Use of dexamethasone in idiopathic, acute pediatric rhabdomyolysis.

Current rhabdomyolysis treatment guidelines vary based on the etiology and diagnosis, yet many cases evade conclusive diagnosis. In these cases, treatment options remain largely limited to fluids and supportive therapy. We present two cases of acute rhabdomyolysis diagnosed in the emergency department: a 5-year-old boy with sudden onset bilateral flank pain, and a 13-year-old boy with 2-3 days of worsening pectoral and shoulder pain. Each patient had a prior similar episode requiring hospitalization in the past. The 5-year-old had no inciting trauma or trigger, medication use, or illness. The 13-year-old previously had an upper respiratory infection during the week prior and had been strenuously exercising at the time of onset. Genetic testing results were unknown for both patients during their hospitalizations, and insurance and other barriers led to delay. Later results for the first patient revealed a heterozygous deletion in intron 19 on the LPIN1 gene interpreted as a variant of unknown significance. During their hospitalizations, both children were started on intravenous (i.v.) fluids, and creatine kinase (CK) initially trended downward, but then began to rise or plateau. After reviewing the cases, prior literature, and anecdotal evidence of benefit from corticosteroid therapy in rhabdomyolysis with our consultant metabolic physicians, dexamethasone was initiated. In both patients, dexamethasone use correlated with relief of patient symptoms, significantly decreased CK value, and our ability to discharge these patients home quickly. Our cases, discussion, and literature review all lead to the consideration of the use of dexamethasone in conjunction with standard therapy for acute rhabdomyolysis.

Histopathological kidney changes and myoglobinuria in neotropical non-human primates attacked by dogs, Brazil.

BACKGROUND: Non-human primates (NHPs) are susceptible to dogs' attacks, events that may cause muscle damage along with stress, and could be in some extent compatible with capture myopathy, a syndrome that results in myoglobinuria and renal damage. METHODS: We aimed to evaluate by histopathology pre-existing lesions and subsequent sequelae related to dogs' attacks, acute tubular necrosis (ATN) and myoglobinuria, as well as the usefulness of Pearls Stain and IHC to diagnose it. Histopathology was performed in available organs, and sections of kidney submitted to Prussian blue stain and myoglobin immunohistochemistry. RESULTS: During January 2014-June 2016, 16/145 (11%) of NHPs received by Adolfo Lutz Institute, Brazil were reported as attacked by dogs. A high frequency of young and debilitated animals was found. Myoglobinuria was observed in more than half animals (9/16; 56.2%), from which (5/9; 55.5%) presented ATN. CONCLUSIONS: Kidney lesions are plausible findings in NHPs attacked by dogs.

Young girl presenting with exercise-induced myoglobinuria.

INTRODUCTION: The sarcoglycanopathies are a heterogeneous group of autosomal recessive limb-girdle muscular dystrophies that cause varying degrees of progressive proximal muscle weakness. METHODS: We describe the case of a Caucasian girl who presented with exercise intolerance, myalgia, and dark urine. Onset of symptoms was at age 4, and she had myalgia with physical activity throughout childhood. Creatine kinase levels were as high as 18,000. RESULTS: Immunostaining of a muscle biopsy showed mildly diminished alpha sarcoglycan staining, and SGCA gene sequencing revealed n.C229T; p.Arg77Cys (R77C) and n.C850T; p.Arg284Cys (R284C), which is associated with alpha sarcoglycanopathy. CONCLUSIONS: This patient presented with exercise intolerance, myoglobinuria, and almost normal muscle strength into adolescence, which is uncommon in sarcoglycanopathies. This uncommon presentation should be kept in mind, so that early recognition and intervention may prevent future comorbidities and help preserve the quality of life. Muscle Nerve 54: 161-164, 2016.

Fatal rhabdomyolysis after torture by reverse hanging.

PURPOSE: Reverse hanging (also known as Palestinian hanging) is a form of positional torture where the victim is suspended for a prolonged period of time by the wrists, after the wrists are bound at the back. We report the first autopsy case of reverse hanging. We have discovered that fatal myoglobinuric renal failure due to rhabdomyolysis can be a complication of Palestinian hanging. METHOD: An adult detainee, who underwent interrogation by authorities, was admitted to hospital from a prison and died in hospital after a few days. Death was due to myoglobinuric renal failure. An autopsy was performed. RESULTS: At autopsy, the body showed anasarca due to renal failure. There were healing ligature marks on the wrist and forearm, but no blunt impact injury to the shoulders or arms. There was extensive necrosis of the pectoralis major, biceps, and deltoid muscles, organizing hemoarthrosis of the right glenohumeral joint and hemorrhage into the joint capsule of the both glenohumeral joints. The kidneys showed evidence of myoglobin deposition grossly. The overstretching of the major muscles of the shoulder, in response to the prolonged Palestinian hanging, gave rise to the muscle necrosis. CONCLUSION: This case underscores the importance of conducting autopsies on people who die in custody, particularly if detained at times of political instability when torture may be practiced by state actors and others. This case also reveals that fatal rhabdomyolysis can occur by positional torture in a stress position, despite the absence of direct trauma due to blunt impacts.

A study on the effect of cimetidine and L-carnitine on myoglobinuric acute kidney injury in male rats.

Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury.

Enhydrina schistosa (Elapidae: Hydrophiinae) the most dangerous sea snake in Sri Lanka: three case studies of severe envenoming.

Sea snakes are highly venomous and inhabit tropical waters of the Indian and Pacific Oceans. Enhydrina schistosa is a common species of sea snake that lives in the coastal waters, lagoons, river mouths and estuaries from the Persian Gulf through Sri Lanka and to Southeast Asia. It is considered one of the most aggressive sea snakes in Sri Lanka where fishermen and people wading are at high risk. However, sea snake bites are rarely reported. In this report, we describe three cases where E. schistosa was the offending species. These three patients presented to two hospitals on the west coast of Sri Lanka within the course of 14 months from November 2011 with different degrees of severity of envenoming. The first patient was a 26-year-old fisherman who developed severe myalgia with very high creatine kinase (CK) levels lasting longer than 7 days. The second patient was a 32-year-old fisherman who developed gross myoglobinuria, high CK levels and hyperkalaemia. Both patients recovered and their electromyographic recordings showed myopathic features. The nerve conduction and neuromuscular transmission studies were normal in both patients suggesting primary myotoxic envenoming. The third patient was a 41-year-old man who trod on a sea snake in a river mouth and developed severe myalgia seven hours later. He had severe rhabdomyolysis and died three days later due to cardiovascular collapse. In conclusion, we confirm that E. schistosa is a deadly sea snake and its bite causes severe rhabdomyolysis.

Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry.

BACKGROUND: Published genotype/phenotype data on McArdle disease are limited in sample size. A single national (Spanish) registry of patients with McArdle disease was created with the purpose of analysing their genotypic and phenotypic characteristics. METHODS: A cross sectional study was conducted, collecting demographic, family history, clinical, genotype and functional capacity data from all patients diagnosed with McArdle disease in the Spanish National Health System up to December 2010. RESULTS: 239 cases were recorded (all of Caucasian descent, 102 women; mean±SD age 44±18 years (range 9, 93)); prevalence of ∼1/167 000 people. Two mutant PYGM alleles were identified in 99.6% of cases. Although there was heterogeneity in the severity of symptoms, there were four common diagnostic features: (1) 99.5% of patients reported a history of acute crises of exercise intolerance (accompanied by recurrent myoglobinuria in 50% of cases); (2) in 58% of patients, symptoms started in the first decade of life; (3) 86% of patients repeatedly experienced the 'second wind' phenomenon over life; and (4) 99% of patients had a high basal serum level of total creatine kinase (>200 U/l). Clinical presentation of the disease was similar in men and women and worsened with age. Patients who were physically active had higher levels of cardiorespiratory fitness (by 23%, p=0.003) and were more likely to improve their clinical course over a 4 year period compared with inactive patients (OR 225; 95% CI 20.3 to 2496.7). CONCLUSIONS: The main clinical features of McArdle disease are generally homogeneous and frequently appear during childhood; clinical condition deteriorates with ageing. Active patients have a better clinical outcome and functional capacity.

Pseudometabolic presentation of dystrophinopathy due to a missense mutation.

Exercise intolerance with myalgia, muscle stiffness, and recurrent rhabdomyolysis due to mutations in the DMD gene can mimic metabolic myopathies leading to delayed or inaccurate diagnoses. In this retrospective chart review, we report 3 unrelated boys with exertional myalgia, muscle stiffness, myoglobinuria, and normal neurological examination due to an identical point mutation in the DMD gene: a hemizygous T-to-C change in exon 15 (c.1724T>C) resulting in an amino acid substitution of leucine to proline at codon 575. Two of the 3 boys had normal dystrophin immunostaining and Western blot analysis in muscle. This missense mutation has been reported twice before, with at least 1 patient exhibiting rhabdomyolysis. Our report, however, is the first to describe in detail the clinical findings associated with this specific mutation. Further studies and clinical reports are needed to better understand the pathogenicity of the mutation.

Necrotizing vacuolar myopathy presenting with recurrent myoglobinuria.

Myoglobinuria occurs in a variety of systemic and neurological disorders and can pose diagnostic challenges. We report on a 23-year-old man in whom recurrent myoglobinuria was observed due to necrotizing vacuolar myopathy confirmed on muscle biopsy. Histopathologically the intramuscular vacuoles lacked the typical findings reported in vacuolar myopathy due to disorders of glycogen and lipid metabolism. We discuss the management approach to recurrent myoglobinuria. Recurrent myoglobinuria in the absence of toxin or drug exposure and seizure is more often due to primary muscle disease. Recognizing the presence of myoglobinuria and the proximate cause is essential in preventing the development of renal dysfunction and the future recurrence of symptoms.

Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria.

Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the direct effect of myoglobin on renal tubules and isolated kidney mitochondria while measuring mitochondrial respiratory control, production of reactive oxygen and nitrogen species and lipid peroxidation. In parallel, we evaluated mitochondrial damage under myoglobinurea in vivo. An increase of lipid peroxidation products in kidney mitochondria and release of cytochrome c was detected on the first day of myoglobinuria. In mitochondria incubated with myoglobin we detected respiratory control drop, uncoupling of oxidative phosphorylation, an increase of lipid peroxidation products and stimulated NO synthesis. Mitochondrial pore inhibitor, cyclosporine A, mitochondria-targeted antioxidant (SkQ1) and deferoxamine (Fe-chelator and ferryl-myoglobin reducer) abrogated these events. Similar effects (oxidative stress and mitochondrial dysfunction) were revealed when myoglobin was added to isolated renal tubules. Thus, rhabdomyolysis can be considered as oxidative stress-mediated pathology with mitochondria to be the primary target and possibly the source of reactive oxygen and nitrogen species. We speculate that rhabdomyolysis-induced kidney damage involves direct interaction of myoglobin with mitochondria possibly resulting in iron ions release from myoglobin's heme, which promotes the peroxidation of mitochondrial membranes. Usage of mitochondrial permeability transition blockers, Fe-chelators or mitochondria-targeted antioxidants, may bring salvage from this pathology.

Experimental myoglobinuric acute renal failure: the effect of vitamin C.

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.

Myoglobinuria in boys with Duchenne muscular dystrophy on corticosteroid therapy.

Myoglobinuria is a recognised complication of Duchenne muscular dystrophy (DMD), but has only once been reported in ambulant boys on corticosteroid therapy [Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Remission of clinical signs in early Duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Eur J Paediatr Neurol 2002;6(3):153-9.]. We present three prednisolone-treated boys with myoglobinuria and in two cases this was recurrent. All three showed improved motor performance in response to the introduction of corticosteroids. The greater activity of steroid-treated individuals may place their dystrophin-deficient muscles under greater mechanical stress, predisposing to further muscle fibre damage and consequent myoglobinuria. Families and physicians need to have an increased awareness of this possibility and of the appropriate management of myoglobinuria.

Rhabdomyolysis and myoglobinuric nephrosis (capture myopathy) in a striped dolphin.

This report describes delayed myoglobinuric capture myopathy in a striped dolphin (Stenella coeruleoalba) found stranded alive on the coast of Fuerteventura (Canary Islands, Spain). The animal was transported to Gran Canaria where it died 48 hr after stranding. The main lesions consisted of acute rhabdomyolysis affecting both cardiac and skeletal muscles, and myoglobinuric nephrosis. Using immunohistochemistry, degenerate myofibers with depletion of myoglobin, and an intracytoplasmatic immunoreaction for fibrinogen were observed. Orange-red pigmented casts in renal tubular lumens were strongly immunolabeled for myoglobin. To our knowledge, this is the first pathologic description of capture myopathy with myoglobinuric nephrosis in stranded cetaceans. Stress, exertion, trauma, and crush injury caused during the stranding, restraint, and transportation were the main causes of rhabdomyolysis in this case.

Rabdomiólisis: patogenesia, aspectos y tratamiento clínicos / Rhabdomyolisis: pathogenesis, clinical features and treatment

La raabdomiólisis es un sindrome causado por la lesión en el músculo esquelético y la resultante liberación del contenido de las células musculares (mioglobina, potasio, fosfato, etc.) dentro del plasma. 5...El diagnóstico de rabdomiólisis queda establecido por una marcada elevación de la CPK sérica mayor a 10.000UI/L. El tratamiento tiene como objetivo prevenir la insuficiencia renal aguda, la cual es la complicación más grave de este sindrome.(AU)

Acute toxic renal failure.

Acute renal failure (ARF) is a common problem in intensive care medicine. Even modest degrees of ARF not requiring dialysis treatment increase the risk of death approximately fivefold. Despite the widespread appreciation of the role of nephrotoxic drugs in their contribution to ARF, these drugs continue to have an ongoing aetiological role. Potentially nephrotoxic drugs include non-steroidal anti-inflammatory drugs, radiocontrast agents, antimicrobial and anaesthetic agents. Endogenous compounds such as myoglobin and haemoglobin may furthermore cause toxic nephropathy. Tubular injury initiated by toxins often results from a combination of acute renal vasoconstriction and direct cellular toxicity due to intracellular accumulation of the toxin, or, alternatively, may be mediated immunologically in case of interstitial nephritis. Patients with reduced renal functional reserve, cardiovascular co-morbidity, diabetes mellitus, and advanced age are at increased risk. Awareness of the range of toxins on the one hand and simple measures such as adequate pre-hydration of the patient and drug monitoring on the other hand may be sufficient to avoid drug-induced ARF or minimize its clinical severity in susceptible patients.

[Acute alcoholism with myoglobinuria: an autopsy case report].

We report an autopsy case of fatal acute alcoholism showing myoglobinuria and myocardial damage. The victim was a 29-year-old male, who was found drunk at his home. Although he was once brought to a hospital following a police officer's advice, he was taken into custody without effective medical care due to his violent behavior, and died about 16 hours later. Autopsy revealed marked congestion of the viscera and fatty liver. Histologically, skeletal muscle and myocardium showed focal degeneration and necrosis. Immunohistochemical investigation revealed a diffuse myoglobin loss from muscle fibers. Alcohol concentrations were 0.54 mg/ml, 0.79 mg/ml and 2.53 mg/ml in the left, right heart blood and urine, respectively. No other drugs or poisons were detected. The urine was dark brown, showing marked myoglobinuria. Cardiac troponin T, I and CK-MB in the pericardial fluid showed elevated levels even when postmortem influence was taken into consideration. From these observations, the cause of death was determined as myocardial damage from advanced acute alcoholic myopathy accompanied by myoglobinuria, possibly with underlying alcohol abuse. The present case suggests that careful clinical observation and adequate management are essential for an alcoholic patient with neurological symptoms.

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats.

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.

Effects of melatonin administration to rats with glycerol-induced acute renal failure.

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.

Disorders of lipid metabolism in skeletal muscle.

Lipid storage myopathies are typically present with recurrent episodes of myoglobinuria and hypoglycemia, triggered by fasting or infection. Dilated cardiomyopathy can occur. This article will discuss an approach to lipid storage myopathies and describes various forms of disorders by fatty acid oxidation.

Myoglobinuria.

Myoglobinuria refers to an abnormal pathologic state in which an excessive amount of myoglobin is found in the urine, imparting a cola-like hue, usually in association with myonecrosis and a clinical picture of weakness, myalgias, and edema. Myoglobinuria is produced by multiple causes: any condition that accelerates the use or interferes with the availability of oxygen or energy substrates to muscle cells can result in myoglobinuria, as can events that produce direct muscle injury, either mechanical or chemical. Acute renal failure is the most serious complication, which can be prevented by prompt, aggressive treatment. In patients surviving acute attacks, recovery of muscle and renal function is usually complete.