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Neuromyotonia and CASPR2 antibodies: electrophysiological clues to disease pathophysiology

2025-09-01Review article Open access
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dc.contributor.authorMoura, João
dc.contributor.authorAntenucci, Pietro
dc.contributor.authorCoutinho, Ester
dc.contributor.authorBhatia, Kailash P.
dc.contributor.authorRocchi, Lorenzo
dc.contributor.authorLatorre, Anna
dc.date.accessioned2025-10-09T09:46:26Z
dc.date.available2025-10-09T09:46:26Z
dc.date.issued2025-09-01
dc.description.abstractContactin-associated protein-like 2 (CASPR2) is a transmembrane protein of the neurexin superfamily, essential for clustering voltage-gated potassium channels, particularly Kv1, at the juxtaparanodal regions of myelinated axons. This precise localisation is essential for maintaining normal axonal excitability and preventing aberrant signal propagation. Autoantibodies targeting CASPR2 have been associated with various neurological syndromes, notably peripheral nerve hyperexcitability (PNH), which presents clinically with neuromyotonia and myokymia. PNH is characterised by distinctive electrophysiological findings, including neuromyotonic discharges, myokymic discharges, and afterdischarges, which provide diagnostic value and insight into underlying pathophysiology. This review explores the mechanisms of anti-CASPR2-associated PNH, focusing on how antibody-mediated disruption of Kv1 channel clustering leads to altered axonal excitability. Current evidence suggests that both the distal and proximal segments of the axon are sites of pathological activity, where impairments in action potential termination and re-entry prevention result in spontaneous, repetitive discharges. While afterdischarges likely originate within the axon, the precise location—whether in the alpha-motoneuron soma or axon—is uncertain. The involvement of spinal inhibitory circuits has also been proposed, though it remains speculative. Understanding the neurophysiological features of anti-CASPR2-associated PNH is essential for improving diagnostic accuracy and guiding treatment strategies. Further research is needed to clarify the mechanisms of CASPR2-related hyperexcitability.eng
dc.identifier.citationMoura, J., Antenucci, P., Coutinho, E., & Bhatia, K. P. et al. (2025). Neuromyotonia and CASPR2 antibodies: electrophysiological clues to disease pathophysiology. Biomolecules, 15(9), Article 1262. https://doi.org/10.3390/biom15091262
dc.identifier.doi10.3390/biom15091262
dc.identifier.eid105017238941
dc.identifier.issn2218-273X
dc.identifier.othera154f0fd-ee2c-474a-a28a-93ef2bf1d8af
dc.identifier.pmcPMC12467067
dc.identifier.pmid41008569
dc.identifier.urihttp://hdl.handle.net/10400.14/55174
dc.identifier.wos001580420300001
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAfterdischarges
dc.subjectCASPR2
dc.subjectClinical neurophysiology
dc.subjectNeuromyotonia
dc.subjectPeripheral nerve hyperexcitability
dc.titleNeuromyotonia and CASPR2 antibodies: electrophysiological clues to disease pathophysiologyeng
dc.typereview article
dspace.entity.typePublication
oaire.citation.issue9
oaire.citation.titleBiomolecules
oaire.citation.volume15
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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