Decreased quality of life in Duchenne muscular disease patients related to functional neurological and cardiac impairment.

In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8-18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.

The role of ataluren in the treatment of ambulatory and non-ambulatory children with nonsense mutation duchenne muscular dystrophy - a consensus derived using a modified Delphi methodology in Eastern Europe, Greece, Israel and Sweden.

BACKGROUND: This paper details the results of an evaluation of the level of consensus amongst clinicians on the use of ataluren in both ambulatory and non-ambulatory patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). The consensus was derived using a modified Delphi methodology that involved an exploration phase and then an evaluation phase. METHODS: The exploration phase involved 90-minute virtual 1:1 interviews of 12 paediatric neurologists who cared for 30-120 DMD patients each and had patient contact every one or two weeks. The respondents managed one to ten nmDMD patients taking ataluren. The Discussion Guide for the interviews can be viewed as Appendix A. Following the exploration phase interviews, the interview transcripts were analysed by an independent party to identify common themes, views and opinions and developed 43 draft statements that the Steering Group (authors) reviewed, refined and endorsed a final list of 42 statements. Details of the recruitment of participants for the exploration and evaluation phases can be found under the Methods section. RESULTS: A consensus was agreed (> 66% of respondents agreeing) for 41 of the 42 statements using results from a consensus survey of healthcare professionals (n = 20) experienced in the treatment of nmDMD. CONCLUSIONS: The statements with a high consensus suggest that treatment with ataluren should be initiated as soon as possible to delay disease progression and allow patients to remain ambulatory for as long as possible. Ataluren is indicated for the treatment of Duchenne muscular dystrophy that results from a nonsense mutation in the dystrophin gene, in ambulatory patients aged 2 years and older (see Summary of Product Characteristics for each country).

Myocardial native T1 mapping and extracellular volume quantification in asymptomatic female carriers of Duchenne muscular dystrophy gene mutations.

BACKGROUND: Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging. MATERIALS AND METHODS: 38 DMD-FC with verified genetic mutation and 22 healthy volunteers were included. Using CMR, native T1 relaxation time and ECV quantification were determined in each group. Late gadolinium enhancement (LGE) was assessed in all cases. RESULTS: There were 38 DMD-FC (mean age 39.1 ± 8.8 years) and 22 healthy volunteers (mean age 39.9 ± 12.6 years) imagined by CMR. The mean global native T1 relaxation time was similar for DMD-FC and CG (1005.1 ± 26.3 ms vs. 1003.5 ± 25.0 ms; p-value = 0.81). Likewise, the mean global ECV value was also similar between the groups (27.92 ± 2.02% vs. 27.10 ± 2.89%; p-value = 0.20). The segmental analysis of mean ECV values according to the American Heart Association classification did not show any differences between DMD-FC and CG. There was a non-significant trend towards higher mean ECV values of DMD-FC in the inferior and inferolateral segments of the myocardium (p-value = 0.075 and 0.070 respectively). CONCLUSION: There were no statistically significant differences in the mean global and segmental native T1 relaxation times and the mean global or segmental ECV values. There was a trend towards higher segmental mean ECV values of DMD-FC in the inferior and inferolateral walls of the myocardium.

Quantitative assessment of left ventricular longitudinal function and myocardial deformation in Duchenne muscular dystrophy patients.

BACKGROUND: Duchenne muscular dystrophy (DMD) manifests in males mainly by skeletal muscle impairment, but also by cardiac dysfunction. The assessment of the early phases of cardiac involvement using echocardiography is often very difficult to perform in these patients. The aim of the study was to use cardiac magnetic resonance (CMR) strain analysis and mitral annular plane systolic excursion (MAPSE) in the detection of early left ventricular (LV) dysfunction in DMD patients. METHODS AND RESULTS: In total, 51 male DMD patients and 18 matched controls were examined by CMR. MAPSE measurement and functional analysis using feature tracking (FT) were performed. Three groups of patients were evaluated: A/ patients with LGE and LV EF < 50% (n = 8), B/ patients with LGE and LVEF ≥ 50% (n = 13), and C/ patients without LGE and LVEF ≥ 50% (n = 30). MAPSE and global LV strains of the 3 DMD groups were compared to controls (n = 18). Groups A and B had significantly reduced values of MAPSE, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in comparison to controls (p < 0.05). The values of MAPSE (11.6 ± 1.9 v 13.7 ± 2.7 mm) and GCS (- 26.2 ± 4.2 v - 30.0 ± 5.1%) were significantly reduced in group C compared to the controls (p < 0.05). CONCLUSION: DMD patients had decreased LV systolic function measured by MAPSE and global LV strain even in the case of normal LV EF and the absence of LGE. FT and MAPSE measurement provide sensitive assessment of early cardiac involvement in DMD patients.

Echocardiographic signs of subclinical cardiac function impairment in Duchenne dystrophy gene carriers.

To assess subclinical cardiac function impairment in Duchenne dystrophy (DMD) female carriers. Forty-four female subjects proved as DMD carriers underwent echocardiographic examination including tissue Doppler imaging (TDI) of mitral and tricuspid annulus. Seventeen age-matched healthy female subjects served as controls. A significant differences in peak systolic annular velocity (Sa) between carriers and controls were found for lateral and septal part of the mitral annulus and for tricuspid annulus (0.09 vs. 0.11 m/s, p < 0.001, 0.08 vs. 0.09 m/s, p < 0.01 and 0.13 vs. 0.14 m/s, p = 0.02 respectively). There was also difference in early diastolic velocity (Ea) of the septal part of the mitral annulus (0.11 vs. 0.13 m/s, p = 0.03). The subclinical deterioration of systolic function is presented even in asymptomatic DMD female carriers.

Anti-Müllerian hormone as an ovarian reserve marker in women with the most frequent muscular dystrophies.

Some muscular dystrophies may have a negative impact on fertility. A decreased ovarian reserve is 1 of the factors assumed to be involved in fertility impairment. AMH (anti-Müllerian hormone) is currently considered the best measure of ovarian reserve.A total of 21 females with myotonic dystrophy type 1 (MD1), 25 females with myotonic dystrophy type 2 (MD2), 12 females with facioscapulohumeral muscular dystrophy (FSHD), 12 female carriers of Duchenne muscular dystrophy mutations (cDMD) and 86 age-matched healthy controls of reproductive age (range 18 - 44 years) were included in this case control study. An enzymatically amplified 2-site immunoassay was used to measure serum AMH level.The MD1 group shows a significant decrease of AMH values (median 0.7 ng/mL; range 0 - 4.9 ng/mL) compared with age-matched healthy controls (P < .01). AMH levels were similar between patients and controls in terms of females with MD2 (P = .98), FSHD (P = .55) and cDMD (P = .60).This study suggests decreased ovarian reserve in women with MD1, but not in MD2, FSHD and cDMD.

Generation of two Duchenne muscular dystrophy patient-specific induced pluripotent stem cell lines DMD02 and DMD03 (MUNIi001-A and MUNIi003-A).

Duchenne muscular dystrophy (DMD) affects 1:3500-5000 newborn boys and manifests with progressive skeletal muscle wasting, respiratory failure and eventual heart failure. Symptoms show different onset from patients' childhood to the second decade of age. We reprogrammed fibroblasts from two independent DMD patients with a complete loss of dystrophin expression, carrying deletions of exons 45-50 and 48-50. The resulting hiPSCs show expression of pluripotency markers (NANOG, OCT4, SSEA4), differentiation capacity into all three germ layers, normal karyotype, genetic identity to the originating parental fibroblasts and the patient-specific dystrophin mutation.

Prognostic factors and seizure outcome in posterior reversible encephalopathy syndrome (PRES) in children with hematological malignancies and bone marrow failure: A retrospective monocentric study.

PURPOSE: The aim of this study was to evaluate seizure outcome in children with hematological malignancies and PRES and to identify prognostic factors that could help manage the syndrome. METHOD: We retrospectively reviewed the report data of 21 patients diagnosed with hematological malignancy or aplastic anemia and PRES between 2008 and 2018. Basic demographic data, oncology treatment, presymptomatic hypertension before PRES manifestation, neurological status, seizure type, and EEG and MRI findings at PRES onset and at the one-year follow-up visit were studied. Patients who developed remote symptomatic seizures or epilepsy were identified. RESULTS: We included 21 children (11 females and 10 males) in the study. Sixteen patients (76.2%) were diagnosed with ALL and the rest individually with AML, CML, T-lymphoma, Burkitt lymphoma, and severe aplastic anemia. Presymptomatic hypertension (PSH) was evaluated in 19 patients and was present in 18 (94.7%). The duration was 9 h and more in 16 patients (88.8%); the severity was grade II in 12 patients (66.7%). Seizures as the initial symptom of PRES were present in 17 patients (80.9%). Four patients (19.0%) were assessed with remote symptomatic seizures. Two of them (9.5%) had ongoing seizures at the one-year follow-up visit and were diagnosed with epilepsy. The presence of gliosis on follow-up MRI indicated worse outcome with development of epilepsy (without statistical significance). CONCLUSIONS: PRES syndrome has an overall good prognosis and the evolution to epilepsy is rare. The severity and duration of PSH or seizure severity and EEG findings at PRES onsetwere not associated with worse neurological outcomes in this study.