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

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.

Examination of the psychometric properties of pediatric-modified total neuropathy score in Turkish children with cancer

“…With the prolongation of life expectancy in cancer, symptoms caused by the chemotherapy agents used in the treatment and the management of these symptoms have gained importance [3]. Some chemotherapy agents cause toxicity in the peripheral nervous system, resulting in chemotherapy-induced peripheral neuropathy (CIPN) [4]. There is less data on the prevalence of CIPN due to the lack of easy-to-use, speci c, and sensitive measurement tools for it [5][6][7].…”

Chemotherapy-Induced Peripheral Neuropathy Leading to Foot Deformity

“…By interrupting the cell cycle, vincristine induces neuronal cell death. These changes are evident in neurophysiological testing, showing a reduction in muscle action potentials which affects approximately 25% of patients 4 . The alterations in action potential among peripheral neurons can cause permanent damage, resulting in a decline in fine motor skills such as balance, mobility, and endurance [5][6][7] .…”

Neurological Involvement in Pediatric Patients with Acute Leukemia: A Retrospective Cohort

“…A retrospective, longitudinal, analytical study involving 607 pediatric patients with AL diagnosis, who attended at the Hematology Department from Centro Médico Nacional “20 de Noviembre” between 1 January 2015 and 31 December 2020, was performed. Inclusion criteria included age younger than 18 y-o, a diagnosis of AL made by a board-certified hematologist with expertise in childhood leukemias and using the criteria proposed by the Franco-British Cooperative Group [ 10 , 12 ]. Patients were excluded if there were incomplete data in the clinical record or a non-clear identification of any clinical manifestation.…”

“…The condition of AL in childhood significantly affects the quality of life at a stage in which the acquisition of motor and cognitive skills is essential [ 10 ]. Fortunately, therapies for Acute Myeloid Leukemia (AML), Mixed-Phenotipe Acute Leukemia (MPAL) [ 11 ] and ALL have increased their effectiveness [ 11 , 12 ]. CNS and Peripheral Nervous System (PNS) involvement in AL has been associated with Leukemic infiltration, chemotherapy, radiotherapy, infection, hemorrhage, cerebrovascular lesions, metabolic/hydroelectrolytic imbalance, syndromes of the inappropriate secretion of antidiuretic hormone or nutritional deficiencies [ 1 , 13 , 14 , 15 , 16 , 17 ], which are all mostly symptoms occurring in the first two months of therapy [ 18 ].…”

“…Atypical clinical manifestations such as headache, loss of balance, fainting, mood swings, seizures, nausea/vomiting and papilledema are often present. Cranial nerve involvement is less common and can cause diplopia, facial numbness, hearing loss, blindness and swallowing difficulties [ 12 ].…”