Unspecified Myopathy Research Articles

Anti-HMGCR myopathy: estimated five-fold higher incidence in Polynesian compared to European populations in Aotearoa New Zealand.

In 2014 the incidence of anti-HMGCR myopathy in New Zealand was ∼1.7 case/million persons/year. Re-estimate the population incidence and assess ethnic variation in those >40-year -olds. An incidence cohort was defined by seropositivity for immunoprecipitating anti-HMGCR autoantibodies tested at a national reference laboratory between 1 October 2019-30 September 2021.Separately, ethnicity standardized incidence in > 40-year-olds discharged from New Zealand public hospitals for idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9), was examined for concordance. The forty patients identified in the incidence cohort were all >40-years-old and all had a prior history of statin use. Annual incidence was 4 cases/million/year (95%CI 2.8-5.5). In those >40 years the incidence in Polynesians (Māori and Pacific peoples combined) was 25cases/million/year (95% CI 15.9 -40.1), in Asians 5.7cases/million/year (95% CI 0.7 -20.5) and in Europeans 7cases/million/year (95% CI 3.1 -8.4). The risk in statin users aged > 40 years was ∼1/9000 in Polynesians and ∼1/48000 in Europeans.Ethnic difference in incidence of idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9) was also found in hospital discharges. In the past half decade the estimated incidence of anti-HMGCR myopathy in New Zealand has doubled. Polynesian peoples of New Zealand >40-years-old have an estimated 5-fold higher risk compared with European and Asian peoples. The estimated absolute risk in statin users >40-year-olds was 108 cases/million/year in Polynesians vs 21 cases/million/year in Europeans.

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.

Patients susceptible to malignant hyperthermia (MH) may experience disabling manifestations of an unspecified myopathy outside the context of anesthesia, including myalgia, fatigue, or episodic rhabdomyolysis. Clinical observations suggest that oral dantrolene may relief myopathic symptoms in MH-susceptible (MHS) patients. However, high-dose oral dantrolene has been associated with severe hepatotoxicity. In a retrospective database review (1994-2018), we investigated a cohort of patients who were diagnosed as MHS by a positive caffeine-halothane contracture test (CHCT), had myopathic manifestations, and received oral dantrolene. Our aim was to investigate the occurrence of serious adverse effects and the adherence to oral dantrolene therapy. We also explored factors associated with self-reported clinical improvement, considering as nonresponders patients with intolerable adverse effects or who reported no improvement 8 weeks after starting treatment. Among 476 MHS patients with positive CHCT, 193 had muscle symptoms, 164 started oral dantrolene, 27 refused treatment, and 2 were excluded due to abnormal liver function before starting therapy. There were no serious adverse effects reported. Forty-six of 164 patients (28%; 95% confidence interval [CI], 22%-35%) experienced mild to moderate adverse effects. Twenty-two patients (22/164, 13%; 95% CI, 9%-19%) discontinued treatment, among which 16 due to adverse effects and 6 due to lack of improvement. One hundred forty-two patients (87%; 95% CI, 80%-90%) adhered to therapy and reported improvement of myalgia (n = 78), fatigue (n = 32), or rhabdomyolysis/hiperCKemia (n = 32). The proportion of responders was larger among patients with MH history than among those referred due to a clinical myopathy with nonpertinent anesthetic history (97% vs 79%, respectively; 95% CI of the difference, 8.5-28; P < .001). Patients with a sarcoplasmic reticulum Ca2+ release channel ryanodine receptor gene ( RYR1 ) variant had higher odds of responding to dantrolene treatment (OR, 6.4; 95% CI, 1.3-30.9; P = .013). Dantrolene median dose was 50 (25-400) and 200 (25-400) mg·day -1 in responders and nonresponders, respectively. We found that oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms. Our study provides dosing and adverse effect data as a basis for further randomized controlled clinical trials to determine the efficacy of oral dantrolene for symptomatic relief in MHS-related myopathies.

Diagnostic yield of exome sequencing in myopathies: Experience of a Slovenian tertiary centre.

BackgroundOur aim was to present the experience of systematic, routine use of next generation sequencing (NGS) in clinical diagnostics of myopathies.MethodsExome sequencing was performed on patients with high risk for inherited myopathy, which were selected based on the history of the disease, family history, clinical presentation, and diagnostic workup. Exome target capture was performed, followed by sequencing on HiSeq 2500 or MiSeq platforms. Data analysis was performed using internally developed bioinformatic pipeline.ResultsThe study comprised 86 patients, including 22 paediatric cases (26%). The largest group were patients referred with an unspecified myopathy (47%), due to non-specific or incomplete clinical and laboratory findings, followed by congenital myopathies (22%) and muscular dystrophies (22%), congenital myotonias (6%), and mitochondrial myopathies (3%). Altogether, a diagnostic yield was 52%; a high diagnostic rate was present in paediatric patients (64%), while in patients with unspecified myopathies the rate was 35%. We found 51 pathogenic/likely pathogenic variants in 23 genes and two pathogenic copy number variations.ConclusionOur results provide evidence that phenotype driven exome analysis diagnostic approach facilitates the diagnostic rate of complex, heterogeneous disorders, such as myopathies, particularly in paediatric patients and patients with unspecified myopathies.

Multicenter Targeted Population Screening of Late Onset Pompe Disease in Unspecified Myopathy Patients in Korea

Background: Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea.Methods: From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of &lt;i&gt;GAA&lt;/i&gt; gene.Results: Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T&gt;A [p.M439K] + c.2015G&gt;A [p.R672Q], c.1857C&gt;G [p.S619R] + c.546G&gt;C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele.Conclusions: This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Polymyositis: is there anything left? A retrospective diagnostic review from a tertiary myositis centre.

The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients. Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case. Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify. Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.

P.75Targeted population screening of late onset Pompe disease in unspecified myopathy patients with 8 neuromuscular centers in Korea

P.75Targeted population screening of late onset Pompe disease in unspecified myopathy patients with 8 neuromuscular centers in Korea

A case of generalized argyria presenting with muscle weakness

BackgroundArgyria is a rare irreversible cutaneous pigmentation disorder caused by prolonged exposure to silver. Herein, we report a case of generalized argyria that developed after chronic ingestion of soluble silver-nano particles and presented with muscle weakness.Case presentationA 74-year-old woman visited our emergency room, complaining of fever and mental deterioration. She was diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At presentation, diffuse slate gray-bluish pigmented patches were noticed on her face and nails. Two months prior to visiting our hospital, she was diagnosed with inflammatory myopathy and given steroid therapy at another hospital. We performed a nerve conduction study that revealed polyneuropathy. In skin biopsies from pigmented areas of the forehead and nose, the histopathologic results showed brown-black granules in basement membranes of sweat gland epithelia, which are diagnostic findings of argyria. We reviewed pathology slides obtained from the left thigh muscles and found markedly degenerated myofibers with disorganization of myofibrils without inflammatory reactions, consistent with unspecified myopathy, rather than inflammatory myopathy. The patient was diagnosed with generalized argyria with polyneuropathy and myopathy and transferred to a rehabilitation institution after being tapered off of steroids.ConclusionsClinicians should be aware of clinical manifestations of argyria and consider it in differential diagnosis when they examine patients who present with skin pigmentation and muscle weakness.

Screening for late-onset Pompe disease in western Denmark.

Late-onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha-glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark. Thus, patients with a diagnosis of unspecified myopathy were screened for LOPD. At seven neurological departments in the western part of Denmark, medical records were evaluated for all patients registered with myopathy diagnosis codes (ICD 10 codes: G 71.0-71.9 and G 72.0-72.9) during the period January 1, 2002, to December 31, 2012. If no specific diagnosis has been reached, patients were invited for screening. Dried blood spot (DBS) test was used to analyze the activity of the enzyme alpha-glucosidase. A total of 654 patients were identified. From the medical records, information was obtained concerning symptoms, family history, electromyography, muscle biopsy results and creatine kinase levels. Eighty-seven patients (13.3%) (males 61%) at a mean age of 53.3years (SD 16.5) fulfilled the criteria for screening. A DBS test was performed in 47 (54%) patients. In all patients, the enzyme activity was within reference values. None of the screened patients had a reduced activity of the enzyme alpha-glucosidase. Although the cohort studied was small, our findings do not suggest that LOPD is underdiagnosed in patients with unspecified myopathy in western Denmark.

Targeted population screening of late onset Pompe disease in unspecified myopathy patients for Korean population

We performed targeted population screening of late onset Pompe disease (LOPD) in unspecified myopathy patients, because early diagnosis is difficult due to its heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic patients who had one or more signs out of five LOPD-like clinical findings (proximal weakness, axial weakness, lingual weakness, respiratory difficulty, idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried blood spot and mixed leukocyte simultaneously. For a final diagnosis of LOPD, 16 patients with decreased enzyme activity were genotyped by GAA molecular analysis. We found two patients with LOPD (2.2%), and the remaining 14 patients had at least one G576S or E689K mutation, known as the pseudodeficiency allele. Acid alpha glucosidase activity of LOPD patients was significantly lower than that of patients with at least one pseudodeficiency allele (p = 0.017). This study is the first LOPD screening study for targeted Korean population, and more generally, an Asian population. Our findings suggest that for diagnosis of LOPD in Asian population, modified cutoff value of acid alpha glucosidase activity with dry blood spot considering that of patients having heterozygote pathogenic variants or pseudodeficiency alleles may reduce time and cost requirements and increase the comfort of patients.

Search for Pompe disease among patients with undetermined myopathies.

Pompe disease is a rare treatable glycogen storage disease with in adults - a limb-girdle muscle weakness. Muscle biopsy may fail to show the typical vacuolar myopathy. We asked if we had un-diagnosed patients with Pompe disease in western Sweden. We searched the muscle biopsy registry during the time period 1986 until 2006 including 3665 biopsies and included patients at our Neuromuscular Center with unspecified myopathy or limb-girdle muscular dystrophy. The dry blood spot test was used to identify patients with Pompe disease. A total of 82 patients (46 from the biopsy register and 36 from our center) were seen and dry blood spot test was obtained. No patient with Pompe disease was found. The dry blood spot test was low in three cases (11, 16, and 18% of normal) but a second blood sample showed a normal result based on GAA enzyme activity in lymphocytes in all three patients. In one patient with low normal result of the analysis in lymphocytes a genetic test showed no pathogenic mutations. Further investigation gave a definite diagnose of another myopathy in 12 patients. The prevalence of Pompe disease in western Sweden (3 in 1.27 million or 0.24 per 100.000 inhabitants) is lower than in the Netherlands and New York. Re-evaluation of patients with myopathies but without definite diagnosis is rewarding since 12 of 82 patients in our study had a definite molecular diagnosis after workup.

Statin-induced muscle toxicity and susceptibility to malignant hyperthermia and other muscle diseases: a population-based case-control study including 1st and 2nd degree relatives.

Case reports have suggested an association between susceptibility to malignant hyperthermia (MH) and other muscle diseases in subjects with statin-induced muscle toxicity. The aim of the study was to further scrutinize this association in a population-based case-control study including 1st and 2nd degree relatives. Spontaneously reported cases with muscle disorders associated with statin therapy until September 2006 were identified in the Swedish Adverse Drug Reaction Registry at the Medical Products Agency. For each case, ten population-based controls, matched on year of birth and gender, were randomly selected from the National Registry of Swedish Citizens. First and 2nd degree relatives to cases and controls were identified in the Swedish Multi-Generation Registry. ICD codes that could be associated with susceptibility to MH or other muscle diseases were chosen, and subjects were followed until December 2007 with regard to occurrence of selected ICD codes in the Swedish Registries for Cause of Death and Hospital Discharge Diagnoses, respectively. The chosen ICD codes were significantly overrepresented in case families compared with control families (RR 1.56; 95 % CI 1.15-2.10). The strongest associations were identified for a diagnosis of drug-induced or specified or unspecified myopathy (RR 52; 95 % CI 22-123) or a diagnosis of unspecified hyperthermia in combination with drug-induced or specified or unspecified myopathy (RR 30; 95 % CI 6-148). In contrast, a diagnosis of unspecified hyperthermia in the absence of drug-induced or specified or unspecified myopathy was significantly underrepresented among case families (RR 0.42; 95 % CI 0.23-0.76). In a case-control study including 1st and 2nd degree relatives, statin-induced muscle toxicity was significantly associated with a diagnosis of drug-induced or specified or unspecified myopathy and with a diagnosis of unspecified hyperthermia in combination with a diagnosis of drug-induced or specified or unspecified myopathy.

Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies

ObjectiveLate-onset Pompe disease is a rare, but potentially treatable metabolic myopathy, and therefore should not be overlooked. However, it is not unusual that patients go undiagnosed for many years. We hypothesized that patients with late-onset Pompe disease may have been overlooked in a population of patients with unclassified neuromuscular disease. MethodsWe used DBS (dried blood spots) to screen for Pompe disease in the two largest neuromuscular clinics and one of the main respiratory centers in Denmark. We selected patients with unclassified LGDM (limb-girdle muscular dystrophy), idiopathic elevation of creatine kinase, unexplained myopathy on muscle biopsy, unexplained restrictive respiratory insufficiency or unspecified myopathy for screening. Results177 patients were found eligible for inclusion, and 103 (58.2%) patients accepted screening. Three patients with Pompe disease were identified with DBS, and subsequent genetic testing revealed known pathogenic mutations in the GAA gene. All three patients were found among 38 patients with unclassified LGMD (8%). ConclusionOur findings indicate that a DBS should be considered early in the diagnostic work-up of patients with an LGMD phenotype, to rule out Pompe disease. Retrospectively, all 3 patients presented with “red flags” more compatible with Pompe disease than LGMD, including; 1) mild non-dystrophic, myopathic features on muscle biopsy, 2) creatine kinase levels below 1000, and 3) disproportionate axial and respiratory muscle involvement in comparison with limb muscle involvement.

Familial Risks for Diseases of Myoneural Junction and Muscle in Siblings Based on Hospitalizations and Deaths in Sweden

AbstractDiseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.

Familial Risks for Diseases of Myoneural Junction and Muscle in Siblings Based on Hospitalizations and Deaths in Sweden

Diseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.

Hyperkalemic Cardiac Arrest During Anesthesia in Infants and Children with Occult Myopathies

In 1992, the Malignant Hyperthermia Association of the United States and The North American Malignant Hyperthermia Registry received reports of cardiac arrest in apparently healthy children given succinylcholine. Using data from 1990 to 1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2) whether survival was associated with certain patient or treatment variables. We reviewed retrospectively all reports of pediatric (age < 18 years) arrests occurring within 24 hours of anesthesia. Etiology of arrests and presence of myopathy were determined. Twenty-five patients (92% male, median 45 months old) arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were evaluated by the anesthesiologist as being healthy with no personal or family history of myopathy. Serum potassium during arrest was measured in 18/25 (72%) patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%) returned to baseline neurologic function. A previously unrecognized Duchenne dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%) patients. Eight of these 12 patients' arrests were associated with hyperkalemia. Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No patient or treatment variables were statistically associated with survival. We conclude that, whenever possible, pediatricians should evaluate their patients (especially male infants and children) preoperatively for the presence of occult myopathy. During perianesthetic resuscitations, the pediatric advanced life support protocol should be modified to detect and treat hyperkalemia, a potentially reversible state even after prolonged resuscitation efforts. Following anesthetic deaths, pathologists should examine body fluid electrolytes and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine kinase screen for myopathy in male patients and restrictions on succinylcholine had been used, 64% of arrests and 60% of deaths might have been prevented. A formal prospective risk/benefit analysis for preventive measures is needed.

Obstetric aspects in women with facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, and congenital myopathies.

To increase the knowledge about pregnancy and delivery in women with certain muscle diseases, which is important for obstetric management and family planning of affected women. The obstetric histories of patients with facioscapulohumeral (FSH) muscular dystrophy, limb-girdle (LG) muscular dystrophy, and congenital myopathies (CM) were retrospectively evaluated using questionnaires and medical reports. The condition of 27 patients with different myopathies (FSH muscular dystrophy, n = 11; LG muscular dystrophy, n = 9; and CM, n = 7 [subdivided into 5 patients with central core disease, 1 patient with cytoplasmic bodies, and 1 patient with unspecified myopathy]) were ascertained from January 1, 1992, to December 31, 1994, through departments of neurology and human genetics, and the German self-support group for muscle diseases. Fifty-eight gestations resulting in 52 live births were reviewed. Miscarriages were reported in 3 of 26 gestations in 11 patients with FSH dystrophy, whereas 3 of 15 pregnancies in patients with LG dystrophy were terminated. Preterm births occurred in 2 patients with FSH dystrophy and in 3 patients with CM. Operative deliveries (vaginal operation or cesarean section) were performed in 6 of 23 gestations in patients with FSH dystrophy (1 emergency section), in 5 of 12 patients with LG dystrophy (2 emergency sections), and in 3 of 17 deliveries in patients with CM. Patients with FSH dystrophy generally coped well with their muscle disease in pregnancy and after delivery; however, 4 women were stated to have difficulties in caring for their families. The situation differed in LG dystrophy, where most women (5 of 9) experienced worsening of weakness in pregnancy and required assistance after delivery. In the patients with CM, 3 women experienced a deterioration during pregnancy, and 4 patients reported difficulties after delivery. No deleterious outcome of pregnancy and labor was observed in this series of patients with muscular dystrophy or CM, although operative deliveries were more frequent. A significant aggravation of symptoms in gestation is more likely to occur in patients with early-onset and progressive myopathy than in those with stable disease courses.

Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies.

In 1992, the Malignant Hyperthermia Association of the United States and The North American Malignant Hyperthermia Registry received reports of cardiac arrest in apparently healthy children given succinylcholine. Using data from 1990 to 1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2) whether survival was associated with certain patient or treatment variables. We reviewed retrospectively all reports of pediatric (age < 18 years) arrests occurring within 24 hours of anesthesia. Etiology of arrests and presence of myopathy were determined. Twenty-five patients (92% male, median 45 months old) arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were evaluated by the anesthesiologist as being healthy with no personal or family history of myopathy. Serum potassium during arrest was measured in 18/25 (72%) patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%) returned to baseline neurologic function. A previously unrecognized Duchenne dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%) patients. Eight of these 12 patients' arrests were associated with hyperkalemia. Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No patient or treatment variables were statistically associated with survival. We conclude that, whenever possible, pediatricians should evaluate their patients (especially male infants and children) preoperatively for the presence of occult myopathy. During perianesthetic resuscitations, the pediatric advanced life support protocol should be modified to detect and treat hyperkalemia, a potentially reversible state even after prolonged resuscitation efforts. Following anesthetic deaths, pathologists should examine body fluid electrolytes and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine kinase screen for myopathy in male patients and restrictions on succinylcholine had been used, 64% of arrests and 60% of deaths might have been prevented. A formal prospective risk/benefit analysis for preventive measures is needed.