Anesthetic Management of Coronary Artery Bypass Grafting in a Patient with Charcot-Marie-Tooth Disease and Multivessel Coronary Artery Disease.

BACKGROUND The anesthetic management of patients with Charcot-Marie-Tooth disease (CMT) requires special deliberation. Previous literature has suggested that patients with CMT may have increased sensitivity to non-depolarizing neuromuscular blocking agents, and hyperkalemia associated with the administration of succinylcholine has been reported. The potential risk of malignant hyperthermia and underlying cardiopulmonary abnormalities, such as pre-existing arrhythmias, cardiomyopathy, or respiratory muscle weakness, must also be considered in patients with CMT. CASE REPORT We describe a case of a patient with a history of CMT and multivessel coronary artery disease who underwent coronary artery bypass grafting (CABG). Careful consideration was given to the anesthetic plan, which consisted of thorough pre- and perioperative evaluation of cardiac function, total intravenous anesthesia with propofol and remifentanil infusions, the use of a non-depolarizing neuromuscular blocking agent, and utilization of a malignant hyperthermia protocol with avoidance of volatile anesthetics to decrease the possible risk of malignant hyperthermia. Following a 3-vessel CABG, no anesthetic or surgical complications were noted and the patient was discharged on postoperative day 6 after an uneventful hospital course. CONCLUSIONS Exacerbation of underlying cardiac and pulmonary abnormalities associated with the pathophysiology of CMT, as well as patient response to neuromuscular blocking and volatile agents, should be of concern for the anesthesiologist when anesthetizing a patient with CMT. Therefore, CMT patients undergoing surgery require special consideration of their anesthetic management plan in order to ensure patient safety and optimize perioperative outcomes.

Muscle Ultrasound Abnormalities in Individuals with RYR1-Related Malignant Hyperthermia Susceptibility.

BACKGROUND: Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. OBJECTIVE: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. METHODS: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. RESULTS: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. CONCLUSIONS: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

An Unusual Combination of Arthrogryposis, Gastroschisis, Cecal Volvulus, and Malignant Hyperthermia in a Young Woman: A Case Report.

BACKGROUND The purpose of this study is to discuss a patient with a history of conditions, including arthrogryposis, gastroschisis, and malignant hyperthermia, who presented with cecal volvulus requiring urgent surgical intervention. CASE REPORT A 29-year-old woman with a history of arthrogryposis, gastroschisis, malignant hyperthermia, and multiple childhood abdominal surgeries presents to the Emergency Department (ED) with 2 days of abdominal pain and bloody diarrhea. A CT abdomen/pelvis revealed findings concerning for a cecal volvulus. The patient was premedicated and monitored closely by the anesthesia team due to her history of malignant hyperthermia. She underwent an exploratory laparotomy, where a dilated cecum and proximal ascending colon were found to be completely volvulized around the mesentery. Manual bowel detorsion was performed, which resulted in reperfusion of the ischemic-appearing bowel, which then appeared viable. She recovered well after the procedure and was discharged on postoperative day 5. CONCLUSIONS This case highlights a patient who presented with a combination of 4 findings: arthrogryposis, gastroschisis, malignant hyperthermia, and cecal volvulus. With arthrogryposis reported to be associated with gastroschisis and malignant hyperthermia, this report not only corroborates this association, but also aims to draw attention to the fact that these conditions have potential to occur jointly with cecal volvulus. Given the patient's history of gastroschisis requiring extensive abdominal surgeries that contribute as risk factors for cecal volvulus, it is possible there may be other arthrogryposis patients who present with cecal volvulus similar to that seen in this patient.

Postoperative weakness and anesthetic-associated rhabdomyolysis in a pediatric patient: a case report and review of the literature.

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.

RYR1-Related Rhabdomyolysis: A Spectrum of Hypermetabolic States Due to Ryanodine Receptor Dysfunction.

Variants in the ryanodine receptor-1 gene (RYR1) have been associated with a wide range of neuromuscular conditions, including various congenital myopathies and malignant hyperthermia (MH). More recently, a number of RYR1 variants, mostly MH-associated, have been demonstrated to contribute to rhabdomyolysis events not directly related to anesthesia in otherwise healthy individuals. This review focuses on RYR1-related rhabdomyolysis in the context of several clinical presentations (i.e., exertional rhabdomyolysis, exertional heat illnesses and MH), and conditions involving a similar hypermetabolic state, in which RYR1 variants may be present (i.e., neuroleptic malignant syndrome and serotonin syndrome). The variety of triggers that can evoke rhabdomyolysis, on their own or in combination, as well as the number of potentially associated complications, illustrates that this is a condition relevant to several medical disciplines. External triggers include but are not limited to strenuous physical exercise, especially if unaccustomed or performed under challenging environmental conditions (e.g., high ambient temperature or humidity), alcohol/illicit drugs, prescription medication (in particular statins, other anti-lipid agents, antipsychotics and antidepressants) infection, or heat. Amongst all patients presenting with rhabdomyolysis, genetic susceptibility is present in a proportion, with RYR1 being one of the most common genetic causes. Clinical clues for a genetic susceptibility include recurrent rhabdomyolysis, creatine kinase (CK) levels above 50 times the upper limit of normal, hyperCKemia lasting for 8 weeks or longer, drug/medication doses insufficient to explain the rhabdomyolysis event, and positive family history. For the treatment or prevention of RYR1-related rhabdomyolysis, the RYR1 antagonist dantrolene can be administered, both in the acute phase or prophylactically in patients with a history of muscle cramps and/or recurrent rhabdomyolysis events. Aside from dantrolene, several other drugs are being investigated for their potential therapeutic use in RYR1-related disorders. These findings offer further therapeutic perspectives for humans, suggesting an important area for future research.

Cardiac anomalies associated with Escobar syndrome: A case report and a review of the literature.

RATIONALE: Escobar syndrome (ES) is an autosomal recessive disorder. It is highly characterized by facial abnormalities, congenital diaphragmatic muscle weakness, myasthenic-like features, and skin pterygiums on multiple body legions. ES is a rare condition associated with many external and internal abnormalities. The internal malformations described in ES affect many organs including the heart, lungs, esophagus, liver, spleen, and intestine. The purpose of this paper is to explore the cardiac manifestations associated with ES. PATIENT CONCERNS: A 3.5-year-old girl, who was born for double first cousins, was admitted to the hospital for neuromuscular evaluation of multiple congenital contractures. DIAGNOSIS: The girl was diagnosed with ES and isolated dextrocardia which is a rare cardiac manifestation. However, to the best of our knowledge, no similar cases have been reported to date, and this case is thus believed to be very rare. INTERVENTIONS: The patient underwent an operative intervention to correct the bilateral fixed flexion deformity at her knees which was related to the posterior bilateral fibrotic bands/pterygia. OUTCOMES: Post-operatively, complete knee extension was obtained, the patient was fitted with a cast and extension night splint. She was discharged alive and had no complications. The patient was followed regularly in the orthopedic clinic and had periodic physiotherapy sessions. CONCLUSIONS: ES and isolated dextrocardia concurrence in the presented case resulted from different pathogenic mechanisms. Our findings suggest that ES might be caused by dysfunction in the acetylcholine receptor throughout fetal life, which may have affected muscle strength and movement. Other cardiac conditions include hypoplastic left-sided heart, Hypertrophic cardiomyopathy, patent ductus arteriosus, and heterotaxia.

The Clinical and Genotypic Spectrum of Scoliosis in Multiple Pterygium Syndrome: A Case Series on 12 Children.

BACKGROUND: Multiple pterygium syndrome (MPS) is a genetically heterogeneous rare form of arthrogryposis multiplex congenita characterized by joint contractures and webbing or pterygia, as well as distinctive facial features related to diminished fetal movement. It is divided into prenatally lethal (LMPS, MIM253290) and nonlethal (Escobar variant MPS, MIM 265000) types. Developmental spine deformities are common, may present early and progress rapidly, requiring regular fo llow-up and orthopedic management. METHODS: Retrospective chart review and prospective data collection were conducted at three hospital centers. Molecular diagnosis was confirmed with whole exome or whole genome sequencing. RESULTS: This case series describes the clinical features and scoliosis treatment on 12 patients from 11 unrelated families. A molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient. The remaining 11 patients spanned the spectrum between mild (curve ≤ 25°) and malignant scoliosis (≥50° curve before 4 years of age); the two patients with MYH3 mutations presented with malignant scoliosis. Bracing and serial spine casting appear to be beneficial for a few years; non-fusion spinal instrumentation may be needed to modulate more severe curves during growth and spontaneous spine fusions may occur in those cases. CONCLUSIONS: Molecular diagnosis and careful monitoring of the spine is needed in children with MPS.

Beneficial effects of dantrolene in the treatment of rhabdomyolysis as a potential late complication associated with COVID-19: a case report.

BACKGROUND: Patients with severe COVID-19 have disorders of the respiratory, cardiovascular, coagulation, skeletal muscle, and central nervous systems. These systemic failures may be associated with cytokine release syndrome, characterized by hyperpyrexia, thrombocytopenia, hyperferritinemia, and the elevation of other inflammatory markers. Rhabdomyolysis with high fever is a complication that is rarely found in COVID-19. The exact relations of these clinical conditions in patients with COVID-19 remain unknown. CASE PRESENTATION: We present the case of a 36-year-old man with severe COVID-19 complicated by rhabdomyolysis and high fever. After admission, his condition continued to deteriorate, with a high body temperature. On day 9, the patient had elevated creatine kinase and myoglobin levels consistent with rhabdomyolysis (26,046 U/L and 3668 ng/mL, respectively). In addition to viral therapy, he was immediately treated with hydration. However, the patient had persistent fever and elevated creatine kinase levels. The patient was diagnosed with malignant hyperthermia as a late complication of COVID-19, although he had no hereditary predisposition to malignant hyperthermia or neuroleptic malignant syndrome. The administration of dantrolene with muscle relaxation and anti-inflammatory function showed potential efficacy for rhabdomyolysis, high fever, and increased plasma inflammatory markers. CONCLUSIONS: Malignant hyperthermia is triggered by not only anesthetic agents but also viral infections. A possible mechanism of malignant hyperthermia is hypersensitivity of calcium release from the sarcoplasmic reticulum. These include mutations in or the activation of the skeletal muscle ryanodine receptor calcium release channel. Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent. The administration of dantrolene showed potential efficacy for rhabdomyolysis, high body temperature due to inflammation, and increased inflammatory markers. The underlying mechanism of the association of rhabdomyolysis and high fever in COVID-19 might be similar to the pathogenesis of malignant hyperthermia.

Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

HyperCKemia and rhabdomyolysis in the neuroleptic malignant and serotonin syndromes: A literature review.

Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with other syndromes that have a clear genetic background, in particular RYR1-related malignant hyperthermia. Through a literature review, performed according to the PRISMA guidelines, we aimed to report the clinical features of both syndromes, and the results of genetic testing performed. 10 case series and 99 case reports were included, comprising 134 patients. A male predominance of 58% was found. The median age was 35 (range 4-84) years. Eight patients experienced recurrent episodes of rhabdomyolysis. Genetic analysis was performed in eleven patients (8%), revealing four RYR1 variants, three likely benign (p.Asp849Asn, p.Arg4645Gln, p.Arg4645Gln) and one variant of uncertain significance (p.Ala612Thr). This review underlines that a subset of patients with neuroleptic malignant syndrome and serotonin syndrome develop recurrent episodes of rhabdomyolysis. This recurrent pattern suggests a possible underlying (genetic) susceptibility. However, the genetic background of neuroleptic malignant syndrome and serotonin syndrome has only been investigated to a very limited degree so far. The increasing availability of next generation sequencing offers an opportunity to identify potentially associated genetic backgrounds, especially in patients with recurrent episodes or a positive family history.

Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes.

Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca2+]cytosol. 42% of MHS patients have hyperglycemia. We show that phosphorylated glycogen phosphorylase (GPa), glycogen synthase (GSa) - respectively activated and inactivated by phosphorylation - and their Ca2+-dependent kinase (PhK), are elevated in microsomal extracts from MHS patients' muscle. Glycogen and glucose transporter GLUT4 are decreased. [Ca2+]cytosol, increased to MHS levels, promoted GP phosphorylation. Imaging at ~100 nm resolution located GPa at sarcoplasmic reticulum (SR) junctional cisternae, and apo-GP at Z disk. MHS muscle therefore has a wide-ranging alteration in glucose metabolism: high [Ca2+]cytosol activates PhK, which inhibits GS, activates GP and moves it toward the SR, favoring glycogenolysis. The alterations probably cause these patients' hyperglycemia. For basic studies, MHS emerges as a variable stressor, which forces glucose pathways from the normal to the diseased range, thereby exposing novel metabolic links.

Animals and humans move by contracting the skeletal muscles attached to their bones. These muscles take up a type of sugar called glucose from food and use it to fuel contractions or store it for later in the form of glycogen. If muscles fail to use glucose it can lead to excessive sugar levels in the blood and a condition called diabetes. Within muscle cells are stores of calcium that signal the muscle to contract. Changes in calcium levels enhance the uptake of glucose that fuel these contractions. However, variations in calcium have also been linked to diabetes, and it remained unclear when and how these 'signals' become harmful. People with a condition called malignant hyperthermia susceptibility (MHS for short) have genetic mutations that allow calcium to leak out from these stores. This condition may result in excessive contractions causing the muscle to over-heat, become rigid and break down, which can lead to death if left untreated. A clinical study in 2019 found that out of hundreds of patients who had MHS, nearly half had high blood sugar and were likely to develop diabetes. Now, Tammineni et al. ­ including some of the researchers involved in the 2019 study ­ have set out to find why calcium leaks lead to elevated blood sugar levels. The experiments showed that enzymes that help convert glycogen to glucose are more active in patients with MHS, and found in different locations inside muscle cells. Whereas the enzymes that change glucose into glycogen are less active. This slows down the conversion of glucose into glycogen for storage and speeds up the breakdown of glycogen into glucose. Patients with MHS also had fewer molecules that transport glucose into muscle cells and stored less glycogen. These changes imply that less glucose is being removed from the blood. Next, Tammineni et al. used a microscopy technique that is able to distinguish finely separated objects with a precision not reached before in living muscle. This revealed that when the activity of the enzyme that breaks down glycogen increased, it moved next to the calcium store. This effect was also observed in the muscle cells of MHS patients that leaked calcium from their stores. Taken together, these observations may explain why patients with MHS have high levels of sugar in their blood. These findings suggest that MHS may start decades before developing diabetes and blood sugar levels in these patients should be regularly monitored. Future studies should investigate whether drugs that block calcium from leaking may help prevent high blood sugar in patients with MHS or other conditions that cause a similar calcium leak.

Growth-Friendly Spine Surgery in Escobar Syndrome.

BACKGROUND: The aims of this study were to characterize the spinal deformity of patients with Escobar syndrome, describe results of growth-friendly treatments, and compare these results with those of an idiopathic early-onset scoliosis (EOS) cohort to determine whether the axial stiffness in Escobar syndrome limited correction. METHODS: We used 2 multicenter databases to review the records of 8 patients with EOS associated with Escobar syndrome who had at least 2-year follow-up after initiation of growth-friendly treatment from 1990 to 2016. An idiopathic EOS cohort of 16 patients matched for age at surgery (±1 y), postoperative follow-up (±1 y), and initial curve magnitude (±10 degrees) was identified. A randomized 1:2 matching algorithm was applied (α=0.05). RESULTS: In the Escobar group, spinal deformity involved 7 to 13 vertebrae and ranged from no vertebral anomalies in 3 patients to multiple segmentation defects in 6 patients. Mean age at first surgery was 5 years (range, 1.4 to 7.8 y) with a mean follow-up of 7.5 years (range, 4.0 to 10 y). Mean major curve improved from 76 degrees at initial presentation, to 43 degrees at first instrumentation, to 37 degrees at final follow-up (both P<0.001). Mean pelvic obliquity improved from 16 degrees (range, 5 to 31 degrees) preoperatively to 4 degrees (range, 0 to 8 degrees) at final follow-up (P=0.005). There were no differences in the mean percentage of major curve correction between the idiopathic EOS and Escobar groups at the immediate postoperative visit (P=0.743) or final follow-up (P=0.511). There were no differences between the cohorts in T1-S1 height at initial presentation (P=0.129) or in growth per month (P=0.211). CONCLUSIONS: Multiple congenital fusions and spinal curve deformity are common in Escobar syndrome. Despite large areas of congenital fusion, growth-friendly constructs facilitate spinal growth and improve curve correction. These results are comparable to those in idiopathic EOS. LEVEL OF EVIDENCE: Level III-case-control study.

Keeping Cool When Things Heat Up During a Malignant Hyperthermia Crisis.

This article describes the experience of a health care team at a maternity center during their care for a woman exhibiting an atypical presentation of malignant hyperthermia and outlines the steps taken to rapidly identify the condition and begin treatment to save her life. Key components in ensuring a positive outcome in a malignant hyperthermia crisis include increased awareness and readiness to effectively treat and reverse the signs and symptoms of this condition.

[Treatment of hyperthermia].

Hyperthermia is an uncontrolled elevation of body temperature exceeding the body's ability to dissipate heat. Hyperthermia can result in dangerously high core temperatures and can rapidly become fatal. Common causes include heat stroke, malignant hyperthermia, serotonin syndrome, neuroleptic syndrome, a few endocrine emergencies as well as numerous intoxications. Rapid diagnosis and prompt cooling are pivotal, since the condition triggers a cascade of metabolic events which may progress to irreversible injury or death. Ice-water immersion and evaporative cooling are the methods of choice.

Skeletal Muscle Metabolic Dysfunction in Patients With Malignant Hyperthermia Susceptibility.

BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls. METHODS: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength. RESULTS: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls. CONCLUSIONS: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population.

Anaesthetic management of a patient with multiple pterygium syndrome for elective caesarean section.

We report a case of a pregnant woman with multiple pterygium syndrome who presented for elective caesarean section. Neuraxial anaesthesia failed and the backup plan of awake intubation was extremely difficult.

Malignant Hyperthermia Susceptibility and Fitness for Duty.

INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia. Treatment consists of stopping triggering agents, administering dantrolene, and actively cooling the patient. MH is a medically disqualifying condition for service in the U.S. Armed Forces. However, patients with MH-causative mutations may never have experienced an MH episode. If they previously have had an event concerning for MH, details are often sparse and a formal evaluation is absent. MATERIALS AND METHODS: We present 2 case reports with military service implications, one as a formal applicant to the service academies and the other as the father of an active duty Navy chief. Both patients experienced prior MH-like reactions to anesthesia but had not undergone testing with a caffeine-halothane contracture test (CHCT) or genetic analysis. Both patients underwent skeletal muscle biopsies of the left vastus lateralis with nontriggering anesthetics at Children's National Medical Center in Washington, DC, and MH diagnostic CHCT at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. The CHCT was performed according to the North American MH Registry Protocol. With USUHS Institutional Review Board approval, ryanodine receptor type 1 gene (RYR1) and L-type calcium channel α-1 subunit gene (CACNA1S) sequencing was performed on the remaining muscle at USUHS. RESULTS: Each subject was CHCT positive, confirming a diagnosis of MH. One was found to have a known MH-causative gene mutation. The applicant to the service academy was therefore determined unfit for military service. The active duty son of the MH-positive patient underwent muscle biopsy and CHCT in order to continue his military career. CONCLUSION: A personal or familial history concerning for MH raises important questions on fitness for duty in the U.S. Armed Forces. Department of Defense regulation uniformly defines MH as a disqualifying condition; however, screening for a history of anesthetic complications during accession into the military is inconsistent. Medical standards across the services are also variable in the context of a familial history of MH. These case reports highlight the need for clinicians to seek expert consultation about how to proceed with MH-related issues. They also stress the importance of applying current understanding of heritable conditions to our fitness for duty determinations. Further investigation is also recommended to establish an MH-susceptible individual's propensity for exercise or heat-related injury outside the operating room. Department of Defense policy may thereafter be updated to reflect a quantitative assessment of MH's relative risk during inherently strenuous military operations.

Preserving brain function in a comatose patient with septic hyperpyrexia (41.6 °C): a case report.

BACKGROUND: Pyrexia is a physiological response through which the immune system responds to infectious processes. Hyperpyrexia is known to be neurodegenerative leading to brain damage. Some of the neurotoxic effects of hyperpyrexia on the brain include seizures, decreased cognitive speed, mental status changes, coma, and even death. In the clinical management of hyperpyrexia, the goal is to treat the underlying cause of elevated temperature and prevent end organ damage. CASE PRESENTATION: This case illustrates a 39-year-old white American man referred from another medical facility where he had undergone an upper gastrointestinal tract diagnostic procedure which became complicated by blood aspiration and respiratory distress. During hospitalization, he developed a core body temperature of 41.6 °C (106.9 °F) leading to cognitive decline and coma with a Glasgow Coma Score of 3. Levetiracetam and amantadine were utilized effectively for preserving and restoring neurocognitive function. Prior studies have shown that glutamate levels can increase during an infectious process. Glutamate is an excitatory neurotransmitter that is utilized by the organum vasculosum laminae terminalis through the neuronal excitatory system and causes an increase in body temperature which can lead to hyperpyrexia. Similar to neurogenic fevers, hyperpyrexia can lead to neurological decline and irreversible cognitive dysfunction. Inhibition of the glutamate aids a decrease in excitatory states, and improves the brain's regulatory mechanism, including temperature control. To further improve cognitive function, dopamine levels were increased with a dopamine agonist. CONCLUSIONS: We propose that a combination of levetiracetam and amantadine may provide neuroprotective and neurorestorative properties when administered during a period of hyperpyrexia accompanied by any form of mental status changes, particularly if there is a decline in Glasgow Coma Score.

Long term oral Dantrolene Improved Muscular Symptoms in a Malignant Hyperthermia Susceptible Individual.

This case report describes a female with p.Lys4876Arg amino acid change in the ryanodine receptor type 1 (RYR1) and a sibling who died of malignant hyperthermia (MH) during anesthesia. After her diagnosis as MH susceptible, this patient was administered low-dose dantrolene daily for greater than 25 years for treatment of chronic muscle spasm and pain in her lower extremities and back limiting sleep. Her creatine phosphokinase (CPK) was as high as 2390 IU/L during labor and 900 IU at rest. With 25 mg dantrolene daily, muscle cramps were eliminated, and sleep was improved. Gait instability was noted with dantrolene in the morning, but not when taken at bedtime. There was no evidence of liver injury. This case suggests that low dose dantrolene by mouth could be considered for the treatment of chronic muscle pain in individuals with MH susceptibility.