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Uctepe E, Mancılar H, Esen FN, Unverengil GG, Vona B, Yesilyurt A. A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis. Am J Med Genet A 2025; 197:e63952. [PMID: 39687948 DOI: 10.1002/ajmg.a.63952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/21/2024] [Accepted: 11/16/2024] [Indexed: 12/18/2024]
Abstract
Rhabdomyolysis is a severe condition involving the breakdown of skeletal muscle fibers, leading to the release of muscle components into the bloodstream, which can lead to potential complications such as acute kidney injury and electrolyte imbalances. The etiology of rhabdomyolysis is multifactorial, encompassing traumatic, exertional, metabolic, infectious, toxic, and genetic causes. Genetic causes, including variants in LPIN1, RYR1, and CACNA1S, are increasingly recognized as significant contributors to recurrent rhabdomyolysis. MYH1 has recently been identified as a candidate gene for recurrent rhabdomyolysis with limited evidence originating from a single patient. In this report, we describe a 35-year-old male, born to consanguineous parents, who presented with recurrent rhabdomyolysis attacks, beginning at age 28, characterized by muscle pain, weakness, and episodes of acute kidney injury requiring dialysis. During attacks, the patient exhibited remarkably elevated markers of muscle breakdown and mildly elevated creatine kinase levels between episodes. A muscle biopsy revealed non-specific myopathic changes. Exome sequencing analysis was carried out and revealed a novel homozygous variant (NM_005963.4: c.1825G>A [p.Val609Met]) in MYH1 segregating in a manner compatible with an autosomal recessive pattern. In summary, this case provides confirmatory support for the role of pathogenic MYH1 variants in the pathogenesis of recurrent rhabdomyolysis and emphasizes the importance of comprehensive genetic testing in patients with unexplained recurrent episodes of muscle breakdown. Further cases are necessary to fully elucidate the genotypic and phenotypic spectrum of MYH1-related muscle disorders.
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Affiliation(s)
- Eyyup Uctepe
- Acibadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye
| | | | | | | | - Barbara Vona
- Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany
- Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany
| | - Ahmet Yesilyurt
- Acibadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye
- Acibadem Maslak Hospital, Istanbul, Türkiye
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Aminifard T, Mehri S, Khajavirad A, Moosavi Z, Hosseinian S, Hosseinzadeh H. Trans-sodium crocetinate attenuates acute kidney injury induced by rhabdomyolysis in rats: focusing on PI3K/AKT, apoptosis, and autophagy pathways. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03910-9. [PMID: 40080154 DOI: 10.1007/s00210-025-03910-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 02/10/2025] [Indexed: 03/15/2025]
Abstract
Rhabdomyolysis (RM) is a clinical disorder characterized by the release of potentially toxic muscle cell components into the bloodstream, with acute kidney injury (AKI). Trans-sodium crocetinate (TSC) is derived from the carotenoid crocetin known for its renoprotective, anti-inflammatory, and antioxidant properties. This study aimed to assess the protective effects of TSC on RM-induced AKI in rats. Six groups of rats (n = 6) were used: control, AKI (50% glycerol 10 mL/kg, intramuscularly), AKI treated with TSC (10, 20, and 40 mg/kg, intraperitoneally), and TSC (40 mg/kg) alone groups. Two days after the initial injection, urine and blood samples were collected over 24 h to investigate creatine phosphokinase (CPK), kidney function markers, and electrolyte levels. Additionally, kidney tissue was collected to assess renal oxidative markers, histological alterations, and the expression of protein markers related to autophagy, apoptosis, renal injury, inflammation, and the PI3K/AKT signaling pathway. After glycerol administration, there was an increase in oxidative stress, autophagy, apoptosis, renal injury, and inflammatory marker levels, accompanied by a decrease in the proteins of the PI3K/AKT signaling pathway in the kidney. The co-administration of TSC with glycerol resulted in the improvement of renal dysfunction and structural abnormalities, achieved through a reduction in oxidative stress. TSC also down-regulated autophagy, apoptotic, renal injury, and inflammatory markers. Furthermore, TSC treatment led to a decrease in the renal expression of PI3K/AKT signaling pathway proteins. In conclusion, TSC exhibited a protective effect against RM-induced AKI by modulating oxidative stress, autophagy, apoptosis, and the PI3K/AKT pathway.
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Affiliation(s)
- Tahereh Aminifard
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soghra Mehri
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Abolfazl Khajavirad
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Moosavi
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Sara Hosseinian
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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Selim OA, Sarcon AK, Tunaboylu MF, Zhao C, Moran SL. A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury. RESEARCH SQUARE 2025:rs.3.rs-5582098. [PMID: 39975916 PMCID: PMC11838728 DOI: 10.21203/rs.3.rs-5582098/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- & limb-threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. To date, studies that evaluated reperfusion injury-induced neuromuscular impairment rely on terminal ex vivo procedures and do not provide clinically translatable measurements. Furthermore, it is unclear if upper extremity musculature exhibits a different ischemic threshold compared to the lower limb given the relatively rare incidence of upper limb ischemia. Here, we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper extremity reperfusion injury and allows for monitoring in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS provided insights on gross motor and electrophysiological alterations upper-extremity reperfusion injury. We identify gait coordination parameters such as stride frequency and forelimb-hindlimb coordination index and electrophysiological metrics including compound muscle action potential amplitude as objective, non-invasive outcome measures for limb function assessment in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction.
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Affiliation(s)
- Omar A. Selim
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
- T32 Musculoskeletal Research Training Program, Mayo Clinic, Rochester, MN
| | | | | | - Chunfeng Zhao
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
| | - Steven L. Moran
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
- Division of Plastic Surgery, Mayo Clinic, Rochester, MN
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Ikanović A, Varshney K. Understanding rhabdomyolysis induced acute kidney injury in patients with COVID-19. World J Virol 2024; 13:101065. [PMID: 39722763 PMCID: PMC11551691 DOI: 10.5501/wjv.v13.i4.101065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/25/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024] Open
Abstract
This work comments on an article published in the recent issue of the World Journal of Virology. Rhabdomyolysis is a complex condition with symptoms such as myalgia, changes to urination, and weakness. With the potential for substantial kidney impairment, it has also been shown to be a severe complication of coronavirus disease 2019 (COVID-19). To date, various theoretical explanations exist for the development of rhabdomyolysis induced acute kidney injury (RIAKI) in COVID-19 infection, including the accumulation of released striated muscle myoglobin in the urine (myoglobinuria). In their article, they (2024) demonstrate in a retrospective study that RIAKI in COVID-19 patients tended to have elevated levels of C-reactive protein, ferritin, and procalcitonin. These patients also had poorer overall prognoses when compared to COVID-19 patients who have acute kidney injury (AKI) due to other causes. It is clear from these findings that clinicians must closely monitor and assess for the presence of rhabdomyolysis in COVID-19 patients who have developed AKIs. Moreover, additional research is required to further understand the mechanisms behind the development of RIAKI in COVID-19 patients in order to better inform treatment guidelines and protocols.
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Affiliation(s)
| | - Karan Varshney
- School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
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Bogomolova AP, Katrukha IA. Troponins and Skeletal Muscle Pathologies. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:2083-2106. [PMID: 39865025 DOI: 10.1134/s0006297924120010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 11/19/2024] [Accepted: 12/01/2024] [Indexed: 01/28/2025]
Abstract
Skeletal muscles account for ~30-40% of the total weight of human body and are responsible for its most important functions, including movement, respiration, thermogenesis, and glucose and protein metabolism. Skeletal muscle damage negatively impacts the whole-body functioning, leading to deterioration of the quality of life and, in severe cases, death. Therefore, timely diagnosis and therapy for skeletal muscle dysfunction are important goals of modern medicine. In this review, we focused on the skeletal troponins that are proteins in the thin filaments of muscle fibers. Skeletal troponins play a key role in regulation of muscle contraction. Biochemical properties of these proteins and their use as biomarkers of skeletal muscle damage are described in this review. One of the most convenient and sensitive methods of protein biomarker measurement in biological liquids is immunochemical analysis; hence, we examined the factors that influence immunochemical detection of skeletal troponins and should be taken into account when developing diagnostic test systems. Also, we reviewed the available data on the skeletal troponin mutations that are considered to be associated with pathologies leading to the development of diseases and discussed utilization of troponins as drug targets for treatment of the skeletal muscle disorders.
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Affiliation(s)
- Agnessa P Bogomolova
- Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
- Hytest Ltd., Turku, Finland
| | - Ivan A Katrukha
- Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia
- Hytest Ltd., Turku, Finland
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Willard J, Green K, Tsega T, Bathi S, Michael MB, Deonarine A. Severe Exertional Rhabdomyolysis in a Healthy 24-Year-Old Woman: A Case Report and Review of Literature. Cureus 2024; 16:e73545. [PMID: 39677125 PMCID: PMC11638380 DOI: 10.7759/cureus.73545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 11/10/2024] [Indexed: 12/17/2024] Open
Abstract
Rhabdomyolysis is characterized by the release of muscle cell components into circulation following muscle cell injury. Common causes include trauma and compression, exposure to drugs and toxins, and intense physical exercise. This study depicts a case of exercise-induced rhabdomyolysis following a cycling class. A 24-year-old African American woman presented to the emergency department with a one-day history of bilateral lower extremity myalgia, weakness, and stiffness, predominantly on the right side. She had participated in a one-hour morning cycling exercise class the previous day and came to the emergency department the following morning after noting dark-colored urine. Her initial creatine phosphokinase (CPK) level was 53,601 IU/L, leading to a diagnosis of exertional rhabdomyolysis. Her CPK continued to rise, peaking at 175,294 IU/L approximately 34 hours after admission. Serum chemistry, liver function, and clinical complications were closely monitored during the patient's hospitalization. The patient responded well to IV fluids, showed clinical improvement, and did not require additional interventions or specialist consultations. Exertional rhabdomyolysis is increasingly common following exercise and may lead to serious complications. Prognosis in rhabdomyolysis is best when treated early and aggressively.
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Affiliation(s)
- Jonathan Willard
- Internal Medicine, Howard University Hospital, Washington, DC, USA
| | - Kelsey Green
- Internal Medicine, Howard University Hospital, Washington, DC, USA
| | - Tenaadam Tsega
- Internal Medicine, Howard University Hospital, Washington, DC, USA
| | - Srilekha Bathi
- Internal Medicine, Howard University Hospital, Washington, DC, USA
| | - Miriam B Michael
- Internal Medicine, Howard University Hospital, Washington, DC, USA
- Internal Medicine, University of Maryland, Baltimore, USA
| | - Anand Deonarine
- Internal Medicine, Howard University Hospital, Washington, DC, USA
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Nawaz MY, Hamdani R, Siddiqui MK, Patel N, Shah K, Langdon L. Rhabdomyolysis Without Acute Kidney Injury in a 14-Year-Old Child With a Sedentary Lifestyle. Cureus 2024; 16:e73381. [PMID: 39659318 PMCID: PMC11630056 DOI: 10.7759/cureus.73381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/10/2024] [Indexed: 12/12/2024] Open
Abstract
A 14-year-old African American female patient presented to the emergency department with moderate right calf pain of unknown origin. The pain was present for a couple of days without radiation and progressed with an inability to bear weight. Physical examination revealed tenderness to palpation over the right calf. The patient had no history of overweight, trauma, infection, or extreme physical exertion. She took no medications, supplements, herbals, or used any illegal drugs. Of note, the patient was sedentary. Her blood work revealed elevated creatine kinase and liver enzymes, diagnostic of rhabdomyolysis. All other diagnostic evaluations, including EKG, chest X-ray, leg ultrasound, creatine kinase-MB, urinalysis, thyroid levels, and CBC were unremarkable. No other inherited conditions were identified in lab work. The patient was given dextrose 5% in water with sodium bicarbonate and switched to aggressive hydration via normal saline until discharge.
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Affiliation(s)
- Muhammad Y Nawaz
- College of Osteopathic Medicine, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - Raza Hamdani
- Pediatrics, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - Mishal K Siddiqui
- Pediatrics, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - Neel Patel
- Pediatrics, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - Khushmi Shah
- Pediatrics, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - Lori Langdon
- Pediatrics, Campbell School of Osteopathic Medicine, Lillington, USA
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Cheng B, Zhang H, Zhao W, Jiang S, Wu Z, Li H, Liu S, Zhang H. The highly hazardous veterinary drug "maduramicin" and its toxicokinetics in rats. Heliyon 2024; 10:e39620. [PMID: 39640695 PMCID: PMC11620213 DOI: 10.1016/j.heliyon.2024.e39620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 12/07/2024] Open
Abstract
Background Maduramicin (MAD) is an anticoccidial veterinary drug, but it frequently causes fatal poisonings in poultry, livestock, or humans. However, there is no specific antidote or guidance on first aid for MAD poisoning. Aim The aim of the present study is to evaluate the acute toxicity and toxicokinetics of MAD after oral exposure, so as to make a foundation for developing diagnostic and therapeutic protocols for human intoxication. Methods Five groups of rats (eight-to-nine-week-old male Wistar rats) were orally administered MAD via gavage at doses of 0, 4.64, 10.0, 21.5, or 46.4 mg/kg bw for only one time. The survival rates of the rats were observed over the following 14 days to assess acute toxicity. To evaluate the toxic effects of MAD, two doses (4.8 mg/kg bw and 10 mg/kg bw) were orally administered via gavage. Biochemical parameters including creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, serum myoglobin, and urinary myoglobin were measured. Liver, kidney, heart, and hind limb skeletal muscle samples from severely poisoned rats were obtained for pathological examination. For toxicokinetic analysis, samples of serum, urine, and feces from the 4.8 mg/kg bw dose group were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Results The LD50 of MAD in male Wistar rats was determined to be 6.81 mg/kg bw. In the 10 mg/kg bw group, elevated serum urea levels and increased myoglobin levels in both serum and urine indicated renal injury and potential muscle damage. Toxicokinetics in serum revealed that following oral administration of 4.8 mg/kg bw MAD, peak serum concentration of 59.8 ± 8.9 μg/L was achieved at 30.0 ± 13.9 h. MAD exhibited a slow elimination from the blood with an elimination half-life of 72.9 ± 36.8 h and a mean residence time of 79.6 ± 25.5 h. Additionally, fecal excretion of MAD was found to be greater than urinary excretion. Conclusion MAD is a highly toxic veterinary drug which requires careful handling. The primary effects of poisoning include kidney injury and suspected rhabdomyolysis. It is excreted very slowly after oral administration. Promoting toxin excretion in individuals poisoned by MAD could potentially serve as an effective treatment method until a specific antidote is identified.
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Affiliation(s)
- Bowen Cheng
- State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing 400038, China
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Huarui Zhang
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Wenjin Zhao
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Shaofeng Jiang
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Zhijun Wu
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Huiling Li
- Occupational Disease and Poisoning Department of Beijing Chaoyang Hospital, Beijing 100020, China
| | - Shuai Liu
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Hongshun Zhang
- State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing 400038, China
- State Key Laboratory of Trauma and Chemical Poisoning, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
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Breedlove A, Rohrschneider A, Virgilio R, Fleming JR. Recurrent Post-viral Rhabdomyolysis: A Case Report. Cureus 2024; 16:e70901. [PMID: 39497864 PMCID: PMC11534438 DOI: 10.7759/cureus.70901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/04/2024] [Indexed: 11/07/2024] Open
Abstract
Rhabdomyolysis is a relatively rare condition caused by the damage and release of myocyte contents. It occurs most commonly secondary to strenuous exercise. Rhabdomyolysis carries the risk of life-threatening negative sequelae such as acute kidney injury or death. This case report describes a middle-aged male patient who has presented with rhabdomyolysis five times over the past nine years, each following a viral illness. No inborn errors of metabolism, neuromuscular junction conditions, or myopathies were found to explain the patient's recurrent rhabdomyolysis except for two variants of unknown significance in the SYNE2 gene that has been linked with Emery-Dreifuss muscular dystrophy.
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Affiliation(s)
- Alyssa Breedlove
- Clinical, Biomedical, and Educational Research, Edward Via College of Osteopathic Medicine, Spartanburg, USA
| | - Ashton Rohrschneider
- Clinical, Biomedical, and Educational Research, Edward Via College of Osteopathic Medicine, Auburn, USA
| | - Richard Virgilio
- Clinical Affairs, Edward Via College of Osteopathic Medicine, Auburn, USA
| | - John R Fleming
- Family Medicine, Edward Via College of Osteopathic Medicine, Spartanburg, USA
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von Deneen KM, Alemayehu DG, Khosla A. Acute Compartment Syndrome and Rhabdomyolysis Caused by a Single Electrical Muscle Stimulation in a 46-Year-Old Female Professional Athlete With Fibromyalgia, Chronic Fatigue Syndrome, and Myofascial Disorder: A Case Report. Clin J Sport Med 2024; 34:506-508. [PMID: 38456638 PMCID: PMC11350174 DOI: 10.1097/jsm.0000000000001216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 11/07/2023] [Indexed: 03/09/2024]
Abstract
ABSTRACT Electrical muscle stimulation (EMS) training has been recognized as an effective modality for improving body composition, enhancing body strength, and facilitating injury recovery. However, individuals who are new to EMS training and those with certain chronic diseases should exercise caution due to the increased risk of rhabdomyolysis. This case report describes the occurrence of rhabdomyolysis and gluteal compartment syndrome following a single session of EMS training in a 46-year-old Caucasian female professional athlete. The patient was successfully managed with intensive intravenous fluid therapy and sodium bicarbonate supplementation, along with close monitoring of electrolytes and renal function. Electrical muscle stimulation training poses an increased risk of severe complications in individuals with chronic diseases and myopathy. Therefore, careful subject selection is required for EMS training in individuals with chronic diseases and myopathy to prevent common side effects. For individuals trying EMS training for the first time, it is recommended to avoid high-frequency EMS exercises.
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Affiliation(s)
- Karen M. von Deneen
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, PR China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of Trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, PR China;
| | - Dereje Gobena Alemayehu
- Department of Orthopedic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; and
| | - Ajit Khosla
- School of Advanced Materials and Nanotechnology, Xidian University, Xi'an, Shaanxi, PR China
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Abouzahir H, Belhouss A, Benyaich H. Postoperative rhabdomyolysis following otoplasty: an autopsy case report. Forensic Sci Med Pathol 2024; 20:990-998. [PMID: 37624532 DOI: 10.1007/s12024-023-00701-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 08/26/2023]
Abstract
Postoperative rhabdomyolysis is a significant complication that can arise from prolonged surgery, causing potential harm to the kidneys and leading to acute renal failure. Despite its importance, the incidence of rhabdomyolysis following ear reconstruction surgery remains undocumented in the literature. In this report, we present a case study of a male patient in his forties who underwent otoplasty for ear reconstruction after the amputation of his right ear due to a physical assault. The surgery lasted for 8 h under general anesthesia, and unfortunately, the patient developed postoperative rhabdomyolysis, which resulted in severe renal failure and ultimately an unrecoverable cardiac arrest, leading to his death. The autopsy findings indicated no identifiable lesions except for organ congestion, while histopathology revealed acute tubular necrosis of the kidney and muscle rhabdomyolysis. Previous literature has explored the association between surgical duration, location, and rhabdomyolysis, underscoring that this condition is an infrequent yet preventable consequence of prolonged surgery. The co-occurrence of rhabdomyolysis and acute renal injury in this case suggests the presence of comorbidity, emphasizing the need for prompt action to mitigate the negative consequences of rhabdomyolysis. Awareness and early intervention are crucial in preventing and managing this condition effectively.
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Affiliation(s)
- Hind Abouzahir
- Medicolegal Institute, Ibn Rochd University Hospital, Casablanca, Morocco.
- Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco.
| | - Ahmed Belhouss
- Medicolegal Institute, Ibn Rochd University Hospital, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - Hicham Benyaich
- Medicolegal Institute, Ibn Rochd University Hospital, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
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Skolka MP, Milone M, Litchy WJ, Laughlin RS, Rubin DI, Liewluck T. The utility of electrodiagnostic testing in unprovoked rhabdomyolysis in the era of next-generation sequencing. Muscle Nerve 2024; 70:180-186. [PMID: 38533679 DOI: 10.1002/mus.28087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 03/03/2024] [Accepted: 03/10/2024] [Indexed: 03/28/2024]
Abstract
INTRODUCTION/AIMS Rhabdomyolysis is an etiologically heterogeneous, acute necrosis of myofibers characterized by transient marked creatine kinase (CK) elevation associated with myalgia, muscle edema, and/or weakness. The study aimed to determine the role of electrodiagnostic (EDX) testing relative to genetic testing and muscle biopsy in patients with unprovoked rhabdomyolysis in identifying an underlying myopathy. METHODS EDX database was reviewed to identify unprovoked rhabdomyolysis patients who underwent EDX testing between January 2012 and January 2022. Each patient's clinical profile, EDX findings, muscle pathology, laboratory, and genetic testing results were analyzed. RESULTS Of 66 patients identified, 32 had myopathic electromyography (EMG). Muscle biopsy and genetic testing were performed in 41 and 37 patients, respectively. A definitive diagnosis was achieved in 15 patients (11 myopathic EMG and 4 nonmyopathic EMG; p = .04) based on abnormal muscle biopsy (4/11 patients) or genetic testing (12/12 patients, encompassing 5 patients with normal muscle biopsy and 3 patients with nonmyopathic EMG). These included seven metabolic and eight nonmetabolic myopathies (five muscular dystrophies and three ryanodine receptor 1 [RYR1]-myopathies). Patients were more likely to have baseline weakness (p < .01), elevated baseline CK (p < .01), and nonmetabolic myopathies (p = .03) when myopathic EMG was identified. DISCUSSION Myopathic EMG occurred in approximately half of patients with unprovoked rhabdomyolysis, more likely in patients with weakness and elevated CK at baseline. Although patients with myopathic EMG were more likely to have nonmetabolic myopathies, nonmyopathic EMG did not exclude myopathy, and genetic testing was primarily helpful to identify an underlying myopathy. Genetic testing should likely be first-tier diagnostic testing following unprovoked rhabdomyolysis.
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Affiliation(s)
| | | | | | | | - Devon I Rubin
- Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
| | - Teerin Liewluck
- Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
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Mathew GG, Jayaprakash V. Hashimoto's thyroiditis masquerading as acute tubular injury and rhabdomyolysis. J Bras Nefrol 2024; 46:e20240022. [PMID: 39132944 DOI: 10.1590/2175-8239-jbn-2024-0022pt] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 06/23/2024] [Indexed: 12/21/2024] Open
Abstract
Hashimoto's thyroiditis manifesting as hypothyroidism has been implicated in glomerular disorders due to autoantibody formation. Here we present the case of a 26-year-old male without any comorbidities presenting with easy fatiguability and weight gain for 2 months. He was found to have a creatinine of 2.1 mg/dL with a history of rhinitis treated with anti-histaminic three days prior to the hospital visit. He had symptoms of intermittent myalgia for the past two weeks. On laboratory evaluation, he was found to have raised CPK, elevated TSH, low normal T4, and positive anti-TPO and anti-Tg antibodies. Neck ultrasound revealed linear echogenic septations in the thyroid gland. Renal biopsy revealed acute tubular injury. Appropriate thyroxine supplementation was started and his creatinine decreased to 1.2 mg/dL after 1 month. It is important that clinicians should be aware of this rare kidney presentation in Hashimoto's thyroiditis.
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Affiliation(s)
- Gerry George Mathew
- SRM Medical College Hospital and Research Centre, Department of Nephrology, Chengalpattu, India
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Mathew GG, Jayaprakash V. Hashimoto's thyroiditis masquerading as acute tubular injury and rhabdomyolysis. J Bras Nefrol 2024; 46:e20240022. [PMID: 39132944 PMCID: PMC11318353 DOI: 10.1590/2175-8239-jbn-2024-0022en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 06/23/2024] [Indexed: 08/13/2024] Open
Abstract
Hashimoto's thyroiditis manifesting as hypothyroidism has been implicated in glomerular disorders due to autoantibody formation. Here we present the case of a 26-year-old male without any comorbidities presenting with easy fatiguability and weight gain for 2 months. He was found to have a creatinine of 2.1 mg/dL with a history of rhinitis treated with anti-histaminic three days prior to the hospital visit. He had symptoms of intermittent myalgia for the past two weeks. On laboratory evaluation, he was found to have raised CPK, elevated TSH, low normal T4, and positive anti-TPO and anti-Tg antibodies. Neck ultrasound revealed linear echogenic septations in the thyroid gland. Renal biopsy revealed acute tubular injury. Appropriate thyroxine supplementation was started and his creatinine decreased to 1.2 mg/dL after 1 month. It is important that clinicians should be aware of this rare kidney presentation in Hashimoto's thyroiditis.
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Affiliation(s)
- Gerry George Mathew
- SRM Medical College Hospital and Research Centre, Department of Nephrology, Chengalpattu, India
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15
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Tawhari M, Aldalaan A, Alanazi R, Aldharman S, Alnafisah T, Alawad N, Alhejji AM, Alhabeeb AY, Alhamadh MS. Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience. Saudi Med J 2024; 45:510-517. [PMID: 38734436 PMCID: PMC11147551 DOI: 10.15537/smj.2024.45.5.20230560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 04/12/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVES To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.
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Affiliation(s)
- Mohammed Tawhari
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Abdulaziz Aldalaan
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Rahaf Alanazi
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Sarah Aldharman
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Turki Alnafisah
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Nawaf Alawad
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Abdullah M. Alhejji
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Abdulrahman Yousef Alhabeeb
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Moustafa S. Alhamadh
- From the Department of Medicine (Tawhari), King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs; from the College of Medicine (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs; and from King Abdullah International Medical Research Center (Tawhari, Aldalaan, Alanazi, Aldharman, Alawad, Alhejji, Alhabeeb, Alhamadh), Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.
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Fink NS, Abubshait L, Deshisky A. Anti-HMGCR (Hydroxy-3-Methylglutaryl-CoA Reductase) Myopathy: A Rare Cause of Proximal Muscle Weakness. Cureus 2024; 16:e61094. [PMID: 38919212 PMCID: PMC11197700 DOI: 10.7759/cureus.61094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2024] [Indexed: 06/27/2024] Open
Abstract
Idiopathic inflammatory myopathy (IIM) represents a rare group of autoimmune conditions resulting in muscle weakness and includes polymyositis, dermatomyositis, immune-mediated necrotizing myopathy (IMNM), overlap myositis, and inclusion body myositis. Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody IMNM represents a rare but increasingly recognized subtype of IIM. Here we report a case of a 65-year-old woman on rosuvastatin who presented with two months of progressive proximal muscle weakness, significant truncal weakness, and elevated creatine kinase concerning for rhabdomyolysis and inflammatory myopathy. The patient was eventually diagnosed on day 8 of her hospital stay with anti-HMGCR antibody IMNM after delayed testing for this specific myopathy. Increased awareness of this IIM subtype, as well as its risk factors and presenting features, might improve rapidity of testing and shorten hospital stays if the diagnosis is considered in the emergency department or early in the hospital course.
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Affiliation(s)
- Nicolas S Fink
- Emergency Medicine, Jefferson Einstein Montgomery Hospital, East Norriton, USA
| | - Layla Abubshait
- Emergency Medicine, Jefferson Einstein Montgomery Hospital, East Norriton, USA
| | - Amanda Deshisky
- Emergency Medicine, Jefferson Einstein Montgomery Hospital, East Norriton, USA
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17
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Akar HT, Yıldız Y, Mutluay R, Tekin E, Tokatlı A. Adult-onset carnitine palmitoyl transferase II (CPT II) deficiency presenting with rhabdomyolysis and acute kidney injury. CEN Case Rep 2024; 13:81-85. [PMID: 37341884 PMCID: PMC10982194 DOI: 10.1007/s13730-023-00804-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 06/12/2023] [Indexed: 06/22/2023] Open
Abstract
Metabolic myopathies are among the treatable causes of rhabdomyolysis and myoglobinuria. Carnitine palmitoyl transferase 2 (CPT II) deficiency is one of the most common causes of recurrent myoglobinuria in adults. It is an inherited disorder of fatty acid oxidation pathway, commonly associated with elevated acylcarnitine levels. In this case report, we present a 49-year-old male patient who developed acute kidney injury after rhabdomyolysis and was thus diagnosed with CPT2 deficiency after his first episode of rhabdomyolysis. Inborn errors of metabolism should be kept in mind in patients with rhabdomyolysis. Acylcarnitine profile may be normal in CPT II deficiency, even during an acute attack, and molecular genetic diagnostics should be applied if there is high index of clinical suspicion.
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Affiliation(s)
- Halil Tuna Akar
- Department of Pediatrics, Pediatric Metabolism Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey.
| | - Yılmaz Yıldız
- Department of Pediatrics, Pediatric Metabolism Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Rüya Mutluay
- Department of Internal Medicine, Nephrology Unit, Osmangazi University Faculty of Medicine, Eskişehir, Turkey
| | - Emel Tekin
- Department of Pathology, Osmangazi University Faculty of Medicine, Eskişehir, Turkey
| | - Ayşegül Tokatlı
- Department of Pediatrics, Pediatric Metabolism Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey
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18
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Sivadasan A, Cortel-LeBlanc MA, Cortel-LeBlanc A, Katzberg H. Peripheral nervous system and neuromuscular disorders in the emergency department: A review. Acad Emerg Med 2024; 31:386-397. [PMID: 38419365 DOI: 10.1111/acem.14861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 11/30/2023] [Accepted: 12/21/2023] [Indexed: 03/02/2024]
Abstract
INTRODUCTION Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies. METHODS An extensive literature search was performed to identify relevant studies. We prioritized meta-analysis, systematic reviews, and position statements where possible to inform any recommendations. SUMMARY The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain-Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders. CONCLUSIONS Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician.
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Affiliation(s)
- Ajith Sivadasan
- Ellen & Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Miguel A Cortel-LeBlanc
- Department of Emergency Medicine, Queensway Carleton Hospital, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Institut du Savoir Montfort, Ottawa, Ontario, Canada
- 360 Concussion Care, Ottawa, Ontario, Canada
| | - Achelle Cortel-LeBlanc
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Institut du Savoir Montfort, Ottawa, Ontario, Canada
- 360 Concussion Care, Ottawa, Ontario, Canada
- Division of Neurology, Department of Medicine, Queensway Carleton Hospital, Ottawa, Ontario, Canada
| | - Hans Katzberg
- Ellen & Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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19
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Ren M, Sambuughin N, Mungunshukh O, Edgeworth DB, Hupalo D, Zhang X, Wilkerson MD, Dalgard CL, O’Connor FG, Deuster PA. Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans. Genes (Basel) 2024; 15:408. [PMID: 38674343 PMCID: PMC11049803 DOI: 10.3390/genes15040408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/22/2024] [Accepted: 03/22/2024] [Indexed: 04/28/2024] Open
Abstract
Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.
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Affiliation(s)
- Mingqiang Ren
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
- Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
| | - Nyamkhishig Sambuughin
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
- Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
| | - Ognoon Mungunshukh
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
- Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- Department of Anatomy, Physiology, and Genetics, Center for Military Precision Health, Uniformed Services University, Bethesda, MD 20814, USA
| | - Daniel Baxter Edgeworth
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
- Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
| | - Daniel Hupalo
- Department of Anatomy, Physiology, and Genetics, Center for Military Precision Health, Uniformed Services University, Bethesda, MD 20814, USA
| | - Xijun Zhang
- Department of Anatomy, Physiology, and Genetics, Center for Military Precision Health, Uniformed Services University, Bethesda, MD 20814, USA
| | - Matthew D. Wilkerson
- Department of Anatomy, Physiology, and Genetics, Center for Military Precision Health, Uniformed Services University, Bethesda, MD 20814, USA
| | - Clifton L. Dalgard
- Department of Anatomy, Physiology, and Genetics, Center for Military Precision Health, Uniformed Services University, Bethesda, MD 20814, USA
| | - Francis G. O’Connor
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
| | - Patricia A. Deuster
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA (D.B.E.); (F.G.O.)
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20
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Safari S, Ghasemi M, Yousefifard M, Ghasemi A, Najafi I. Uric acid in predicting the traumatic rhabdomyolysis induced acute kidney injury; a systematic review and meta-analysis. BMC Nephrol 2024; 25:82. [PMID: 38443920 PMCID: PMC10916315 DOI: 10.1186/s12882-024-03509-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/17/2024] [Indexed: 03/07/2024] Open
Abstract
OBJECTIVE The objective of this systematic review and meta-analysis was to assess the value of uric acid in predicting acute kidney injury caused by traumatic rhabdomyolysis. METHODS The search was conducted in MEDLINE, Scopus, Embase and Web of Science until November 1, 2023. Based on the inclusion and exclusion criteria, the articles were included by two independent researchers. Data regarding study design, patient characteristics, number of patients with and without AKI, mean and SD of uric acid and prognostic characteristics of uric acid were extracted from relevant studies. STATA version 17.0 was used to compute pooled measures of standardized mean differences, odds ratios, and diagnostic accuracy. I2 and chi-square tests were used to assess heterogeneity between studies. RESULTS We found 689 non-redundant studies, 44 of them were potentially relevant. Six articles met the inclusion criteria and were included in the review. The results of the meta-analysis confirmed that there was a significant correlation between serum uric acid levels and the occurrence of AKI (SMD = 1.61, 95% CI = 0.69 to 2.54, I2 = 96.94%; p value = 0.001). There were no significant publication biases. CONCLUSION According to this meta-analysis, uric acid levels could be considered as a predictor of acute kidney injury following traumatic rhabdomyolysis.
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Affiliation(s)
- Saeed Safari
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Emergency Department, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammadreza Ghasemi
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mahmoud Yousefifard
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Ghasemi
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Iraj Najafi
- Nephrology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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21
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Belk MG, Ku PM, George DL, Hobbs ALV. Rhabdomyolysis Suspected to be Caused by Eravacycline Therapy: A Case Report. J Pharm Pract 2024; 37:239-242. [PMID: 36656727 DOI: 10.1177/08971900221117872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Eravacycline is approved by the U.S. Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections. It is a novel, fully synthetic fluorocycline antibiotic belonging to the tetracycline class with a broad-spectrum of activity and an appealing side effect profile. This report describes a 74-year-old female who presented to the hospital with non-ST-elevation myocardial infarction (NSTEMI) requiring coronary artery bypass graft surgery. After surgery, she developed a sternal wound infection that grew multidrug resistant organisms, leading to a much longer than anticipated hospital stay. Eravacycline was eventually added to the antimicrobial regimen for the persistent infection. Shortly after therapy with eravacycline began, the patient started experiencing muscle pain and the creatine phosphokinase (CPK) level was noted to be elevated. Other causes, such as concomitant administration of an HMG-CoA reductase inhibitor, were explored in this case but not thought to be the cause of rhabdomyolysis. The patient's CPK dropped considerably upon discontinuation of the novel antibiotic, and symptoms resolved. The adverse drug event was reported to the drug manufacturer; however, there are no reports up until this time that address a possible relationship between eravacycline administration and the development of rhabdomyolysis.
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Affiliation(s)
- Madeline G Belk
- Department of Pharmacy, Huntsville Hospital, Huntsville, AL, USA
| | - Pam M Ku
- Department of Pharmacy, Augusta University Medical Center, Augusta, GA, USA
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22
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Gkiourtzis N, Tramma D, Papadopoulou-Legbelou K, Moutafi M, Evangeliou A. Α rare case of myopathy, lactic acidosis, and severe rhabdomyolysis, due to a homozygous mutation of the ferredoxin-2 (FDX2) gene. Am J Med Genet A 2023; 191:2843-2849. [PMID: 37565517 DOI: 10.1002/ajmg.a.63368] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/26/2023] [Accepted: 07/29/2023] [Indexed: 08/12/2023]
Abstract
Mitochondrial myopathy is a severe metabolic myopathy related to nuclear or mitochondrial DNA dysfunction. We present a rare case of mitochondrial myopathy, presented with multiple episodes of proximal muscle weakness, lactic acidosis, and severe rhabdomyolysis (CPK 319,990 U/L, lactic acid 22.31 mmol/L, and GFR 3.82 mL/min/1.73m2 ). She was hospitalized in the pediatric intensive care unit due to acute kidney injury, elevated blood pressure, and deterioration of respiratory and cardiac function. Investigation for inherited metabolic disorders showed elevated levels of ammonia, lactic acid to pyruvic acid ratio, and urine ketone bodies. Exome sequencing detected a homozygous pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) and a heterozygous variant of uncertain significance in MSTO1 (ENST00000538143:p.Leu137Pro/c.410 T > C). After Sanger sequencing, the p.Met4Leu pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) was identified in a heterozygous state in both her parents and sister. Recently, pathogenic variants in the FDX2 gene have been associated with mitochondrial myopathy, lactic acidosis, optic atrophy, and leukoencephalopathy. Only four reports of FDX2-related rhabdomyolysis have been described before, but none of the previous patients had hyperammonemia. This is a rare case of severe mitochondrial myopathy in a pediatric patient related to a pathogenic FDX2 variant, suggesting the need for genetic analysis of the FDX2 gene in cases of suspicion of mitochondrial myopathies.
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Affiliation(s)
- Nikolaos Gkiourtzis
- 4th Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Despoina Tramma
- 4th Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kyriaki Papadopoulou-Legbelou
- 4th Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Moutafi
- 4th Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios Evangeliou
- 4th Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Nasello M, Ippolito M, Federico A, Ronga F, Di Fede A, Campanella S, Accetta S, Gargano A, Scrudato GL, Urso L, Giarratano A, Cortegiani A. Rhabdomyolysis as cause, consequence, or mimicker of myocardial infarction: A case report. Clin Case Rep 2023; 11:e8133. [PMID: 37927986 PMCID: PMC10622404 DOI: 10.1002/ccr3.8133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/16/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023] Open
Abstract
Key Clinical Message A timely diagnosis is essential to start appropriate therapy and to reduce risks of life-threatening complications of rhabdomyolysis. Some cases can undergo differential diagnosis with other clinical conditions, e.g., myocardial infarction. Abstract We present the case of a 65-years-old male who was admitted to the emergency department with a clinical presentation related to myocardial infarction. The patient underwent coronary angioplasty and was then admitted to ICU due to hemodynamical instability, elevated potassium levels, and anuria. Further investigations revealed rhabdomyolysis. The patient received vasopressors, oxygenation support and renal replacement therapy. Outcomes at ICU discharge were favorable. The temporal association between rhabdomyolysis and myocardial infarction, together with an unclear pathophysiological relationship, made differential diagnosis difficult. We discuss this uncertainty in light of published literature.
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Affiliation(s)
- Marina Nasello
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Mariachiara Ippolito
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
- Department of Anesthesia, Intensive Care, and Emergency Policlinico Paolo GiacconeUniversity of PalermoPalermoItaly
| | - Antonino Federico
- Department of Anesthesia, Intensive Care, and Emergency Policlinico Paolo GiacconeUniversity of PalermoPalermoItaly
| | - Fiammetta Ronga
- Department of Anesthesia, Intensive Care, and Emergency Policlinico Paolo GiacconeUniversity of PalermoPalermoItaly
| | - Antonino Di Fede
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Salvatore Campanella
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Sara Accetta
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Alessandra Gargano
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Giulia Lo Scrudato
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Lucrezia Urso
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
| | - Antonino Giarratano
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
- Department of Anesthesia, Intensive Care, and Emergency Policlinico Paolo GiacconeUniversity of PalermoPalermoItaly
| | - Andrea Cortegiani
- Department of Surgical, Oncological, and Oral Science (Di.Chir.On.S.)University of PalermoPalermoItaly
- Department of Anesthesia, Intensive Care, and Emergency Policlinico Paolo GiacconeUniversity of PalermoPalermoItaly
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Luo Y, Liu C, Li D, Yang B, Shi J, Guo X, Fan H, Lv Q. Progress in the Diagnostic and Predictive Evaluation of Crush Syndrome. Diagnostics (Basel) 2023; 13:3034. [PMID: 37835777 PMCID: PMC10572195 DOI: 10.3390/diagnostics13193034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/15/2023] [Accepted: 09/15/2023] [Indexed: 10/15/2023] Open
Abstract
Crush syndrome (CS), also known as traumatic rhabdomyolysis, is a syndrome with a wide clinical spectrum; it is caused by external compression, which often occurs in earthquakes, wars, and traffic accidents, especially in large-scale disasters. Crush syndrome is the second leading cause of death after direct trauma in earthquakes. A series of clinical complications caused by crush syndrome, including hyperkalemia, myoglobinuria, and, in particular, acute kidney injury (AKI), is the main cause of death in crush syndrome. The early diagnosis of crush syndrome, the correct evaluation of its severity, and accurate predictions of a poor prognosis can provide personalized suggestions for rescuers to carry out early treatments and reduce mortality. This review summarizes various methods for the diagnostic and predictive evaluation of crush syndrome, including urine dipstick tests for a large number of victims, traditional and emerging biomarkers, imaging-assisted diagnostic methods, and developed evaluation models, with the aim of providing materials for scholars in this research field.
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Affiliation(s)
- Yu Luo
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Chunli Liu
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Duo Li
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Bofan Yang
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Jie Shi
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Xiaoqin Guo
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Haojun Fan
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
| | - Qi Lv
- Institution of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; (Y.L.)
- Key Laboratory of Medical Rescue Key Technology and Equipment, Ministry of Emergency Management, Wenzhou 325000, China
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Christison KS, Sol JA, Gurney SC, Dumke CL. Twenty-Four Percent of Wildland Firefighters Reach Critical Levels of Serum Creatine Kinase During 80-Hour Critical Training. Wilderness Environ Med 2023; 34:334-340. [PMID: 37258394 DOI: 10.1016/j.wem.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 03/03/2023] [Accepted: 04/10/2023] [Indexed: 06/02/2023]
Abstract
INTRODUCTION Wildland firefighters (WLFFs) must undergo a 2-wk critical training (CT) period prior to deployment to the field. This stress may result in clinical risks, including severe muscle damage and rhabdomyolysis. We aimed to document the effects of WLFFs' CT on physiologic markers of muscle damage and soreness. METHODS Two interagency hotshot crews (n=25) were followed during spring 2022 for 80 h of training. Activity counts as well as records of upper-body (US) and lower-body (LS) muscle soreness were collected daily. Body weight (BW) and skinfold measurements were recorded on Day 1 (D1) and D11 to estimate body fat (BF) and lean body weight (LBW). Blood was collected on D1 and D11 to measure muscle and liver damage markers. RESULTS Critical training resulted in significant elevations in creatine kinase (CK) (216.9±57.4 U/L vs 5166.4±1927.8 U/L, P=0.017) and lactate dehydrogenase (LDH) (175.5±4.0 IU/L vs 340.0±42.6 IU/L, P=0.001) despite no significant changes in BW, BF, LBW, cortisol, or testosterone. Main effects of time were seen in US and LS, peaking on D11 (US: 5.2±0.4 cm, P<0.001; LS: 5.5±0.4 cm, P<0.001). Those who spent the most minutes with activity counts of >1500 counts/min showed the greatest increase in CK and LDH. CONCLUSIONS These data suggest that WLFFs undergo significant physiologic stressors, resulting in muscle soreness and damage during CT, with 6 of the 25 subjects reaching critical levels of serum CK. It appears that much of the muscle damage and soreness occurred because of unaccustomed WLFF job-specific tasks.
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Affiliation(s)
- Katherine S Christison
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT
| | - Joseph A Sol
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT; United States Department of Agriculture, Forest Service, National Technology and Development Program, Missoula, MT
| | - Shae C Gurney
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT
| | - Charles L Dumke
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT.
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26
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Batten K, Bhattacharya K, Simar D, Broderick C. Exercise testing and prescription in patients with inborn errors of muscle energy metabolism. J Inherit Metab Dis 2023; 46:763-777. [PMID: 37350033 DOI: 10.1002/jimd.12644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/02/2023] [Accepted: 06/21/2023] [Indexed: 06/24/2023]
Abstract
Skeletal muscle is a dynamic organ requiring tight regulation of energy metabolism in order to provide bursts of energy for effective function. Several inborn errors of muscle energy metabolism (IEMEM) affect skeletal muscle function and therefore the ability to initiate and sustain physical activity. Exercise testing can be valuable in supporting diagnosis, however its use remains limited due to the inconsistency in data to inform its application in IEMEM populations. While exercise testing is often used in adults with IEMEM, its use in children is far more limited. Once a physiological limitation has been identified and the aetiology defined, habitual exercise can assist with improving functional capacity, with reports supporting favourable adaptations in adult patients with IEMEM. Despite the potential benefits of structured exercise programs, data in paediatric populations remain limited. This review will focus on the utilisation and limitations of exercise testing and prescription for both adults and children, in the management of McArdle Disease, long chain fatty acid oxidation disorders, and primary mitochondrial myopathies.
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Affiliation(s)
- Kiera Batten
- School of Health Sciences, University of New South Wales, Sydney, Australia
- The Children's Hospital at Westmead, Sydney, Australia
| | - Kaustuv Bhattacharya
- The Children's Hospital at Westmead, Sydney, Australia
- School of Clinical Medicine, University of New South Wales, Sydney, Australia
| | - David Simar
- School of Health Sciences, University of New South Wales, Sydney, Australia
| | - Carolyn Broderick
- School of Health Sciences, University of New South Wales, Sydney, Australia
- The Children's Hospital at Westmead, Sydney, Australia
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27
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Labella B, Lanzi G, Cotti Piccinelli S, Caria F, Damioli S, Risi B, Bertella E, Poli L, Padovani A, Filosto M. Juvenile-Onset Recurrent Rhabdomyolysis Due to Compound Heterozygote Variants in the ACADVL Gene. Brain Sci 2023; 13:1178. [PMID: 37626534 PMCID: PMC10452278 DOI: 10.3390/brainsci13081178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/30/2023] [Accepted: 08/06/2023] [Indexed: 08/27/2023] Open
Abstract
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive long-chain fatty acid oxidation disorder caused by mutations in the ACADVL gene. The myopathic form presents with exercise intolerance, exercise-related rhabdomyolysis, and muscle pain, usually starting during adolescence or adulthood. We report on a 17-year-old boy who has presented with exercise-induced muscle pain and fatigue since childhood. In recent clinical history, episodes of exercise-related severe hyperCKemia and myoglobinuria were reported. Electromyography was normal, and a muscle biopsy showed only "moth-eaten" fibers, and a mild increase in lipid storage in muscle fibers. NGS analysis displayed the already known heterozygote c.1769G>A variant and the unreported heterozygote c.523G>C change in ACADVL both having disease-causing predictions. Plasma acylcarnitine profiles revealed high long-chain acylcarnitine species levels, especially C14:1. Clinical, histopathological, biochemical, and genetic tests supported the diagnosis of VLCAD deficiency. Our report of a novel pathogenic missense variant in ACADVL expands the allelic heterogeneity of the disease. Since dietary treatment is the only therapy available for treating VLCAD deficiency and it is more useful the earlier it is started, prompt diagnosis is essential in order to minimize muscle damage and slow the disease progression.
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Affiliation(s)
- Beatrice Labella
- Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy; (B.L.); (S.C.P.); (A.P.)
- Unit of Neurology, ASST “Spedali Civili”, 25100 Brescia, Italy;
| | - Gaetana Lanzi
- Medical Genetics Laboratory, Diagnostic Department, ASST-Pedali Civili of Brescia, 25100 Brescia, Italy;
| | - Stefano Cotti Piccinelli
- Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy; (B.L.); (S.C.P.); (A.P.)
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
| | - Filomena Caria
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
| | - Simona Damioli
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
| | - Barbara Risi
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
| | - Enrica Bertella
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
| | - Loris Poli
- Unit of Neurology, ASST “Spedali Civili”, 25100 Brescia, Italy;
| | - Alessandro Padovani
- Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy; (B.L.); (S.C.P.); (A.P.)
- Unit of Neurology, ASST “Spedali Civili”, 25100 Brescia, Italy;
| | - Massimiliano Filosto
- Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy; (B.L.); (S.C.P.); (A.P.)
- NeMO—Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy; (F.C.); (S.D.); (B.R.); (E.B.)
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28
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Toeback J, de Pagter M, Exalto L, Koop K, Van der Heijden J. Rhabdomyolysis, encephalopathy, epilepsy and cardiac arrhythmia. Pract Neurol 2023; 23:356-359. [PMID: 37116950 DOI: 10.1136/pn-2023-003715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/11/2023] [Indexed: 04/30/2023]
Affiliation(s)
- Jonas Toeback
- Intensive Care, UMC, Utrecht, The Netherlands
- intensive Care, MUMC+, Maastricht, The Netherlands
| | | | | | - Klaas Koop
- Metabolic Disorders, UMC, Utrecht, The Netherlands
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29
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Invernizzi F, Izzo R, Colangelo I, Legati A, Zanetti N, Garavaglia B, Lamantea E, Peverelli L, Ardissone A, Moroni I, Maggi L, Bonanno S, Fiori L, Velardo D, Magri F, Comi GP, Ronchi D, Ghezzi D, Lamperti C. NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia. Genes (Basel) 2023; 14:1393. [PMID: 37510298 PMCID: PMC10379733 DOI: 10.3390/genes14071393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/26/2023] [Accepted: 06/28/2023] [Indexed: 07/30/2023] Open
Abstract
Introduction/Aims HyperCKemia is considered a hallmark of neuromuscular diseases. It can be either isolated or associated with cramps, myalgia, weakness, myoglobinuria, or rhabdomyolysis, suggesting a metabolic myopathy. The aim of this work was to investigate possible genetic causes in order to help diagnose patients with recurrent hyperCKemia or clinical suspicion of inherited metabolic myopathy. Methods A cohort of 139 patients (90 adults and 49 children) was analyzed using a custom panel containing 54 genes associated with hyperCKemia. Results A definite genetic diagnosis was obtained in 15.1% of cases, while candidate variants or variants of uncertain significance were found in a further 39.5%. Similar percentages were obtained in patients with infantile or adult onset, with some different causative genes. RYR1 was the gene most frequently identified, either with single or compound heterozygous variants, while ETFDH variants were the most common cause for recessive cases. In one patient, mRNA analysis allowed identifying a large LPIN1 deletion missed by DNA sequencing, leading to a certain diagnosis. Conclusion These data confirm the high genetic heterogeneity of hyperCKemia and metabolic myopathies. The reduced diagnostic yield suggests the existence of additional genes associated with this condition but also allows speculation that a significant number of cases presenting with hyperCKemia or muscle symptoms are due to extrinsic, not genetic, factors.
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Affiliation(s)
- Federica Invernizzi
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Rossella Izzo
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Isabel Colangelo
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Andrea Legati
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Nadia Zanetti
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Barbara Garavaglia
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Eleonora Lamantea
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Lorenzo Peverelli
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
| | - Anna Ardissone
- Child Neurology Unit-Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
| | - Isabella Moroni
- Child Neurology Unit-Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
| | - Lorenzo Maggi
- Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
| | - Silvia Bonanno
- Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
| | - Laura Fiori
- UOS di Malattie Metaboliche e Nutrizione, Ospedale dei Bambini Vittore Buzzi, 20154 Milan, Italy
| | - Daniele Velardo
- Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Francesca Magri
- Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Giacomo P Comi
- Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy
| | - Dario Ronchi
- Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy
| | - Daniele Ghezzi
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
- Lab of Neurogenetics and Mitochondrial Disorders, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Costanza Lamperti
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
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30
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Sahagian M, Mastrocco A, Prittie J. Phenibut toxicosis in a dog. J Vet Emerg Crit Care (San Antonio) 2023; 33:472-476. [PMID: 37436877 DOI: 10.1111/vec.13313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 07/14/2023]
Abstract
OBJECTIVE To describe the successful treatment of severe neurological and cardiovascular abnormalities in a dog following ingestion of the neuropsychotropic drug, phenibut. CASE SUMMARY A 2-year-old neutered male Weimaraner was found unresponsive and laterally recumbent in his urine after ingesting approximately 1600 mg/kg of phenibut. On presentation to an emergency clinic, the dog was neurologically inappropriate, tachycardic, hypertensive, and exhibiting a profoundly decreased respiratory rate. Because of progressive clinical signs, electrolyte abnormalities, increased hepatic enzyme activity and bilirubin concentrations, and the development of pigmenturia, referral to specialist care was sought. On presentation, the dog was intermittently somnolent and then maniacal. Sinus tachycardia persisted, and hyperthermia was documented. Hospitalization for supportive care was undertaken, and the dog was administered IV fluids, flumazenil, antiepileptics, and IV lipid emulsion therapy. The dog developed hypoglycemia and treated with dextrose supplementation. Progressive increases in liver enzyme activities as well as pronounced increase in creatine kinase activity, consistent with rhabdomyolysis, were noted. Over the course of 48 hours, the hypoglycemia resolved, and clinical signs significantly improved. Ultimately, the dog was discharged with improved clinical signs, with the owner reporting that 1 week after discharge, a full recovery had been made, and no residual clinical signs persisted. NEW INFORMATION PROVIDED To the authors' knowledge, there are no previous reports of phenibut intoxication in small animals. The growing availability and use of this drug by people in the past several years highlight the need for a greater understanding of its effects in companion animals.
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Affiliation(s)
- Michael Sahagian
- Department of Emergency and Critical Care, The Animal Medical Center, New York, New York, USA
| | - Alicia Mastrocco
- Department of Emergency and Critical Care, The Animal Medical Center, New York, New York, USA
| | - Jennifer Prittie
- Department of Emergency and Critical Care, The Animal Medical Center, New York, New York, USA
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31
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Eliyan Y, Rezania K, Gomez CM, Seibert K. Pontine stroke in a patient with Chronic Progressive External Ophthalmoplegia (CPEO): a case report. BMC Neurol 2023; 23:231. [PMID: 37316776 DOI: 10.1186/s12883-023-03249-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 05/15/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke. CASE PRESENTATION A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic "hot spot" of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools. CONCLUSIONS This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.
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Affiliation(s)
- Yazan Eliyan
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
| | - Kourosh Rezania
- Department of Neurology, University of Chicago Medical Center, Chicago, IL, USA
| | - Christopher M Gomez
- Department of Neurology, University of Chicago Medical Center, Chicago, IL, USA
| | - Kaitlin Seibert
- Department of Neurology, University of Chicago Medical Center, Chicago, IL, USA.
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32
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Munankami S, Shrestha M, Amin S, Bajracharya A, Paudel R. Rhabdomyolysis Secondary to Severe Hypothyroidism Due to Hashimoto's Thyroiditis: A Case Report. Cureus 2023; 15:e39919. [PMID: 37409195 PMCID: PMC10317787 DOI: 10.7759/cureus.39919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2023] [Indexed: 07/07/2023] Open
Abstract
Hashimoto's thyroiditis, a chronic autoimmune inflammation of the thyroid glands, is the most common cause of hypothyroidism in iodine-sufficient areas, which can have varied clinical manifestations. It is more common in females and usually has an insidious course. Most patients present with mild clinical symptoms, such as constipation, fatigue, and weakness. Symptoms are associated with a slight increase in thyroid-stimulating hormone (TSH) levels and the presence of thyroid antibodies. However, overt hypothyroidism is uncommon. We hereby present an interesting case of rhabdomyolysis secondary to severe hypothyroidism due to Hashimoto's thyroiditis.
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Affiliation(s)
| | | | - Shefali Amin
- Internal Medicine, Reading Hospital/Tower Health, West Reading, USA
| | | | - Rubina Paudel
- Internal Medicine, Reading Tower Health, Reading, USA
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33
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Patil P, Davidson J, Patel S. An undifferentiated cause of rhabdomyolysis: a case report. Int J Emerg Med 2023; 16:35. [PMID: 37170192 PMCID: PMC10173214 DOI: 10.1186/s12245-023-00507-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 05/03/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Rhabdomyolysis can occur secondary to infections, trauma, or myotoxic substances. Rhabdomyolysis secondary to autoimmune myositis occurs rarely. Distinguishing autoimmune rhabdomyolysis from rhabdomyolysis secondary to other causes is paramount in considering the long-term management of autoimmune rhabdomyolysis. It is further important to continue close follow-up and further testing to completely understand the extent of this disease as diagnoses may be ever-changing. CASE PRESENTATION A previously healthy female presented to the hospital with myalgias and myoglobinuria following a respiratory infection treated with azithromycin and promethazine. Labs demonstrating elevated creatine kinase (CK) prompted treatment for rhabdomyolysis and rheumatology consultation. The patient was given 3 l of intravenous (IV) 0.9% sodium chloride in the Emergency Department. Upon admission, the patient was placed on a continuous IV drip of 0.9% sodium chloride running at 300 cc/hour for all 8 days of her hospital admission. The rheumatology autoantibody panel pointed towards autoimmune myositis as a potential cause of her rhabdomyolysis. The patient was discharged to follow up with rheumatology for further testing. CONCLUSION Autoimmune myositis, although less common than other etiologies of rhabdomyolysis, is important to consider as the long-term management of autoimmune myositis includes the use of immunosuppressants, antimalarials, or IV immunoglobulins, which may be inappropriate for other etiologies of rhabdomyolysis.
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Affiliation(s)
- Pallavi Patil
- Cooper Medical School of Rowan University, Camden, NJ, USA.
| | | | - Sundip Patel
- Department of Emergency Medicine, Cooper University Hospital, Camden, NJ, USA
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Xu J, He J, Xu S, Wang R, Peng N, Zhang M. Gitelman syndrome with Graves' disease leading to rhabdomyolysis: a case report and literature review. BMC Nephrol 2023; 24:123. [PMID: 37131142 PMCID: PMC10152583 DOI: 10.1186/s12882-023-03180-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 04/21/2023] [Indexed: 05/04/2023] Open
Abstract
A 14-year-old male patient who suffered from limb numbness, fatigue, and hypokalemia was considered Graves' disease (GD) complicated with thyrotoxic periodic paralysis (TPP) at the first diagnosis. Although with the treatment of antithyroid drugs, he developed severe hypokalemia and rhabdomyolysis (RM). Further laboratory tests revealed hypomagnesemia, hypocalciuria, metabolic alkalosis, hyperrenin, and hyperaldosteronemia. Genetic testing revealed compound heterozygous mutations in the SLC12A3 gene (c.506-1G > A, c.1456G > A) encoding the thiazide-sensitive sodium-chloride cotransporter, which presented a definitive diagnosis of Gitelman syndrome (GS). Moreover, gene analysis revealed his mother diagnosed with subclinical hypothyroidism due to Hashimoto's thyroiditis carried the c.506-1G > A heterozygous mutation in the SLC12A3 gene and his father carried the c.1456G > A heterozygous mutation in the SLC12A3 gene. His younger sister who had hypokalemia and hypomagnesemia carried the same compound heterozygous mutations as the proband and was diagnosed with GS as well, but with a much milder clinical presentation and better treatment outcome. This case suggested the potential relationship between GS and GD, clinicians should strengthen the differential diagnosis to avoid missed diagnosis.
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Affiliation(s)
- Jing Xu
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Juan He
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
| | - Shujing Xu
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Rui Wang
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Nianchun Peng
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Miao Zhang
- Department of Endocrinology and Metabolism, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
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Nath RK, Somasundaram C. Foot drop secondary to rhabdomyolysis: improved foot dorsiflexion and gait after neurolysis and distal nerve transfer-a case series and literature review. J Surg Case Rep 2023; 2023:rjad257. [PMID: 37220591 PMCID: PMC10200358 DOI: 10.1093/jscr/rjad257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/14/2023] [Indexed: 05/25/2023] Open
Abstract
Rhabdomyolysis is a triad syndrome of myalgia, muscle weakness and myoglobinuria due to muscle necrosis. Trauma, exertions, strenuous exercise, infections, metabolic and electrolyte disorders, drug overdoses, toxins and genetic defects are the most common causes of rhabdomyolysis. The etiologies of foot drop are diverse. A few cases of rhabdomyolysis-associated foot drop are reported in the literature. We present five patients with foot drop secondary to rhabdomyolysis; two underwent neurolysis and distal nerve transfer (superficial peroneal nerve to the deep peroneal nerve) surgeries and follow-up evaluations. We found five-foot drop patients secondary to rhabdomyolysis among the 1022-foot drop patients who consulted our clinic since 2004, representing a 0.5% incidence. In two patients, rhabdomyolysis was caused by drug overdose and abuse. In the other three patients, the causes were an assault with a hip injury, a prolonged hospitalization due to multiple illnesses, and an unknown cause with compartment syndrome. Pre-operatively, a 35-year-old male patient had aspiration pneumonia, rhabdomyolysis and foot drop resulting from prolonged ICU hospitalization and a medically induced coma due to a drug overdose. The second patient (a 48-year-old male) had no history of trauma but had a sudden onset of right foot drop after compartment syndrome following the insidious onset of rhabdomyolysis. Both patients had difficulty dorsiflexing their involved foot and walked with a steppage gait before surgery. In addition, the 48-year-old patient had foot slapping while walking. However, both patients had strong plantar flexion (5/5). After 14 and 17 months of surgery, both patients had improved foot dorsiflexion to an MRC grade of 4/5 with an improved gait cycle and walked with no or minimal slapping, respectively. Distal motor nerve transfers in the lower limb facilitate faster recovery and less surgical dissection because of the shorter regeneration distance from the donor axons to the targeted motor end plates through residual neural network connections and descending motor signals.
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Affiliation(s)
- Rahul K Nath
- Corresponding address. Texas Nerve and Paralysis Institute, 6400, Fannin Street, Houston, TX-77030, Texas, USA. Fax: +1 713-592-9921; E-mail:
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Gartz M, Haberman M, Sutton J, Slick RA, Luttrell SM, Mack DL, Lawlor MW. ACTA1 H40Y mutant iPSC-derived skeletal myocytes display mitochondrial defects in an in vitro model of nemaline myopathy. Exp Cell Res 2023; 424:113507. [PMID: 36796746 PMCID: PMC9993434 DOI: 10.1016/j.yexcr.2023.113507] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023]
Abstract
Nemaline myopathies (NM) are a group of congenital myopathies that lead to muscle weakness and dysfunction. While 13 genes have been identified to cause NM, over 50% of these genetic defects are due to mutations in nebulin (NEB) and skeletal muscle actin (ACTA1), which are genes required for normal assembly and function of the thin filament. NM can be distinguished on muscle biopsies due to the presence of nemaline rods, which are thought to be aggregates of the dysfunctional protein. Mutations in ACTA1 have been associated with more severe clinical disease and muscle weakness. However, the cellular pathogenesis linking ACTA1 gene mutations to muscle weakness are unclear To evaluate cellular disease phenotypes, iPSC-derived skeletal myocytes (iSkM) harboring an ACTA1 H40Y point mutation were used to model NM in skeletal muscle. These were generated by Crispr-Cas9, and include one non-affected healthy control (C) and 2 NM iPSC clone lines, therefore representing isogenic controls. Fully differentiated iSkM were characterized to confirm myogenic status and subject to assays to evaluate nemaline rod formation, mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP) formation, superoxide production, ATP/ADP/phosphate levels and lactate dehydrogenase release. C- and NM-iSkM demonstrated myogenic commitment as evidenced by mRNA expression of Pax3, Pax7, MyoD, Myf5 and Myogenin; and protein expression of Pax4, Pax7, MyoD and MF20. No nemaline rods were observed with immunofluorescent staining of NM-iSkM for ACTA1 or ACTN2, and these mRNA transcript and protein levels were comparable to C-iSkM. Mitochondrial function was altered in NM, as evidenced by decreased cellular ATP levels and altered mitochondrial membrane potential. Oxidative stress induction revealed the mitochondrial phenotype, as evidenced by collapsed mitochondrial membrane potential, early formation of the mPTP and increased superoxide production. Early mPTP formation was rescued with the addition of ATP to media. Together, these findings suggest that mitochondrial dysfunction and oxidative stress are disease phenotypes in the in vitro model of ACTA1 nemaline myopathy, and that modulation of ATP levels was sufficient to protect NM-iSkM mitochondria from stress-induced injury. Importantly, the nemaline rod phenotype was absent in our in vitro model of NM. We conclude that this in vitro model has the potential to recapitulate human NM disease phenotypes, and warrants further study.
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Affiliation(s)
- Melanie Gartz
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Margaret Haberman
- Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA; Diverge Translational Science Laboratory, Milwaukee, WI, USA
| | - Jessica Sutton
- Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA; Diverge Translational Science Laboratory, Milwaukee, WI, USA
| | - Rebecca A Slick
- Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Shawn M Luttrell
- Curi Bio Inc., 3000 Western Avenue, Seattle, WA, 98121, USA; Institute for Stem Cell and Regenerative Medicine, UW Medicine, Seattle, WA, USA
| | - David L Mack
- Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, UW Medicine, Seattle, WA, USA
| | - Michael W Lawlor
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA; Diverge Translational Science Laboratory, Milwaukee, WI, USA
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Al Amrani F, Al-Thihli K, Narayanappa G, Al-Maawali A. MLIP-Associated Myopathy: A Case Report and Review of the Literature. J Neuromuscul Dis 2023; 10:293-299. [PMID: 36641683 DOI: 10.3233/jnd-221520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Muscular A-type lamin-interacting protein (MLIP) has a regulatory role in myoblast differentiation and organization of myonuclear positioning in skeletal muscle. It is ubiquitously expressed but abundantly in cardiac, skeletal, and smooth muscles. Recently, two studies confirmed the causation of biallelic pathogenic variants in the MLIP gene of a novel myopathy phenotype. OBJECTIVE Description of the phenotypic spectrum and features of MLIP-related myopathy. METHODS report a patient with biallelic variants in MLIP gene with the clinical features, and histomorphological findings of MLIP-related myopathy and provide a literature review of the previously reported 12 patients. RESULTS MLIP-related myopathy is characterized by episodes of rhabdomyolysis, myalgia triggered by mild to moderate exercise, mild muscle weakness, and sometimes cardiac involvement characterized by cardiomyopathy and cardiac rhythm abnormalities. CONCLUSIONS This report reviews and extends the clinical features of a novel myopathy caused by biallelic pathogenic variants in the MLIP gene.
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Affiliation(s)
- Fatema Al Amrani
- Pediatric Neurology Unit, Department of Child Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Oman
| | - Khalid Al-Thihli
- Department of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Sultanate of Oman, Oman
| | - Gayathri Narayanappa
- Department of Neuropathology, National Institute of Mental Health and Neuroscience (NIMHANS), Bangalore, India
| | - Almundher Al-Maawali
- Department of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Sultanate of Oman, Oman
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Erfanifar A, Mahjani M, Gohari S, Hassanian-Moghaddam H. Fatal overdose from injection of human growth hormone; a case report and review of the literature. BMC Endocr Disord 2022; 22:271. [PMID: 36348360 PMCID: PMC9644502 DOI: 10.1186/s12902-022-01193-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 10/29/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Human growth hormone (HGH) is a categorized as a performance-enhancing substance. HGH has been abused by athletes for doping purposes. CASE PRESENTATION We present a first lethal case of HGH acute toxicity. A young-agitated-athlete with a history of somatropin for the past 2-year, who had hallucinations referred to the emergency department reporting to have abused of 300 mg subcutaneous injections of HGH. He was tachycardic with mild hypertension. Lab data revealed hypernatremia (157 mEq/L), hyperkalemia (5.3 mEq/L), high LDH (1448 U/L), and CPK (2620 U/L), in favor of rhabdomyolysis. Routine drug screening tests were negative for all substances. He was intubated due to low O2 saturation and progressive loss of consciousness. After several episodes of hyperthermia, hypertension, and possibly pulmonary embolism, he died subsequent to somatropin overdose. CONCLUSIONS Complications of HGH misuse can be life-threatening and athletes should be warned of its deleterious effects.
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Affiliation(s)
- Azam Erfanifar
- Department of Internal Medicine, School of Medicine, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Mahjani
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Family Medicine, Alborz University of Medical Science, Alborz, Iran
| | - Sepehr Gohari
- Department of Family Medicine, Alborz University of Medical Science, Alborz, Iran
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Hassanian-Moghaddam
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Clinical Toxicology, Loghman-Hakim Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, South Karegar Street, Kamali St, Tehran, Iran.
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Lee SK, Gosselin NH, Jomphe C, McKeever K, Putnam W. Population Pharmacokinetics of Heptanoate in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation Disorders Treated With Triheptanoin. Clin Pharmacol Drug Dev 2022; 11:1264-1272. [PMID: 35908210 PMCID: PMC9795984 DOI: 10.1002/cpdd.1145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 06/28/2022] [Indexed: 01/27/2023]
Abstract
Triheptanoin is an odd-carbon, medium-chain triglyceride consisting of three fatty acids with seven carbons each on a glycerol backbone, indicated for the treatment of adult and pediatric patients with long-chain fatty acid oxidation disorders (LC-FAOD). A total of 562 plasma concentrations of heptanoate, the most abundant and pharmacologically active metabolite of triheptanoin, from 13 healthy adult subjects and 30 adult and pediatric subjects with LC-FAOD were included in the population pharmacokinetic (PK) analyses. Multiple peaks of heptanoate observed in several subjects were characterized by dual first-order absorption with a lag time in the second absorption compartment. The disposition of heptanoate in human plasma was adequately described by one-compartmental distribution with a linear elimination. The apparent clearance (CL/F) and apparent volume of distribution were allometrically scaled with body weight to describe PK data across a wide range of age groups in subjects with LC-FAOD. The typical CL/F in adult subjects with LC-FAOD was ≈19% lower than that in healthy subjects. Model-estimated elimination half-life for LC-FAOD patients was ∼1.7 hours, supporting a recommended dosing frequency of ≥4 times per day. Covariate analyses indicate that age, race, and sex did not lead to clinically meaningful changes in the exposure of heptanoate.
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Affiliation(s)
- Sun Ku Lee
- Ultragenyx Pharmaceutical Inc.NovatoCaliforniaUSA
| | | | | | | | - Wendy Putnam
- Ultragenyx Pharmaceutical Inc.NovatoCaliforniaUSA
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Floridis J, Barbour R. Postoperative weakness and anesthetic-associated rhabdomyolysis in a pediatric patient: a case report and review of the literature. J Med Case Rep 2022; 16:387. [PMID: 36280855 PMCID: PMC9594916 DOI: 10.1186/s13256-022-03629-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 09/27/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Anesthesia-associated rhabdomyolysis is a rare complication of surgery that causes postoperative myalgia, weakness, and potential renal failure if not managed promptly. Predisposing conditions that may lead to this complication include muscular dystrophies and myopathies. CASE PRESENTATION This rare case describes a pediatric non-Indigenous Australian patient developing this complication, with no known predisposing risk factors, and no clear etiology. A 9-year-old child with a background of asthma underwent an elective removal of keloid scar on her chest wall. The procedure was brief and uncomplicated, with an uneventful induction of anesthesia. During the emergence period, she developed acutely raised airway pressures with bronchospasm and laryngospasm requiring the use of salbutamol and suxamethonium with good effect. In the initial postoperative period, the patient complained of generalized myalgia and muscle weakness and was unable to mobilize independently. There was transient recovery to normal function; however, a recurrence of symptoms the following day with associated myalgias warranted admission to hospital. She was found to have rhabdomyolysis that was managed conservatively with a full recovery of several weeks. She was thoroughly investigated for any underlying cause, including genetic testing for malignant hyperthermia susceptibility (she had a variant of unknown significance but was negative for the known genetic abnormalities that cause malignant hyperthermia). CONCLUSION This case report demonstrates the importance of considering anesthesia-associated rhabdomyolysis as a differential for acute postoperative weakness, and outlines an investigative approach. To the best of our knowledge, it is the first case described in the pediatric literature to report biphasic progression of symptoms.
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Affiliation(s)
- John Floridis
- Gove District Hospital, Nhulunbuy, Northern Territory Australia
| | - Ruth Barbour
- Royal Darwin Hospital, Darwin, Northern Territory Australia
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Miranda LHL, de Lima DN, Dourado MMC. An Unusual Presentation of Rhabdomyolysis and Acute Kidney Injury after Physical Activity: A Case Report. Case Rep Nephrol Dial 2022; 12:193-200. [PMID: 36465573 PMCID: PMC9710430 DOI: 10.1159/000527194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 09/11/2022] [Indexed: 12/31/2022] Open
Abstract
Exercise-induced rhabdomyolysis refers to the breakdown of striated muscle, which releases intracellular elements into the bloodstream due to heavy physical activity. In rare instances, this condition may be the first clinical manifestation of sickle cell trait (SCT). We report on a 31-year-old woman with post-infectious fatigue who, after suffering mild COVID-19 symptoms 3 weeks prior, presented with intense muscle pain in the ankles, dyspnea, and choluria hours after strenuous physical exercise during a practical test. She sought emergent care the next day, where serum creatinine was measured at 2.4 mg/dL (baseline 1.0 mg/dL) and creatine phosphokinase at 118,000 U/L. She was previously healthy, without regular use of any medication, and habitually sedentary except in training, with no personal or family history of blood or muscle diseases. She was admitted without hemodialysis and discharged after 2 weeks. At 3 months, she had normalization of creatine phosphokinase and creatinine. As an outpatient, other tests were requested. Hemoglobin (Hb) electrophoresis revealed HbA1 of 57.8%, HbA2 of 3.1%, HbF of 0.3%, and HbS of 38.8%, which were compatible with SCT. Evaluation for SCT should be considered in cases of exercise-induced rhabdomyolysis, especially in young, healthy patients.
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Affiliation(s)
- Luiz Henrique Lélis Miranda
- Division of Internal Medicine, Center of Medical Science (CCM), Federal University of Pernambuco, Recife-PE, Brazil
| | - Débora Nóbrega de Lima
- Division of Internal Medicine, Center of Medical Science (CCM), Federal University of Pernambuco, Recife-PE, Brazil
| | - Marclébio Manuel Coêlho Dourado
- Adjunct Professor, Division of Nephrology, Center of Medical Science (CCM), Federal University of Pernambuco, Recife-PE, Brazil
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Gao H, Xiang Q, Li J, Yu M, Lan Y, Ba J, Liu Y, Tian H. Clinical analysis of the serum muscle enzyme spectrum of patients with newly diagnosed Sheehan's syndrome. Medicine (Baltimore) 2022; 101:e30834. [PMID: 36181079 PMCID: PMC9524868 DOI: 10.1097/md.0000000000030834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
We investigated the factors associated with serum muscle enzyme elevation in patients with Sheehan's syndrome. A total of 48 patients who were newly diagnosed with Sheehan's syndrome were included and divided into 3 groups: Group 1, creatine kinase (CK) ≥ 1000 U/L; Group 2, 140 < CK < 1000 U/L; and Group 3, CK ≤ 140 U/L. Differences in serum muscle enzymes, serum electrolytes, blood glucose and hormones were compared among the 3 groups. A Spearman correlation analysis and multiple linear regression analysis were performed on serum muscle enzymes and the other variables. Four patients in Group 1 underwent electromyography. Fourteen, 26 and 8 patients were divided into Group 1, Group 2, and Group 3, respectively. The levels of plasma osmolality, serum sodium, free triiodothyronine (FT3) and free thyroxine (FT4) in Group 1 were lower than those in Group 3 at admission (P < .05). There were significant differences in CK, CK-MB, aspartate aminotransferase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase among the three groups (P < .05). CK was correlated with serum sodium (r = -0.642, P < .001), serum potassium (r = -0.29, P = .046), plasma osmolality (r = -0.65, P < .001), FT3 (r = -0.363, P = .012), and FT4 (r = -0.450, P = .002). Moreover, creatine kinase isoenzyme-MB (CK-MB) was correlated with serum sodium (r = -0.464, P = .001) and plasma osmolality (r = -0.483, P < .001). The multiple linear regression showed that serum sodium was independently and negatively correlated with CK (r = -0.352, P = .021). The electromyogram results supported the existence of myogenic injury. Sheehan's syndrome is prone to be complicated by nontraumatic rhabdomyolysis, with both a chronic course and acute exacerbation. Serum muscle enzymes should be routinely measured. For patients with CK levels > 1000 U/L, a CK-MB/CK ratio < 6% can be a simple indicator to differentiate rhabdomyolysis from acute myocardial infarction. Abnormal serum muscle enzymes observed in Sheehan's syndrome may be associated with hypothyroidism and with hyponatremia in particular.
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Affiliation(s)
- Hongjiao Gao
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
- Department of Endocrinology, the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, China
| | - Qiao Xiang
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
| | - Jindie Li
- Department of Endocrinology, the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, China
| | - Meng Yu
- Department of Endocrinology, the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, China
| | - Yalin Lan
- Department of Endocrinology, the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, China
| | - Junqiang Ba
- Department of Endocrinology, the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, China
| | - Yan Liu
- Department of Laboratory Medicine, the Third Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Haoming Tian
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Haoming Tian, West China Hospital of Sichuan University, Chengdu 610041, China (e-mail: )
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Torr L, Mortimore G. The management and diagnosis of rhabdomyolysis-induced acute kidney injury: a case study. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2022; 31:844-852. [PMID: 36094035 DOI: 10.12968/bjon.2022.31.16.844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Rhabdomyolysis is characterised by a rapid dissolution of damaged or injured skeletal muscle that can be the result of a multitude of mechanisms. It can range in severity from mild to severe, leading to multi-organ failure and death. Rhabdomyolysis causes muscular cellular breakdown, which can cause fatal electrolyte imbalances and metabolic acidosis, as myoglobin, creatine phosphokinase, lactate dehydrogenase and other electrolytes move into the circulation; acute kidney injury can follow as a severe complication. This article reflects on the case of a person who was diagnosed with rhabdomyolysis and acute kidney injury after a fall at home. Understanding the underpinning mechanism of rhabdomyolysis and the associated severity of symptoms may improve early diagnosis and treatment initiation.
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Affiliation(s)
- Leah Torr
- Acute Kidney Injury Specialist Nurse, Royal Derby Hospital, University Hospitals of Derby and Burton Foundation Trust, Derby
| | - Gerri Mortimore
- Associate Professor in Advanced Clinical Practice, University of Derby, Derby
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Katz J, Labilloy A, Lee A. Recurrent, non-traumatic, non-exertional rhabdomyolysis after immunologic stimuli in a healthy adolescent female: a case report. BMC Pediatr 2022; 22:515. [PMID: 36042458 PMCID: PMC9426381 DOI: 10.1186/s12887-022-03561-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 08/21/2022] [Indexed: 11/10/2022] Open
Abstract
Background Dysferlinopathy refers to a heterogenous group of autosomal recessive disorders that affect a skeletal muscle protein called dysferlin. These mutations are associated with limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, asymptomatic hyperCKemia, and distal myopathy with anterior tibial onset. Case presentation A 16 year old female presented with myalgia, weakness and dark urine one week after her second BNT162b2 mRNA (Pfizer) vaccine. Initial serum creatine kinase (CK) was measured at 153,000 IU/L, eventually up-trending to over 200,000 IU/L. However, stable renal function precluded hemodialysis allowing discharge after 10 days of intravenous (IV) hydration and alkaline diuresis. Just two years prior to the current presentation, the patient was hospitalized following Group A Streptococcal pharyngitis infection complicated by rhabdomyolysis. She presented with fatigue, lower extremity weakness, and dark oliguria with CK measuring 984,800 IU/L. IV hydration was attempted however hemodialysis was ultimately required throughout her 24-day hospital stay. Her episode was presumed to be idiopathic and no further work-up was performed at that time. During the patient’s current hospitalization, she reported similar symptomology (myalgias and weakness) following her first quadrivalent Gardasil vaccine at age 11. No hospitalization was required at that time. A comprehensive workup was now initiated while the patient was being treated for her suspected second or third non-exertional, non-traumatic rhabdomyolysis. Rheumatologic, metabolic, infectious, and endocrinologic workup were all unremarkable. Patient eventually had whole exome sequencing performed which revealed a heterozygous pathogenic variant in the DYSF gene (DYSF c.2643 + 1G > A) encoding dysferlin. No clinically significant sequelae occurred thus far. Conclusions While there have been reports of symptomatic heterozygote carriers of dysferlinopathies, to our knowledge none have been associated with recurrent rhabdomyolysis after immunogenic stimuli. This unique case presentation highlights the importance of a multi-disciplinary care team, the utility of modern whole-exome gene sequencing, and the future challenges of balancing vaccine risk vs benefit. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-022-03561-2.
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Affiliation(s)
- Jason Katz
- College of Medicine, UF College of Medicine, Gainesville, FL, 32610, USA.
| | - Anatalia Labilloy
- Department of Pediatrics, Division of Pediatric Genetics, UF College of Medicine, Jacksonville, FL, 32207, USA
| | - Andrew Lee
- Department of Pediatrics, Division of General Pediatrics, UF College of Medicine, Jacksonville, FL, 32217, USA
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Fredrickson KA, Carver TW. Trauma-related electrolyte disturbances: From resuscitation to rhabdomyolysis. Nutr Clin Pract 2022; 37:1004-1014. [PMID: 36036224 DOI: 10.1002/ncp.10908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 07/20/2022] [Accepted: 08/04/2022] [Indexed: 11/08/2022] Open
Abstract
Traumatic injury results in drastic changes to a patient's normal physiology. The hormonal stress response, as well as some treatment strategies, lead to significant disruptions in electrolyte homeostasis that are important for clinicians to understand. In addition, advances in fluid resuscitation and modern transfusion practices have led to their own unique set of consequences, which we are just beginning to appreciate. Special attention is placed on rhabdomyolysis, as this distinct entity represents an extreme example of injury induced electrolyte derangements. This review describes the physiologic response to trauma and highlights some of the important electrolyte abnormalities that can be encountered while caring for the injured patient.
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Affiliation(s)
- Kyla A Fredrickson
- Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Thomas W Carver
- Department of Trauma and Acute Care Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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Rhabdomyolysis-Induced AKI (RIAKI) Including the Role of COVID-19. Int J Mol Sci 2022; 23:ijms23158215. [PMID: 35897810 PMCID: PMC9329740 DOI: 10.3390/ijms23158215] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/14/2022] [Accepted: 07/22/2022] [Indexed: 01/08/2023] Open
Abstract
Rhabdomyolysis is a compound disease that may be induced by many factors, both congenital and acquired. Statin therapy is considered one of the most common acquired factors. However, recent scientific reports suggest that serious complications such as rhabdomyolysis are rarely observed. Researchers suggest that, in many cases, side effects that occur with statin therapy, including muscle pain, can be avoided with lower-dose statin therapy or in combination therapy with other drugs. One of the most recent agents discovered to contribute to rhabdomyolysis is COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rhabdomyolysis is defined as a damage to striated muscle cells with escape of intracellular substances into the bloodstream. These substances, including myoglobin, creatine kinase (CK), potassium, and uridine acid, are markers of muscle damage and early complications of rhabdomyolysis. Symptoms may be helpful in establishing the diagnosis. However, in almost 50% of patients, they do not occur. Therefore, the diagnosis is confirmed by serum CK levels five times higher than the upper limit of normal. One of the late complications of this condition is acute kidney injury (AKI), which is immediately life-threatening and has a high mortality rate among patients. Therefore, the prompt detection and treatment of rhabdomyolysis is important. Markers of muscle damage, such as CK, lactate dehydrogenase (LDH), myoglobin, troponins, and aspartate aminotransferase (AST), are important in diagnosis. Treatment of rhabdomyolysis is mainly based on early, aggressive fluid resuscitation. However, therapeutic interventions, such as urinary alkalinization with sodium bicarbonate or the administration of mannitol or furosemide, have not proven to be beneficial. In some patients who develop AKI in the course of rhabdomyolysis, renal replacement therapy (RRT) is required.
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Longitudinal Changes of Serum Creatine Kinase and Acute Kidney Injury among Patients with Severe COVID-19. Int J Nephrol 2022; 2022:8556793. [PMID: 35497933 PMCID: PMC9044194 DOI: 10.1155/2022/8556793] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 03/30/2022] [Indexed: 01/04/2023] Open
Abstract
Background Acute kidney injury (AKI) is a common complication of COVID-19. Several etiologies have been identified, including pigment deposition likely associated with myopathic damage. Nevertheless, the relationship between longitudinal creatine-kinase trends and renal outcomes is uncertain. Aim To correlate longitudinal changes in serum creatine-kinase levels with hospital-acquired AKI (beyond 48 h of hospital admission) in severe COVID-19 patients. Methods This is a retrospective cohort study, and creatine-kinase levels were assessed over time in 1551 hospitalized patients with normal renal function at the time of hospital admission. Results In subjects who developed hospital-acquired AKI (n = 126, 8.1%), the serum creatine-kinase concentration before AKI onset was not different when compared to patients without AKI (slope of log creatine-kinase/day = −0.09 [95% CI −0.17 to +0.19] vs. +0.03 [95% CI −0.1 to +0.1]). After AKI diagnosis, serum creatine-kinase levels showed a significantly ascendent slope (slope of log creatine-kinase/day after AKI diagnosis = +0.14; 95% CI + 0.05 to +0.3). The AKI evolution was the main factor associated with the creatine-kinase trend. Subjects with persistent AKI (n = 40, 32%) had rising creatine-kinase levels during hospitalization (slope of log creatine-kinase/day = +0.30 95% CI + 0.19 to +0.51). A rising creatine-kinase trend (n = 114, 8%) was associated with a 1.89-fold higher risk of in-hospital death (95% CI 1.14 to 3.16). Nevertheless, this association disappeared after adjusting AKI evolution and LDH baseline levels. Conclusion In severe COVID-19 patients, a slight increase in creatine-kinase levels was observed after AKI occurrence but not before. Our results show that, at least for the appearance of hospital-acquired AKI, the CK rise does not meet the temporality criterion of causality regarding the occurrence of AKI. Rising creatine-kinase trends were associated with a higher risk of mortality, but this association was modified by AKI evolution and inflammation. There is a limited efficiency for AKI prognosis in the serial follow-up of CK levels in severe COVID-19 patients with normal renal function.
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Schnadthorst PG, Schulze C, Grunwald M. Sportmedizinische Beratung nach akuter Rhabdomyolyse bei erblicher Myopathie – eine herausfordernde Leistungsdiagnostik. Dtsch Med Wochenschr 2022; 147:481-484. [PMID: 35405752 DOI: 10.1055/a-1769-9073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Increased serum creatinine kinase after physical activity is well known and there is currently no cut-off value. We present the systematic diagnosis after rhabdomyolysis in a rare cause. HISTORY A 36-year-old soldier developed acute kidney failure due to rhabdomyolysis after intense physical exertion. FINDINGS AND DIAGNOSIS Sporty habitus, CK elevation and highly normal kidney values. Massive CK increase after step loading on the bicycle ergometer. We stopped further physical stress and initiated diagnostics. THERAPY AND COURSE The genetic diagnosis found a hereditary myopathy of the lipid metabolism (VLCAD deficiency). We used individualized performance analysis to determine the safe load limit. In the ordinary athletic testing of these performance limits, no excessive CK activation could be determined. CONCLUSION Recurrent rhabdomyolyses characterize the late onset of VLCAD, which can occur after intense physical activity, periods of fasting or dehydration. Patients can continue physical exercise safely after determining the individual tolerance.
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Affiliation(s)
| | - Christoph Schulze
- Zentrum für Sportmedizin der Bundeswehr, Warendorf.,Orthopädische Klinik und Poliklinik, Universitätsmedizin Rostock
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Mittal N, Del Rio-Pertuz G, Abohelwa M. COVID-19 causing rhabdomyolysis requiring hemodialysis in a young adult. Proc AMIA Symp 2022; 35:510-511. [DOI: 10.1080/08998280.2022.2051787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Nitish Mittal
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Gaspar Del Rio-Pertuz
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Mostafa Abohelwa
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
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Li C, Su HB, Li H, Li X, Wang HM, Song Q, Hu JH. Severe acute liver injury in patients with exertional heat stroke associated with poor short-term prognosis. World J Emerg Med 2022; 13:124-129. [PMID: 35237366 DOI: 10.5847/wjem.j.1920-8642.2022.047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 12/26/2021] [Indexed: 12/29/2022] Open
Affiliation(s)
- Chen Li
- Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hai-Bin Su
- Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hui Li
- Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xin Li
- Department of Emergency, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hong-Min Wang
- Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Qing Song
- Department of Critical Care Medicine, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Jin-Hua Hu
- Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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