Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):1135-41. doi: 10.1016/j.ijrobp.2011.04.017. Epub 2011 Jun 12.
Therapy and tumor-related effects such as hypoperfusion, internal hydrocephalus, chemotherapy, and irradiation lead to significant motor and cognitive sequelae in pediatric posterior fossa tumor survivors. A distinct proportion of those factors related to the resulting late effects is hitherto poorly understood. This study aimed at separating the effects of neurotoxic factors on central nervous system metabolism by using H-1 MR spectroscopy to quantify cerebral metabolite concentrations in these patients in comparison to those in age-matched healthy peers.
Fifteen patients with World Health Organization (WHO) I pilocytic astrocytoma (PA) treated by resection only, 24 patients with WHO IV medulloblastoma (MB), who additionally received chemotherapy and craniospinal irradiation, and 43 healthy peers were investigated using single-volume H-1 MR spectroscopy of parietal white matter and gray matter.
Concentrations of N-acetylaspartate (NAA) were significantly decreased in white matter (p < 0.0001) and gray matter (p < 0.0001) of MB patients and in gray matter (p = 0.005) of PA patients, compared to healthy peers. Decreased creatine concentrations in parietal gray matter correlated significantly with older age at diagnosis in both patient groups (MB patients, p = 0.009, r = 0.52; PA patients, p = 0.006, r = 0.7). Longer time periods since diagnosis were associated with lower NAA levels in white matter of PA patients (p = 0.008, r = 0.66).
Differently decreased NAA concentrations were observed in both PA and MB groups of posterior fossa tumor patients. We conclude that this reflects a disturbance of the neurometabolic steady state of normal-appearing brain tissue due to the tumor itself and to the impact of surgery in both patient groups. Further incremental decreases of metabolite concentrations in MB patients may point to additional harm caused by irradiation and chemotherapy. The stronger decrease of NAA in MB patients may correspond to the additional damage of combined irradiation and chemotherapy on neuroaxonal cell viability and number.
治疗和与肿瘤相关的影响，如灌注不足、内部脑积水、化疗和放疗，导致儿童后颅窝肿瘤幸存者出现显著的运动和认知后遗症。迄今为止，人们对这些与晚期效应相关的因素中相当一部分的了解还很有限。本研究旨在通过使用 H-1 磁共振波谱（MRS）定量测量这些患者的脑代谢物浓度，来分离神经毒性因素对中枢神经系统代谢的影响，并将其与年龄匹配的健康同龄人的结果进行比较。
对 15 例经手术切除的世卫组织（WHO）I 级毛细胞星形细胞瘤（PA）患者、24 例接受化疗和颅脊髓放疗的 WHO IV 级髓母细胞瘤（MB）患者以及 43 例健康同龄人进行了单容积 H-1 MRS 检查，对顶叶白质和灰质进行了研究。
MB 患者的白质（p < 0.0001）和灰质（p < 0.0001）以及 PA 患者的灰质（p = 0.005）中的 N-乙酰天冬氨酸（NAA）浓度明显降低，与健康同龄人相比。顶叶灰质中的肌酸浓度降低与两组患者的诊断时年龄较大显著相关（MB 患者，p = 0.009，r = 0.52；PA 患者，p = 0.006，r = 0.7）。PA 患者自诊断以来时间越长，其白质中的 NAA 水平越低（p = 0.008，r = 0.66）。
在后颅窝肿瘤患者的 PA 和 MB 两组中观察到不同程度的 NAA 浓度降低。我们得出的结论是，这反映了肿瘤本身以及两组患者的手术对正常脑组织结构的神经代谢稳态的干扰。MB 患者的代谢物浓度进一步降低可能表明放疗和化疗造成了额外的损害。MB 患者 NAA 降低更明显，可能对应于联合放疗和化疗对神经轴突细胞活力和数量的额外损害。
