Neuroleptic malignant syndrome following BMT
Neuroleptic malignant syndrome following BMT
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BMT 后抗精神病药恶性综合征
DOI：
--
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发表时间：
2002
影响因子：
4.8
通讯作者：
H. Kanamori
中科院分区：
文献类型：
--
作者：
Masanari Onose;C. Kawanishi;H. Onishi;Tomoki Yamada;M. Itoh;Kenji Kosaka;Jun Taguchi;Shin Fujisawa;H. Kanamori
抗精神病药恶性综合征(NMS)是一种严重的精神药物不良反应，以体温升高、锥体外系症状、自主神经不稳定、意识改变、血清肌酸磷酸激酶升高和白细胞增多为特征。由于移植前放疗、化疗、移植物抗宿主病和无病原体保护性隔离室带来的生理和心理压力，骨髓移植患者经常出现调整障碍、情绪障碍和精神错乱等精神障碍。精神药物通常用于治疗这些患者的精神症状。据报道，在接受抗精神病药物和相关药物治疗的患者中，NMS的发生率为0.1%至12.2%。NMS的死亡率约为10%。移植受者是NMS的高危人群，因为精疲力竭和在移植后患者中常见的多种内科疾病被认为是NMS的危险因素。然而，在这种情况下，NMS相对很难识别，因为骨髓移植后会出现粒细胞缺乏症和发烧，以及偶尔出现的免疫抑制剂不良反应的神经症状。在这里，我们描述了一例骨髓移植后NMS患者在早期诊断后成功治疗。一位52岁的女性急性髓系白血病(FAB M0)患者接受了人类白细胞抗原相合的骨髓移植。在移植前，她接受了6个疗程的阿糖胞苷和盐酸阿克拉霉素治疗。除了在BMT前几个月首次发现抑郁症状外，她没有中枢神经系统疾病的病史。骨髓移植采用环磷酰胺(60 mg/kg)、硫代替巴(200g/m)连续2d预适应+全身照射(12Gy4次3Gy4次，连续4d)。移植前一天开始给予他克莫司1.2 mg/d预防移植物抗宿主病。患者在BMT前已抑郁4个月，根据第四版《精神障碍诊断与统计手册》(DSM-IV)诊断为适应障碍，伴有焦虑和抑郁情绪。移植前16天开始口服盐酸阿米替林50 mg/d。在移植时，神经系统检查是正常的，尽管焦虑和抑郁仍然存在。移植后继续使用盐酸阿米替林4d。当她神志不清时，加入氟哌啶醇(10毫克/天)。48h内，患者开始发热(39.5℃)，并出现震颤、上肢僵硬和意识水平波动。在移植后第6天，除了持续发热外，她还出现全身僵硬、心动过速、高血压和横纹肌溶解(肌酸磷酸酶，538U/L；正常，160U/100U)。血肌酐浓度为1.73 mg/dl。我们根据Pope等人的标准诊断患者为可能的NMS，尽管BMT后的粒细胞太少而无法计数。停用氟哌啶醇和水合他克莫司。环孢素(100 mg/d)和甲基强的松龙(125~500 mg/d)预防移植物抗宿主病。在接下来的4天里，发烧、震颤、高血压和心动过速都有所改善。在接下来的12天里，神志不清和僵硬消失了，但低烧仍在继续。随后，肌酸磷酸激酶在移植后第19天逐渐上升，达到2088U/L，第25天恢复正常。在发烧期间没有发现感染、内分泌疾病或脑血管事件的证据。这名患者在骨髓移植后出现NMS，但在停用氟哌啶醇后有所改善，氟哌啶醇是一种已知与NMS相关的神经镇静剂。只有加里多和昌西报道了NMS使BMT复杂化的情况。根据Caroff和Mann列出的诊断标准，NMS在接受抗精神病药物治疗后7天内出现。在我们的患者中，NMS的临床症状在开始使用氟哌啶醇后48小时内出现。除无白细胞增多和多汗等自主神经表现外，均有典型的NMS症状。骨髓移植准备方案后，粒细胞太少，无法计数，出汗也很难评估。我们根据广泛使用的诊断标准诊断我们的患者为可能的NMS。NMS的临床症状在停止致病药物后消失。莱文森和辛普森质疑NMS作为一个单一实体的概念，并建议在大多数情况下可以找到导致发烧的特定医学原因。虽然NMS是药物引起的体温升高的一种形式，与锥体外系症状发热是分开的，但这种区别可能是一个困难的诊断挑战。在我们的病例中，NMS在存在多种复杂因素时很难诊断，如粒细胞缺乏症、移植物抗宿主病、免疫抑制等，但考虑到死亡的风险，诊断非常重要。由于骨髓移植的特殊情况导致的临床病程有些不典型，在一些类似的病例中可能被漏诊，NMS的患病率可能比人们所认识的要高。及早认识NMS是至关重要的。除了停用致病药物外，有时可能还需要使用溴隐亭和/或丹曲林。NMS是移植受者中一个不常见但对预后有重要意义的因素。
Neuroleptic malignant syndrome (NMS), a severe adverse effect of psychotropic drugs, is characterized by hyperthermia, extrapyramidal symptoms, autonomic instability, alterations in consciousness, elevated creatine phosphokinase in serum, and leukocytosis. Mental disturbances such as adjustment disorder, mood disorder, and delirium, are frequent in BMT patients because of physical and psychological stress from pretransplant irradiation, chemotherapy, GVHD, and pathogen-free protective isolation rooms. Psychotropic drugs are used commonly to treat psychiatric symptoms in these patients. The reported occurrence of NMS in patients receiving neuroleptic and related medications is 0.1 to 12.2%. Mortality in NMS is about 10%. Transplant recipients represent a group at high risk for NMS since exhaustion and multiple medical illnesses, frequently seen in post-transplantation patients, are considered to be risk factors for NMS. However, NMS is relatively difficult to identify in this setting because of the agranulocytosis and fever that follow BMT, and also the neurologic symptoms that occasionally occur as adverse effects of immunosuppressants. Here, we describe a patient with NMS following BMT successfully treated after early diagnosis. A 52-year-old woman with acute myeloid leukemia (FAB M0) underwent HLA–matched BMT. Before transplantation she had been treated with six courses of cytarabine and aclarubicin hydrochloride. She had no history of central nervous system disease except for depressive symptoms first noted a few months before BMT. BMT was carried out following conditioning with cyclophosphamide (60 mg/kg), thiotepa (200 g/m) on 2 consecutive days and total body irradiation (12 Gy in four 3 Gy doses on 4 consecutive days). Tacrolimus hydrate (1.2 mg/day) was given as prophylaxis against GVHD beginning on the day before transplantation. The patient had been depressed for 4 months before BMT and was diagnosed as adjustment disorder with mixed anxiety and depressed mood according to the forth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Amitriptyline hydrochloride (50 mg/day) was started 16 days before transplantation. At the time of transplantation neurologic examination was normal, although anxiety and depression were still present. Amitriptyline hydrochloride was continued for 4 days after transplantation. When she became delirious, haloperidol (10 mg/day) was added. Within 48 h the patient became febrile (39.5°C) and developed tremors, rigidity in the upper extremities and fluctuating consciousness levels. On post-transplant day 6, in addition to the continuing fever, she developed generalized rigidity, tachycardia, hypertension, and rhabdomyolysis (creatine phosphokinase, 538 U/l; normal, 160). The serum creatinine concentration was 1.73 mg/dl. We diagnosed the patient as probable NMS according to the criteria of Pope et al, although following BMT granulocytes were too few to be counted. Haloperidol and tacrolimus hydrate were discontinued. Cyclosporine (100 mg/day) and methylprednisolone (125 to 500 mg/day) were initiated as GVHD prophylaxis. Within the next 4 days the fever, tremor, hypertension, and tachycardia all improved. Within the next 12 days the disturbed consciousness and rigidity resolved, but low-grade fever continued. Subsequently, the creatine phosphokinase gradually rose to reach 2088 U/l on post-transplant day 19, returning to normal on day 25. No evidence of infections, endocrinopathies, or cerebrovascular events was noted during the febrile episode. This patient developed NMS after BMT but improved after discontinuation haloperidol, a neuroleptic drug known to be associated with NMS. NMS complicating BMT has only been reported by Garrido and Chauncy. According to the diagnostic criteria listed by Caroff and Mann, NMS develops within 7 days after treatment with neuroleptics. In our patient, clinical symptoms of NMS developed within 48 h after commencing haloperidol. Characteristic NMS symptoms were present, except for the absence of leukocytosis and autonomic manifestations, such as hyperhidrosis. Granulocytes were too few to count, and sweating was difficult to assess after the preparatory regimen for BMT. We diagnosed our patient as probable NMS according to the diagnostic criteria, which have been widely used. Clinical symptoms of NMS resolved after discontinuation of the causative drug. Levinson and Simpson questioned the concept of NMS as a single entity, and suggested that in most cases a specific medical cause of fever could be found. Although NMS is a form of drug-induced hyperthermia separate from extrapyramidal symptoms with fever, this distinction can present a difficult diagnostic challenge. As in our case, NMS can be difficult to diagnose in the presence of multiple complicating factors such as agranulocytosis, GVHD, immunosuppression and so on, but the diagnosis is highly important given the risk of death. Given the somewhat atypical clinical course resulting from the special circumstances of BMT, the diagnosis may have been missed in some similar cases and prevalence of NMS might be higher than is recognized. Early recognition of NMS is vital. In addition to discontinuation of the causative drug, administration of bromocriptine and/or dantrolene may sometimes be needed. NMS represents an uncommon but prognostically important factor in transplant recipients.
大型精神病医院抗精神病药恶性综合征的频率和表现。
DOI：
10.1176/ajp.143.10.1227
发表时间：
1986
期刊：
The American journal of psychiatry
影响因子：
--
作者：
PopeJr,HG;KeckJr,PE;McElroy,SL
通讯作者：
McElroy,SL