Chemotherapy-induced peripheral neuropathy — diagnosis, evolution and treatment

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activities and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

“…Changes at the level of the tubulin dimer can also influence intracellular transport as the nucleotide (GTP/GDP) bound to the tubulin dimer determines its conformation 28,48 and consequently affects motor protein activity 21,25,26,49 . Drugs interfering with tubulin conformations such as taxol, a drug that favors GTP-tubulin and locks it in its elongated conformational state 15,28,48,50 , have also been shown to disrupt transport dynamics [30][31][32] . However, exactly how transport is affected upon changes in the conformational state of the tubulin dimer is not fully understood.…”

“…In summary, we show that the molecular conformation of the tubulin dimer influences mitochondrial transport in two distinct ways depending on mitochondrial localization. On one hand, the increased straightness of microtubules enriched in elongated tubulin hinders specifically those mitochondria travelling within the microtubule bundle, possibly explaining why studies investigating CIPN linked to taxol treatment observe a decrease in motile organelles and vesicles [30][31][32]61 . On the other hand, mitochondria mobile at the rim of the microtubule bundle are transported at increased velocities as the molecular conformation of tubulin affects kinesin binding and processive velocity in neuronal projections.…”

“…As taxol raises the amount of stable and elongated tubulin dimers, increased kinesin binding and thus more efficient anterograde transport is expected. However, a conundrum arises as one of taxol's common side effects is rather an interruption of axonal transport, possibly leading to chemotherapy induced peripheral neuropathy (CIPN) [30][31][32] . Thus, how the conformational state of tubulin regulates organelle transport is poorly understood.…”

Chemotherapy-induced peripheral neuropathy and its association with quality of life among cancer patients

“…These findings are similar to the findings of Cavaletti, and Marmiroli ( 2015) [29] who reported that numbness and aching/burning pain in toes and feet were significantly worse in patients managed with chemotherapy. Moreover studies by Dermitzakis et al (2016); [30] and Starobova and Vetter (2017) [33] clarify that the sensory subscale of the EORTC QLQ-CIPN20 showing clearly CIPN related manifestations that appears initially in the feet and hands as numbness, tingling, paresthesia and dysesthesias induced by touch, warmer cool temperatures, compromised vibration and changed touch sensations.…”

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy

“…Most often, this type of toxicity is associated with the use of platinum agents, taxanes and vinka alkaloids. Usually the symptoms get worse as the chemotherapy is continued, but may partially or completely resolve after treatment cessation [2]. In a subset of patients the symptoms have been reported as irreversible despite the time that passed since the administration of last dose of chemotherapy [3].…”