Postconvulsive Central Apnea as a Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Laura Vilella, MD, Nuria Lacuey, MD, Johnson P. Hampson, MSBME, M. R. Sandhya Rani, PhD, Rup K. Sainju, MBBS, Daniel Friedman, MD, Maromi Nei, MD, Kingman Strohl, MD, Catherine Scott, MPhil, Brian K. Gehlbach, MD, Bilal Zonjy, MD, Norma J. Hupp, Anita Zaremba, BA, Nassim Shafiabadi, MD, Xiuhe Zhao, MD, Victoria Reick-Mitrisin, MS, Stephan Schuele, MD, MPH, Jennifer Ogren, PhD, Ronald M. Harper, PhD, Beate Diehl, MD, PhD, FRCP, Lisa Bateman, MD, Orrin Devinsky, MD, George B. Richerson, MD, PhD, Philippe Ryvlin, MD, PhD, and Samden D. Lhatoo, MD, FRCP. Neurology. 2019;92:e171-e182. OBJECTIVE To characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy. METHODS This was a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of sudden unexpected death in epilepsy (SUDEP) in patients ≥18 years old with intractable epilepsy and monitored GCS. Video electroencephalography, thoracoabdominal excursions, nasal airflow, capillary oxygen saturation, and electrocardiogram were analyzed. RESULTS We studied 148 GCS in 87 patients. Nineteen patients had generalized epilepsy, 65 had focal epilepsy, 1 had both, and the epileptogenic zone was unknown in 2. Ictal central apnea (ICA) preceded GCS in 49 (40.4%) of 121 seizures in 23 patients, all with focal epilepsy. Postconvulsive central apnea (PCCA) occurred in 31 (22.1%) of 140 seizures in 22 patients, with generalized, focal, or unknown epileptogenic zones. In 2 patients, PCCA occurred concurrently with asystole (near-SUDEP), with an incidence rate of 10.2 per 1000 patient-years. One patient with PCCA died of probable SUDEP during follow-up, suggesting a SUDEP incidence rate 5.1 per 1000 patient-years. No cases of laryngospasm were detected. Rhythmic muscle artifact synchronous with breathing was present in 75 of 147 seizures and related to stertorous breathing (odds ratio: 3.856, 95% confidence interval: 1.395-10.663, P = .009). CONCLUSIONS Postconvulsive central apnea occurred in both focal and generalized epilepsies, suggesting a different pathophysiology from ICA, which occurred only in focal epilepsy. Postconvulsive central apnea was seen in 2 near-SUDEP cases and 1 probable SUDEP case, suggesting that this phenomenon may serve as a clinical biomarker of SUDEP. Larger studies are needed to validate this observation. Rhythmic postictal muscle artifact is suggestive of post-GCS breathing effort rather than a specific biomarker of laryngospasm. Hypoxemia Following Generalized Convulsive Seizures: Risk Factors and Effect of Oxygen Therapy Sylvain Rheims, MD, PhD, Blanca Mercedes Alvarez, MD, Veriano Alexandre, MD, PhD, Jonathan Curot, MD, Louis Maillard, MD, PhD, Fabrice Bartolomei, MD, PhD, Philippe Derambure, MD, PhD, Edouard Hirsch, MD, PhD, V´eronique Michel, MD, Francine Chassoux, MD, PhD, Didier Tourniaire, MD, Arielle Crespel, MD, Arnaud Biraben, MD, Vincent Navarro, MD, PhD, Philippe Kahane, MD, PhD, Bertrand De Toffol, MD, PhD, Pierre Thomas, MD, PhD, Sarah Rosenberg, MD, PhD, Luc Valton, MD, PhD, Laurent Bezin, PhD, and Philippe Ryvlin, MD, PhD, on behalf of the REPO2MSE Study Group. Neurology. 2019;92:e183-e193. OBJECTIVE To analyze the factors that determine the occurrence or severity of postictal hypoxemia in the immediate aftermath of a generalized convulsive seizure (GCS). METHODS We reviewed the video electroencephalography (EEG) recordings of 1006 patients with drug-resistant focal epilepsy included in the REPO2MSE study to identify those with ≥1 GCS and pulse oximetry (SpO2) measurement. Factors determining recovery of SpO2 ≥ 90% were investigated using Cox proportional hazards models. Association between SpO2 nadir and person- or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS A total of 107 GCS in 73 patients were analyzed. A transient hypoxemia was observed in 92 (86%) GCS. Rate of GCS with SpO2 < 70% dropped from 40% to 21% when oxygen was administered early (P = .046). Early recovery of SpO2 ≥ 90% was associated with early administration of oxygen (P = .004), absence of postictal generalized EEG suppression (PGES; P = .014), and extratemporal lobe epilepsy (P = .001). Lack of early administration of O2 (P = .003), occurrence of PGES (P = .018), and occurrence of ictal hypoxemia during the focal phase (P = .022) were associated with lower SpO2 nadir. CONCLUSION Postictal hypoxemia was observed in the immediate aftermath of nearly all GCS, but administration of oxygen had a strong preventive effect. Severity of postictal hypoxemia was greater in temporal lobe epilepsy and when hypoxemia was already observed before the onset of secondary GCS.

中文翻译：

---

SUDEP的生物标志物：我们还存在吗？

惊厥后中枢性呼吸暂停是癫痫猝死的生物标志物（Laude Vilella，MD，Nuria Lacuey，MD），Johnson P.Hampson，MSBME，MR Sandhya Rani，PhD，Rup K.Sainju，MBBS，Daniel Friedman，MD，医学博士Maromi Nei，医学博士Kingman Strohl，医学博士Catherine Scott，医学博士Brian K.Gehlbach，医学博士Bilal Zonjy，医学博士Norma J.Hupp，文学硕士Anita Zaremba，医学博士Nassim Shafiabadi，医学博士赵秀河，Victoria Reick- Mitrisin，MS，Stephan Schuele，MD，MPH，Jennifer Ogren，PhD，Ronald M.Harper，PhD，Beate Diehl，MD，PhD，FRCP，Lisa Bateman，MD，Orrin Devinsky，MD，George B.Richerson，MD，博士，医学博士Philippe Ryvlin和FRCP医学博士Samden D.Lhatoo。神经病学。2019; 92：e171-e182。目的在难治性癫痫的全身性惊厥性癫痫发作（GCS）中明确其周围性呼吸暂停和收缩期停搏的特征。方法这是一个前瞻性的方法，多中心癫痫监测研究≥18岁顽固性癫痫并监测GCS的癫痫猝死中的自主神经和呼吸生物标志物（SUDEP）。分析了视频脑电图，胸腹腔偏移，鼻气流，毛细血管氧饱和度和心电图。结果我们在87例患者中研究了148个GCS。全身性癫痫19例，全身性癫痫65例，两者均1，且致癫痫区未知。2例均患有局灶性癫痫的121例癫痫中，发作性中枢性呼吸暂停（ICA）在GCS之前占49（40.4％）。抽搐后中枢性呼吸暂停（PCCA）发生在22例患者中，其中140例发作中有31例（占22.1％）具有全身性，局灶性或未知的癫痫发生区。在2例患者中，PCCA与心搏停止同时发生（靠近SUDEP），发生率为10。每1000个病人年2个。一名PCCA患者在随访期间死于可能的SUDEP，表明SUDEP的发生率为5.1 / 1000患者-年。未检测到喉痉挛病例。147例癫痫发作中，有75例与呼吸同步的节律性肌肉伪影与立体呼吸有关（比值：3.856，95％置信区间：1.395-10.663，P = 0.009）。结论惊厥后中枢性呼吸暂停在局灶性癫痫和全身性癫痫中均发生，提示其病理生理学与ICA不同，后者仅在局灶性癫痫中发生。在2例近SUDEP病例和1例SUDEP病例中发现了惊厥后中枢性呼吸暂停，这表明该现象可能是SUDEP的临床生物标志。需要更大的研究来验证这一观察结果。有节律的姿势性肌肉伪影暗示了GCS后的呼吸努力，而不是喉痉挛的特定生物标志物。全身性惊厥发作后的低氧血症：氧气治疗的危险因素和作用西尔万·海姆斯（Sylvain Rheims），医学博士，布兰卡·梅赛德斯·阿尔瓦雷斯（Blanca Mercedes Alvarez），医学博士维里亚诺·亚历山大（Veriano Alexandre），医学博士，博士，乔纳森·库洛（Jonathan Curot）医学博士，路易·迈拉德（Louis Maillard），医学博士，纤维织物博士，菲利普·德拉姆布雷（Philippe Derambure），医学博士，爱德华·赫希（Edouard Hirsch），医学博士，弗洛里克·米歇尔（V´eronique Michel），医学博士，弗朗辛·查索克斯（Francine Chassoux），医学博士，迪迪埃·图尼尔（Didier Tourniaire），医学博士，阿里埃勒·克里斯佩尔（Arielle Crespel），医学博士博士学位，医学博士Philippe Kahane，医学博士Bertrand De Toffol，医学博士Pierre Thomas，医学博士Sarah Rosenberg，医学博士Luc Valton，医学博士Laurent Bezin和Philippe Ryvlin医学博士，代表REPO2MSE研究组。神经病学。2019; 92：e183-e193。目的分析决定全身性惊厥性癫痫发作（GCS）发生后立即发生低氧血症或严重程度的因素。方法我们回顾了REPO2MSE研究中包含的1006例耐药性局灶性癫痫患者的视频脑电图（EEG）记录，以鉴定≥1 GCS和脉搏血氧饱和度（SpO2）的患者。使用Cox比例风险模型调查了确定SpO2≥90％回收率的因素。在校正个体影响和癫痫发作次数变化后，分析了SpO2最低点和特定于个人或癫痫发作的变量之间的关联。结果对73例患者的107个GCS进行了分析。在92（86％）GCS中观察到短暂性低氧血症。SpO2的GCS率< 早期给予氧气时，70％从40％降至21％（P = .046）。SpO2≥90％的早期恢复与早期给予氧气有关（P = .004），缺乏术后全身性EEG抑制（PGES; P = .014）和颞外叶癫痫（P = .001）。缺乏早期给予O2（P = .003），发生PGES（P = .018）和在局灶期出现缺氧性低氧血症（P = .022）与SpO2最低点有关。结论几乎所有GCS发生后都出现了术后低氧血症，但给予氧气有很强的预防作用。颞叶癫痫发作以及继发于GCS发作之前已经观察到低氧血症时，邮政低氧血症的严重程度更高。没有发生全身性脑电图抑制（PGES； P = .014），以及颞叶癫痫（P = .001）。缺乏早期给予O2（P = .003），发生PGES（P = .018）和在局灶期出现缺氧性低氧血症（P = .022）与SpO2最低点有关。结论几乎所有GCS发生后都出现了术后低氧血症，但给予氧气有很强的预防作用。颞叶癫痫发作以及继发于GCS发作之前已经观察到低氧血症时，邮政低氧血症的严重程度更高。没有发生全身性脑电图抑制（PGES； P = .014），以及颞叶癫痫（P = .001）。缺乏早期给予O2（P = .003），发生PGES（P = .018）和在局灶期出现缺氧性低氧血症（P = .022）与SpO2最低点有关。结论几乎所有GCS发生后都出现了术后低氧血症，但给予氧气有很强的预防作用。颞叶癫痫发作以及继发于GCS发作之前已经观察到低氧血症时，邮政低氧血症的严重程度更高。022）与较低的SpO2最低点有关。结论几乎所有GCS发生后都出现了邮政低氧血症，但给予氧气有很强的预防作用。颞叶癫痫发作以及继发于GCS发作之前已经观察到低氧血症时，邮政低氧血症的严重程度更高。022）与SpO2最低点相关。结论几乎所有GCS发生后都出现了术后低氧血症，但给予氧气有很强的预防作用。颞叶癫痫发作以及继发于GCS发作之前已经观察到低氧血症时，邮政低氧血症的严重程度更高。