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Acta Myologica : Myopathies and... Dec 2020Congenital myopathies represent a clinically and genetically heterogeneous group of early-onset neuromuscular diseases with characteristic, but not always specific,... (Review)
Review
Congenital myopathies represent a clinically and genetically heterogeneous group of early-onset neuromuscular diseases with characteristic, but not always specific, histopathological features, often presenting with stable and/or slowly progressive truncal and proximal weakness. It is often not possible to have a diagnosis on clinical ground alone. Additional extraocular, respiratory, distal involvement, scoliosis, and distal laxity may provide clues. The "core myopathies" collectively represent the most common form of congenital myopathies, and the name pathologically corresponds to histochemical appearance of focally reduced oxidative enzyme activity and myofibrillar changes on ultrastructural studies. Because of the clinical, pathological, and molecular overlaps, central core disease and multiminicore disease will be discussed together.
Topics: Humans; Myopathies, Structural, Congenital; Myopathy, Central Core; Ophthalmoplegia; Ryanodine Receptor Calcium Release Channel
PubMed: 33458581
DOI: 10.36185/2532-1900-029 -
Neuromuscular Disorders : NMD Oct 2023Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression in...
Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression in a wide range of tissues, non-skeletal muscle manifestations associated with RYR1 mutations have only been rarely reported. Here, we report three patients with a diagnosis of Central Core Disease (CCD), King-Denborough Syndrome (KDS) and Malignant Hyperthermia Susceptibility (MHS), respectively, who in addition to their (putative) RYR1-related disorder also developed symptoms and signs of acute pancreatitis. In two patients, episodes were recurrent, with severe multisystem involvement and sequelae. RyR1-mediated calcium signalling plays an important role in normal pancreatic function but has also been critically implicated in the pathophysiology of acute pancreatitis, particularly in bile acid- and ethanol-induced forms. Findings from relevant animal models indicate that pancreatic damage in these conditions may be ameliorated through administration of the specific RyR1 antagonist dantrolene and other compounds modifying pancreatic metabolism including calcium signalling. These observations suggest that patients with RYR1 gain-of-function variants may be at increased risk of developing acute pancreatitis, a condition which should therefore be considered in the health surveillance of such individuals.
Topics: Animals; Humans; Acute Disease; Calcium; Malignant Hyperthermia; Mutation; Pancreatitis; Ryanodine Receptor Calcium Release Channel
PubMed: 37783627
DOI: 10.1016/j.nmd.2023.09.003 -
Frontiers in Pharmacology 2022The ryanodine receptors (RyRs) are large cation-selective ligand-gated channels that are expressed in the sarcoplasmic reticulum (SR) membrane. They mediate the... (Review)
Review
The ryanodine receptors (RyRs) are large cation-selective ligand-gated channels that are expressed in the sarcoplasmic reticulum (SR) membrane. They mediate the controlled release of Ca from SR and play an important role in many cellular processes. The mutations in RyRs are associated with several skeletal muscle and cardiac conditions, including malignant hyperthermia (MH), central core disease (CCD), catecholaminergic polymorphic ventricular tachycardia (CPVT), and arrhythmogenic right ventricular dysplasia (ARVD). Recent breakthroughs in structural biology including cryo-electron microscopy (EM) and X-ray crystallography allowed the determination of a number of near-atomic structures of RyRs, including wildtype and mutant structures as well as the structures in complex with different modulating molecules. This allows us to comprehend the physiological gating and regulatory mechanisms of RyRs and the underlying pathological mechanisms of the disease-causing mutations. In this review, based on the insights gained from the available high-resolution structures of RyRs, we address several questions: 1) what are the gating mechanisms of different RyR isoforms; 2) how RyRs are regulated by multiple channel modulators, including ions, small molecules, and regulatory proteins; 3) how do disease-causing mutations affect the structure and function of RyRs; 4) how can these structural information aid in the diagnosis of the related diseases and the development of pharmacological therapies.
PubMed: 35677449
DOI: 10.3389/fphar.2022.897494 -
Brain Communications 2022Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to...
Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to an external trigger. However, recent studies have demonstrated a clinical and histopathological continuum between patients with a history of malignant hyperthermia susceptibility and/or exertional rhabdomyolysis and -related congenital myopathies. We hypothesize that patients with a history of -related exertional rhabdomyolysis or malignant hyperthermia susceptibility do have permanent neuromuscular symptoms between malignant hyperthermia or exertional rhabdomyolysis episodes. We performed a prospective cross-sectional observational clinical study of neuromuscular features in patients with a history of -related exertional rhabdomyolysis and/or malignant hyperthermia susceptibility ( = 40) compared with healthy controls ( = 80). Patients with an -related congenital myopathy, manifesting as muscle weakness preceding other symptoms as well as other (neuromuscular) diseases resulting in muscle weakness were excluded. Study procedures included a standardized history of neuromuscular symptoms, a review of all relevant ancillary diagnostic tests performed up to the point of inclusion and a comprehensive, standardized neuromuscular assessment. Results of the standardized neuromuscular history were compared with healthy controls. Results of the neuromuscular assessment were compared with validated reference values. The proportion of patients suffering from cramps ( < 0.001), myalgia ( < 0.001) and exertional myalgia ( < 0.001) was higher compared with healthy controls. Healthcare professionals were consulted because of apparent neuromuscular symptoms by 17/40 (42.5%) patients and 7/80 (8.8%) healthy controls ( < 0.001). Apart from elevated creatine kinase levels in 19/40 (47.5%) patients and mild abnormalities on muscle biopsies identified in 13/16 (81.3%), ancillary investigations were normal in most patients. The Medical Research Council sum score, spirometry and results of functional measurements were also mostly normal. Three of 40 patients (7.5%) suffered from late-onset muscle weakness, most prominent in the proximal lower extremity muscles. Patients with variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. These symptoms result in frequent consultation of healthcare professionals and sometimes in unnecessary invasive diagnostic procedures. Most patients do have normal strength at a younger age but may develop muscle weakness later in life.
PubMed: 36751502
DOI: 10.1093/braincomms/fcac292 -
Cureus May 2021Malignant hyperthermia (MH) is a genetic skeletal muscle disorder characterized by hypermetabolic crisis usually triggered by anesthetic drugs. Non-anesthesia-triggered...
Malignant hyperthermia (MH) is a genetic skeletal muscle disorder characterized by hypermetabolic crisis usually triggered by anesthetic drugs. Non-anesthesia-triggered or awake MH is rare or under-reported. Other than anesthetic drugs, identified common triggers are exercise, fever, and viral infection. The literature does not report any awake MH cases triggered by dengue fever. We report a possible case of dengue fever-triggered awake MH. The main aim of reporting this case is to raise awareness of possible malignant hyperthermia in dengue patients and of a clinical grading system (CGS) for early diagnosis, as early treatment with dantrolene sodium reduces the mortality rate.
PubMed: 34159023
DOI: 10.7759/cureus.15121 -
International Journal of Hyperthermia :... 2020The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and... (Review)
Review
The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.
Topics: Heating; Hot Temperature; Humans; Hyperthermia, Induced; Neoplasms; Technology
PubMed: 32579419
DOI: 10.1080/02656736.2020.1779357 -
British Journal of Anaesthesia Dec 2020
Topics: Electronic Health Records; Genetic Testing; Genomics; Mutation
PubMed: 32958205
DOI: 10.1016/j.bja.2020.08.046 -
Notfall & Rettungsmedizin 2021These guidelines of the European Resuscitation Council (ERC) Cardiac Arrest under Special Circumstances are based on the 2020 International Consensus on Cardiopulmonary... (Review)
Review
These guidelines of the European Resuscitation Council (ERC) Cardiac Arrest under Special Circumstances are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required for basic and advanced life support for the prevention and treatment of cardiac arrest under special circumstances; in particular, specific causes (hypoxia, trauma, anaphylaxis, sepsis, hypo-/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), specific settings (operating room, cardiac surgery, cardiac catheterization laboratory, dialysis unit, dental clinics, transportation [in-flight, cruise ships], sport, drowning, mass casualty incidents), and specific patient groups (asthma and chronic obstructive pulmonary disease, neurological disease, morbid obesity, pregnancy).
PubMed: 34127910
DOI: 10.1007/s10049-021-00891-z -
Minerva Anestesiologica Aug 2021Children with symptoms of hypotonia (reduction of postural tone of lower limbs and trunk with or without changes in phasic tone) are frequently anesthetized for... (Review)
Review
Children with symptoms of hypotonia (reduction of postural tone of lower limbs and trunk with or without changes in phasic tone) are frequently anesthetized for diagnostic and therapeutic interventions. This review outlines the underlying causes and classifications, and the anesthesiologic pre- and peri-operative management of hypotonic children. Hypotonia may have a large range of etiologies that are categorized into central and peripheral hypotonia. A multidisciplinary approach towards the (differential) diagnosis of the underlying cause of the symptoms in cooperation with a pediatrician and/or pediatric neurologist is emphasized. Anesthetic management involves the anticipation of an increased risk in difficult airway management because of macroglossia, reduced mouth opening, obesity and limited neck mobility, which increases with age. There are no specific restrictions towards the use of intravenous or inhalational anesthetics. Short acting opioids and hypnotics, avoiding neuromuscular blockade, and locoregional techniques are preferred. Most patients are sensitive to the cardiac and depressive effects of anesthetics and all dystrophic myopathies are considered at risk of malignant hyperthermia. Depolarizing neuromuscular blockers are contraindicated. The use of a peripheral nerve stimulator is recommended to detect the severity of muscle relaxation before extubating. Accurate control and management of IV fluids, electrolytes and temperature is mandatory. Adequate postoperative pain treatment is essential to limit stress and metabolic alteration. Preferably a locoregional technique is used to reduce the increased risk of respiratory depression. A multidisciplinary preoperative approach taking into account the differential diagnosis of the underlying disease of the floppy child is recommended.
Topics: Anesthetics, Inhalation; Child; Electric Stimulation Therapy; Humans; Muscle Hypotonia; Obesity; Pain, Postoperative
PubMed: 33432795
DOI: 10.23736/S0375-9393.20.15011-9 -
Cells Sep 2023Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas,... (Review)
Review
Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.
Topics: Adult; Humans; Child; Neurofibromatosis 1; Optic Nerve Glioma; Brain Neoplasms; Hyperthermia, Induced; Immunotherapy; Tumor Microenvironment
PubMed: 37830595
DOI: 10.3390/cells12192380