Effect of cilostazol in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR = 0.47; 95% CI, 0.31–0.72; p < 0.001), severe vasospasm (RR = 0.48; 95% CI, 0.28–0.82; p = 0.007), vasospasm-related new cerebral infarctions (RR = 0.38; 95% CI, 0.22–0.67; p = 0.001), and poor outcome (RR = 0.57; 95% CI, 0.37–0.88; p = 0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm-related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH.     

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p < 0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p < 0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.     

Transcranial Doppler findings in a population with clinical probable reversible cerebral vasoconstriction syndrome

ObjectiveTo describe transcranial Doppler (TCD) findings in a population with clinical probable RCVS. Exploratory objectives included the study of clinical characteristics of probable RCVS patients with and without spasm detected by TCD.MethodsCross-sectional cohort study of patients with thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) of our neurology and headache center between 2010 and 2019, selecting patients with clinical diagnosis of probable RCVS (negative angiography study) by ICHD-3 criteria and with at least two TCD studies.ResultsFrom 114 TCH patients, 36/114 had probable RCVS by ICHD-3 criteria and had at least two TCD studies available. The mean age at RCVS onset was 42.9 years (21–72 years); 29/36 (80.6%) were female, 7/28 (25%) had cardiovascular risk factors and 20/36 (55.6%) had history of migraine. Most common triggers were stressful emotion, drugs, valsalva maneuvers and sexual activity. Five/36 (13.9%) had complications and 3/36 (8.3%) had late recurrence. Initial TCD was performed on average of 16 (6–26) days after headache onset. Twenty-nine had vasospasm on TCD, presenting mean flow velocity of MCA (VMCA) of 135.7 ± 17.0 cm/s and mean maximum VMCA of 138.3 ± 17.2. Vasospasm was mild in 21/29 patients (72.4%) and moderate in 8/29 (27.6%). Complete VMCA normalization occurred on average 41 (30–70) days after headache onset and 24 (11–47) days after initial TCD. The group of patients with vasospasm detected by TCD had more female patients (26/29, 89.7% vs. 3/7, 42.8%, P = 0.016), and more TCH attacks (mean of 3.6 vs. 2.14, P = 0.049).ConclusionTCD may be a useful tool in the identification of vasospasm in patients with probable RCVS, supporting the diagnosis of RCVS in patients presenting with recurrent TCH without SAH.     

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.     

Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: Characterization of differential expression patterns in cerebral vasospasm

Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00] = 16.33, p = 0.005), angiogenin (F [1.00,7.00] = 7.65, p = 0.028), apolipoprotein A-IV (F [1.00,7.00] = 6.308, p = 0.040), granulocyte colony-stimulating factor (F [1.00,7.00] = 9.08, p = 0.020), macrophage-stimulating protein (F [1.00,7.00] = 24.21, p = 0.002), tetranectin (F [1.00,7.00] = 5.46, p < 0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00] = 6.94, p = 0.034), and significantly increased for vitronectin (F [1.00,7.00] = 5.79, p = 0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration.     

Statins may not protect against vasospasm in subarachnoid haemorrhage

Statins have been shown in two recent small phase I/II trials to be associated with a marked reduction in clinical and transcranial Doppler (TCD) evidence of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). The purpose of this study was to assess the clinical impact of this treatment in a larger number of patients. Fifty-eight individuals were treated in the year before, and 72 patients treated in the year after, the introduction of a 2 week course of 40 mg/day pravastatin therapy for SAH. Statins did not result in reduced TCD velocities, clinical or angiographic vasospasm, or improvements in global outcome at the time of hospital discharge. A measurable reduction in the rates of vasospasm was expected, based on the size of the effect of statin therapy in the previous small studies. There remains significant uncertainty as to the role of statins in preventing vasospasm after SAH.     

Vertebrobasilar dissections: Case series comparing patients with and without dissecting aneurysms

Vertebrobasilar dissections are being increasingly diagnosed due to better awareness and increased availability of modern imaging techniques of the intracranial and extracranial arteries. The clinical presentation and outcome in patients with vertebrobasilar dissections may be complicated by dissecting aneurysms. The aim of this retrospective study was to compare the clinical profile of patients with vertebrobasilar dissections with and without dissecting aneurysms, and to determine predisposing factors to the development of aneurysms. Thirty patients (19 [63%] male; median age 44.5 years) were identified. The patients were divided into two groups, an aneurysmal dissection group with seven patients and a non-aneurysmal dissection group with 23 patients. Eight (27%) patients presented with dissection after trivial trauma, three (10%) following high-speed vehicular trauma, two (7%) were associated with infection, but most (57%) were apparently spontaneous. Migraine with aura (p = 0.008) and female sex (p = 0.03) were observed more frequently in the aneurysmal dissection group. Though vascular risk factors other than hypertension and atrial fibrillation were seen in a greater percentage of patients in the non-aneurysmal dissection group, this was not statistically significant. Patients were treated with antiplatelet agents (n = 8) or warfarin (n = 13) or underwent an endovascular intervention (n = 6). Post-discharge data were available in 19 patients, of whom 14 (74%) were independent at a median follow-up of 4 months. Female sex and migraine with aura may predispose to the formation of acute dissecting aneurysms and this requires further research. Larger, prospective studies are required to ascertain epidemiologic and etiologic factors predisposing patients to the development of both intracranial and extracranial dissecting aneurysms in the vertebrobasilar circulation.     

Effect of vardenafil on cerebral vasospasm following experimental subarachnoid hemorrhage in rats

We examined the effects of the phosphodiesterase 5 (PDE-5) inhibitor vardenafil on cerebral vasospasm in an experimental rat subarachnoid hemorrhage (SAH) model. Thirty-two albino Wistar rats were divided into five groups: G1, no experimental intervention; G2, administered subarachnoid physiological saline after sham surgery; G3, subjected to SAH; G4, subjected to SAH and administered low-dose (0.5 mg/kg) vardenafil treatment; and G5, subjected to SAH and administered high-dose (5 mg/kg) vardenafil treatment. For animals in G3, G4 and G5, SAH was induced by an injection of autologous non-heparinized blood into the cisterna magna. Immediately after SAH, for animals in G4 and G5, vardenafil was administered by gavage at intervals of 8 hours for 2 days. The rats were then decapitated, and basilar arteries and blood samples were taken for biochemical and histopathological examination. Malonyldialdehyde values in G2 (p = 0.004) and G3 (p = 0.002) were significantly higher than those in G1. G4 and G5 had significantly lower values than G2 and G3 (p = 0.014, G4 v. G2; p = 0.005, G4 v. G3; p = 0.005, G5 v. G2; p = 0.002, G5 v. G3). Total antioxidant capacity (TAC) values in G3 were significantly lower than those in G1 (p = 0.041). TAC values in G4 and G5 were significantly higher than those in G3 (p = 0.043). Mean luminal diameter in G3 was significantly smaller compared with G1 and G2 (p = 0.002), but larger in G4 (p = 0.002) and G5 (p = 0.001) compared with G3. Mean luminal diameter was also significantly larger in G5 than in G2 (p = 0.008) and G4 (p = 0.038). Mean wall thickness in G2 (p = 0.015) and G3 (p = 0.002) was significantly thicker compared with G1. Wall thickness was significantly thinner in G4 and G5 compared with G2 and G3 (p = 0.008, G4 v. G2; p = 0.001, G4 v. G3; p = 0.005, G5 v. G2; p = 0.001, G5 v. G3). Our results confirm that vardenafil may induce vasodilatation and provide potential benefits in SAH therapy by preventing vasospasm.     

Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats

Angiographic vasospasm, especially in the early phases (<72 h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague–Dawley rats. Then, the underlying mechanism of the anti-vasospasm effect of SCU was investigated using a modified Garcia scale, India ink angiography, cross-sectional area analysis, immunohistochemistry staining and western blot. SCU (50 μM, 100 mg/kg) alleviated angiographic vasospasm and improved neurological function 48 h after SAH and enhanced the expression of endothelial nitric oxide synthase (eNOS) at the intima of cerebral arteries. In addition, SCU upregulated the expression of phosphorylated extracellular-regulated kinase 5 (p-Erk5) and Kruppel-like factor 2 (KLF2) at 48 h after SAH. However, the effects of SCU were reversed by the Erk5 inhibitor XMD8-92. Our results indicate that SCU could attenuate vasospasm and neurological deficits via modulating the Erk5-KLF2-eNOS pathway after SAH, which may provide an experimental basis for the clinical use of SCU treatment in SAH patients.     

Effects of ebselen versus nimodipine on cerebral vasospasm subsequent to experimental subarachnoid hemorrhage in rats

We investigated the effect of ebselen relative to nimodipine in an animal model of subarachnoid hemorrhage. Thirty Wistar albino rats were divided into 5 groups: G1, no intervention; G2, sham surgery without subarachnoid hemorrhage (SAH); G3, SAH only; G4, SAH plus nimodipine treatment; G5, SAH plus ebselen treatment. For G2 animals, physiological saline (0.9% NaCl) was injected into the cisterna magna. For G3, G4 and G5 animals, SAH was induced by injecting autologous non-heparinized blood into the cisterna magna. One hour after injection, G4 animals received nimodipine at 6-hour intervals and G5 animals received ebselen twice a day for 48 hours. After treatment, brain tissue and blood samples were taken for biochemical and histopathological examination. Mean malonyldialdehyde concentration was significantly higher in G3 than in G1 (p < 0.0001), G2 (p = 0.01), G4 (p = 0.002) and G5 (p = 0.014), and significantly higher in G5 than in G1 (p = 0.013). Mean superoxide dismutase activity was significantly lower in G4 than in both G1 (p = 0.025) and G2 (p = 0.02). Mean wall thickness was significantly greater in G3 than in G1 (p < 0.0001), G2 (p = 0.01), G4 (p < 0.0001) and G5 (p < 0.0001). Mean wall thickness was also significantly greater in both G1 and G2 than in G4 (p < 0.0014 and p < 0.0001) and G5 (p < 0.0001 and p < 0.0001). Mean luminal diameter of the basilar artery was significantly smaller in G3 than in G2 (p = 0.02), G4 (p < 0.018) and G5 (p < 0.001). Our results confirm that ebselen may have neuroprotective effects by acting to prevent vasospasm.     

Aneurysmal acute subdural hemorrhage: Prognostic factors associated with treatment

Acute subdural hematoma is an uncommon presentation of aneurysmal hemorrhage that has been identified as a poor prognostic sign. Current series are small, have short follow-up, or were collected over a long period during which treatment evolved. To evaluate prognostic factors, we analyzed a large modern series of aneurysmal subdural hematoma (aSDH) with long-term follow-up. A prospectively maintained database was queried for patients presenting with aSDH from 2001–2013. Thirty patients met the study criteria. Statistical analysis was performed with unpaired t-test or Fisher’s exact test. Aneurysm treatment involved open clipping (n = 18), endosaccular coiling (n = 8), both (n = 1), or no treatment (n = 3). Good Glasgow Outcome Scale score at discharge was present in 20% and increased to 40% at 6–12 months postoperatively. Good clinical presentation was associated with good final outcome in 75%, whereas poor clinical presentation correlated with good outcome in 30%. Good outcome correlated with younger age (p = 0.04), smaller aneurysm (p = 0.04), and lower Hunt-Hess score (HH) at intervention (p = 0.04). Favorable outcome did not correlate with sex, race, presence of subarachnoid or intraparenchymal hemorrhage, size or laterality of hemorrhage, midline shift, aneurysm treatment modality, or HH at admission (p > 0.15). There was no difference between good and poor outcomes in terms of time to treatment or hematoma evacuation. Poor clinical presentation may be exaggerated by mass effect of hematoma; aggressive treatment is not futile. Presenting neurological status, age, and aneurysm size are predictors of outcome, while laterality and size of hematoma and extent of midline shift are not, suggesting that clinical status is more important than radiographic findings.     

Changing paradigm in the management of elderly patients with intracranial aneurysms: An institutional review

Optimal treatment of intracranial aneurysms (IAs) in elderly patients has not yet been well established. We have investigated the clinical and radiological outcomes and predictors of unfavorable outcome of IAs in elderly patients. Radiological and clinical data of 85 elderly patients from 2010 through 2015 were retrospectively reviewed. Significant differences between the groups were determined by a chi-square test. Regression analysis was performed to identify the predictors of unfavorable outcome. Among the 85 patients with IAs, the number of patients with >7 mm size aneurysm (p = 0.01), diabetes mellitus (DM) (p = 0.02), smoking (0.009) and Hunt and Hess grade 4–5 (p = 0.003) was significantly higher in the ruptured group compared to the unruptured group. Similarly, the number of patients who underwent clipping was higher in the ruptured aneurysm group (p = 0.01). The overall clinical outcome was comparatively better in the unruptured group (p = 0.03); however, microsurgical clipping of aneurysms provides a significantly higher rate of complete aneurysmal occlusion (p = 0.008). Overall, there was no significant difference in outcome in respect to treatment approach. In regression analysis, hypertension (HTN), obstructive sleep apnea (OSA), prior stroke, ruptured aneurysms and partial occlusion of aneurysms were identified as predictors of unfavorable outcome of IAs. Intracranial aneurysms in elderly patients reveals that endovascular treatment provides better clinical outcome; however, microsurgical clipping yields higher complete occlusion. Retreatment of residual aneurysms was comparatively more in the coiling group. Practice pattern has shifted from clipping to coiling for aneurysms in posterior circulation but not for aneurysms in anterior circulation.     

Nicotine replacement therapy in patients with aneurysmal subarachnoid hemorrhage: Systematic review of the literature,and survey of Canadian practice

Tobacco smoke increases the risk of aneurysmal subarachnoid hemorrhage (SAH), as well as complications such as vasospasm. Most patients presenting with aneurysmal SAH smoke, and many survivors continue to smoke after discharge. Neurosurgeons often hesitate to use nicotine replacement therapy (NRT) during hospitalization of patients with SAH due to concerns of inducing vasospasm. We aimed to evaluate the safety and efficacy, and patterns of use of NRT in smokers hospitalized for SAH. We performed a systematic review of MEDLINE, CENTRAL, Embase, and unpublished sources of literature to October 2016 for randomized and observational studies comparing exposure to non-exposure of smoking cessation products in the acute phase of aneurysmal SAH. Additionally, we surveyed 50 Canadian vascular neurosurgeons to evaluate patterns of NRT use in SAH. Four cohort studies (n = 1210) met our eligibility criteria. Three studies enrolled patients with aneurysmal SAH, and one study enrolled all neurocritically ill patients. We rated the quality of evidence as very low using the GRADE approach. We could not meta-analyze studies due to methodological heterogeneity. Individual studies reported beneficial or neutral effects of NRT on functional outcome, death, and clinical or radiographic vasospasm. None of the studies assessed long-term abstinence from tobacco. Of the 14 vascular neurosurgeons responding to our survey, most never used NRT in patients hospitalized with SAH, often citing training or standard of practice as the reason. Current evidence suggests that NRT does not induce vasospasm, and is associated with improved outcomes in smokers hospitalized for SAH.Protocol registered in PROSPERO, available at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016037200.     

Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fisher’s exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8–14 (8–14 versus 3–7, p = 0.016; 15 versus 3–7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8–14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3–7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8–14. To clarify and strengthen these observations, prospective, randomized trials are needed.     

Traumatic interhemispheric subdural haematoma: Study of 35 cases

The clinical and radiological findings, management, and outcomes in 35 patients with traumatic interhemispheric subdural haematoma (ISH) were reviewed retrospectively. Twenty-five patients had favourable outcomes and 10 had poor outcomes. All patients were treated conservatively for ISH. Univariate analysis found that the Glasgow Coma Scale (GCS) score (p < 0.001), hypovolemic shock (p = 0.018), skull fracture (p = 0.008), convexity or posterior fossa subdural haematoma (p = 0.008), and subarachnoid haemorrhage (SAH) were correlated with outcome (p < 0.001). Multivariate analysis showed that GCS score (p = 0.031; odds ratio [OR], 0.6; 95% confidence interval [CI], 0.3–0.9) and the presence of SAH (p = 0.023; OR, 14.2; 95% CI, 1.5–138.2) were significantly related to poor outcome. This study provides important information on the clinicoradiological findings and prognoses in patients with traumatic ISH.     

Elderly age associated with poor functional outcome after rupture of anterior communicating artery aneurysms

The effect of age on patient outcomes after rupture of the anterior communicating artery (Acom) aneurysms is not well-defined. We performed a retrospective cohort study of patients presenting to our institution with a ruptured Acom aneurysm between 2003 and 2012. Patients were divided into two groups on the basis of age at presentation, with patients 65 years and older categorized as the elderly group. The effect of elderly age on patient outcomes was then evaluated using multivariate logistic regression analysis. There were 147 patients presenting with a ruptured Acom aneurysm. Of these, 41 (27.9%) were 65 years or older. Patients in the elderly group were more likely to be female (68.3% vs. 40.6%, p = 0.0026), and less likely to be active smokers (22.0% vs. 60.4%, p < 0.0001) or to abuse alcohol (7.3% vs. 21.7%, p = 0.0404). Elderly patients were more likely to have a history of hypertension (70.7% vs. 52.8%, p = 0.0487) and coronary artery disease (19.5% vs. 2.8%, p = 0.0006). Elderly patients were more likely to require a ventriculostomy (61.0% vs. 37.7%, p = 0.0109) and ultimately to require permanent cerebrospinal fluid diversion (36.6% vs. 17.0%, p = 0.0106). On adjusted analysis, age 65 years or older was associated with a greater likelihood of poor outcome at last follow-up within 1 year of aneurysmal subarachnoid hemorrhage (odds ratio = 3.76, 95% confidence interval: 1.30–11.78, p = 0.0144). Our results suggest that elderly age is an independent risk factor for poor functional outcome after rupture of an Acom aneurysm.     

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage in Japanese patients

To elucidate the pituitary function of Japanese patients after aneurysmal subarachnoid hemorrhage (aSAH) and implicative factors related to growth hormone deficiency (GHD) after aSAH. We evaluated basal pituitary hormone levels among 59 consecutive aSAH patients with a modified Rankin Scale (mRS) ⩽4 at 3 months after aSAH onset. Patients with low insulin-like growth factor 1 (IGF-1) SD score (SDS) or who seemed to develop pituitary dysfunction underwent provocative endocrine testing during a period of 3–36 months after SAH onset. The relationship between IGF-1 SDS and clinical factors of the patients such as severity of SAH, aneurysm location, and treatment modalities, were assessed. Six patients (10.2%) demonstrated their IGF-1 SDS less than −2. Multiple logistic regression analyses revealed that patients who underwent surgical clipping had a significantly lower IGF-1 SDS (<−1 SD) than patients who underwent endovascular embolization with an odds ratio of 5.83 (p = 0.032). Thirty-three patients took provocative tests and five (15.6%) patients were identified as having GHD. The mean IGF-1 SDS of these five GHD patients was 0.08 SD. The aneurysms in all GHD patients were located in internal carotid artery (ICA) or anterior cerebral artery (ACA). To the best of our knowledge, this is the first report describing the prevalence of GHD in Japanese patients after aSAH, and it was not as high as that of previous European studies. We recommend that screening pituitary dysfunction for aSAH survivors with their aneurysms located in ICA or ACA.     

Relationship between microemboli in the internal carotid artery and the occurrence of ischemic stroke after transient ischemic attack

Microembolic signals (MES) have been reported to be an independent risk factor for stroke and transient ischemic attack (TIA). We examined the relationship between MES in the internal carotid artery and the occurrence of ischemic stroke in patients with TIA. A total of 67 patients who had a TIA were examined with transcranial Doppler ultrasonography to detect microemboli in the internal carotid artery 1, 3, and 7 days after admission, and 3 months after discharge. The relationship between the presence of MES and the subsequent occurrence of ischemic stroke was the primary outcome of interest. 35.8% (24/67) of patients were MES(+). During follow-up, ischemic stroke occurred significantly more frequently in patients who were MES(+) compared with patients who were MES(?) (6/24; 25.0% versus 2/43; 4.7%, p = 0.021), as did TIA (11/24; 45.8% versus 4/43; 9.3%). MES(+) status was significantly associated with the occurrence of ischemic stroke after adjusting for age, sex, hypertension, diabetes mellitus, and drug therapy (odds ratio: 8.30; 95% confidence interval: 1.37–50.42; p = 0.021). The positive and negative predictive values of MES status for predicting ischemic stroke were 25.0% and 95.4%, respectively. The presence of microemboli in the internal carotid artery appears to be an important risk factor for the occurrence of ischemic stroke after TIA. The MES(+) rate in patients with transient ischemic attack with severe internal carotid artery stenosis is markedly higher than in patients without internal carotid artery stenosis.     

In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA

Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007–2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p < 0.001), predominantly male (53.3% versus 38.5%, p < 0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p < 0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p < 0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p < 0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27–1.61, p < 0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69–0.87, p < 0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted.     

Increased levels of soluble triggering receptor expressed on myeloid cells-1 in cerebrospinal fluid of subarachnoid hemorrhage patients

Triggering receptor expressed on myeloid cells-1 (TREM-1) has been highlighted as a key amplifier of inflammatory response in various diseases. To determine the contribution of TREM-1 in the inflammatory cascade after subarachnoid hemorrhage (SAH), concentrations of soluble TREM-1 (sTREM-1) in cerebrospinal fluid (CSF) from 30 SAH patients and 9 healthy volunteers were measured by enzyme-linked immunosorbent assay. It was shown that the CSF sTREM-1 levels of SAH patients increased significantly than that of the volunteers (P < 0.05). Interestingly, the levels were up-regulated dynamically over time with an early increase within 2 days and a late peak at day 6 after SAH onset. In addition, it was found that the early sTREM-1 levels (within 3 days post-SAH) were negatively correlated with Glasgow Coma Scale (r = −0.550, P = 0.022) and positively correlated with the Hunt and Hess scale (r = 0.603, P = 0.010) respectively conducted on admission, also the early sTREM-1 levels were negatively correlated with Glasgow Outcome Scale (r = −0.505, P = 0.039) and positively correlated with modified Rankin Scale (r = 0.557, P = 0.020) respectively conducted one month after SAH. Altogether, this is the first study showing CSF sTREM-1 dynamics in SAH patients, and exploring the correlations of early CSF sTREM-1 levels to patients’ severity and prognosis, which suggests that TREM-1 may play an important role in the inflammatory cascade after SAH and act as a monitoring biomarker facilitated to assess the severity and prognosis of SAH patients.