Chessells J M, Cox T C, Kendall B, Cavanagh N P, Jannoun L, Richards S
Hospital for Sick Children, London.
Arch Dis Child. 1990 Apr;65(4):416-22. doi: 10.1136/adc.65.4.416.
Serial cranial computed tomograms were carried out in 136 children with acute lymphoblastic leukaemia who were receiving 24 Gy or 18 Gy of cranial irradiation and continuing treatment with doses of methotrexate given weekly orally or intramuscularly. The findings were correlated with treatment variables, the development of fits, and the intelligence quotient (IQ). Reversible brain shrinkage, attributed to treatment with steroids, was found on 87 of 114 initial scans (76%); 14 showed changes in white matter during treatment (10%), and calcification was found in 13 either during or after treatment (10%). Eight children (6%) had fits, and in six of the eight there were changes in white matter or calcification on the scans. Comparison of the two radiotherapy dosages showed no difference in the incidence of abnormalities seen on computed tomography, fits, or serial IQ measurements, but children receiving intramuscular methotrexate had a higher incidence of calcification and a lower mean IQ at one year than those who received the drug orally, although this difference was not apparent later. Younger children were more likely to develop changes on computed tomograms and fits, and to have low IQs on completion of treatment, with changes most apparent in those less than 2 years of age. There were highly significant correlations between abnormalities on computed tomography, fits, and IQ. These findings confirm the neurological vulnerability of younger children with acute lymphoblastic leukaemia, show an association between abnormalities on computed tomography and intellectual deficit, and suggest that methotrexate is more toxic when given intramuscularly than orally. They provide no evidence that 18 Gy of cranial irradiation is less toxic than 24 Gy, and indicate the need for alternative treatment regimens.
对136例接受24 Gy或18 Gy颅脑照射并持续每周口服或肌肉注射甲氨蝶呤进行治疗的急性淋巴细胞白血病患儿进行了系列头颅计算机断层扫描。将扫描结果与治疗变量、癫痫发作情况以及智商（IQ）进行了相关性分析。在114例首次扫描中，87例（76%）发现了归因于类固醇治疗的可逆性脑萎缩；14例（10%）在治疗期间出现了白质变化，13例在治疗期间或治疗后发现了钙化（10%）。8名儿童（6%）出现了癫痫发作，其中6名儿童的扫描显示有白质变化或钙化。比较两种放疗剂量发现，计算机断层扫描所见异常、癫痫发作或系列智商测量的发生率没有差异，但接受肌肉注射甲氨蝶呤的儿童钙化发生率较高，且在1岁时的平均智商低于口服该药的儿童，尽管这种差异在之后并不明显。年龄较小的儿童在计算机断层扫描上更易出现变化和癫痫发作，且在治疗结束时智商较低，在2岁以下的儿童中变化最为明显。计算机断层扫描异常、癫痫发作和智商之间存在高度显著的相关性。这些发现证实了急性淋巴细胞白血病患儿中年龄较小者的神经易损性，显示了计算机断层扫描异常与智力缺陷之间的关联，并提示肌肉注射甲氨蝶呤比口服毒性更大。没有证据表明18 Gy颅脑照射的毒性低于24 Gy，并表明需要替代治疗方案。
