Abstract
PurposeTo investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP) by magnetic resonance neurography (MRN).MethodsTwenty patients (7 female, 13 male, 58.9±10.0 years) with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years) were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG), sciatic nerve normalized T2 (nT2) signal and caliber, and fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD). Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.ResultsDRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001) was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80) and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16). AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.ConclusionOXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.
Highlights
Oxaliplatin (OXA) is a third-generation platinum derivative that is currently utilized as firstline adjuvant and palliative therapy in advanced colorectal cancer [1, 2] and is increasingly applied in other forms of gastrointestinal malignancies.[3, 4] Used in combined regimens with other substances, OXA is associated with prolonged disease progression-free and overall survival.[5]
oxaliplatin-induced peripheral neuropathy (OXA-peripheral neuropathy (PNP)) manifests with morphological and functional correlates that can be detected in vivo by magnetic resonance neurography (MRN)
We report hypertrophy of the dorsal root ganglia (DRG) that stands in contrast to experimental and postmortem studies
Summary
Oxaliplatin (OXA) is a third-generation platinum derivative that is currently utilized as firstline adjuvant and palliative therapy in advanced colorectal cancer [1, 2] and is increasingly applied in other forms of gastrointestinal malignancies.[3, 4] Used in combined regimens with other substances, OXA is associated with prolonged disease progression-free and overall survival.[5] OXA has a good tolerability profile except for a painful peripheral neuropathy (PNP). As principal adverse effect of the substance, which manifests itself in two forms. The acute form of cold-induced transient hyperexcitability phenomena occurs during or shortly after administration of the substance and is probably due to interaction with sodium voltage-gated channels.[6] This form is fully reversible and does not require discontinuation of treatment. The chronic form presents as a distal-symmetric sensory neuropathy with sensory loss, paresthesia, and dysesthesia, and is only incompletely reversible.[7]
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