Cerebrospinal fluid creatine kinase-BB isoenzyme activity and outcome after subarachnoid hemorrhage.

BACKGROUND: The brain is rich in creatine kinase-BB isoenzyme activity (CK-BB), which is not normally present in cerebrospinal fluid (CSF). Results of previous studies have shown that CK-BB can be detected in the CSF of patients with aneurysmal subarachnoid hemorrhage (SAH), but whether CK-BB levels correlate with patients' neurologic outcomes is unknown. OBJECTIVE: To evaluate the relationship between CSF CK-BB level and outcome after SAH. DESIGN: Prospective observational cohort. SETTING: University-affiliated tertiary care center. PATIENTS: Convenience sample of 30 patients seen for cerebral aneurysm clipping. INTERVENTIONS: We sampled and assayed CSF for CK isoenzymes a median of 3 days after SAH in 27 patients, and at the time of unruptured aneurysm clipping in 3 patients. MAIN OUTCOME MEASURES: Without knowledge of CK results, we assigned the Glasgow Outcome Scale score early (approximately 1 week) and late (approximately 2 months) after surgery. RESULTS: Higher CSF CK-BB levels were associated with higher Hunt and Hess grades at hospital admission (Spearman rank correlation, p = 0.69; P<.001), lower Glasgow Coma Scale scores at hospital admission (p = -0.72; P<.001), and worse early outcomes on the Glasgow Outcome Scale (p = -0.64; P<.001). For patients with a favorable early outcome (Glasgow Outcome Scale score, 3-5), all CK-BB levels were less than 40 U/L. With a cutoff value of 40 U/L, CK-BB had a sensitivity of 70% and a specificity of 100% for predicting unfavorable early outcome (Glasgow Outcome Scale score, 1-2). Having a CK-BB level greater than 40 U/L increased the chance of an unfavorable early outcome, from 33% (previous probability) to 100%, whereas a CK-BB level of 40 U/L or less decreased it to 13%. Similar findings were obtained when considering late outcomes. CONCLUSION: The level of CSF CK-BB may help predict neurologic outcome after SAH.     

Cerebrospinal fluid and neutrophil respiratory burst after subarachnoid hemorrhage

OBJECTIVES: To investigate the effect of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on the activation of polymorphonuclear neutrophils (PMN) in response to receptor-dependent stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine and TNFalpha or non-receptor-dependent stimulation with phorbol 12-myristate 13-acetate. METHODS: CSF from 12 patients with SAH due to ruptured cerebral aneurysm was collected. Samples of CSF were drawn at different time points. CSF from 6 healthy subjects receiving spinal anesthesia served as the control group. After stimulation of PMN the generation of reactive oxygen intermediates was analyzed on a flow cytometer. RESULTS: In the presence of CSF, PMN showed a significant suppression of the oxidative burst following stimulation compared to stimulation without CSF. The reduction of the oxidative burst following stimulation was higher in the presence of CSF from patients with SAH. After pretreatment at 56 degrees C, the extent of the suppression observed following receptor-dependent stimulation and CSF from patients with SAH was similar to that seen after stimulation with CSF from healthy individuals. CONCLUSIONS: These data show that the presence of CSF resulted in a suppression of neutrophil oxidative function. A more distinct depression was seen in the presence of CSF from patients with SAH. We suggest a complex physiological inhibitory and protective mechanism against unfavorable activation of PMN by CSF.     

Cerebrospinal fluid ferritin in chronic hydrocephalus after aneurysmal subarachnoid hemorrhage

Objectives Subarachnoid hemorrhage (SAH) is a common cause of chronic hydrocephalus. Blood in the subarachnoid space is intracranially metabolized to bilirubin and iron, and free iron is thereafter detoxified by ferritin. However, no studies have reported the relationship between intracranial heme metabolism and chronic hydrocephalus after SAH. The goal of this prospective study was to clarify the relationship between intracranial heme metabolism and chronic hydrocephalus after SAH. Methods The authors measured the levels of bilirubin, iron and ferritin in the cerebrospinal fluid (CSF) of 70 consecutive patients with aneurysmal SAH of Fisher computed tomography Group III, and determined the relationship between these substances’ levels and hydrocephalus requiring ventriculoperitoneal shunting. Results The CSF concentrations of ferritin and inflammatory cells were significantly higher in shunted patients (n = 27) than in non-shunted patients (n = 43) on Days 3 and 4 (p<0.05 in ferritin and p<0.01 in inflammatory cells) and 11 to 14 (p<0.005 in ferritin) post-SAH. These results were independent of other clinical factors. The occurrence of chronic hydrocephalus was not affected by the extent of the intracranial heme metabolism in terms of the bilirubin and iron levels. Conclusions This is the first study to show that patients who subsequently had chronic hydrocephalus requiring CSF shunting were associated with higher CSF levels of ferritin in the acute stage of SAH. Higher CSF ferritin levels may not reflect the amount of blood in the subarachnoid space that was intracranially metabolized, but rather more intense subarachnoid inflammatory reactions which may cause chronic hydrocephalus after SAH. Received in revised form: 19 January 2006     

Cerebrospinal fluid superoxide dismutase and serum malondialdehyde levels in patients with aneurysmal subarachnoid hemorrhage: preliminary results

OBJECTIVES: Experimental studies provide evidence that oxidative damage plays a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) but data from human studies is still limited. The purpose of this study was to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH. METHODS: SOD in CSF and MDA in the serum were detected on days 1-3, 5 and 7 after aneurysmal SAH in 21 patients, and the results were compared with 15 patients with hydrocephalus. The results were also compared with those of clinical parameters including the patient's outcome at 6 months. RESULTS: The mean CSF SOD levels were lower and serum MDA levels were higher than the controls. Patients with a high amount of blood within the cisterns had a trend to decreased SOD while increasing MDA levels. CONCLUSION: These preliminary results suggest that the levels of antioxidants are decreased after the onset of SAH in the early period, possibly because of increased oxidative stress. Reactive oxygen-mediated oxidative damage may play an important role in inflammation after SAH.     

Cerebrospinal fluid nitrate levels in patients with Parkinson's disease

It has been suggested that nitric oxide could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease. Recently, it has been reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in Parkinson's disease patients, assessed with a colorimetric method. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's disease patients and 38 matched controls. The CSF and plasma nitrate levels were not correlated either in patient or in the control group, and they did not differ significantly between the two study groups. They were not influenced significantly by antiparkinsonian drugs in patients, although there was a trend for CSF nitrate levels to be higher in patients treated with levodopa or with dopamine agonists. CSF and plasma nitrate levels did not correlate with age at onset, duration, scores of the unified Parkinson's disease rating scales and Hoehn & Yahr staging in the patients group. These data suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for PD.     

Cerebrospinal fluid nitrate levels in patients with Alzheimer's disease

It has been suggested that nitric oxide could be implicated in the pathogenesis of Alzheimer's disease (AD). Recently Kuiper et al. reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in AD patients, assessed with a colorimetric method. However other group, using a microplate version of the Griess reaction, did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 32 AD patients and 36 matched controls. The CSF and plasma nitrate levels did not differ significantly between the two study groups. CSF and plasma nitrate levels did not correlate with age at onset and duration in the patient group. These data suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for AD.     

Cerebrospinal fluid superoxide dismutase and serum malondialdehyde levels in patients with aneurysmal subarachnoid hemorrhage: preliminary results

Abstract

Objectives: Experimental studies provide evidence that oxidative damage plays a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) but data from human studies is still limited. The purpose of this study was to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH.

Methods: SOD in CSF and MDA in the serum were detected on days 1–3, 5 and 7 after aneurysmal SAH in 21 patients, and the results were compared with 15 patients with hydrocephalus. The results were also compared with those of clinical parameters including the patient's outcome at 6 months.

Results: The mean CSF SOD levels were lower and serum MDA levels were higher than the controls. Patients with a high amount of blood within the cisterns had a trend to decreased SOD while increasing MDA levels.

Conclusion: These preliminary results suggest that the levels of antioxidants are decreased after the onset of SAH in the early period, possibly because of increased oxidative stress. Reactive oxygen-mediated oxidative damage may play an important role in inflammation after SAH.     

Cerebrospinal fluid nitrite and malondialdehyde levels in patients with motor neuron disease

Nitric oxide (NO) mediated oxidative damage may be involved in the pathogenesis of neuronal degeneration in motor neuron disease (MND). The present study was undertaken to evaluate the role of NO and oxidative stress in MND by estimating nitrite and malondialdehyde (MDA) levels in the cerebrospinal fluid (CSF) in 22 patients of MND and 20 control subjects suffering from neurological disorders not known to affect NO metabolism. There was no significant change in the CSF nitrite and MDA levels in MND. The nitrite and MDA levels did not have any significant correlation with age, duration of illness, or severity of disease. Univariate analysis of the clinical features in patients with MND and the nitrite levels revealed that two patients with a positive family history had significantly higher CSF nitrite levels as compared to those with a negative family history. There was no correlation between the CSF nitrite and MDA levels. Results of the present study did not indicate significant alterations in the MDA and NO levels in the CSF of MND patients. However, involvement of NO in MND with positive family history is suggested by the results obtained.     

Relation of cerebral energy metabolism and extracellular nitrite and nitrate concentrations in patients after aneurysmal subarachnoid hemorrhage.

In a prospective clinical investigation on neurochemical intensive care monitoring, the authors' aim was to elucidate the temporal profile of nitric oxide metabolite concentrations-that is, nitrite and nitrate (NO(x))--and compounds related to energy-metabolism in the cerebral interstitium of patients after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery, microdialysis probes were implanted in cerebral white matter of the vascular territory most likely affected by vasospasm. Temporal profiles of NO(x) were analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 +/- 14 years). Microdialysis was performed for 152 +/- 63 hours. Extracellular metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the extracellular fluid of the cerebral parenchyma. NO(x) was measured using a fluorometric assay. After early surgery, SAH patients revealed characteristic decreases of NO(x) from initial values of 46.2 +/- 34.8 micromol/L to 23.5 +/- 9.0 micromol/L on day 7 after SAH (P < 0.05). Decreases in NO(x) were seen regardless of development of delayed ischemia (DIND). Overall NO(x) correlated intraindividually with glucose, lactate, and glutamate (r = 0.58, P < 0.05; r = 0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral extracellular concentrations of NO metabolites decrease over time and are associated with concomitant alterations in energy-or damage-related compounds. This could be related to reduced NO availability, potentially leading to an imbalance of vasodilatory and vasoconstrictive factors. On the basis of the current findings, however, subsequent development of DIND cannot be explained by a lack of vasodilatory NO alone.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

Risk factors and outcome in 100 patients with aneurysmal subarachnoid hemorrhage

OBJECTIVE: Clinical and surgical outcome of patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysm were assessed in comparison to pre-operative data and risk factors such as previous medical history, clinical presenting condition, CT findings and site of bleeding. METHODS: We evaluated 100 consecutive patients with aneurysmal SAH. Gender, color, history of hypertension, smoking habit, site and size of aneurysm, admittance and before surgery Hunt Hess scale, need for cerebro-spinal fluid shunt, presence of complications during the surgical procedure, Glasgow Outcome Scale, presence of vasospasm and of rebleeding were assessed and these data matched to outcome. For statistical analysis, we applied the chi-squared test or Fisher's test using the pondered kappa coefficient. Kruskal-Wallis test was used for comparison of continue variables. Tendency of proportion was analyzed through Cochran-Armitage test. Significance level adopted was 5%. RESULTS: Patients studied were mainly white, female, without previous history of hypertension and non-smokers. Upon hospital admittance, grade 2 of Hunt-Hess scale was most frequently observed (34%), while grade 3 of Fisher scale was the most prevalent. Single aneurysms were most frequent at anterior circulation, between 12 and 24 mm. The most frequent Glasgow Outcome Scale observed was 5 (60%). Hunt Hess upon the moment of surgery and presence of complications during surgical procedure showed positive correlation with clinical outcome (p=0.00002 and p=0.001, respectively). Other variables were not significantly correlated to prognosis. Tendency of proportion was observed between Hunt-Hess scale and Fisher scale. CONCLUSION: Among variables such as epidemiological data, previous medical history and presenting conditions of patients with ruptured aneurysms, the Hunt-Hess scale upon the moment of surgery and the presence of surgical adversities are statistically related to degree of disability.     

Risk factors and short-term outcome in patients with angiographically negative subarachnoid hemorrhage

Objectives

The objective of this study was to identify prognostic factors for clinical outcome in patients with non-traumatic, angiographically negative subarachnoid hemorrhage. Furthermore, the aim was to investigate if patients on anticoagulant therapy may have a more unfavorable outcome than patients not receiving anticoagulant therapy.

Materials and methods

This study contains a retrospective analysis of 95 patients with non-traumatic, non-aneurysmal subarachnoid hemorrhage who were admitted to our institution in the period 2000–2011. The patients were classified according to risk factors, clinical presentation at admission, anticoagulant therapy at the time of hemorrhage and complications. The outcome was assessed with modified Rankin Score at discharge.

Results

Patients who were exposed to risk factors combined with a higher WFNS score at admission had an unfavorable outcome according to the modified Rankin Score at discharge. Unfavorable outcome was evaluated in relation to sex, anticoagulant therapy, hypertension, smoking and alcohol abuse. A strong correlation with anticoagulant therapy, smoking and alcohol abuse was found. None of the patients who developed vasospasms in this study were receiving anticoagulant therapy.

Conclusion

There is a correlation between antithrombotic state at admission and unfavorable outcome for patients with non-traumatic, non-aneurysmal subarachnoid hemorrhage. The results from this study indicate that patients on anticoagulant therapy have a higher risk of developing complications after non-aneurysmal angiographically negative subarachnoid hemorrhage compared to patients who were not receiving anticoagulant therapy.     

The relation between aneurysm size and outcome in patients with subarachnoid hemorrhage

The balance of risks of treatment for unruptured aneurysms might change if the prognosis after rupture depends on the size of the aneurysm. In a prospective series of patients with subarachnoid hemorrhage in whom aneurysmal size was measured by CT angiography performed on admission, poor outcome occurred more often in patients with large (> or =10 mm) aneurysms (63%) than in patients with small (<10 mm) aneurysms (41%; RR = 1.5; 95% CI 1.0 to 2.2). The relative risk remained essentially the same after adjustment for age, gender, location of the aneurysm, and amount of cisternal blood.     

脑脊液置换术在蛛网膜下腔出血患者中的应用

目的探讨脑脊液置换术对蛛网膜下腔出血(SAH)患者脑血管痉挛、脑积水的防治作用及缓解头痛的疗效,并评估其安全性。方法将颅内动脉瘤破裂引起的SAH患者96例分为保守治疗组(对照组)、脑脊液置换组(置换组)及颅内动脉瘤填塞术后脑脊液置换组(治疗组),比较3组脑血管痉挛、脑积水发生率和头痛缓解时间等方面的差异及再出血发生率。结果置换组及治疗组脑血管痉挛和脑积水并发症的发生率较对照组明显降低(PO.05);头痛缓解时间较对照组明显缩短(P0.05);治疗组及对照组再出血发生率较置换组明显降低(PO.05)。结论脑脊液置换术对预防SAH患者的脑血管痉挛、脑积水有效,可明显缩短患者头痛缓解时间,但为降低再出血发生率,脑脊液置换术应在动脉瘤填塞术后进行。     

107例动脉瘤性蛛网膜下腔出血患者预后的多因素分析

目的探讨动脉瘤性蛛网膜下腔出血(aSAH)患者的临床特点及其与预后的相关因素。方法回顾性分析大连医科大学附属第二医院神经外科2012年1月至2015年10月收治的107例SAH患者,根据GOS评分将病例分为预后良好组及不良组,采用单因素分析及对多因素Logistic回归分析,探讨上述各因素对预后的影响。结果全部107例患者经单因素分析显示,诱因、动脉瘤大小、Hunt-Hess评分、脑血管痉挛与患者预后明显相关(均P0.05)。多因素Logistic回归分析显示,诱因(P=0.026)、动脉瘤大小(P=0.002)、Hunt-Hess评分(P=0.016)及脑血管痉挛(P=0.003)为影响a SAH患者预后的独立危险因素。结论 a SAH患者的发病诱因、动脉瘤大小、Hunt-Hess分级和脑血管痉挛是影响患者预后的危险因素。