Leitinger Markus, Broggi Serena, Spendel Mathias, Kalss Gudrun, Petrović Ivan, Krainz Herbert, Rossini Fabio, Höfler Julia, Toma Andreea, Kuchukhidze Giorgi, Mauritz Matthias, Poppert Kai-Nicolas, Crespo-Pimentel Bernardo, Bosque-Varela Pilar, Pleyers Anna, Ganger Patricia, Kotzot Dieter, Lessel Davor, Griessenauer Christoph J, Trinka Eugen
Department of Neurology, Neurocritical Care, and Neurorehabilitation, Center for Cognitive Neuroscience, European Reference Network EpiCARE, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
Neuroscience Institute, Center for Cognitive Neuroscience, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
Epilepsia Open. 2025 Feb;10(1):329-335. doi: 10.1002/epi4.13102. Epub 2024 Nov 23.
Intracerebral hemorrhages (ICH) during implantation of stereo-EEG electrodes are rare. The impact of tobacco-free nicotine consumption on periprocedural bleeding is uncertain. We present a 20+ year-old man with drug-resistant epilepsy who underwent stereo-EEG with 17 depth electrodes. Within a few days after insertion, the patient developed multiple ICHs in the electrode trajectories and an intradural hemorrhage after a diagnostic spinal tap. We performed the investigation of the clotting system and whole-exome sequencing (WES). WES identified a heterozygous mutation c.4698G>T, p.(Trp1566Cys) in COL4A2 (NM_001846.4) encoding a collagen type-IV alpha-2 chain inherited from his seemingly healthy mother. As COL4A2 mutations had been identified in four adult patients with ICH we postulated that the identified variant presents a potential risk factor. Notably, mutations encoding other collagens have been linked to cerebral hemorrhages (COL4A1) and increased propensity to trigger ICH upon smoking (COL1A2). Our patient consumed at least 24 oral nicotine pouches (containing 11 mg nicotine each) per day. We consider the patient's COL4A2 mutation in combination with his substantial nicotine consumption as likely predisposition to multiple ICHs precipitated by stereo-EEG. Patients with nicotine consumption and any collagen mutation may have a substantially higher risk for hemorrhagic complications in SEEG and other neurosurgical procedures. PLAIN LANGUAGE SUMMARY: A young man with drug-resistant epilepsy experienced multiple intracerebral hemorrhages after implantation of SEEG electrodes for presurgical evaluation and concomitantly a intradural hemorrhage after a lumbar spinal tap. A collagen IV mutation of unclear significance and heavy use of oral nicotine pouches were the only potential risk factors identified. As collagen mutations were previously described risk factors and smoking in particular worsens the bleeding risk in collagen mutations, further research is warranted to prevent hemorrhages in neurosurgical procedures. Nicotine consumption in any form is a preventable risk factor.
立体定向脑电图（stereo-EEG）电极植入过程中发生脑出血（ICH）的情况较为罕见。无烟型尼古丁摄入对围手术期出血的影响尚不确定。我们报告一名20多岁的耐药性癫痫男性患者，其接受了17根深部电极的立体定向脑电图检查。电极插入后的几天内，患者在电极轨迹处出现多处脑出血，并在诊断性腰椎穿刺后发生硬膜内出血。我们对凝血系统进行了检查并进行了全外显子测序（WES）。WES在编码IV型胶原α-2链的COL4A2（NM_001846.4）中鉴定出一个杂合突变c.4698G>T，p.（Trp1566Cys），该突变遗传自他看似健康的母亲。由于在4名成年脑出血患者中已鉴定出COL4A2突变，我们推测所鉴定的变异是一个潜在的风险因素。值得注意的是，编码其他胶原蛋白的突变与脑出血（COL4A1）以及吸烟时引发脑出血的倾向增加（COL1A2）有关。我们的患者每天至少食用24个口服尼古丁袋（每个含有11毫克尼古丁）。我们认为患者的COL4A2突变与大量尼古丁摄入相结合，可能是立体定向脑电图诱发多处脑出血的易患因素。有尼古丁摄入且存在任何胶原蛋白突变的患者在立体定向脑电图及其他神经外科手术中发生出血并发症的风险可能会显著更高。通俗易懂的总结：一名患有耐药性癫痫的年轻男性在植入立体定向脑电图电极进行术前评估后发生多处脑出血，同时在腰椎穿刺后发生硬膜内出血。唯一确定的潜在风险因素是意义不明的IV型胶原突变和大量使用口服尼古丁袋。由于胶原突变先前已被描述为风险因素，尤其是吸烟会使胶原突变患者的出血风险恶化，因此有必要进行进一步研究以预防神经外科手术中的出血。任何形式的尼古丁摄入都是一个可预防的风险因素。
