Paraneoplastic myopathy-related rhabdomyolysis and pancreatic cancer:A case report and review of the literature

BACKGROUND Rhabdomyolysis is a life-threatening condition,often leading to progressive renal failure and death.It is caused by destruction of skeletal muscle and the release of myoglobin and other intracellular contents into the circulation.The most frequent cause of this condition is“crush syndrome”,although several others have been described and paraneoplastic inflammatory myopathies associated with various types of cancer are repeatedly reported.CASE SUMMARY We describe a rare case of a patient with pancreatic cancer who developed rhabdomyolysis early on,possibly due to paraneoplastic myositis leading to acute renal failure and eventually to rapid death.A 78-year-old Caucasian woman was referred to our hospital for obstructive jaundice and weight loss due to a lesion in the pancreatic head.She presented increasingly severe renal insufficiency with anuria,a dramatic increase in creatine phosphokinase(36000 U/L,n.v.20-180 U/L)and myoglobin(>120000μg/L,n.v.12-70μg/L).On clinical examination,the patient showed increasing pain in the lower limbs associated with muscle weakness which was severe enough to immobilize her.Paraneoplastic myopathy linked to the malignant lesion of the pancreatic head was suspected.The patient was treated with hemodialysis and intravenous methylprednisolone.Despite all the efforts to prepare the patient for surgery,her general condition rapidly deteriorated and she eventually died 30 d after hospital admission.CONCLUSION The possible causes of rhabdomyolysis in this patient with pancreatic cancer are discussed,the development of paraneoplastic myopathy being the most likely.Clinicians should bear in mind that these syndromes may become clinically manifest at any stage of the cancer course and their early diagnosis and treatment could improve the patient’s prognosis.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Immune-mediated necrotizing myopathy:Report of two cases

BACKGROUND Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase,with unique skeletal muscle pathology and magnetic resonance imaging features.CASE SUMMARY In this paper,two patients are reported:One was positive for anti-signal recognition particle antibody,and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody.CONCLUSION The clinical characteristics and treatment of the two patients were analysed,and the literature was reviewed to improve the recognition,diagnosis,and treatment of this disease.

Treatment of a patient with severe lactic acidosis and multiple organ failure due to mitochondrial myopathy:A case report

BACKGROUND Mitochondrial myopathy is a rare genetic disease with maternal inheritance that may involve multiple organ systems.Due to the lack of typical characteristics,its clinical diagnosis is difficult,and it is often misdiagnosed or even missed.CASE SUMMARY The patient was a young college student.When he presented at the hospital,he had severe lactic acidosis,respiratory failure,and shock with multiple organ dysfunction syndrome(MODS).He was treated by mechanical ventilation,venoarterial extracorporeal membrane oxygenation,and other organ support.However,his condition continued to worsen.After a thorough and detailed medical and family history was taken,a mitochondrial crisis was suspected.A muscle biopsy was taken.Further genetic testing confirmed a mitochondrial gene mutation(TRNL13243A>G).The final diagnosis of mitochondrial myopathy was made.Although there is no known specific treatment,intravenous methylprednisone and intravenous immunoglobulin were started.The patient’s shock eventually improved.The further course was complicated by severe infection in multiple sites,severe muscle weakness,and recurrent MODS.After 2 mo of multidisciplinary management and intensive rehabilitation,the patient could walk with assistance 4 mo after admission and walk independently 6 mo after admission.CONCLUSION More attention should be paid to mitochondrial myopathy to avoid missed diagnosis and misdiagnosis.

EMG STUDY IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF LIPID STORAGE MYOPATHY

Clinical, electromyographic and pathological features were studied in 18 patients with lipid storage myopathy (group I ) and 18 patients with polymyositis and dermatomyositis (group II). The results showed a remarkable lower spontaneous activity(SA) incidence (14% ) in group I than that (55% ) in group II; 46% and 34% short-duration motor unit potentials (MUAPs) with polyphasic potentials and 74% and 71% short-duration MUAPs without polyphasic potentials respectively; the percentages of increased polyphasic MUAPs were same in the two groups. The reduced or pathologic interference patterns accounted for 61 % in the group I and 50% in group II. Increased CPK, LDH and HBD were also found in both of them. It is suggested that the lipid storage myopathy may be diagnosed when patients have muscle weakness and myalgia with short-duration and low-amplitude and polyphasic MUAPs without or with occasional spontaneous activities, and increased CPK, LDH and HBD.

Nemaline myopathy with dilated cardiomyopathy and severe heart failure: A case report

BACKGROUND Nemaline myopathy(NM)is a rare type of congenital myopathy,with an incidence of 1:50000.Patients with NM often exhibit hypomyotonia and varying degrees of muscle weakness.Skeletal muscles are always affected by this disease,while myocardial involvement is uncommon.However,with improvements in genetic testing technology,it has been found that NM with a mutation in the myopalladin(MYPN)gene not only causes slow,progressive muscle weakness but also results in dilated or hypertrophic cardiomyopathy.CASE SUMMARY A 3-year-old pre-school boy was admitted to our hospital with cough,edema,tachypnea,and an increased heart rate.The patient was clinically diagnosed with severe dilated cardiomyopathy and heart failure,and subsequent gene examination confirmed the diagnosis of NM with a mutation in MYPN.Captopril,diuretics,low-dose digoxin,and dobutamine were administered.After 22 d of hospitalization,the patient was discharged due to the improvement of clinical symptoms.During the follow-up period,the patient died of refractory heart failure.CONCLUSION Decreased muscular tone and dilated cardiomyopathy are common features of MYPN-mutated NM.Heart transplantation may be a solution to this type of cardiomyopathy.

Differential Diagnosis of Thyrotoxic Myopathy

Along with hereditary myopathies, there are many exogenic (the same a not hereditary) muscle affections due to the pathology of endocrine gland’s functioning. These forms of muscle pathology are called endocrine myopathies. In the cases of thyroid gland hyperfunction (the same a thyrotoxicosis), different regions of neuromuscular system may be involved in the pathological process. Thyrotoxic myopathy (TM) which is a subject of this investigation, occupies one of the first places between thyrotoxic (the same a thyrotoxicosis) neuromuscular affections. Meanwhile, for a long time in literature there was no clarity about the degree of muscle weakness and atrophy to diagnose TM in a patient. It’s because of the fact that the majority of patients complain of increased fatigue and general weakness due to thyrotoxicosis. In present time TM diagnostics is very rare. TM is a phenocopy (the clinical similar) of many neuromuscular diseases. However in literature, the data about peculiarities of clinical picture of TM is almost completely absent, it isn’t known about the frequency of affection of the isolated muscles or muscle groups, the topography of muscle weakness and successive involvement of isolated muscles in the pathological process during different stages of thyrotoxicosis and myopathy. The questions of differential diagnosis with similar neuromuscular disorders are described very poorly. In present article, we accent our attention at the clinical differentiation of the TM with other neuromuscular diseases, namely muscular dystrophy, myasthenia gravis, polymyositis, Addison’s disease, proximal spinal muscular atrophy, steroid myopathy and neurosis. In our opinion, the early diagnosis of TM may help the diagnosis of thyrotoxicosis in patients who have no classical clinical signs of this disease, i.e. in patients with latent thyrotoxicosis.

Critical illness polyneuropathy and myopathy:a systematic review

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitat- ing neurological disease.

Mucosal necrosis of the small intestine in myopathy,encephalopathy,lactic acidosis,and stroke-like episodes syndrome

This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),which particularly affects the brain,nervous system and muscles.A 45-year-old Japanese female,with an established diagnosis of MELAS,presented with vomiting.Computed tomography showed portomesenteric venous gas and pneumatosis intestinalis.She underwent a resection of the small intestine.A microscopic study showed necrosis of the mucosa and vacuolar degeneration of smooth muscle cells in the arterial wall.Immunohistochemistry showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent the necrotic mucosa.The microscopic and immunohistochemical findings suggested the presence of a large number of abnormal mitochondria in MELAS to be closely linked to mucosal necrosis of the small intestine.

Collagen VI-related myopathy with scoliosis alone: A case report and literature review

BACKGROUND Scoliosis is a complex three-dimensional deformity of spine and one of the common complications of collagen VI-related myopathy,caused by mutations in collagen type VI alpha 1 chain(COL6A1),COL6A2,and COL6A3 genes.The typical clinical presentations of collagen VI-related myopathy include weakness,hypotonia,laxity of distal joints,contractures of proximal joints,and skeletal deformities.CASE SUMMARY A 28-year-old female presented with scoliosis for 28 years without weakness,hypotonia,laxity of distal joints,and contracture of proximal joints.Computed tomography and magnetic resonance imaging revealed hemivertebra,butterfly vertebra,and the missing vertebral space.Patients underwent orthopedic surgery and paravertebral muscle biopsy.The Cobb angle dropped from 103.4°to 52.9°.However,the muscle biopsy showed neurogenic muscular atrophy with myogenic lesions,suggesting congenital muscular dystrophy.Gene analysis indicated that mutations in COL6A1(c.1612-10G>A)and COL6A2(c.115+10G>T,c.2749G>A).Immunohistochemistry staining for collagen VI displayed shallow and discontinuous.Eventually,the patient was diagnosed as collagen VI-related myopathy.CONCLUSION This newly found subtype of collagen VI-related myopathy has no typical manifestations;however,it is characterized by severe scoliosis and congenital vertebral deformity.

BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia:A Case Report and Literature Review

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209 Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209 Leu mutation in BAG3.Totally twentyone patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen(one could not tolerate non-invasive assisted ventilation)required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients’muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.

Acute myopathy associated with liver cirrhosis

AIM： Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis. METHODS： We retrospectively reviewed the medical records of 5440 cirrhotic patients who had been admitted to Gyeongsang National University Hospital from August 1997 to January 2003. Among these, 99 developed acute myopathies, and they were analyzed with respect to clinical and laboratory parameters, and outcomes. RESULTS： The Child-Pugh classification at the time of myopathy onset was A in 3（3.1%） cases, B in 33（33.3%）, and C in 63 （63.6%）. Infection was identified as the most predisposing factor to myopathy. Fifty percent of 18 idiopathic cases who were tested for influenza antibody were positive. Forty-two of the 99 cases were complicated by acute renal failure, and 25 （59.5%） of these expired. Apart from 6 cases lost to follow-up, 64 of 93 recovered, giving a mortality rate of 31.2%. Mortality was higher in Child-Pugh class C than in B or A. CONCLUSION： Acute myopathy can develop as a serious complication in liver cirrhosis. Its frequency, severity and mortality depend on underlying liver function, and are higher in decompensated liver cirrhosis. Influenza should be considered as an etiologic factor in idiopathic cases. It is proposed that acute myopathy associated with liver cirrhosis be called ＇hepatic myopathy; and that careful monitoring for hepatic myopathy is necessary in the patients with advanced liver cirrhosis.

Rituximab as a treatment for human immunodeficiency virusassociated nemaline myopathy:What does the literature have to tell us?

We presented a letter about a case of a 37-year-old Black female with a history of human immunodeficiency virus and an undetectable viral load.She was evaluated with weakness in the scapular(grade III)and pelvic girdles(grade II),elevation of creatine phosphokinase levels and muscle biopsy compatible with nemaline myopathy.She was treated with rituximab showing improvement of the condition.

THE PATHOGENESIS OF EXPERIMENTAL MODEL OF MITOCHONDRIAL MYOPATHY INDUCED BY GERMANIUM DIOXIDE

Objective. The purpose of the study was to build up an animal model of mitochondrial myopathy in order to analyse the pathogenesis of the disease. Methods. The skeletal muscles from Wistar rats treated with germanium dioxide for 24 weeks were analysed by histopathologic and electron- microscopic studies. A quantitative analysis was carried out in mitochondrial DNAs of these samples. The biological function of the model was determined. Results. An animal model of mitochondrial myopathy was built up, in which oxygen free radicals were increased and mitochondrial DNA copies were decreased contrasted with controls. Conclusion. It suggested that environmental toxin may play a role in the pathogenesis of mitochondrial myopathy. The increase of oxygen free radicals is an important link causing the disease.

Ultrastructural Aspects of Apoptosis in Systemic Sclerosis Inflammatory Myopathy

Muscle biopsies from two female patients with systemic sclerosis (SS) and an inflammatory myopathy were studied ultrastructurally in relation to the possible presence of apoptosis in skeletal muscle fibers. Undergoing apoptosis showed characteristic morphological features of this process, including chromatin aggregation as well as nuclear and sarcoplasmic partition into membrane bound-vacuoles (apoptotic bodies) which contained autophagosomes, mitochondria, isolated myofilaments and nuclear material. Vacuoles exhibited different diameters and were covered by single membranes, appearing beneath basement membrane. Apoptosis occurred in some fiber segments as in necrosis or included whole atrophied fibers. These results indicate that apoptosis coexists with necrosis in the inflammatory myopathy of SS.

A woman by successful IVF and caesarean delivery without complications in autosomal dominant centronuclear myopathy

Autosomal-dominant centronuclear myopathy is a rare hereditary disease in adolescents,mainly involving the distal muscles of the lower extremity.It is extremely rare in pregnancy.This study presented a case of a woman by successful IVF and caesarean delivery without complications in autosomal dominant centronuclear myopathy.This report also reviewed the clinical spectrum of CNM and its management,which resulted in the delivery of a healthy infant.It is important that the clinician has a clear understanding of the clinical spectrum of CNM,the available methods for perinatal diagnosis,and optimal antenatal care.A multidisciplinary team approach is emphasized,with specific reference to the method of analgesia and anesthesia during labor and route of delivery.

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy.However,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1.Here,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal myopathy.The CGG repeat expansions range from 161 to 669 repeat units.Most of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle weakness.Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging.Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles.Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to pathogenesis.Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

Clinical,muscle pathology and molecular genetic analysis of myofibrillar myopathy 3 associated with MYOT gene mutation

Objective To analyze the clinical phenotypic characteristics,muscle pathology,genetic mutations and related proteins of myofibrillar myopathy 3 caused by mutation in MYOT gene,and to conduct a literature review and summary of this disease.Methods A retrospective analysis of the clinical phenotypic characteristics.

Intensive care unit-acquired weakness–preventive,and therapeutic aspects;future directions and special focus on lung transplantation

In this editorial,comments are made on an interesting article in the recent issue of the World Journal of Clinical Cases by Wang and Long.The authors describe the use of neural network model to identify risk factors for the development of intensive care unit(ICU)-acquired weakness.This condition has now become common with an increasing number of patients treated in ICUs and continues to be a source of morbidity and mortality.Despite identification of certain risk factors and corrective measures thereof,lacunae still exist in our understanding of this clinical entity.Numerous possible pathogenetic mechanisms at a molecular level have been described and these continue to be increasing.The amount of retrievable data for analysis from the ICU patients for study can be huge and enormous.Machine learning techniques to identify patterns in vast amounts of data are well known and may well provide pointers to bridge the knowledge gap in this condition.This editorial discusses the current knowledge of the condition including pathogenesis,diagnosis,risk factors,preventive measures,and therapy.Furthermore,it looks specifically at ICU acquired weakness in recipients of lung transplantation,because–unlike other solid organ transplants-muscular strength plays a vital role in the preservation and survival of the transplanted lung.Lungs differ from other solid organ transplants in that the proper function of the allograft is dependent on muscle function.Muscular weakness especially diaphragmatic weakness may lead to prolonged ventilation which has deleterious effects on the transplanted lung–ranging from ventilator associated pneumonia to bronchial anastomotic complications due to prolonged positive pressure on the anastomosis.