Oxaliplatin‐induced neurotoxicity: Acute hyperexcitability and chronic neuropathy

Abstract

Oxaliplatin, a platinum-based chemotherapeutic agent, is effective in the treatment of solid tumors, particularly colorectal cancer. During and immediately following oxaliplatin infusion, patients may experience cold-induced paresthesias, throat and jaw tightness, and occasionally focal weakness. We assessed nerve conduction studies and findings on needle electromyography of patients with metastatic colorectal cancer before and during treatment with oxaliplatin. Twenty-two patients had follow-up studies within 48 h following oxaliplatin infusions, and 14 patients had follow-up studies after 3-9 treatment cycles. Repetitive compound muscle action potentials and neuromyotonic discharges were observed in the first 24-48 h following oxaliplatin infusion, but resolved by 3 weeks. After 8-9 treatment cycles, sensory nerve action potential amplitudes declined, without conduction velocity changes or neuromyotonic discharges. The acute neurological symptoms reflect a state of peripheral nerve hyperexcitability that likely represents a transient oxaliplatin-induced channelopathy. Chronic treatment causes an axonal neuropathy similar to other platinum-based chemotherapeutic agents.

Polymorphism of CAG motif of SK3 gene is associated with acute oxaliplatin neurotoxicity

“…In particular, in patients developing acute neurotoxicity, a single electrical stimulus to the motor nerves produces a compound muscle action potential (CMAP) followed by repetitive discharges. At the same time, electromyography (EMG) studies show spontaneous high frequency discharges of motor unit multiplets [7,8]. Overall, these findings are consistent with those observed in neuromyotomia [9,10], an autoimmune disease caused by auto-antibodies against voltagegated potassium channels (VGKC).…”

“…The first is probably related to an axonopathy due to the accumulation of platinum compounds within the dorsal root ganglia, the second to a transient impairment of ion channel function, but there is still no agreement about which channel is involved [6][7][8][11][12][13], neither about the possible correlation between acute and chronic neurotoxocity.…”

Variable Threshold of Trigeminal Cold-Thermosensitive Neurons Is Determined by a Balance between TRPM8 and Kv1 Potassium Channels

“…Furthermore, coldevoked hyperalgesia is a disabling condition in postherpetic neuralgia (Pappagallo et al, 2000) and in neuropathies caused by cancer chemotherapy, often limiting the maximal dosage of prescribed antitumoral drugs (Lehky et al, 2004). These effects have been generally interpreted as the result of an altered processing of the information provided by low-threshold cold receptors and nociceptors at spinal cord neurons (Wahren et al, 1989).…”

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

“…Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity [4][5][6] . In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons [7][8][9] .…”