A Study Of Clinic And Serum Creatine Kinase And Muscle Pathology In Patients With Duchenne Muscular Dystrophy

Objective:To find the relationship between serum creatine kinase level in DMD patients with the course of the disease and age of onset; Analyze serum myocardial enzymes changes and early myocardial injury in DMD patients; Explore correlation between extent of clinical damage and degree of pathological lesions, immunohistochemical staining resistance a-sarcoglycan, dysferlin, laminA/C, MHC-I monoclonal antibodies.Methods:Using a retrospective study method, departments of Neurology and Pediatrics in the first hospital of jilin university, out-patient and in-patient cases, collection of 18 cases of male patients fitting DMD and 2 cases of female carriers from Oct.2008 to Oct.2010 period. The patients underwent serum myocardial enzymes detection, electromyography, and muscle ultrasound, skeletal muscle biopsy, continuous freezing in liquid nitrogen,histochemistry dyeing, all cases chosen in the study having loss of immunohistochemical staining to N-terminal, Rod and C-terminal of dystrophin portion of muscle cell membrane, parallel resistance ofα-sarcoglycan, dysferlin, laminA/C, MHC-I monoclonal antibody immunohisto-chemical, and then compared, analyzed and summarized the results.Results:1. Initial complains are different, with bilateral lower limbs weakness accounting for majority (14 cases,77.8%), asymptomatic myocardial enzymes elevation in 3 cases (16.7%), transaminase elevation in 1 case (5.5%); different degrees of scapular winging, pseudo hypertrophy of calf muscles, Gower sign,11 cases of different degree muscle wasting (61.1%).11 cases of proximal muscle strength grade 3-4 (61.1%).7 cases proximal muscle normal (38.9%).11 cases knee flection is affected (61.1%) and 12 cases cannot walk on ankle (66.7%),3 cases cannot walk on toes (16.7%), All denied muscle pain and Babinski negative on examination. All patients were not mental retarded.14 patients showed myopathic changes on EMG, the two female carriers had no obvious positive signs.2. Serum creatine kinase level varied, during the course, all show ascending trend coming on earlier with progression, about coming on 2-3 years, range between (17577.78-16963.7U/L), as disease progress, pathological damages are progressive, serum CK whole show downtrend gradually; from onset ages view point, serum Ck reached peak in 2-5 years old, with range (10838.25-12937U/L). With age, the pathological damages are aggravating, muscle necrosis increased, serum CK decreased.3. serum myocardial enzyme level done in all of our cases, results showed varying degree of increase but CK elevation was particularly remarkable, the average increase (10331.16±8095.62) U/L, CK-MB(417.88±304.69) U/L, LDH (1023.19±393.18) U/L, HBD (910.23±358.19) U/L, AST (217.96±108.12) U/L. CK-MB/CK>6%,7 cases.4. Only in 6 cases muscle ultrasound were done, to have the varying degree subcutaneous fat thickening, bilateral symmetric muscle wasting, about 0.3-0.5mm or so, muscle bundle membrane echogenicity increased and its continuity interrupted or disappeared, its texture was also unclear, diffuse exquisite sample fat echo.5. Histochemical staining, H/E slides, atrophied muscle fiber diameter between 10-70μm sizes, round in shape in cross section,majority are opaque fibers, scattered muscle necrosis and regeneration, some slides showed increasing in membranous nuclei, internal nuclei,fibromuscular stroma widened, muscle connective tissue hyperplasia of different level.6. Immunohistochemical staining with dystrophin-N,-C,-R monoclonal antibody,muscle membrane dystrophin are totally or almost totally absent,14 casesα-SG staining showed different degree of deficiency,4 cases express normal, all are dysferlin and laminA/C normally expressed,6 cases MHC-Ⅰdown-regulated, 12 cases MHC-Ⅰnormally expressed.Conclusions:1. DMD patients serum CK values significantly increased, can reach dozens to hundreds times, this research from course and onset ages, two aspects of the changes in serum CK, analyze and obtain during the course of the 2-3 years, age 2-5 years old, serum CK peak, later decline as the disease progress and age year by year.2. CK-MB/CK>6% to determine early myocardial damaged clinically meaningful and can be used as early detection DMD myocardial injury indexes.3. Muscle ultrasonic examination are gradually becoming an effective means for new research of muscle diseases.4. Muscle fiber co-existence degenerative, hyperplasic, Opaque fiber lesions is DMD characteristic changes, but has no specificity. With progression, muscle fibers quantity gradually decrease, to the end almost disappear, replaced by fat and connective tissue, the more serious clinical symptoms, the more increase in fat & C.T.5. Absence of dystrophin, reduction in a-sarcoglycan, explains that dystrophin missing affect a-sarcoglycan expression, presumably, the sarcoglycans participated in the muscle degeneration necrosis process.6. Normal expression of dysferlin and laminA/C, presumably, indicates that their synthesis and assembly has no direct correlation with dystrophin, also further prove that dysferlin and DGC are not related. MHC-Ⅰup regulation indicates DMD skeletal muscle over-active, it is postulated that inflammatory reaction secondary to muscle cells degeneration and necrosis, exact mechanism is unknown, needs for further researches.