Rikke Heide1, Hugh Bostock2, Lise Ventzel3, Peter Grafe4, Joseph Bergmans5, Anders Fuglsang-Frederiksen6, Nanna B Finnerup7, Hatice Tankisi8. 1. Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark; Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 2. Institute of Neurology, Queen Square House, London, United Kingdom. 3. Department of Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 4. Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany. 5. Laboratory of Clinical Neurophysiology, Faculty of Medicine, University of Louvain, Brussels, Belgium. 6. Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark. 7. Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 8. Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: hatitank@rm.dk.
Abstract
OBJECTIVE: Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity. METHODS: Questionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3 days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination). RESULTS: The most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho = 0.80, p < .01). The motor nerve excitability changes were well modeled by a slowing of sodium channel inactivation, and were proportional to dose/m2 with a half-life of about 10d. CONCLUSIONS: Oxaliplatin induces reversible slowing of sodium channel inactivation in motor axons, and these changes are closely related to the reversible cold allodynia. However, further studies are required due to small sample size in this study. SIGNIFICANCE: Nerve excitability data provide an index of sodium channel dysfunction: an objective biomarker of acute oxaliplatin neurotoxicity.
OBJECTIVE:Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity. METHODS: Questionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3 days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination). RESULTS: The most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho = 0.80, p < .01). The motor nerve excitability changes were well modeled by a slowing of sodium channel inactivation, and were proportional to dose/m2 with a half-life of about 10d. CONCLUSIONS:Oxaliplatin induces reversible slowing of sodium channel inactivation in motor axons, and these changes are closely related to the reversible cold allodynia. However, further studies are required due to small sample size in this study. SIGNIFICANCE: Nerve excitability data provide an index of sodium channel dysfunction: an objective biomarker of acute oxaliplatinneurotoxicity.
Authors: Andreas C Themistocleous; Alexander G Kristensen; Roma Sola; Sandra S Gylfadottir; Kristine Bennedsgaard; Mustapha Itani; Thomas Krøigård; Lise Ventzel; Søren H Sindrup; Troels S Jensen; Hugh Bostock; Jordi Serra; Nanna B Finnerup; Hatice Tankisi; David L H Bennett Journal: Ann Neurol Date: 2022-03-07 Impact factor: 11.274
Authors: Kristine Bennedsgaard; Lise Ventzel; Peter Grafe; Jenny Tigerholm; Andreas C Themistocleous; David L Bennett; Hatice Tankisi; Nanna B Finnerup Journal: Muscle Nerve Date: 2020-03-20 Impact factor: 3.217
Authors: Alex Molassiotis; Hui Lin Cheng; Violeta Lopez; Joseph S K Au; Alexandre Chan; Aishwarya Bandla; K T Leung; Y C Li; K H Wong; Lorna K P Suen; Choi Wan Chan; Janelle Yorke; Carole Farrell; Raghav Sundar Journal: BMC Cancer Date: 2019-02-08 Impact factor: 4.430
Authors: Kristine Bennedsgaard; Lise Ventzel; Andreas C Themistocleous; David L Bennett; Anders B Jensen; Anni R Jensen; Niels T Andersen; Troels S Jensen; Hatice Tankisi; Nanna B Finnerup Journal: Cancer Med Date: 2020-05-29 Impact factor: 4.452