14-3-3蛋白与吉兰-巴雷综合征早期诊断关系的研究

目的 观察吉兰-巴雷综合征(GBS)急性期脑脊液中是否存在14-3-3蛋白,探讨其与GBS早期诊断是否具有相关性. 方法 采用ELISA KiT方法检测40例GBS患者起病后3 d内、第7天、第14天脑脊液14-3-3蛋白浓度,对照组为10例同期骨科手术患者及25例同期住院的其它神经系统疾病患者;并同时用罗氏P.800全自动生化分析仪检测脑脊液蛋白;观察早期GBS患者脑脊液中14-3-3蛋白含量变化及其与脑脊液蛋白是否具有相关性.结果 GBS组在起病后3 d内、第7天、第14天脑脊液中测得的14-3-3蛋白含量分别为(6.237±2.627)ng/mL、(8.369±3.003)ng/mL、(13.431±6.461)ng/mL;脑脊液蛋白含量分别为(0.308±0.1 13)g/L、(0.378±0.135)g/L、(0.587±0.273)g/L;GBS组脑脊液14-3-3蛋白最早可于起病后20～48 h出现,其含量在起病后第7天、第14天明显高于对照组,差异有统计学意义(P<0.05);GBS组脑脊液蛋白含量在起病后第14天明显高于对照组,差异有统计学意义(P<0.05);脑脊液14-3-3蛋白含量与脑脊液蛋白含量存在正相关关系(P<0.05).结论 GBS早期脑脊液中存在14-3-3蛋白,其含量增高可使脑脊液蛋白量随之增高:用ELISA KiT方法检测脑脊液中14-3-3蛋白浓度可用于GBS的早期诊断.     

Protein composition of cerebrospinal fluid in the developing chick embryo

Proteins from cerebrospinal fluid of chick embryos at 4-19 days of development were qualitative and quantitatively analyzed. The total protein concentration and the relative concentration of each protein fraction were calculated for each day. The main proteins found along development were immunoglobulin G, transferrin, alpha-fetoprotein, serum albumin, ovalbumin, prealbumin, and an unidentified component. alpha-Fetoprotein was found to be the major protein at 4-16 days, and serum albumin at 17-19 days of development. The unidentified fraction was present from 4 to 11 days; at day 5 it represented 28% of the total cerebrospinal fluid protein concentration.     

人工脑脊液冲洗治疗对实验性大鼠脑外伤后低氧诱导因子表达的影响

目的探讨人工脑脊液局灶冲洗治疗对实验性大鼠创伤性脑损伤后脑水肿及低氧诱导因子-1α(HIF-1α)表达的影响。方法采用自由落体打击装置制备大鼠创伤性脑损伤模型,分正常对照组、外伤对照组、生理盐水冲洗治疗组及人工脑脊液冲洗治疗组。于伤后30min开始分别以37℃的生理盐水和人工脑脊液进行局灶冲洗治疗维持3h。伤后4h、1、3、5、7d处死留取脑组织标本,采用干湿重法测伤灶脑组织含水量,RT-PCR方法检测HIF-1αmRNA的表达。结果与外伤对照组相比,生理盐水和人工脑脊液治疗组伤灶脑组织水含量明显降低(P<0.05);脑外伤后4h伤灶脑组织中HIF-1αmRNA表达即明显上升,1d达到高峰,持续至3d,5d开始下降,7d降至正常水平;局灶冲洗治疗后,伤后4h、1d、3d和5d各组脑组织HIF-1αmRNA表达均低于外伤对照组相应各时间点(P<0.05);其中以局灶人工脑脊液冲洗治疗效果最佳。结论局灶人工脑脊液冲洗治疗能明显减轻大鼠伤灶脑水肿,有良好的治疗作用;调节HIF-1α的表达是其脑保护作用的机制之一。     

吉兰-巴雷综合征脑脊液14—3—3蛋白与脑脊液蛋白关系的研究

目的观察吉兰-巴雷综合征（GBS）脑脊液（CSF）中14—3—3蛋白与脑脊液蛋白在病程中的变化情况,探讨两者的相关性。方法采用酶联免疫吸附试验法（ELISA）检测43例GBS患者发病后3d内、第1,2,4,12周的脑脊液14—3—3蛋白含量,并同时用罗氏P-800全自动生化分析仪检测脑脊液蛋白含量。观察脑脊液14—3—3蛋白与脑脊液蛋白是否具有相关性。结果GBS组在发病3d内、第1,2,4,12周脑脊液14—3—3蛋白含量分别为（6．339±2．356）、（8．569±3．454）、（14．561±6．621）、（9．563±3．486）、（6．262±2．643）ng／ml,脑脊液蛋白分剐为（O．336±0．126）、（O．368±0．102）、（0．653±0．246）、（0．446±0．178）、（0．364±0．158）g／L。GBS组脑脊液14—3—3蛋白第1、2、4周高于对照组,差异有统计学意义（P〈0．05）,GBS组脑脊液蛋白第2、4周高于对照组,差异有统计学意义（P〈0．05）,脑脊液14—3—3蛋白含量与脑脊液蛋白含量存在正相关关系（P〈0．05）。结论GBS脑脊液中14—3—3蛋白含量的变化可引起脑脊液蛋白含量发生相应变化。     

CSF tau protein is a useful marker for effective treatment of superficial siderosis of the central nervous system: Two case reports

We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies.     

神经内镜下经鼻-扩大蝶窦入路术后颅底重建(附20例分析)

目的探讨神经内镜下经鼻-扩大蝶窦入路术后的颅底重建技术。方法回顾性分析20例神经内镜下经鼻-扩大蝶窦入路术后的颅底重建经验。其中鞍结节脑膜瘤7例,颅咽管瘤3例,垂体腺瘤10例。在切除肿瘤后均采用人工硬脑膜-明胶海绵和生物胶-人工硬脑膜的"三明治"式方法,同时辅以球囊支持修补材料和持续腰池引流。结果1次手术修补成功15例,短暂性脑脊液鼻漏经保守治疗治愈3例,2例2次内镜下经鼻入路行颅底重建得以修复。术后随访6个月～4年,疗效满意。结论"三明治"式修补方法加球囊支撑和持续性腰池引流,可显著降低术后脑脊液鼻漏的发生,是神经内镜下经鼻-扩大蝶窦入路术后颅底重建的可靠技术。     

VIRUS TITRES AND PERSISTENTLY RAISED WHITE CELL COUNTS IN CEREBROSPINAL FLUID IN MICE AFTER PERIPHERAL INFECTION WITH DEMYELINATING SEMLIKI FOREST VIRUS

Parsons L.M. & Webb H.E.1982 Neuropathology and Applied Neurobiology 8, 395–401
Virus titres and persistently raised white cell counts in cerebrospinal fluid in mice after peripheral infection with demyelinating Semliki Forest virus
Virus titres and cell counts in the cerebrospinal fluid of mice have been examined following intraperitoneal inoculation of demyelinating Semliki Forest virus (SFV). Virus titres in cerebrospinal fluid were highest 2–4 days after infection and fell again after day 4, 48 h before reduction in brain titres. White cell counts were very low in the first 48 h and showed a steep rise from 4 days after infection to a peak on day 6. After day 8, cell numbers fell to a plateau level which was sustained up to day 61. The significance of these findings in relation to the pathogenesis of virus-induced disease of the central nervous system is discussed.     

Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction

BACKGROUND AND PURPOSE: We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction. METHODS: We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein). RESULTS: We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients. CONCLUSIONS: Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients.     

Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation

L-Asparaginase, a widely used antileukemic agent, inhibits liver protein synthesis leading to hypofibrinogenemia and hypoprothrombinemia together with a severe reduction of antithrombin III and protein C. An increased risk of thrombosis has been reported in leukemic patients treated with this agent. We measured fibrinopeptide A (FPA) changes in 14 patients with acute lymphoblastic leukemia during induction remission treatment with a protocol including L-Asparaginase (10,000 U/m2/daily intravenous for 14 days). At diagnosis, 9/14 patients had FPA level above upper limit of normal range (mean = 4.1 ng/ml). After two days of therapy, FPA rose to 5.2 ng/ml and thereafter showed a slight increase throughout. Antithrombin III, protein C and fibrinogen dropped to its nadir on day 6 and 9. However, the ratio FPA/fibrinogen on a molar basis showed a three-fold increase during this days, demonstrating that the thrombin-dependent consumption of fibrinogen was also increased. In conclusion, our data show that activation of blood coagulation occurs in concomitance with the hemostatic derangement caused by L-Asparaginase. Replacement therapy with the recently available antithrombin III concentrates may be worthy of a clinical trial to test its effectiveness in preventing the thrombotic phenomena reported in these patients.     

Coagulation-fibrinolysis abnormalities in acute stage of subarachnoid hemorrhage (Part 1)--With special reference to the relation between cerebral vasospasm and fibrinopeptides A and B beta

It is well known that abnormalities of coagulation and fibrinolysis frequently take place during the course of cerebrovascular diseases. In this paper, coagulation and fibrinolytic studies were performed during the course of acute stage through chronic stage of subarachnoid hemorrhage. Tested items were partial thromboplastin time, prothrombin time, FDP, alpha 2-plasmin inhibitor, antithrombin III, fibrinogen, besides, fibrinopeptide A (FPA), and fibrinopeptide B beta (FPB beta) which were being worthy of note. Blood were sampled from peripheral vein (V) and internal jugular vein at jugular bulb (J). And, moreover, cerebrospinal fluid (L) were collected as possible as we could for measuring FPA and FPB beta. The obtained results were summarized as follows; Within forty-eight hours from the onset of subarachnoid hemorrhage, FPA-V, J,L and FPB beta-V, J,L were statistically higher than those of control. FPA-J and FPB beta-V, J, within forty-eight hours from the onset were statistically higher in the cases with brain death than in the survived cases. On the third to fifth day from the onset when so called cerebral vasospasm became apparent to begin, FPA and FPB beta had a tendency to be higher than other periods. Increase of fibrinogen delayed from the peaks of FPA and FPB beta showing the peaks at the seventh to the fourteenth day from the onset of subarachnoid hemorrhage. In three cases with symptomatic vasospasm, FPA and FPB beta showed maximal values two to four days prior to the appearance of symptomatic cerebral vasospasm. Other tests were all within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)     

自发性颅内出血患者开颅术后腰大池置管引流过度的临床研究

目的探讨自发行颅内出血患者开颅术后腰大池持续引流过度现象、预防措施及脑脊液安全引流量。方法回顾性分析117例自发性颅内出血开颅术后并行腰大池置管引流的患者临床资料,发现101例患者未出现腰大池引流过度(B组),16例患者出现引流过度症状(A组),比较两组患者在第1、2、3、4、5、6、7天平均脑脊液引流量的差异。结果 116例出现引流过度的患者中,第1~7天出现的例数分别是1例、1例、6例、3例、3例、1例、1例。2比较两组患者第1~7天的脑脊液引流量,第1、2、6、7天两组患者脑脊液的引流量没有统计学差异(P0.05);第3、4、5天两组患者的脑脊液引流量有统计学差异(P0.05)。两组7天的平均脑脊液引流量有统计学差异(P0.05)。3未发生引流过度症状患者的99%单侧医学参考值范围上限是196.33 ml。结论 1患者在一周的腰大池引流过程都有可能出现引流过度出现相关临床症状,主要集中在第3~5天发生。2腰大池脑脊液引流每日不超过196.33 ml,可明显降低患者出现引流过度症状的发生率。     

Diagnostischer Wert der Siderophagen im Liquorcytogramm

The demonstration of siderophages in the cerebrospinal fluid is a very reliable diagnostic tool for identifying hemorrhage in the subarachnoid space and ventricular system. Siderophages are found 4 days after spontaneous or traumatic subarachnoid hemorrhage and persist in some cases up to 120 days, which makes them a reliable indicator of a previous hemorrhage. These findings are the result of an investigation in which 110 samples of cerebrospinal fluid, obtained from 105 patients, were examined for siderophages by the membrane filtration method.     

S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system

The development of a radioimmunoassay for S-100 protein is described. This method was used in combination with a recently developed radioimmunoassay for neuron-specific enolase in cerebrospinal fluid and serum from 47 patients with cerebral infarction, transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, and head injury. In cerebrospinal fluid, increased concentrations of both S-100 and neuron-specific enolase were found after large infarcts, whereas after small infarcts and transient ischemic attacks, only neuron-specific enolase increased. The increased concentrations of S-100 and/or neuron-specific enolase were noted 18 hours to 4 days after cerebral infarction and transient ischemic attacks. Cerebrospinal fluid concentrations of these proteins also reflected the severity of the disease in patients with intracerebral hematoma, subarachnoid hemorrhage, or head injury. Temporal changes in serum S-100 and neuron-specific enolase concentrations reflected the clinical course in 4 patients. In stroke patients, the S-100 and neuron-specific enolase concentrations may reflect the extent of brain damage and could be useful in selecting patients with major stroke for more aggressive treatment during the acute phase.     

Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.     

室管膜型原发性中枢神经系统淋巴瘤四例:临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤(PCNSL)的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果 4例患者平均发病年龄为44岁,发病至就诊时间13 d～5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征(2例)、多组脑神经麻痹(1例)和偏瘫(1例);病程中有间断低热(3例)。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力(2例)、白细胞计数(4例)和蛋白定量(4例)升高,葡萄糖降低(3例)。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶(2例)和鞍区病变(1例)。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

鞘内阶梯浓度用药治疗术后颅内葡萄球菌感染的临床研究

目的探讨单纯应用万古霉素鞘内阶梯浓度注射对术后颅内葡萄球菌感染的治疗作用。方法31例颅内葡萄球菌感染患者腰穿后鞘内注入生理盐水20ml＋盐酸万古霉素，1次，d，剂量从20mg、40mg、60mg、80mg、100mg、120mg、140mg逐日递增，共7d。在治疗前、后监测患者体温、颅内压、脑脊液常规、生化指标及细菌培养。结果万古霉素鞘内注射治疗前各项指标明显异常，治疗2～3d后逐渐改善，5～7d即出现颅内压降低，体温、脑脊液生化及常规指标趋于正常；治疗前与治疗后3～7d各项指标差异明显（P＜0．05），无并发症发生。结论单纯应用万古霉素鞘内阶梯浓度注射治疗术后颅内葡萄球菌感染疗效显著，操作简便，无毒副作用．是临床治疗颅内感染可行的方法。     

室管膜型原发性中枢神经系统淋巴瘤四例：临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤（PCNSL）的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果4例患者平均发病年龄为44岁,发病至就诊时间13d-5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征（2例）、多组脑神经麻痹（1例）和偏瘫（1例）;病程中有间断低热（3例）。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力（2例）、白细胞计数（4例）和蛋白定量（4例）升高,葡萄糖降低（3例）。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶（2例）和鞍区病变（1例）。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

Oxidant and antioxidant parameters in the treatment of meningitis

The aim of this study was to assess the effects of meningitis treatment on the serum and cerebrospinal-fluid oxidant and antioxidant status in children with bacterial meningitis. Forty children with bacterial meningitis, at ages ranging from 4 months to 12 years (mean age, 4 years), were enrolled in the study. Within 8 hours after admission (before treatment) and 10 days after clinical and laboratory indications of recovery (after treatment), cerebrospinal fluid and venous blood were collected. Thirty-seven healthy children (mean age, 4 years) were enrolled as control subjects, and only venous blood was collected. Serum total oxidant status, lipid hydroperoxide, oxidative stress index, uric acid, albumin, and ceruloplasmin levels were lower in the patient group after treatment (P<0.05). Serum total antioxidant capacity levels, vitamin C, total bilirubin, and catalase concentrations were not significantly altered by treatment (P>0.05). However, cerebrospinal fluid total oxidant status, lipid hydroperoxide, and oxidative stress index levels were higher, and cerebrospinal fluid total antioxidant capacity levels were lower after treatment than before treatment (P<0.05). In conclusion, we demonstrated that serum oxidative stress was lower, and cerebrospinal fluid oxidative stress was higher, after rather than before treatment in children with bacterial meningitis.     

Thoracolumbar intraspinal tumours presenting features of raised intracranial pressure.

Five patients are described in whom a benign or malignant thoracolumbar tumour, producing increased level of cerebrospinal fluid protein, was associated with hydrocephalus or papilloedema or both. A review of the clinical and laboratory features in these and 40 published cases underlines the difficulty in explaining the increased intracranial pressure in such patients. Slow absorption of cerebrospinal fluid as a result of the elevated protein levels or recurrent subarachnoid bleeding may play a part. When patients are discovered to have communicating hydrocephalus or a syndrome resemlbing benign intracranial hypertension, the finding of increased cerebrospinal fluid protein or any symptoms or signs relative to the spine should suggest the possibility of an intraspinal tumour.     

视神经脊髓炎谱系疾病患者脑脊液蛋白水平与致残状况的相关性研究

目的探讨视神经脊髓炎谱系疾病(Neuromyelitis optica disorders,NMOSDs)患者脑脊液蛋白与临床致残状况的关系及其临床意义。方法回顾性分析2010年1月~2016年2月我院神经内科确诊的108例NMOSD患者临床与生化资料,根据临床扩展致残量表评分(Expanded disability status scale,EDSS)将患者分为独立行走受限与不受限组,并比较两组患者间的临床、生化特征;根据脑脊液蛋白值将患者分为脑脊液蛋白正常组与异常组,并比较两组间EDSS评分的变化;分析脑脊液蛋白与临床致残状况的相关性。结果独立行走受限组与不受限组之间患者年龄、二便障碍、外周血白细胞(WBC)、中性粒细胞比(N%)、脑脊液蛋白、脑脊液Ig G较有统计学差异(P0.05);性别、病程、视力损害、AQP4抗体、24 h鞘内合成率、寡克隆带比较无统计学差异(P0.05),两组不同脑脊液蛋白水平与患者EDSS值比较有统计学差异(T=3.13,P=0.002);脑脊液蛋白水平与独立行走受限呈正相关(r=0.286,P0.01)。结论 NMOSD患者脑脊液蛋白值越高,患者致残发生的可能性越大,脑脊液蛋白有助于视神经脊髓炎谱系疾病患者致残状况的病情评估。