5. Neurophysiological dysfunction in chemotherapy-treated patients: Comparison of different platinum analogues

Publication date: April 2018
Source:Clinical Neurophysiology, Volume 129, Issue 4
Author(s): Hannah C. Timmins, Tiffany Li, Peter Grimison, Jenna E. Murray, Keith M. Cox, Lisa G. Horvath, Craig R. Lewis, David Goldstein, Matthew C. Kiernan, Susanna B. Park
ObjectiveChemotherapy-induced peripheral neuropathy is a prominent side effect of treatment with platinum-based chemotherapies cisplatin and oxaliplatin. Progressive abnormalities in sensory axonal excitability have been linked to neuropathy severity in oxaliplatin-treated patients, but not examined in cisplatin-treated patients.MethodsSensory axonal excitability studies were undertaken in median nerve. Neuropathy was assessed via total neuropathy score reduced (TNSr).ResultsClinical severity of neuropathy was greater (TNSr: 6.9 ± 1.2) in oxaliplatin-treated patients (N = 16, Age: 57.1 ± 3 years, cumulative dose: 801 ± 63.5 mg/m², median 6 months post-completion IQR: 4–12.5) than in cisplatin-treated patients (TNSr: 3.2 ± 0.6, p<.01, N = 17, Age: 48.5 ± 4.3 years, cumulative dose: 316.5 ± 19.3 mg/m², median 7 months post-completion IQR: 3–30.5). Cisplatin and oxaliplatin-treated patients demonstrated deficits in sensory nerve function compared to controls, with increased threshold change in excitability (TEh90-100 ms Cis: −128.7 ± 4.7%; Ox: −140.9 ± 5.9%; control: −116.6 ± 3.1%, p<.01) and reduced median sensory amplitudes (Cis: 24.4 ± 3.0 μV; Ox: 15.7 ± 3.0 μV; control: 43.9 ± 1.1 μV, p<.01) with greater abnormalities in oxaliplatin-treated patients (p<.01). TEh90-100 ms was correlated to median amplitude (r = .418, p<.05), with patients demonstrating greater excitability abnormalities also demonstrating greater reduction in sensory amplitude.ConclusionsChanges in axonal excitability parameters are consistent between platinum-based chemotherapies and linked to neuropathy severity.SignificancePlatinum analogues demonstrate similar pathophysiological mechanisms of nerve dysfunction. Axonal excitability techniques may provide a marker of axonal dysfunction across different platinum chemotherapies.



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