Bechstein W O
Department of Surgery, Ruhr-University Bochum, Knappschaftskrankenhaus Bochum-Langendreer, Germany.
Transpl Int. 2000;13(5):313-26. doi: 10.1007/s001470050708.
Between 10%-28% of patients who receive the immunosuppressant cyclosporine (CsA) experience some form of neurotoxic adverse event. Both sensorial motoric functions may be adversely affected, and thus patients present with a wide range of neurological and psychiatrical disorders. Mild symptoms are common and include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect up to 5 % of patients and include psychoses, hallucinations, blindness, seizures, cerebellar ataxia, motoric weakness, or leukoencephalopathy. Tacrolimus is associated with similar neurotoxic adverse events. Neurotoxicity may result in serious complications for some patients, particularly recipients of orthotopic liver transplants. Factors that may promote the development of serious complications include advanced liver failure, hypertension, hypocholesterolemia, elevated CsA or tacrolimus blood levels, hypomagnesemia, and methylprednisolone. Occipital white matter appears to be uniquely susceptible to the neurotoxic effects of CsA; injury to both the major and minor vasculature may cause hypoperfusion or ischemia and local secondary toxicity in the white matter. Calcineurin inhibition by CsA and tacrolimus alters sympathetic outflow, which may play a role in the mediation of neurotoxic and hypertensive adverse events. The symptoms of CsA- and tacrolimus-associated neurotoxicity may be reversed in most patients by substantially reducing the dosage of immunosuppressant or discontinuing these drugs. However, some patients have experienced permanent or even fatal neurological damage even after dose reduction or discontinuation. CsA-sparing and tacroli-mus-sparing drug regimens that use the immunosuppressant mycophenolate mofetil, which has no neurotoxic effects, may reduce the incidence and severity of neurotoxic adverse events while maintaining an adequate level of immunoisuppression.
接受免疫抑制剂环孢素（CsA）治疗的患者中，10%至28%会经历某种形式的神经毒性不良事件。感觉运动功能均可能受到不利影响，因此患者会出现多种神经和精神障碍。轻微症状很常见，包括震颤、神经痛和周围神经病变。严重症状影响高达5%的患者，包括精神病、幻觉、失明、癫痫发作、小脑共济失调、运动无力或白质脑病。他克莫司也会引发类似的神经毒性不良事件。神经毒性可能给一些患者带来严重并发症，尤其是原位肝移植受者。可能促使严重并发症发生的因素包括晚期肝功能衰竭、高血压、低胆固醇血症、CsA或他克莫司血药浓度升高、低镁血症和甲泼尼龙。枕叶白质似乎对CsA的神经毒性作用特别敏感；主要和次要血管的损伤可能导致白质灌注不足或局部缺血以及继发性毒性。CsA和他克莫司对钙调神经磷酸酶的抑制会改变交感神经输出，这可能在神经毒性和高血压不良事件的介导中起作用。在大多数患者中，大幅降低免疫抑制剂剂量或停用这些药物，CsA和他克莫司相关神经毒性的症状可能会得到缓解。然而，一些患者即使在减量或停药后仍经历了永久性甚至致命的神经损伤。使用无神经毒性作用的免疫抑制剂霉酚酸酯的CsA和他克莫司减量用药方案，在维持足够免疫抑制水平的同时，可能会降低神经毒性不良事件的发生率和严重程度。
