与贝伐单抗相关的后部可逆性脑病综合征

E. Katada
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摘要

后可逆性脑病综合征(PRES)以神经系统症状为特征,磁共振成像显示高强度病变,其体征包括突然发作的头痛、高血压和发烧。PRES的病理生理机制被认为是严重的高血压导致脑血管自身调节失败和内皮损伤/血管源性水肿,血管收缩导致脑缺血和随后的血管源性水肿。PRES可能与最近的化疗药物有关,特别是贝伐单抗,这是一种重组、人源化、单克隆IgG1抗体,结合并抑制血管内皮生长因子。我们经历了一例PRES与可逆性脑血管收缩综合征(RCVS)相关的病例,15个月后,各种联合化疗包括贝伐单抗治疗转移性结肠癌。PRES和RCVS经常与本病例相关,并且具有重叠或相似的病理生理机制。我们推测贝伐单抗可能诱发血管痉挛并伴有高血压和/或内皮功能障碍,因为贝伐单抗已被证明能够影响脑动脉张力的调节并引发血管收缩,导致血流灌注不足、血脑屏障破裂和血管源性水肿。重要的是,在临床过程的早期,当患者接受贝伐单抗治疗时,出现类似脑血管疾病的体征和症状时,要记住PRES。
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Posterior Reversible Encephalopathy Syndrome Associated with Bevacizumab
Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by neurologic symptoms with hyperintense lesions on magnetic resonance imaging and it presents signs including a sudden onset headache, hypertension, and fever. The pathophysiology underlying PRES have been postulated to be severe hypertension leading to failed cerebral vascular auto-regulation and endothelial injury/vasogenic edema, vasoconstriction leading to brain ischemic and subsequent vasogenic edema. PRES may be associated with recent chemotherapy agents, in particular, bevacizumab which is a recombinant, humanized, monoclonal IgG1 antibody that binds and inhibits vascular endothelial growth factor. We experienced the case of PRES associated with Reversible Cerebral Vasoconstriction Syndrome (RCVS) 15 months later after a variety of combined chemotherapies containing bevacizumab for metastatic colon cancer. PRES and RCVS are frequently associated like this case and have overlapping or similar pathophysiological mechanism. We speculated that bevacizumab may have induced vasospasm coupled with hypertension and/or endothelial dysfunction due to bevacizumab has been shown able to affect the regulation of the cerebral arterial tone and trigger vasoconstriction with subsequent hypoperfusion, breakdown of the blood-brain barrier, and vasogenic edema, and which led to PRES. It is important to come to mind PRES early in the clinical course when the patient treated with bevacizumab shows the sign and symptoms resembling the cerebrovasucular disease.
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