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Journal article
The effect of lamotrigine on cortical inhibition and plasticity in Neurofibromatosis type 1: exploratory analysis of a randomized controlled trial (NF1-EXCEL)
Clinical Neurophysiology, Vol.173, In Press
2025
Abstract
Objective
Neurofibromatosis type 1 (NF1) is a genetic disorder associated with cognitive and behavioral deficits. In NF1, decreased neurofibromin levels attenuate hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) activity, thereby increasing inhibitory interneuron activity and decreasing synaptic plasticity. Lamotrigine, an HCN1-agonist, rescued this electrophysiological phenotype in an NF1 mouse model. We investigated whether lamotrigine can alter cortical inhibition and plasticity in adolescents with NF1 using transcranial magnetic stimulation (TMS).
Methods
We performed an explorative analysis of secondary outcomes in the NF1-EXCEL trial (Clinicaltrials.gov identifier NCT02256124). Thirty-one adolescents with NF1 were randomized to either receive lamotrigine or a placebo. Using TMS, cortical inhibition was assessed with short-interval intracortical inhibition (SICI) and cortical plasticity with paired associative stimulation (PAS) at baseline and after 10 weeks of intervention.
Results
Lamotrigine did not affect baseline cortical excitability. Additionally, no significant effects on either SICI or PAS responses were found after lamotrigine treatment in adolescents with NF1. Finally, lamotrigine did not affect pre-PAS single-pulse cortical excitability measures.
Conclusion
10-week lamotrigine treatment does not alter cortical inhibition and plasticity in adolescents with NF1.
Significance
While limited by a small sample size, our study indicates that lamotrigine cannot consistently modulate SICI or PAS in adolescents with NF1, suggesting limited potential for treating the underlying pathophysiological mechanisms.
Details
- Title
- The effect of lamotrigine on cortical inhibition and plasticity in Neurofibromatosis type 1: exploratory analysis of a randomized controlled trial (NF1-EXCEL)
- Authors/Creators
- Myrthe J. OttenhoffAnouk HeuvelmansJesminne CastricumJoke H. M. TulenGuy RensHakuei Fujiyama - Murdoch University, Centre for Healthy AgeingOron LevinStephan P. SwinnenHenriette A. MollMarie-Claire Y. de WitYpe Elgersma
- Publication Details
- Clinical Neurophysiology, Vol.173, In Press
- Publisher
- Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology.
- Number of pages
- 13
- Grant note
- Let's Beat NFNetherlands Organization for Health Research and Development (ZonMW): 40-41900-98-224 EpilepsieNL: 20-13
This study was financially supported by Let's Beat NF, The Netherlands Organization for Health Research and Development (ZonMW) (grant number 40-41900-98-224). AH is supported by EpilepsieNL (grant number 20-13). Teva pharmaceuticals sponsored this study by providing the study drug. The sponsors of the study had no role in the conception and design of the trial, the collection, analysis, and interpretation of the data, the writing of the manuscript, or the decision to publish the results.
- Identifiers
- 991005751130207891
- Copyright
- © 2025 The Authors.
- Murdoch Affiliation
- Centre for Healthy Ageing
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.118 Soft Tissue, Bone & Nerve Cancers
- 1.118.1130 Neurofibromatosis Tumors
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior