Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties: Insights from Clinical Practice.

Background: Emerging evidence underscores the high prevalence of neurobehavioral difficulties like ADHD, ASD and OCD, in patients with Duchenne muscular dystrophy (DMD). The substantial impact of these complex behavioral challenges in addition to motor function decline on the well-being of affected individuals and their families is increasingly evident. However, a uniform approach for effective screening, assessment and management of the neurobehavioral symptoms remains elusive. Objective: We explored strategies used by healthcare professionals with clinical expertise in DMD to address neurobehavioral symptoms, in order to uncover diverse practices and to identify potential directions for clinical approaches in managing DMD neurobehavioral symptoms. Methods and results: Twenty-eight respondents from 16 different countries completed an online survey. Only 35% of the centers systematically screened for neurobehavioral difficulties in their DMD population. Predominant screening methods included history taking and clinical observation. Common neurobehavioral difficulties encompassed learning challenges, dependency from adults, anxiety, concentration difficulties, and social deficits. The participating centers frequently employed parental counseling and liaison with psychosocial healthcare professionals for psychosocial intervention. Conclusion: This study underscores the complex behavioral landscape in DMD, highlighting the need for validated screening, assessment and management strategies and collaborative efforts in implementing these. We advocate for international consensus recommendations for screening, assessment and management of neurobehavioral difficulties in DMD to enhance patient care and communication across healthcare settings.

Development and Pilot Validation of the DuMAND Checklist to Screen for Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties (DuMAND).

Background: Patients with Duchenne muscular dystrophy (DMD) face a higher risk of neurobehavioral problems, yet an international consensus on screening, assessing, and managing these difficulties is lacking. Objective: This report introduces the term Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties (DuMAND) to comprehensively cover the spectrum of neurobehavioral issues in DMD patients, including behavior, psychiatric disorders, and various cognitive, academic, and psychosocial deficits. To facilitate screening, the DuMAND Checklist, a 43-item tool with five subscales, was developed. Methods and results: DuMAND categories were derived through literature review, parent (48 mothers and 37 fathers), and expert (n = 28) input and feedback. The DuMAND Checklist subscales were developed iteratively, incorporating item selection, expert panel (n = 10) assessment for face validity, comprehensiveness, and a pilot validation study in a DMD sample (n = 20). DuMAND encompasses five categories: cognition and learning, social responsiveness, emotion regulation, externalizing behavior, and eating and sleeping. Preliminary validation of the DuMAND Checklist indicates acceptable-to-excellent internal consistency and construct validity. Conclusion: By introducing the DuMAND concept, this study seeks to inspire a consensus approach for screening, assessing, and managing neurobehavioral issues in DMD. Incorporating screening, using the DuMAND Checklist, in addition to medical follow-up will facilitate early intervention, addressing a critical gap in identification of neurobehavioral disorders in DMD. Future research is needed to further evaluate psychometric properties of the DuMAND Checklist and investigate the natural course of DuMAND.

Testing a Home Solution for Preparing Young Children for an Awake MRI: A Promising Smartphone Application.

Thanks to its non-invasive nature and high-resolution imaging capabilities, magnetic resonance imaging (MRI) is a valuable diagnostic tool for pediatric patients. However, the fear and anxiety experienced by young children during MRI scans often result in suboptimal image quality and the need for sedation/anesthesia. This study aimed to evaluate the effect of a smartphone application called COSMO@home to prepare children for MRI scans to reduce the need for sedation or general anesthesia. The COSMO@home app was developed incorporating mini-games and an engaging storyline to prepare children for learning goals related to the MRI procedure. A multicenter study was conducted involving four hospitals in Belgium. Eligible children aged 4-10 years were prepared with the COSMO@home app at home. Baseline, pre-scan, and post-scan questionnaires measured anxiety evolution in two age groups (4-6 years and 7-10 years). Eighty-two children participated in the study, with 95% obtaining high-quality MRI images. The app was well-received by children and parents, with minimal technical difficulties reported. In the 4-6-year-old group (N = 33), there was a significant difference between baseline and pre-scan parent-reported anxiety scores, indicating an increase in anxiety levels prior to the scan. In the 7-10-year-old group (N = 49), no significant differences were observed between baseline and pre-scan parent-reported anxiety scores. Overall, the COSMO@home app proved to be useful in preparing children for MRI scans, with high satisfaction rates and successful image outcomes across different hospitals. The app, combined with minimal face-to-face guidance on the day of the scan, showed the potential to replace or assist traditional face-to-face training methods. This innovative approach has the potential to reduce the need for sedation or general anesthesia during pediatric MRI scans and its associated risks and improve patient experience.

The impact of clinical trial participation on quality of life and psychosocial well-being in children with Duchenne muscular dystrophy and their parents.

Clinical trials provide Duchenne muscular dystrophy (DMD) patients access to medication. Nevertheless, such involvement can impose certain burdens, as the protocol may entail strict adherence and additional demands. This study assessed the psychosocial functioning and quality of life in boys with DMD and their parents who participate in clinical trials. DMD families participating in clinical trials (n = 25) and families with DMD patients not involved in clinical trials (N = 18) were included. Questionnaires assessing psychosocial well-being and quality of life were completed by the participants and their parents. MANOVAs were employed to compare outcomes between groups. The results showed that mothers in the clinical trial group experienced significantly higher scores of somatic complaints. Fathers in the clinical trial group reported significantly fewer psychological issues compared to fathers from the other group. DMD patients participating in clinical trials reported a better overall and emotional quality of life compared to them not involved in clinical trials. This study suggests that clinical trial participation may have positive effects on quality of life and psychosocial outcomes. It highlights the importance of providing support and counseling throughout the clinical trial decision making process to minimize potential burden for both eligible and ineligible patients.

Comparison of two corticosteroid regimens on brain volumetrics in patients with Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI). METHODS: In a cross-sectional, two-center study, T1-weighted MRI scans were obtained from three age-matched groups (9-18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel-based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate. RESULTS: Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume. INTERPRETATION: Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.

Psychopharmaceutical treatment for neurobehavioral problems in Duchenne muscular dystrophy: a descriptive study using real-world data.

Patients with Duchenne muscular dystrophy (DMD) are at risk to develop neurobehavioral problems. Evidence on how to treat these difficulties is scarce. This descriptive study reports the clinical experience with psychopharmaceutical treatment in 52 patients with DMD. Electronic patient files were searched for patients with DMD that had been treated with psychopharmaceuticals between 2008 and 2022. Information about neurobehavioral symptoms, type of medication, side effects, and behavioral changes were collected. Two independent clinicians used the clinical global impression scale (CGI) to assess severity of the neurobehavioral problems before and the change in symptoms after treatment. Descriptive statistics were used. Our results include 52 males with DMD (mean age 11 years) treated with psychopharmaceuticals of which 55.8% had four or more comorbid neurobehavioral symptoms. The clinical condition was much improved on the GCI in 54.2% treated with methylphenidate, in 38.9% of the patients treated with fluoxetine, and in 22.2% treated with risperidone. Minimal effects and side effects were also reported. In conclusion, patients with DMD may experience severe neurobehavioral symptoms interfering with learning and/or development. Treatment with psychopharmaceuticals can improve these neurobehavioral symptoms, but further research is needed to gain better insights in psychopharmaceutical treatment in patients with DMD.

Illness Perceptions and Illness Identity in Adolescents and Emerging Adults With Neuromuscular Disorders.

BACKGROUND: Neuromuscular disorders (NMD) are intrusive medical conditions with implications for psychosocial development. OBJECTIVES: This paper explores illness perceptions and illness identity dimensions of youth with NMD. First, we compare illness identity outcomes and illness perceptions of NMD patients with a comparison group of adolescents with type 1 diabetes mellitus (DM). Second, we report about the relationships between NMD-related variables and illness perceptions and illness identity. METHODS: Scores on the Brief Illness Perception Questionnaire and the Illness Identity Questionnaire were compared between a group of NMD patients (N = 59; 12-22 years) and an age- and gender-matched group of DM patients (N = 118). NMD-related variables included time since diagnosis, prognosis, wheelchair use, and physical limitations. RESULTS: Youth with NMD scored significantly higher on two of the four illness identity dimensions than youth with DM. NMD patients reported significantly less positive illness perceptions, experienced more physical symptoms, and had a lower score on understanding of their illness. Within the NMD group, wheelchair-users have a better understanding of their disease than those who are not wheelchair-bound. CONCLUSIONS: The present study is the first to investigate illness identity and illness perceptions in NMD. More research is needed to provide insight in the identity formation process of the growing group of adolescents with NMDs.

Autism in patients with propionic acidemia.

Certain inborn errors of metabolism have been suggested to increase the risk of autistic behavior. In an animal model, propionic acid ingestion triggered abnormal behavior resembling autism. So far only a few cases were reported with propionic acidemia and autistic features. From a series of twelve consecutively diagnosed cases with propionic acidemia, we report on eight patients with autistic features. The patients were followed 2-4 times a year and underwent regular clinical, dietary and laboratory investigations. Psychological evaluation was performed every second to fourth year. All patients were compliant with the standard diet and carnitine supplementation. None of the patients had frequent metabolic decompensations. From the metabolic factors known to impact neuropsychological outcome we detected chronically decreased valine levels and altered valine to leucine ratios in five out of the eight patients. Recurrent lactic acid elevations were present in six out of the eight patients. Five of the eight patients were diagnosed with Autism Spectrum Disorder, four of them had pathogenic variants in PCCB. Disorder according to DSM-IV and/or DSM-5 criteria. One of the patients diagnosed with propionic acidemia by newborn screening had the most significant behavioral features and another was diagnosed with Autism Spectrum Disorder prior to propionic acidemia. We hypothesize that chronic suboptimal intracellular metabolic balance may be responsible for the increased risk for autistic features in propionic acidemia. We propose that patients diagnosed with propionic acidemia should be screened for Autism Spectrum Disorder.