A case report of central core disease with repeated foaming at the mouth as the initial symptom.

BACKGROUND: Central core disease (CCD) is a congenital myopathy primarily observed in infants and children. It frequently manifests as limb weakness or delayed motor development, characterized by gradually progressing or non-worsening weakness and muscle atrophy primarily affecting the proximal limbs. Joint deformity is a prevalent clinical feature. Presently, there is no targeted treatment available for this condition. CASE DESCRIPTION: The infant, who was 42 days old, showed a repeated occurrence of foaming at the mouth for more than a month as the initial symptom. Initially, the local clinic misdiagnosed it as softening of the thyroid cartilage. However, when the infant underwent bronchoscopy at our hospital, it was discovered that the pharyngeal muscle was loose, and there was noticeable retraction of the base of the tongue. Additionally, the infant displayed evident hypotonia and an increase in creatine kinase levels. By conducting a thorough genetic examination, we confirmed that the infant had CCD. CONCLUSION: The onset of CCD may manifest as various symptoms. Medical practitioners need to be attentive in recognizing individuals who experience recurring pneumonia along with reduced muscle tone during the course of clinical diagnosis and treatment.

A case of dermatomyositis in a patient with central core disease: unusual association with autoimmunity and genetic muscle disease.

BACKGROUND: Dermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy. CASE PRESENTATION: Here, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patient's muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength. CONCLUSIONS: We present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.

[Anesthetic Management of a Patient with Central Core Disease for Scoliosis Surgery].

Central core disease (CCD) is a dominantly inherited congenital myopathy. CCD is also associated with muscular and skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities. CCD and malignant hyperthermia (MH) are both associated with mutations in the ryanodine receptor on chromosome 19q13.1. An 11-year-old boy with CCD complicated with severe scoliosis was scheduled for spinal fusion surgery under general anesthesia. Furthermore, he had trismus caused by temporomandibular contracture. He was considered as MH susceptible. Anesthesia was managed with remifentanil and propofol without using muscle relaxtants and volatile anesthetics. We could intubate the trachea with Airtraq laryngoscope without any complications. The perioperative course was uneventful.

Bilateral congenital lumbar hernias in a patient with central core disease--A case report.

Congenital lumbar hernias are rare malformations caused by defects in the development of the posterior abdominal wall. A known association exists with lumbocostovertebral syndrome; however other associated anomalies, including one case with arthrogryposis, have been previously reported. We present an infant girl with bilateral congenital lumbar hernias, multiple joint contractures, decreased muscle bulk and symptoms of malignant hyperthermia. Molecular testing revealed an R4861C mutation in the ryanodine receptor 1 (RYR1) gene, known to be associated with central core disease. This is the first reported case of the co-occurrence of congenital lumbar hernias and central core disease. We hypothesize that ryanodine receptor 1 mutations may interrupt muscle differentiation and development. Further, this case suggests an expansion of the ryanodine receptor 1-related myopathy phenotype to include congenital lumbar hernias.

Congenital myopathies: Natural history of a large pediatric cohort.

OBJECTIVE: To assess the natural history of congenital myopathies (CMs) due to different genotypes. METHODS: Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012. RESULTS: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p = 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchair-dependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8% (at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years). CONCLUSIONS: We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling.

[Malignant hyperthermia - problem in dental surgery. An introductory report]. / Hipertermia zlosliwa - problem w chirurgii stomatologicznej. Doniesienie wstepne.

Malignant hyperthermia is a genetic defect of uncontrolled hypermetabolic skeletal muscle response to anesthetic triggering drugs. Some congenital myopathies are regarded as risk increasing factors. The use of volatile anaesthetics or suxamethonium (succinylcholine) in patients who are predisposed to malignant hyperthermia leads to an increase in Ca2+ release from sarcoplasmic reticulum, which in turn causes a set of biochemical and clinical symptoms, which can be a cause of death, if dantrolene is not administered adequately. The aim of the study was to draw attention to the problem of malignant hyperthermia, which is hardly ever described in Polish literature, and requires the necessity of intensifying the cooperation between the dentist and specialists from other medical fields. The origin of the article was a case of congenital myopathy with recognized malignant hyperthermia in an 18-year-old patient, in whom surgical extraction of teeth was indicated. The course of diagnostics and treatment showed once more that contemporary medicine is in need of holistic approach, and in consequence, promising and effective cooperation of many specialists.

Core myopathies and malignant hyperthermia susceptibility: a review.

The core myopathies are a subset of myopathies that present in infancy with hypotonia and muscle weakness. They were formerly considered a rare type of congenital myopathy but are now recognized as being more prevalent. Due to their genetic linkage to mutations in the ryanodine receptor gene (RYR1), core myopathies (in particular, central core disease) carry a high risk of malignant hyperthermia susceptibility. In this review article, we describe the phenotypical, genetic, and histopathological characteristics of core myopathies and further describe the currently understood nature of their risk of malignant hyperthermia. We also review the level of suspicion a clinician should exhibit with a child who has a possible core myopathy or other congenital myopathy presenting for an anesthetic prior to a definitive genetic analysis. For this review article, we performed literature searches using the key words anesthesiology, core myopathies, pediatric neurology, malignant hyperthermia, genetics, ryanodine receptor, and molecular biology. We also relied on literature accumulated by the two authors, who served as hotline consultants for the Malignant Hyperthermia Hotline of the Malignant Hyperthermia Association of the United States (MHAUS) for the past 12 years.

[Onset of a fulminant malignant hyperthermia crisis. Case report of a 74-year-old patient with previously subclinical central core disease]. / Erstmanifestation einer fulminanten malignen-hyperthermie-krise. Fall eines 74-jährigen patienten mit bislang subklinischer "central core disease".

Malignant hyperthermia (MH) is a latent, autosomal dominant inherited syndrome of skeletal musculature which results in excessive hypermetabolism induced by halogenated anesthetic agents and depolarizing muscle relaxants and is caused by an uncontrolled intramuscular calcium release. This case report focuses on the description of symptoms of a fulminant MH crisis. A possible link between central core disease (CCD) and the clinical severity of MH crisis is postulated in this paper.

A study of a family with the skeletal muscle RYR1 mutation (c.7354C>T) associated with central core myopathy and malignant hyperthermia susceptibility.

Congenital myopathies are early onset hereditary muscle disorders. A sub-group of these is associated with malignant hyperthermia susceptibility. Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with various congenital myopathy phenotypes and may also cause malignant hyperthermia susceptibility. We describe nine affected members of an extended family presenting with a myopathy typically manifesting as upper eye lid ptosis, quadriceps atrophy and patellar dislocation. Three affected members underwent extensive genetic testing and have a RYR1 exon 46 c.7354C>T gene mutation; two of whom had muscle biopsies--both demonstrated central core myopathy. The only affected family member who underwent testing for malignant hyperthermia susceptibility was shown to be positive. The clinical phenotypes seen among affected family members varies widely in severity, and have features in common with those congenital myopathies associated with malignant hyperthermia susceptibility, raising the possibility that these conditions represent a spectrum of disease.

[Anesthetic management for a patient with scoliosis combined with central core disease].

We gave general anesthesia to a patient with scoliosis combined with central core disease (CCD). CCD is a slowly progressive autosomal dominant congenital myopathy. CCD is presented typically in infancy with hypotonia and delay of motor development, characterized by predominantly proximal weakness pronounced in the hip girdle. Orthopedic complications are common with congenital dislocation of the hips, scoliosis and foot deformity. CCD is due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene at chromosome 19q13.1, which is also implicated in the malignant hyperthermia (MH). A patient with CCD is at risk of MH, with an abnormal response to suxamethonium and volatile anesthetics. The anesthetist ought to be aware of the diagnosis of CCD and to plan anesthetic management accordingly, avoiding potentially MH-triggering agents. We used total intravenous anesthesia (TIVA) in this case, and he showed no MH symptoms perioperatively. This report demonstrates that anesthesia in a patient with CCD could be successfully maintained with TIVA.

Can inhalation agents be used in the presence of a child with myopathy?

PURPOSE OF REVIEW: Anaesthesia for a child with a muscle disease is always challenging because there is a risk of malignant hyperthermia, rhabdomyolysis or hypermetabolic reaction if a halogenated agent is used. Ongoing progress in genetics helps in clarifying the link between malignant hyperthermia (a calcium channelopathy) and muscle diseases. RECENT FINDINGS: We provide a summary of the most recent clinical, pathophysiological and genetic information on those risks when the diagnosis is known or suspected preoperatively. Some simple clues are also given to help make a decision in the presence of an infant or child with hypotonia or motor delay but no diagnosis. SUMMARY: Only a few muscle diseases are really associated with a risk of malignant hyperthermia. The risk of rhabdomyolysis is more difficult to clarify and a multicentric database would be useful to evaluate the risk/benefit ratio of all anaesthetic drugs in patients with muscle diseases.

Core myopathies and risk of malignant hyperthermia.

In this article, we analyze myopathies with cores, for which an association to malignant hyperthermia (MH) has been suggested. We discuss the clinical features, the underlying genetic defects, subsequent effects on cellular calcium metabolism, and in vitro muscle responses to MH triggers. We describe in detail central core disease, multiminicore disease, and nemaline rod myopathy. We categorize the diseases according to the affected proteins and discuss the risk for MH, which is high or theoretically possible when the calcium-conducting proteins are affected.

Mortality and morbidity associated with correction of severe cervical hyperextension.

STUDY DESIGN: Three case reports of patients with treatment of severe cervical hyperextension. OBJECTIVE: Cervical hyperextension is a rare spine deformity that is associated with myopathies. Previous reports of surgical correction have reported no major operative complications. This report outlines our experience with 3 patients who experienced significant complications. SUMMARY OF BACKGROUND DATA: The limited literature on the treatment of cervical hyperextension has good to excellent outcomes. METHODS: Three case reports are presented. RESULTS: Three cases with severe cervical hyperextension with intraoperative correction had associated morbidity and mortality. One case had a failed intubation requiring tracheotomy. This was followed by a successful posterior release with halo traction for 2 weeks and then an instrumented posterior cervical fusion. This patient died at home 2 weeks after surgery. The second and third cases had an intraoperative spinal cord injury during a posterior release for cervical hyperextension. CONCLUSION: Patients with severe cervical hyperextension have high neurologic perioperative risk.

Caesarean section in a complicated case of central core disease.

We describe the anaesthetic management of a 21-year-old lady with central core disease for elective Caesarean section. Central core disease is characterised by muscle weakness, skeletal deformities and susceptibility to malignant hyperthermia. Total intravenous anaesthesia was used because of the combination of potential malignant hyperthermia, severe kyphoscoliosis and extensive spinal scarring. The authors believe there is no previous report of propofol and remifentanil being used in these circumstances. A short review of central core disease and its anaesthetic implications is provided.

Surgical treatment of scoliosis associated with central core disease: minimizing the effects of malignant hyperthermia with provocation tests.

We report the case of a 7-year-old boy with thoracolumbar scoliosis and central core disease who had a history of malignant hyperthermia. He had scoliosis with Cobb's angle deteriorating to 67 degrees (thoracic) and 59 degrees (lumbar). A provocation test of general anesthesia was performed to confirm no hyperthermic reaction. Then, he underwent surgical correction by a posterior approach. The thoracic curve was reduced to 38 degrees and the lumbar curve to 42 degrees . He has been followed up for 2 years without any complications. This is the first report with a detailed description of perioperative management on surgical treatment of scoliosis associated with central core disease.

Malignant hyperthermia.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000-100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%.