Background: Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e. nusinersen and risdiplam, improve motor function in SMA, but treatment effects vary. Experimental studies indicate that motor unit dysfunction encompasses multiple features, including abnormal function of the motor neuron, axon, neuromuscular junction and muscle fibres. The relative contributions of dysfunction of different parts of the motor unit to the clinical phenotype are unknown. Predictive biomarkers for clinical efficacy are currently lacking. The goals of this project are to study the association of electrophysiological abnormalities of the peripheral motor system in relation to 1) SMA clinical phenotypes and 2) treatment response in patients treated with SMN2-splicing modifiers (nusinersen or risdiplam).
Methods: We designed an investigator-initiated, monocentre, longitudinal cohort study using electrophysiological techniques ('the SMA Motor Map') in Dutch children (≥ 12 years) and adults with SMA types 1-4. The protocol includes the compound muscle action potential scan, nerve excitability testing and repetitive nerve stimulation test, executed unilaterally at the median nerve. Part one cross-sectionally assesses the association of electrophysiological abnormalities in relation to SMA clinical phenotypes in treatment-naïve patients. Part two investigates the predictive value of electrophysiological changes at two-months treatment for a positive clinical motor response after one-year treatment with SMN2-splicing modifiers. We will include 100 patients in each part of the study.
Discussion: This study will provide important information on the pathophysiology of the peripheral motor system of treatment-naïve patients with SMA through electrophysiological techniques. More importantly, the longitudinal analysis in patients on SMN2-splicing modifying therapies (i.e. nusinersen and risdiplam) intents to develop non-invasive electrophysiological biomarkers for treatment response in order to improve (individualized) treatment decisions.
Trial Registration: NL72562.041.20 (registered at https://www.toetsingonline.nl . 26-03-2020).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124000 | PMC |
| http://dx.doi.org/10.1186/s12883-023-03207-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Assessment of Occupational Hazards and Role of Life-Saving Gadgets Among Small-Scale Motorised Fishers on India's Southernmost Coasts.
J Agromedicine
January 2025
ICAR, Central Marine Fisheries Research Institute, FRAEED, Ernakulam, India.
Objective: Marine fishing ranks among the most hazardous occupations globally, with risks intensifying for small-sized vessels venturing deeper into the sea due to the scarcity of near-shore fish and high market demand. This study identifies various occupational hazards and the use of safety equipment among small-scale motorized fishers using traditional fishing methods in the southernmost coastal regions of India.
Methods: The primary data were collected from 253 artisanal small-scale motorized fishers through a multi-stage stratified random sampling method.
Development, Measurement Properties and Reference Values of the Upper Extremity Motor Coordination Test: A New Motor Coordination Test of the Upper Limbs.
Physiother Res Int
January 2025
Department of Physiotherapy, Centro Universitário FUNCESI, Itabira, Brazil.
Background And Purpose: To develop a new test to assess the motor coordination of the upper limbs, and to investigate the test-retest and inter-rater reliability, construct validity, standard error of measurement (SEM), minimum detectable change (MDC), and the reference values.
Methods: The Upper Extremity Motor Coordination Test (UEMOCOT)was applied for 20 s, with the individual touching two targets (one right and one left) as quickly as possible, first with the hand (manual task) and then with the index finger (finger task). To test-retest reliability, the UEMOCOT was administered two times.
A preliminary clinical study related to vestibular migraine and cognitive dysfunction.
Front Hum Neurosci
December 2024
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Background And Purpose: Vestibular migraine (VM) is a common clinical disorder with a genetic predisposition characterized by recurrent episodes of dizziness/vertigo. Patients often complain of the presence of cognitive dysfunction manifestations such as memory loss, which causes great distress in daily life. In this study, we will explore the characteristics and possible risk factors of VM-related cognitive dysfunction by observing the cognitive function and vestibular function status of VM patients, laying the foundation for further exploration of the mechanisms of VM-related cognitive dysfunction.
View Article and Find Full Text PDFSevere Delayed-Onset Meningitis Developed One Year After a Basilar Skull Fracture Without a Cerebrospinal Fluid Leak: A Case Report.
Cureus
December 2024
Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, JPN.
Traumatic cerebrospinal fluid (CSF) leakage from skull base fractures increases the risk of bacterial meningitis, which is associated with a high mortality rate in adults, and commonly results in severe neurological outcomes. While most cases of CSF leakage occur within three months post-injury and generally resolve spontaneously, delayed-onset meningitis remains a challenging complication. Herein, we report a rare case of severe bacterial meningitis with an intraventricular abscess one year following a frontal skull base fracture, despite no CSF leak.
View Article and Find Full Text PDFTraumatic Posterior Sternoclavicular Joint Dislocation With a Five-Day Delayed Presentation: A Case Report.
Cureus
December 2024
Orthopedic Department, King Fahad Medical City, Riyadh, SAU.
Posterior sternoclavicular joint (SCJ) dislocation is a rare but potentially life-threatening injury due to its proximity to critical mediastinal structures. Early diagnosis and prompt management are essential to prevent severe complications such as vascular or respiratory compromise. We report a case of a 23-year-old male who presented to our emergency department five days after a high-energy motor vehicle accident with isolated, closed posterior dislocation of the SCJ.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!