硼替佐米中枢神经系统毒性五例报告并文献复习

Central nervous system toxicity caused by bortezomib:five case reports and a review of literature

目的探讨硼替佐米中枢神经系统(CNS)毒性的临床特点、诊断和治疗。方法报道5例由硼替佐米引起的CNS毒性患者并结合现有文献探讨其临床特点。结果 5例患者中有4例在应用硼替佐米后出现了中枢性发热,主要表现为持续性高热、周身无汗、未能找到感染病灶、对退热药不敏感,停用硼替佐米后症状好转。4例患者中有3例伴随顽固性低钠血症,1例明确诊断为抗利尿不当综合征(SIAD),可能是硼替佐米同时影响了下丘脑体温调节中枢和抗利尿激素神经分泌细胞所致。1例患者诊断为可逆性后部脑病综合征(PRES),表现为应用硼替佐米后出现意识障碍,头CT示双侧半卵圆中心白质密度减低,停用硼替佐米后患者症状消失且未再复发。此外,我们还发现血小板计数可能与硼替佐米CNS毒性的严重程度相关。结论硼替佐米的CNS毒性非常罕见,表现为3种形式:SIAD、PRES和中枢性发热,及时识别和治疗对于预防不可逆的神经并发症非常重要。

Objective To investigate the clinical features,diagnosis,and treatment of the central nervous system(CNS)toxicity caused by bortezomib.Methods This study reports five new cases of CNS toxicity caused by bortezomib to elucidate its characteristics along with a review of the literature.Results CNS toxicity caused by bortezomib presents in three clinical forms:syndrome of inappropriate antidiuresis(SIAD),posterior reversible encephalopathy syndrome(PRES),and central fever,which is the most common clinical manifestation.Four of our five patients developed central fever after the administration of bortezomib,manifested as persistent high fever,anhidrosis,and absence of infective foci;the symptom could be improved by discontinuance of bortezomib.Of these patients,three concurrently presented with refractory hyponatremia and one was clearly diagnosed with SIAD.The bortezomib could have caused damages to the hypothalamus and induced both central fever and SIAD.In addition,one patient was diagnosed with PRES due to disturbance of consciousness and epilepsy after taking bortezomib.After discontinuation of bortezomib,the symptoms disappeared and did not recur.We also found that thrombocytopenia may be related to the severity of the CNS toxicity of bortezomib.Conclusion Cases of CNS toxicity of bortezomib are extremely rare and present as SIAD,PRES and central fever.Early detection and treatment of bortezomib are very important to prevent irreversible neurological complications.