ArticlePloS one2016
Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.Pflugers Archiv : European journal of physiology · 2024Pooled it
- Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial.Muscle & nerve · 2021Trial
- The Diagnostic Potential of Axon Excitability Is Consistent Across Hand Muscles in Amyotrophic Lateral Sclerosis.Muscle & nerve · 2026Article
- Article
- Super excitability at 7 ms: a superior prognostic biomarker beyond CMAP in amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Nerve Excitability in Asymptomatic Carriers and Amyotrophic Lateral Sclerosis Patients With C9orf72.Annals of clinical and translational neurology · 2025Article
- Motor neuron axonal excitability changes in the clinical course of amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Monoclonal Gammopathy in Amyotrophic Lateral Sclerosis: No Impact on Clinical Progression and Immunotherapy Outcomes.European journal of neurology · 2025Article
- Neurophysiological biomarkers of networks impairment in amyotrophic lateral sclerosis.Journal of neurology · 2025Review
- Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- Article
- ICA-27243 improves neuromuscular function and preserves motoneurons in the transgenic SOD1Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.Frontiers in neuroscience · 2024Review
- Biomarkers in amyotrophic lateral sclerosis: current status and future prospects.Nature reviews. Neurology · 2023Review
- The Node of Ranvier as an Interface for Axo-Glial Interactions: Perturbation of Axo-Glial Interactions in Various Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Neurofilament accumulations in amyotrophic lateral sclerosis patients' motor neurons impair axonal initial segment integrity.Cellular and molecular life sciences : CMLS · 2023Article
- Acute retigabine-induced effects on myelinated motor axons in amyotrophic lateral sclerosis.Pharmacology research & perspectives · 2022Article
- A multiparametric activity profiling platform for neuron disease phenotyping and drug screening.Molecular biology of the cell · 2022Article
- Neuronal Hyperexcitability and Free Radical Toxicity in Amyotrophic Lateral Sclerosis: Established and Future Targets.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Role of EphA4 in Mediating Motor Neuron Death in MND.International journal of molecular sciences · 2021Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.
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