嚴重腦部靜脈竇血栓之治療研究

Treatments for Severe Cerebral Venous Sinus Thrombosis

廖致翔(Chih-Hsiang Liao)

指導教授 ： 楊順發

中山醫學大學/醫學院/醫學研究所/博士(2021年)

https://doi.org/10.6834/csmu202100169

摘要

腦部靜脈竇血栓(cerebral venous sinus thrombosis, CVST)是腦梗塞的罕見原因。一旦患者在急性期中倖存下來，長期預後通常令人滿意。具有預後不良的危險因素(例如意識/神經功能惡化和癲癇發作)的CVST患者通常對全身肝素(heparin)治療無反應。與僅使用肝素治療相比，醫學文獻尚未證明血管內機械血栓切除術(endovascular mechanical thrombectomy, EMT)和當下化學溶栓治療(on-site chemical thrombolysis, OCT)與肝素併用於CVST治療的優勢。本論文回顧2005年至2015年連續發生的CVST患者以進行分析。定義肝素治療後臨床改善或疾病穩定的患者為I/S組(improving/stable group)；肝素治療後意識/神經功能持續惡化或難治性癲癇發作(儘管使用多種抗癲癇藥)的患者為D組(deteriorating group)。 臨床上，於D組內之患者適合接受積極治療(EMT和OCT)。回顧此兩群患者之影像學研究和病歷以進行統計分析。安全問題包括症狀性腦出血(intracerebral hemorrhages, ICH)的新發/進展或與手術相關的併發症。結果發現，於這段時間內，共有30名CVST患者(I/S組 = 16；D組 = 14)。在D組中，從開始肝素治療到介入治療的平均時間為3.2天。與I/S組相比，D組所有患者皆屬於靜脈竇完全狹窄，初始modified Rankin Scale (mRS)較高，初始Glasgow Coma Scale (GCS)較低，癲癇發作較多(p值分別為0.006、0.007和0.031)，但出院時之mRS並無差別(p = 0.504)。較短的血栓和較低的初始mRS與較好的預後相關(p值分別為0.009和0.003)。涉及上矢狀竇(superior sagittal sinus; SSS)的血栓與不良預後相關(p = 0.026)共2例(6.7％)有症狀性腦出血惡化，每組1例。該研究的總死亡率為6.7％(2/30)。本論文發現，肝素合併EMT和OCT治療嚴重CVST是安全的，在急性期對肝素無反應且伴有SSS大量血栓之嚴重CVST患者，可以考慮將其作為挽救性療法，但是需要進一步的研究以確認其功效/效力。

關鍵字

腦靜脈竇血栓形成 ； 介入治療 ； 介入神經放射學 ； 血栓切除術 ； 溶栓

並列摘要

Cerebral venous sinus thrombosis (CVST) is a rare cause of cerebral infarction. Once patients survive the acute phase, long-term prognosis is generally satisfactory. CVST patients who harbored risk factors known for poor prognosis (e.g., deterioration of consciousness/neurological functions and seizures) were oftentimes unresponsive to systemic heparin treatment. The advantage of combined endovascular mechanical thrombectomy (EMT) and on-site chemical thrombolysis (OCT) plus systemic heparin for CVST over the heparin treatment alone has not been proved. A retrospective study was conducted to analyze consecutive patients with CVST from 2005 to 2015. Patients having clinical improvement or stable disease after heparin treatment were in I/S group; patients having continuous deterioration of consciousness/neurological functions and refractory seizures (despite the use of multiple anti-epileptic drugs) after heparin treatment were in D group. EMT and OCT were indicated for patients in D group. Imaging studies and medical records were reviewed for statistical analysis. Safety issues included new-onset/progression of symptomatic intracerebral hemorrhages (ICH) or procedure-related complications. Total thirty patients were included (I/S group = 16; D group = 14). In D group, the mean time frame from the start of heparin treatment to the endovascular treatment was 3.2 days. Compared with I/S group, all patients in D group had complete stenosis of the sinuses, with higher initial Modified Rankin Scale (mRS), lower initial Glasgow Coma Scale (GCS), and more seizures (p = 0.006, 0.007, and 0.031, respectively), but no significant differences in the mRS at discharge (p = 0.504). Shorter length of thrombosis and lower initial mRS were associated with better outcomes (p = 0.009 and 0.003, respectively). Thrombosis involving the superior sagittal sinus (SSS) was associated with bad outcomes (p = 0.026). There were two patients (6.7%) with worsening symptomatic ICH, one in each group, managed surgically. The overall mortality of the study was 6.7% (2/30). In conclusion, combined EMT and OCT after heparin treatment for severe CVST were reasonably safe, which might be considered as a salvage treatment in severe CVST patients who are unresponsive to heparin with heavy clot burden involving SSS in the acute phase. However, further studies are needed to confirm its efficacy and validity.

並列關鍵字

cerebral venous sinus thrombosis ； endovascular treatment ； interventional neuroradiology ； thrombectomy ； thrombolysis

參考文獻

1. Welfare MoHa. Cause of Death Statistics 2020 [Available from: https://dep.mohw.gov.tw/dos/np-1776-113.html.

2. Chang KC, Tseng MC. Costs of acute care of first-ever ischemic stroke in Taiwan. Stroke. 2003;34(11):e219-21.

3. Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003;2(1):43-53.

4. Hu HH, Sheng WY, Chu FL, Lan CF, Chiang BN. Incidence of stroke in Taiwan. Stroke. 1992;23(9):1237-41.

5. Ferro JM, Bousser MG, Canhao P, Coutinho JM, Crassard I, Dentali F, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol. 2017;24(10):1203-13.