Shin Wonsuk, Kim Min-Kyoung, Kim Jinkwon, Woo Min-Hee, Cho Doo-Yeon, Lim Kyoung Soo
Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea.
Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea.
Transl Clin Pharmacol. 2017 Dec;25(4):162-165. doi: 10.12793/tcp.2017.25.4.162. Epub 2017 Dec 20.
A lumbar puncture can be used to measure the concentrations of drugs and/or pharmacodynamic biomarkers during clinical trials of central nervous system drugs. We report a case of a post lumbar puncture headache (PLPH) in a first-in-human study, which was reported as a serious adverse event. A 20-year-old man received 200 mg of the investigational product (IP) for 7 days and underwent a lumbar puncture for cerebrospinal fluid sampling before IP administration (Day 1, pre-dose) and after 7 days and multiple IP administrations (Day 7, 1 hour post-dose). After discharge on Day 8, the subject complained of headache, nausea, vomiting, neck stiffness, and numbness of the extremities. The symptoms occurred when he got up and disappeared after he remained in the supine position for several minutes. Five days later, he visited the neurology clinic of the main hospital. The neurologist recommended hospitalization for further evaluation and symptom management, and the subject was then admitted to the hospital. There were no abnormal findings in vital signs, laboratory results, or brain-computed tomography. His symptoms disappeared during the hospitalization period. It was important to distinguish whether the headache was IP-related or lumbar puncture-related. Therefore, knowledge of clinical characteristics and differential diagnosis of PLPH is paramount. Furthermore, if severe PLPH occurs, a consultation with a neurologist and imaging studies should be considered for a differential diagnosis of PLPH.
在中枢神经系统药物的临床试验中，腰椎穿刺可用于测量药物和/或药效学生物标志物的浓度。我们报告了一例在首次人体研究中发生的腰椎穿刺后头痛（PLPH）病例，该病例被报告为严重不良事件。一名20岁男性接受了200mg研究产品（IP），为期7天，并在IP给药前（第1天，给药前）以及7天和多次IP给药后（第7天，给药后1小时）进行了腰椎穿刺以采集脑脊液样本。在第8天出院后，受试者出现头痛、恶心、呕吐、颈部僵硬和四肢麻木的症状。这些症状在他起身时出现，在仰卧几分钟后消失。五天后，他前往主医院的神经科门诊就诊。神经科医生建议住院进行进一步评估和症状管理，随后该受试者入院。生命体征、实验室检查结果或脑部计算机断层扫描均未发现异常。他的症状在住院期间消失。区分头痛是与IP相关还是与腰椎穿刺相关很重要。因此，了解PLPH的临床特征和鉴别诊断至关重要。此外，如果发生严重的PLPH，应考虑咨询神经科医生并进行影像学检查以对PLPH进行鉴别诊断。
