Acute neurotoxicity following vincristine due to Charcot–Marie–Tooth disease in a young child with medulloblastoma

Abstract

Vincristine (VCR), a microtubule inhibitor that arrests the cell cycle by blocking metaphase of mitosis, is unique among the vinca alkaloids for causing polyneuropathy. Patients with increased risk of VCR neurotoxicity include the elderly and those with prior history of neuropathy-prone medical conditions. Identifying such risk factors prior to the development of neurotoxicity should be a goal prior to VCR administration. Clinicians should obtain a thorough medical and family history of neuropathies in any child scheduled to receive neurotoxic medications to avoid exacerbating an underlying disorder. We report a case of a young child with newly diagnosed medulloblastoma who started treatment on a VCR-containing chemotherapy regimen following surgery and craniospinal radiation. She subsequently developed severe peripheral polyneuropathy and new enhancement of the cranial and nerve roots following a relatively low cumulative dose of VCR and was diagnosed with previously unidentified Charcot–Marie–Tooth disease (CMTD) Type 1A. This case highlights that an evaluation of risk factors should be completed prior to initiation of neurotoxic chemotherapies and advocates for testing for inherited neuropathies such as CMTD even in asymptomatic patients when hereditary neuropathy is suspected.

Severe Vincristine-related Neurotoxicity in 5 Patients With Pediatric Acute Lymphoblastic Leukemia Requiring Discontinuation of Vincristine: A Description of Long-term Outcome

“…Severe vincristine neurotoxicity may be the first presenting symptom of an inherited neuropathy 3. Such toxicity resulting in diagnosis of CMT as well as upfront omission of vincristine in patients with known CMT has been documented in other pediatric malignancies such as medulloblastoma, where vincristine is also part of treatment backbones 7,9,10…”

“…3 Such toxicity resulting in diagnosis of CMT as well as upfront omission of vincristine in patients with known CMT has been documented in other pediatric malignancies such as medulloblastoma, where vincristine is also part of treatment backbones. 7,9,10 In this retrospective chart review, we present the clinical course and outcomes of 5 pediatric patients with ALL who developed severe neurotoxicity that prompted discontinuation of vincristine.…”