Neurobehavioral Profile of Young Steroid-Naive Boys With Duchenne Muscular Dystrophy

Beyond Muscle Weakness: Understanding Neurobehavioral Aspects of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is widely recognized as a progressive neuromuscular disorder primarily characterized by muscle degeneration, yet its impact extends significantly to the central nervous system [1, 2]. While the physical manifestations of DMD, such as muscle weakness and cardiomyopathy, receive considerable attention [3], the associated neurobehavioral and cognitive challenges are increasingly understood as critical components of the disease spectrum [4, 5]. Dystrophin, the protein deficient in DMD, has multiple isoforms expressed in various brain regions, and their absence is linked to cognitive impairments and neuropsychiatric comorbidities, including intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder [2, 6, 5]. Despite growing interest, comprehensive and standardized neurobehavioral data, particularly in young, steroid-naive children with DMD, have been limited [7, 1]. A new study now offers fresh insights into these early neurobehavioral profiles, underscoring the importance of early psychosocial screening and targeted interventions.

Characterizing Early Neurobehavioral Challenges in DMD

Previous neurobehavioral data in steroid-naive children with Duchenne muscular dystrophy (DMD) have been limited, often nonstandardized, and frequently derived from small cohorts. Addressing these gaps, the primary objective of the current multinational study was to characterize the baseline neurobehavioral profile of young steroid-naive boys with DMD. The researchers performed a baseline cross-sectional neurobehavioral analysis, recruiting participants from the "Finding the Optimum Regimen for Duchenne Muscular Dystrophy" trial.

Eligible participants were glucocorticoid-naive boys aged 4 to less than 8 years with genetically confirmed DMD; boys with severe behavioral problems affecting participation were excluded. The cohort ultimately included 196 boys aged 4 to less than 8 years, with a mean age of 5.9 ± 1.0 years. To assess neurobehavioral profiles, four parent-reported scales were analyzed: the Strengths and Difficulties Questionnaire (SDQ), the Personal Adjustment and Role Skills Scale (PARS-III), the IOWA Conners-Parent Scale, and the Revised Rutter Scale.

Prevalence of Speech, Learning, and Emotional Difficulties

The study revealed a notable prevalence of developmental challenges among young boys with Duchenne muscular dystrophy. Specifically, approximately 40% of participants reported speech difficulties, while approximately 25% reported learning difficulties. A significant overlap was observed, with 20% of the boys presenting with both speech and learning difficulties. These findings underscore the early emergence of these neurodevelopmental concerns within this population.

Despite these reported difficulties, the overall neurobehavioral assessment indicated that scores across the various parent-reported scales, including the Strengths and Difficulties Questionnaire (SDQ) and Personal Adjustment and Role Skills Scale (PARS-III), were strongly correlated. However, only a smaller proportion of boys, 5%-10%, exceeded screening cutoffs on these neurobehavioral scales. Critically, the presence of speech and learning difficulties was associated with worse scores across all neurobehavioral scales, highlighting their impact on broader social and emotional functioning. For boys who registered an above-threshold SDQ Impact score, indicating significant distress or impairment, classroom learning was the most frequently reported difficulty. These results collectively suggest that young boys with Duchenne muscular dystrophy may experience social, emotional, and learning difficulties that can interfere with everyday life, including schoolwork, even in the absence of a formal neurobehavioral diagnosis, emphasizing the need for early clinical attention.

Factors Not Associated With Neurobehavioral Profiles

Beyond characterizing the baseline neurobehavioral profile, the researchers also pursued several secondary objectives, specifically examining associations between these profiles and various developmental and demographic features. These explorations included developmental features such as speech and learning difficulties, motor function, the type of parent respondent completing the questionnaires, brain dystrophin isoform, the child's age, and their country of origin. The study explored these associations to identify potential contributing or modifying factors for the observed neurobehavioral challenges. Notably, the analysis revealed no significant associations with age, brain dystrophin isoforms, or country of origin, indicating that these factors did not substantially influence the neurobehavioral profiles within this cohort of young boys with Duchenne muscular dystrophy.

While many factors showed no significant association, the study did identify some nuanced relationships. Weak correlations were identified between motor function and scores on the Personal Adjustment and Role Skills Scale (PARS-III), a parent-reported measure of adaptive functioning. More specifically, weak correlations were found between the North Star Ambulatory Assessment total score, a measure of motor function, and the PARS-III Total, Peer Relations, and Productivity scores. This suggests a subtle link between physical ability and certain aspects of social and adaptive behavior. Additionally, the researchers observed a difference in reporting patterns based on the parent completing the questionnaire: mothers more frequently reported inattentive-overactive behaviors than fathers, a finding that may reflect differences in observation, interaction, or reporting bias between parents.

Clinical Implications and Future Directions

The findings from this multinational study underscore the critical need for early and routine psychosocial screening in young boys diagnosed with Duchenne muscular dystrophy (DMD), which is recognized as the most common pediatric hereditary neuromuscular disorder. Despite the absence of a formal neurobehavioral diagnosis in many cases, the observed social, emotional, and learning difficulties can significantly interfere with daily life, including school performance. The researchers emphasize that these challenges warrant targeted interventions to support affected children and their families. Integrating such screening into standard clinical care could facilitate earlier identification of difficulties, allowing for timely implementation of educational and behavioral support strategies.

It is important for clinicians to consider that this investigation involved a selected cohort of steroid-naive boys aged 4 to less than 8 years, meaning the generalizability of these specific prevalence rates to all boys with DMD, particularly those on glucocorticoid therapy or outside this age range, may require further study. This research was conducted as part of the "Finding the Optimum Regimen for Duchenne Muscular Dystrophy" trial, which is registered on ClinicalTrials.gov under identifier NCT01603407. The trial was initially submitted on April 3, 2012, and the first participant was enrolled on January 30, 2013, providing a robust framework for these baseline neurobehavioral assessments.

References

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3. Gandhi S, Sweeney HL, Hart CC, Han R, Perry CGR. Cardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response. Cells. 2024. doi:10.3390/cells13141168

4. Tizzoni F, Canella G, Fave AD, et al. Living with Duchenne Muscular Dystrophy Beyond the Physical Implications: Cognitive Features, Psychopathology Aspects, and Psychosocial Resources—A Narrative Review. Brain Sciences. 2025. doi:10.3390/brainsci15070695

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7. Gadaleta G, Geagan C, Schiava M, et al. Neurobehavioral Profiles in Young Steroid-Naive Boys With Duchenne Muscular Dystrophy: A Baseline Data Analysis From the FOR-DMD Trial.. Neurology. 2026. doi:10.1212/WNL.0000000000218094