two PNPLA2 heterozygous mutations result in neutral lipid storage disease with myopathy: a case report

BackgroundNeutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by PNPLA2 gene mutations. Clinical manifestations are heterogeneous, and diagnosis is often delayed, usually gaining patients’ attention due to the increased risk of cardiomyopathy.Case presentationWe herein report a 36-year-old Asian male presenting with progressive limb weakness, muscle atrophy of limbs and trunk, dysarthria, and heart failure. Electromyography indicated myogenic changes, and muscle biopsy results revealed characteristics of lipid storage myopathy. Genetic analysis of PNPLA2 revealed two heterozygous mutations: c.757 + 1G > T (chr11-823588, splice-5) on intron 6 and c.919delG (chr11-823854, p.A307Pfs*13) on exon 7. The patient improved limb strength, and dysarthria disappeared after the Medium Chain Fatty Acids diet.ConclusionsIn conclusion, we report for the first time that the two heterozygous mutations PNPLA2 c.919delG and c.757 + 1G > T together induced NLSDM, which was confirmed by muscle biopsy.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

The adult environment promotes the transcriptional maturation of human iPSC-derived muscle grafts

Pluripotent stem cell (PSC)-based cell therapy is an attractive option for the treatment of multiple human disorders, including muscular dystrophies. While in vitro differentiating PSCs can generate large numbers of human lineage-specific tissue, multiple studies evidenced that these cell populations mostly display embryonic/fetal features. We previously demonstrated that transplantation of PSC-derived myogenic progenitors provides long-term engraftment and functional improvement in several dystrophic mouse models, but it remained unknown whether donor-derived myofibers mature to match adult tissue. Here, we transplanted iPAX7 myogenic progenitors into muscles of non-dystrophic and dystrophic mice and compared the transcriptional landscape of human grafts with respective in vitro-differentiated iPAX7 myotubes as well as human skeletal muscle biospecimens. Pairing bulk RNA sequencing with computational deconvolution of human reads, we were able to pinpoint key myogenic changes that occur during the in vitro–to–in vivo transition, confirm developmental maturity, and consequently evaluate their applicability for cell-based therapies.

Dropped head syndrome in anti‐MuSK antibody‐positive myasthenia gravis with possible concurrent axial myopathy

AbstractBackgroundDropped head syndrome (DHS) is a group of disorders that result in anterior neck flexion. Myasthenia gravis (MG) is a common cause of DHS. Previous reports have suggested that concurrent myopathy involving the paraspinal musculature may underlie DHS in patients with anti‐acetylcholine receptor antibody‐positive or thymoma‐associated MG.Case PresentationA 64‐year‐old woman presented with a 3‐month history of head drop and lordosis. Neurological examination revealed bilateral ptosis and weakness of the posterior neck extensors. Electrophysiology suggested neuromuscular junction involvement. Serum anti‐MuSK antibodies were positive, and generalized anti‐MuSK antibody‐positive myasthenia gravis (MuSK‐MG) was diagnosed. Needle electromyography (nEMG) of the splenius capitus and paraspinal muscles revealed acute and chronic myogenic changes. Imaging suggested paraspinal muscle atrophy. nEMG and magnetic resonance imaging (MRI) of both extremities were normal, and autoimmune myopathy‐related antibody testing was negative.ConclusionThymoma‐negative MuSK‐MG, demonstrating treatment‐refractory DHS, may present with concurrent axial myopathy.

Electromyography varies by stage in inclusion body myositis.

Inclusion body myositis (IBM) is a chronic inflammatory muscle disease that is characterized by mixed myogenic and neurogenic electromyography (EMG) findings. We investigated the association between EMG findings and the IBM stage. We included consecutive patients diagnosed with IBM based on muscle biopsy and had needle EMG performed within 1 month of biopsy. Motor unit potential waveform (MUP) in EMG and pathological findings were compared between patients in early and late phases. In total, 30 patients with biopsy-confirmed IBM and 254 muscles were included. The rate of abnormal discharge did not differ according to disease stage. There was a difference in the frequency of occurrence between myogenic suggestive MUP and neurogenic of biceps and flexor digitorum profundus in the late phase. Abnormal MUP was observed even in muscles without muscle weakness, and myogenic changes were predominant in biceps and gastrocnemius with muscle weakness. The biopsy findings on the contralateral side of the muscle where electromyography was performed revealed a tendency for muscles that exhibited myogenic origin to have more inflammatory cells and RV; however, the difference was not significant. The target muscles for EMG must be selected considering the disease stage as well. In the early stages of IBM, EMG results should be interpreted cautiously, as neurogenic suggestive pattern of MUP might also be exhibited. Contralateral electromyography findings may be helpful in selecting muscles for muscle biopsies, such as biceps and quadriceps.

Interventional Study of Flunarizine Therapy on Symptom Relief and Vestibular Evoked Myogenic Potential Changes in Individuals with Vestibular Migraine

Introduction: Migraine is the third most common disease in the world with an estimated prevalence of 14.7%. The purpose of this study was to identify the characteristic changes in cervical and ocular vestibular evoked myogenic potential (VEMP) and analyse changes in symptoms and VEMP after flunarizine therapy in patients diagnosed with vestibular migraine (VM). Methods: Prospective interventional study was conducted on 31 VM patients. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) were recorded. Flunarizine (10 mg) was given once daily for two consecutive months. Prophylactic therapy was monitored with a monthly follow-up assessment of their symptoms and VEMP was repeated after 2 months. Results: Headache was the chief complaint (67.7%). Vertigo was spontaneous and mostly moderate in intensity (93%). cVEMP was absent in 1 patient and oVEMP was absent in 3 patients. Post prophylactic treatment with flunarizine, there was significant reduction in the frequency (p = 0.001) and duration (p = 0.001) of headache and frequency (p = 0.001), duration (p = 0.001), and intensity (p = 0.009) of vertigo. cVEMP and oVEMP showed no significant differences (p > 0.05) between pre- and post-treatment recordings. Conclusion: Treatment with flunarizine helps in considerably reducing the episodes and duration of headache, as well as episodes, duration, and intensity of vertigo.

Routine Use of Bladder Scans After Primary Total Joint Arthroplasty is Not Necessary: Results of a Protocol Change

BackgroundPostoperative urinary retention is a common concern after total joint arthroplasty (TJA) and can cause discomfort, incontinence and, if left untreated, myogenic changes to the bladder. However, overdiagnosis of postoperative urinary retention by bladder scans may lead to unnecessary interventions and delayed discharges. The purpose of this study was to compare the safety of two bladder management protocols following TJA. MethodsFrom January 3, 2022 to April 29, 2022, 519 consecutive patients operated on by thirteen surgeons underwent routine postoperative bladder scanning (standard protocol). From February 28, 2022 to April 29, 2022, a new protocol was introduced by three surgeons in 209 consecutive patients using a specific algorithm (selective protocol) so that only symptomatic patients had bladder scans. The primary outcome of interest was catheterization rate. Chi-square and Students t-tests were used for analyses. There were 37.7% of patients in the selective group who received scans. ResultsTimes to catheterization, readmissions, emergency department visits, and straight catheterization rates (15.0 versus 14.8% P = .999) were similar. More scans in the selective group resulted in intervention (39.2 versus 15.0%, P < .001). Prevoid volumes were higher in the selective protocol (608 versus 448 mL, P < .001). Postvoid volumes were similar (233 versus 223 mL, P = .497). There was one readmission for a urinary tract infection in the standard group and no urinary-related readmissions in the selective group. ConclusionThe selective protocol had a higher rate of same day discharge, fewer bladder scans, and did not lead to increased rates of urinary-related complications. These findings suggest that selective bladder scanning for symptomatic patients can be safely instituted for TJA patients.

Mitochondrial DNA involvement in patients with autism spectrum disorders and intellectual disability

BackgroundAutism spectrum disorders (ASD) are neurodevelopmental disorders, with heterogeneous etiology, characterized by deficiencies in social interaction, communication, and by repetitive and stereotyped behaviors.Mitochondrial encephalomyopathies are inherited disorders of oxidative metabolism, with a wide clinical, biochemical and genetic heterogeneity, requiring a complex diagnostic flow-chart. Infantile forms often occur with defects in development, intellectual disabilities and dysmorphisms.ASD has been associated with mitochondrial respiratory chain deficiency and/or mitochondrial DNA (mtDNA) mutations. However, few studies carried out detailed clinical, instrumental, morphological, biochemical investigations, and mtDNA sequencing in ASD patients. MethodThe purpose of this study was the identification of mitochondrial dysfunction due to mtDNA variants in 19 selected subjects presenting ASD and clinical features of mitochondrial disease. For these patients we adopted a multidisciplinary approach combining clinical and laboratory investigations on muscle biopsy, with biochemical, histological and genetic techniques. ResultsThe histological examination showed myogenic or neurogenic changes in 79 % of patients; furthermore, 58 % of the patients had lipid accumulation, mitochondrial proliferation and COX deficient fibers. The biochemical investigations reported in three patients impairments involving one or more of the respiratory chain complexes. In addition, genetic studies revealed in one patient with normal histology and biochemistry multiple mtDNA deletions, and in four patients different mtDNA point mutations. ConclusionsThe present study confirms the hypothesis of an association between ASD and mitochondrial dysfunction. However, further studies in a larger group of subjects are needed.

WE-211. Audio-frequency-based machine learning can differentiate between myogenic and neurogenic changes in needle EMG

WE-211. Audio-frequency-based machine learning can differentiate between myogenic and neurogenic changes in needle EMG

Spectral Changes in Skin Blood Flow Do Not Reflect Pressure Manipulations

Skin blood flow is commonly assessed by laser Doppler flowmetry. It has been suggested that pathophysiological conditions can be assessed by analysis of frequency domains of the laser Doppler signals. The frequency range of 0.06‐0.15 Hz has been associated with myogenic control of skin blood flow. We tested the hypothesis that changes in blood pressure would be detectable by short‐time Fourier transform of the myogenic portion of the laser Doppler signal. Laser Doppler sensors were placed on the right ventral forearm of fourteen healthy young volunteers (8 males, 6 females, age 30±6 years, mean ± SD) and a photoplethysmography sensor on the middle finger of the right arm. Measurements of skin blood flow were made with the right arm supported at heart level. Intravascular pressure of the forearm was manipulated by positioning the arm ~50˚ above the heart level to decrease pressure and lowering the arm ~50˚ below the heart level to increase pressure. Short‐time Fourier analyses were computed over the range 0.06 to 0.15 Hz. There were no statistically significant differences (p = 0.526) in spectral densities for baseline (5±7 x 10‐4dB, median ± SD), arm above heart (7±54 x 10‐4dB), and arm below heart (7±14 x 10‐4dB). The results demonstrate that spectral density in the myogenic frequency range is unchanged by manipulation of intravascular pressure. We conclude that spectral analysis of laser Doppler signals in the myogenic range does not reflect changes in blood pressure. These findings suggest that myogenic changes in the skin vasculature cannot be inferred from spectral analysis of laser Doppler signals.

Spinulosis revealing dermatomyositis relapse: A new description of Wong’s dermatomyositis

Sir, Dermatomyositis (DM) is a systemic autoimmune disease affecting characteristically the skin and muscles. The typical cutaneous features include Gottron’s papules, a heliotrope rash, and edema of the eyelids. Spinulosis is an unusual sign, not raising suspicion for a DM diagnosis. Herein, we report a case of DM relapsing as Wong’s dermatomyositis (WDM) as an isolated spinulosic eruption. A 42-year-old female presented with a pruritic papular eruption involving both arms and the back persistent for the last two months. An anamnesis included a history of DM diagnosed five years earlier, in complete remission under the administration of corticosteroids for three years. A physical examination revealed erythematous and violaceous scaly plaques resulting from confluent follicular papules, resembling pityriasis rubra pilaris (PRP) on the lateral sides of the arms (Fig. 1) and the upper back (Fig. 2). Muscular testing was subnormal and the general status was conserved. Laboratory findings revealed a high level of blood CPK (3×N), LDH (4×N), and ASAT (3.5×N), while electromyography displayed myogenic changes. A muscular biopsy revealed necrotic muscular cells with perifascicular atrophy and lymphocytic inflammatory infiltrate. A histological skin examination found follicular hyperkeratosis with perifollicular interface dermatitis and interstitial mucin deposits in the dermis (Fig. 3). Based on these findings, the diagnosis of WDM was retained. A malignancy workup was negative. Corticosteroid therapy was initiated with prednisone 1 mg/kg/day in combination with hydroxychloroquine 200 mg twice a day, resulting in a remarkable clinical and biological improvement.WDM is characterized by the presence of PRP-like follicular papules in a patient with dermatomyositis (DM) [1]. Some authors suggest that this exceptional presentation should be considered a true association of DM with PRP rather than a variant of DM [2]. In this rare form, spinulosic lesions are mainly located on the trunk or limbs with occasional palmoplantar keratoderma [2]. Follicular lesions are usually associated with the typical signs of DM but some cases of isolated PRP features related to WDM have been reported [3]. To our knowledge, none has been reported as a relapse of a previous classic DM. Our patient relapsed showing spinulosic lesions absent in the prior episode five years earlier, not displaying at this time any classic cutaneous signs of DM. Such puzzling presentations are very unusual and may be confusing for physicians. In our patient, the diagnosis was retained on the basis of the histopathological findings of interface dermatitis and interstitial mucin deposits in the dermis, increased serum levels of muscle enzymes with a myogenic electromyographic pattern, the typical muscular histological changes, and a medical history of DM diagnosed five years earlier. In WDM, histology usually reveals follicular hyperkeratosis with keratotic plugs filling dilated follicular infundibula, which may raise several differential diagnoses, including PRP, discoid lupus erythematosus (DLE), and, to a lesser degree, follicular psoriasis and keratosis pilaris [4]. Interface dermatitis and mucin deposits, as in our patient, are the hallmarks of distinguishing DM from PRP, follicular psoriasis, and keratosis pilaris. Although these findings may also be observed in DLE [4], in our patient, there were no clinical or histological arguments supporting DLE rather than a diagnosis of DM. Myositis as, well as interstitial lung disease, appears to be comparable to the classic variant [5]. The risk of associated internal malignancy is unknown but could be lower than in the classic form [4]. Treatment and management do not differ from classic dermatomyositis.

HP42: EMG is a potential biomarker for myositis in patients with antisynthetase syndrome without muscle symptoms

Anti-aminoacyl-tRNA synthetase (ARS) antibodies positive patients sometimes present interstitial lung disease (ILD) without muscle symptoms. We investigated needle electromyography (nEMG) to explore whether there are some myogenic changes or not in patients with antisynthetase syndrome without muscle symptoms. Method: We enrolled three patients who fulfilled anti ARS antibodies positive and ILD of the Connor's criteria for antisynthetase syndrome, and not fulfill the PM/DM criteria. We investigated the nEMG, and magnetic resonance imaging (MRI) of muscles to explore whether there are some myogenic changes or not. Serum creatine kinase (CK), manual muscle testing of 8 muscle groups (MMT8), Inclusion Body Myositis-Functional Rating Scale (IBM-FRS) were measured. This study was approved by the ethics committee of the Nara Medical University School of Medicine. Results: All subjects were females and their ages at the examination were 54 years old (P1), 44(P2) and 69(P3). P1 and P2 had already initiated oral steroid therapy. Although all three patients had no high serum CK level nor decline in IBM-FRS, nEMG revealed that abnormally short durations of the motor unit potential (MUP) patterns in the deltoid and biceps. P3 presented the same MUP pattern in vastus lateralis. MRI revealed inflammatory changes in P2 at left triceps and P3 at anterolateral femurs and posterolateral lower legs. Conclusion: nEMG is usually performed when patients exhibit muscle weakness, but this examination tool can be applicated to detect muscle damage in patients with anti-ARS antibody-associated ILD, prior to muscle weakness, myalgia, and declines in ADLs.

Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report

BackgroundCharcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary neuropathy, and CMT1A is the most common form; it is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Mutations in the transient sodium channel Nav1.4 alpha subunit (SCN4A) gene underlie a diverse group of dominantly inherited nondystrophic myotonias that run the spectrum from subclinical myopathy to severe muscle stiffness, disabling weakness, or frank episodes of paralysis.Case presentationWe describe a Chinese family affected by both CMT1A and myotonia with concomitant alterations in both the PMP22 and SCN4A genes. In this family, the affected proband inherited the disease from his father in an autosomal dominant manner. Genetic analysis confirmed duplication of the PMP22 gene and a missense c.3917G > C (p. Gly1306Ala) mutation in SCN4A in both the proband and his father. The clinical phenotype in the proband showed the combined involvement of skeletal muscle and peripheral nerves. Electromyography showed myopathic changes, including myotonic discharges. MRI revealed the concurrence of neurogenic and myogenic changes in the lower leg muscles. Sural nerve biopsies revealed a chronic demyelinating and remyelinating process with onion bulb formations in the proband. The proband’s father presented with confirmed subclinical myopathy, very mild distal atrophy and proximal hypertrophy of the lower leg muscles, pes cavus, and areflexia.ConclusionThis study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations.

NEUROMUSCULAR JUNCTION RELATED DISORDERS: EP.295 Brachio-cervical inflammatory myopathy associated with myasthenia gravis

Among idiopathic inflammatory myopathies (IIM), brachio-cervical inflammatory myopathy (BCIM) constitutes a rare entity basically characterized by progressive weakness in the proximal regions of the arms and neck, the frequent association with other autoimmune diseases, and peculiar histopathological features at muscle biopsy. A 57-year-old woman presented with a 1-yr history of weight loss (-10kg), cervicalgia, bulbar signs and weakness in upper limbs. Clinical examination showed drop head with cervical muscle atrophy, severe proximal muscle weakness in upper limbs and nasal voice with swallowing disorders. No sign of scleroderma. Biological assessment disclosed increased CK serum levels and anti-AChR and anti-Scl autoantibodies. EMG showed myogenic changes in upper limbs but no decrement. Deltoid muscle biopsy revealed type-II fiber atrophy, randomly distributed active myonecrosis, and nodular inflammatory infiltrates, mainly perivascular. Immunohistochemical techniques showed ubiquitous myofiber expression of major histocompatibility complex (MHC)-class I and multifocal MHC-II-expressing myofibers. B-cells (CD20) were majority in infiltrates. C5b-9 immunostaining showed deposition in endomysium and capillaries walls. Significant clinical improvement was observed under medical treatment (anticholinesterase, corticosteroid, immunoglobulin and rituximab), ventilatory and nutritional support. Present case enlightened the specificities of BCIM, including (i) the remarkable distribution of muscle deficit, (ii) the frequent association with myasthenia gravis, and (iii) the highly recognizable histopathological pattern with active myopathy, C5b-9 staining of endomysium, focal perivascular and perimysial inflammation often with a prominent B cell component. Treatment is usually modeled on that of IIM, but considering histopathological features and the association with myasthenia, BCIM could constitute a privileged indication for anti-CD20 biotherapy.

AUTOIMMUNE & INFLAMMATORY NMD: EP.04 Exploring the mechanism of myogenic and neurogenic changes on electromyography by quantifying muscle pathology in sporadic inclusion body myositis

AUTOIMMUNE & INFLAMMATORY NMD: EP.04 Exploring the mechanism of myogenic and neurogenic changes on electromyography by quantifying muscle pathology in sporadic inclusion body myositis

MP63-12 UTILITY OF TRANSVAGINAL ULTRASOUND SHEAR WAVE ELASTOGRAPHY FOR INVESTIGATING THE POSTERIOR BLADDER WALL OF ACONTRACTILE BLADDER (ACB)/DETRUSOR UNDERACTIVITY (DU) IN WOMEN

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II (MP63)1 Sep 2021MP63-12 UTILITY OF TRANSVAGINAL ULTRASOUND SHEAR WAVE ELASTOGRAPHY FOR INVESTIGATING THE POSTERIOR BLADDER WALL OF ACONTRACTILE BLADDER (ACB)/DETRUSOR UNDERACTIVITY (DU) IN WOMEN Cheng Chu, Chih-Chieh Lin, William J. Huang, and Alex T.L. Lin Cheng ChuCheng Chu More articles by this author , Chih-Chieh LinChih-Chieh Lin More articles by this author , William J. HuangWilliam J. Huang More articles by this author , and Alex T.L. LinAlex T.L. Lin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002103.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Acontractile bladder (AcB)/detrusor underactivity (DU) were urodynamic-based diagnosis with similar pathologenic mechanism but different clinical presentations. They share common pathophysiology with myogenic changes related to ischemia, which lead to bladder detrusor wall fibrosis and loss of detrusor muscle contractility. The aim of this study was to investigate the correlation between the thickness and stiffness (measured by shear wave velocity, SWE) of detrusor muscle, both measured by transvaginal ultrasonography, in women with acontractile bladder (AcB)/detrusor underactivity (DU) under different degree of bladder filling. METHODS: During the period from October of 2019 to January of 2021, 26 patents were enrolled in this prospective study. According to urodynamic results, 17 women were classified as AcB/DU and remaining 9 women were classified as detrusor normoreflexia. Transvaginal ultrasound were performed by using an ultrasound machine (Aplio i-Series A800, Canon Medical System) with a transcavitary curvilinear probe (3 to 11 mHz) equipped with SWE. Detrusor wall thickness (DWT) and SWE of posterior bladder wall were acquired sequentially starting from empty bladder, different degree of bladder filling (50ml, 100ml, 150ml, 200ml), and once again empty bladder. Pearson correlation coefficients were applied to evaluate the relationship between shear wave modulus and DWT in both AcB/DU and detrusor normoreflexia. An independent t-test was used for comparing two groups under different bladder volume. Two-tailed p value of less than 0.05 was considered statistically significant. RESULTS: The mean age was 68.0±15.1 years old for patients with AcB/DU, 67.8±11.5 years old for patients with detrusor normoreflexia. DWT decreases during the bladder filling, and no statistical difference was found between AcB/DU and normoreflexia. Patients with AcB/DU showed significantly greater mean shear wave modulus than those with detrusor normoreflexia under distended bladder (at 100cc, 150cc and 200cc). The AcB/DU group also showed positive correlation between increased mean shear wave modulus and increased DWT at initial empty bladder (r=0.500, p=0.015), 150cc (r=0.716, p =0.001), 200cc (r=0.737, p =0.000) and second-time empty bladder (after distention) (r=0.397, p=0.033). We also observed, although not statistically significant, a trend of negative correlation between DWT and stiffness in women with detrusor normoreflexia under distended bladder (at 150cc, r= - 0.196, p=0.466; at 200cc, r= -0.181, p=0.472). CONCLUSIONS: Both mean DWT of AcB/DU and detrusor normoreflexia became thinner under bladder distention. AcB/DU women had significant increase in detrusor stiffness under bladder distention. Even under thinner detrusor, there is a positive correlation between DWT and stiffness in women with AcB/DU. This finding may be explained by fibrotic changes of detrusor muscle that resulted in AcB/DU. In summary, shear wave elastography is a feasible and reliable tool for predicting AcB/DU. Source of Funding: Departmental © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1106-e1106 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cheng Chu More articles by this author Chih-Chieh Lin More articles by this author William J. Huang More articles by this author Alex T.L. Lin More articles by this author Expand All Advertisement PDF downloadLoading ...

Acute Knockdown of MG29 in Mouse Muscle Cells Reveals Signaling Mechanisms Associated with Polyunsaturated Fatty Acid (PUFA) – Implications for Sarcopenia

Estimates of humans with sarcopenia (i.e., the age related loss of muscle loss and strength) ranges from 30% to over 70% depending on the age group, and specific population studied. Mitsugumin 29 (MG29), a muscle-specific protein, is a member of the synaptophysin-like protein family (SYPL2) that contain MAL and related proteins for vesicle trafficking and membrane link (MARVEL) domains. MG29 is important for the formation of the transverse-tubule (TT) system in skeletal muscles, efficient signaling between RyR1 and the store-operated Ca2+ entry (SOCE) machinery, and maintenance of lipid content of the sarcolemmal membrane. Our previous in vivo studies using a global knockout model of MG29 suggested a role of MG29 in the aging decline in muscle function. To avoid potential adaptive effects of the global absence of MG29, we also tested the siRNA-mediated acute knockdown of MG29 in mouse primary skeletal muscle cells, which led to extensive myogenic changes characterized by increased myogenic differentiation that led to abnormally thinner and longer myotubes. To examine the mechanistic basis of these changes, we measured changes in lipid signaling following knockdown of MG29. We collected both cell culture medium and cell homogenates 72 h after siRNA transfection, and applied a custom-targeted LC/MS lipidomics approach to quantify specific Lipid Signaling Mediators (LMs) in cell culture media and we used our customized skeletal muscle-specific RT-qPCR gene array to investigate specific genes showing alteration expression following acute MG29 knockdown. Compared with negative control siRNA treated cells, in MG29 siRNA treated cells, the cell culture media levels of arachidonoylethanolamine (AEA), oleoylethanolamide (OEA) increased significantly (p < 0.05) and the levels of prostaglandin D2 (PGD2), 9,10-DiHOME, 9-HOTrE, 9-HODE decreased significantly (p < 0.05). In addition, the PCR gene array revealed that in MG29 siRNA treated cells the expression of Cacna1s, RyR3, Btk and Sod3 increased 2.6 ± 0.48, 4.5 ± 0.89, 2.7 ± 0.51 and 6.5 ± 1.06 fold, respectively, while Fkbp1b and Ccl2 decreased 2.8 ± 0.38 and 7.3 ± 1.74 fold, respectively. These genes have function in calcium signaling and homeostasis and oxidative stress as well as inflammation and immune-regulation. We conclude that MG29 modulation of myogenic differentiation occurs via a complex signaling mechanism related to changes in LMs derived from polyunsaturated fatty acid (PUFA). This study further positions MG29 as an important regulator of signaling pathways associated with intracellular calcium homeostasis, oxidative stress, and inflammation, which emphasizes the role of MG29 as an orchestrator of alterations in skeletal muscle during sarcopenia.

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

BackgroundCentronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported.Case presentationThe child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy.ConclusionsThe clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.

Updated size index valid for both neurogenic and myogenic changes.

Size index (SI) is a motor unit potential (MUP) parameter in concentric needle electromyography calculated from amplitude and area/amplitude, which can sensitively discriminate between control and neurogenic MUPs. In this study, we investigated the application of SI to myogenic MUPs based on expanded data. MUPs were collected from the biceps brachii (BB) and tibialis anterior (TA) muscles. Muscles showing unequivocal neurogenic or myogenic changes by visual inspection were selected for patients. In addition to the original SI, a revised SI (rSI) was defined using the logarithmic scale for area/amplitude. The coefficient for area/amplitude was varied and that achieving the best sensitivity both for BB and TA was selected. Analyzed were 1619, 340, and 498 MUPs from the BB of 26, 10, and 14 subjects (control, neurogenic, and myogenic), respectively, and 1245, 536, and 473 MUPs from the TA of 23, 18, and 13 subjects (control, neurogenic, and myogenic), respectively. For neurogenic MUPs, the original SI and the newly defined rSIn were similarly sensitive (82.1% and 81.8% sensitivity for SI and rSIn, respectively, for BB, and 68.1% and 69.6% for TA), and were more sensitive than area (72.6% for BB and 57.6% for TA), the most sensitive parameter among conventional ones. For myogenic MUPs, the sensitivity of rSIm was 9.0% for BB and 24.5% for TA, which was not significantly different from duration (7.4% for BB and 21.8% for TA), the most sensitive parameter among conventional ones. SI, rSIn, and rSIm are promising as new MUP parameters.

Reactive oxygen species in renal vascular function.

Reactive oxygen species (ROS) are produced by the aerobic metabolism. The imbalance between production of ROS and antioxidant defence in any cell compartment is associated with cell damage and may play an important role in the pathogenesis of renal disease. NADPH oxidase (NOX) family is the major ROS source in the vasculature and modulates renal perfusion. Upregulation of Ang II and adenosine activates NOX via AT1R and A1R in renal microvessels, leading to superoxide production. Oxidative stress in the kidney prompts renal vascular remodelling and increases preglomerular resistance. These are key elements in hypertension, acute and chronic kidney injury, as well as diabetic nephropathy. Renal afferent arterioles (Af), the primary resistance vessel in the kidney, fine tune renal hemodynamics and impact on blood pressure. Vice versa, ROS increase hypertension and diabetes, resulting in upregulation of Af vasoconstriction, enhancement of myogenic responses and change of tubuloglomerular feedback (TGF), which further promotes hypertension and diabetic nephropathy. In the following, we highlight oxidative stress in the function and dysfunction of renal hemodynamics. The renal microcirculatory alterations brought about by ROS importantly contribute to the pathophysiology of kidney injury, hypertension and diabetes.