出现精神状态改变、肌强直、自主神经功能障碍和体温过高四联征时,可做出诊断。如今鉴于这一综合征的危重特征,高怀疑指数使得临床医生在进行诊断性评估的同时,即停止使用抗精神病药物,并开始采用支持性治疗措施。这意味着与原来危及生命的严重表现相比,可能会更常出现不那么严重的病例(部分 NMS、轻度 NMS)。这也使得诊断更加具有挑战性,因为许多其他病症也会出现 NMS 的一些或全部特征。一个国际专家组基于共识制定了诊断标准,该标准可用于帮助指导临床评估,[35]Gurrera RJ, Caroff SN, Cohen A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry. 2011;72:1222-1228.http://www.ncbi.nlm.nih.gov/pubmed/21733489?tool=bestpractice.com并且已被纳入精神疾病诊断与统计手册第五版 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; DSM-5) 。[36]American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th edition (DSM-5). Washington, DC: American Psychiatric Publishing; 2013.
NMS 仍然是一种排除诊断。需进行细致评估(包括体格检查和全面的评估试验),以排除其他潜在原因。[3]Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993;77:185-202.http://www.ncbi.nlm.nih.gov/pubmed/8093494?tool=bestpractice.com[12]Sewell DD, Jeste DV. Distinguishing neuroleptic malignant syndrome (NMS) from NMS-like acute medical illnesses: a study of 34 cases. J Neuropsychiatry Clin Neurosci. 1992;4:265-269.http://www.ncbi.nlm.nih.gov/pubmed/1354002?tool=bestpractice.com
病史和体格检查
NMS 更可能出现在开始抗精神病治疗或剂量增加时。[1]Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164:870-876.http://www.ncbi.nlm.nih.gov/pubmed/17541044?tool=bestpractice.com[5]Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry. 1998;155:1113-1116.http://www.ncbi.nlm.nih.gov/pubmed/9699705?tool=bestpractice.com[30]Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. 1997;154:1156-1158.http://www.ncbi.nlm.nih.gov/pubmed/9247408?tool=bestpractice.com[37]Marshall PB, Mellman TA, Nguyen SX. Neuroleptic malignant syndrome with the addition of aripiprazole to olanzapine. Am J Psychiatry. 2008;165:1488-1489.http://www.ncbi.nlm.nih.gov/pubmed/18981078?tool=bestpractice.com[38]Croarkin PE, Emslie GJ, Mayes TL. Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric patients: a review of published cases. J Clin Psychiatry. 2008;69:1157-1165.http://www.ncbi.nlm.nih.gov/pubmed/18572981?tool=bestpractice.com[39]Berardi D, Amore M, Keck PE Jr, et al. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case-control study. Biol Psychiatry. 1998;44:748-754.http://www.ncbi.nlm.nih.gov/pubmed/9798079?tool=bestpractice.com[40]Viejo LF, Morales V, Punal P, et al. Risk factors in neuroleptic malignant syndrome: a case-control study. Acta Psychiatr Scand. 2003;107:45-49.http://www.ncbi.nlm.nih.gov/pubmed/12558541?tool=bestpractice.com[41]Rosebush P, Stewart T. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry. 1989;146:717-725.http://www.ncbi.nlm.nih.gov/pubmed/2567121?tool=bestpractice.com通常认为先前发作过 NMS 的患者,再次发作的风险显著增加。经常很难与抗精神病药物的超敏反应区分开来,特别是在病历中对先前发作描述很少的情况下。[3]Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993;77:185-202.http://www.ncbi.nlm.nih.gov/pubmed/8093494?tool=bestpractice.com[9]Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42;1290-1297.http://www.ncbi.nlm.nih.gov/pubmed/18628446?tool=bestpractice.com[33]Mall GD, Hake L, Benjamin AB, et al. Catatonia and mild neuroleptic malignant syndrome after initiation of long-acting injectable risperidone: case report. J Clin Psychopharmacol. 2008;28:572-573.http://www.ncbi.nlm.nih.gov/pubmed/18794658?tool=bestpractice.com[39]Berardi D, Amore M, Keck PE Jr, et al. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case-control study. Biol Psychiatry. 1998;44:748-754.http://www.ncbi.nlm.nih.gov/pubmed/9798079?tool=bestpractice.com[42]Groff K, Coffey BJ. Psychosis or atypical neuroleptic malignant syndrome in an adolescent? J Child Adolesc Psychopharmacol. 2008;18:529-532.http://www.ncbi.nlm.nih.gov/pubmed/18928418?tool=bestpractice.com询问关于谵妄、痴呆、脑外伤、Wilson 病和帕金森病的病史是有帮助的,因为在使用抗精神病药物/多巴胺能药物的情况下,它们似乎与 NMS 的风险增加有关。[16]Takubo H, Harada T, Hashimoto T, et al. A collaborative study on the malignant syndrome in Parkinson's disease and related disorders. Parkinsonism Relat Disord. 2003;9(suppl 1):S31-S41.http://www.ncbi.nlm.nih.gov/pubmed/12735913?tool=bestpractice.com[30]Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. 1997;154:1156-1158.http://www.ncbi.nlm.nih.gov/pubmed/9247408?tool=bestpractice.com[31]Keck PE Jr, Pope HG Jr, Cohen BM, et al. Risk factors for neuroleptic malignant syndrome: a case-control study. Arch Gen Psychiatry. 1989;46:914-918.http://www.ncbi.nlm.nih.gov/pubmed/2572206?tool=bestpractice.com
做出诊断的关键临床特征
精神状态改变:表现为意识模糊、谵妄或木僵。
肌强直:患者可出现新发肌强直或之前存在的肌强直恶化。可能难以区分这两种情况。
体温过高:可能同时出现发汗,表明正常体温调节协调能力被破坏。
自主神经系统功能障碍:可能包括不稳定性高血压、心动过速、呼吸急促、尿失禁和发汗。
检查
实验室检查对排除其他疾病或并发症很关键。
FBC:以排除脓毒症。
血清肌酸激酶水平:NMS 患者可能出现血清肌酸激酶显著增加,并且存在发生肌红蛋白尿性急性肾损伤的风险。应进行后续试验,经常需每日进行,直至症状和实验室检查异常消失。
基础代谢检查(尿素、肌酐):以评估并发症的存在,例如急性肾损伤和水合状态。
肌红蛋白水平和尿液分析:肌红蛋白尿是预后不良的标志。
可获取尿液/血液培养物和胸部 X 线检查,以排除脓毒症和肺炎。
CT/MRI 脑部扫描:以排除脑部感染、肿块或出血。[12]Sewell DD, Jeste DV. Distinguishing neuroleptic malignant syndrome (NMS) from NMS-like acute medical illnesses: a study of 34 cases. J Neuropsychiatry Clin Neurosci. 1992;4:265-269.http://www.ncbi.nlm.nih.gov/pubmed/1354002?tool=bestpractice.com
毒理学筛查:排除药物滥用/过量/停药。
腰椎穿刺术:排除存在体温过高、精神状态改变和强直患者的脑膜炎/脑炎。
更具体的检查由临床情况指导。[12]Sewell DD, Jeste DV. Distinguishing neuroleptic malignant syndrome (NMS) from NMS-like acute medical illnesses: a study of 34 cases. J Neuropsychiatry Clin Neurosci. 1992;4:265-269.http://www.ncbi.nlm.nih.gov/pubmed/1354002?tool=bestpractice.com[43]Keshevan MS, Stecker J, Kambhampati RK. Creatine kinase elevations with clozapine. Br J Psychiatry. 1994;164:118-120.http://www.ncbi.nlm.nih.gov/pubmed/7802755?tool=bestpractice.com