Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study
Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study
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DOI：
10.1007/s00415-017-8631-8
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发表时间：
2017-11-01
影响因子：
6
通讯作者：
Manto, Mario
中科院分区：
文献类型：
--
作者：
Perrotta, Gaetano;Metens, Thierry;Manto, Mario
最近有确凿的证据表明，在反复使用线形Gd造影剂(GBCA)后，特别是在小脑水平上，Gd在大脑中蓄积。虽然关于大环GBCA在大脑中积累的数据更令人放心，但现在人们确实担心Gd沉积可能产生的长期后果，特别是在小脑后遗症方面。因此，我们对大环GBCA加多特罗葡胺连续给药的临床影响提出了质疑。在这项2000-2016年的回顾性研究中，我们对服用加多特罗20次以上的患者的医疗档案进行了回顾研究，以寻找在定期随访期间发生的小脑症状和体征。我们查阅了10例患者(平均年龄34.4±20.8岁；男性4例，女性6例)接受28.2+/-5.3剂量的加多特罗(GBCA518+/-226毫升，范围185-785毫升)的医疗档案。根据最初的诊断，患者至少要接受两名内科专家的检查，至少要接受一名神经外科医生的检查。平均随访时间为91个月(范围49-168)，10名患者中有6名出现了新的症状或体征。没有临床医生报告出现小脑综合征升高，也没有新出现的症状或体征提示小脑毒性。这项回顾性临床研究显示，反复服用加多特罗后没有出现新的临床小脑综合征。我们的结果反对这种大环状化合物的小脑毒性。尽管如此，还需要在更多的受试者中进行确认，以及关于线性GBCA的临床研究，这些线性GBCA的结构和体内稳定性是不同的。
Sound evidence of gadolinium accumulation in brain has been recently provided after repeated administrations of linear gadolinium-based contrast agents (GBCAs), especially at the cerebellum level. Although data regarding brain accumulation of macrocyclic GBCAs are more reassuring, there is now a genuine concern ("gadolinium-phobia") about possible long-term consequences of gadolinium deposits, especially in terms of cerebellar sequelae. We, therefore, questioned about the clinical impact of serial administration of gadoterate meglumine, a macrocyclic GBCA. In this retrospective study (2000-2016) of medical files of patients who received more than 20 administrations of gadoterate, we searched for cerebellar symptoms and signs developing during the regular follow-up. We reviewed medical files of ten patients (mean age 34.4 +/- 20.8 years; 4 males, 6 females) who received 28.2 +/- 5.3 doses of gadoterate (average total dose of GBCA 518 +/- 226 ml; range 185-785 ml). Patients were examined by at least two medical specialists depending on initial diagnosis, and at least once by a neurosurgeon. Mean follow-up time was 91 months (range 49-168) and six out of ten patients experienced new symptoms or signs. No clinician reported the appearance of a rising cerebellar syndrome, nor newly appeared symptoms or signs suggested cerebellar toxicity. This retrospective clinical study shows no de novo clinical cerebellar syndrome following repeated administrations of gadoterate. Our results argue against a cerebellar toxicity of this macrocyclic agent. Still, confirmation in a larger number of subjects is required, as well as clinical studies concerning linear GBCAs whose structure and in vivo stability are distinct.