Peripheral Nervous System Involvement in Non-Primary Pediatric Cancer: From Neurotoxicity to Possible Etiologies.

Stefano Pro,Elisa Farina,Umberto Raucci,Margherita Velardi,Alessandra Boni,Antonino Reale,Angela Mastronuzzi,Fausto Badolato,Andrea Carai,Giovanni Di Nardo,Anna Maria Caroleo,Pasquale Parisi,Martina Scilipoti,Massimiliano Valeriani,Iside Alessi,Luciana Vinti

doi:10.3390/jcm10143016

Abstract

Peripheral neuropathy is a well described complication in children with cancer. Oncologists are generally well aware of the toxicity of the main agents, but fear the side effects of new drugs. As chemotherapeutic agents have been correlated with the activation of the immune system such as in Chemotherapy Induced Peripheral Neuropathy (CIPN), an abnormal response can lead to Autoimmune Peripheral Neuropathy (APN). Although less frequent but more severe, Radiation Induced Peripheral Neuropathy may be related to irreversible peripheral nervous system (PNS). Pediatric cancer patients also have a higher risk of entering a Pediatric Intensive Care Unit for complications related to therapy and disease. Injury to peripheral nerves is cumulative, and frequently, the additional stress of a malignancy and its therapy can unmask a subclinical neuropathy. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication along with patient factors, namely age and inherited susceptibilities. The recent identification of individual genetic variations has advanced the understanding of physiopathological mechanisms and may direct future treatment approaches. More research is needed on pharmacological agents for the prevention or treatment of the condition as well as rehabilitation interventions, in order to allow for the simultaneous delivery of optimal cancer therapy and the mitigation of toxicity associated with pain and functional impairment. The aim of this paper is to review literature data regarding PNS complications in non-primary pediatric cancer.

Highlights

This article is an open access articlePeripheral nervous system (PNS) complications almost always appear during and immediately after chemotherapeutic treatment, while others present months or even years later
Involvement in pediatric cancer, to improve surveillance strategies, for young children and those with central nervous system (CNS) tumors, and most importantly, to define effective treatment options that will allow the optimization of cancer treatment and the attenuation of toxicity associated with pain and functional impairment
As chemotherapeutic agents have been correlated with the activation of the immune system [134], an abnormal response can lead to Autoimmune Peripheral Neuropathy (APN) (Table 3)

Summary

Introduction

Peripheral nervous system (PNS) complications almost always appear during and immediately after chemotherapeutic treatment, while others present months or even years later. The chemotherapy regimen, thereby limiting its efficacy, which is why finding strategies to overcome this complication is important. Chemotherapy is widely recognized as the more common cause of peripheral neuropathy in cancer patients, and neurotoxicity is the second most important cause as a dose-limiting factor of cancer treatment [1]. The recognition of neurotoxicity patterns is important both to differentiate treatment-related symptoms from cancer involvement of the nervous system and to permit assessing dose adjustment or interruption of the treatment in order to prevent further neurologic injury

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Conclusion