Clinical, pathological, imaging and genetic analysis of two cases of central core disease with different inheritance modes / 中国神经精神疾病杂志

Objective To study the clinical, pathological, imaging features of two cases of central core disease (CCD) with different inheritance and to explore the similarities and differences between autosomal recessive CCD (AR-CCD) and autosomal dominant CCD (AD-CCD). Methods Clinical manifestations, family history, muscle MRI and muscle biopsy were collected. Targeted next generation sequencing (NGS) and sanger sequencing were applied for genetic analysis. Co-segregation analysis was further conducted in one family. Results Their common clinical manifestations included childhood early-onset proximal limbs muscle weakness and dystrophy accompanied with facial involvement. The MRI revealed extensive muscular dystrophy and fatty filtration in the both thighs, but not in rectus femoris. Pathology of skeletal muscle showed typical central cores in type Ⅰ muscle fibers and eccentric cores only in AR-CCD. Targeted NGS identified 3 missense mutations in RYR1, including one novel mutation. Conclusion The present study has described clinical and pathological features of two typical CCD patients with different inheritance, which may be associated with the different mutations in RYR1 gene. Targeted NGS apparently improves the genetic diagnosis of CCD.

Multi-modality CT study about the impact of human urinary kallidinogenase (HUK) on collateral circulation and blood perfusion in patients with acute cerebral ischemia (ACI) / 中国神经精神疾病杂志

Objective To study the impact of human urinary kallidinogenase (HUK) on collateral circulation and blood perfusion in patients with acute cerebral ischemia (ACI) using multi-modality CT methods. Methods In a randomized controlled clinical trial, 75 patients diagnosed with ACI were enrolled and divided into experiment group (treated with HUK)and control group (untreated with HUK). All participants underwent computer technology perfusion (CTP) and computed tomographic angiography (CTA) examination before and fourteenth day after treatment. The CT cerebral perfusion imaging (CTP), CT cerebrovascular imaging (CTA) and National Institutes of Health Stroke Scale (NIHSS) score were analyzed in two groups. The NIHSS score, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were compared between the two groups before and after 14 days therapy. Results ① After treatment, The two group showed increased CBF and CBV values and decreased MTT and TTP values. The CBF improvement was significantly better in the HUK-treated group than in the control group (t=2.470,P<0.05).②MTT and TTP were shorter in the HUK-treated group than in the control group (t=2.126, t=2.213, P<0.05).③ CTA maximum intensity projection (MIP) sequence revealed that the number of patients collateral vessels was significantly increased in the HUK-treated group than in the control group ( x2=4.265, P<0.05). ④The NIHSS score improvement was significantly better in the HUK-treated group after 14 days treatment than in the control group (t=4.330, P<0.05). Conclusion Human urinary kallidinogenase can improve blood perfusion and ameliorates neurological deficits. It is a safe and effective drug for treating ACI patients. The multi-modality CT methods are effective measure to assess blood perfusion and collateral circulation in patients with acute cerebral ischemia.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region

BACKGROUND: Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients. CASE REPORT: Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A). CONCLUSIONS: We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

Progress on genotypic and phenotypic features of central core disease / 国际儿科学杂志

Central core disease (CCD) is a dominantly inherited congenital myopathy,manifesting as static or slowly progressive weakness ofproximal muscles.Histological characteristics on muscle biopsy are the well defined areas devoid of oxidative enzyme stains.Ryanodine receptor 1 gene mutations are associated with CCD.Great progress has been made in recent years about the RYR1 gene mutaion and the clinical feature of CCD.Genotypic and Phenotypic variations of RYR1 related CCD are reviewed.

Characteristic Muscle Involvement on Magnetic Resonance Imaging in Central Core Disease

Central core disease (CCD) is a rare congenital myopathy characterized by central cores on muscle biopsy. We present three familial cases of CCD. The muscle pathology manifested as a predominance of type 1 muscle fibers and highly oxidative fibers with central cores. Muscle MRI showed selective involvement of the sartorius, vastus lateralis, and adductor magnus muscles. We suggest that muscle MRI can be used as an additional tool in the diagnosis of CCD.

A Double Mutation of the Ryanodine Receptor Type 1 Gene in a Malignant Hyperthermia Family with Multiminicore Myopathy

BACKGROUND AND PURPOSE: At least 100 Ryanodine receptor type 1 (RYR1) mutations associated with malignant hyperthermia (MH) and central core disease (CCD) have been identified, but 2 RYR1 mutations accompanying multiminicore myopathy in an MH and/or CCD family have been reported only rarely. METHODS: Fifty-three members of a large MH family were investigated with clinical, histopathologic, RYR1 mutation, and haplotyping studies. Blood creatine kinase (CK) and myoglobin levels were also measured where possible. RESULTS: Sequencing of the entire RYR1 coding region identified a double RYR1 mutation (R2435H and A4295V) in MH/CCD regions 2 and 3. Haplotyping analysis revealed that the two missense heterozygous mutations (c.7304G>A and c.12891C>T) were always present on a common haplotype allele, and were closely cosegregated with histological multiminicores and elevated serum CK. All the subjects with the double mutation showed elevated serum CK and myoglobin, and the obtained muscle biopsy samples showed multiminicore lesions, but only two family members presented a late-onset, slowly progressive myopathy. CONCLUSIONS: We found multiminicore myopathy with clinical and histological variability in a large MH family with an unusual double RYR1 mutation, including a typical CCD-causing known mutant. These results suggest that multiminicore lesions are associated with the presence of more than two mutations in the RYR1 gene.

Morbidity of Malignant Hyperthermia in Central Core Disease Patients Undergoing Orthopedics / 中国康复理论与实践

@#ObjectiveTo investigate the incidence of skeletal and/or articular malformations in central core disease (CCD) patients, and their risk of malignant hyperthermia (MH) in orthopedics. Methods28 unrelated patients with central core disease collected in the past 23 years were analyzed retrospectively. Results22 patients showed limb muscle weakness, while 6 patients didn't show any clinical symptom. Skeletal and/or articular malformations appeared in 21 patients, including joint contracture in 11, joint dislocation in 9, scoliosis in 12, lordosis in 5 and thoracic deformity in 1. 6 of the 10 patients could not endure orthopedic operation because of MH attack or dubitable MH attack. Calcium-induced calcium release (CICR) test performed on other 8 patients with MH family history or MH attack showed all those patients were MH susceptibilities. ConclusionSkeletal and/or articular malformations are common in CCD, as well as MH attack in orthopedics.

Central core disease

Central core disease is a rare congenital myopathy characterized by the formation of cores that consist of abnormal arrangement of myofibrils inside the myofibers. We report a 5-year-old Korean girl who showed a fairly typical clinical course of non-progressive muscle weakness. Electrodiagnostic studies showed low-amplitude polyphasic electromyograph and normal nerve conduction velocity. Gastrocnemius muscle biopsy showed central cores in over 80% of the fibers on H&E section. Histochemistry revealed deficient or absent mitochondrial enzyme in the cores and type I predominance. Ultrastructurally both structured and non-structured cores were found separately or simultaneously in one fiber. This case is the first report in the Korean literature.