Renal dysfunction can occur in advanced-stage Duchenne muscular dystrophy.

INTRODUCTION: With improved treatments, patients with Duchenne muscular dystrophy (DMD) can survive far beyond adolescence. However, advanced-stage DMD patients are at risk of developing renal dysfunction. In this study, long-term renal function outcomes and associated risk factors in advanced stage DMD were analyzed. METHODS: Fifty-one patients were classified into three different age groups (<20, 20-29, and ≥30 years of age), and cystatin C (CysC) levels were compared among groups. RESULTS: Median serum CysC levels were 0.74 mg/L, 0.63 mg/L, and 0.76 mg/L in the age groups of <20, 20-29, and ≥30 years, respectively (P = .003). Five of the nine patients in the ≥30 years age group showed elevated serum CysC and decreased cardiac function compared with the other four in the group (P = .014). DISCUSSION: Our results indicate an association between cardiac and renal dysfunction in patients with advanced-stage DMD.

[Changes in clinical condition and causes of death of inpatients with Duchenne muscular dystrophy in Japan from 1999 to 2012].

To elucidate changes in medical treatment for Duchenne muscular dystrophy (DMD) in Japan, we analyzed the clinical courses and causes of death of inpatients with DMD registered in the muscular dystrophy ward database of 27 hospitals in Japan specializing in muscular dystrophy treatment since 1999. The total number of hospitalized cases in 1999 was 873, which gradually reduced to 733 in 2012. The mean age of DMD patients in 1999 was 23.6 years old, while that was 30.1 years old in 2012, with patients 40 years and older accounting for 94 cases in the latest year. The respirator dependent rate gradually increased from 58.6% in 1999 to 86.1% in 2012. Artificial respiration therapy was introduced earlier in more recent years and the mean age in recent years was shown to be 17.2 years old. The oral nutritional supply rate in 1999 was 95.1%, which fell to 66.8% in 2012, while gastrostomy feeding gradually increased to 129 cases in 2012. The rate of clinical diagnosis of DMD was 52.3% in 1999 and decreased to 43.7% in 2012, which showed progress towards more accurate diagnosis of DMD. From 2000 to 2012, 521 deaths were reported, with approximately half of the causes heart related, followed by respiratory related. The mean age of death gradually increased to 32.4 years old in 2012 from 26.7 years old in 2000. The mean age of survival of all DMD patients was 37.5 years old. Progress in multidisciplinary medical care for respiratory failure, cardiomyopathy, nutritional problems, and other related factors has extended the lifespan of DMD patients.

Decreased resting energy expenditure in patients with Duchenne muscular dystrophy.

BACKGROUND: Skeletal muscle metabolism is a major determinant of resting energy expenditure (REE). Although the severe muscle loss that characterizes Duchenne muscular dystrophy (DMD) may alter REE, this has not been extensively investigated. METHODS: We studied REE in 77 patients with DMD ranging in age from 10 to 37 years using a portable indirect calorimeter, together with several clinical parameters (age, height, body weight (BW), body mass index (BMI), vital capacity (VC), creatine kinase, creatinine, albumin, cholinesterase, prealbumin), and assessed their influence on REE. In addition, in 12 patients maintaining a stable body weight, the ratio of energy intake to REE was calculated and defined as an alternative index for the physical activity level (aPAL). RESULTS: REE (kcal/day, mean±SD) in DMD patients was 1123 (10-11 years), 1186±188 (12-14 years), 1146±214 (15-17 years), 1006±136 (18-29 years) and 1023±97 (≥30 years), each of these values being significantly lower than the corresponding control (p<0.0001). VC (p<0.001) was the parameter most strongly associated with REE, followed by BMI (p<0.01) and BW (p<0.05). The calculated aPAL values were 1.61 (10-11 years), 1.19 (12-14 years), 1.16 (15-17 years), and 1.57 (18-29 years). CONCLUSION: The REE in DMD patients was significantly lower than the normal value in every age group, and strongly associated with VC. Both the low REE and PAL values during the early teens, resulting in a low energy requirement, might be related to the obesity that frequently occurs in this age group. In contrast, the high PAL value in the late stage of the disease, possibly due to the presence of respiratory failure, may lead to a high energy requirement, and thus become one of the risk factors for development of malnutrition.

Efficacy and tolerance of gastrostomy feeding in Japanese muscular dystrophy patients.

Although muscular dystrophy patients often have feeding difficulty and need long-term enteral nutrition, only a few reports have described gastrostomy feeding in these patients. This study was designed to evaluate the efficacy and tolerance of gastrostomy feeding in patients with muscular dystrophy. We performed a retrospective, multicenter study on 144 patients with muscular dystrophy who received gastrostomy feeding between 2007 and 2009 in 25 neuromuscular centers in Japan. There were 77 Duchenne muscular dystrophy (median age at gastrostomy placement 26 years, range 13-47 years), 40 myotonic dystrophy (median age 54.5 years, range 13-70 years), 11 Fukuyama congenital muscular dystrophy (median age 22 years, range 13-29 years), 5 limb girdle muscular dystrophy (median age 62 years, range 43-78 years), and 5 facioscapulohumeral muscular dystrophy (median age 52 years, range 28-67 years) patients. Many benefits including amelioration of malnutrition, swallowing difficulty and respiratory status were observed after the introduction of gastrostomy feeding. Especially in patients with Duchenne muscular dystrophy, mean body weight significantly increased after gastrostomy placement. Although most complications, which are commonly observed in other populations, were tolerable, respiratory failure and peritonitis were important concerns. These findings suggest that gastrostomy placement at an appropriate time is advisable in patients with muscular dystrophy.

Increased mid-left ventricular rotation in patients with Duchenne muscular dystrophy using two-dimensional speckle tracking echocardiography.

BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), cardiomyopathy initially occurs during adolescence. In routine echocardiographic examination, we often recognize increased rotational movement of the left ventricle in DMD patients even if their conventional echocardiographic finding is normal. Two-dimensional speckle tracking echocardiography can assess left ventricular (LV) rotation. The aim of this study was to analyze the mid-LV rotation and to investigate the clinical implication of this abnormal movement. METHODS: Nineteen DMD patients (age 15.5 ± 3.1 years) and 22 age-matched healthy subjects were recruited. The two-dimensional speckle tracking method was used to determine the mid-LV rotation at the papillary muscle level. The mid-LV rotation and rotational velocity were calculated and were compared with other echocardiographic data and indices of autonomic function. RESULTS: Total rotation was greater in the DMD group than in the normal group (7.3 ± 1.4° versus 5.2° ± 1.3°, p < 0.05). Both peak diastolic clockwise and counterclockwise rotational velocity were greater in the DMD group (p < 0.005 and p < 0.05, respectively). Time from the second heart sound to peak diastolic clockwise rotation (% diastolic duration) was greater in the DMD group (p < 0.005). Total rotation and percentage of adjacent normal R-R intervals more than 50 ms different showed a negative correlation (r = -0.72) in the DMD group. CONCLUSION: In DMD patients, cases diagnosed with normal LV fractional shortening showed an increase in mid-LV rotation that might be due to relative increase of sympathetic nervous function before global cardiac function decreases.

Autonomic function in patients with Duchenne muscular dystrophy.

BACKGROUND: Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. METHODS: Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 +/- 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. RESULTS: Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R-R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R-R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut-off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). CONCLUSION: In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.

[Videofluorographic assessment of swallowing function in patients with Duchenne muscular dystrophy].

OBJECTIVE: To identify the characteristics of swallowing function in patients with Duchenne muscular dystrophy (DMD). METHODS: Swallowing function was evaluated using videofluorography (VF) in a cross-sectional observational study of 102 DMD patients (mean age 21.5 years) who had dysphagia or in whom dysphagia was suspected based on clinical signs. Reduced tongue movement, impaired bolus transport to the pharynx, decreased pharyngeal contraction, bolus delivery into the airway, and bolus residue at the epiglottic vallecula and at the piriform recess were qualitatively evaluated for test swallows of jelly and juice. During VF, the length of time of both the oral and pharyngeal phases of swallowing was measured in 59 patients. RESULTS: Patients started to show oral phase abnormalities in their mid-teens and pharyngeal phase abnormalities such as pharyngeal residue around age 20. Oral phase abnormalities was higher with juice than with jelly. Total oral/pharyngeal transit duration was longer with age, and total duration of hyoid maximum elevation was shorter with age. CONCLUSION: The weak positive correlation of total oral/pharyngeal transit duration and age was presumably due to gradual onset of functional abnormalities associated with deteriorated swallowing muscles starting in the teenage years. Reduced tongue movement and impaired bolus transport to the pharynx was more common in teenage DMD patients because they have limited tongue movements associated with structural abnormalities such as macroglossia and open bite. VF showed that the swallowing difficulties were more severe during the oral phase than in the pharyngeal phase in the teenage patients. The pharyngeal phase disorders such as pharyngeal residue and decreased pharyngeal contraction were seen more often in the patients in their 20s, presumably due to deterioration of swallowing muscles that becomes more apparent in the older age group.

Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne's progressive muscular dystrophy.

OBJECTIVE: In patients with Duchenne's progressive muscular dystrophy (DMD), myocardial fibrosis begins from the epicardial half of the left ventricular posterior wall. Myocardial strain imaging by tissue Doppler echocardiography is a new method for assessing regional myocardial function. We hypothesized that this method might be useful for the early detection of subclinical myocardial involvement in DMD patients. METHODS: Myocardial radial strain of the left ventricle was measured in 25 DMD patients (age: 14.8 +/- 3.1 years) with a normal left ventricular shortening fraction and 25 age-matched healthy controls. RESULTS: Peak systolic radial strain of the posterior wall in a short-axis view of the left ventricle was significantly lower in DMD patients compared to control subjects (P < 0.0001). In the interventricular septum, peak systolic radial strain was not significantly different between the two groups. Receiver operating characteristic curve analysis differentiated DMD patients from control patients with 92% sensitivity and 92% specificity, when the cutoff value for systolic peak strain of the posterior wall was 61%. When radial strain was measured separately for the inner and outer halves of the posterior wall, a systolic negative strain was more frequently observed in the outer half than in the inner half of the posterior wall (6/25 vs. 0/25, P < 0.05). CONCLUSIONS: Myocardial strain imaging in DMD patients was characterized by decreased peak systolic strain of the posterior wall despite normal standard echocardiographic findings. Strain measurement might be useful for early detection of subtle regional myocardial dysfunction.

Peak negative myocardial velocity gradient and wall-thickening velocity during early diastole are noninvasive parameters of left ventricular diastolic function in patients with Duchenne's progressive muscular dystrophy.

Myocardial velocity gradient and wall-thickening velocity were measured in the interventricular septum and left ventricular posterior wall (LVPW) by color-coded M-mode Doppler tissue echocardiography in patients with Duchenne's progressive muscular dystrophy (DMD) with a normal shortening fraction (n = 14) and age-matched control subjects (n = 40). In the LVPW, peak myocardial velocity gradients during systole and early diastole were significantly lower for patients with DMD than in control subjects (P <.0005, and P <.0001, respectively). Peak myocardial wall-thickening velocities of the LVPW during systole and early diastole were also lower for patients with DMD (P <.0005 and P <.0001, respectively). Mitral peak atrial to early filling velocity ratio was not significantly different between the 2 groups. The cut-off values of peak myocardial velocity gradients and wall-thickening velocities of the LVPW during early diastole for differentiation between patients with DMD and control subjects were -5.8/s and -6.0 cm/s, respectively (sensitivity/specificity: 93%/93% and 93%/85%, respectively). In conclusion, wall thinning during early diastole is frequently abnormal in patients with DMD, even when conventional echocardiographic findings are normal.