Neuro-Cardio-Autonomic Modulations in Children with Duchenne Muscular Dystrophy

Article type: Research Article

Authors: Inbaraj, Ganagarajan^{a; #} | Arjun, Krishnamurthy^{b; #} | Meghana, Adoor^a | Preethish-Kumar, Veeramani^c | John, Anu P^a | Polavarapu, Kiran^c | Nashi, Saraswati^c | Sekar, Deepha^d | Udupa, Kaviraja^a | Prathuysha, Parthipulli V.^e | Prasad, Krishna^a | Bardhan, Mainak^c | Raju, Trichur R.^a | Kramer, Boris W.^f | Nalini, Atchayaram^c | Sathyaprabha, Talakad N.^{a; *}

Affiliations: [a] Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India | [b] Department of CSE, School of Engineering, Dayananda Sagar University, Bangalore | [c] Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India | [d] Department of Molecular Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India | [e] Department of Biostatistics, National Institute of Mental Health and Neurosciences, Bangalore, India | [f] Department of Paediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands | [g] National Institute of Mental Health and Neuro Sciences, Bengaluru, India

Correspondence: [*] Correspondence to: Dr Talakad Sathyaprabha, MD, PhD, Professor NeuroPhysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Near Bangalore Milk Dairy, 560029, Bengaluru, Karnataka, India. E-mail: [email protected].; Orcid ID 0000-0001-9865-0586

Note: [#] These authors contributed equally.

Abstract: Background and Objective:Duchenne muscular dystrophy (DMD) is a degenerative X-linked muscle disease. Death frequently results from complications in cardiopulmonary systems. Preclinical/early diagnosis of cardiac autonomic abnormalities may aid initiate cardioprotective therapy and enhance prognosis. Methods:A cross sectional, prospective study of 38 DMD boys compared with 37 age-matched healthy controls was conducted. Lead II electrocardiography and beat-to-beat blood pressure were recorded to assess heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) in a standardized environment. Data were analysed and correlated with disease severity and genotype. Results:In the DMD group, the median age at assessment was 8 years [IQR 7–9 years], the median age at disease onset was 3 years [IQR, 2–6 years], and the mean duration of illness was 4 years [IQR, 2.5–5]. DNA sequencing showed deletions in 34/38 (89.5 %) and duplications in 4/38 (10.5%) patients. The median heart rate in DMD children was significantly higher [101.19 (Range, 94.71–108.49)] /min compared to controls [81 (Range, 76.2–92.76)] /min (p < 0.05). All the assessed HRV and BPV parameters were significantly impaired in DMD cases except for the coefficient of variance of systolic blood pressure. Further, BRS parameters were also significantly reduced in DMD, excluding alpha-LF. A positive correlation was found between alpha HF with age at onset and duration of illness. Conclusion:This study demonstrates a distinct early impairment of neuro-cardio-autonomic regulation in DMD. Simple yet effective non-invasive techniques such as HRV, BPV, and BRS may help identify cardiac dysfunction in a pre-clinical state, paving the way for early cardio-protective therapies and limiting disease progression in DMD patients.

Keywords: Duchenne muscular dystrophy, autonomic modulation, heart rate variability, blood pressure variability, baroreflex sensitivity

DOI: 10.3233/JND-221621

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 2, pp. 227-238, 2023