Symptoms Of Myopathy Research Articles

Interplay of Statins, Clopidogrel, and Repaglinide: Unraveling the Nexus of Hypoglycemia and Myopathy in a Geriatric Type 2 Diabetes Patient: A Case Report

Abstract Background: The management of cardiovascular diseases often includes the use of statins, which, while reducing cardiovascular risk, can interact with other medications leading to significant adverse effects. This case report explores the complex interactions between atorvastatin, clopidogrel, and repaglinide, which precipitated severe hypoglycemia and myopathy in a patient with multiple comorbidities. Case Presentation: We describe a 68-year-old female with a history of type 2 diabetes mellitus, hypertension, and ischemic heart disease, who developed severe hypoglycemia and myopathy following the adjustment of her statin therapy post-cardiac diagnosis. Her treatment regimen was modified to include an increased dose of atorvastatin and the introduction of clopidogrel, shortly after which she presented with hypoglycemia and symptoms of myopathy. Investigations revealed significantly elevated muscle injury markers and magnetic resonance imaging findings consistent with myositis. Discussion: The pharmacokinetic interactions between clopidogrel with repaglinide and repaglinide with atorvastatin exacerbated by the increased dose of atorvastatin, likely led to the observed clinical manifestations. This case highlights the critical need for careful monitoring of drug interactions, especially in patients with polypharmacy. Adjustments in drug dosages and consideration of alternative medications with fewer interaction risks are essential components of managing similar cases. Conclusion: This case underscores the importance of vigilant therapeutic management and individualized patient care in the context of complex drug regimens. Understanding and anticipating drug interactions can prevent significant adverse effects and improve patient outcomes in a population at high risk of polypharmacy complications.

Acase report on rosuvastatin-induced myopathy

Statins are the most commonly used lipid-lowering drugs in cardiovascular patients. Rosuvastatin is a majorly used statin. Rosuvastatin will induce myopathy; it is a rare side effect. In my case report, the patient experiencing muscle cramps for 3 years on and off. He consulted a cardiologist. The doctor advised Atorvastatin. He has been on rosuvastatin for 6 months. From the last 6 months, he has not experienced and myopathy symptoms.

A case report on atorvastatin-induced myopathy

Statins are the most commonly used lipid-lowering drugs in cardiovascular patients. Atorvastatin is a majorly used statin. Atorvastatin will induce myopathy; it is a rare side effect. In my case report, the patient experiencing muscle cramps for 3 years on and off. He consulted a cardiologist. The doctor advised rosuvastatin. He has been on rosuvastatin for 6 months. From the last 6 months, he had not experienced any myopathy symptoms.

P358 Slowly progressive ophthalmoplegia as a presenting symptom of mitochondrial myopathy

P358 Slowly progressive ophthalmoplegia as a presenting symptom of mitochondrial myopathy

Abstract #1405039: Melting Muscle: Rhabdomyolysis as a Rare Initial Presentation of Hashimoto’s Thyroiditis

Rhabdomyolysis is characterized by muscular necrosis and the release of intracellular muscle contents into circulation. The most common cause of primary hypothyroidism is Hashimoto’s thyroiditis (HT) in iodine-adequate areas. Although hypothyroid myopathy is commonly seen, rhabdomyolysis is a rare reported but serious complication in patients with HT. This case report aims to highlight this rare complication, so that diagnosticians will consider this in their differential diagnosis. A 44-year-old African American male with a history of asthma and hypertension presented to the emergency room due to mild generalized muscle cramps started several weeks ago. It worsened recently after he started a new job that required him to work in the yard for 3-6 hours daily. He denied any new medications, recent trauma, drug use, insect bites, sick contacts, recent travel, or strenuous exercise. His vital signs were stable. Initial laboratory workups were significant for elevated creatinine kinase at 4299 unit/L and creatinine of 1.57 mg/dl. Notably, his thyroid stimulating hormone was 42.94 uIU/mL, free thyroxine (T4) was 0.48 ng/mL, and his anti-microsomal antibody was >1300 units/mL. He was admitted to hospital for rhabdomyolysis secondary to Hashimoto’s thyroiditis. Levothyroxine therapy and intravenous fluid were given. His condition improved and was ultimately discharged with close primary and endocrinology follow-up. Hypothyroidism is well-associated with musculoskeletal problems, and it is estimated that around one-third of patients are accompanied with myopathy symptoms. Mechanism of hypothyroidism-induced myopathy is not fully understood. It is thought, however, to be linked to thyroxine’s role in glycogenolysis and mitochondrial oxidative processes. Thus, insufficiency of thyroxine may damage myocytes due to oxidative stress and may eventually lead to rhabdomyolysis. Although Hashimoto’s thyroiditis is recognized as one of the most common causes of hypothyroidism, as per our knowledge, this is the first case that a patient initially presenting with rhabdomyolysis was found out to have Hashimoto’s thyroiditis. Thus, hypothyroidism should be kept on the differential in patients with suspicion of rhabdomyolysis, and a thyroid panel should be considered as one of the initial workups.

The frequency of major ABCG2, SLCO1B1 and CYP2C9 variants in Asian, Native Hawaiian and Pacific Islander women subgroups: implications for personalized statins dosing.

Aim: The frequencies of SLCO1B1*5 and CYP2C9*2 and *3 in specific Asian, Native Hawaiian and Pacific Islander (NHPI) subgroups are unknown. Patients & methods: Repository DNA samples from 1064 women self-identifying as Filipino, Korean, Japanese, Native Hawaiian, Marshallese or Samoan and aged 18years or older were used for targeted sequencing of three genetic variants (rs4149056, rs1799853 and rs1057910). Results: SLCO1B1*5 was significantly less frequent in NHPI women (0.5-6%) than in Europeans (16%). Except for Koreans, CYP2C9*2 (0-1.4%) and *3 (0.5-3%) were significantly less frequent in all subgroups than in Europeans (8 and 12.7%, respectively). Prior reports showed that Asian and NHPI individuals have significantly higher ABCG2 Q141K allele frequency (13-46%) than Europeans (9.4%). Combined phenotype rates for rosuvastatin and fluvastatin revealed that Filipinos and Koreans had the highest frequencies of statin-associated myopathy symptoms risk alleles. Conclusion: Differences in ABCG2, SLCO1B1 and CYP2C9 allele frequencies among different racial and ethnic subgroups highlight the need for increased diversity in pharmacogenetic research. Risk alleles for statin-associated myopathy symptoms are more prevalent in Filipinos, underscoring the importance of genotype-based statin dosing.

Duchenne muscular dystrophy diagnosed in infancy – a case report

Duchenne muscular dystrophy is the most common inherited neuromuscular disorder. The onset of myopathic symptoms is observed at an average age of 2.5 years. However, the definitive diagnosis is not reached until between 3 and 5 years of age, indicating a delay in relation to the onset of first symptoms. The diagnosis is confirmed with genetic testing. This paper presents a case of a 6.5-month-old boy with reduced motor activity already in the foetal period, hypertransaminasaemia, constipation and reduced muscle tone. Extensive differential diagnosis of these abnormalities, including genetic testing, confirmed Duchenne muscular dystrophy. Detection of this disease at an early, poorly symptomatic stage offers a chance to achieve better treatment outcomes and improve the patient’s quality of life. Modern gene therapies implemented before irreversible changes are induced by the disease may in the future give the patient a chance to be completely cured. In the presented case, the symptoms of myopathy were present already in foetal life, and the diagnosis was reached at a younger age than the typical age reported in most of the available literature data.

Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution

ObjectiveTo identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses. MethodsA systematic review of case reports was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA methodology). PubMed and EMBASE were searched through October 2021 for case reports of neuropathy and/or myopathy associated with the use of colchicine at therapeutic doses. ResultsA total of 143 cases of neuromyopathy from 99 articles were identified as having a “definite” or “probable” association with colchicine usage, as assessed by the Naranjo algorithm. Most of these cases presented with features of both neuropathy and myopathy (n=72, 51%) but symptoms of myopathy were predominant. The mean total daily dose was 1.25±0.60 mg and 48% had been taking colchicine for more than 12 months before presenting with neuromyopathy. A total of 117 (82%) of all reports had either a significant co-morbidity or possible colchicine drug-drug interaction, while 57 (40%) had both risk factors. A total of 26 cases (18%) had no significant risk factor but only 15 of these reports contained complete descriptions of the patient's co-morbidities and co-medications. Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days. There were 3 deaths reported which were due to multi-organ failure despite cessation of colchicine and medical management. Colchicine was restarted at reduced doses in 15 cases and 73% had no symptom recurrence. ConclusionNeuromyopathy is an uncommon but reported adverse effect of colchicine. Cases generally present with proximal myopathy symptoms. Cases of colchicine neuromyopathy are largely reported in patients on commonly used doses. Renal and hepatic dysfunction and medications that inhibit cytochrome P450 3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most significant risk factors. Fortunately, cessation of colchicine generally leads to complete resolution of symptoms. Recommencement of colchicine at reduced doses appeared to be usually safe.

Additional Pathogenic Pathways in RBCK1 Deficiency

RBCK1 deficiency is a rare congenital autoinflammatory disease that causes inflammatory disruption on the molecular level. This deficiency has three major clinical manifestations: increased sensitivity to bacterial infections, autoinflammation syndrome, and the accumulation of amylopectin in skeletal muscle. The amylopectinosis causes myopathy and cardiomyopathy. The pathogenesis of the disease is poorly investigated and may include unnoticed relationships. We performed gene expression analysis on patients with RBCK1 deficiency and three other autoinflammatory diseases. The identification of differentially expressed genes revealed a large number of downregulated genes that are involved in the activation of essential metabolic and immune pathways, including NF-kB and Pi3k-Akt-mTOR. Signaling pathways were analysed using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and Gene Ontology resource. Predicted protein-protein interactions were retrieved from the STRING (Search Tool for the Retrieval of Interacting proteins database). Besides the primary involvement of RBCK1 in disease pathology, several downregulated pathways aggravate symptoms of myopathy, cardiomyopathy, and bacterial disease. The studied pathways may serve as new targets for the development of compensatory therapies for patients with RBCK1 deficiency.

Association of acute hepatitis B and acute myopathy: a case report

BackgroundHepatitis B virus infection is a global public health problem. Although hepatitis B virus primarily affects hepatocytes, it sometimes develops disease manifestations outside the liver, such as myopathy, which is commonly caused by chronic hepatitis B.Case presentationThis case report describes a 57-year-old Iranian woman admitted to the hospital with jaundice, fever, body itching, abdominal pain, progressive muscle weakness, icteric sclera, right upper quadrant pain, and decreased muscle force. Examination on the first day of admission revealed that the patient was negative for hepatitis D antibody, positive for hepatitis B core (IgM) antibody, positive for hepatitis B surface antigen, and negative for hepatitis B e antibody but positive for hepatitis B e antigen. Moreover, she showed high levels of hepatitis B virus DNA viral load, creatine kinase, lactate dehydrogenase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total bilirubin, direct bilirubin, and alkaline phosphatase, and electromyography/nerve conduction velocity showed acute myopathic process.ConclusionsInterestingly, myopathy symptoms improved after improving hepatitis symptoms and decreasing hepatitis B viral load, suggesting a close association between hepatitis B infection and myopathy.

Nemaline myopathy in newly diagnosed systemic lupus erythematosus and Sj\xf6gren\u2019s overlap syndrome complicated by macrophage activation syndrome

BackgroundNemaline myopathies are congenital or acquired muscle disorders that typically present in childhood but can occasionally occur in adults with underlying malignant, infectious or autoimmune disorders. There is a great genetic heterogeneity as well as clinical variability among the disease.Case presentationHere, we present a case of nemaline myopathy in a young woman who was newly diagnosed with systemic lupus erythematosus (SLE) and Sjögren’s overlap syndrome complicated by macrophage activation syndrome (MAS). She had no personal or family history of myopathy and was reporting progressive thigh weakness. A muscle biopsy revealed type 1 myofiber predominance with granular material in atrophic myocytes consistent with nemaline myopathy. Her symptoms markedly improved with immunotherapy for her SLE and MAS supporting the diagnosis of sporadic late-onset nemaline myopathy (SLONM) associated with her autoimmune disease.ConclusionsSLONM is a type of nemaline myopathy that presents in adults and can occasionally be associated with autoimmune disease. In these cases, treatment of the underlying disorder with immunosuppression appears to improve symptoms of myopathy.

Vitamin D Supplementation reduces Atorvastatin induced Myopathy in Dyslipedemic patients

Background: Dyslipidemia is becoming one of the most common problems worldwide predisposing towards atherosclerotic cardiovascular events and other issues like obesity. Statins are imperative for treating dyslipidemia. However statin-intolerance is a major hurdle due to the myopathy incurred with their usage, ranging from mild aches and pains without CPK elevation to marked increase in CPK levels with myonecrosis and even death in rare cases. Aim: Local identification of dyslipedemic patients with reduced vitamin D levels and intolerance to ≥2 statins (especially Atorvastatin), exhibiting statin induced myopathy with CPK elevation. Assessment of 3 months vitamin D therapy on myopathy and patient compliance to statins Place and duration of study: A 13 months study conducted in Army Cardiac Center Lahore . Methods: Upon Ethical Board Clearance (Ref No:F.39/NHRC/Admn/IRB/40)(IRB- Number: 1547) 60 dyslipidemic patients ranging from 40-70years of age, having CPK confirmed myopathy (CK levels >120micrograms/L) and intolerance to ≥2 statins (including Atorvastatin) along with hypovitaminosis D were assessed for enrollment based on strict inclusion and exclusion criteria at Army Cardiac Center Lahore. Results: Baseline investigations including CBC, renal, liver and thyroid function tests, vit D, vit B12, hepatitis B, C, FBS, CK, CK MB and lipid profile were performed.At the end of the study at 3rd month (2ndfollowup) investigations such as 25 hydroxy vitamin D levels, presence or absence of muscular pain as symptom of myopathy and CPK with its isoenzymes CK MB levels were repeated and compared with the baseline values Conclusion: In this study it is concluded that by replenishing vitamin D levels, Atorvastatin induced myopathy improves leading to more compliance towards the drug and resulting in improvement in lipid profile. Keywords: Dyslipidemia, Vitamin D, Myopathy, Atorvastatin

Advances in understanding of the natural history, mechanism, extra‐muscular manifestations and treatment of GNE myopathy

AbstractGNE myopathy is an autosomal recessive adult‐onset distal myopathy caused by biallelic variants in the GNE gene, which encodes a protein with two key enzymatic activities in the biosynthesis of sialic acid. In 1981, there was a report of a Japanese family in which muscle biopsies showed rimmed vacuoles in tibialis anterior with relative sparing of the quadriceps muscles. Twenty years later, the causative gene was identified to be GNE. Our group has constructed a mouse model that recapitulates the symptoms of GNE myopathy in patients and demonstrates the therapeutic effects of oral sialic acid supplementation on muscle phenotypes. The first clinical trial of N‐acetylneuraminic acid (NeuAc) was conducted in 2010 at Tohoku University, and several clinical trials are now underway at multiple sites. Patient registries have also been started, including the Japanese Registry of Muscular Dystrophy (Remudy, established in 2012) and the online international GNE Myopathy Disease Monitoring Program (launched in 2014). These registries have allowed collection of comprehensive patient data, including new clinical features suggesting that GNE myopathy is not only a disease of skeletal muscle. In this review, we summarize the history of research on GNE myopathy and discuss the mechanism of the disease and its more recently identified features.

Thyrotoxic myopathy: research status, diagnosis, and treatment.

Thyrotoxic myopathy is hyperthyroidism accompanied by muscle lesions. It is recognized as the general term for a group of symptoms with several main manifestations of several hyperthyroidism patients in the course (e.g. muscle weakness, muscle paralysis, or pain). From the clinical perspective, it may only be manifested as muscle-related symptoms. The symptoms of high metabolic syndrome (e.g. thyrotoxicosis) are absent, obscured, or relatively delayed, so it can be easily misdiagnosed. Accordingly, patients experiencing the first symptom of myopathy should concentrate on the possibility of thyrotoxic myopathy. Given the clinical characteristics, thyrotoxic myopathy can be devided into chronic thyrotoxic myopathy, thyrotoxicosis with periodic paralysis, acute thyrotoxic myopathy, hyperthyroidism with myasthenia gravis, as well as infiltrating exophthalmos with ophthalmoplegia. In this paper, we review thyrotoxic myopathy research status, diagnoses, and treatments.

Expression pattern of mitochondrial respiratory chain enzymes in skeletal muscle of patients with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant.

Two homoplasmic variants in tRNAGlu (m.14674T>C/G) are associated with reversible infantile respiratory chain deficiency. This study sought to further characterize the expression of the individual mitochondrial respiratory chain complexes and to describe the natural history of the disease. Seven patients from four families with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant were investigated. All patients underwent skeletal muscle biopsy and mtDNA sequencing. Whole‐genome sequencing was performed in one family. Western blot and immunohistochemical analyses were used to characterize the expression of the individual respiratory chain complexes. Patients presented with hypotonia and feeding difficulties within the first weeks or months of life, except for one patient who first showed symptoms at 4 years of age. Histopathological findings in muscle included lipid accumulation, numerous COX‐deficient fibers, and mitochondrial proliferation. Ultrastructural abnormalities included enlarged mitochondria with concentric cristae and dense mitochondrial matrix. The m.14674T>C variant in MT‐TE was identified in all patients. Immunohistochemistry and immunoblotting demonstrated pronounced deficiency of the complex I subunit NDUFB8. The expression of MTCO1, a complex IV subunit, was also decreased, but not to the same extent as NDUFB8. Longitudinal follow‐up data demonstrated that not all features of the disorder are entirely transient, that the disease may be progressive, and that signs and symptoms of myopathy may develop during childhood. This study sheds new light on the involvement of complex I in reversible infantile respiratory chain deficiency, it shows that the disorder may be progressive, and that myopathy can develop without an infantile episode.

Современный взгляд на проблему влияния противоэпилептических препаратов на статус витамина D (клинический случай с обзором литературных источников)

В данной статье представлены клинический случай влияния противоэпилептических препаратов (ПП) на уровень витамина D (в частности, длительного приема препарата вальпроата натрия) и современные данные зарубежных публикаций по этой проблеме. Как известно, существует перечень лекарственных препаратов, отрицательно влияющих на метаболизм витамина D. В частности, к препаратам, снижающим всасывание витамина D, относят препараты для лечения эпилепсии. Противоэпилептические средства — это лекарственные препараты различного происхождения, используемые для предотвращения или уменьшения судорог, соответствующих им эквивалентов (потеря или нарушение сознания, поведенческие и вегетативные нарушения и др.), которые наблюдаются при периодически возникающих приступах различных форм эпилепсии. Широкое применение в медицинской практике данных лекарственных препаратов требует изучения их возможных побочных реакций и проведения своевременной их коррекции, поскольку иностранные источники указывают на то, что ПП усиливают дефицит витамина D и ухудшают симптомы при проксимальной миопатии, что требует обязательной медикаментозной коррекции препаратами витамина D; пациенты, страдающие эпилепсией, имеют дефицит витамина D; хроническая терапия вальпроатами связана с более низкими показателями минеральной плотности костной ткани у молодых пациентов с эпилепсией. Данный клинический случай показал, как длительный прием вальпроата натрия привел к развитию у пациентки вторичного системного остеопороза и дефицита витамина D, о чем свидетельствуют результаты лабораторных и инструментальных исследований, а отмена врачом противоэпилептического препарата и назначение препарата витамина D3 улучшили общее состояние больного и нормализовали уровень данного витамина в сыворотке крови. На основании данных литературного обзора и собственных наблюдений, в частности клинического случая, можно сделать вывод, что пациенты, которые страдают эпилепсией и принимают ПП, должны получать препараты витамина D3 в целях предотвращения развития остеопороза и дефицита данного витамина.

A novel mutation in MTM1 gene in newborn, resulting in centronuclear myopathy phenotype: a case report

BackgroundThe X-linked myotubular myopathy (XLMTM) is a rare congenital disease. Its main symptoms are hypotonia, dysmorphic facial features, respiratory failure, and feeding disorder.Case presentationThis study reports on a male patient from Neonatal Intensive Care Unit, who presented symptoms of congenital myopathy. After eliminating many other possible causes, he was eventually proven to bear a c.197C>G, p.(Thr66Arg) MTM1 mutation, a variant of uncertain significance, never described in the literature before. Family of the patient underwent the same genetic tests that proved the mother to be the carrier of mutation.ConclusionThe article is a first report on abovementioned, newly discovered mutation in MTM1 gene, with high probability leading to the centronuclear myopathy phenotype. It also summarizes the diagnostic process and current state of knowledge about the therapy and prognosis for children with XLMTM. The authors hope that the findings will contribute to the diagnostic process of subsequent patients.

ПОКАЗАТЕЛИ ИДЕНТИФИКАЦИИ PSE-ПОРОКА И МИОПАТИИ ИНФЕКЦИОННОЙ И ИНВАЗИОННОЙ ЭТИОЛОГИИ

The materials on identification in broiler meat the features of PSE- defect and myopathy are shown, associated by causative agents of various infectious and infective diseases. Specific differences in pathomorphology symptoms of PSE-meat and myopathy of infectious origin are established. Symptoms of PSE- defect in broiler meat emerge more often (11,7 – 21,7%), than signs of degenerative changes from exposure of infectious disease agents and muscle invasion(4,19-7,61 %). It was established that changes in muscles depend on degree of development PSE-defect. That’s why during veterinary –sanitary inspection of organs and broiler carcasses we can determine not only features of PSE-defect, but degree of their development . During veterinary- sanitary inspection of poultry meat, four development stages of PSE-defect can be determined: extreme, florid, moderate, ill-defined. The criteria of such meat assessment are best attested рН value, muscle color, water capacity, muscle consistency on a cut and other deviations in organo-leptic attribute. The most reasonable procedure of poultry meat processing with signs of PSE-defect and myopathy of infectious aetiology. It is recommended in all cases of muscle fiber defeat as a result of PSE- defect or infectious and invasive diseases, broiler carcasses, to consider “limitedly suitable” and undergo laboratory research. In case of weak localized muscular tissue affect of carcasses it is wise to aim for boiling. In case of infectious and invasive disease, associated with evident muscle disorder, carcasses need to aim for utility waste. Meat of forcedly killed poultry after thermal antisepsis can be used for production of cooked sausages and tinned meat.

SUN-155 A Complex Case of Adrenal Insufficiency Associated with NLRP1 Gene Mutation in a Patient with Myopathy and Mitochondrial Cytopathy

Most cases of Addison’s disease are due to an autoimmune response, with the most commonly associated genes belonging to human leukocyte antigen (HLA) complex. Genome wide association studies have shown a significant association of variants of Nuclear Localization Leucine-Rich-Repeat Protein 1 (NLRP1) with Addison’s disease. NLRP1 protein is involved in the assembly of inflammasome which promotes the secretion of interleukin-1β, interleukin-18 and downstream inflammatory responses to regulate inflammation. With underlying myopathy and mitochondrial disease, coexisting adrenal insufficiency may be challenging to identify. A 36-year-old female presented for evaluation of fatigue, myalgia, and dyspnea for several years. She carried a diagnosis of asthma, myopathy, gastroparesis requiring a gastric stimulator, and recently diagnosed adrenal insufficiency secondary to long term fluticasone use. Beside low blood pressure of 91/64 millimetres of mercury, physical exam was unremarkable. Lab findings were significant for dehydroepiandrosterone-sulfate (DHEAS) of 7.0 micrograms per deciliter (mcg/dL), Adrenocorticotropic hormone (ACTH) of 7.2 picograms per milliliter and cortisol of 1.4 mcg/dL. Adrenal insufficiency was confirmed with cosyntropin stimulation test. Methacholine challenge test showed worsening asthma. She was managed with empiric stress dose steroids when indicated. Muscle fatigue progressed despite taking ubiquinol, B100 and carnitine. She was further evaluated with muscle biopsy that showed type two fiber atrophy. Muscle coenzyme Q10 was 0.08 mcg/dL, and citrate synthase was 50% of normal, insufficient for electron transport complex I. Whole exome sequencing showed mutations in NLRP1 in addition to Myosin Heavy Chain 2 (MYH2) and Sodium voltage-gated Channel alpha subunit 4 (SCN4a) both of which are associated with myopathy. She was then started on a short-acting glucocorticoid regimen. While her adrenal insufficiency was initially thought to be secondary to inhaled steroids, subsequent mutation analysis suggested that she was prone to autoimmunity. This case illustrates the association of adrenal insufficiency with NLRP1 mutation. Furthermore, the symptoms of adrenal insufficiency and myopathy can overlap making it difficult to delineate. While so far most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial deoxyribonucleic acid (DNA), a new field of investigation is that of syndromes due to mutations in the nuclear DNA.

Early Neuromuscular Blockade in Children with Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is a challenging problem with high mortality. Role of neuromuscular blockade in the management of ARDS to date has been controversial, and this study was done to study the role of neuromuscular blockade in children having PARDS and development of associated complications, if any. This was a prospective, case-control study conducted in the pediatric intensive care unit (PICU) of a tertiary care teaching hospital, over a period of 24 months. Patients of age 1 to 18 years who presented with or developed PARDS during their course of hospitalization were included after written informed consent was obtained from their parents and/or guardians. Patients with PARDS requiring invasive mechanical ventilation were partitioned into a case group and a control group. Case group patients were sedated and paralyzed using midazolam (1 µg/kg/min) and vecuronium (1 µg/kg/min), respectively, along with institution of definitive management. Control group patients were given definitive and supportive therapy, but no neuromuscular blocking agents (NMBAs). All patients were followed up for signs and symptoms of myopathy or neuropathy during the entire duration of hospital stay and up to 3 months after discharge. During the study period, 613 patients were admitted to the PICU of which 91 patients qualified as having PARDS. Sepsis was the main etiology in 67 of the 91 patients (73.6%) with PARDS. Fifty-nine patients were included in the study, of which 29 patients were included in the case group and 30 patients were included in the control group. Among the 29 case group patients, 25 patients (86.2%) were successfully extubated. Four patients from the case group expired, while 14 out of 30 control group patients (46.7%) expired. Hypotension was present in 26 case group patients (89.6%), of which all showed resolution within 48 hours of definitive treatment. The mean time to resolution of hypotension was 41.6 hours (standard deviation [SD]: 5.759; range: 24-48) for case group patients, significantly lower ( p < 0.0001) than the mean time to resolution of 103 hours (SD: 18.995; range: 90-126) for the 10 control group patients with hypotension that survived. Mean oxygenation index (OI) following 48 hours of vecuronium therapy was significantly lower ( p < 0.0001; 95% confidence interval: 5.9129-9.9671) than mean OI at admission for case group patients. None of the patients receiving vecuronium exhibited neuromuscular deficit during their hospital stay, at time of discharge, or at follow-up evaluation up to 3 months after discharge. In this study, pediatric cases diagnosed with PARDS and managed with mechanical ventilation and vecuronium therapy had improved mean OI following 48 hours of NMBA therapy and a lower mortality when compared with matched control group patients. Incidence of NMBA-related weakness was not commonly observed in these patients.