Orbach D, Brisse H, Doz F
Département de pédiatrie, institut Curie, 26, rue d'Ulm, 75005 Paris, France.
Arch Pediatr. 2003 Jun;10(6):533-9. doi: 10.1016/s0929-693x(03)00105-2.
The central neurotoxicity of cytotoxic drugs depends on their ability to cross the blood-brain barrier (BBB). The drugs with the highest neurotoxicity are therefore those that cross the BBB most easily: alkylating agents (metabolites of cyclophosphamide and ifosfamide, thiotepa and high-dose melphalan), busulfan, platinum derivatives, aracytine and methotrexate. Apart from aracytine-induced cerebellar toxicity, the clinical signs suggestive of chemotherapy neurotoxicity are relatively nonspecific: altered level of consciousness, seizures, behavioural disorders and motor deficits. Nevertheless, a good knowledge of the various neurological syndromes likely to occur can allow them to be attributed to a drug-induced cause. However, as patients may be receiving several potentially neurotoxic treatments (chemotherapy, concomitant drugs, neurosurgery, radiotherapy), it is difficult to formally confirm the responsibility of the drug, which should only be considered after confirming the absence of radiological and metabolic abnormalities. A specific antagonist treatment can be administered in rare cases (ifosfamide-induced encephalopathy).
细胞毒性药物的中枢神经毒性取决于它们穿越血脑屏障（BBB）的能力。因此，神经毒性最高的药物是那些最容易穿越血脑屏障的药物：烷化剂（环磷酰胺和异环磷酰胺的代谢产物、噻替派和大剂量美法仑）、白消安、铂衍生物、阿糖胞苷和甲氨蝶呤。除了阿糖胞苷引起的小脑毒性外，提示化疗神经毒性的临床体征相对非特异性：意识水平改变、癫痫发作、行为障碍和运动缺陷。然而，对可能发生的各种神经综合征有充分了解可以将它们归因于药物引起的原因。然而，由于患者可能正在接受几种潜在的神经毒性治疗（化疗、伴随药物、神经外科手术、放射治疗），很难正式确认药物的责任，只有在确认没有放射学和代谢异常后才应考虑药物责任。在罕见情况下（异环磷酰胺引起的脑病）可以给予特异性拮抗剂治疗。
