Trusted Resources: Education
Scientific literature and patient education texts
Axonal Excitability Changes in Children With Spinal Muscular Atrophy Treated With Nusinersen
source: The Journal of Physiology
year: 2022
authors: Kariyawasam DST, D'Silva AM, Herbert K, Howells J, Carey K, Kandula T, Farrar MA, Lin CS
summary/abstract:Spinal muscular atrophy (SMA) is associated with developmental disruption of motor axons in ventral roots of the spinal cord alongside motor axon degeneration. The pathogenesis of peripheral axonal change during development is pertinent to understand treatment response. Nerve excitability techniques, stimulating the median motor nerve at the wrist, were utilised to investigate axonal change during neurodevelopment in 24 children with SMA, compared with 71 age-matched controls. Longitudinal axonal response to nusinersen treatment in 18 children was also investigated. Significant differences in axonal development were noted in the youngest children with SMA, signified by reduced compound muscle action potential (CMAP) (P = 0.030), higher axonal threshold (P = 0.016), rheobase (minimal current amplitude of infinite duration, required to generate an action potential) (P = 0.012) and greater changes in depolarising and hyperpolarising threshold electrotonus. Subexcitability increased in all children with SMA, compared to controls. With treatment, nerve excitability changes were observed prominently in young children, with increases in CMAP, reduction in axonal threshold, fanning-in of threshold electrotonus, increase in resting current-threshold slope and reduction in subexcitability. Whilst motor axons continue to mature in SMA, developmental delays in passive and active membrane properties occur especially in early childhood. Concurrently, motor axons actively undergo degeneration. Nusinersen restores the developmental trajectory of motor axons reducing degeneration, especially in children with early treatment initiation. Our findings move the field forward in understanding the developmental aspect of childhood-onset motor neurone diseases and changes in axonal function associated with disease modification.
organization: Sydney Children's Hospital, Australia; University of New South Wales, Australia; University of Sydney, AustraliaDOI: 10.1113/JP282249
read more
Related Content
-
SMA Type 1 – Looking After Your Child Who Has Had a Recent DiagnosisThe aim of everyone involved in your chi...
-
Spinal Muscular Atrophy: From Rags to RichesThe aim of this paper is to provide a sh...
-
Spinal Muscular Atrophy With Respiratory Distress <br /> Type 1: A Novel Variant of IGHMBP2 GeneSpinal muscular atrophy (SMA) with respi...
-
Nonrespiratory Complications of Nusinersen-Treated Spinal Muscular Atrophy Type 1 PatientsBackground: Emergence of new treatments ...
-
New Gene Therapy Transforms SMA (Spinal Muscular Atrophy)https://www.youtube.com/watch?v=C5Dl3iMv...
-
Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening AssaySpinal muscular atrophy (SMA) is an auto...
-
Patient and Caregiver Treatment Preferences in Type 2 and Non-Ambulatory Type 3 Spinal Muscular Atrophy: A Discrete ...Background: Spinal muscular atrophy (SMA...