Cardiac treatment in neuro-muscular diseases.

The authors have been treating heart involvement in muscle dystrophy since 1978. However, this study aimed to define recent therapeutic protocols, evaluating the results of cardiac treatment, performed between 1st February 2004 and 31st July, 2006. In this period, 100 Becker, 136 Duchenne, 44 Limb-girdle and 116 Steinert patients were treated. In that same period, a large group of MD patients refusing cardiac therapy have also been followed. All patients had previously been classified in the appropriate stage of cardiomyopathy and examined at least twice every year and even every week if presenting heart failure. The results show the usefulness of the recent protocols of treatment of cardiac involvement in muscle dystrophy patients.

Deflazacort in Duchenne muscular dystrophy: a comparison of two different protocols.

We compare the long-term benefits and side effects of deflazacort using two treatment protocols from Naples (N) and Toronto (T). Boys with Duchenne muscular dystrophy between the ages of 8 and 15 years and who had four or more years of deflazacort treatment were reviewed. Diagnostic criteria included males with proximal muscle weakness evident before 5 years, increased serum creatine kinase and genetic testing and/or a muscle biopsy consistent with Duchenne muscular dystrophy. Thirty-seven boys were treated with protocol-N using deflazacort at a dose of 0.6 mg/kg per day for the first 20 days of the month and no deflazacort for the remainder of the month. Boys with osteoporosis received daily vitamin D and calcium. Deflazacort treatment started between 4 and 8 years of age. Thirty-two were treated with protocol-T using deflazacort at a dose of 0.9 mg/kg per day, plus daily vitamin D and calcium. Treatment started between 6 and 8 years of age. All boys were monitored every 4-6 months. The results were compared with age-matched controls in the two groups (19 for protocol-N and 30 for protocol-T). For the boys treated with protocol-N, 97% were ambulatory at 9 years (control, 22%), 35% at 12 years (control, 0%), 25% at 15 years (control, 0%). For the 32 boys treated with protocol-T, 100% were ambulatory at 9 years (control, 48%), 83% at 12 years (control, 0%) and 77% at 15 years (control, 0%). No aids or leg braces were used for ambulation. In boys 13 years and older, a scoliosis of >20 degrees developed in 30% of the boys on protocol-N, 16% on protocol-T and 90% of controls. For protocol-N, no cataracts were observed while in protocol-T, 30% of boys had asymptomatic cataracts that required no treatment. Fractures occurred in 19% (control 16%) of boys on protocol-N and 16% (control, 20%) of boys on protocol-T. This report illustrates: (a) the importance of collaborative studies in developing treatment protocols in Duchenne muscular dystrophy and (b) the long-term beneficial effects of deflazacort treatment in both protocols. However, the protocol-T seems to be more effective and frequently is associated with asymptomatic cataracts.

ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis?

An electrocardiographic pattern resembling myocardial infarction is a rare condition in Duchenne muscular dystrophy. We report the case of a Duchenne boy, aged 12 years and 7 month, who, during a programmed examination, showed electrocardiographic signs of ST segment elevation, without symptoms usually accompanying myocardial infarction (chest pain, dyspnoea, sweating). The biological markers of myocardial damage became positive on the 2nd day and recovered on the 5th day. Clinical features of this uncommon pattern are described, with the retrospective evaluation of similar cases from personal records. The differential diagnosis between myocardial necrosis and apoptosis is discussed.

Evaluation of cardiac and respiratory involvement in sarcoglycanopathies.

Sarcoglycanopathies constitute a subgroup of limb-girdle recessive muscular dystrophies due to defects in sarcoglycan complex that comprises five distinct transmembrane proteins called alpha-, beta-, gamma-, delta-and epsilon-sarcoglycans. As it is well known that sarcoglycans are expressed both in heart and in skeletal muscles and a complete deficiency in delta-sarcoglycan is the cause of the Syrian hamster BIO.14 cardiomyopathy, we studied cardiac and respiratory involvement in 20 patients with sarcoglycanopathies by clinical, electrocardiographic, echocardiographic, scintigraphic and spirometric assessments. A normal heart function was found in 31.3% of all patients; a preclinical cardiomyopathy in 43.7%; an arrhythmogenic cardiomyopathy in 6.3% and initial signs of dilated cardiomyopathy in 18.7%. In one patient the data were examined retrospectively. No correlation was found between cardiac and skeletal muscle involvement. With reference to the type of sarcoglycanopathy, signs of hypoxic myocardial damage occurred in beta-, gamma- and delta-sarcoglycanopathies, while initial signs of a dilated cardiomyopathy in gamma- and delta-sarcoglycanopathies were found. A normal respiratory function was observed in 23.5% of all patients, a mild impairment in 35.4%, a moderate impairment in 29.4%, and a severe impairment in 11.7%.

Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies.

OBJECTIVE: To characterize the presence and behavior of the dystrophinopathic myocardial damage in female carriers of a gene defect at the Xp21 locus of the X chromosome that causes Duchenne and Becker muscular dystrophies (DMD and BMD). DESIGN: Cohort study from April 1, 1985, to April 30, 1995, with cardiologic follow-up performed yearly for a minimum of 3 to a maximum of 10 years. SETTING: Counseling center for genetic muscular disorders. PATIENTS: A total of 197 women and girls aged 5 to 60 years ascertained to be carriers of the DMD (n = 152) or BMD (n = 45) gene. MAIN OUTCOME MEASURES: Cardiac status at yearly examinations as determined by 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, M-mode and 2-dimensional echocardiography, and carotid pulse tracing. Myocardial scintigram was performed on each individual at least twice during the study. Immunohistochemical analysis of dystrophin from myocardium and/or skeletal muscle biopsy was performed in 12 carriers. RESULTS: Preclinical or clinically evident myocardial involvement was found in 166 cases (84.3%), without significant differences in percentage and behavior between DMD and BMD carriers. Its occurrence increased significantly with age, from 54.5% (18 cases) in carriers aged between 5 and 16 years to 90.2% (148 cases) in carriers older than 16 years. Dystrophin anomalies were detected at the membrane level of the myocardial fibers in all endomyocardial biopsy specimens. CONCLUSIONS: Genetic anomalies can be considered the primary cause of myocardial damage in carriers of dystrophinopathic myopathies; myocardial damage shows the same behavior already described in DMD and BMD patients and progresses from preclinical to dilated cardiomyopathy, passing through stages of myocardial hypertrophy or dysrhythmias.

Evaluation of the cardiomyopathy in Becker muscular dystrophy.

To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients--identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis--were followed in the years 1976-1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy.

Prospective study of X-linked progressive muscular dystrophy in Campania.

Within the Campania region of southern Italy a prospective study on X-linked progressive muscular dystrophy was conducted over a period of 12 years from 1969 to 1980, inclusive. The mean incidence rate was 21.7 per 100,000 male livebirths for Duchenne muscular dystrophy (DMD) cases and 3.2 per 100,000 male livebirths for Becker muscular dystrophy (BMD) cases. The familial cases were 38.5% among the DMD patients and 50% among the BMD patients. Myocardial involvement appeared in DMD patients at about 6 years of age in a high percentage of cases and increased progressively until the last years of life, when cardiac damage occurred in 95% of cases. The percentage of myocardial involvement in BMD patients was very low before 13 years of age, but increased progressively until 20 years, when cardiac damage occurred in 80% of cases studied; severe cardiomyopathy did not occur before the age of 21. The data reported also include the effects of age on physical performance, serum creatine kinase activity and serum myoglobin levels, the types of cardiac damage, and the causes of death.