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自发性蛛网膜下腔出血治疗后内源性神经肽Y过度释放至脑脊液及其对自我报告的神经心理表现的可能影响——对病情良好患者的前瞻性临床初步研究结果

Excessive release of endogenous neuropeptide Y into cerebrospinal fluid after treatment of spontaneous subarachnoid haemorrhage and its possible impact on self-reported neuropsychological performance - results of a prospective clinical pilot study on good-grade patients.

作者信息

Bründl Elisabeth, Proescholdt Martin, Schödel Petra, Bele Sylvia, Höhne Julius, Zeman Florian, Stoerr Eva-Maria, Brawanski Alexander, Schebesch Karl-Michael

机构信息

a Department of Neurosurgery , University Medical Centre Regensburg , Regensburg , Germany.

b Centre for Clinical Studies , University Medical Centre Regensburg , Regensburg , Germany.

出版信息

Neurol Res. 2018 Dec;40(12):1001-1013. doi: 10.1080/01616412.2018.1508547. Epub 2018 Sep 14.

DOI:10.1080/01616412.2018.1508547
PMID:30213237
Abstract

OBJECTIVES

Neuropsychological dysfunction after treatment of spontaneous subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric disorders. We prospectively analysed the treatment-specific differences in the secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage after sSAH and its impact on cognitive processing.

METHODS

A total of 26 consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Ventricular CSF was drawn daily from day 1-10. CSF NPY levels were determined with competitive enzyme immunoassay. All patients underwent neuropsychological self-report assessment [36-Item Short Form Health Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of sSAH (day 11-35; t) and at the 6-month follow-up (t).

RESULTS

At t, increased mean levels of NPY in CSF significantly correlated with impaired performance in most ISR scores (ISR total p = .018, depression p = .035, anxiety p = .008, nutrition disorder p = .047, supplementary items p = .038) and in several psychological SF-36 items (vitality p = .019, general mental health p = .001, mental component summary p = .025).

DISCUSSION

To the best of our knowledge, this study is the first to correlate the levels of endogenous NPY in supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive NPY release into CSF may have a short-term influence on the pathogenesis of neuropsychological deficits. The impact of cerebrovascular manipulation on NPY release has to be further elucidated.

ABBREVIATIONS

ANOVA: analysis of variance; aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF: cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA: digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up; GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10-Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental health; min: minute/s; min-max: minimum - maximum; ml: millilitre; mRS: modified Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng: nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain; PCS: physical component summary; Pfi: physical functioning; pSAH: perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder; QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations because of emotional problems; Rolph: role limitations due to physical health problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item Short Form Health Survey; Social: social functioning; sSAH: spontaneous subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t: test in the sub-acute phase after the onset of bleeding (between day 11 and 35 after subarachnoid haemorrhage); (test) t: test in the short-term (chronic phase) after treatment at 6-month follow-up; test t - t: intergroup development from t to t; Vital: vitality; vs: versus.

摘要

目的

自发性蛛网膜下腔出血(sSAH)治疗后神经心理功能障碍很常见,但报告不足。血管收缩剂神经肽Y(NPY)在sSAH后及精神疾病中会过度释放。我们前瞻性分析了sSAH急性期内源性脑脊液(CSF)NPY分泌的治疗特异性差异及其对认知加工的影响。

方法

连续纳入26例病情分级良好的sSAH患者(女∶男 = 13∶8;平均年龄50.6岁)(5例退出研究):9例行血管内动脉瘤栓塞术,6例行显微手术,6例中脑周围SAH患者接受标准化强化医疗护理。从第1天至第10天每天抽取脑室CSF。采用竞争性酶免疫测定法测定CSF NPY水平。所有患者在sSAH发病后(第11 - 35天;t)及6个月随访时(t)均接受神经心理自评评估[36项简明健康调查(SF - 36)和ICD - 10症状评定问卷(ISR)]。

结果

在t时,CSF中NPY平均水平升高与大多数ISR评分(ISR总分p = 0.018,抑郁p = 0.035,焦虑p = 0.008,营养障碍p = 0.047,补充项目p = 0.038)及几个SF - 36心理项目(活力p = 0.019,总体心理健康p = 0.001,心理成分总分p = 0.025)的表现受损显著相关。

讨论

据我们所知,本研究首次将幕上CSF中内源性NPY水平与病情分级良好的sSAH患者的认知结果相关联。CSF中NPY过度释放可能对神经心理缺陷的发病机制有短期影响。脑血管操作对NPY释放的影响有待进一步阐明。

缩写

ANOVA:方差分析;aSAH:动脉瘤性蛛网膜下腔出血;AUC:曲线下面积;CBF:脑血流量;CSF:脑脊液;CT(扫描):计算机断层扫描(扫描);CV:脑血管痉挛;DIND:迟发性缺血性神经功能缺损;DSA:数字减影血管造影;EIA:酶免疫测定;EV:血管内动脉瘤栓塞;EVD:脑室外引流;FU:6个月随访;GCS:格拉斯哥昏迷量表;Ghp:总体健康感知;GOS:格拉斯哥预后量表;h:小时/秒;HH:Hunt和Hess;ICU:重症监护病房;ISR:ICD - 10症状评定问卷;MCS:心理成分总分;Mhi:总体心理健康;min:分钟/秒;min - max:最小值 - 最大值;ml:毫升;mRS:改良Rankin量表;MS:显微手术夹闭,显微手术动脉瘤栓塞;ng:纳克;数量[n];NPY:神经肽Y;p:p值;疼痛:身体疼痛;PCS:身体成分总分;Pfi:身体功能;pSAH:中脑周围蛛网膜下腔出血;PTSD:创伤后应激障碍;QoL:生活质量;Rawhtran:健康转变项目;Rolem:因情绪问题导致的角色限制;Rolph:因身体健康问题导致的角色限制;SAH:蛛网膜下腔出血;SD:标准差;SF - 36:36项简明健康调查;社会:社会功能;sSAH:自发性蛛网膜下腔出血;TCD:经颅多普勒超声;(测试)t:出血后亚急性期(蛛网膜下腔出血后第11天至35天之间)的测试;(测试)t:6个月随访治疗后短期(慢性期)的测试;测试t - t:从t到t的组间发展;活力:活力;vs:与……相对

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