Acute Myopathy Research Articles

A RARE CASE OF ACIDOSIS-INDUCED DELAYED REVERSIBILITY OF NEUROMUSCULAR BLOCKADE.

Introduction A group of neuromuscular disorders are described to accompany critical illness. Generally, three distinct types of muscle weaknesses are now recognized, namely critical illness polyneuropathy, prolonged neuromuscular blockade, and acute myopathy (with combined use of a glucocorticoid and a neuromuscular blocking drug). Complete quadriplegic paralysis is the most dramatic manifestation of these conditions. We discuss below a case of prolonged neuromuscular blockade, attributable to a rare and relatively unknown cause. Case Report A 41-year-old lady with advanced AIDS was admitted with Pneumocystis carinii pneumonia. Despite treatment with Bactrim and corticosteroids, the patient rapidly went into respiratory failure (requiring mechanical ventilation) and septic shock with multiorgan dysfunction (predominantly renal tubular acidosis). To achieve adequate oxygenation, a neuromuscular blocking agent was used to achieve synchrony with the ventilator. In view of renal dysfunction, we chose cis-atracurium (the clearance of which is known to be much less affected by renal failure) as the preferred agent. Respiratory status soon improved, the patient9s chest radiograph looked better, the A-a gradiant narrowed, and oxygenation improved dramatically. However, the patient9s renal failure worsened, with significant metabolic acidosis, and her pH remained around 7.2. After discontinuation of the neuromuscular blocking agent, patient was found to be quadriplegic, with persistent suppression of the train-of-four twitch response to peripheral nerve stimulation, and her muscle strength transiently improved with pyridostigmine. This was puzzling because even with renal dysfunction, we had not expected a prolonged neuromuscular blockade with cis-atracurium. Also, the patient was not sick long enough to fit the criteria of critical illness polyneuropathy. She was on corticosteroids for only 5 days, so steroid myopathy also seemed unlikely. The only caveat that remained was the persistence of severe acidosis, and true enough, as the renal failure resolved and the pH rose to 7.35, the patient recovered from the quadriplegia dramatically and regained normal neuromuscular functions. Conclusion We are aware of the fact that prolonged neuromuscular blockade (sometimes up to 1 week) can occur in critical care settings with agents such as pancuronium and vecuronium, which produce functionally active 3-hydroxy metabolites that accumulate and persist in the blood in renal failure. It is also important for physicians to know that ‘acidosis alone’ can prolong the effect of agents such as cis-atracurium, in the absence of other identifiable reasons.

Experimental animal models of muscle wasting in intensive care unit patients

The muscle wasting and loss of muscle function associated with critical illness and intensive care have significant negative consequences for weaning from the respirator, duration of hospital stay, and quality of life for long periods after hospital discharge. There is, accordingly, a significant demand for focused research aiming at improving our understanding of the mechanisms underlying the impaired neuromuscular function in intensive care unit (ICU) patients. However, the study of generalized muscle weakness in critically ill ICU patients is further complicated by the coexistence of multiple independent factors, such as different primary diseases, large variability in pharmacologic treatment, collection of muscle samples several weeks after admission to the ICU, and exposure to causative agents. This has led to the design of specific animal models mimicking ICU conditions. These models have often been used to study the mechanisms underlying the paralysis and muscle wasting associated with acute quadriplegic myopathy in ICU patients. This short review aims at presenting existing and recently introduced experimental animal models mimicking the conditions in the ICU (i.e., models designed to determine the mechanisms underlying the muscle wasting associated with ICU treatment).

Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency

Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. We describe four novel mutations of the alpha- and beta-subunits of the mitochondrial trifunctional protein in four patients from three unrelated families. Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). Patients 1 and 2 had siblings who had died of lactic acidemia during the neonatal period. These patients also manifested lactic acidemia and died in the neonatal period. Patient 3 had a family history of Reye-like syndrome. She exhibited acute renal failure, rhabdomyolysis, pericardial effusion, and myopathy at the age of 12 years. DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. Patient 3 was a compound heterozygosity of the HADHB gene, N307D/N389D. Patient 4, a 25-month-old baby, manifested recurrent episodes of lethargy, metabolic acidosis, elevated liver enzymes, and dark urine from the age of 10 months. Mutation analysis of the HADHB gene of patient 4 identified compound heterozygosity of N114D/N307D.

Molecular and cellular defects of skeletal muscle in an animal model of acute quadriplegic myopathy

Muscle denervation and concomitant high-dose dexamethasone treatment in rodents produces characteristic pathologic features of severe muscle atrophy and selective myosin heavy filament (MyHC) depletion, identical to those seen in acute quadriplegic myopathy (AQM), also known as critical illness myopathy. We tested the hypothesis that defective pre-translational processes contribute to the atrophy and selective MyHC depletion in this model. We examined the effects of combined glucocorticoid-denervation treatment on MyHC and actin mRNA populations; we also studied mRNA expression of the myogenic regulatory factors (MRFs), primary transcription factors for MyHC. Adult female rats were subjected to proximal sciatic denervation followed by high-dose dexamethasone (DD) treatment (5 mg/kg body weight daily) for 7 days. Disease controls included rats treated with denervation alone (DN) or dexamethasone alone (DX). At 1 week the plantaris atrophied by approximately 42% in DD muscles. DD treatment resulted in selective MyHC protein depletion; actin protein concentration was not significantly changed. Despite an increase in total RNA concentration in DN and DD muscles, MyHC and actin mRNA concentrations were significantly decreased in these muscles. MyHC mRNA showed a significantly more extensive depletion relative to actin mRNA in DD muscles. Glucocorticoid treatment did not influence a denervation-induced increase in the mRNA expression of the MRFs. We conclude that a deleterious interaction between glucocorticoid and denervation treatments in skeletal muscle is responsible for pre-translational defects that reduce actin and MyHC mRNA substrates in a disproportionate fashion. The resultant selective MyHC depletion contributes to the severe muscle atrophy.

Olanzapine overdose is associated with acute muscle toxicity

Olanzapine is an atypical antipsychotic that is reported to cause myopathy and raised creatine kinase (CK) levels. The prevalence and severity of acute myopathy after deliberate olanzapine ingestion are unclear. Therefore, we reviewed case notes from 64 consecutive patients admitted to our institution after olanzapine overdose. Overall, serum CK was higher than five times the upper limit of normal in 17% of patients. The prevalence of raised CK values was positively correlated with the stated quantity of olanzapine ingested, suggesting a dose-dependent relationship for acute muscle toxicity. There was an apparent delay of 12 hours or more between olanzapine ingestion and the occurrence of maximum CK. Despite the high prevalence of acute muscle toxicity after olanzapine ingestion, none of the patients developed renal failure.

A porcine model of acute quadriplegic myopathy: a feasibility study

The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms. Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR). A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation. The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

BackgroundManagement of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)?MethodsThe base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed.ResultsOur computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137.ConclusionARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS.

Acute Severe Myopathy Following a Single Infusion of Omeprazole

Acute Severe Myopathy Following a Single Infusion of Omeprazole

Síndrome neuromuscular adquirido en el paciente crítico

To analyse the causes and signs of the muscle weakness that critically ill patients develop during their stay in the ICU and to review the literature. In the early 80s, Bolton reported a mixed axonal polyneuropathy that he called 'polyneuropathy in critically ill patients'. Clinically it was characterised by muscle weakness that varied in intensity and caused quadriplegia and/or the need for assisted ventilation in its severest forms. It is currently considered to be the most common neurological disorder among critically ill patients. Many patients made a complete recovery after a few months or even a year. Running almost parallel to this, he also described 'acute myopathy in intensive care' among asthmatic patients who were hospitalised in the ICU due to exacerbation of their illness. It was later observed how other types of patients also had this myopathy, for instance, those who had undergone a transplant, sepsis or burns. Some authors consider acute myopathy in intensive care to be the primary cause of muscle weakness in the ICU. On many occasions 'polyneuropathy of critically ill patients' and 'acute myopathy in intensive care' can be differentiated and to do so neurophysiological and, if necessary, muscle biopsy studies are a valuable aid. Although some authors prefer to group these conditions under the name 'polyneuromyopathy', we propose the general term 'acquired neuromuscular syndrome in critically ill patients' -a more descriptive expression that does not presuppose a particular mechanism or a single aetiology.

Acute myopathy associated with liver cirrhosis

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. 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. 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. 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.

Lipidsenker- und andere toxische Myopathien

A growing number of therapeutic agents and exogenous toxins are harmful to structure and function of human skeletal muscle. The clinical syndrome encompasses asymptomatic creatine kinase elevation, myalgia, exercise intolerance, muscle paresis and atrophy, and lastly acute rhabdomyolysis. Toxic myopathies are potentially reversible, hence a prompt recognition is particularly helpful for the early diagnosis and in conclusion elimination of a myopathy inducing toxin. Toxic myopathies may be classified as acute or chronic accordingly to the exposition time to a toxin. Main source of an exogenous induced toxic myopathy is chronic alcohol abuse. Alcohol excess induces acute and/or chronic neuropathy and myopathy, consequently muscle wasting and weakness occurs. Drug-induced myopathies are most frequently seen due to amplified utilization of corticosteroids or lipid lowering agents.

Acute myopathy in a type 2 diabetic patient on combination therapy with metformin, fenofibrate and rosiglitazone

This report describes the case of a 75-year-old male type 2 diabetic Caucasian who was admitted to the clinical ward because of acute pain and cramps in both calf muscles. Neuromuscular function was assessed by electromyography and electroneurography of the right leg. An open biopsy was taken from the left vastus lateralis muscle for histological and histochemical analyses. Southern blotting was performed to detect defects in mitochondrial DNA and tRNA. Cytochrome P450 (CYP-P450) polymorphisms were analysed in blood cells. Fifteen weeks before admission, the patient's lipid-lowering medication was switched from simvastatin to fenofibrate because of predominant hypertriglyceridaemia; this did not affect creatine kinase levels. Three weeks before admission, rosiglitazone was added to his existing metformin therapy because of worsening metabolic control. Upon admission, serum enzymes indicating myopathy were elevated (creatine kinase 6897 U/l, myoglobin 902 ng/ml) and kidney function was impaired (creatinine 0.116 mmol/l, blood urea nitrogen 2.3 mmol/l). Electrophysiology revealed myopathy and sensory polyneuropathy. Histology showed multiple damage of the myofibrillar architecture. There was no evidence of defects in mitochondrial DNA or tRNA. Furthermore, no functional limitations in CYP2C9, CYP2C19 and CYP2D6 were detected. Following withdrawal of the oral medication and intravenous hydration, clinical symptoms and laboratory parameters gradually decreased. Until more data from controlled trials are available, we recommend that combination therapy with fibrates and thiazolidinediones should be monitored frequently by measurements of serum creatine kinase and creatinine, specifically in patients with pre-existing nephropathy and polyneuropathy.

Deep White Matter Pathologic Features in Watershed Regions

Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome typically manifests in adults younger than 40 years with encephalopathy, stroke-like episodes, and lactic acidosis. Magnetic resonance imaging (MRI) abnormalities typically involve the cortical gray and the adjacent subcortical white matter. To describe a 58-year-old woman diagnosed with MELAS who was initially seen with acute myopathy, cardiac ischemia, psychosis, and MRI changes in a watershed distribution. Initial MRI of the brain showed the characteristic parieto-occipital gray matter lesions involving the adjacent white matter. Follow-up MRI revealed striking deep white matter involvement in a watershed distribution. A cerebral angiogram and thorough hypercoagulable workup results were normal. Electromyography showed acute denervation and myopathy. A muscle biopsy specimen revealed ragged red and cytochrome-c oxidase-negative fibers. Mitochondrial DNA analysis revealed an A3243G mutation. Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes should be considered in older patients with myopathy, cardiomyopathy, encephalopathy, and unaccountable MRI findings. Watershed pathologic features are a rare pattern of cerebral involvement in MELAS.

Acute Myopathy in a Patient with Concomitant Use of Pravastatin and Colchicine

To report a case of acute myopathy after concomitant use of colchicine and pravastatin. A 65-year-old woman was admitted to the hospital with an acute episode of gout. She had been taking pravastatin 20 mg once daily for 6 years. On admission, blood urea nitrogen and serum creatinine levels were 48 mg/dL and 1.3 mg/dL, respectively. Colchicine 1.5 mg/day was added to the treatment regimen, but 20 days after the initiation of colchicine therapy, symmetrical proximal muscle weakness developed in the woman's legs. Physical examination, laboratory findings, and electromyelogram findings suggested myopathy. The Naranjo probability scale indicated a probable relationship between myopathy and combined therapy. Seven days after discontinuation of colchicine and pravastatin, the patient's weakness improved and enzyme levels returned to normal. Colchicine was restarted at 1.0 mg/day 5 days later; no myopathy occurred. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) and colchicine are known to cause myopathy. Most of the statins and colchicine are biotransformed in the liver primarily by the CYP3A4 system, which may increase the risk of myopathy when concurrent therapy is used. However, pravastatin is not primarily metabolized by cytochrome P450 isoenzymes. The cause of myopathy in our patient may be related to the interaction of colchicine and pravastatin via P-glycoprotein. In addition, the presence of mild renal dysfunction could have contributed to the development of myopathy. We suggest that clinicians be aware that neuromuscular toxicity can occur in patients with mild renal dysfunction with combined use of colchicine and pravastatin.

Myopathies in Critical Illness: Characterization and Nutritional Aspects

Myopathies related to critical illness have received increasing recognition over the past decade and are common in patients even after a brief period in the intensive care unit. Recent studies have revealed that myopathies in the critically ill may in fact be more prevalent than neuropathies and that morbidity and mortality may be greater. Protein catabolism, an increase in urinary nitrogen loss, and muscle wasting are observed in critical illness myopathy. Muscle biopsies in critically ill patients demonstrate low glutamine levels, low protein/DNA levels, and high concentrations of extracellular water. The increased flux of glutamine in muscle in these patients is thought to be insufficient to meet the body's requirement for glutamine, and thus in critical illness this amino acid may be classified as "conditionally essential." Three subtypes of critical illness myopathy have been described that are often grouped together as acute quadriplegic myopathy: thick-filament myopathy, critical illness myopathy, and necrotizing myopathy. These can be differentiated based on clinical features and muscle biopsy. Treatments for critical illness myopathies range from primary prevention, i.e., avoiding myopathy-inducing drugs, to novel nutritional therapies, such as glutamine and glutathione supplementation. One should be particularly vigilant for the development of myopathies in critically ill alcoholic patients, who may have a chronic alcoholic myopathy at baseline. In the past decade, advances have been made in characterizing and identifying patients with myopathies due to critical illness. However, additional studies must be performed in order to develop appropriate therapies for this potentially devastating disorder.

Acute quadriplegic myopathy in a 16-month-old child

We present a case of a 16-month old previously healthy child who was hospitalized because of an acute respiratory insufficiency most likely caused by a viral infection and who then developed a severe acute quadriplegic myopathy (AQM). Initial clinical symptoms were respiratory acidosis, dypnea, intense wheezing, and deterioration of the level of consciousness, which required orotracheal intubation and mechanical ventilation. We administered neuromuscular blocking agents, corticosteroids, and antibiotics. After 9 days the clinical picture improved. An attempt to wean from the ventilator failed. We diagnosed AQM. This paper discusses AQM and its clinical importance.

Myosin Loss in Denervated Rat Soleus Muscle after Dexamethasone Treatment

Objective: Critical illness myopathy (CIM) is an acute myopathy that appears in the setting of critical illness or during exposure to corticosteroids and neuromuscular blocking agents. Its pathological feature is selective loss of thick myosin filaments. Our aim is to gain further insight into the pathomechanism of myosin loss in this myopathy. Methods: To clarify the expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after saline and dexamethasone treatments. Results: Denervated muscles from dexamethasone-treated rats showed marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was significantly increased in denervated dexamethasone-treated muscles, suggesting that the ubiquitin-proteasome pathway plays an important role in muscular wasting in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in the denervated dexamethasone-treated muscles. Conclusion: Our findings suggest that an altered transcription rate of myosin, as well as the upregulation of multiple ubiquitin ligases, may be responsible for selective myosin loss in this myopathy.

Approach to neuromuscular disorders in the intensive care unit.

Neuromuscular disorders increasingly are recognized as a complication in patients in the intensive care unit (ICU) and represent a common cause of prolonged ventilator dependency. The distinct syndromes of critical illness myopathy, prolonged neuromuscular blockade, and critical illness polyneuropathy (CIP) may arise as a consequence of sepsis, multi-organ failure, and exposure to various medications—notably, intravenous corticosteroids and neuromuscular blocking agents—but the pathophysiology of these disorders remains poorly understood. More than one syndrome may occur simultaneously, and the distinctions may be difficult in a particular patient, but a specific diagnosis usually can be established after careful clinical, electrodiagnostic, and, when necessary, histological evaluation. For example, asthmatics requiring treatment with corticosteroids and neuromuscular blocking agents may develop an acute myopathy characterized by generalized weakness, preserved eye movements, elevated creatine kinase levels, and myopathic motor units on electromyography (EMG). Muscle biopsy demonstrates distinctive features of thick (myosin) filament loss on ultrastructural studies. Conversely, those with a prolonged ICU course that is complicated by episodes of sepsis with failure to wean from the ventilator, distal or generalized flaccid limb weakness, and areflexia probably have CIP. EMG in these patients demonstrates reduced or absent motor and sensory potentials with neurogenic motor units. Prolonged neuromuscular blockade most commonly occurs in patients with renal failure who have received prolonged infusions of neuromuscular blockers. There is severe flaccid, areflexic paralysis with normal sensation, facial weakness, and ophthalmoparesis that persists for days or weeks after the neuromuscular blockers have been discontinued. Repetitive nerve stimulation shows a decrement of the compound muscle action potential and, in most cases, establishes a disorder of neuromuscular transmission. With the recent epidemic of West Nile virus infection, a clinical syndrome of acute flaccid paralysis with several features indistinguishable from poliomyelitis has emerged. This article critically examines the clinical, electrophysiological, and pathological features of these and other acute neuromuscular syndromes that arise in the context of ICU care and summarizes the current understanding of the pathophysiology and treatment of these disorders.

Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease

To determine incidence, risk factors and impact on various outcome parameters of the development of acute quadriplegic myopathy in a selected population of critically ill patients. A prospective cohort study carried out in the intensive care unit of a tertiary-level university hospital. All patients admitted due to acute exacerbation of chronic obstructive pulmonary disease who required intubation and mechanical ventilation, and received high doses of intravenous corticosteroids. A neurophysiological study was performed in all cases at the onset of weaning. Muscular biopsy was taken when the neurophysiological study revealed a myopathic pattern. Twenty-six patients were enrolled in the study. Nine patients (34.6%) developed myopathy. Only seven patients were treated with muscle relaxants. Histology confirmed the diagnosis in the three patients who underwent muscle biopsy. APACHE II score at admission, the rate of sepsis and the total doses of corticosteroids were significantly higher in patients with myopathy compared with those patients that did not develop it. Myopathy is associated with an increase in the duration of mechanical ventilation [15.4 (9.2) versus 5.7 (3.9) days; p<0.006], the length of ICU stay [23.6 (10.7) versus 11.4 (7.05) days; p<0.003] and hospital stay [33.3 (19.2) versus 21.2 (16.1) days; p<0.034)]. Myopathy was not associated with increased mortality. In the population under study, severity of illness at admission, the development of sepsis and the total dose of corticosteroids are factors associated with the occurrence of myopathy after the administration of corticosteroids. Myopathy was associated with prolonged mechanical ventilation and in-hospital stay.

High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients

Prospective cohort study. Although Bracken et al have demonstrated a significant neuroprotective effect of high-dose intravenous (i.v.) methylprednisolone (MP) within 8 h post spinal cord injury (SCI), this practice has recently been challenged. We hypothesized it is possible that acute corticosteroid myopathy (ACM) may occur secondary to the MP. This pilot study was performed to test this hypothesis. University of Miami School of Medicine/Jackson Memorial Hospital, Miami VA Medical Center, FL, USA. Subjects included five nonpenetrating traumatic SCI patients, who received 24 h MP according to National Acute Spinal Cord Injury Studies (NASCIS) protocol, and three traumatic patients who suffered SCI and did not receive MP. Muscle biopsies and electromyography (EMG) were performed to determine if myopathic changes existed in these patients. Muscle biopsies from the SCI patients who received 24 h of MP showed muscle damage consistent with ACM in four out of five cases. EMG studies demonstrated myopathic changes in the MP-treated patients. In the three patients who had SCI but did not receive MP, muscle biopsies were normal and EMGs did not reveal evidence of myopathy. Our data suggest that MP in the dose recommended by the NASCIS may cause ACM. If this is true, part of the improvement of neurological recovery showed in NASCIS may be only a recording of the natural recovery of ACM, instead of any protection that MP offers to the injured spinal cord.