In rarer situations, this can be due to paraneoplastic syndromes, which tend to have a subacute onset and may be associated with the presence of antineuronal antibodies. In Table 2, examples regarding the possible peripheral neurotoxic effect of cancer-targeted drugs are reported. Patients most at risk are children, those who have received previous cranial radiotherapy, or those receiving concomitant intravenous and intrathecal therapy. The symptom and effect of neurotoxin may also depend on factors such as the type of neurotoxin, person exposed to the amount of neurotoxin, body’s ability to metabolize the toxin and throw out from the system etc.Some of the major symptoms of neurotoxicity are as follows: 1. They also cause cell-cycle kinetics alterations: postmitotic DRG neurons would reenter into the cell cycle and be induced into apoptosis.15 Other pathogenetic hypotheses have been proposed, which involve oxidative stress, mitochondrial dysfunction, reduction in the activity of enzymes involved in DNA base excision, repair of oxidative damage, redox regulation, and cellular transport.16–18, The most obvious mechanism of PNS damage by taxanes is related to their hyper-polymerizing action on microtubules. A number of trials have investigated the benefits of agents such as calcium-magnesium infusions, carbamazepine, gabapentin, amifostine, and glutathione.7,35–52 However, the trials are small studies and no specific prophylaxis can be routinely recommended. Myelin basic protein levels in the CSF may be elevated.24 Typically, only half of those affected will show any sign of recovery. Paola Alberti. The risk of neurotoxicity is increased by age, dose/ schedule (particularly cumulative dose), renal or hepatic impairment, and the concurrent use of neurotropic antiemetics such as phenothiazines.8,75,76, The mechanism of toxicity is not well-understood, but it appears that cytarabine directly causes neuronal death, possibly by the inhibition of cytidine-dependent neurotropic signal transduction,77 although it has also been shown to stimulate the production of reactive oxygen species that may also damage DNA directly by inducing strand breaks.78, Acute cerebellar dysfunction is the commonest central neurotoxicity, occurring in approximately 14% of patients; they typically present with dysarthria, nystagmus, gait ataxia, and confusion. There is no universal grading system for the evaluation of patients with neurological toxicity although two neurotoxicity scoring systems are frequently used: NCI-CTC 3 (National Cancer Institute Common Toxicity Criteria version 3) and ECOG (Eastern Cooperative Oncology Group).30 The NCI-CTCAE scores a variety of symptoms from ataxia to motor neuropathy on a scale of 0 to 5, with 0 being normal, 1 mild self-limiting, 2 moderate, 3 severe undesirable, 4 life-threatening, and 5 death induced by adverse event. Chemotherapy neurotoxicity can effect both the peripheral and central nervous systems. Cytarabine and 5-fluorouracil are the cytotoxics most likely to cause cerebellar dysfunction including truncal ataxia, gait disturbance, and ataxia.8,14,21,22 Acutely, the MRI tends to be normal, but subsequent scans may show chronic atrophy due to irreversible Purkinje cell loss.15–18. A dying-back process that starts from distal nerve endings and is followed by disturbed axonal flow has been demonstrated in models of CIPN associated with taxanes.19 However, macrophage activation in both the DRG and the peripheral nerve, and microglial activation within the spinal cord, also have been demonstrated.20 In an animal study, paclitaxel-induced swelling and vacuolation of axonal mitochondria in A and C fibers was demonstrated.21, Competition studies with paclitaxel demonstrated that epothilones might act on the same or on an overlapping binding site on tubulin. However, it can result in painful and dose-limiting neurotoxic side effects such as hand-foot syndrome and chemotherapy-induced peripheral neuropathy. Neurotoxicity is rare, but may include acute cerebellar dysfunction in 3% to 7% of patients, causing gait ataxia, nystagmus, and scanning speech. Another study was reported in 2014 by Ezendam et al,47 who investigated a cohort of patients with ovarian cancer by using two EORTC QoL scales; the results demonstrated that CIPN symptoms were significantly associated with QoL impairment. Epub 2018 Nov 22. Central nervous system toxicity occurs in approximately 10% to 20% of patients receiving ifosfamide, who present with personality changes, confusion, hallucinations, stupor, and coma.9 More unusually, patients may experience seizures, myoclonus, cranial nerve palsies, or extrapyramidal symptoms.86,87 Symptoms usually begin 12 to14 hours after initiation of an ifosfamide infusion and spontaneously resolve 2 to 3 days after its cessation, although rarely symptoms may persist or even be fatal. Cancer.Net, ASCO.org The effect is cumulative,6 and patients frequently complain of acute subjective paresthesia of the extremities 2 to 3 days after chemotherapy. 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