Muñoz Patricia, Valerio Maricela, Palomo Jesús, Fernández-Yáñez Juan, Fernández-Cruz Ana, Guinea Jesús, Bouza Emilio
From Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Medicine (Baltimore). 2010 May;89(3):166-175. doi: 10.1097/MD.0b013e3181dfa59c.
Neurologic complications are important causes of morbidity and mortality in heart transplant (HT) recipients. New immunomodulating agents have improved survival rates, although some have been associated with a high rate of neurologic complications (infectious and non-infectious). We conducted this study to analyze the frequency of these complications, before and after the use of daclizumab induction therapy. We reviewed all neurologic complications in our HT cohort, comparing infectious with non-infectious complications over 2 periods of time in which different induction therapies were used (316 patients with OKT3 or antithymocyte globulin from 1988 to 2002, and 68 patients with daclizumab from 2003 to 2006). Neurologic complications were found in 75/384 patients (19.5%) with a total of 78 episodes. Non-infectious complications accounted for 68% of the 78 episodes of neurologic complications. A total of 51 patients and 53 episodes were detailed as follows: 25 episodes of stroke (25 of 78 total episodes, 32%; 19 ischemic, 6 hemorrhagic); 7 neuropathies; 6 seizures; 4 episodes of transient ischemic attack (TIA); 3 anoxic encephalopathy; 2 each brachial plexus palsy and metabolic encephalopathy; and 1 each myoclonia, central nervous system (CNS) lymphoma, subdural hematoma, and Cotard syndrome. Mean time to presentation of stroke, TIA, and encephalopathy was 1 day (range, 1-19 d) posttransplant. Mortality rate among non-infectious complications was 12/53 (22.6%). Infectious complications accounted for 32% of the 78 total episodes. We found 25 episodes in 24 patients: 17 herpes zoster (median, 268 d after HT), 3 CNS aspergillosis (median, 90 d after HT), 1 CNS toxoplasmosis and tuberculosis (51 d after HT), 1 pneumococcal meningitis (402 d after HT), and 2 Listeria meningitis (median, 108 d after HT). The 3 patients with CNS aspergillosis died. The mortality rate among patients with infectious neurologic complications was 12% (42.8% if the CNS was involved). When we compared the OKT3-ATG and daclizumab groups, we found that the incidence of non-infectious complications was 15.1% vs. 7.3%, respectively, and the incidence of infectious complications was 7.5% vs. 1.4%, respectively. All but 1 opportunistic infection occurred in the OKT3-ATG time period. In conclusion, a wide variety of neurologic complications affected 19.5% of HT recipients. Non-infectious causes clearly predominated, but infections still accounted for 32% of the episodes. New monoclonal induction therapies have contributed to diminished CNS opportunistic infections in our program.
神经并发症是心脏移植（HT）受者发病和死亡的重要原因。新型免疫调节药物提高了生存率，尽管有些药物与高神经并发症发生率（感染性和非感染性）相关。我们开展这项研究以分析使用达利珠单抗诱导治疗前后这些并发症的发生频率。我们回顾了我们HT队列中的所有神经并发症，比较了在使用不同诱导治疗的两个时间段内感染性与非感染性并发症（1988年至2002年使用OKT3或抗胸腺细胞球蛋白的316例患者，以及2003年至2006年使用达利珠单抗的68例患者）。在384例患者中有75例（19.5%）出现神经并发症，共78次发作。非感染性并发症占78次神经并发症发作的68%。共有51例患者和53次发作详细情况如下：25次中风（占78次总发作的25次，32%；19次缺血性，6次出血性）；7次神经病变；6次癫痫发作；4次短暂性脑缺血发作（TIA）；3次缺氧性脑病；2次臂丛神经麻痹和代谢性脑病各2例；肌阵挛、中枢神经系统（CNS）淋巴瘤、硬膜下血肿和科塔尔综合征各1例。中风、TIA和脑病出现的平均时间为移植后1天（范围1 - 1十九天）。非感染性并发症的死亡率为12/53（22.6%）。感染性并发症占78次总发作的32%。我们在24例患者中发现25次发作：17次带状疱疹（中位数，HT后268天），3次CNS曲霉菌病（中位数，HT后90天），1次CNS弓形虫病和结核病（HT后51天），1次肺炎球菌脑膜炎（HT后402天），以及2次李斯特菌脑膜炎（中位数，HT后108天）。3例CNS曲霉菌病患者死亡。感染性神经并发症患者的死亡率为12%（如果累及CNS则为42.8%）。当我们比较OKT3 - ATG组和达利珠单抗组时，我们发现非感染性并发症的发生率分别为15.1%和7.3%，感染性并发症的发生率分别为7.5%和1.4%。除1例机会性感染外，所有机会性感染均发生在OKT3 - ATG时间段。总之，多种神经并发症影响了19.5%的HT受者。非感染性原因明显占主导，但感染仍占发作的32%。新型单克隆诱导治疗有助于减少我们项目中的CNS机会性感染。
