Spinal Anesthesia of a Patient with Central Core Disease for Caesarean Section: A Case Report

Central core disease is an autosomal dominant congenital myopathy. It typically manifests as muscle weakness and developmental delay. Central core disease is also associated with malignant hyperthermia which can be developed by volatile agent or succinylcholine. Here, we are reporting a case of a 34-year-old primigravida with central core disease who underwent an emergency cesarean section under spinal anesthesia without complications.

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.

Early Osteoporosis in RYR1-Related Central Core Disease

Background: Central core disease(CDC) is a congenital neuromuscular myopathy with a wide range of phenotypic presentations, ranging from delayed motor development, frequent falls, and difficulty maintaining posture. CDC is a rare presentation of RYR1 (Calcium release channel gene) mutation, which is also linked with the etiology of malignant hyperthermia. Clinical Case: We present a case of a 57-year-old woman who was diagnosed with osteoporosis at age of 52 with a T score of -2.3 after she had a fragility fracture of the knee. She suffered from multiple falls from poor balance. Her most recent DXA bone density scan from December of 2018 showed a T score of -2.6. On genetic testing, she was found to have a RYR1 heterozygous mutation, on exon 28.c.3800C to G(p.P1267 Arg). This sequence change led to the replacement of proline with arginine at codon 1267 of RyR1 protein. None of her immediate and extended family members showed any signs of CDC. We assume that the loss of sufficient muscle strain on bone and the catabolic effect of RYR1 myopathy are major causes of osteoporosis in our patient, although menopause, personal history of smoking, and alcohol intake could also be contributing factors. Teriparatide along with daily Calcium and Vitamin-D was prescribed. Later on, denosumab injection was also added to the regimen. The patient still has at least one episode of unprovoked fall in a month, but luckily she has not had any more fractures. Conclusion: To our knowledge, this is the first case where early osteoporosis in RYR1 myopathy has been reported.

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

BackgroundDermatomyositis 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 presentationHere, 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.ConclusionsWe 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.

Evaluation of the Core Formation Process in Congenital Neuromuscular Disease With Uniform Type 1 Fiber and Central Core Disease

Typical central core disease (CCD) is characterized pathologically by the presence of a core and is accompanied by type 1 fiber uniformity. Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is characterized pathologically by the presence of type 1 fiber uniformity but without the abnormal structural changes in muscle fibers. Interestingly, typical CCD and 40% of CNMDU1 cases are caused by the same mutations in RYR1, and thus CNMDU1 has been considered an early precursor to CCD. To better understand the nature of CNMDU1, we re-evaluated muscle biopsies from 16 patients with CNMDU1 using immunohistochemistry to RYR1, triadin and TOM20, and compared this to muscle biopsies from 36 typical CCD patients. In CCD, RYR1, and triadin were present in the core regions, while TOM20 was absent in the core regions. Interestingly, in 5 CNMDU1 cases with the RYR1 mutation, RYR1, and triadin were similarly present in core-like areas, while TOM20 was absent in the subsarcolemmal region. Furthermore, there was a correlation between the core position and the disease duration or progression—the older patients in more advanced stages had more centralized cores. Our results indicate that CNMDU1 due to RYR1 mutation is a de facto core myopathy.

In vivo RyR1 reduction in muscle triggers a core-like myopathy

Mutations in the RYR1 gene, encoding the skeletal muscle calcium channel RyR1, lead to congenital myopathies, through expression of a channel with abnormal permeability and/or in reduced amount, but the direct functional whole organism consequences of exclusive reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specific RYR1 deletion. Tamoxifen-induced recombination in the RYR1 gene at adult age resulted in a progressive reduction in the protein amount reaching a stable level of 50% of the initial amount, and was associated with a progressive muscle weakness and atrophy. Measurement of calcium fluxes in isolated muscle fibers demonstrated a reduction in the amplitude of RyR1-related calcium release mirroring the reduction in the protein amount. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution and membrane remodeling. An increase in the expression level of many proteins was observed, as well as an inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Dusty Core Disease patients (a subtype of Central Core Disease), pointing to common pathophysiological mechanisms related to RyR1 reduction.

In vivo RyR1 reduction in muscle triggers a core-like myopathy

Some mutations in the RYR1 gene lead to congenital myopathies, through reduction in this calcium channel expression level, but the functional whole organism consequences of reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specific RYR1 deletion. Recombination in the RYR1 gene resulted in a progressive reduction in the protein amount and was associated with a progressive muscle weakness and atrophy. Calcium fluxes in isolated muscle fibers were accordingly reduced. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution, membrane remodeling, associated with increase in the expression level of many proteins and inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Central Core Disease patients, pointing to common pathophysiological mechanisms related to RyR1 reduction.