Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

PubMed

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

History from within? Contextualizing the new neurohistory and seeking its methods.

PubMed

Burman, Jeremy Trevelyan

2012-02-01

"Histories from below" sought to give voice to those ordinary folk whose social position had failed to afford them great power, wealth, or responsibility: the neglected undocumented. Now, Lynn Hunt (2009) calls for a revolution that would task historians with giving voice to feelings--what I will call a "history from within." This is what led her to endorse Daniel Lord Smail's (2008) suggestion that historians appeal to neuroscience and thereby construct a "new neurohistory." The purpose would be to introduce a common factor to all human stories: a tool to think with when describing what it was like (cf. Nagel, 1974). If successful, this would be quite powerful: in Hunt's view, such a project could lead to a universalization of human rights. But the program is not without challenges, one of which is to provide an acceptable explanation for the type of looping causation that applies to bio-cultural kinds. Smail's solution involves an appeal to evolutionary theory, but how this solves the problem of causation is not clear. Here, therefore, an attempt is made to clarify his solution. Smail and Hunt's views on the role of evidence in history are also made plain. The paper then concludes by importing related ideas from the recent history of philosophy. If one is going to have a brain-based view of felt-history, then the neurohistorian's task is to situate historical individuals in contexts of shared experience--to not just read evidence through lenses of intellectual "thought collectives" (generalized from paradeigma), but also through "experiential" or "moral categories" (aisthánomai).

Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

PubMed Central

2011-01-01

Background Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH. Results Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm2) is significantly smaller than that in control group (462,128 ± 74,756 μm2), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm2) and SAH + vitamin C group (237,820 ± 21,703 μm2). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm2, which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05). Conclusion Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so. PMID:21801458

Does magnetic resonance imaging produce further benefit for detecting a bleeding source in subarachnoid hemorrhage of unknown origin?

PubMed

Maslehaty, Homajoun; Petridis, Athanassios K; Barth, Harald; Doukas, Alexandros; Mehdorn, Hubertus Maximilian

2011-01-01

Spontaneous subarachnoid hemorrhage (SAH) without evidence of a bleeding source on the first digital subtraction angiogram (DSA) - also called SAH of unknown origin - is observed in up to 27% of all cases. Depending on the bleeding pattern on CT scanning, SAH can be differentiated into perimesencephalic (PM-SAH) and non-perimesencephalic SAH (NON-PM-SAH). The aim of our study was to investigate the effectiveness of magnetic resonance imaging (MRI) for detecting a bleeding source in SAH of unknown origin. We retrospectively reviewed 1,226 patients with spontaneous SAH between January 1991 and December 2008 in our department. DSA was performed in 1,068 patients, with negative results in 179 patients. Forty-seven patients were categorized as having PM-SAH and 132 patients as having NON-PM-SAH. MRI of the brain and the craniocervical region was performed within 72 h after diagnosis of SAH and demonstrated no bleeding sources in any of the PM-SAH and NON-PM-SAH patients (100% negative). In our experience MRI did not produce any additional benefit for detecting a bleeding source after SAH with a negative angiogram. The costs of this examination exceeded the clinical value. Despite our results MRI should be discussed on a case-by-case basis because rare bleeding sources are periodically diagnosed in cases of NON-PM-SAH.

Effects of blockade of cerebral lymphatic drainage on regional cerebral blood flow and brain edema after subarachnoid hemorrhage.

PubMed

Sun, Bao-Liang; Xia, Zuo-Li; Wang, Jing-Ru; Yuan, Hui; Li, Wen-Xia; Chen, Yu-She; Yang, Ming-Feng; Zhang, Su-Ming

2006-01-01

The study was designed to observe the influence of blockade of cerebral lymphatic drainage on the regional cerebral blood flow (rCBF) and brain edema after experimental subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and SAH plus cervical lymphatic blockade (SAH + CLB) groups. Autologous arterial hemolysate was injected into rat's cisterna magna to induce SAH. The rCBF was recorded continuously by a laser Doppler flowmeter. Intracranial pressure (ICP) was also monitored. After 24 hours and 72 hours of SAH, the rats were sacrificed and the brain was harvested for water content detection. It was found that there was no obvious change of rCBF and brain water content during the experiment in non-SAH group. An immediate and persistent drop in rCBF was found in SAH group. The drop in rCBF was more obvious in SAH + CLB group. CLB also worsened the SAH-induced increase in ICP. The brain water content 24 hours and 72 hours after induction of SAH in SAH group increased significantly. CLB led to a further increase of brain water content. In conclusion, blockade of cerebral lymphatic drainage pathway deteriorates the secondary cerebral ischemia and brain edema after SAH.

Long-term reintegration and quality of life in patients with subarachnoid hemorrhage and a good neurological outcome: findings after more than 20 years.

PubMed

Sonesson, Bengt; Kronvall, Erik; Säveland, Hans; Brandt, Lennart; Nilsson, Ola G

2018-03-01

OBJECTIVE The goal of this study was to examine long-term quality of life (QOL) and reintegration in patients with good neurological recovery after aneurysmal subarachnoid hemorrhage (aSAH) and SAH of unknown cause (SAH NUD). METHODS A long-term follow-up was performed in an original cohort of 113 individuals who had suffered SAH (93 with aSAH and 20 with SAH NUD) between 1977 and 1984. Self-reporting assessments, performed > 20 years after the bleeding episode, included the Quality of Life Scale (QOLS), Psychological General Well-Being (PGWB) index, and Reintegration to Normal Living (RNL) index, along with information on sleep disturbances and work status. RESULTS Seventy-one survivors were identified. Questionnaires were returned by 67 individuals who had suffered SAH 20-28 years previously. The QOL was rated in the normal range for both the QOLS score (aSAH 90.3 vs SAH NUD 88.6) and the PGWB index (aSAH 105.9 vs SAH NUD 102.8). Ninety percent of patients had returned to their previous employment. Complete RNL was reported by 40% of patients with aSAH and by 46% of patients with SAH NUD; mild to moderate readjustment difficulties by 55% and 38%, respectively; and severe difficulties by 5% of patients with aSAH and 15% of patients with SAH NUD. Self-rated aspects of cognition, mood, and energy resources in addition resulted in a substantial drop in overall reintegration. Sleep disturbances were reported by 26%. CONCLUSIONS More than half of patients with SAH who had early good neurological recovery experienced reintegration difficulties after > 20 years. However, the general QOL was not adversely affected by this impairment. Inability to return to work after SAH was associated with lower QOLS scores. Sleep disturbances were associated with lower PGWB scores.

Incidence and outcome of subarachnoid haemorrhage in the general and emergency department populations in Queensland from 2010 to 2014.

PubMed

Chu, Kevin H; Mahmoud, Ibrahim; Hou, Xiang-Yu; Winter, Craig D; Jeffree, Rosalind L; Brown, Nathan J; Brown, Anthony Ft

2018-02-05

To determine: (i) incidence and outcome of subarachnoid haemorrhage (SAH) in the general population; and (ii) proportions of SAH in both the general ED population and in ED patients presenting with headache. A population-based study in Queensland from January 2010 to December 2014 was conducted. Data were sourced from the Australian Bureau of Statistics, Queensland Hospital Admitted Patient Data Collection linked to the Queensland death registry and ED Information System. Admitted patients with SAH were identified from ICD-10-AM codes. Inter-hospital transfers and repeat admissions for previously diagnosed SAH were excluded. Pre-hospital deaths from SAH were included. ED patients with headache were identified from ICD-10-AM codes and finding 'headache' in the triage free-text entry. The incidence of SAH, in-hospital mortality, proportions of SAH in the general ED population and ED patients with headache were calculated. There were 1975 incident cases of SAH in admitted patients and 294 pre-hospital deaths from SAH. The incidence of SAH was 9.9 (95% confidence interval [CI] 9.5-10.4) per 100 000 person-years. The incidence standardised to the 'World Standard Population' was 7.0 per 100 000 person-years. The in-hospital mortality was 23.8% (95% CI 22.0-25.8%). SAH was found in 1407 (1.9%, 95% CI 1.8-2.0) of ED patients with headache. Overall, there were 2.4 (95% CI 2.3-2.5) SAH per 10 000 of all ED attendances. The incidence of SAH was similar to that previously reported for Australia. One in 50 ED patients with headache had SAH. Ten in 50 000 ED attendances had a SAH. These estimates can assist in the risk assessment for SAH. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Using a 17th-Century Experiment as a Gateway to Critical Assessment of Scientific Reports

ERIC Educational Resources Information Center

Shodell, Michael

2010-01-01

It is certainly widely appreciated that there is much to be gained in the fertile crosstalk between science and history--whether bringing a historical perspective into the science classroom (Wieder, 2006) or a scientific perspective to the study of history (McElvaine, 2002; Smail, 2008). Perhaps the major impetus for using history in teaching…

Crystal structure of secretory abundant heat soluble protein 4 from one of the toughest “water bears” micro‐animals Ramazzottius Varieornatus

PubMed Central

Fukuda, Yohta

2018-01-01

Abstract Though anhydrobiotic tardigrades (micro‐animals also known as water bears) possess many genes of secretory abundant heat soluble (SAHS) proteins unique to Tardigrada, their functions are unknown. A previous crystallographic study revealed that a SAHS protein (RvSAHS1) from one of the toughest tardigrades, Ramazzottius varieornatus, has a β‐barrel architecture similar to fatty acid binding proteins (FABPs) and two putative ligand binding sites (LBS1 and LBS2) where fatty acids can bind. However, some SAHS proteins such as RvSAHS4 have different sets of amino acid residues at LBS1 and LBS2, implying that they prefer other ligands and have different functions. Here RvSAHS4 was crystallized and analyzed under a condition similar to that for RvSAHS1. There was no electron density corresponding to a fatty acid at LBS1 of RvSAHS4, where a putative fatty acid was observed in RvSAHS1. Instead, LBS2 of RvSAHS4, which was composed of uncharged residues, captured a putative polyethylene glycol molecule. These results suggest that RvSAHS4 mainly uses LBS2 for the binding of uncharged molecules. PMID:29493034

Tendencies in cerebral aneurism treatment: Analysis of a hospital series.

PubMed

Lago, A; López-Cuevas, R; Tembl, J I; Fortea, G; Górriz, D; Aparici, F; Parkhutik, V

To discover if there have been changes in the treatment time for SAH in our hospital environment. Comparative analysis of 571 patients treated at Hospital Universitari la Fe during 2 different time periods. The SAH-OLD group consisted of 462 patients attended consecutively between April 1997 and March 2005, while SAH-NEW comprised 109 patients attended consecutively between March 2007 and April 2010. We analysed demographic factors, risk factors, severity at time of admission, time to arteriography, diagnosis of aneurysm, use of surgical or endovascular treatment and time to treatment, frequency of neurological complications, in-hospital deaths, and modified Rankin Scale (mRS) at discharge. Mean time to arteriography was 2.18 ± 2.5 days for the SAH-OLD group and 2.37 ± 2.23 days, for the SAH-NEW group (P=.49). Mortality rates for SAH-OLD patients were calculated at 30%, compared to 18.3% in SAH-NEW patients (P=.01). Among patients surviving the hospital stay in the SAH-OLD group, 13.3% had an mRS > 3, compared to 21.3% of survivors in the SAH-NEW group (P=.06). Two hundred forty-five patients in the SAH-OLD group had cerebral aneurysms and 208 were treated (45% of the patient total). Sixty-five of the SAH-NEW patients received treatment (60% of the patient total, P=.007). In the SAH-OLD group, 62.9% of the patients underwent embolisation vs 74.6% in the SAH-NEW group (P=.08). Time to embolisation was 4.7 ± 8.2 days for SAH-OLD patients and 2.12 ± 2.2 days for SAH-NEW patients (P=.01). Twenty-two percent of SAH-OLD patients underwent surgery, compared to 25.4% in the SAH-NEW group (P=.62). Care for SAH patients has improved in this hospital: results include fewer mortalities, a higher number of treatments with a smaller proportion of endovascular treatments, and shorter times to treatment. Elapsed time to arteriography remains stable. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The impact of traumatic subarachnoid hemorrhage on outcome: a study with grouping of traumatic subarachnoid hemorrhage and transcranial Doppler sonography.

PubMed

Lin, Tzu-Kang; Tsai, Hong-Chieh; Hsieh, Tsung-Che

2012-07-01

To clarify the clinical role of traumatic subarachnoid hemorrhage (tSAH), stratified analysis with grouping of tSAH was performed. Their blood flow changes and correlations with outcome were assayed. One hundred seventeen tSAH patients were classified into several groups according to their initial computerized tomography scans. Group I included patients with tSAH only in the posterior interhemispheric fissure, whereas Group II contained patients with tSAH located elsewhere. Group II was further subdivided into IIa, little SAH; IIb, extensive SAH; IIc, little SAH with intraventricular hemorrhage (IVH); and IId, extensive SAH with IVH. The cerebral blood flow velocity was monitored using transcranial Doppler sonography (TCD). Both age and initial coma scale were independent predictors of poor outcome. The poor outcome rates in various subgroups of tSAH increased stepwise from group I to group IId (I, 7.4%; IIa, 18.4%; IIb, 33.3%; IIc, 62.5%; and IId, 90.9%) (p = 0.0010). Stratified analyses revealed that patients with extensive tSAH (group IIb + IId) were more likely to have unfavorable outcomes (47.7%) than patients with little tSAH (group IIa + IIc) (26.1%) (p = 0.0185); patients with IVH (group IIc + IId) also displayed a higher incidence (78.9%) of poor outcomes than patients without IVH (group IIa + IIb) (25.4%) (p = 0.0030). TCD study demonstrated that patients with extensive tSAH (group IIb + IId) were more likely to have the vasospasm based on TCD criteria than did patients in group I and group IIa + IIc (37.5% vs. 5.9% and 7.7%, p = 0.0105). Notably, there was a tendency of worse outcome in patients with vasospasm on the basis of TCD-derived criteria than those without, with the unfavorable outcome rates being 47.4% and 24.7% (p = 0.0799). Age, initial coma scale, extensive tSAH, and IVH are independent predictors of poor outcome in the cohort of tSAH patients. Statistically, patients with extensive tSAH are significantly more likely to have vasospasm.

6-Mercaptopurine attenuates adhesive molecules in experimental vasospasm.

PubMed

Chang, Chih-Zen; Lin, Chih-Lung; Kassel, Neal F; Kwan, Aij-Lie; Howng, Shen-Long

2010-05-01

Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important inflammatory mediators which are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) was effective in preventing and reversing arterial narrowing in a rodent SAH model. The present study was to examine whether levels of adhesion molecules were altered after treatment with 6-mp in this animal model. Animals were each injected with autologous blood into the cisterna magna, and intraperitoneal treatment with 6-mp (2 mg/kg) was initiated 1 h before (prevention) or later (treatment). The compound was subsequently administered at 24 and 48 h post-SAH. Blood samples were collected at 72 h post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. The basilar arteries were harvested and sliced, and their cross-sectional areas were measured. Morphologically, convolution of the internal elastic lamina, distorted endothelial wall, and myonecrosis of the smooth muscle were prominently observed in the SAH only and vehicle-treated SAH groups, but not in the 6-mp-treated SAH group or in healthy controls. No significant differences were found in the levels of VCAM-1 among all groups. However, the levels of E-selectin were increased in all animals subjected to SAH (SAH only and SAH plus vehicle groups) compared with healthy controls (no SAH), but not in the 6-mp group (SAH plus 6-mp treatment and preventive treatment with 6-mp).Likewise, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and pretreatment and treatment with 6-mp reduced ICAM-1 to control levels. These results show that ICAM-1 and E-selectin may play a role in mediating SAH-induced vasospasm and that a reduction of both adhesive molecules after SAH may partly contribute to the antispastic effect of 6-mp.

Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.

Controversies and Evolving New Mechanisms in Subarachnoid Hemorrhage

PubMed Central

Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, John H.

2013-01-01

Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms “early brain injury” and “delayed brain injury” are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications. PMID:24076160

Cognitive deficits after aneurysmal and angiographically negative subarachnoid hemorrhage: Memory, attention, executive functioning, and emotion recognition.

PubMed

Buunk, Anne M; Groen, Rob J M; Veenstra, Wencke S; Metzemaekers, Jan D M; van der Hoeven, Johannes H; van Dijk, J Marc C; Spikman, Jacoba M

2016-11-01

The authors' aim was to investigate cognitive outcome in patients with aneurysmal and angiographically negative subarachnoid hemorrhage (aSAH and anSAH), by comparing them to healthy controls and to each other. Besides investigating cognitive functions as memory and attention, they focused on higher-order prefrontal functions, namely executive functioning (EF) and emotion recognition. Patients and healthy controls were assessed with tests measuring memory (15 Words Test, Digit Span), attention and processing speed (Trail Making Test A and B), EF (Zoo Map, Letter Fluency, Dysexecutive Questionnaire), and emotion recognition (Facial Expressions of Emotion Stimuli and Tests). Between-groups comparisons of test performances were made. Patients with aSAH scored significantly lower than healthy controls on measures of memory, processing speed, and attention, but anSAH patients did not. In the higher-order prefrontal functions (EF and emotion recognition), aSAH patients were clearly impaired when compared to healthy controls. However, anSAH patients did not perform significantly better than aSAH patients on the majority of the tests. In the subacute phase after SAH, cognitive functions, including the higher-order prefrontal functions EF and emotion recognition, were clearly impaired in aSAH patients. Patients with anSAH did not perform better than aSAH patients, which indicates that these functions may also be affected to some extent in anSAH patients. Considering the importance of these higher-order prefrontal functions for daily life functioning, and following the results of the present study, tests that measure emotion recognition and EF should be part of the standard neuropsychological assessment after SAH. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Atmospheric Pressure Variation is a Delayed Trigger for Aneurysmal Subarachnoid Hemorrhage.

PubMed

van Donkelaar, Carlina E; Potgieser, Adriaan R E; Groen, Henk; Foumani, Mahrouz; Abdulrahman, Herrer; Sluijter, Rob; van Dijk, J Marc C; Groen, Rob J M

2018-04-01

There is an ongoing search for conditions that induce spontaneous subarachnoid hemorrhage (SAH). The seasonal pattern of SAH is shown in a large meta-analysis of the literature, but its explanation remains undecided. There is a clear need for sound meteorologic data to further elucidate the seasonal influence on SAH. Because of the stable and densely monitored atmospheric situation in the north of the Netherlands, we reviewed our unique cohort on the seasonal incidence of SAH and the association between SAH and local atmospheric changes. Our observational cohort study included 1535 patients with spontaneous SAH admitted to our neurovascular center in the north of the Netherlands between 2000 and 2015. Meteorologic data could be linked to the day of the ictus. To compare SAH incidences over the year and to test the association with meteorologic conditions, incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs) were used, calculated by Poisson regression analyses. Atmospheric pressure variations were significantly associated with aneurysmal SAH. In particular, the pressure change on the second and third day before the ictus was independently correlated to a higher incidence of aneurysmal SAH (IRR, 1.11; 95% CI, 1.00-1.23). The IRR for aneurysmal SAH in July was calculated 0.67 (95% CI, 0.49-0.92) after adjustment for temperature and atmospheric pressure changes. Atmospheric pressure variations are a delayed trigger for aneurysmal SAH. Also, a significantly decreased incidence of aneurysmal SAH was noted in July. Copyright © 2018 Elsevier Inc. All rights reserved.

Triggers of subarachnoid hemorrhage: role of physical exertion, smoking, and alcohol in the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS).

PubMed

Anderson, Craig; Ni Mhurchu, Cliona; Scott, David; Bennett, Derrick; Jamrozik, Konrad; Hankey, Graeme

2003-07-01

Unaccustomed strenuous physical exertion can trigger myocardial infarction, but little is known about the mechanisms precipitating subarachnoid hemorrhage (SAH). We identified all cases of first-ever SAH among the combined populations (2.8 million) of 4 urban centers in Australia and New Zealand. Information on the type, time, and intensity of exposures in the 26 hours before the onset of SAH was ascertained by structured interviews. We used the case-crossover technique to assess the risk of SAH associated with transient exposures of moderate to extreme physical exertion, heavy cigarette smoking, and binge alcohol consumption. We registered 432 first-ever cases of SAH (62% women; mean age, 56.5 years). A definite time of onset of SAH was established for 393 patients (91%), and information on the levels of physical activity in the preceding 26 hours was obtained in 338 (78%). Of these patients, 19% engaged in moderate to extreme exertion (>or=5 metabolic equivalents) in the 2 hours before SAH, which was associated with a tripling in the risk of SAH (odds ratio [OR], 2.7; 95% CI, 1.6 to 4.6). There was no evidence of any association between heavy cigarette smoking or binge drinking and risk of SAH in the subsequent 2 hours (OR, 1.1; 95% CI, 0.4 to 3.7; and OR, 0.41; 95% CI, - infinity to 5.3). Habitual exercise did not appear to alter the risk of SAH associated with moderate to extreme exertion. Moderate to extreme physical exertion tripled the risk of SAH, but there was no association between transient heavy smoking or binge drinking and risk of SAH. These data suggest that heavy physical activity may trigger SAH.

Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage.

PubMed

Li, Yanjiang; Yang, Heng; Ni, Wei; Gu, Yuxiang

2017-01-01

Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis.

PubMed

Han, Yuwei; Su, Jingyuan; Liu, Xiujuan; Zhao, Yuan; Wang, Chenchen; Li, Xiaoming

2017-07-01

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40mg/kg and 80mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence of aneurysmal subarachnoid hemorrhage in Shimokita, Japan, from 1989 to 1998.

PubMed

Ohkuma, Hiroki; Fujita, Seiichiroh; Suzuki, Shigeharu

2002-01-01

The incidence of subarachnoid hemorrhage (SAH) has been investigated in many studies. A recent study in Izumo, Japan, indicates that the incidence of SAH is as high as that in Finland. The purpose of this study was to confirm the high incidence of SAH in Japan. The incidence rate of SAH was investigated from 1989 through 1998 in the Shimokita peninsula, which is a clearly defined closed-boundary area in northern Japan with a population of 89 991. The registration was based on the complete referral system of SAH patients. All cases suspected of SAH underwent CT scan, and the images were referred to stroke specialists. The moribund cases and dead-on-arrival cases suspected of SAH also underwent CT scan. From 1989 through 1998, 198 cases were diagnosed as having aneurysmal SAH. Out of these, 26 cases were moribund or dead when the initial CT scan was performed. The age-adjusted annual incidence of SAH was 21 per 100 000 person-years. The age and sex distribution of the cases indicated that the incidence plateaued after age 45 in men and the incidence increased after age 45 and reached the peak after 75 years in women. The high incidence of SAH in Japan is confirmed. The incidence of SAH obtained in this study is near to that of the Izumo study, of which the size of the geographic region and denominator and diagnostic criteria were similar to this study.

Structural insights into a secretory abundant heat-soluble protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus.

PubMed

Fukuda, Yohta; Miura, Yoshimasa; Mizohata, Eiichi; Inoue, Tsuyoshi

2017-08-01

Upon stopping metabolic processes, some tardigrades can undergo anhydrobiosis. Secretory abundant heat-soluble (SAHS) proteins have been reported as candidates for anhydrobiosis-related proteins in tardigrades, which seem to protect extracellular components and/or secretory organelles. We determined structures of a SAHS protein from Ramazzottius varieornatus (RvSAHS1), which is one of the toughest tardigrades. RvSAHS1 shows a β-barrel structure similar to fatty acid-binding proteins (FABPs), in which hydrophilic residues form peculiar hydrogen bond networks, which would provide RvSAHS1 with better tolerance against dehydration. We identified two putative ligand-binding sites: one that superimposes on those of some FABPs and the other, unique to and conserved in SAHS proteins. These results indicate that SAHS proteins constitute a new FABP family. © 2017 Federation of European Biochemical Societies.

Mental versus physical fatigue after subarachnoid hemorrhage: differential associations with outcome.

PubMed

Buunk, Anne M; Groen, Rob J M; Wijbenga, Rianne A; Ziengs, Aaltje L; Metzemaekers, Jan D M; van Dijk, J Marc C; Spikman, Jacoba M

2018-06-20

Fatigue is a major consequence of subarachnoid hemorrhage (SAH), but the specific characteristics are unclear. Our objective was to investigate the nature of post-SAH fatigue (mental or physical) and to determine the relationship with functional outcome in the chronic stage. Also, the possible influence of mood disorders and acute SAH-related factors (SAH type and external cerebrospinal fluid (CSF) drainage) on the presence of fatigue was investigated. Patients with an aneurysmal SAH (aSAH) or angiographically negative SAH (anSAH) were assessed 3 to 10 years post-SAH (N = 221). Questionnaires were used to investigate mental and physical fatigue and mood. Functional outcome was examined with the Glasgow Outcome Scale Extended (GOSE). Between-group comparisons and binary logistic regression analysis were performed. Frequencies of mental and physical fatigue were 48.4% and 38.5% respectively, with prevalence of mental fatigue being significantly higher. A two-way ANOVA with SAH type and external CSF drainage as independent variables and mental fatigue as dependent variable, showed a significant main effect of CSF drainage only (p < 0.001). Only mental fatigue explained a significant part of the variance in long-term functional outcome (Model χ 2 = 52.99, p < 0.001; Nagelkerke R² = 0.32). Mental fatigue after SAH is a serious burden to the patient and is associated with impaired long-term functional outcome. Distinguishing different aspects of fatigue is relevant as mental post-SAH fatigue might be a target for treatment aimed to improve long-term outcome. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nonaneurysmal "Pseudo-Subarachnoid Hemorrhage" Computed Tomography Patterns: Challenges in an Acute Decision-Making Heuristics.

PubMed

Hasan, Tasneem F; Duarte, Walter; Akinduro, Oluwaseun O; Goldstein, Eric D; Hurst, Rebecca; Haranhalli, Neil; Miller, David A; Wharen, Robert E; Tawk, Rabih G; Freeman, William D

2018-06-05

Acute aneurysmal subarachnoid hemorrhage (SAH) is a medical and neurosurgical emergency from ruptured brain aneurysm. Aneurysmal SAH is identified on brain computed tomography (CT) as increased density of basal cisterns and subarachnoid spaces from acute blood products. Aneurysmal SAH-like pattern on CT appears as an optical illusion effect of hypodense brain parenchyma and/or hyperdense surrounding cerebral cisterns and blood vessels termed as "pseudo-subarachnoid hemorrhage" (pseudo-SAH). We reviewed clinical, laboratory, and radiographic data of all SAH diagnoses between January 2013 and January 2018, and found subsets of nonaneurysmal SAH, originally suspected to be aneurysmal in origin. We performed a National Library of Medicine search methodology using terms "subarachnoid hemorrhage," "pseudo," and "non-aneurysmal subarachnoid hemorrhage" singly and in combination to understand the sensitivity, specificity, and precision of pseudo-SAH. Over 5 years, 230 SAH cases were referred to our tertiary academic center and only 7 (3%) met the definition of pseudo-SAH. Searching the National Library of Medicine using subarachnoid hemorrhage yielded 27,402 results. When subarachnoid hemorrhage and pseudo were combined, this yielded 70 results and sensitivity was 50% (n = 35). Similarly, search precision was relatively low (26%) as only 18 results fit the clinical description similar to the 7 cases discussed in our series. Aneurysmal SAH pattern on CT is distinct from nonaneurysmal and pseudo-SAH patterns. The origin of pseudo-SAH terminology appears mostly tied to comatose cardiac arrest patients with diffuse dark brain Hounsfield units and cerebral edema, and is a potential imaging pitfall in acute medical decision-making. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

PubMed

Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie

2017-04-04

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage.

PubMed

Hao, Shuangying; Song, Chuanhui; Shang, Longcheng; Yu, Jiang; Qiao, Tong; Li, Kuanyu

2016-03-10

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague-Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Molecular diagnosis of infectious hematopoietic necrosis and viral hemorrhagic septicemia

USGS Publications Warehouse

Winton, James R.; Einer-Jensen, Katja

2002-01-01

The fish rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), cause extensive losses among salmon and trout in several areas of the world (Bootland and Leong, 1999; Smail, 1999; Wolf, 1988). Historically, IHNV was endemic among wild anadromous salmonids in the western portion of North America, but the virus has spread to stocks of cultured rainbow trout (Oncorhynchus mykiss) in the United States, Asia and Western Europe, probably as a result of the movement of infected fish or eggs (Winton, 1991). Prior to 1989, VHSV was thought to be largely restricted to freshwater fishes in Western Europe (Wolf, 1988); however, in the last decade, VHSV has been isolated from an increasing number of free-living marine fish species in the North Pacific and North Atlantic Oceans (Dixon et al., 1997; Dixon, 1999; Kent et al., 1998; Meyers and Winton, 1995; Meyers et al., 1999; Mortensen et al., 1999; Smail; 2000, Takano et al., 2000). These findings have lead to the conclusion that both viruses are principally endemic among marine or anadromous fish species, but have established themselves in freshwater among cultured salmonids where their effects are most frequently observed.

Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

PubMed

Kuo, Chang-Po; Lu, Chueng-He; Wen, Li-Li; Cherng, Chen-Hwan; Wong, Chih-Shung; Borel, Cecil O; Ju, Da-Tong; Chen, Chun-Mei; Wu, Ching-Tang

2011-12-01

Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population.

PubMed

Zawada, Adam M; Rogacev, Kyrill S; Hummel, Björn; Berg, Judith T; Friedrich, Annika; Roth, Heinz J; Obeid, Rima; Geisel, Jürgen; Fliser, Danilo; Heine, Gunnar H

2014-05-01

Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available. We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation. Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = -0.335; p < 0.001; eGFR vs homocysteine: r = -0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors. In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Phlebotomus Sandflies of the Paloich Area in the Sudan (Diptera, Psychodidae)

DTIC Science & Technology

1964-10-01

Hamster, Cricetus auratus Toad, Bufo regularis (?) Gecko, H. turicus Skink, M. striata Puff adder Snake, CMNH HH-9111’ Snake, CMNH HH-9112’ Hedgehog ...Pharynx unarmed distally or only with few, smail spines ; pigment patch not dark enough to obscure teeth .................. 8 Pharynx heavily...armed distally with numerous, dark spines ; pigment patch very dark, 1964 Quate: Sudanese sandflies 237 often obscuring teeth unless specimen well

Role of Gap Junctions in Early Brain Injury Following Subarachnoid Hemorrhage

PubMed Central

Ayer, Robert; Chen, Wanqiu; Sugawara, Takashi; Suzuki, Hidenori; Zhang, John H.

2010-01-01

Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380g. Octanol (260.46mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 hour after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 hours after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH induced apoptosis. Despites previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study. PMID:20018179

Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage.

PubMed

Charidimou, Andreas; Boulouis, Grégoire; Fotiadis, Panagiotis; Xiong, Li; Ayres, Alison M; Schwab, Kristin M; Gurol, Mahmut Edip; Rosand, Jonathan; Greenberg, Steve M; Viswanathan, Anand

2018-04-01

Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage. MRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression. We included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH. This probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis. © Article author(s) (or their employer(s) unless otherwise stated in the

Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.

PubMed

Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

2016-01-01

Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.

PubMed

Provencio, Jose Javier; Swank, Valerie; Lu, Haiyan; Brunet, Sylvain; Baltan, Selva; Khapre, Rohini V; Seerapu, Himabindu; Kokiko-Cochran, Olga N; Lamb, Bruce T; Ransohoff, Richard M

2016-05-01

Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

PubMed

Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

2017-01-01

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

Memantine Attenuates Delayed Vasospasm after Experimental Subarachnoid Hemorrhage via Modulating Endothelial Nitric Oxide Synthase.

PubMed

Huang, Chih-Yuan; Wang, Liang-Chao; Shan, Yan-Shen; Pan, Chia-Hsin; Tsai, Kuen-Jer

2015-06-23

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.

[Curcumin alleviates early brain injury following subarachnoid hemorrhage in rats by inhibiting JNK/c-Jun signal pathway].

PubMed

Li, Xia; Zhu, Ji

2018-03-01

Objective To investigate the inhibitory effect of curcumin on early brain injury following subarachnoid hemorrhage (SAH) by inhibiting JNK/ c-Jun signal pathway. Methods Sixty adult male SD rats were randomly divided into four groups: sham operation group (sham group), SAH group, SAH group treated with 100 mg/(kg.d) curcumin and SAH group treated with 200 mg/(kg.d) curcumin, with 15 rats in each group. Endovascular puncture was used to induce SAH model. Nissl staining was used to test whether neurons were broken. TUNEL staining was used to detect apoptosis. Immunohistochemistry was used to investigate the expression of caspase-3. Western blot analysis was used to detect the expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3. Results Nissl staining indicated the decrease of Nissl bodies in SAH group, but increase of Nissl bodies in SAH group treated with curcumin. TUNEL staining showed that there were more apoptotic neurons in SAH group compared with sham group, while apoptotic neurons decreased after the treatment with curcumin, more obviously in the group treated with 200 mg/(kg.d) curcumin. The expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3 were up-regulated in SAH group compared with sham group. However, the expressions of those proteins were down-regulated after the treatment with curcumin, especially by higher-dose curcumin treatment. Conclusion Curcumin might suppress early brain injury after SAH by inhibiting JNK/c-Jun signal pathway and neuron apoptosis.

Early Elevation of Serum TNFα is Associated with Poor Outcome in Subarachnoid Hemorrhage

PubMed Central

Chou, Sherry HY.; Feske, Steven K.; Atherton, Juli; Konigsberg, Rachael G.; De Jager, Philip L.; Du, Rose; Lo, Eng H.; Ning, MingMing

2013-01-01

Objective Subarachnoid hemorrhage (SAH) is associated with inflammation which may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6) are associated with vasospasm and poor outcome in SAH. Methods In 52 consecutive SAH subjects, we compared TNFα and IL-6 levels on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to poor outcome at 3- and 6-months. Vasospasm was defined as >50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score >2. Results Elevated TNFα on post-SAH days 2–3 was associated with poor 3-month outcome (p=0.0004). Global elevation of TNFα over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (p=0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNFα nor IL-6 levels were associated with vasospasm. Conclusions Elevation in serum TNFα on post-SAH days 2–3 and global elevation of TNFα over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNFα in SAH-related brain injury and its potential as a SAH outcome biomarker. PMID:22918199

Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: possible involvement of mitochondrial S-adenosylmethionine transport.

PubMed

Song, Zhenyuan; Zhou, Zhanxiang; Song, Ming; Uriarte, Silvia; Chen, Theresa; Deaciuc, Ion; McClain, Craig J

2007-08-01

Hepatocytes are resistant to tumor necrosis factor-alpha- (TNF) induced killing/apoptosis under normal circumstances, but primary hepatocytes from rats chronically fed alcohol have increased TNF cytotoxicity. Therefore, there must be mechanism(s) by which alcohol exposure "sensitizes" to TNF hepatotoxicity. Abnormal metabolism of methionine and S-adenosylmethionine (SAM) are well-documented acquired metabolic abnormalities in ALD. S-adenosylhomocysteine (SAH) is the product of SAM in hepatic transmethylation reactions, and SAH hydrolase (SAHH) is the only enzyme to metabolize SAH to homocysteine and adenosine. Our previous studies demonstrated that chronic intracellular accumulation of SAH sensitized hepatocytes to TNF cytotoxicity in vitro. In the current study, we extended our previous observations by further characterizing the effects of chronic alcohol intake on mitochondrial SAM levels in liver and examining its possible involvement in SAH sensitization to TNF hepatotoxicity. Chronic alcohol consumption in mice not only increased cytosolic SAH levels, but also decreased mitochondrial SAM concentration, leading to decreased mitochondrial SAM to SAH ratio. Moreover, accumulation of hepatic SAH induced by administration of 3-deaza-adenosine (DZA-a potent inhibitor of SAHH) enhanced lipopolysaccharide (LPS)/TNF hepatotoxicity in mice in vivo. Inhibition of SAHH by DZA resulted not only in accumulation of cytoplasmic SAH, but also in depletion of the mitochondrial SAM pool. Further studies using mitochondrial SAM transporter inhibitors showed that inhibition of SAM transport into mitochondria sensitized HepG2 cells to TNF cytotoxicity. In conclusion, our results demonstrate that depletion of the mitochondrial SAM pool by SAH, which is elevated during chronic alcohol consumption, plays a critical role in SAH induced sensitization to TNF hepatotoxicity.

Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system.

PubMed

Lee, Won Kyung; Oh, Chang Wan; Lee, Heeyoung; Lee, Kun Sei; Park, Hyeonseon

2018-06-22

Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking. Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH. The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH. The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The relationship between perimesencephalic subarachnoid hemorrhage and deep venous system drainage pattern and calibrations.

PubMed

Buyukkaya, Ramazan; Yıldırım, Nalan; Cebeci, Hakan; Kocaeli, Hasan; Dusak, Abdürrahim; Ocakoğlu, Gökhan; Erdoğan, Cüneyt; Hakyemez, Bahattin

2014-01-01

The purpose of this study is to investigate the relationship between Rosenthal basal vein (BVR) type and diameter and perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH). Aneurysmal subarachnoid hemorrhage (A-SAH), P-SAH, and control groups were evaluated, and BVRs were classified by type. BVR diameters in patients were measured. There was a statistically significant difference of BVR drainage types between groups (P=.002). BVR diameters of patients with normal drainage pattern in P-SAH group were significantly smaller than those in both other groups (P<.001). There is a relationship between P-SAH and BVR primitive drainage type. P-SAH risk increases in parallel with decreasing caliber of BVR in patients with normal drainage pattern. Copyright © 2014 Elsevier Inc. All rights reserved.

Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

PubMed

Zhang, Hong-Mei; Zhang, Yin-Xi; Zhang, Qing; Song, Shui-Jiang; Liu, Zhi-Rong

2016-08-01

Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. A retrospective chart review of the patient was performed. We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Subarachnoid Haemorrhage and Sports

PubMed Central

Sousa Nanji, Liliana; Melo, Teresa P.; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Background Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. Methods We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Results Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Conclusions Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation. PMID:26648972

Subarachnoid Haemorrhage and Sports.

PubMed

Sousa Nanji, Liliana; Melo, Teresa P; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation.

Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats.

PubMed

You, Wanchun; Wang, Zhong; Li, Haiying; Shen, Haitao; Xu, Xiang; Jia, Genlai; Chen, Gang

2016-08-15

Here, we aimed to study the role and underlying mechanism of mTOR in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experiment 1, the time course of mTOR activation in the cortex following SAH. Experiment 2, the role of mTOR in SAH-induced EBI. Adult SD rats were divided into four groups: sham group (n=18), SAH+vehicle group (n=18), SAH+rapamycin group (n=18), SAH+AZD8055 group (n=18). Experiment 3, we incubated enriched microglia with OxyHb. Rapamycin and AZD8055 were also used to demonstrate the mTOR's role on microglial polarization in vitro. The phosphorylation levels of mTOR and its substrates were significantly increased and peaked at 24h after SAH. Rapamycin or AZD8055 markedly decreased the phosphorylation levels of mTOR and its substrates and the activation of microglia in vivo, and promoted the microglial polarization from M1 phenotype to M2 phenotype. In addition, administration of rapamycin and AZD8055 following SAH significantly ameliorated EBI, including neuronal apoptosis, neuronal necrosis, brain edema and blood-brain barrier permeability. Our findings suggested that the rapamycin and AZD8055 could attenuate the development of EBI in this SAH model, possibly through inhibiting the activation of microglia by mTOR pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of 18β-glycyrrhetinic acid on cerebral vasospasm caused by asymmetric dimethylarginine after experimental subarachnoid hemorrhage in rats.

PubMed

Zhao, Dong; Liu, Qi; Ji, Yunxiang; Wang, Ganggang; He, Xuejun; Tian, Weidong; Xu, Hui; Lei, Ting; Wang, Yezhong

2015-06-01

Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is characterized by the severe constriction of an artery, which often leads to unfavorable outcomes. CVS after SAH is closely associated with asymmetric dimethylarginine (ADMA) and connexin. The effect of 18β-glycyrrhetinic acid (18β-GA), an inhibitor of gap junction, on ADMA, connexin, and CVS after SAH were investigated. Sprague-Dawley rats (n  =  120), weighing 300-350 g, were divided into the control group, sham, SAH, and SAH + 18β-GA groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats, and 18β-GA (10 mg/kg) was intraperitoneally injected. The neurological score, basilar artery diameter, ADMA, and connexin protein contents (Cx40, Cx43, and Cx45) were measured using Kaoutzanis scoring system, pressure myograph, enzyme linked immunosorbent assay kit, and Western blot, respectively, 1, 3, 5, 7, and 14 days after SAH. The neurological score significantly decreased 3, 5, 7, and 14 days after SAH. The basilar artery diameter significantly decreased, and the ADMA level in the cerebrospinal fluid (CSF) significantly increased at all time points. The level of Cx40 significantly decreased on days 3, 5, 7, and 14, and the level of Cx43 and Cx45 significantly increased at all time points. ADMA and Cx43 are positively correlated. However, the upregulated level of ADMA, Cx43, and Cx45 were attenuated. The neurology result significantly improved in the SAH + 18β-GA group. Treatment with 18β-GA in SAH rats decreases Cx43 and Cx45 in basilar artery and ADMA in CSF. ADMA is probably involved in the pathophysiological events of CVS after SAH by altering connexin proteins. The mechanism of connexin protein changes caused by ADMA needs to be further studied.

Netrin-1 Preserves Blood-Brain Barrier Integrity Through Deleted in Colorectal Cancer/Focal Adhesion Kinase/RhoA Signaling Pathway Following Subarachnoid Hemorrhage in Rats.

PubMed

Xie, Zongyi; Enkhjargal, Budbazar; Reis, Cesar; Huang, Lei; Wan, Weifeng; Tang, Jiping; Cheng, Yuan; Zhang, John H

2017-05-19

Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH. Recombinant NTN-1 was administered intravenously 1 hour after SAH induction. NTN-1 small interfering RNA or Deleted in Colorectal Cancer small interfering RNA was administered intracerebroventricular at 48 hours before SAH. Focal adhesion kinase inhibitor was administered by intraperitoneal injection at 1 hour prior to SAH. Neurological scores, brain water content, BBB permeability, RhoA activity, Western blot, and immunofluorescence staining were evaluated. The expression of endogenous NTN-1 and its receptor Deleted in Colorectal Cancer were increased after SAH. Administration of exogenous NTN-1 significantly reduced brain water content and BBB permeability and ameliorated neurological deficits at 24 and 72 hours after SAH. Exogenous NTN-1 treatment significantly promoted phosphorylated focal adhesion kinase activation and inhibited RhoA activity, as well as upregulated the expression of ZO-1 and Occludin. Conversely, depletion of endogenous NTN-1 aggravated BBB breakdown and neurological impairments at 24 hours after SAH. The protective effects of NTN-1 at 24 hours after SAH were also abolished by pretreatment with Deleted in Colorectal Cancer small interfering RNA and focal adhesion kinase inhibitor. NTN-1 treatment preserved BBB integrity and improved neurological functions through a Deleted in Colorectal Cancer/focal adhesion kinase/RhoA signaling pathway after SAH. Thus, NTN-1 may serve as a promising treatment to alleviate early brain injury following SAH. © 2017 The Authors. Published on behalf of the American Heart

Immunoassay of S-adenosylmethionine and S-adenosylhomocysteine: the methylation index as a biomarker for disease and health status.

PubMed

Hao, Xiujuan; Huang, Yan; Qiu, Ming; Yin, Chunlin; Ren, Huiming; Gan, Hongjie; Li, Huijun; Zhou, Yaxia; Xia, Jiazhi; Li, Wenting; Guo, Lijuan; Angres, Isaac A

2016-11-28

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are relevant to a variety of diseases. Previous reports that quantified SAM and SAH were based on HPLC or LC-MS/MS. No antibody against SAM has been generated, and the antibody against SAH cannot be used with blood samples. Immunoassays have not been used to measure SAM and SAH. In this study, ELISA was used to measure blood SAM and SAH levels. Specific antibodies against SAM were produced for the first time using a stable analog as the antigen. The monoclonal antibodies against SAM and SAH were characterized. No cross-reactivity was detected for the analyzed analogs. For the anti-SAM antibodies, the ELISA sensitivity was ~2 nM, and the affinity was 7.29 × 10 10 L/mol. For the anti-SAH antibodies, the sensitivity was ~15 nM, and the affinity was 2.79 × 10 8 L/mol. Using high-quality antibodies against SAM and SAH, immunoassays for the detection of SAM and SAH levels in blood and tissue samples were developed. Clinical investigations using immunoassays to measure SAM, SAH and the methylation index (MI) in normal and diseased samples indicated that (1) the SAM level is age and gender dependent; (2) the SAM level is associated with the severity of liver diseases, inflammatory reactions and other diseases; and (3) the methylation index (MI) is significantly reduced in many diseases and may serve as a screening biomarker to identify potentially unfavorable health conditions. It is possible to generate antibodies against active small biomolecules with weak immunogenicity, such as SAM and SAH, using traditional hybridoma technology. The antigens and antibodies described here will contribute to the development of immunoassays to measure SAM, SAH and related molecules. These assays enable the MI to be measured specifically, accurately, easily and quickly without costly equipment. This preliminary study indicates that the MI could be an effective indicator of general health, except under conditions that may

Navigation-assisted trans-inferotemporal cortex selective amygdalohippocampectomy for mesial temporal lobe epilepsy; preserving the temporal stem.

PubMed

Kishima, Haruhiko; Kato, Amami; Oshino, Satoru; Tani, Naoki; Maruo, Tomoyuki; Khoo, Hui Ming; Yanagisawa, Takufumi; Edakawa, Kotaro; Kobayashi, Maki; Tanaka, Masataka; Hosomi, Koichi; Hirata, Masayuki; Yoshimine, Toshiki

2017-03-01

Selective amygdalohippocampectomy (SAH) can be used to obtain satisfactory seizure control in patients with mesial temporal lobe epilepsy (MTLE). Several SAH procedures have been reported to achieve satisfactory outcomes for seizure control, but none yield fully satisfactory outcomes for memory function. We hypothesized that preserving the temporal stem might play an important role. To preserve the temporal stem, we developed a minimally invasive surgical procedure, 'neuronavigation-assisted trans-inferotemporal cortex SAH' (TITC-SAH). TITC-SAH was performed in 23 patients with MTLE (MTLE on the language-non-dominant hemisphere, n = 11). The inferior horn of the lateral ventricle was approached via the inferior or middle temporal gyrus along the inferior temporal sulcus under neuronavigation guidance. The hippocampus was dissected in a subpial manner and resected en bloc together with the parahippocampal gyrus. Seizure control at one year and memory function at 6 months postoperatively were evaluated. One year after TITC-SAH, 20 of the 23 patients were seizure-free (ILAE class 1), 2 were class 2, and 1 was class 3. Verbal memory improved significantly in 13 patients with a diagnosis of hippocampal sclerosis, for whom WMS-R scores were available both pre- and post-operatively. Improvements were seen regardless of whether the SAH was on the language-dominant or non-dominant hemisphere. No major complication was observed. Navigation-assisted TITC-SAH performed for MTLE offers a simple, minimally invasive procedure that appears to yield excellent outcomes in terms of seizure control and preservation of memory function, because this procedure does not damage the temporal stem. TITC-SAH should be one of the feasible surgical procedures for MTLE. SAH: Amygdalohippocampectomy; MTLE: Mesial temporal lobe epilepsy (MTLE); TITC-SAH: Ttrans-inferotemporal cortex SAH; ILAE: International League Against Epilepsy (ILAE); MRI: Magnetic resonance imaging; EEG

Influence of experimental subarachnoid hemorrhage on nicotine-induced contraction of the rat basilar artery in relation to arachidonic acid metabolites signaling pathway.

PubMed

Ji, Xu; Wang, Aimin; Trandafir, Cristina C; Kurahashi, Kazuyoshi

2013-10-01

Smoking is one of the most important risk factors for cerebral circulatory disorders. The purpose of this study was to investigate the influence of experimental subarachnoid hemorrhage (SAH) on nicotine-induced contraction (arachidonic acid metabolites) in the basilar arteries of rats. Rats were killed at 1 hour and 1 week after blood injection, and the basilar artery was isolated and cut into a spiral strip. Testing of cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors revealed no significant differences in their effects on normal and SAH (1 hour and 1 week). Phospholipase C (PLC) inhibitor (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17yl)amino)hexyl)-1H-pyrrole-2,5,-dione [U-73122]) slightly inhibited contraction of SAH (1 hour and 1 week) when compared to controls. Phospholipase A2 (PLA2) inhibitor (manoalide) and cytosolic PLA2 (cPLA2) inhibitor (arachidonyltrifluoromenthylketone [AACOCF3]) more strongly attenuated contraction in SAH (1 hour and 1 week) than in controls. Secreted PLA2 (sPLA2) inhibitor (indoxam), PLC inhibitor (2-nitro-4-carboxyphenyl N, N-diphenylcarbamate [NCDC]), and COX-2 inhibitors (nimesulide, (5-methanesulfonamido-6-(2,4-difluorothiophenyl)-1-indanone) [L-745337], and celecoxib) only slightly inhibited contraction of SAH (1 week) when compared to normal and SAH (1 hour). The calcium-independent PLA2 (iPLA2) inhibitor bromoenol lactone (BEL) showed greater inhibition of contraction in SAH (1 hour) when compared to normal and SAH (1 week). One week after exposure to SAH, PLC, sPLA2, and COX-2 activity were enhanced and cPLA2 activity was inhibited. One hour after exposure to SAH, PLC activity was enhanced and cPLA2 and iPLA2 activity was inhibited. Such changes of inflammatory arachidonic acid metabolites by smoking after SAH may play important roles in fatal cerebral circulatory disorders, suggesting important implications for the etiology and pathogenesis of SAH. Copyright © 2013 National Stroke Association. Published by

Phosphodiesterase 5 Inhibition Attenuates Cerebral Vasospasm and Improves Functional Recovery after Experimental Subarachnoid Hemorrhage

PubMed Central

Han, Byung Hee; Vellimana, Ananth Kesav; Zhou, Meng-Liang; Milner, Eric; Zipfel, Gregory Joseph

2014-01-01

Background Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic GMP (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5) – an enzyme that degrades cGMP – may play a role, as the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. Objective To elucidate the mechanism of action of sildenafil against vasospasm, and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. Methods SAH was induced via endovascular perforation in male C57BL6 mice. Beginning two hours later, mice received sildenafil citrate (0.7, 2 or 5mg/kg P.O. BID) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH Day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure (BP), and intracranial pressure (ICP) were examined. Results We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to reduce vasospasm, decrease neuronal cell death, and markedly improve neurological outcome, without causing significant physiological side effects. Conclusion Sildenafil–an FDA-approved drug with a proven track record of safety in humans –is a promising new therapy for vasospasm and neurological deficits following SAH. PMID:21796010

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants.

PubMed

Feigin, Valery; Parag, Varsha; Lawes, Carlene M M; Rodgers, Anthony; Suh, Il; Woodward, Mark; Jamrozik, Konrad; Ueshima, Hirotsugu

2005-07-01

The cause of subarachnoid hemorrhage (SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian (predominantly white) populations. Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Individual participant data from 26 prospective cohort studies (total number of participants 306,620) that reported incident cases of SAH (fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP >140 mm Hg (HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP (> or =140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

PubMed

Zhang, Tingting; Su, Jingyuan; Guo, Bingyu; Wang, Kaiwen; Li, Xiaoming; Liang, Guobiao

2015-09-01

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption. Copyright © 2015 Elsevier B.V. All rights reserved.

Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model

PubMed Central

Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Kwan, Aij-Lie

2015-01-01

Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH. PMID:26539501

Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model.

PubMed

Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Lin, Chih-Lung; Kwan, Aij-Lie

2015-01-01

Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH.

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control

PubMed Central

Luo, C; Yao, X; Li, J; He, B; Liu, Q; Ren, H; Liang, F; Li, M; Lin, H; Peng, J; Yuan, T F; Pei, Z; Su, H

2016-01-01

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control. PMID:27031957

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control.

PubMed

Luo, C; Yao, X; Li, J; He, B; Liu, Q; Ren, H; Liang, F; Li, M; Lin, H; Peng, J; Yuan, T F; Pei, Z; Su, H

2016-03-31

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

2013-06-01

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

Can mobile phone technology support a rapid sharing of information on novel psychoactive substances among health and other professionals internationally?

PubMed

Simonato, Pierluigi; Bersani, Francesco S; Santacroce, Rita; Cinosi, Eduardo; Schifano, Fabrizio; Bersani, Giuseppe; Martinotti, Giovanni; Corazza, Ornella

2017-05-01

The diffusion of novel psychoactive substances (NPSs), combined with the ability of the Internet to act as an online marketplace, has led to unprecedented challenges for governments, health agencies, and substance misuse services. Despite increasing research, there is a paucity of reliable information available to professionals working in the field. The paper will present the pilot results of the first mobile application (SMAIL) for rapid information sharing on NPSs among health professionals. The development of SMAIL was divided into 2 parts: (a) the creation of the application for registered users, enabling them to send an SMS or email with the name or "street name" of an NPS and receive within seconds emails or SMS with the information, when available and (b) the development of a database to support the incoming requests. One hundred twenty-two professionals based in 22 countries used the service over the pilot period of 16 months (from May 2012 to September 2013). Five hundred fifty-seven enquires were made. Users received rapid information on NPSs, and 61% of them rated the service as excellent. This is the right time to use mobile phone technologies for rapid information sharing and prevention activities on NPSs. Copyright © 2017 John Wiley & Sons, Ltd.

6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism-a laboratory study.

PubMed

Chang, Chih-Zen; Wu, Shu-Chuan; Kwan, Aij-Lie; Lin, Chih-Long; Hwang, Shiuh-Lin

2011-04-01

Increased endothelin-1 (ET-1) production and diminished nitric oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is effective in preventing and reversing arterial narrowing in a rodent SAH model. This present study is of interest to examine the effect of 6-mp on ET-1/endothelial nitric oxide synthase (eNOS) in this animal model. A rodent double hemorrhage SAH model was employed. Animals were randomly assigned to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg(-1) day(-1) 6-mp treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were determined. Radiolabeled NOS assay kit was applied to detect eNOS. Morphologically, convolution of internal elastic lamina, endothelial cells distortion, and necrotic smooth muscle were prevalently present in the basilar artery of SAH groups, which was absent in the 1 and 2 mg kg(-1) day(-1) 6-mp plus SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen patency, 54.6%, p ≤ 0.01 compared with the sham group), but it was less prominent in the 2 mg kg(-1) day(-1) 6-mp treatment group (lumen patency, 87.6%, p < 0.05). In addition, administration with 2 mg kg(-1) day(-1) 6-mp reduced cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-α, respectively, and increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg(-1) day(-1) 6-mp) except in the 2 mg kg(-1) day(-1) 6-mp SAH group, when compared with the healthy controls (no SAH). Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs in the 6-mp groups (0.5, 1.0, and 2 mg kg(-1) day(-1) 6-mp

Effects of Meteorological Variables on the Incidence of Rupture of Intracranial Aneurysms in Central New Jersey.

PubMed

Kellogg, Marissa; Petrov, Dimitriy; Agarwal, Nitin; Patel, Nitesh V; Hansberry, David Richard; Agarwal, Prateek; Brimacombe, Michael; Gandhi, Chirag D; Prestigiacomo, Charles

2017-05-01

Introduction  Previous studies have suggested relationships between the rupture of intracranial aneurysms and meteorological variables such as season, barometric pressure, and temperature. Our objective was to examine the relationship between the incidence of hospital admissions secondary to aneurysmal subarachnoid hemorrhage (aSAH) and meteorological variables in central New Jersey. Methods  The study population consisted of 312 patients who presented to University Hospital in Newark, New Jersey, between January 1, 2003, and December 31, 2008, with aSAH. Days in the 6-year period were classified as nonbleed days (no aSAH), bleed days (one or more aSAHs within 1 calendar day), cluster days (two or more aSAHs within 2 calendar days), and multiple-bleed days (two or more aSAHs within 1 calendar day). Results  The only significant meteorological risk factor for the occurrence of multiple-bleed days was high barometric pressure (1018.5 versus 1016.5 millibars [mbars]; p <  0.04), but an increase in barometric pressure (+ 2.8 mbars) over the 2 days prior to the multiple-bleed day, although not statistically significant, may be a risk factor ( p <  0.09). Barometric pressure was also noted to be increased on bleed days (1017.2 versus 1016.5 mbars) and cluster days (1017.7 versus 1016.5 mbars), but this relationship was not significant ( p <  0.1 and p <  0.1, respectively). Although aSAH days demonstrated consistently lower temperatures than non-aSAH days and dropping temperatures were consistently found in the days preceding the aSAH, these relationships were not significant. Conclusion  Among meteorological factors, high barometric pressure and low temperature may be risk factors for the onset of aSAH. Georg Thieme Verlag KG Stuttgart · New York.

How large is the typical subarachnoid hemorrhage? A review of current neurosurgical knowledge.

PubMed

Whitmore, Robert G; Grant, Ryan A; LeRoux, Peter; El-Falaki, Omar; Stein, Sherman C

2012-01-01

Despite the morbidity and mortality of subarachnoid hemorrhage (SAH), the average volume of a typical hemorrhage is not well defined. Animal models of SAH often do not accurately mimic the human disease process. The purpose of this study is to estimate the average SAH volume, allowing standardization of animal models of the disease. We performed a MEDLINE search of SAH volume and erythrocyte counts in human cerebrospinal fluid as well as for volumes of blood used in animal injection models of SAH, from 1956 to 2010. We polled members of the American Association of Neurological Surgeons (AANS) for estimates of typical SAH volume. Using quantitative data from the literature, we calculated the total volume of SAH as equal to the volume of blood clotted in basal cisterns plus the volume of dispersed blood in cerebrospinal fluid. The results of the AANS poll confirmed our estimates. The human literature yielded 322 publications and animal literature, 237 studies. Four quantitative human studies reported blood clot volumes ranging from 0.2 to 170 mL, with a mean of ∼20 mL. There was only one quantitative study reporting cerebrospinal fluid red blood cell counts from serial lumbar puncture after SAH. Dispersed blood volume ranged from 2.9 to 45.9 mL, and we used the mean of 15 mL for our calculation. Therefore, total volume of SAH equals 35 mL. The AANS poll yielded 176 responses, ranging from 2 to 350 mL, with a mean of 33.9 ± 4.4 mL. Based on our estimate of total SAH volume of 35 mL, animal injection models may now become standardized for more accurate portrayal of the human disease process. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical features of subarachnoid hemorrhage in patients with positive cancer history.

PubMed

Shibahara, Ichiyo; Watanabe, Takashi; Ezura, Masayuki; Inoue, Takashi; Fujimura, Miki; Kimura, Naoto; Inoue, Tomoo; Suzuki, Ichiro; Nishino, Akiko; Nishimura, Shinjitsu; Uenohara, Hiroshi; Tominaga, Teiji

2016-05-01

Advances in cancer treatment have dramatically increased long-term survivors. Prolonged survival increases comorbidity risk, but there is a paucity of studies on how cancer history alters clinical outcomes from subsequent diseases. This study aims to investigate whether positive cancer history influences clinical outcome following subarachnoid hemorrhage (SAH). We retrospectively reviewed consecutive SAH patients admitted between January 2008 and March 2014. Medical histories, known SAH risk factors, and outcome were compared between SAH patients with and without cancer history. Out of the 498 SAH patients, 55 cases had cancer history, 438 cases had no cancer history and 5 cases had an unknown cancer history. Compared with SAH patients without cancer history, those with cancer history had poorer Hunt & Hess grade at SAH presentation (P = 0.021), and poorer modified Rankin Scale (mRS) score at discharge (P < 0.001). After adjustment for age, sex, modified Fisher, previous SAH, history of hypertension, current smoking status, and current alcohol consumption, positive cancer history remained an independent risk factor for poorer mRS0-6 [odds ratio (OR) = 2.25, 95 % confidence interval (CI) 1.28-3.94] and mRS6 (OR = 2.74, 95 % CI 1.40-5.37). Furthermore, stratified analysis by Hunt & Hess grade adjusted by age, sex, and modified Fisher scale, OR of poorer mRS0-6 was 2.12 (95 % CI 0.89-5.05) and OR of mRS6 was 3.68 (95 % CI 1.35-10.04). After adjustment of patients for demographic factors, classical risk factors for SAH and Hunt & Hess grade, previous cancer history is a risk factor for the poor functional outcome of SAH.

Treatment of Spontaneous Subarachnoid Hemorrhage and Self-Reported Neuropsychological Performance at 6 Months - Results of a Prospective Clinical Pilot Study on Good-Grade Patients.

PubMed

Bründl, Elisabeth; Schödel, Petra; Bele, Sylvia; Proescholdt, Martin; Scheitzach, Judith; Zeman, Florian; Brawanski, Alexander; Schebesch, Karl-Michael

2018-01-01

Limited focus has been placed on neuropsychological patient profiles after spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled study in good-grade sSAH patients to evaluate the time course of treatment-specific differences in cognitive processing after sSAH. Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients received endovascular aneurysm occlusion (EV), 6 patients were treated microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent standardized intensive medical care. No patient experienced serious vasospasm-related ischemic or hemorrhagic complications. All patients were subjected to neuropsychological self-report assessment (36-Item Short Form Health Survey and ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of bleeding (t1) and at the 6-month follow-up (FU; t < sub > 2 < /sub > ). From t1 to t < sub > 2 < /sub > , MS and EV patients significantly improved in physical functioning (Pfi; p=.001 each) and the physical component summary (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened. At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of test differences showed a significant alleviation in nutrition disorder in MS (vs. EV p=.009). All sSAH groups reported a significant deterioration in health. Though both MS and EV patients, improved in several physical items over time, our data suggest a better short-term Pfi, less Pain and improved nutrition disorder in surgically treated patients. pSAH patients performed significantly better in various aspects of physical and psychological functioning than patients with aneurysmal SAH.

Decorin alleviated chronic hydrocephalus via inhibiting TGF-β1/Smad/CTGF pathway after subarachnoid hemorrhage in rats.

PubMed

Yan, Hui; Chen, Yujie; Li, Lingyong; Jiang, Jiaode; Wu, Guangyong; Zuo, Yuchun; Zhang, John H; Feng, Hua; Yan, Xiaoxin; Liu, Fei

2016-01-01

Chronic hydrocephalus is one of the severe complications after subarachnoid hemorrhage (SAH). However, there is no efficient treatment for the prevention of chronic hydrocephalus, partially due to poor understanding of underlying pathogenesis, subarachnoid fibrosis. Transforming growth factor-β1(TGF-β1) is a potent fibrogenic factor implicated in wide range of fibrotic diseases. To investigate whether decorin, a natural antagonist for TGF-β1, protects against subarachnoid fibrosis and chronic hydrocephalus after SAH, two-hemorrhage-injection SAH model was conducted in 6-week-old rats. Recombinant human decorin(rhDecorin) (30ug/2ul) was administered before blood injection and on the 10th day after SAH. TGF-β1, p-Smad2/3, connective tissue growth factor (CTGF), collagen I and pro-collagen I c-terminal propeptide were assessed via western blotting, enzyme-linked immunosorbent assay, radioimmunoassay and immunofluorescence. And neurobehavioral tests and Morris water maze were employed to evaluate long-term neurological functions after SAH. We found that SAH induced heightened activation of TGF-β1/Smad/CTGF axis, presenting as a two peak response of TGF-β1 in cerebrospinal fluid, elevation of TGF-β1, p-Smad2/3, CTGF, collagen I in brain parenchyma and pro-collagen I c-terminal propeptide in cerebrospinal fluid, and increased lateral ventricle index. rhDecorin treatment effectively inhibited up-regulation of TGF-β1, p-Smad2/3, CTGF, collagen I and pro-collagen I c-terminal propeptide after SAH. Moreover, rhDecorin treatment significantly reduced lateral ventricular index and incidence of chronic hydrocephalus after SAH. Importantly, rhDecorin improved neurocognitive deficits after SAH. In conclusion, rhDecorin suppresses extracellular matrix accumulation and following subarachnoid fibrosis via inhibiting TGF-β1/Smad/CTGF pathway, preventing development of hydrocephalus and attenuating long-term neurocognitive defects after SAH. Copyright © 2015 Elsevier B

Traumatic midline subarachnoid hemorrhage on initial computed tomography as a marker of severe diffuse axonal injury.

PubMed

Mata-Mbemba, Daddy; Mugikura, Shunji; Nakagawa, Atsuhiro; Murata, Takaki; Ishii, Kiyoshi; Kushimoto, Shigeki; Tominaga, Teiji; Takahashi, Shoki; Takase, Kei

2018-01-05

OBJECTIVE The objective of this study was to test the hypothesis that midline (interhemispheric or perimesencephalic) traumatic subarachnoid hemorrhage (tSAH) on initial CT may implicate the same shearing mechanism that underlies severe diffuse axonal injury (DAI). METHODS The authors enrolled 270 consecutive patients (mean age [± SD] 43 ± 23.3 years) with a history of head trauma who had undergone initial CT within 24 hours and brain MRI within 30 days. Six initial CT findings, including intraventricular hemorrhage (IVH) and tSAH, were used as candidate predictors of DAI. The presence of tSAH was determined at the cerebral convexities, sylvian fissures, sylvian vallecula, cerebellar folia, interhemispheric fissure, and perimesencephalic cisterns. Following MRI, patients were divided into negative and positive DAI groups, and were assigned to a DAI stage: 1) stage 0, negative DAI; 2) stage 1, DAI in lobar white matter or cerebellum; 3) stage 2, DAI involving the corpus callosum; and 4) stage 3, DAI involving the brainstem. Glasgow Outcome Scale-Extended (GOSE) scores were obtained in 232 patients. RESULTS Of 270 patients, 77 (28.5%) had DAI; tSAH and IVH were independently associated with DAI (p < 0.05). Of tSAH locations, midline tSAH was independently associated with both overall DAI and DAI stage 2 or 3 (severe DAI; p < 0.05). The midline tSAH on initial CT had sensitivity of 60.8%, specificity of 81.7%, and positive and negative predictive values of 43.7% and 89.9%, respectively, for severe DAI. When adjusted for admission Glasgow Coma Score, the midline tSAH independently predicted poor GOSE score at both hospital discharge and after 6 months. CONCLUSIONS Midline tSAH could implicate the same shearing mechanism that underlies severe DAI, for which midline tSAH on initial CT is a probable surrogate.

Evaluation of Hematological Parameters in the Differentiation of Subarachnoid Hemorrhage and Other Headache Syndromes.

PubMed

Goktekin, Mehmet C; Yilmaz, Mustafa

2018-06-01

In this research, the aim was to compare hematological data for the differentiation of subarachnoid hemorrhage, migraine attack, and other headache syndromes during consultation in emergency service. In this research, which was designed as retrospective case control study, hematological parameters (WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte rates) of the patients consulting to emergency service with SAH and migraine and other consulting patients complaining mainly from headache and having normal cranial CT were analysed. Sixty migraine attack patients (F/M:47/13), 57 SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT (F/M:36/17) who were consulted to emergency service with headache complaint were included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY, and Neu rates were found to differentiate between SAH and HS patients. Only Hct, HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and migraine patients but these rates were not found to have meaningful difference between SAH and HS patients. In addition, an increase in WBC counts and NY/LY rates and decrease in MPV counts in ROC analysis were found to be more specific for SAH. WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT, lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH and other headache syndromes.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report - An experimental study.

PubMed

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. This was an experimental study conducted on rabbits. This study was conducted on 22 rabbits which were randomly divided into three groups: control ( n = 5), physiologic serum saline (SS; n = 6), SAH groups ( n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6-C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups ( P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. We noticed interestingly that C6-C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms.

Immediate coma and poor outcome in subarachnoid haemorrhage are independently associated with an aneurysmal origin.

PubMed

Tsermoulas, Georgios; Flett, Lisa; Gregson, Barbara; Mitchell, Patrick

2013-08-01

Subarachnoid haemorrhage (SAH) may present with coma and this is known to be associated with aneurysmal origin and blood load. Aneurysmal origin is associated with increased blood load and existing data do not allow us to determine if the association between coma and aneurysmal SAH is wholly due to blood load or if aneurysmal origin has an additional independent effect. The objective of our study is to find if an aneurysmal origin is a predictor of acute onset of coma independent of blood load. A series of consecutive patients with spontaneous SAH were divided into two groups: aneurysmal (aSAH) and non-aneurysmal--angiographically negative SAH (naSAH). Blood load was quantified so that the effect of aneurysmal origin could be resolved from the effect of the amount of blood spilled. Non-parametric regression was used to relate blood load to coma and poor outcome rates for aneurysmal bleeds. We analysed a total of 421 patients presenting during the period 2009-2011. Ninety aneurysmal cases presented with coma, seventy immediately in the early phase and seven shortly after rebleeding. None of the naSAH cases presented with immediate coma and 1 developed delayed coma. Delayed coma was associated with acute hydrocephalus in both groups. Aneurysmal origin was found to be an independent determinant of immediate coma (p=0.02) and poor outcome (p<0.001). Immediate coma and poor outcome in SAH are associated with an aneurysmal origin and do not characterize naSAH. Copyright © 2013 Elsevier B.V. All rights reserved.

Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis.

PubMed

Lee, Chu-I; Chou, An-Kuo; Lin, Ching-Chih; Chou, Chia-Hua; Loh, Joon-Khim; Lieu, Ann-Shung; Wang, Chih-Jen; Huang, Chi-Ying F; Howng, Shen-Long; Hong, Yi-Ren

2012-01-01

Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and γ-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.

Exploratory study of the course of posttraumatic stress disorder after aneurysmal subarachnoid hemorrhage.

PubMed

Huenges Wajer, Irene M C; Smits, Anouk R; Rinkel, Gabriel J E; van Zandvoort, Martine J E; Wijngaards-de Meij, Leoniek; Visser-Meily, Johanna M A

2018-05-09

Posttraumatic stress disorder (PTSD) occurs often in aneurysmal subarachnoid hemorrhage (aSAH) survivors, but how PTSD develops over time post-aSAH is still unclear. We examined the course of PTSD symptoms during the first year after aSAH. In this prospective cohort study, the Impact of Event Scale (IES) was applied in 128 patients 3, 6 and 12 months after aSAH. Multilevel modelling was used to assess changes in levels of PTSD symptoms over time and to explore if demographic characteristics, aSAH characteristics, level of education, cognitive functioning and neuroticism are associated to the course of PTSD symptoms. Multilevel analyses showed at group level no differences in the average level of PTSD symptoms between 3, 6 of 12 months post-aSAH (p = 0.22). At individual level, changes in PTSD symptoms over time were present (X 2 (121) = 149.73 p = 0.04). None of the factors could explain the variance in change of PTSD symptoms over time. The course of PTSD appears to differ between individuals after aSAH. We found no factors that explain these differences. There is not one optimal moment in time to assess PTSD. Therefore, it is important to assess PTSD at several time points after aSAH. Copyright © 2018. Published by Elsevier Inc.

Diagnosis of subarachnoid haemorrhage: a survey of Australasian emergency physicians and trainees.

PubMed

Rogers, Andrew; Furyk, Jeremy; Banks, Colin; Chu, Kevin

2014-10-01

This study aims to establish current practice among Australasian emergency physicians and trainees on several aspects of the investigation of suspected subarachnoid haemorrhage (SAH). An electronic questionnaire (SurveyMonkey™) was distributed to emergency physicians and trainees by email through the ACEM. Survey recipients were asked about demographics, followed by a series of questions relating to the investigation of SAH. There were 878 survey respondents (response rate 24%). Our data showed that 47.3% of respondents agreed or strongly agreed that a CT brain within 6 h of headache onset is sufficient to exclude a diagnosis of SAH. For a CT performed within 12 h of ictus, 14.4% were satisfied that SAH could be excluded. After a negative CT scan, for further investigation of SAH, 88% of respondents preferred lumbar puncture to CT angiography. For detection of xanthochromia in the cerebrospinal fluid, 57.7% of respondents felt that spectrophotometry (vs visual inspection) is necessary to accurately diagnose SAH. A range of information was collected regarding the investigation of suspected SAH. We report significant differences in the diagnostic approach of Australasian emergency physicians and trainees to this condition, in particular the utility of CT within 6 h for exclusion of SAH. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Necrostatin-1 attenuates early brain injury after subarachnoid hemorrhage in rats by inhibiting necroptosis.

PubMed

Chen, Fuxiang; Su, Xingfen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Cai, Jiawei; Kang, Dezhi; Hu, Liwen

2017-01-01

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH ( P <0.05) and peaked at 48 hours after SAH ( P <0.05). However, they were greatly reduced after treatment with necrostatin-1 ( P <0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment ( P <0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.

Convexity Subarachnoid Hemorrhage Due to Cardioembolic Stroke in a Woman with Thyrotoxicosis: Α Case Report.

PubMed

Spanou, Ioanna; Vassilopoulou, Sophia; Koroboki, Eleni; Tountopoulou, Argyro; Velonakis, Georgios; Mitsikostas, Dimos Dimitrios

2017-10-01

Non-traumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with a wide spectrum of etiologies. Cerebral ischemia secondary to extracranial or intracranial atherosclerotic disease has been identified as a relatively uncommon cause of cSAH. We report a case of cSAH caused by cardioembolic stroke. A 69-year old female patient developed suddenly left-sided face and body weakness and numbness and visual neglect on the left. She was newly detected with paroxysmal atrial fibrillation on the ground of thyrotoxicosis. Brain magnetic resonance imaging revealed ischemia of embolic pattern with cSAH. Further evaluation excluded other cause of hemorrhage. Dilation of leptomeningeal collateral vessels and rupture of pial vessels in distal cortical arteries may caused cSAH. Full anticoagulation was initiated. After one month, her condition improved significantly (NIHSS from 6 to 2). cSAH may be a rare complication of cardioembolic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome.

PubMed

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung; Kim, Tackeun

2016-03-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH.

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome

PubMed Central

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung

2016-01-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH. PMID:27114963

Whether the decadal shift of South Asia High intensity around the late 1970s exists or not

NASA Astrophysics Data System (ADS)

Xue, Xu; Chen, Wen; Nath, Debashis; Zhou, Dingwen

2015-05-01

This study compares the decadal means of the seasonal (June-July-August (JJA)) mean geopotential heights available from the NCEP1 and ERA-40 reanalysis data in the Northern Hemisphere. The interdecadal changes in the South Asia High (SAH) intensity derived from the reanalysis data are also compared with ground-based radiosonde observations and atmospheric model outputs. The JJA mean geopotential heights in the 1980s are distinctly larger than the 1970s in NCEP1 over most of the regions in the Northern Hemisphere, while no obvious difference is observed in ERA-40. The interannual variation of the SAH strength is very close in the two reanalysis data, so that it is appropriate to utilize the reanalysis data to study the interannual variation of SAH strength after removing the interdecadal trend. However, the discrepancy in SAH intensity between NCEP1 and ERA-40 mainly exists on the interdecadal time scale. The SAH intensity in the NCEP1 was close to that in the ERA-40 before the late 1970s but became remarkably stronger after the late 1970s, leading to a much larger decadal strengthening during the period 1970-1990. Based on the six radiosonde observation stations in the area of the SAH, the results indicate that the decadal reinforcing in the SAH strength occurs around the mid-1980s. Thus, NCEP1 may overestimate the decadal shift in the SAH intensity around the late 1970s, while ERA-40 may underestimate it. Much attention needs to be paid when we use the reanalysis data to study the decadal variability of the SAH intensity.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report – An experimental study

PubMed Central

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Context: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. Aims: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. Settings and Design: This was an experimental study conducted on rabbits. Materials and Methods: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6–C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. Results: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. Conclusion: We noticed interestingly that C6–C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms. PMID:28250634

Increasing numbers of nonaneurysmal subarachnoid hemorrhage in the last 15 years: antithrombotic medication as reason and prognostic factor?

PubMed

Konczalla, Juergen; Kashefiolasl, Sepide; Brawanski, Nina; Senft, Christian; Seifert, Volker; Platz, Johannes

2016-06-01

OBJECT Subarachnoid hemorrhage (SAH) is usually caused by a ruptured intracranial aneurysm, but in some patients no source of hemorrhage can be detected. More recent data showed increasing numbers of cases of spontaneous nonaneurysmal SAH (NASAH). The aim of this study was to analyze factors, especially the use of antithrombotic medications such as systemic anticoagulation or antiplatelet agents (aCPs), influencing the increasing numbers of cases of NASAH and the clinical outcome. METHODS Between 1999 and 2013, 214 patients who were admitted to the authors' institution suffered from NASAH, 14% of all patients with SAH. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Risk factors were identified based on the outcome. RESULTS The number of patients with NASAH increased significantly in the last 15 years of the study period. There was a statistically significant increase in the rate of nonperimesencephalic (NPM)-SAH occurrence and aCP use, while the proportion of elderly patients remained stable. Favorable outcome (mRS 0-2) was achieved in 85% of cases, but patients treated with aCPs had a significantly higher risk for an unfavorable outcome. Further analysis showed that elderly patients, and especially the subgroup with a Fisher Grade 3 bleeding pattern, had a high risk for an unfavorable outcome, whereas the subgroup of NPM-SAH without a Fisher Grade 3 bleeding pattern had a favorable outcome, similar to perimesencephalic (PM)-SAH. CONCLUSIONS Over the years, a significant increase in the number of patients with NASAH has been observed. Also, the rate of aCP use has increased significantly. Risk factors for an unfavorable outcome were age > 65 years, Fisher Grade 3 bleeding pattern, and aCP use. Both "PM-SAH" and "NPM-SAH without a Fisher Grade 3 bleeding pattern" had excellent outcomes. Patients with NASAH and a Fisher Grade 3 bleeding pattern had a significantly higher risk for an unfavorable outcome and death. Therefore, for further

The Biochemical Basis of Hydroxymethylglutaryl-CoA Reductase Inhibitors as Neuroprotective Agents in Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Wong, George Kwok Chu; Poon, Wai Sang

2010-01-01

Aneurysmal subarachnoid hemorrhage (SAH) has the highest morbidity and mortality rates of all types of stroke. Many aneurysmal SAH patients continue to suffer from significant neurological morbidity and mortality directly related to delayed cerebral ischemia. Pilot clinical studies of the use of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) in aneurysmal SAH patients have reported a reduction in delayed cerebral ischemia and better clinical outcomes. We review the biochemical effects of statins on endothelium vascular function, glutamate-mediated neurotoxicity, inflammatory changes, and oxidative injuries, with reference to their possible neuroprotective effects in aneurysmal SAH.

Possible Role of Inflammation and Galectin-3 in Brain Injury after Subarachnoid Hemorrhage

PubMed Central

2018-01-01

Aneurysmal subarachnoid hemorrhage (SAH) is known as one of the most devastating diseases in the central nervous system. In the past few decades, research on SAH has focused on cerebral vasospasm to prevent post-SAH delayed cerebral ischemia (DCI) and to improve outcomes. However, increasing evidence has suggested that early brain injury (EBI) is an important mechanism contributing to DCI, cerebral vasospasm as well as poor outcomes. Though the mechanism of EBI is very complex, inflammation is thought to play a pivotal role in EBI. Galectin-3 is a unique chimera type in the galectin family characterized by its β-galactoside-binding lectin, which mediates various pathologies, such as fibrosis, cell adhesion, and inflammation. Recently, two clinical studies revealed galectin-3 to be a possible prognostic biomarker in SAH patients. In addition, our recent report suggested that higher acute-stage plasma galectin-3 levels correlated with subsequent development of delayed cerebral infarction that was not associated with vasospasm in SAH patients. We review the possible role and molecular mechanisms of inflammation as well as galectin-3 in brain injuries, especially focusing on EBI after SAH, and discuss galectin-3 as a potential new therapeutic or research target in post-SAH brain injuries. PMID:29414883

Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

PubMed

Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

2016-12-15

Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression. Copyright © 2016. Published by Elsevier B.V.

Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

PubMed

Yuan, Jichao; Liu, Wei; Zhu, Haitao; Zhang, Xuan; Feng, Yang; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

2017-01-01

Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between Temperature and Hospital Admissions for Subarachnoid Hemorrhage in Korea

PubMed Central

Lee, Suji; Guth, Matthias

2017-01-01

The relationship between temperature and subarachnoid hemorrhage (SAH) is less studied than that between temperature and myocardial infarction or other cardiovascular diseases. This study investigated the association between daily temperature and risk of SAH by analyzing the hospital admission records of 111,316 SAH patients from 2004 to 2012 in Korea. A Poisson regression model was used to examine the association between temperature and daily SAH hospital admissions. To analyze data and identify vulnerable groups, we used the following subgroups: sex, age, insurance type, area (rural or urban), and different climate zones. We confirmed a markedly higher SAH risk only for people of low socioeconomic status in both hot and cold temperatures; the relative risk (RR) in the Medicaid group was significantly increased and ranged from 1.04 to 1.11 for cold temperatures and 1.10 to 1.11 for hot temperatures. For the National Health Insurance group, the RR was increased to 1.02 for the maximum temperature only. The increased risk for SAH was highest in the temperate zone. An increase above the heat threshold temperature and a decrease below the cold threshold temperature were correlated with an increased risk of SAH in susceptible populations and were associated with different lag effects and RRs. PMID:28430143

The effects of intrathecal nicergoline and nimodipine in cerebral vasospasm: an experimental study in rabbits.

PubMed

Solmaz, Ilker; Onal, Mehmet Bulent; Civelek, Erdinc; Kircelli, Atilla; Ongoru, Onder; Ugurel, Sahin; Erdogan, Ersin; Gonul, Engin

2011-01-01

the aim of this study was to assess and to compare the ability of intrathecal nicergoline and nimodipine in prevention of cerebral vasospasm in a rabbit model of subarachnoid hemorrhage (SAH). twenty male New Zealand white rabbits were allocated into four groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) control [no SAH (n = 5)], (2) SAH only (n = 5), (3) SAH plus nimodipine (n = 5), and (4) SAH plus nicergoline (n = 5). there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 3 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). There was no significant difference between basilar artery vessel diameter and basilar artery luminal section areas in group 3 and group 4. these findings demonstrate that intrathecal nicergoline has a vasodilatatory effect in an experimental model of SAH in rabbits but not more than that of nimodipine.

Adverse lipid profile elevates risk for subarachnoid hemorrhage: A prospective population-based cohort study.

PubMed

Lindbohm, Joni; Korja, Miikka; Jousilahti, Pekka; Salomaa, Veikko; Kaprio, Jaakko

2018-05-05

Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00-1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07-1.55)) and men (HR 1.20 (95% CIs 1.14-1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74-0.97)) and men (HR 0.88 (95% CIs 0.76-1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01-1.31) and HR 1.26 (95% CIs 1.10-1.44) per one SD increase. Age did not change these findings. An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. Copyright © 2018 Elsevier B.V. All rights reserved.

Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis Describing the Diagnostic Accuracy of History, Physical Examination, Imaging, and Lumbar Puncture With an Exploration of Test Thresholds.

PubMed

Carpenter, Christopher R; Hussain, Adnan M; Ward, Michael J; Zipfel, Gregory J; Fowler, Susan; Pines, Jesse M; Sivilotti, Marco L A

2016-09-01

Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. The objective was to perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). PubMed, Embase, Scopus, and research meeting abstracts were searched up to June 2015 for studies of emergency department patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratios. To identify test and treatment thresholds, we employed the Pauker-Kassirer method with Bernstein test indication curves using the summary estimates of diagnostic accuracy. A total of 5,022 publications were identified, of which 122 underwent full-text review; 22 studies were included (average SAH prevalence = 7.5%). Diagnostic studies differed in assessment of history and physical examination findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low risk of biases. A history of neck pain (LR+ = 4.1; 95% confidence interval [CI] = 2.2 to 7.6) and neck stiffness on physical examination (LR+ = 6.6; 95% CI = 4.0 to 11.0) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Noncontrast cranial CT within 6 hours of headache onset accurately ruled in (LR+ = 230; 95

Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Describing the Diagnostic Accuracy of History, Physical Exam, Imaging, and Lumbar Puncture with an Exploration of Test Thresholds

PubMed Central

Carpenter, Christopher R.; Hussain, Adnan M.; Ward, Michael J.; Zipfel, Gregory J.; Fowler, Susan; Pines, Jesse M.; Sivilotti, Marco L.A.

2016-01-01

Background Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. Objectives To perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). Methods PUBMED, EMBASE, SCOPUS, and research meeting abstracts were searched up to June 2015 for studies of emergency department (ED) patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, positive (LR+) and negative (LR−) likelihood ratios. To identify test- and treatment-thresholds, we employed the Pauker-Kassirer method with Bernstein test-indication curves using the summary estimates of diagnostic accuracy. Results A total of 5,022 publications were identified, of which 122 underwent full text-review; 22 studies were included (average SAH prevalence 7.5%). Diagnostic studies differed in assessment of history and physical exam findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low-risk of biases. A history of neck pain (LR+ 4.1 [95% CI 2.2-7.6]) and neck stiffness on physical exam (LR+ 6.6 [4.0-11.0]) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Non-contrast cranial CT within 6 hours of headache onset accurately ruled-in (LR+ 230 [6-8700]) and ruled-out SAH (LR− 0

The rabbit blood-shunt model for the study of acute and late sequelae of subarachnoid hemorrhage: technical aspects.

PubMed

Andereggen, Lukas; Neuschmelting, Volker; von Gunten, Michael; Widmer, Hans Rudolf; Takala, Jukka; Jakob, Stephan M; Fandino, Javier; Marbacher, Serge

2014-10-02

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH. This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

Socioeconomic Disadvantage Is Associated with a Higher Incidence of Aneurysmal Subarachnoid Hemorrhage.

PubMed

Nichols, Linda; Stirling, Christine; Otahal, Petr; Stankovich, Jim; Gall, Seana

2018-03-01

Aneurysmal subarachnoid hemorrhage (aSAH) incidence is not well studied. Varied definitions of "subarachnoid hemorrhage" have led to a lack of clarity regarding aSAH incidence. The impact of area-level socioeconomic disadvantage and geographical location on the incidence of aSAH also remains unclear. Using a population-based statewide study, we examined the incidence of aSAH in relation to socioeconomic disadvantage and geographical location. A retrospective cohort study of nontraumatic subarachnoid hemorrhages from 2010 to 2014 was undertaken. Researchers manually collected data from multiple overlapping sources including statewide administrative databases, individual digital medical records, and death registers. Age-standardized rates (ASRs) per 100,000 person years were calculated using the 2001 Australian population. Differences in incidence rate ratios were calculated by age, sex, area-level socioeconomic status, and geographical location using Poisson regression. The cohort of 237 cases (mean age, 61.0 years) with a female predominance of 166 (70.04%) included 159 confirmed aSAH, 52 community-based deaths, and 26 probable cases. The ASR for aSAH was 9.99 (95% confidence interval [CI], 8.69-11.29). A significant association between area-level socioeconomic disadvantage and incidence was observed, with the rate of aSAH in disadvantaged geographical areas being 1.40 times higher than that in advantaged areas (95% CI, 1.11-1.82; P = .012). This study uses a comprehensive search of multiple data sources to define a new baseline of aSAH within an Australian population. This study presents a higher incidence rate of aSAH with socioeconomic variations. As a key risk factor that may explain this paradox, addressing socioeconomic inequalities is important for effective prevention and management interventions. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patterns of convexal subarachnoid haemorrhage: clinical, radiological and outcome differences between cerebral amyloid angiopathy and other causes.

PubMed

Calviere, Lionel; Raposo, Nicolas; Cuvinciuc, Victor; Cognard, Christophe; Bonneville, Fabrice; Viguier, Alain

2018-01-01

Cerebral amyloid angiopathy (CAA) is a common aetiology of convexal subarachnoid haemorrhage (cSAH) but little is known about its specific characteristics in comparison with cSAH from other causes. In this study we compared patients with CAA vs. non-CAA-related cSAH. Retrospective review of baseline and follow-up data of consecutive patients admitted with a symptomatic acute cSAH. Sixty-two patients were included (mean age 66.2 ± 14.1 years), of whom 31 with probable CAA. CAA patients presented more frequently with transient symptoms (83.9 vs. 19.3%; p < 0.001) usually without headache (19.0 vs. 58.1%; p = 0.002). In CAA, these were essentially positive sensory disturbance that met the criteria of transient focal neurological episodes (TFNE). CAA was more often associated with cortical superficial siderosis (cSS) (80.6 vs. 0%; p < 0.001) and lobar cerebral microbleeds (83.4 vs. 9%; p < 0.001). During a mean of 22 months of follow-up, recurrent symptomatic cSAH occurred in 4/27 (12.9%) CAA patients and in 0/27 non-CAA patients. Among 40 patients with MRI follow-up, cSAH recurrences were observed in 44% of CAA patients vs. 13.3% of other cases (p = 0.08) and extension of cSS was detected only in CAA (60%) (p < 0.001). Acute cSAH evolved to cSS in 96 and 73.3% of CAA and non-CAA patients, respectively (p = 0.06). CAA differs from other cSAH in having TFNE as a frequent clinical presentation, a high prevalence of cSS and an increased risk of recurrent subarachnoid bleeding. However, evolution from acute cSAH to focal cSS may not be specific to CAA.

Consequences and coping strategies six years after a subarachnoid hemorrhage – A qualitative study

PubMed Central

Törnbom, Karin; Sunnerhagen, Katharina S.; Törnbom, Marie

2017-01-01

Background After a subarachnoid haemorrhage (SAH), continuing impairment is common and may impact the person’s life. There is a lack of knowledge regarding long-term consequences experienced. Purpose To explore experiences of the care and rehabilitation as well as the consequences and strategies used to cope with everyday life six years post SAH. Methods An explorative interview study with a qualitative design. Individual interviews, with open ended questions, using an interview guide were performed with sixteen participants (mean age 63, 8 men, 8 women) six years post SAH. Data was analyzed according to a descriptive thematic analysis, and themes were discovered inductively. Results Two major themes from the analysis, both including four sub-themes, were identified; these themes were consequences of the SAH and coping strategies. Participants were grateful to have survived the SAH and most were satisfied with their acute medical care. If discharged directly from the neurosurgical unit participants can feel abandoned. In contrast, participants who were referred to a rehabilitation clinic felt supported and informed. Cognitive problems, such as impaired memory and mental fatigue, were reported as still present six years post SAH. Coping strategies were; receiving support from family, society, employers, or technical equipment. At work, talking to colleagues and to taking breaks were common. Participants described hiding their symptoms from employers and friends, as well as trying to continue doing tasks in the same manner as prior to the SAH. If this was not possible, some refrained from doing these tasks. They went through a mourning process, fear, and worries. Conclusions Participants reported several long-term consequences which impacted on their daily lives post SAH, and different coping strategies were used to cope with these problems. Participants reported lack of awareness regarding the consequences of SAH and stressed the importance of structured

Association of Recreational Marijuana Use with Aneurysmal Subarachnoid Hemorrhage.

PubMed

Rumalla, Kavelin; Reddy, Adithi Y; Mittal, Manoj K

2016-02-01

Our objective was to evaluate the effect of cannabis use on hospitalizations for aneurysmal subarachnoid hemorrhage (aSAH). The Nationwide Inpatient Sample (2004-2011) was used to identify all patients (age 15-54) with a primary diagnosis of aSAH (International Classification of Diseases, Ninth Edition, Clinical Modification 430). We identified patients testing positive for cannabis use using all available diagnosis fields. The incidence and characteristics of aSAH hospitalizations among cannabis users were examined. Bivariate and multivariate analyses were performed to determine the effect of cannabis use on aSAH and in-hospital outcomes. Prior to adjustment, the incidence of aSAH in the cannabis cohort was slightly increased relative to the noncannabis cohort (relative risk: 1.07, 95% confidence interval [CI]: 1.02-1.11). Cannabis use in aSAH was more frequent among younger patients (40.44 ± 10.17 versus 43.74 ± 8.68, P < .0001), males (53.3% versus 40.76%, P < .0001), black patients (35.92% versus 19.10%, P < .0001), and Medicaid enrollees (31.13% versus 18.31%, P < .0001). The cannabis use cohort had greater overall illicit drug use but fewer medical risk factors for aSAH. Cannabis use (odds ratio: 1.18, 95% CI: 1.12-1.24) was found to be an independent predictor of aSAH when adjusting for demographics, substance use, and risk factors. Cannabis use was not associated with symptomatic cerebral vasospasm, inpatient mortality, or adverse discharge disposition. Our analysis suggests that recreational marijuana use is independently associated with an 18% increased likelihood of aSAH. Further case-control studies may analyze inpatient outcomes and other understudied mechanisms behind cannabis-associated stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

30-day mortality and readmission after hemorrhagic stroke among Medicare beneficiaries in Joint Commission primary stroke center-certified and noncertified hospitals.

PubMed

Lichtman, Judith H; Jones, Sara B; Leifheit-Limson, Erica C; Wang, Yun; Goldstein, Larry B

2011-12-01

Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC)-certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC-certified versus noncertified hospitals. The study included all fee-for-service Medicare beneficiaries aged 65 years or older with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC-certified hospital on 30-day mortality and readmission. There were 2305 SAH and 8708 ICH discharges from JC-PSC-certified hospitals and 3892 SAH and 22 564 ICH discharges from noncertified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% versus 33.2%, P<0.0001; ICH: 27.9% versus 29.6%, P=0.003) and 30-day mortality (SAH: 35.1% versus 44.0%, P<0.0001; ICH: 39.8% versus 42.4%, P<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% versus 17.0%, P=0.97; ICH: 16.0% versus 15.5%, P=0.29). Risk-adjusted 30-day mortality was 34% lower (odds ratio, 0.66; 95% confidence interval, 0.58-0.76) after SAH and 14% lower (odds ratio, 0.86; 95% confidence interval, 0.80-0.92) after ICH for patients discharged from JC-PSC-certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Patients treated at JC-PSC-certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with noncertified hospitals.

Life satisfaction and return to work after aneurysmal subarachnoid hemorrhage.

PubMed

Passier, Patricia E C A; Visser-Meily, Johanna M A; Rinkel, Gabriel J E; Lindeman, Eline; Post, Marcel W M

2011-01-01

This study was conducted to investigate life satisfaction and employment status after aneurysmal subarachnoid hemorrhage (SAH) and to explain the associations between life satisfaction and demographic, disease-related, psychological, and personality characteristics. Subjects with SAH (n = 141) living at home 2-4 years after the SAH responded to a mailed questionnaire. Outcomes were life satisfaction, as measured with the Life Satisfaction Questionnaire 9 (LiSat-9), and employment status. Determinants in multiple regression analysis were demographic and SAH characteristics, subjective complaints (eg, mood disorder, fatigue, cognitive complaints), and personality characteristics (eg, neuroticism, passive coping style). Of the 141 subjects, 64 (46.7%) had a Glasgow Outcome Scale score of V (good outcome) at discharge. Mean subject age was 51.4 ± 12.3 years, and mean time after SAH was 36.1 ± 7.9 months. Of the 88 subjects who were working at the time of the SAH, 54 (61.4%) returned to work, but only 31 (35.2%) resumed their work completely. The subjects were least satisfied with their vocational situation (51.9% satisfied) and sexual life (51.7%) and were most satisfied with their relationships (75.2%-88.7%) and self-care ability (88.6%). Age (β value = 0.17), return to work after SAH (0.19), disability at hospital discharge (0.25), worsened mood (-0.37), and passive coping (-0.25) together accounted for 47.2% of the life satisfaction scores. Our data indicate that return to work is a major issue for individuals who survive an SAH. Not returning to work, disability, depression, and passive coping are associated with reduced life satisfaction. Thus, vocational reintegration after SAH merits more attention during rehabilitation. Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification.

PubMed

Vlak, Monique H M; Rinkel, Gabriel J E; Greebe, Paut; Greving, Jacoba P; Algra, Ale

2013-06-01

The overall incidence of aneurysmal subarachnoid haemorrhage (aSAH) in western populations is around 9 per 100 000 person-years, which confers to a lifetime risk of around half per cent. Risk factors for aSAH are usually expressed as relative risks and suggest that absolute risks vary considerably according to risk factor profiles, but such estimates are lacking. We aimed to estimate incidence and lifetime risks of aSAH according to risk factor profiles. We used data from 250 patients admitted with aSAH and 574 sex-matched and age-matched controls, who were randomly retrieved from general practitioners files. We determined independent prognostic factors with multivariable logistic regression analyses and assessed discriminatory performance using the area under the receiver operating characteristic curve. Based on the prognostic model we predicted incidences and lifetime risks of aSAH for different risk factor profiles. The four strongest independent predictors for aSAH, namely current smoking (OR 6.0; 95% CI 4.1 to 8.6), a positive family history for aSAH (4.0; 95% CI 2.3 to 7.0), hypertension (2.4; 95% CI 1.5 to 3.8) and hypercholesterolaemia (0.2; 95% CI 0.1 to 0.4), were used in the final prediction model. This model had an area under the receiver operating characteristic curve of 0.73 (95% CI 0.69 to 0.76). Depending on sex, age and the four predictors, the incidence of aSAH ranged from 0.4/100 000 to 298/100 000 person-years and lifetime risk between 0.02% and 7.2%. The incidence and lifetime risk of aSAH in the general population varies widely according to risk factor profiles. Whether persons with high risks benefit from screening should be assessed in cost-effectiveness studies.

Parahippocampectomy as a New Surgical Approach to Mesial Temporal Lobe Epilepsy Caused By Hippocampal Sclerosis: A Pilot Randomized Comparative Clinical Trial.

PubMed

Alonso-Vanegas, Mario Arturo; Freire Carlier, Iván D; San-Juan, Daniel; Martínez, Alma Rosa; Trenado, Carlos

2018-02-01

The parahippocampal gyrus plays an important role in the epileptogenic pathways of mesial temporal lobe epilepsy caused by hippocampal sclerosis (mTLE-HS); its resection could prevent epileptic seizures with fewer complications. This study evaluates the initial efficacy and safety of anterior temporal lobectomy (ATL), selective amygdalohipppocampectomy (SAH), and parahippocampectomy (PHC) surgical approaches in mTLE-HS. A randomized comparative pilot clinical trial (2008-2011) was performed that included patients with mTLE-HS who underwent ATL, trans-T3 SAH, and trans-T3 PHC. Their sociodemographic characteristics, visual field profiles, verbal and visual memory profiles, and Engel scale outcome at baseline and at 1 and 5 years are described, using descriptive statistics along with parametric and nonparametric tests. Forty-three patients with a mean age of 35.2 years (18-56 years), 65% female, were analyzed: 14 underwent PHC, 14 ATL, and 15 SAH. The following percentages refer to those patients who were seizure free (Engel class IA) at 1-year and 5-year follow-up, respectively: 42.9% PHC, 71.4% ATL, and 60% SAH (P = 0.304); 28.6% PHC, 50% ATL, and 53.3% SAH (P = 0.353). Postoperative visual field deficits were 0% PHC, 85.7% ATL, and 46.7% SAH (P = 0.001). Verbal and/or visual memory worsening were present in 21.3% PHC, 42.8% ATL, and 33.4% SAH (P = 0.488) and preoperative and postoperative visual memory scores were significantly different in the SAH group only (P = 0.046). PHC, ALT, and SAH show a preliminary similar efficacy in short-term seizure-free rates in patients with mTLE-HS. However, PHC efficacy in the long-term decreases compared with the other surgical techniques. PHC does not produce postoperative visual field deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.

PubMed

Ohkuma, Hiroki; Tabata, Hidefumi; Suzuki, Shigeharu; Islam, Md Shafiqul

2003-01-01

Japan is known to have an incidence of aneurysmal subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially common. However, the risk factors for SAH in Japan are unknown. The purpose of this study was to identify the risk factors and then examine their possible roles in cases of SAH in Japan. Case-control data were collected in the Aomori prefecture between June 2000 and May 2001 and in the Shimokita area between 1989 and 1998. A history of hypertension, cigarette smoking, alcohol consumption, hypercholesterolemia, and diabetes mellitus were examined as possible risk factors for SAH by using stepwise logistic regression analysis. Stepwise logistic regression analysis showed that a history of hypertension and current smoking increased the risk of SAH and that a history of hypercholesterolemia decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus were excluded from the model, because their log-likelihood ratios were not significant. The adjusted odds ratios, obtained by forcing matching factors, were 2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was 27% in men and 31% in women, whereas the prevalence of cigarette smoking in control subjects was 46% in men and 9% in women. Hypertension and cigarette smoking seem to be independent risk factors for SAH in Japan. The high prevalence of hypertension in both sexes and the high prevalence of cigarette smoking in men in the general population might contribute to the high incidence of SAH in Japan.

Recovery from a Subarachnoid Hemorrhage: Days 1 through 22

ERIC Educational Resources Information Center

Brice, Alejandro E.; Brice, Roanne G.; Wallace, Sarah E.

2016-01-01

Subarachnoid hemorrhages (SAHs) are a serious medical emergency, as 30% to 50% of all SAHs can result in death. Personal accounts and case studies are an important aspect of evidence-based practice. This first article of two presents a review of AB's (patient) condition immediately following an SAH in the intensive care and immediately post…

Epilepsy-associated long-term mortality after aneurysmal subarachnoid hemorrhage.

PubMed

Huttunen, Jukka; Lindgren, Antti; Kurki, Mitja I; Huttunen, Terhi; Frösen, Juhana; Koivisto, Timo; von Und Zu Fraunberg, Mikael; Immonen, Arto; Jääskeläinen, Juha E; Kälviäinen, Reetta

2017-07-18

To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1-3.0). Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

PubMed

Okada, Takeshi; Kawakita, Fumihiro; Nishikawa, Hirofumi; Nakano, Fumi; Liu, Lei; Suzuki, Hidenori

2018-05-31

There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation. The effects were evaluated by survival rates, neurological scores, and brain water content at 24-72 h and immunoglobulin G immunostaining and Western blotting at 24 h post-SAH. IAXO-102 significantly prevented post-SAH neurological impairments, brain edema, and BBB disruption, resulting in improved survival rates. IAXO-102 also significantly suppressed post-SAH activation of a major isoform of MAPK p46 c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 as well as periostin induction and preserved tight junction protein zona occludens-1. Another selective TLR4 antagonist TAK-242, which has a different binding site from IAXO-102, also showed similar effects to IAXO-102. This study first provided the evidence that TLR4 signaling is involved in post-SAH acute BBB disruption and that the signaling is mediated at least partly by JNK activation. TLR4-targeted therapy may be promising to reduce post-SAH morbidities and mortalities.

Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

PubMed Central

Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

2017-01-01

Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever. PMID:28469408

[Arterial hypertension and sleep apnea hypopnea syndrome in primary care].

PubMed

Bayó Llibre, J; Riel Cabrera, R; Mellado Breña, E; Filomena Paci, J; Priego Artero, M; García Alfaro, F J; Grau Granero, J M; Vázquez González, D; López Solana, J; Fernández San Martín, M I

2015-01-01

Sleep apnea hypopnea syndrome (SAHS) is frequent in hypertensive patients and plays a role in a greater incidence of cardiovascular morbidity-mortality. This study aims to know the clinical profile of hypertensive patients with SAHS compared to hypertensive patients without SAHS to know which variables should be used to orient their screening from primary care. An observational, descriptive, retrospective study of cases (hypertensive patients with SAHS) and controls (hypertensive patients without) was performed in an urban health care center. Based on a computerized registry of the site, patients diagnosed of SAHS and hypertension over 30 years of age were selected. For each case, one control case of hypertensive patients without SAHS paired by age and gender was randomly obtained. A total of 64 cases and 64 controls were selected. Standing out in the bivariate analysis were greater BMI (34.3±12.8 vs. 28.6±3.6), predominance of obesity (70.3 vs. 35.9%), metabolic syndrome (77.3 vs. 42.2%), consumption of psychopharmaceuticals (19.7 vs. 7.8%) and anithypertensive drugs (26.5 vs. 14.0%), ischemic heart disease (20.3 vs. 9.4%) in the case group versus control group (P<.05 for all the variables). The multivariate analysis showed that only the presence of metabolic syndrome was related with the presence of SAHS in hypertensive patients (OR 4.65; 95% CI: 2.03-10.64; P<.001). Screening for SAHS should be performed in hypertensive patients seen in primary care if they have metabolic syndrome criteria. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case-Control Study.

PubMed

Huttunen, Jukka; Lindgren, Antti; Kurki, Mitja I; Huttunen, Terhi; Frösen, Juhana; von Und Zu Fraunberg, Mikael; Koivisto, Timo; Kälviäinen, Reetta; Räikkönen, Katri; Viinamäki, Heimo; Jääskeläinen, Juha E; Immonen, Arto

2016-09-01

To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication. © 2016 American Heart Association, Inc.

Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage.

PubMed

Mutoh, Tomoko; Mutoh, Tatsushi; Sasaki, Kazumasu; Nakamura, Kazuhiro; Tatewaki, Yasuko; Ishikawa, Tatsuya; Taki, Yasuyuki

2017-02-15

Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH. Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively. Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (P<0.05). MIL raised CBF in a dose-dependent manner (P<0.001), resulted in lower incidence of DCI (P=0.008) and better recovery from neurobehavioral decline than control (P<0.001). The CBF values on day 1 predicted DCI with a cut-off of 42.5ml/100g/min (82% specificity and 83% sensitivity), which was greater in mice treated with MIL than those of control (51.7 versus 37.6ml/100g/min; P<0.001). MIL improves post-SAH acute hypoperfusion that can lead to the prevention of DCI and functional worsening, acting as a neurocardiac protective agent against EBI. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of levosimendan in the management of subarachnoid hemorrhage.

PubMed

Varvarousi, Giolanda; Xanthos, Theodoros; Sarafidou, Pavlina; Katsioula, Ellisavet; Georgiadou, Marianthi; Eforakopoulou, Maria; Pavlou, Hlias

2016-02-01

Aneurysmal subarachnoid hemorrhage (aSAH) is one of the leading causes of neurologic disability accounting for dismal long term survival rates. aSAH leads to a sudden increase in intracranial pressure and a massive sympathetic discharge. Excessive sympathetic stimulation leads to catecholamine mediated myocardial dysfunction and hemodynamic instability which may critically hamper brain perfusion and oxygenation. In the setting of acute aSAH, administration of vasoactive drugs aims at stabilizing impaired hemodynamics. However, studies have shown that conventional treatment with vasoactive drugs that lead to Ca(+2) overload and increase myocardial oxygen consumption, fail to restore hemodynamics and decrease cerebral blood flow. Levosimendan is a non-adrenergic inotropic Ca(+2) sensitizer with not only beneficial hemodynamic properties but also pleiotropic effects, contributing to its cardioprotective and neuroprotective role. Although there have been limited data available regarding the use of levosimendan in patients with aSAH, current evidence suggests that levosimendan may have a role in the setting of post-aSAH cardiomyopathy and decreased cerebral blood flow both in the emergency departments and in intensive care units. The purpose of this review is to provide an overview of studies of levosimendan therapy for aSAH, and describe current knowledge about the effects of levosimendan in the management of aSAH. Copyright © 2015 Elsevier Inc. All rights reserved.

MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage

PubMed Central

Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten

2017-01-01

Background and Purpose— Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. Methods— In a prospective case–control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. Results— MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients (P<0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without (P<0.05) in both the screening and validation. Conclusions— SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. PMID:28768799

MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage.

PubMed

Bache, Søren; Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten

2017-09-01

Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. In a prospective case-control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients ( P <0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without ( P <0.05) in both the screening and validation. SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. © 2017 The Authors.

Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

PubMed

Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

2017-08-01

Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

Subarachnoid hemorrhage admissions retrospectively identified using a prediction model

PubMed Central

McIntyre, Lauralyn; Fergusson, Dean; Turgeon, Alexis; dos Santos, Marlise P.; Lum, Cheemun; Chassé, Michaël; Sinclair, John; Forster, Alan; van Walraven, Carl

2016-01-01

Objective: To create an accurate prediction model using variables collected in widely available health administrative data records to identify hospitalizations for primary subarachnoid hemorrhage (SAH). Methods: A previously established complete cohort of consecutive primary SAH patients was combined with a random sample of control hospitalizations. Chi-square recursive partitioning was used to derive and internally validate a model to predict the probability that a patient had primary SAH (due to aneurysm or arteriovenous malformation) using health administrative data. Results: A total of 10,322 hospitalizations with 631 having primary SAH (6.1%) were included in the study (5,122 derivation, 5,200 validation). In the validation patients, our recursive partitioning algorithm had a sensitivity of 96.5% (95% confidence interval [CI] 93.9–98.0), a specificity of 99.8% (95% CI 99.6–99.9), and a positive likelihood ratio of 483 (95% CI 254–879). In this population, patients meeting criteria for the algorithm had a probability of 45% of truly having primary SAH. Conclusions: Routinely collected health administrative data can be used to accurately identify hospitalized patients with a high probability of having a primary SAH. This algorithm may allow, upon validation, an easy and accurate method to create validated cohorts of primary SAH from either ruptured aneurysm or arteriovenous malformation. PMID:27629096

TRADOC Library and Information Network (TRALINET). Union List of Periodicals (TULIP) (6th Edition)

DTIC Science & Technology

1993-12-01

Clarke Community Library 3202 Nebraska Avenue North Ft. Leonard Wood, MO 65473-5000 E-Mail: resercewood-emhl.army.mil TRX US Army Ordnance Center and...Ft. Story Leslie Smail Community Recreation Division DSN 438-7548 Ft. Story Library CML (804) 422-7548 Building T-530 Ft. Story, VA 23459-5067 E-Mail...Army CASCOM and Ft. Lee Connie Baker Community Recreation Div. DSN 687-6844 General Library COL (804) 734-6844 Building P-9023 Ft. Lee, VA 23801-5142 E

Extra-intracranial blood shunt mimicking aneurysm rupture: intracranial-pressure-controlled rabbit subarachnoid hemorrhage model.

PubMed

Marbacher, Serge; Sherif, Camillo; Neuschmelting, Volker; Schläppi, Janine-Ai; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2010-08-30

The achieved degree of delayed cerebral vasospasm (DCVS) in the rabbits most frequently applied cistern magna blood injection model is often mild. The aim of this study was to characterize and evaluate the feasibility of an experimental SAH technique that mimics pathophysiological mechanisms and triggers higher degrees of DCVS. SAH was induced by extracranial-intracranial (EC/IC) shunting of blood from the subclavian artery into the great cerebral cistern. Intracranial pressure (ICP), arterial blood pressure, heart rate, arterial blood gas analysis, and neurological status were monitored throughout the experiments. The magnitude of spasm was determined by comparison of pre-SAH (day 0) and post-SAH (day 3) angiograms and postmortem morphometric analysis of the basilar artery. A total of 13 experiments (SAH, n=11; controls, n=2) were performed. Two animals died after initiation of the EC/IC blood shunt in respiratory arrest. In SAH animals, ICP (baseline: 12+/-1 [mean+/-SD]; peak: 51+/-4; steady-state level: 15+/-2 mm Hg) rose to diastolic blood pressure levels (56+/-3 mm Hg) within 98+/-20s, and fell to a steady state within 186+/-41 s. SAH-induced vasoconstriction of the basilar artery was 53.1+/-2.8% on day 3 compared to baseline (P<0.05) and histology confirmed marked vasoconstriction. This novel technique of SAH induction closely mimics the pathophysiological sequelae of aneurysm rupture and triggers constant higher degrees of delayed cerebral vasospasm than previously described rabbit models. The severity of vasospasm attained offers a unique opportunity to evaluate future therapeutic treatment options. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

PubMed

Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

2017-04-01

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

The initial time-course of headache in patients with spontaneous subarachnoid hemorrhage.

PubMed

Čomić, Hata; Rinkel, Gabriel J E; Vergouwen, Mervyn D I

2017-08-15

If acute severe headache disappears early after its onset, the question arises whether subarachnoid hemorrhage (SAH) should still be ruled out. We studied the initial time-course and minimal duration of headache in a consecutive series of neurologically intact patients with spontaneous SAH. We included patients admitted between 2012 and 2015 within 48h after spontaneous SAH with a normal level of consciousness and no focal deficits. We retrieved data on headache severity, measured with a Numeric Rating Scale (NRS), <48h after ictus. We analyzed the proportion of patients with a first NRS 0 and NRS <3 within 48h after ictus and minimal headache duration. Patients were censored in case of a decrease in level of consciousness, aneurysm treatment, or early discharge. We included 106 patients (62 aneurysmal SAH, 33 perimesencephalic hemorrhage, 11 other spontaneous SAH). All patients were treated with analgesics. Within 48h after ictus, a first NRS 0 was reported by 9 patients (8%;95%CI:3%-14%) and a first NRS <3 by 22 patients (21%;95%CI:13%-28%). Shortest time lapse until NRS 0 was 10h in a patient with aneurysmal SAH who had been on acetaminophen and tramadol since 2:35h after ictus. In a cohort of SAH patients with a normal level of consciousness and no focal deficits who all used analgetics, headache disappeared in around 10% within 48h after ictus. Our data indicate that a diagnostic work-up for SAH is also needed in patients using analgesics in whom headache has disappeared after 10h. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

PubMed Central

Leclerc, Jenna L.; Garcia, Joshua M.; Diller, Matthew A.; Carpenter, Anne-Marie; Kamat, Pradip K.; Hoh, Brian L.; Doré, Sylvain

2018-01-01

Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the different approaches to simulating SAH in rodents, in particular elucidating the key pathophysiology of the various methods and models. Ultimately, we suggest the development of standardized model of rodent SAH that better replicates human pathophysiology for moving forward with translational research. PMID:29623028

Quality of Life after Brain Injury (QOLIBRI) Overall Scale for patients after aneurysmal subarachnoid hemorrhage.

PubMed

Wong, George Kwok Chu; Lam, Sandy Wai; Ngai, Karine; Wong, Adrian; Mok, Vincent; Poon, Wai Sang

2014-06-01

The Quality of Life after Brain Injury Overall Scale (QOLIBRI-OS) is a recently developed instrument that provides a brief summary measure of health-related quality of life (HRQoL) in domains typically affected by brain injury. This study examined the application of the six item QOLIBRI-OS in patients after aneurysmal subarachnoid hemorrhage (aSAH). Hong Kong Chinese aSAH patients were evaluated prospectively within the chronic phase of 1 year after aSAH in this multi-center observational study. Cronbach's α was 0.88, and correlations were satisfactory for all six items. QOLIBRI-OS demonstrated good criterion validity with other 1 year outcome assessments. In conclusion, QOLIBRI-OS can be used as a brief index for disease-specific HRQoL assessment after aSAH. Further validation in another population of aSAH patients is recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.

PubMed

Wanderer, Stefan; Mrosek, Jan; Gessler, Florian; Seifert, Volker; Konczalla, Juergen

2018-02-01

Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH. To investigate the effect of losartan on PGF2a-enhanced vasoconstriction after SAH, cerebral vasospasm was induced by a double-haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by measurement of the isometric force of basilar artery ring segments in an organ bath. PGF2a induced a dose-dependent contraction. After pre-incubation with losartan, the maximum contraction (E max ) for sham-operated animals was significantly lowered [E max 6% in losartan 3 × 10 -4  molar (M) vs. 56% without losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre-incubated vessels with losartan 3 × 10 -4  M on day 3 (d3) as well as on day 5 (d5). For the vasorelaxative investigations, vessel segments were pre-incubated with PFG2a. Cumulative application of losartan completely resolved the pre-contraction in sham-operated animals (non SAH: 95% relaxation). After SAH, losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the pre-contraction (d3: 119%). Therefore, a statistically significantly increased and earlier relaxation was calculated for all losartan concentrations [E max (d3/d5) and pD 2 (d3/d5)] compared with the solvent control group. In a physiological and pathophysiological setup, losartan reduces a PGF2-induced vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be integrated in pushing forward further concepts trying to antagonise

Methionine Metabolites in Patients With Sepsis.

PubMed

Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

2018-01-01

Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes

30-Day Mortality and Readmission after Hemorrhagic Stroke among Medicare Beneficiaries in Joint Commission Primary Stroke Center Certified and Non-Certified Hospitals

PubMed Central

Lichtman, Judith H.; Jones, Sara B.; Leifheit-Limson, Erica C.; Wang, Yun; Goldstein, Larry B.

2012-01-01

Background and Purpose Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC) certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC certified versus non-certified hospitals. Methods The study included all fee-for-service Medicare beneficiaries ≥65 years old with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC certified hospital on 30-day mortality and readmission. Results There were 2,305 SAH and 8,708 ICH discharges from JC-PSC certified hospitals and 3,892 SAH and 22,564 ICH discharges from non-certified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% vs. 33.2%, p<0.0001; ICH: 27.9% vs. 29.6%, p=0.003) and 30-day mortality (SAH: 35.1% vs. 44.0%, p<0.0001; ICH: 39.8% vs. 42.4%, p<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% vs. 17.0%, p=0.97; ICH: 16.0% vs. 15.5%; p=0.29). Risk-adjusted 30-day mortality was 34% lower (OR 0.66, 95% CI 0.58–0.76) after SAH and 14% lower (OR 0.86, 95% CI 0.80–0.92) after ICH for patients discharged from JC-PSC certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Conclusions Patients treated at JC-PSC certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with non-certified hospitals. PMID:22033986

Validation of the WristOx 3100 oximeter for the diagnosis of sleep apnea/hypopnea syndrome.

PubMed

Nigro, Carlos Alberto; Aimaretti, Silvia; Gonzalez, Sergio; Rhodius, Edgardo

2009-05-01

To evaluate the diagnostic accuracy of the Nonin WristOx 3100 and its software (nVision 5.0) in patients with suspicion of sleep apnea/hypopnea syndrome (SAHS). All participants (168) had the oximetry and polysomnography simultaneously. The two recordings were interpreted blindly. The software calculated: adjusted O(2) desaturation index [ADI]-mean number of O(2) desaturation per hour of total recording analyzed time of > or = 2%, 3%, 4%, 5%, and 6% (ADI2, 3, 4, 5, and 6) and AT90-accumulated time at SO(2) < 90%. The ADI2, 3, 4, 5, and 6 and the AT90 cutoff points that better discriminated between subjects with or without SAHS arose from the receiver operating characteristic curve analysis. The sensitivity (S), specificity (E), and positive and negative likelihood ratio (LR+, LR-) for the different thresholds for ADI were calculated. One hundred and fifty-four patients were included (119 men, mean age 51, median apnea/hypopnea index [AHI] 14, median body mass index [BMI] 28.3 kg/m(2)). The best cutoff points of ADI were: SAHS = AHI > or = 5: ADI2 > 19.3 (S 89%, E 94%, LR+ 15.5 LR- 0.11); SAHS =AHI > or = 10: ADI3 > 10.5 (S 88%, E 94%, LR+ 15 LR- 0.12); SAHS = AHI > or = 15: ADI3 > 13.4 (S 88%, E 90%, LR+ 8.9, LR- 0.14). AT90 had the lowest diagnosis accuracy. An ADI2 < or = 12.2 excluded SAHS (AHI > or = 5 and 10; S 100%, LR- 0) and ADI3 > 4.3 (AHI > or = 5 and 10) or 32 (AHI > or = 15) confirmed SAHS (E 100%). A negative oximetry defined as ADI2 < or = 12.2 excluded SAHS defined as AHI > or = 5 or 10 with a sensitivity and negative likelihood ratio of 100% and 0%, respectively. Furthermore, a positive oximetry defined as an ADI3 > 32 (SAHS = AHI > or = 15) had a specificity of 100% to confirm the pathology.

[Angiopoietins predict long-term outcomes after aneurysmal subarachnoid hemorrhage during an early period].

PubMed

Wang, Yi; Wang, Dong; Wei, Huijie; Tian, Ye; Jiang, Rongcai; Yue, Shuyuan; Zhang, Jianning

2015-05-19

To evaluate the association between serum levels of angiopoietins (Ang) during an early period (within 72 h) and clinical outcomes after aneurysmal subarachnoid haemorrhage (aSAH). This prospective study was conducted at Department of Neurosurgery, Tianjin Medical University General Hospital. Blood samples from 37 aSAH patients were collected at 8 h (or < 8 h), 24 h, 72 h after an onset of SAH. The serum levels of Ang-1, Ang-2 and Tie-2 were measured by enzyme-linked immunosorbent assay (ELISA). They were followed up for 3 months by Glasgow outcome score extended (GOSE). Those with GOSE > 5 were counted as a good outcome while those with GOSE ≤ 5 had a poor outcome. A total of 37 patients with aSAH and 39 healthy controls (HC) were enrolled. The aSAH patients showed a significant rise of Ang-1 within 8 h as compared with HC. The outcomes were good (n = 15) and poor (n = 22). Serum Ang-1 at 8 h (or < 8 h), 24 h and 72 h in good outcomers showed significantly higher than that in poor outcomers [(52 ± 24) vs (37 ± 17) mg/L, (62 ± 26) vs (45 ± 17) mg/L, (107 ± 27) vs (72 ± 18) mg/L]. The serum level of Ang-1 at 8 h and 24 h was one of independent risk factors for aSAH patients by multiariable Logistic regression analysis [adjected OR (95% CI) 1.095 (1.015-1.181) and 1.109 (1.016-1.211)] (P < 0.05). High serum level of Ang-1 during an early period (within 72 h) was associated with good outcomers (r = 0.627, P < 0.001). The serum levels of angiopoietins are significantly altered in aSAH patients, especially higher in good outcomers. And abnormal levels of angiopoietins may affect early brain injury (EBI) after SAH, structural integrity and recovery of blood-brain barrier (BBB) and long-term outcomes in aSAH patients.

Relationship between weather conditions and admissions for ischemic stroke and subarachnoid hemorrhage

PubMed Central

Tarnoki, Adam D.; Türker, Acar; Tarnoki, David L.; İyisoy, Mehmet S; Szilagyi, Blanka K.; Duong, Hoang; Miskolczi, Laszlo

2017-01-01

Aim To assess impacts of different weather conditions on hospitalizations of patients with ischemic strokes and subarachnoid hemorrhages (SAH) in South Florida. Methods Diagnostic data of patients with spontaneous SAH and strokes were recorded between June 2010 and July 2013. Daily synchronous forecast charts were collected from the National Weather Service and the whole data were matched prospectively. The incidence rate ratio (IRR) was calculated. Results Increased incidence rate of ischemic stroke was consistent with the daily lowest and highest air pressure (IRR 1.03, P = 0.128 and IRR 0.98, P = 0.380, respectively), highest air temperature (IRR 0.99, P = 0.375), and presence of hurricanes or storms (IRR 0.65, P = 0.054). Increased incidence of SAH cases was consistent with daily lowest and highest air pressure (IRR 0.87, P < 0.001 and IRR 1.08, P = 0.019, respectively) and highest air temperature (IRR 0.98, P < 0.001). Presence of hurricanes and/or tropical storms did not influence the frequency of SAH. We found no relationship between the presence of fronts and the admissions for ischemic stroke or SAH. Conclusion Higher number of ischemic stroke and SAH cases can be expected with the daily lowest and highest air pressure, highest air temperature. Presence of hurricanes or tropical storms increased the risk of ischemic stroke but not the SAH. These findings can help to develop preventive health plans for cerebrovascular diseases. PMID:28252876

Relationship between weather conditions and admissions for ischemic stroke and subarachnoid hemorrhage.

PubMed

Tarnoki, Adam D; Turker, Acar; Tarnoki, David L; Iyisoy, Mehmet S; Szilagyi, Blanka K; Duong, Hoang; Miskolczi, Laszlo

2017-02-28

To assess impacts of different weather conditions on hospitalizations of patients with ischemic strokes and subarachnoid hemorrhages (SAH) in South Florida. Diagnostic data of patients with spontaneous SAH and strokes were recorded between June 2010 and July 2013. Daily synchronous forecast charts were collected from the National Weather Service and the whole data were matched prospectively. The incidence rate ratio (IRR) was calculated. Increased incidence rate of ischemic stroke was consistent with the daily lowest and highest air pressure (IRR 1.03, P=0.128 and IRR 0.98, P=0.380, respectively), highest air temperature (IRR 0.99, P=0.375), and presence of hurricanes or storms (IRR 0.65, P=0.054). Increased incidence of SAH cases was consistent with daily lowest and highest air pressure (IRR 0.87, P<0.001 and IRR 1.08, P=0.019, respectively) and highest air temperature (IRR 0.98, P<0.001). Presence of hurricanes and/or tropical storms did not influence the frequency of SAH. We found no relationship between the presence of fronts and the admissions for ischemic stroke or SAH. Higher number of ischemic stroke and SAH cases can be expected with the daily lowest and highest air pressure, highest air temperature. Presence of hurricanes or tropical storms increased the risk of ischemic stroke but not the SAH. These findings can help to develop preventive health plans for cerebrovascular diseases.

Alteration of S-adenosylhomocysteine levels affects lignin biosynthesis in switchgrass.

PubMed

Bai, Zetao; Qi, Tianxiong; Liu, Yuchen; Wu, Zhenying; Ma, Lichao; Liu, Wenwen; Cao, Yingping; Bao, Yan; Fu, Chunxiang

2018-04-28

Methionine (Met) synthesized from aspartate is a fundamental amino acid needed to produce S-adenosylmethionine (SAM) that is an important cofactor for the methylation of monolignols. As a competitive inhibitor of SAM-dependent methylation, the effect of S-adenosylhomocysteine (SAH) on lignin biosynthesis, however, is still largely unknown in plants. Expression levels of Cystathionine γ-synthase (PvCGS) and S-adenosylhomocysteine hydrolase1 (PvSAHH1) were downregulated by RNAi technology, respectively, in switchgrass, a dual-purpose forage and biofuel crop. The transgenic switchgrass lines were subjected to studying the impact of SAH on lignin biosynthesis. Our results showed that downregulation of PvCGS in switchgrass altered the accumulation of aspartate-derived and aromatic amino acids, reduced the content of SAH, enhanced lignin biosynthesis, and stunted plant growth. In contrast, downregulation of PvSAHH1 raised SAH levels in switchgrass, impaired the biosynthesis of both guaiacyl and syringyl lignins, and therefore significantly increased saccharification efficiency of cell walls. This work indicates that SAH plays a crucial role in monolignol methylation in switchgrass. Genetic regulation of either PvCGS or PvSAHH1 expression in switchgrass can change intracellular SAH contents and SAM to SAH ratios and therefore affect lignin biosynthesis. Thus, our study suggests that genes involved in Met metabolism are of interest as new valuable targets for cell wall bioengineering in future. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

PubMed

Turan, Nefize; Miller, Brandon A; Huie, J Russell; Heider, Robert A; Wang, Jun; Wali, Bushra; Yousuf, Seema; Ferguson, Adam R; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2018-02-01

Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

PubMed

Sasaki, Kazumasu; Mutoh, Tatsushi; Nakamura, Kazuhiro; Kojima, Ikuho; Taki, Yasuyuki; Suarez, Jose Ignacio; Ishikawa, Tatsuya

2017-07-13

Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r 2 =0.31, P=0.0002). Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

MSK1 downregulation is associated with neuronal and astrocytic apoptosis following subarachnoid hemorrhage in rats.

PubMed

Ning, Bo; Guo, Geng; Liu, Hong; Ning, Lei; Sun, Bao-Liang; Li, Zhen; Wang, Shuo; Lv, Zheng-Wen; Fan, Cun-Dong

2017-09-01

MSK (mitogen- and stress-activated protein kinase) proteins are a family of mitogen-activated protein kinases. MSKs represent a novel type of pro-survival genes, potentially enhancing the phosphorylation of Bcl2-associated agonist of cell death. However, MSK's function and expression are poorly understood in the central nervous system. In the present study, a subarachnoid hemorrhage (SAH) model was established in SD rats and the expression of MSK1 in the brain subsequent to experimental SAH was investigated. In response to SAH, MSK1 mRNA and protein levels gradually declined, reaching the lowest point at 3 days, and increased thereafter. The expression of active caspase-3 was negatively correlated with MSK1 level. Colocalization and correlating changes in expression of MSK1 and active caspase-3 at neurons and astrocytes indicated that MSK1 downregulation may contribute to SAH-induced apoptosis, validating that MSK1 may be involved in the pathophysiology of the brain cortex subsequent to SAH.

Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

PubMed

Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

2012-07-01

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

Validity and reliability of haemoglobin colour scale and its comparison with clinical signs in diagnosing anaemia in pregnancy in Ahmedabad, India.

PubMed

Bala, D V; Vyas, S; Shukla, A; Tiwari, H; Bhatt, G; Gupta, K

2012-07-01

This study compared the validity of the haemoglobin colour scale (HCS) and clinical signs in diagnosing anaemia against Sahli's haemoglobinometer method as the gold standard, and assessed the reliability of HCS. The sample comprised 129 pregnant women recruited from 6 urban health centres in Ahmedabad. The prevalence of anaemia was 69.8% by Sahli's method, 78.3% by HCS and 89.9% by clinical signs; there was no statistically significant difference between Sahli's method and HCS whereas there was between Sahlis method and clinical signs. The mean haemoglobin level by Sahli's method and HCS differed significantly. The sensitivity, specificity, positive predictive value and negative predictive value of HCS was 83.3%, 33.3%, 74.3% and 46.4% respectively and that of clinical signs was 91.1%, 12.8%, 70.7% and 38.5% respectively. Interobserver agreement for HCS was moderate (K = 0.43). Clinical signs are better than HCS for diagnosing anaemia. HCS can be used in the field provided assessors are adequately trained.

Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes.

PubMed

James, Robert F; Khattar, Nicolas K; Aljuboori, Zaid S; Page, Paul S; Shao, Elaine Y; Carter, Lacey M; Meyer, Kimberly S; Daniels, Michael W; Craycroft, John; Gaughen, John R; Chaudry, M Imran; Rai, Shesh N; Everhart, D Erik; Simard, J Marc

2018-05-11

OBJECTIVE Cognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls. METHODS A retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors. RESULTS No significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications. CONCLUSIONS This preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.

Psychosocial Comorbidities Related to Return to Work Rates Following Aneurysmal Subarachnoid Hemorrhage.

PubMed

Turi, Eleanor R; Conley, Yvette; Crago, Elizabeth; Sherwood, Paula; Poloyac, Samuel M; Ren, Dianxu; Stanfill, Ansley G

2018-05-21

Purpose Ability to return to work (RTW) after stroke has been shown to have positive psychosocial benefits on survivors. Although one-fifth of aneurysmal subarachnoid hemorrhage (aSAH) survivors suffer from poor psychosocial outcomes, the relationship between such outcomes and RTW post-stroke is not clear. This project explores the relationship between age, gender, race, marital status, anxiety and depression and RTW 3 and 12 months post-aSAH. Methods Demographic and clinical variables were collected from the electronic medical record at the time of aSAH admission. Anxiety and depression were assessed at 3 and 12 months post-aSAH using the State Trait Anxiety Inventory (STAI) and Beck's Depression Inventory-II (BDI-II) in 121 subjects. RTW for previously employed patients was dichotomized into yes/no at their 3 or 12 month follow-up appointment. Results Older age was significantly associated with failure to RTW at 3 and 12 months post-aSAH (p = 0.003 and 0.011, respectively). Female gender showed a trending but nonsignificant relationship with RTW at 12 months (p = 0.081). High scores of depression, State anxiety, and Trait anxiety all had significant associations with failure to RTW 12 months post-aSAH (0.007 ≤ p ≤ 0.048). At 3 months, there was a significant interaction between older age and high State or Trait anxiety with failure to RTW 12 months post-aSAH (p = 0.025, 0.042 respectively). Conclusions Patients who are older and suffer from poor psychological outcomes are at an increased risk of failing to RTW 1-year post-aSAH. Our interactive results give us information about which patients should be streamlined for therapy to target their psychosocial needs.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

PubMed

Hannon, M J; Behan, L A; O'Brien, M M; Tormey, W; Javadpour, M; Sherlock, M; Thompson, C J

2015-01-01

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients. © 2014 John Wiley & Sons

Mortality after hemorrhagic stroke: data from general practice (The Health Improvement Network).

PubMed

González-Pérez, Antonio; Gaist, David; Wallander, Mari-Ann; McFeat, Gillian; García-Rodríguez, Luis A

2013-08-06

To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87, 95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.

Restrictions and satisfaction with participation in patients who are ADL-independent after an aneurysmal subarachnoid hemorrhage.

PubMed

Huenges Wajer, Irene M C; Visser-Meily, Johanna M A; Greebe, Paut; Post, Marcel W M; Rinkel, Gabriel J E; van Zandvoort, Martine J E

2017-03-01

Most survivors of an aneurysmal subarachnoid hemorrhage (aSAH) are ADL-independent, but they often experience restrictions in (social) activities and, therefore, cannot regain their pre-morbid level of participation. In this study, participation restrictions and participation satisfaction experienced after aSAH were assessed. Moreover, possible predictors of participation after aSAH were examined to identify goals for rehabilitation. Participation restrictions experienced by a series of 67 patients visiting our SAH outpatient clinic were assessed as part of standard clinical care using the Participation Restrictions and Satisfaction sections of the Utrecht Scale for Evaluation of Rehabilitation Participation (USER-Participation) 6 months after aSAH. Cognitive impairments, cognitive and emotional complaints, and symptoms of depression and anxiety, assessed 10 weeks after aSAH, were examined as possible predictors of participation by means of linear regression analysis. Although patients were ADL-independent, 64% reported one or more participation restrictions and 60% were dissatisfied in one or more participation domains. Most commonly experienced restrictions concerned housekeeping, chores in and around the house, and physical exercise. Dissatisfaction was most often reported about outdoor activities, mobility, and work/housekeeping. The main predictors of participation restrictions as well as satisfaction with participation were cognitive complaints (subjective) (β = -.30, p = .03 and β = -.40, p = .002, respectively) and anxiety (β = .32, p = .02 and β = -.34, p = .007, respectively). Almost two-thirds of the ADL-independent patients experienced problems of participation 6 months after aSAH. Cognitive complaints (subjective) and anxiety symptoms showed the strongest association with participation restrictions and satisfaction. Cognitive rehabilitation and anxiety-reducing interventions may help to optimize rehabilitation and increase

First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model.

PubMed

Turkmenoglu, Osman N; Kanat, Ayhan; Yolas, Coskun; Aydin, Mehmet Dumlu; Ezirmik, Naci; Gundogdu, Cemal

2017-01-01

The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH ( n = 8), serum saline (SS) (SS; n = 6) and control ( n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. The mean alive neuron density of the L4DRG was 15420 ± 1240/mm 3 and degenerated neuron density was 1045 ± 260/mm 3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm 3 and 1365 ± 480/mm 3 in serum saline (SS), 9845 ± 1028/mm 3 and 4560 ± 1340/mm 3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm 3 in the control group and 1,030 ± 0,240 mm 3 in the SF group and 0,910 ± 0,170 mm 3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups ( P < 0.05). Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model

PubMed Central

Turkmenoglu, Osman N.; Kanat, Ayhan; Yolas, Coskun; Aydin, Mehmet Dumlu; Ezirmik, Naci; Gundogdu, Cemal

2017-01-01

Background: The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. Materials and Methods: This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), serum saline (SS) (SS; n = 6) and control (n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. Results: The mean alive neuron density of the L4DRG was 15420 ± 1240/mm3 and degenerated neuron density was 1045 ± 260/mm3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm3 and 1365 ± 480/mm3 in serum saline (SS), 9845 ± 1028/mm3 and 4560 ± 1340/mm3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm3 in the control group and 1,030 ± 0,240 mm3 in the SF group and 0,910 ± 0,170 mm3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies. PMID:28413527

The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage.

PubMed

Boyko, Matthew; Melamed, Israel; Gruenbaum, Benjamin Fredrick; Gruenbaum, Shaun Evan; Ohayon, Sharon; Leibowitz, Akiva; Brotfain, Evgeny; Shapira, Yoram; Zlotnik, Alexander

2012-07-01

Blood glutamate scavengers have been shown to effectively reduce blood glutamate concentrations and improve neurological outcome after traumatic brain injury and stroke in rats. This study investigates the efficacy of blood glutamate scavengers oxaloacetate and pyruvate in the treatment of subarachnoid hemorrhage (SAH) in rats. Isotonic saline, 250 mg/kg oxaloacetate, or 125 mg/kg pyruvate was injected intravenously in 60 rats, 60 minutes after induction of SAH at a rate of 0.1 ml/100 g/min for 30 minutes. There were 20 additional rats that were used as a sham-operated group. Blood samples were collected at baseline and 90 minutes after SAH. Neurological performance was assessed at 24 h after SAH. In half of the rats, glutamate concentrations in the cerebrospinal fluid were measured 24 h after SAH. For the remaining half, the blood brain barrier permeability in the frontal and parieto-occipital lobes was measured 48 h after SAH. Blood glutamate levels were reduced in rats treated with oxaloacetate or pyruvate at 90 minutes after SAH (p < 0.001). Cerebrospinal fluid glutamate was reduced in rats treated with pyruvate (p < 0.05). Neurological performance was significantly improved in rats treated with oxaloacetate (p < 0.05) or pyruvate (p < 0.01). The breakdown of the blood brain barrier was reduced in the frontal lobe in rats treated with pyruvate (p < 0.05) and in the parieto-occipital lobes in rats treated with either pyruvate (p < 0.01) or oxaloacetate (p < 0.01). This study demonstrates the effectiveness of blood glutamate scavengers oxaloacetate and pyruvate as a therapeutic neuroprotective strategy in a rat model of SAH.

Aspirin and Risk of Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

PubMed

Phan, Kevin; Moore, Justin M; Griessenauer, Christoph J; Ogilvy, Christopher S; Thomas, Ajith J

2017-05-01

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P =0.99). We found a significant association between short-term use of aspirin (<3 months) and the risk of aSAH (odds ratio, 1.61; 95% confidence interval, 1.20-2.18; P =0.002). No significant difference was found in terms of risk of aSAH for 3 to 12 months, 1 to 3 years, and >3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (<3 months) use of aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial. © 2017 American Heart Association, Inc.

From monitoring physiological functions to using psychological strategies. Nurses' view of caring for the aneurysmal subarachnoid haemorrhage patient.

PubMed

Hedlund, Mathilde; Ronne-Engstrom, Elisabeth; Ekselius, Lisa; Carlsson, Marianne

2008-02-01

The aims of this study were: (1) to describe nurses' views of the physical and supportive needs of patients who have suffered a subarachnoid haemorrhage (SAH), (2) to describe nurses' views of changes in social circumstances and (3) changes in the mental condition of patients after SAH. As patients with SAH are generally younger and predominantly female compared with other stroke groups they may have different needs of nursing support to facilitate adaptation. Caring for persons surviving stroke involves advanced nursing skills such as monitoring neurological functions in neurointensive care and providing physical care during rehabilitation. Explorative descriptive design. Semi-structured interviews were performed with 18 nurses in neurointensive and rehabilitation care. A qualitative latent content analysis was conducted. Nurses viewed patients' need for support as a process ranging from highly advanced technological care to 'softer' more emotional care. However, shortages in the communication between neurointesive and rehabilitation nurses regarding this support were acknowledged. Changes in social circumstances and mental conditions were viewed both as obstacles and advantages regarding return to everyday life. Nurses also viewed that the characteristics of the group with SAH was not particularly different from the group with other types of stroke. Support to patients with SAH is viewed as a process carried out by nurses at neurointensive care units and rehabilitation units. Shortages in communication, regarding this support, were acknowledged. Obstacles and advantages with respect to returning to everyday life could apply to any stroke group, which could make it more difficult for nurses to detect the specific needs of patients with SAH. The communication between neurointensive nurses and rehabilitation nurses regarding support to patients with SAH is not satisfactory. Occasionally the specific needs of patients with SAH are not recognized.

Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns.

PubMed

Guerra-Shinohara, Elvira M; Morita, Olga E; Peres, Sabrina; Pagliusi, Regina A; Sampaio Neto, Luiz F; D'Almeida, Vânia; Irazusta, Silvia P; Allen, Robert H; Stabler, Sally P

2004-11-01

Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.

Embolic Signals during Routine Transcranial Doppler Ultrasonography in Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Paschoal, Fernando Mendes; de Almeida Lins Ronconi, Karla; de Lima Oliveira, Marcelo; Nogueira, Ricardo de Carvalho; Paschoal, Eric Homero Albuquerque; Teixeira, Manoel Jacobsen; Figueiredo, Eberval Gadelha; Bor-Seng-Shu, Edson

2015-01-01

Introduction. Cerebral emboli may occur in subarachnoid hemorrhage (SAH) and intracranial aneurysm surgery. Although embolic signs (ES) have been reported in SAH, their origin remains unclear. The aim of this study was to report the detection of ES during routine TCD monitoring in patients with aneurysmal SAH. Methods. A total of 105 patients with aneurysmal SAH were submitted to TCD evaluation. Patients were monitored almost daily (5 times per week). In each monitoring session, one experienced operator performed TCD to detect or assess vasospasm and ES in arteries of the Willis polygon. Results. Four patients out of a total of 105 patients with aneurysmal SAH were found to present spontaneous cerebral embolization during routine TCD monitoring. The average age of the 4 patients (mean ± standard deviation) was 59.5 ± 8.34 years (range 49–68 ys); female patients predominated representing 75% (3/4) of subjects. Conclusion. Although detection of ES was relatively rare in this study, rates of emboli occurrence may be higher under systematic monitoring. The detection of ES after SAH surgery reinforces the need to study the role of embolus in this condition and may be an indicator for prophylactic antithrombotic treatment. PMID:25893190

The impact of nonsteroidal anti-inflammatory drugs on inflammatory response after aneurysmal subarachnoid hemorrhage.

PubMed

Muroi, Carl; Hugelshofer, Michael; Seule, Martin; Keller, Emanuela

2014-04-01

The degree of inflammatory response with cytokine release is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). Previously, we reported on an association between systemic IL-6 levels and clinical outcome in patients with aneurysmal SAH. The intention was to assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the inflammatory response after SAH. Our method involved exploratory analysis of data and samples collected within a previous study. In 138 patients with SAH, systemic interleukin (IL-6) and c-reactive protein (CRP) were measured daily up to day 14 after SAH. The correlations among the cumulatively applied amount of NSAIDs, inflammatory parameters, and clinical outcome were calculated. An inverse correlation between cumulatively applied NSAIDs and both IL-6 and CRP levels was found (r = -0.437, p < 0.001 and r = -0.369, p < 0.001 respectively). Multivariable linear regression analysis showed a cumulative amount of NSAIDs to be independently predictive for systemic IL-6 and CRP levels. The cumulative amount of NSAIDs reduced the odds for unfavorable outcome, defined as Glasgow outcome scale 1-3. The results indicate a potential beneficial effect of NSAIDs in patients with SAH in terms of ameliorating inflammatory response, which might have an impact on outcome.

A Twelve-Week Moderate Exercise Programme Improved Symptoms of Depression, Insomnia, and Verbal Learning in Post-Aneurysmal Subarachnoid Haemorrhage Patients: A Comparison with Meningioma Patients and Healthy Controls.

PubMed

Colledge, Flora; Brand, Serge; Pühse, Uwe; Holsboer-Trachsler, Edith; Zimmerer, Stefan; Schleith, Ramona; Gerber, Markus

2018-04-25

Deficits in psychological functioning, cognitive functioning, and sleep are frequently experienced by individuals who have survived aneurysmal subarachnoid haemorrhage (aSAH). Exercise has been shown to improve these domains; to date, it has never been explored in patients following aSAH. The aim of this exploratory study is to compare the effects of an exercise programme in this population with another patient group, and a group of healthy controls. The present study explored the effects of 12 weeks of moderate aerobic exercise training on 15 aSAH patients, 16 meningioma patients, and 17 healthy controls. Data on symptoms of depression, hypochondria, perceived stress, satisfaction with life, verbal learning and memory, and subjective and objective sleep, were gathered at baseline, following intervention, and at 6-month follow-up. aSAH patients and meningioma patients had decreased symptoms of depression and insomnia at follow-up. While perceived stress decreased in the meningioma group, in aSAH patients it increased. Total learning performance increased in all three groups. An exercise programme had a positive effect on symptoms of depression, insomnia, and verbal learning in patients following aSAH. No positive changes in other domains were observed. This may be due to the cautious approach taken with regard to exercise intensity. © 2018 S. Karger AG, Basel.

The CHESS score: a simple tool for early prediction of shunt dependency after aneurysmal subarachnoid hemorrhage.

PubMed

Jabbarli, R; Bohrer, A-M; Pierscianek, D; Müller, D; Wrede, K H; Dammann, P; El Hindy, N; Özkan, N; Sure, U; Müller, O

2016-05-01

Acute hydrocephalus is an early and common complication of aneurysmal subarachnoid hemorrhage (SAH). However, considerably fewer patients develop chronic hydrocephalus requiring shunt placement. Our aim was to develop a risk score for early identification of patients with shunt dependency after SAH. Two hundred and forty-two SAH individuals who were treated in our institution between January 2008 and December 2013 and survived the initial impact were retrospectively analyzed. Clinical parameters within 72 h after the ictus were correlated with shunt dependency. Independent predictors were summarized into a new risk score which was validated in a subsequent SAH cohort treated between January and December 2014. Seventy-five patients (31%) underwent shunt placement. Of 23 evaluated variables, only the following five showed independent associations with shunt dependency and were subsequently used to establish the Chronic Hydrocephalus Ensuing from SAH Score (CHESS, 0-8 points): Hunt and Hess grade ≥IV (1 point), location of the ruptured aneurysm in the posterior circulation (1 point), acute hydrocephalus (4 points), the presence of intraventricular hemorrhage (1 point) and early cerebral infarction on follow-up computed tomography scan (1 point). The CHESS showed strong correlation with shunt dependency (P = 0.0007) and could be successfully validated in both internal SAH cohorts tested. Patients scoring ≥6 CHESS points had significantly higher risk of shunt dependency (P < 0.0001) than other patients. The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies. © 2016 EAN.

Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

PubMed Central

Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H.; Chen, Yujie; Feng, Hua

2016-01-01

Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia. PMID:27698742

Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage: a series of 22 cases.

PubMed

Boukobza, Monique; Crassard, Isabelle; Bousser, Marie-Germaine; Chabriat, Hugues

2016-01-01

The main objectives of the present study are to assess the incidence of cerebral venous thrombosis (CVT) presenting as isolated subarachnoid hemorrhage (SAH) and to determine the occurrence of cortical venous thrombosis (CoVT). Among 332 patients with CVT, investigated with the same CT and MR standardized protocol, 33 (10 %) presented with SAH, associated in 11 cases with hemorrhagic infarct or intracerebral hemorrhage. This study is based on 22 cases of CVT presenting as SAH in the absence of hemorrhagic brain lesion. Diagnosis of sinus thrombosis was established on T2* and magnetic resonance venography and that of CoVT on T2* sequence. Diagnostic of SAH was based on fluid-attenuated inversion recovery (FLAIR) sequence. CVT involved lateral sinus in 18 patients, superior sagittal sinus in 16, and straight sinus in 1. Cortical veins were involved in all patients, in continuity with dural sinus thrombosis when present. SAH was circumscribed to few sulci in all cases and mainly localized at the convexity (21 cases). CoVT implied different areas on the same side in four patients and was bilateral in seven. There was no perimesencephalic or basal cisterns hemorrhage. Cortical swelling was present in 12 cases, associated with localized edema. All patients except one had a favorable outcome. This report shows that the incidence of CVT presenting as isolated SAH is evaluated to 6.4 % and that SAH is, in all cases, in the vicinity of CoVT and when dural thrombosis is present in continuity with it.

Calcitonin-gene related peptide and cerebral vasospasm.

PubMed

Schebesch, Karl-Michael; Herbst, Andreas; Bele, Sylvia; Schödel, Petra; Brawanski, Alexander; Stoerr, Eva-Maria; Lohmeier, Annette; Kagerbauer, Simone Maria; Martin, Jan; Proescholdt, Martin

2013-04-01

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Marriage and Partnership Integrity After Aneurysmal Subarachnoid Hemorrhage: Small Alterations in Neurologic Status Matter Most.

PubMed

Schöni, Daniel; Lauber, Lara; Fung, Christian; Goldberg, Johannes; Müri, René; Raabe, Andreas; Nyffeler, Thomas; Beck, Jürgen

2018-05-01

Common sequelae of subarachnoid hemorrhage (SAH) include somatic and/or cognitive impairment. This can cause emotional stress, social tensions, and difficulties in relationships. To test our hypothesis that more severe somatic and cognitive impairments increased the likelihood of disruption of a relationship after SAH, we assessed the integrity of marriage or partnership status in a well-evaluated subset of SAH patients. Our sample comprised 50 SAH patients who were discharged to a neurologic, in-house rehabilitation center between 2005 and 2010. Deficits on admission to the rehabilitation center were divided into 18 categories and grouped into minor and major somatic deficits, as well as cognitive deficits. Clinical outcome scores, marital/partnership status, and duration of partnership before ictus were recorded. A follow-up questionnaire after 4.3 (2012) and 8.8 (2017) years was used to assess changes in marital/partnership status. Possible predictor parameters were estimated and included in a stepdown regression analysis. In 2012, after a mean follow-up of 4.3 years, 8 of the 50 SAH patients were divorced or separated, whereas after 8.8 years only 1 additional relationship had ended. In our regression model analysis, a "short duration of relationship" before SAH and the presence of a "few minor somatic deficits" were associated with a higher likelihood of divorce or separation in the near future and remained unchanged at long-term follow-up. Contrary to our hypothesis, neither the presence of severe somatic or cognitive deficits nor clinical evaluation scores reliably predicted divorce or separation after SAH. Copyright © 2018 Elsevier Inc. All rights reserved.

Factors Associated with Acute and Chronic Hydrocephalus in Nonaneurysmal Subarachnoid Hemorrhage.

PubMed

Kang, Peter; Raya, Amanda; Zipfel, Gregory J; Dhar, Rajat

2016-02-01

Hydrocephalus requiring external ventricular drain (EVD) or shunt placement commonly complicates aneurysmal subarachnoid hemorrhage (SAH), but its frequency is not as well known for nonaneurysmal SAH (NA-SAH). Those with diffuse bleeding may have greater risk of hydrocephalus compared to those with a perimesencephalic pattern. We evaluated the frequency of hydrocephalus in NA-SAH and whether imaging factors could predict the need for EVD and shunting. We collected admission clinical and imaging variables for 105 NA-SAH patients, including bicaudate index (BI), Hijdra sum score (HSS), intraventricular hemorrhage (IVH) score, modified Fisher scale (mFS), and bleeding pattern. Hydrocephalus was categorized as acute (need for EVD) or chronic (shunt). We applied logistic regression to determine whether hydrocephalus risk was independently related to bleeding pattern or mediated through blood volume or ventriculomegaly. Acute hydrocephalus was seen in 26 (25%) patients but was more common with diffuse (15/28, 54%) versus perimesencephalic (10/59, 17%, p < 0.001) bleeding. Patients developing acute hydrocephalus had worse clinical grade and higher BI, HSS, and IVH scores. Adjusting the relationship between hydrocephalus and diffuse bleeding for HSS (but not BI) nullified this association. Nine (35%) patients requiring EVD eventually required shunting for chronic hydrocephalus, which was associated with greater blood burden but not poor clinical grade. Acute hydrocephalus occurs in one-quarter of NA-SAH patients. The greater risk in diffuse bleeding appears to be mediated by greater cisternal blood volume but not by greater ventriculomegaly. Imaging characteristics may aid in anticipatory management of hydrocephalus in NA-SAH.

Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study.

PubMed

Yolas, Coskun; Kanat, Ayhan; Aydin, Mehmet Dumlu; Altas, Ender; Kanat, Ilyas Ferit; Kazdal, Hizir; Duman, Aslihan; Gundogdu, Betul; Gursan, Nesrin

2016-02-01

Cardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH. Twenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed. Increased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed. We found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of trends and abrupt changes of the South Asia high from 1979 to 2014 in reanalysis and radiosonde datasets

NASA Astrophysics Data System (ADS)

Shi, Chunhua; Huang, Ying; Guo, Dong; Zhou, Shunwu; Hu, Kaixi; Liu, Yu

2018-05-01

The South Asian High (SAH) has an important influence on atmospheric circulation and the Asian climate in summer. However, current comparative analyses of the SAH are mostly between reanalysis datasets and there is a lack of sounding data. We therefore compared the climatology, trends and abrupt changes in the SAH in the Japanese 55-year Reanalysis (JRA-55) dataset, the National Centers for Environmental Prediction Climate Forecast System Reanalysis (NCEP-CFSR) dataset, the European Center for Medium-Range Weather Forecasts Reanalysis Interim (ERA-interim) dataset and radiosonde data from China using linear analysis and a sliding t-test. The trends in geopotential height in the control area of the SAH were positive in the JRA-55, NCEP-CFSR and ERA-interim datasets, but negative in the radiosonde data in the time period 1979-2014. The negative trends for the SAH were significant at the 90% confidence level in the radiosonde data from May to September. The positive trends in the NCEP-CFSR dataset were significant at the 90% confidence level in May, July, August and September, but the positive trends in the JRA-55 and ERA-Interim were only significant at the 90% confidence level in September. The reasons for the differences in the trends of the SAH between the radiosonde data and the three reanalysis datasets in the time period 1979-2014 were updates to the sounding systems, changes in instrumentation and improvements in the radiation correction method for calculations around the year 2000. We therefore analyzed the trends in the two time periods of 1979-2000 and 2001-2014 separately. From 1979 to 2000, the negative SAH trends in the radiosonde data mainly agreed with the negative trends in the NCEP-CFSR dataset, but were in contrast with the positive trends in the JRA-55 and ERA-Interim datasets. In 2001-2014, however, the trends in the SAH were positive in all four datasets and most of the trends in the radiosonde and NCEP-CFSR datasets were significant. It is

Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal subarachnoid hemorrhage: evidence from accelerometer-based activity monitoring.

PubMed

Harmsen, Wouter J; Ribbers, Gerard M; Heijenbrok-Kal, Majanka H; Bussmann, Johannes B J; Sneekes, Emiel M; Khajeh, Ladbon; van Kooten, Fop; Neggers, Sebastian J C M M; van den Berg-Emons, Rita J

2017-11-23

Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life-threatening stroke. Because survivors may be at increased risk for inactive and sedentary lifestyles, this study evaluates physical activity (PA) and sedentary behavior (SB) in the chronic phase after a-SAH. PA and SB were objectively measured at six months post a-SAH with an accelerometer-based activity monitor, with the aim to cover three consecutive weekdays. Total time spent in PA (comprising walking, cycling, running and non-cyclic movement) and SB (comprising sitting and lying) was determined. Also, in-depth analyses were performed to determine the accumulation and distribution of PA and SB throughout the day. Binary time series were created to determine the mean bout length and the fragmentation index. Measures of PA and SB in persons with a-SAH were compared to those in sex- and age-matched healthy controls. The 51 participants comprised 33 persons with a-SAH and 18 controls. None of the participants had signs of paresis or spasticity. Persons with a-SAH spent 105 min/24 h being physically active, which was 35 min/24 h less than healthy controls (p = 0.005). For PA, compared with healthy controls, the mean bout length was shorter in those with a-SAH (12.0 vs. 13.5 s, p = 0.006) and the fragmentation index was higher (0.053 vs. 0.041, p < 0.001). Total sedentary time during waking hours showed no significant difference between groups (514 min vs. 474 min, p = 0.291). For SB, the mean bout length was longer in persons with a-SAH (122.3 vs. 80.5 s, p = 0.024), whereas there was no difference in fragmentation index between groups (0.0032 vs 0.0036, p = 0.396). Persons with a-SAH are less physically active, they break PA time into shorter periods, and SB periods last longer compared to healthy controls. Since inactive lifestyles and prolonged uninterrupted periods of SB are independent risk factors for poor cardiovascular health, interventions seem necessary and should target both

Haemoglobin scavenging after subarachnoid haemorrhage.

PubMed

Durnford, A; Dunbar, J; Galea, J; Bulters, D; Nicoll, J A R; Boche, D; Galea, I

2015-01-01

Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.

Cyclosporine A alleviated matrix metalloproteinase 9 associated blood-brain barrier disruption after subarachnoid hemorrhage in mice.

PubMed

Pan, Pengyu; Zhang, Xuan; Li, Qiang; Zhao, Hengli; Qu, Jie; Zhang, John H; Liu, Xin; Feng, Hua; Chen, Yujie

2017-05-10

The aim of this study was to investigate whether Cyclosporine A (CsA) attenuates early brain injury by alleviating matrix metalloproteinase 9 (MMP-9) associated blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in C57B6J mice. Dosages of 5mg/kg, 10mg/kg and 15mg/kg CsA were evaluated for effects on neurological score, brain water content, Evans blue extravasation and fluorescence, P-p65, MMP-9 and BBB components' alterations after SAH. We found that CsA 15mg/kg is effective in attenuating BBB disruption, lowering edema, and improving neurological outcomes. In addition, Collagen IV, ZO-1, Occludin and Claudin 5 expressions in ipsilateral/left hemisphere were downregulated after SAH, but increased after CsA treatment. Our results suggest that CsA exert a neuroprotective role in SAH pathophysiology, possibly by alleviating MMP-9 associated BBB disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetic Resonance Imaging in Aneurysmal Subarachnoid Hemorrhage: Current Evidence and Future Directions.

PubMed

Nelson, Sarah E; Sair, Haris I; Stevens, Robert D

2018-04-09

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with an unacceptably high mortality and chronic disability in survivors, underscoring a need to validate new approaches for treatment and prognosis. The use of advanced imaging, magnetic resonance imaging (MRI) in particular, could help address this gap given its versatile capacity to quantitatively evaluate and map changes in brain anatomy, physiology and functional activation. Yet there is uncertainty about the real value of brain MRI in the clinical setting of aSAH. In this review, we discuss current and emerging MRI research in aSAH. PubMed was searched from inception to June 2017, and additional studies were then chosen on the basis of relevance to the topics covered in this review. Available studies suggest that brain MRI is a feasible, safe, and valuable testing modality. MRI detects brain abnormalities associated with neurologic examination, outcomes, and aneurysm treatment and thus has the potential to increase knowledge of aSAH pathophysiology as well as to guide management and outcome prediction. Newer pulse sequences have the potential to reveal structural and physiological changes that could also improve management of aSAH. Research is needed to confirm the value of MRI-based biomarkers in clinical practice and as endpoints in clinical trials, with the goal of improving outcome for patients with aSAH.

Milrinone via lumbar subarachnoid catheter for vasospasm after aneurysmal subarachnoid hemorrhage.

PubMed

Sadamasa, Nobutake; Yoshida, Kazumichi; Narumi, Osamu; Chin, Masaki; Yamagata, Sen

2014-12-01

Delayed ischemic neurological deficit (DIND) due to symptomatic vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to elucidate the safety and feasibility of intrathecal milrinone infusion via lumber subarachnoid catheter for prevention of DIND after aSAH. We diagnosed 425 consecutive patients with aSAH who received clipping or coil embolization within 48 h after arrival. Patients with the evidence of vasospasm on CT angiography (CTA) received the milrinone therapy via lumbar subarachnoid catheter. DIND, delayed cerebral infarction (DCI), and modified Rankin scale at 3 months after SAH were used for the assessment of outcome. Of 425 patients, 170 patients (40.0 %) with CTA-proven vasospasm received the milrinone therapy. DIND was observed in 68 patients (16.0 %), DCI in 30 patients (7.1 %), and the overall mortality was 7.2 %. In patients with WFNS grade IV and V aSAH, 26 out of 145 patients (17.9 %) were presented with DIND, 12 (8.3 %) with DCI, and the mortality was 16.0 %. No major complication related to the milrinone injection was observed. Intrathecal milrinone injection via lumbar catheter was safe and feasible, and further randomized prospective studies are needed to confirm the effectiveness of this regimen in the patients with SAH.

Retrospective review of previous minor leak before major subarachnoid hemorrhage diagnosed by MRI as a predictor of occurrence of symptomatic delayed cerebral ischemia.

PubMed

Oda, Shinri; Shimoda, Masami; Hirayama, Akihiro; Imai, Masaaki; Komatsu, Fuminari; Shigematsu, Hideaki; Nishiyama, Jun; Hotta, Kazuko; Matsumae, Mitsunori

2018-02-01

OBJECTIVE This study attempted to determine whether a previous minor leak correlated with the occurrence of symptomatic delayed cerebral ischemia (sDCI). METHODS The authors retrospectively evaluated sDCI-related clinical features and findings from MRI, including T1-weighted imaging (T1WI)-FLAIR mismatch at the time of admission, in 151 patients admitted with subarachnoid hemorrhage (SAH) within 48 hours of ictus. RESULTS The overall incidence of sDCI was 23% (35 of 151 patients). In all subjects, multivariate analysis revealed that World Federation of Neurosurgical Societies Grades II-V, age 70 years or older, presence of rebleeding after admission, a previous minor leak before the major SAH attack as diagnosed by T1WI-FLAIR mismatch, acute infarction on diffusion-weighted imaging, and CT SAH score were significantly associated with occurrence of sDCI. In patients with no previous minor leak before major SAH as diagnosed by T1WI-FLAIR mismatch, the incidence of sDCI was only 7% (7 of 97 patients). CONCLUSIONS A previous minor leak before major SAH as diagnosed by T1WI-FLAIR mismatch represents an important sDCI-related factor. When the analysis was restricted to patients with true acute SAH without a previous minor leak diagnosed by T1WI-FLAIR mismatch, the incidence of sDCI was extremely low.

Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

PubMed

Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin

2015-12-10

Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical prevalence and outcome impact of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a systematic review with meta-analysis.

PubMed

Robba, Chiara; Bacigaluppi, Susanna; Bragazzi, Nicola; Lavinio, Andrea; Gurnell, Mark; Bilotta, Federico; Menon, David K

2016-10-01

Pituitary dysfunction is reported to be a common complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this meta-analysis is to analyze the literature on clinical prevalence, risk factors and outcome impact of pituitary dysfunction after aSAH, and to assess the possible need for pituitary screening in aSAH patients. We performed a systematic review with meta-analysis based on a comprehensive search of four databases (PubMed/MEDLINE, ISI/Web of Science, Scopus and Google Scholar). A total of 20 papers met criteria for inclusion. The prevalence of pituitary dysfunction in the acute phase (within the first 6 months after aSAH) was 49.30 % (95 % CI 41.6-56.9), decreasing in the chronic phase (after 6 months from aSAH) to 25.6 % (95 % CI 18.0-35.1). Abnormalities in basal hormonal levels were more frequent when compared to induction tests, and the prevalence of a single pituitary hormone dysregulation was more frequent than multiple pituitary hormone dysregulation. Increasing age was associated with a lower prevalence of endocrine dysfunction in the acute phase, and surgical treatment of the aneurysm (clipping) was related to a higher prevalence of single hormone dysfunction. The prevalence of pituitary dysfunction did not correlate with the outcome of the patient. Neuroendocrine dysfunction is common after aSAH, but these abnormalities have not been shown to consistently impact outcome in the data available. There is a need for well-designed prospective studies to more precisely assess the incidence, clinical course, and outcome impact of pituitary dysfunction after aSAH.

Time-courses of plasma IL-6 and HMGB-1 reflect initial severity of clinical presentation but do not predict poor neurologic outcome following subarachnoid hemorrhage.

PubMed

Kiiski, Heikki; Långsjö, Jaakko; Tenhunen, Jyrki; Ala-Peijari, Marika; Huhtala, Heini; Hämäläinen, Mari; Moilanen, Eeva; Öhman, Juha; Peltola, Jukka

2017-03-01

Patients with aneurysmal subarachnoid hemorrhage (aSAH) experience high mortality and morbidity. Neuroinflammation causes brain damage expansion after aSAH. Due to the complexity of the inflammatory response multiple biomarkers are needed to evaluate its' progression. We studied inflammatory process after aSAH by measuring two inflammatory biomarkers, interleukin-6 (IL-6) and high-mobility group box 1 (HMGB1) at simultaneous time-points after aSAH. In this prospective population-based study, IL-6 and HMGB1 were measured in aSAH patients (n = 47) for up to five days. Plasma concentrations of IL-6 and HMGB1 were measured at 0, 12 and 24 h after hospital admission, and thereafter daily for up to five days or until the patient was transferred from the intensive care unit (ICU). The patients' neurological outcomes were evaluated with the modified Rankin Scale at six months after aSAH. A high IL-6 level during the first day after aSAH was associated with a severe initial clinical presentation (p = 0.002) and infection during follow-up (p = 0.031). The HMGB1 level did not associate with these parameters. There was no correlation between IL-6 and HMGB1 levels at any time point during the follow-up. The concentrations of IL-6 and HMGB1 were not associated with neurological outcome. High initial IL-6 values seem to reflect the intensity of the inflammatory response but not the brain damage per se. An early inflammatory response might even be beneficial since although elevated IL-6 levels were observed in patients with a more severe initial clinical presentation, they were not associated with neurological outcome. The lack of correlation between IL-6 and HMGB1 questions the role of macrophages in the process of the secretion of these inflammatory markers after aSAH, instead pointing to the activation of alternative pro-inflammatory pathways.

Predicting symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage with an artificial neural network in a pediatric population.

PubMed

Skoch, Jesse; Tahir, Rizwan; Abruzzo, Todd; Taylor, John M; Zuccarello, Mario; Vadivelu, Sudhakar

2017-12-01

Artificial neural networks (ANN) are increasingly applied to complex medical problem solving algorithms because their outcome prediction performance is superior to existing multiple regression models. ANN can successfully identify symptomatic cerebral vasospasm (SCV) in adults presenting after aneurysmal subarachnoid hemorrhage (aSAH). Although SCV is unusual in children with aSAH, the clinical consequences are severe. Consequently, reliable tools to predict patients at greatest risk for SCV may have significant value. We applied ANN modeling to a consecutive cohort of pediatric aSAH cases to assess its ability to predict SCV. A retrospective chart review was conducted to identify patients < 21 years of age who presented with spontaneously ruptured, non-traumatic, non-mycotic, non-flow-related intracranial arterial aneurysms to our institution between January 2002 and January 2015. Demographics, clinical, radiographic, and outcome data were analyzed using an adapted ANN model using learned value nodes from the adult aneurysmal SAH dataset previously reported. The strength of the ANN prediction was measured between - 1 and 1 with - 1 representing no likelihood of SCV and 1 representing high likelihood of SCV. Sixteen patients met study inclusion criteria. The median age for aSAH patients was 15 years. Ten underwent surgical clipping and 6 underwent endovascular coiling for definitive treatment. One patient experienced SCV and 15 did not. The ANN applied here was able to accurately predict all 16 outcomes. The mean strength of prediction for those who did not exhibit SCV was - 0.86. The strength for the one patient who did exhibit SCV was 0.93. Adult-derived aneurysmal SAH value nodes can be applied to a simple AAN model to accurately predict SCV in children presenting with aSAH. Further work is needed to determine if ANN models can prospectively predict SCV in the pediatric aSAH population in toto; adapted to include mycotic, traumatic, and flow

Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide.

PubMed

Poggi, Andreina; Rossi, Cosmo; Casella, Nicola; Bruno, Cristiana; Sturiale, Luisella; Dossi, Carla; Naggi, Annamaria

2002-08-01

Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4

Designated Stroke Center Status and Hospital Characteristics as Predictors of In-Hospital Mortality among Hemorrhagic Stroke Patients in New York, 2008-2012.

PubMed

Gatollari, Hajere J; Colello, Anna; Eisenberg, Bonnie; Brissette, Ian; Luna, Jorge; Elkind, Mitchell S V; Willey, Joshua Z

2017-01-01

Although designated stroke centers (DSCs) improve the quality of care and clinical outcomes for ischemic stroke patients, less is known about the benefits of DSCs for patients with intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Compared to non-DSCs, hospitals with the DSC status have lower in-hospital mortality rates for hemorrhagic stroke patients. We believed these effects would sustain over a period of time after adjusting for hospital-level characteristics, including hospital size, urban location, and teaching status. We evaluated ICH (International Classification of Diseases, Ninth Revision; ICD-9: 431) and SAH (ICD-9: 430) hospitalizations documented in the 2008-2012 New York State Department of Health Statewide Planning and Research Cooperative System inpatient sample database. Generalized estimating equation logistic regression was used to evaluate the association between DSC status and in-hospital mortality. We calculated ORs and 95% CIs adjusted for clustering of patients within facilities, other hospital characteristics, and individual level characteristics. Planned secondary analyses explored other hospital characteristics associated with in-hospital mortality. In 6,352 ICH and 3,369 SAH patients in the study sample, in-hospital mortality was higher among those with ICH compared to SAH (23.7 vs. 18.5%). Unadjusted analyses revealed that DSC status was related with reduced mortality for both ICH (OR 0.7, 95% CI 0.5-0.8) and SAH patients (OR 0.4, 95% CI 0.3-0.7). DSC remained a significant predictor of lower in-hospital mortality for SAH patients (OR 0.6, 95% CI 0.3-0.9) but not for ICH patients (OR 0.8, 95% CI 0.6-1.0) after adjusting for patient demographic characteristics, comorbidities, hospital size, teaching status and location. Admission to a DSC was independently associated with reduced in-hospital mortality for SAH patients but not for those with ICH. Other patient and hospital characteristics may explain the benefits of DSC

Evaluation of the success rate of cone beam computed tomography in determining the location and direction of screw access holes in cement-retained implant-supported prostheses: An in vitro study.

PubMed

Neshandar Asli, Hamid; Dalili Kajan, Zahra; Gholizade, Fatemeh

2018-02-21

Cement-retained implant-supported restorations have advantages over screw-retained restorations but are difficult to retrieve. Identifying the approximate location of the screw access hole (SAH) may reduce damage to the prosthesis. The purpose of this in vitro study was to evaluate the ability of cone beam computed tomography (CBCT) imaging to determine the location and direction of SAHs in cement-retained implant prostheses. Five clear acrylic resin casts were made based on a mandibular model. Several implant osteotomies (n=30) were created on the models with surgical burs, and crowns were made using the standard laboratory method with a transfer coping and the closed tray impression technique. CBCT images from the acrylic resin casts were evaluated by a maxillofacial radiologist who was blind to the locations and angles of the osteotomies. The locations of the access holes were determined on multiplanar reconstruction images and transferred to the clinical crown surface as defined points. Based on cross-sectional images, the predicted angle of the access hole was provided to a prosthodontist who was requested to pierce the crown at the proposed location in the specified direction. If the location and/or direction of the access hole were found, the process was considered successful, as the crown could then be removed from the implant abutment through the SAH. The success rate in the detection of the location and direction of the SAH was calculated, and chi-square and Fisher exact tests were applied for data analysis (α=.05). According to the results of this study, the success rate of CBCT to define the location of SAHs was 83.3% and 80% to determine the direction. No significant differences were found among the different dental groups in determination of the location (P=.79) or the direction (P=.53) of the SAHs. Most of the failures in determining the location and direction of the access hole in the buccolingual and mesiodistal directions were in the buccal and

Aneurysmal subarachnoid hemorrhage lead to systemic upregulation of IL-23/IL-17 inflammatory axis.

PubMed

Chaudhry, Shafqat Rasul; Güresir, Erdem; Vatter, Hartmut; Kinfe, Thomas M; Dietrich, Dirk; Lamprecht, Alf; Muhammad, Sajjad

2017-09-01

IL-23 and IL-17 are pro-inflammatory cytokines. IL-23 is secreted by activated macrophages and dendritic cells, while IL-17 by Th17 cells. Serum IL-23 and IL-17 are known to be elevated in numerous inflammatory diseases including neurodegenerative diseases. The role of serum IL-23 and IL-17 in aneurysmal subarachnoid hemorrhage (aSAH) has still not been investigated. The present work investigates the serum IL-23 and IL-17 levels and their association with post hemorrhagic complications and clinical outcome in patients with aSAH. In this study, 80 patients with aSAH (Hunt and Hess grade I-V) were prospectively recruited. We enrolled 24 control patients with lumbar spinal stenosis. Peripheral venous blood was withdrawn from controls and from aSAH patients at day 1 and day 7, allowed to clot and centrifuged to obtain serum. Enzyme linked immunoassay kits were employed to quantify the serum levels of IL-23 and IL-17 by applying 50µL of serum samples. Post hemorrhagic complications and clinical outcome were documented prospectively from patient's hospital record. Serum IL-23 and IL-17 levels were significantly elevated in aSAH patients at day 1 and day 7 (n=80) as compared to control patients (n=24). Further analysis after dichotomy of patients who suffered from post hemorrhagic complications including cerebral vasospasm, chronic hydrocephalus, seizures, cerebral ischemia, delayed neurological deficits showed differential correlations with different post hemorrhagic complications (Table 1). Serum IL-23 and IL-17 levels did not correlate with clinical outcome. Serum IL-23 and IL-17 levels were elevated in patients with aSAH showing upregulation of IL-23/IL-17 inflammatory axis after aSAH. Serum IL-23 and IL-17 showed differential correlations with post hemorrhagic complications and no correlation with clinical outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice.

PubMed

Schallner, Nils; Lieberum, Judith-Lisa; Gallo, David; LeBlanc, Robert H; Fuller, Patrick M; Hanafy, Khalid A; Otterbein, Leo E

2017-09-01

Subarachnoid hemorrhage (SAH) is associated with a temporal pattern of stroke incidence. We hypothesized that natural oscillations in gene expression controlling circadian rhythm affect the severity of neuronal injury. We moreover predict that heme oxygenase-1 (HO-1/ Hmox1 ) and its product carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection. Murine SAH model was used where blood was injected at various time points of the circadian cycle. Readouts included circadian clock gene expression, locomotor activity, vasospasm, neuroinflammatory markers, and apoptosis. In addition, cerebrospinal fluid and peripheral blood leukocytes from SAH patients and controls were analyzed for clock gene expression. Significant elevations in the clock genes Per-1 , Per-2 , and NPAS-2 were observed in the hippocampus, cortex, and suprachiasmatic nucleus in mice subjected to SAH at zeitgeber time (ZT) 12 when compared with ZT2. Clock gene expression amplitude correlated with basal expression of HO-1, which was also significantly greater at ZT12. SAH animals showed a significant reduction in cerebral vasospasm, neuronal apoptosis, and microglial activation at ZT12 compared with ZT2. In animals with myeloid-specific HO-1 deletion ( Lyz-Cre-Hmox1 fl/fl ), Per-1, Per-2 , and NPAS-2 expression was reduced in the suprachiasmatic nucleus, which correlated with increased injury. Treatment with low-dose CO rescued Lyz-Cre-Hmox1 fl/fl mice, restored Per-1, Per-2 , and NPAS-2 expression, and reduced neuronal apoptosis. Clock gene expression regulates, in part, the severity of SAH and requires myeloid HO-1 activity to clear the erythrocyte burden and inhibit neuronal apoptosis. Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH. © 2017 American Heart Association, Inc.

The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage.

PubMed

Schebesch, Karl-Michael; Brawanski, Alexander; Kagerbauer, Simone Maria; Martin, Jan; Bele, Sylvia; Herbst, Andreas; Feigl, Günther; Stoerr, Eva-Maria; Lohmeier, Anette; Proescholdt, Martin

2011-08-01

Neuropeptide Y (NPY), a highly potent vasoconstrictive neuropeptide, is widely expressed in the human brain, regulating vessel diameter and cerebral blood flow. Earlier studies focusing on the possible role of NPY in the context of aneurismal subarachnoid hemorrhage (SAH) and vasospasm have produced conflicting results. However, despite extensive research efforts, the pathophysiological mechanisms underlying the SAH-related vasospasm and delayed cerebral ischemia (DCI) have not been clarified. We, therefore, attempted to investigate the role of NPY in SAH-induced vasospasm in a larger, well documented patient population utilizing modern analytical tools. We focused on the release of the potent vasoconstrictor NPY in cerebrospinal fluid (CSF) and blood, and its correlation to vasospasm and stroke in the early clinical stage. Thirty-seven patients with SAH and a control group consisting of 29 patients were included. Eighteen patients developed stroke, 21 patients met the Doppler sonographical criteria for vasospasm. Twenty-nine patients had aneurysms of the anterior circulation and four patients of the posterior circulation. All patients had ventricular drainage inserted and an arterial catheter. Blood and CSF were drawn daily for NPY analysis during a 10-day interval. The levels of NPY in CSF and plasma were significantly higher after SAH than in the control group (p = 0.001). The vasospasm group showed NPY levels in CSF which continuously ranged above the NPY levels of the non-vasospasm group (p = 0.001). Patients with stroke caused by vasospasm had significantly higher levels of NPY (p = 0.001). NPY is released excessively into blood and CSF following SAH. Patients with cerebral infarction caused by vasospasm had significantly higher levels of NPY. Our results indicate a certain role for NPY in the pathophysiology of vasospasm due to SAH and justify further studies in this area of research.

Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable.

PubMed

Broderick, Joseph P; Viscoli, Catherine M; Brott, Thomas; Kernan, Walter N; Brass, Lawrence M; Feldmann, Edward; Morgenstern, Lewis B; Wilterdink, Janet Lee; Horwitz, Ralph I

2003-06-01

To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

PubMed

Ehlert, Angelika; Schmidt, Christoph; Wölfer, Johannes; Manthei, Gerd; Jacobs, Andreas H; Brüning, Roland; Heindel, Walter; Ringelstein, E Bernd; Stummer, Walter; Pluta, Ryszard M; Hesselmann, Volker

2016-01-01

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

Role of von Willebrand Factor and ADAMTS13 in early brain injury after experimental subarachnoid hemorrhage.

PubMed

Wan, H; Wang, Y; Ai, J; Brathwaite, S; Ni, H; Macdonald, R L; Hol, E M; Meijers, J C M; Vergouwen, M D I

2018-05-05

Early brain injury is an important determinant of poor functional outcome and case-fatality after aneurysmal subarachnoid hemorrhage (SAH) and associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated if von Willebrand Factor (VWF) is involved in the pathogenesis of early brain injury, and if ultra-early treatment with recombinant ADAMTS13 (rADAMTS13) reduces early brain injury after experimental SAH. Experimental SAH in mice was induced by prechiasmatic injection of non-anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control (n=21), VWF -/- (n=25), ADAMTS13 -/- (n=23), and C57BL/6J treated with rADAMTS13 (n=26). Mice were sacrificed at 2 hours post-SAH. Primary outcome measures were microglial activation (Iba-1 surface area) and neuronal injury (number of cleaved caspase-3 positive neurons). Compared with controls, microglial activation was decreased in VWF -/- mice (mean difference -20.0%; 95% CI: -4.0% to -38.6%), increased in ADAMTS13 -/- mice (mean difference +34.0%; 95% CI: 16.2% to 51.7%), and decreased in rADAMTS13 treated mice (mean difference -22.1%; 95% CI: -3.4% to -39.1%). Compared with controls (185 neurons [IQR 133-353]), neuronal injury in the cerebral cortex was decreased in VWF -/- mice (63 neurons [IQR 25-78]), not changed in ADAMTS13 -/- mice (53 neurons [IQR 26-221]), and reduced in rADAMTS13 treated mice (45 neurons [IQR 9-115]). Our findings suggest that VWF is involved in the pathogenesis of early brain injury and support the further study of rADAMTS13 as a treatment option for early brain injury after SAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

PubMed

Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

2015-01-01

Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P < 0.001), initial lactate dehydrogenase (LDH) (HR = 1.000, P = 0.045) and total cholesterol (HR = 0.978, P < 0.001) were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100%) patients with s-AH and 22/28 (78.6%) patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004) and HAV RNA titer (HR = 2.076, P = 0.012) were independent factors for s-AH. Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

Important casual association of carotid body and glossopharyngeal nerve and lung following experimental subarachnoid hemorrhage in rabbits. First report.

PubMed

Yolas, Coskun; Kanat, Ayhan; Aydin, Mehmet Dumlu; Turkmenoglu, Osman Nuri; Gundogdu, Cemal

2014-01-15

The glossopharyngeal nerves (GPNs) and carotid bodies (CBs) have an important role in the continuation of the cerebral autoregulation and cardiorespiratory functions. The relationship between degenerative injury of CB and the GPN in subarachnoid hemorrhage (SAH) was studied. Twenty rabbits were included in this study. Five of them (n=5) were used as control group. The remaining animals (n=15) were exposed to experimental SAH. In the six animals of the SAH group, severe signs of illness were observed, and these six animals were killed in the first week after SAH. Others animals (n=9) were followed for 20 days and then sacrificed. GPNs and CBs were examined and, the live and degenerated GPN axon number, and of CB neuron numbers were stereologically estimated. The mean number of live neurons in CBs was 4206.67±148.35 and live axons of GPNs were 1211.66±14.29 in the animals of the control group. The number of degenerated neurons of CBs was 2065±110.27 and the number of degenerated axons of GPNs was 530.83±43.48 in early killed animals with SAH. The number of degenerated neurons of CBs and the number of degenerated axons of GPNs were found as 1013.89±4184 and 2270.5±134.38 in the living animals with SAH, respectively. High number of degenerated axons of GPN and neurons of CBs of the early killed animals suggest that the mortality in early SAH might be due to GPNs injury secondary to compression of their axons or supplying vessels by the probably herniated brainstem, and secondary denervation injury of CBs, and lung. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Epidemiology of aneurysmal subarachnoid hemorrhage in Australia and New Zealand: incidence and case fatality from the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS).

PubMed

2000-08-01

More data on the epidemiology of subarachnoid hemorrhage (SAH) are required to increase our understanding of etiology and prevention. This study sought to determine the incidence and case fatality of SAH from 4 prospective, population-based registers in Australia and New Zealand. We identified all cases of "aneurysmal" SAH from November 1995 to June 1998 in Adelaide, Hobart, Perth (Australia), and Auckland (New Zealand), a total population of approximately 2.8 million, using standard diagnostic criteria and uniform community-wide surveillance and data extraction procedures. A total of 436 cases of SAH were registered, including 432 first-ever events and 4 recurrent events. The mean age of cases was 57 years (range, 16 to 94 years), and 62% were female. From the 400 first-ever events registered over whole years, the crude annual incidence for the total population was 8.1 per 100 000 (95% CI, 7.4, 9.0), with rates higher for females (9. 7; 95% CI, 8.6, 11.0) than for males (6.5; 95% CI, 5.5, 7.6). Age-specific rates showed a continuous upward trend with age, although the shape and strength of this association differed between the sexes. Standardized annual incidence of SAH varied across centers, being highest in Auckland largely because of the high rate in Maori and Pacific people. The 28-day case fatality rate for the total population was 39% (95% CI, 34%, 44%), with little variation in ratios across centers. There is variation in the incidence of SAH in Australia and New Zealand, but the rates are consistently higher for females. A monotonic increase in incidence with age suggests that exposures with cumulative effects and long induction times may be less relevant in the etiology of SAH.

Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis of Ruptured Aneurysms.

PubMed

Hughes, Joshua D; Bond, Kamila M; Mekary, Rania A; Dewan, Michael C; Rattani, Abbas; Baticulon, Ronnie; Kato, Yoko; Azevedo-Filho, Hildo; Morcos, Jacques J; Park, Kee B

2018-04-09

There is increasing acknowledgement that surgical care is important in global health initiatives. In particular, neurosurgical care is as limited as 1 per 10 million people in parts of the world. We performed a systematic literature review to examine the worldwide incidence of central nervous system vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH) to define the disease burden and inform neurosurgical global health efforts. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to estimate the global epidemiology of central nervous system vascular lesions, including unruptured and ruptured aneurysms, arteriovenous malformations, cavernous malformations, dural arteriovenous fistulas, developmental venous anomalies, and vein of Galen malformations. Results were organized by World Health Organization regions. After literature review, because of a lack of data from particular World Health Organization regions, we determined we could only provide an estimate of aSAH. Using data from studies with aSAH and 12 high-quality stroke studies from regions lacking data, we meta-analyzed the yearly crude incidence of aSAH per 100,000 persons. Estimates were generated via random-effects models. From an initial yield of 1492 studies, 46 manuscripts on aSAH incidence were included. The final meta-analysis included 58 studies from 31 different countries. We estimated the global crude incidence for aSAH to be 6.67 per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38 per 100,000 persons. Worldwide, almost 500,000 individuals will suffer from aSAH each year, with almost two-thirds in low- and middle-income countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

PubMed Central

Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

2015-01-01

Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P<0.001), initial lactate dehydrogenase (LDH) (HR = 1.000, P = 0.045) and total cholesterol (HR = 0.978, P<0.001) were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100%) patients with s-AH and 22/28 (78.6%) patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004) and HAV RNA titer (HR = 2.076, P = 0.012) were independent factors for s-AH. Conclusions Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A. PMID:26090677

Determination of a Testing Threshold for Lumbar Puncture in the Diagnosis of Subarachnoid Hemorrhage after a Negative Head Computed Tomography: A Decision Analysis.

PubMed

Taylor, Richard Andrew; Singh Gill, Harman; Marcolini, Evie G; Meyers, H Pendell; Faust, Jeremy Samuel; Newman, David H

2016-10-01

The objective was to determine the testing threshold for lumbar puncture (LP) in the evaluation of aneurysmal subarachnoid hemorrhage (SAH) after a negative head computed tomography (CT). As a secondary aim we sought to identify clinical variables that have the greatest impact on this threshold. A decision analytic model was developed to estimate the testing threshold for patients with normal neurologic findings, being evaluated for SAH, after a negative CT of the head. The testing threshold was calculated as the pretest probability of disease where the two strategies (LP or no LP) are balanced in terms of quality-adjusted life-years. Two-way and probabilistic sensitivity analyses (PSAs) were performed. For the base-case scenario the testing threshold for performing an LP after negative head CT was 4.3%. Results for the two-way sensitivity analyses demonstrated that the test threshold ranged from 1.9% to 15.6%, dominated by the uncertainty in the probability of death from initial missed SAH. In the PSA the mean testing threshold was 4.3% (95% confidence interval = 1.4% to 9.3%). Other significant variables in the model included probability of aneurysmal versus nonaneurysmal SAH after negative head CT, probability of long-term morbidity from initial missed SAH, and probability of renal failure from contrast-induced nephropathy. Our decision analysis results suggest a testing threshold for LP after negative CT to be approximately 4.3%, with a range of 1.4% to 9.3% on robust PSA. In light of these data, and considering the low probability of aneurysmal SAH after a negative CT, classical teaching and current guidelines addressing testing for SAH should be revisited. © 2016 by the Society for Academic Emergency Medicine.

Detection of aneurysmal subarachnoid hemorrhage 3 months after initial bleeding: evaluation of T2* and FLAIR MR sequences at 3 T in comparison with initial non-enhanced CT as a gold standard.

PubMed

Mulé, Sébastien; Soize, Sébastien; Benaissa, Azzedine; Portefaix, Christophe; Pierot, Laurent

2016-08-01

To investigate the ability of T2* and fluid-attenuated inversion recovery (FLAIR) MR sequences to detect hemosiderin deposition 3 months after aneurysmal subarachnoid hemorrhage (SAH) in comparison with early non-enhanced CT (NECT) as a gold standard. From September 2008 through May 2013, patients with aneurysmal SAH were included if a NECT less than 24 h after the onset of symptoms showed a SAH, and MRI, including T2* and FLAIR sequences, was performed 3 months later. All aneurysms were treated endovascularly. NECT and MR sequences were blindly analyzed for the presence of SAH (NECT) or hemosiderin deposition (MRI). When positive, details of the spatial distribution of SAH or hemosiderin deposits were noted. Sensitivities were calculated for each patient. Sensitivities, specificities, and positive predictive values (PPVs) were calculated for each location. Forty-nine patients (mean age 52.9 years) were included. Bleeding-related patterns were identified in 43 patients (87.8%) on T2* and 10 patients (20.4%) on FLAIR. T2* was highly predictive of the location of the initial hemorrhage, especially in the Sylvian cisterns (PPVs 95% and 100%) and the anterior interhemispheric fissure (PPV 90%). The T2* sequence can detect and localize a previous SAH a few months after aneurysmal bleeding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Preventive Role of Hilar Parasympathetic Ganglia on Pulmonary Artery Vasospasm in Subarachnoid Hemorrhage: An Experimental Study.

PubMed

Araz, Omer; Aydin, Mehmet Dumlu; Gundogdu, Betul; Altas, Ender; Cakir, Murteza; Calikoglu, Cagatay; Atalay, Canan; Gundogdu, Cemal

2015-01-01

Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.

Low prevalence of hypopituitarism after subarachnoid haemorrhage using confirmatory testing and with BMI-specific GH cut-off levels.

PubMed

Gardner, Chris J; Javadpour, Mohsen; Stoneley, Catherine; Purthuran, Mani; Biswas, Shubhabrata; Daousi, Christina; MacFarlane, Ian A; Cuthbertson, Daniel J

2013-04-01

Hypopituitarism following subarachnoid haemorrhage (SAH) has been reported to be a frequent occurrence. However, there is considerable heterogeneity between studies with differing patient populations and treatment modalities and most importantly employing differing endocrine protocols and (normal) reference ranges of GH. We aimed to examine prospectively a cohort of SAH survivors for development of hypopituitarism post-SAH using rigorous endocrine testing and compare GH response to glucagon stimulation with a cohort of healthy controls of a similar BMI. Sixty-four patients were investigated for evidence of hypopituitarism 3 months post-SAH with 50 patients tested again at 12 months. Glucagon stimulation testing (GST), with confirmation of deficiencies by GHRH/arginine testing for GH deficiency (GHD) and short synacthen testing for ACTH deficiency, was used. Basal testing of other hormonal axes was undertaken. Mean age of patients was 53±11.7 years and mean BMI was 27.5±5.7 kg/m(2). After confirmatory testing, the prevalence of hypopituitarism was 12% (GHD 10%, asymptomatic hypocortisolaemia 2%). There was no association between hypopituitarism and post-SAH vasospasm, presence of cerebral infarction, Fisher grade, or clinical grading at presentation. There was a significant correlation between BMI and peak GH to glucagon stimulation in both patients and controls. Identification of 'true' GHD after SAH requires confirmatory testing with an alternative stimulation test and application of BMI-specific cut-offs. Using such stringent criteria, we found a prevalence of hypopituitarism of 12% in our population.

Sleep apnea-hypopnea syndrome and type 2 diabetes. A reciprocal relationship?

PubMed

Martínez Cerón, Elisabet; Casitas Mateos, Raquel; García-Río, Francisco

2015-03-01

Epidemiological data suggest that sleep apnea-hypopnea syndrome (SAHS) is independently associated with the development of insulin resistance and glucose intolerance. Moreover, despite significant methodological limitations, some studies report a high prevalence of SAHS in patients with type 2 diabetes mellitus (DM2). A recent meta-analysis shows that moderate-severe SAHS is associated with an increased risk of DM2 (relative risk=1.63 [1.09 to 2.45]), compared to the absence of apneas and hypopneas. Common alterations in various pathogenic pathways add biological plausibility to this relationship. Intermittent hypoxia and sleep fragmentation, caused by successive apnea-hypopnea episodes, induce several intermediate disorders, such as activation of the sympathetic nervous system, oxidative stress, systemic inflammation, alterations in appetite-regulating hormones and activation of the hypothalamic-pituitary-adrenal axis which, in turn, favor the development of insulin resistance, its progression to glucose intolerance and, ultimately, to DM2. Concomitant SAHS seems to increase DM2 severity, since it worsens glycemic control and enhances the effects of atherosclerosis on the development of macrovascular complications. Furthermore, SAHS may be associated with the development of microvascular complications: retinopathy, nephropathy or diabetic neuropathy in particular. Data are still scant, but it seems that DM2 may also worsen SAHS progression, by increasing the collapsibility of the upper airway and the development of central apneas and hypopneas. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Determining rural risk for aneurysmal subarachnoid hemorrhages: A structural equation modeling approach.

PubMed

Nichols, Linda Jayne; Gall, Seana; Stirling, Christine

2016-01-01

An aneurysmal subarachnoid hemorrhage (aSAH) carries a high disability burden. The true impact of rurality as a predictor of outcome severity is unknown. Our aim is to clarify the relationship between the proposed explanations of regional and rural health disparities linked to severity of outcome following an aSAH. An initial literature search identified limited data directly linking geographical location, rurality, rural vulnerability, and aSAH. A further search noting parallels with ischemic stroke and acute myocardial infarct literature presented a number of diverse and interrelated predictors. This a priori knowledge informed the development of a conceptual framework that proposes the relationship between rurality and severity of outcome following an aSAH utilizing structural equation modeling. The presented conceptual framework explores a number of system, environmental, and modifiable risk factors. Socioeconomic characteristics, modifiable risk factors, and timely treatment that were identified as predictors of severity of outcome following an aSAH and within each of these defined predictors a number of contributing specific individual predictors are proposed. There are considerable gaps in the current knowledge pertaining to the impact of rurality on the severity of outcome following an aSAH. Absent from the literature is any investigation of the cumulative impact and multiplicity of risk factors associated with rurality. The proposed conceptual framework hypothesizes a number of relationships between both individual level and system level predictors, acknowledging that intervening predictors may mediate the effect of one variable on another.

Pattern not volume of bleeding predicts angiographic vasospasm in nonaneurysmal subarachnoid hemorrhage.

PubMed

Raya, Amanda; Zipfel, Gregory J; Diringer, Michael N; Dacey, Ralph G; Derdeyn, Colin P; Rich, Keith M; Chicoine, Michael R; Dhar, Rajat

2014-01-01

Spontaneous idiopathic subarachnoid hemorrhage (SAH) with a perimesencephalic bleeding pattern is usually associated with a benign course, whereas a diffuse bleeding pattern has been associated with a higher risk of vasospasm and disability. We evaluated whether volume of bleeding explains this disparity. Pattern and amount of bleeding (by Hijdra and intraventricular hemorrhage scores) were assessed in 89 patients with nonaneurysmal SAH. Outcomes included angiographic vasospasm, delayed cerebral ischemia, and functional outcome at 1 year. Diffuse bleeding was associated with significantly higher Hijdra and intraventricular hemorrhage scores than perimesencephalic SAH, P≤0.003. Angiographic vasospasm was more likely in diffuse versus perimesencephalic SAH (45% versus 27%; odds ratio, 2.9; P=0.08), but adjustment for greater blood burden only partially attenuated this trend (adjusted odds ratio, 2.2; 95% confidence interval, 0.69-7.2; P=0.18); delayed cerebral ischemia was only seen in those with diffuse bleeding. Patients with diffuse bleeding were less likely to be discharged home (68% versus 90%; P=0.01) and tended to have more residual disability (modified Rankin scale, 3-6; 20% versus 6%; P=0.18). Nonaneurysmal SAH can still result in vasospasm and residual disability, especially in those with diffuse bleeding. This disparity is only partially accounted for by greater cisternal or intraventricular blood, suggesting that the mechanism and distribution of bleeding may be as important as the amount of hemorrhage in patients with idiopathic SAH.

3D fluid-attenuated inversion recovery imaging: reduced CSF artifacts and enhanced sensitivity and specificity for subarachnoid hemorrhage.

PubMed

Lummel, N; Schoepf, V; Burke, M; Brueckmann, H; Linn, J

2011-12-01

FLAIR images are highly sensitive for SAH. However, CSF flow artifacts caused by conventional FLAIR can produce false-positive results. Here, we compare 3D and 3D FLAIR sequences, focusing on their potential for containing these artifacts and their sensitivity and specificity for detection of SAHs. We evaluated the following 4 FLAIR sequences: 1) 2D FLAIR at 1.5T, 2) 2D FLAIR, 3) 2D PROPELLER-FLAIR, and 4) 3D Cube-FLAIR at 3T. All sequences were performed in 5 healthy volunteers; sequences 2 and 4 were also performed under routine conditions in 10 patients with focal epilepsy and in 10 patients with SAH. Two neuroradiologists independently conducted the analysis. The presence of flow artifacts in the ventricles and cisterns of healthy volunteers and patients with epilepsy was evaluated and scored on a 4-point scale. Mean values were calculated and compared by using paired t tests. Sensitivity and specificity for SAH detection in sequences 2 and 4 were determined. Cube-FLAIR showed almost no CSF artifacts in the volunteers and the patients with epilepsy; therefore, it was superior to any other FLAIR (P < .001). Sensitivity and specificity of SAH detection by 3T FLAIR were 58.3% and 89.4%, respectively, whereas Cube-FLAIR had a sensitivity of 95% and a specificity of 100%. Cube-FLAIR allows FLAIR imaging with almost no CSF artifacts and is, thus, particularly useful for SAH detection.

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

PubMed

Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

2016-05-01

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

Reducing length of stay in aneurysmal subarachnoid hemorrhage: A three year institutional experience.

PubMed

Alaraj, Ali; Hussein, Ahmed E; Esfahani, Darian R; Amin-Hanjani, Sepideh; Aletich, Victor A; Charbel, Fady T

2017-08-01

Hospital length of stay is a common metric of excellence in health care. With limited data evaluating hospital length of stay (LOS) and cost in subarachnoid hemorrhage (SAH), in this study we explore multiple prognostic factors and present our institutional experience in shortening LOS. 345 SAH patients were reviewed over a three year period. Patient demographics, hemorrhage grade, hospital course, hospital costs, and LOS were reviewed. Angiogram-negative SAH, Hunt and Hess (HH) Grade 5, and early mortalities were excluded. During this period a physician-led daily multidisciplinary huddle was established to identify and expedite patient discharge needs. 174 patients met inclusion criteria. Significant predictors of increased hospital LOS on univariate analysis included higher HH grade, hydrocephalus, need for ventriculostomy or ventriculoperitoneal shunt, clinical vasospasm, pneumonia, respiratory failure, deep venous thrombosis, and urinary tract infection. Need for shunt, clinical vasospasm, and pneumonia remained significant on multivariate analysis. Mean LOS times decreased to less than those cited in earlier studies, with mean hospital LOS dropping from 21.6days to 14.1. Total hospital costs per SAH patient decreased from $328K to $269K. Readmission rate and breakdown by patient discharge site remained unchanged. Need for ventriculoperitoneal shunt, clinical vasospasm, and pneumonia were found predictive of longer LOS in SAH patients. A physician-led daily multidisciplinary huddle is a potentially valuable tool to identify patient discharge needs and lower LOS and cost in SAH patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time imaging of subarachnoid hemorrhage in piglets with electrical impedance tomography.

PubMed

Dai, Meng; Wang, Liang; Xu, Canhua; Li, Lianfeng; Gao, Guodong; Dong, Xiuzhen

2010-09-01

Subarachnoid hemorrhage (SAH) is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would significantly reduce the rate of disability and mortality, and improve the prognosis of the patients. Although the present medical imaging techniques generally have high sensitivity to identify bleeding, the use of an additional, non-invasive imaging technique capable of continuously monitoring SAH is required to prevent contingent bleeding or re-bleeding. In this study, electrical impedance tomography (EIT) was applied to detect the onset of SAH modeled on eight piglets in real time, with the subsequent process being monitored continuously. The experimental SAH model was introduced by one-time injection of 5 ml fresh autologous arterial blood into the cisterna magna. Results showed that resistivity variations within the brain caused by the added blood could be detected using the EIT method and may be associated not only with the resistivity difference among brain tissues, but also with variations of cerebrospinal fluid dynamics. In conclusion, EIT has unique potential for use in clinical practice to provide invaluable real-time neuroimaging data for SAH after the improvement of electrode design, anisotropic realistic modeling and instrumentation.

["Thunder clap headache": an independent form of headache?].

PubMed

Strittmatter, M; Zimmermann, C; Schimrigk, K; Hamann, G F

1996-01-01

Acute severe headache indicative of subarachnoid haemorrhage (SAH), but without the requisite proof, is defined as thunderclap. A special pathophysiological mechanism for the development of this headache is not known as yet. This retrospective study comprised 84 patients. All had the typical clinical signs of a SAH, but cranial computer tomography and lumbar puncture excluded this diagnosis. In 82% of these patients the headache was classified according to aetiologically defined symptomatic groups. One patient with headache of vascular aetiology had an angiographically proven, but not ruptured aneurysm. No definite cause for the headache was found in 18% of cases. None of the patients followed up over a period of between 12 months and 6 years developed SAH or any other severe neurological disorder. 9% reported repeat of the headache event. Thunderclap headache seems to be only a descriptive term for patients with symptoms typical of a SAH without signs of bleeding. Thunderclap headache has no diagnostic or prognostic specificity and therefore we recommend use of this term only as a description of the headache characteristic. Thunderclap headache is not a predictor of a future SAH. Cerebral angiography should be restricted to cases with neurological deficits.

Inhibitor designing, virtual screening, and docking studies for methyltransferase: A potential target against dengue virus

PubMed Central

Singh, Jagbir; Kumar, Mahesh; Mansuri, Rani; Sahoo, Ganesh Chandra; Deep, Aakash

2016-01-01

Aim: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. Introduction: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. Materials and Methods: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. Results: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. Conclusion: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation. PMID:27413346

Hypercholesterolemia increases vasospasm resulting from basilar artery subarachnoid hemorrhage in rabbits which is attenuated by Vitamin E

PubMed Central

Sasani, Mehdi; Yazgan, Burak; Celebi, Irfan; Aytan, Nurgul; Catalgol, Betul; Oktenoglu, Tunc; Kaner, Tuncay; Ozer, Nesrin Kartal; Ozer, Ali Fahir

2011-01-01

Background: Aneurysm rupture results in subarachnoid hemorrhage (SAH) with subsequent vasospasm in the cerebral and cerebellar major arteries. In recent years, there has been increasing evidence that hypercholesterolemia plays a role in the pathology of SAH. It is known that hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. Among the factors that have been found to retard the development of atherosclerosis is the intake of a sufficient amount of Vitamin E. An inverse association between serum Vitamin E and coronary heart disease mortality has been demonstrated in epidemiologic studies. Therefore, we tested, in an established model of enhanced cholesterol feed in rabbits, the effects of hypercholesterolemia on vasospasm after SAH by using computed tomography (CT) angiograms of the rabbit basilar artery; in addition, we tested the effects of Vitamin E on these conditions, which have not been studied up to now. Methods: In this study rabbits were divided into 3 major groups: control, cholesterol fed, and cholesterol + Vitamin E fed. Hypercholesterolemia was induced by a 2% cholesterol-containing diet. Three rabbit groups were fed rabbit diet; one group was fed a diet that also contained 2% cholesterol and another group was fed a diet containing 2% cholesterol and they received i.m. injections of 50 mg/kg of Vitamin E. After 8 weeks, SAH was induced by the double-hemorrhage method and distilled water was injected into cisterna magna. Blood was taken to measure serum cholesterol and Vitamin E levels. Basilar artery samples were taken for microscopic examination. CT angiography and measurement of basilar artery diameter were performed at days 0 and 3 after SAH. Results: Two percent cholesterol diet supplementation for 8 weeks resulted in a significant increase in serum cholesterol levels. Light microscopic analysis of basilar artery of hypercholesterolemic rabbits showed disturbances in the subendothelial and medial layers

Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage.

PubMed

Risselada, R; Straatman, H; van Kooten, F; Dippel, D W J; van der Lugt, A; Niessen, W J; Firouzian, A; Herings, R M C; Sturkenboom, M C J M

2011-03-01

Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role. The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH. We applied population-based case-control, case-crossover and case-time-control designs to estimate the risk of SAH while addressing issues both of confounding by indication and time varying exposure within the PHARMO Record Linkage System database. This system includes drug dispensing records from community pharmacies and hospital discharge records of more than 3 million community-dwelling inhabitants in the Netherlands. Patients were considered a case if they were hospitalized for a first SAH (ICD-9-CM code 430) in the period between 1st January 1998 and 31st December 2006. Controls were selected from the source population, matched on age, gender and date of hospitalization. Conditional logistic regression was used to estimate multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of SAH during use of platelet aggregation inhibitors or vitamin K antagonists. In the case-crossover and case-time-control designs we selected 11 control periods preceding the index date in successive steps of 1 month in the past. In all, 1004 cases of SAH were identified. In the case-control analysis the adjusted OR for the risk of SAH in current use of platelet aggregation inhibitors was 1.32 (95% CI: 1.02-1.70) and in current use of vitamin K antagonists 1.29 (95% CI: 0.89-1.87) compared with no use. In the case-crossover analysis the ORs for the risk of SAH in current use of platelet aggregation inhibitors and vitamin K antagonists were 1.04 (95% CI: 0.56-1.94) and 2.46 (95% CI

Identification of nine genes as novel susceptibility loci for early-onset ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.

PubMed

Yamada, Yoshiji; Kato, Kimihiko; Oguri, Mitsutoshi; Horibe, Hideki; Fujimaki, Tetsuo; Yasukochi, Yoshiki; Takeuchi, Ichiro; Sakuma, Jun

2018-07-01

Given that substantial genetic components have been shown in ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), heritability may be higher in early-onset than late-onset individuals with these conditions. Although genome-wide association studies (GWASs) have identified various genes and loci significantly associated with ischemic stroke, ICH, or intracranial aneurysm mainly in European ancestry populations, genetic variants that contribute to susceptibility to these disorders remain to be identified definitively. We performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, ICH, or SAH in early-onset subjects with these conditions. A total of 6,649 individuals aged ≤65 years were examined. For the EWAS of ischemic or hemorrhagic stroke, 6,224 individuals (450 subjects with ischemic stroke, 5,774 controls) or 6,179 individuals (261 subjects with ICH, 176 subjects with SAH, 5,742 controls), respectively, were examined. EWASs were performed with the use of Illumina Human Exome-12 v1.2 DNA Analysis BeadChip or Infinium Exome-24 v1.0 BeadChip. To compensate for multiple comparisons of allele frequencies with ischemic stroke, ICH, or SAH, we applied a false discovery rate (FDR) of <0.05 for statistical significance of association. The association of allele frequencies of 31,245 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic stroke was examined with Fisher's exact test, and 31 SNPs were significantly (FDR <0.05) associated with ischemic stroke. The association of allele frequencies of 31,253 or 30,970 SNPs to ICH or SAH, respectively, was examined with Fisher's exact test, and six or two SNPs were significantly associated with ICH or SAH, respectively. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension and diabetes mellitus revealed that 12 SNPs were significantly [P<0.0004 (0

Virological course of hepatitis A virus as determined by real time RT-PCR: Correlation with biochemical, immunological and genotypic profiles.

PubMed

Hussain, Zahid; Das, Bhudev C; Husain, Syed A; Polipalli, Sunil K; Ahmed, Tanzeel; Begum, Nargis; Medhi, Subhash; Verghese, Alice; Raish, Mohammad; Theamboonlers, Apiradee; Poovorawan, Yong; Kar, Premashis

2006-08-07

To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated immunity. Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2). The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients. Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.

Virological course of hepatitis A virus as determined by real time RT-PCR: Correlation with biochemical, immunological and genotypic profiles

PubMed Central

Hussain, Zahid; Das, Bhudev C; Husain, Syed A; Polipalli, Sunil K; Ahmed, Tanzeel; Begum, Nargis; Medhi, Subhash; Verghese, Alice; Raish, Mohammad; Theamboonlers, Apiradee; Poovorawan, Yong; Kar, Premashis

2006-01-01

AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4+/ CD8+ lymphocyte populations that control cell-mediated immunity. METHODS: Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS: Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 ± 894.3; P = 0.0014) and s-AH (1713.9 ± 886.3; P = 0.001) compared to normal controls (23.6 ± 7.2). The prothrombin time in s-AH patients (21.0 ± 2.0; P = 0.02) was significantly higher than in AHA (14.3 ± 1.1; P = 0.44). The CD4+/CD8+ ratio in AHA patients (1.17 ± 0.11; P = 0.22) and s-AH (0.83 ± 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients. CONCLUSION: Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases. PMID

MR Angiography Follow-Up 10 Years after Cryptogenic Nonperimesencephalic Subarachnoid Hemorrhage

PubMed Central

Wenz, Holger; Wenz, Ralf; al Mahdi, Mohamad-Motaz; Scharf, Johann; Groden, Christoph; Schmiedek, Peter; Seiz-Rosenhagen, Marcel

2015-01-01

Objectives Long-term magnetic resonance angiography (MRA) follow-up studies regarding cryptogenic nonperimesencephalic subarachnoid hemorrhage (nSAH) are scarce. This single-centre study identified all patients with angiographically verified cryptogenic nSAH from 1998 to 2007: The two main objectives were to prospectively assess the incidence of de novo aneurysm with 3.0-MRI years after cryptogenic nSAH in patients without evidence for further hemorrhage, and retrospectively assess patient demographics and outcome. Methods From prospectively maintained report databases all patients with angiographically verified cryptogenic nSAH were identified. 21 of 29 patients received high-resolution 3T-MRI including time-of-flight and contrast-enhanced angiography, 10.2 ± 2.8 years after cryptogenic nSAH. MRA follow-up imaging was compared with initial digital subtraction angiography (DSA) and CT/MRA. Post-hemorrhage images were related to current MRI with reference to persistent lesions resulting from delayed cerebral ischemia (DCI) and post-hemorrhagic siderosis. Patient-based objectives were retrospectively abstracted from clinical databases. Results 29 patients were identified with cryptogenic nSAH, 17 (59%) were male. Mean age at time of hemorrhage was 52.9 ± 14.4 years (range 4 – 74 years). 21 persons were available for long-term follow-up. In these, there were 213.5 person years of MRI-follow-up. No de novo aneurysm was detected. Mean modified Rankin Scale (mRS) during discharge was 1.28. Post-hemorrhage radiographic vasospasm was found in three patients (10.3%); DCI-related lesions occurred in one patient (3.4%). Five patients (17.2%) needed temporary external ventricular drainage; long-term CSF shunt dependency was necessary only in one patient (3.4%). Initial DSA retrospectively showed a 2 x 2 mm aneurysm of the right distal ICA in one patient, which remained stable. Post-hemorrhage siderosis was detected 8.1 years after the initial bleeding in one patient (4

SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model.

PubMed

Qian, Cong; Jin, Jianxiang; Chen, Jingyin; Li, Jianru; Yu, Xiaobo; Mo, Hangbo; Chen, Gao

2017-12-01

Early brain injury is considered to be a major risk that is related to the prognosis of subarachnoid hemorrhage (SAH). In SAH model rats, brain edema and apoptosis have been closely related with death rate and neurological function. Sirtuin 1 (SIRT1) was reported to be involved in apoptosis in cerebral ischemia and brain tumor formation through p53 deacetylation. The present study aimed to evaluate the role of SIRT1 in a rat endovascular perforation model of SAH. The SIRT1 activator resveratrol (RES) was administered 48 h prior to SAH induction and the SIRT1 inhibitor Sirtinol (SIR) was used to reverse the effects of RES on SIRT1 expression. Mortality rate, neurological function and brain water content were measured 24 h post‑SAH induction. Proteins associated with the blood brain barrier (BBB), apoptosis and SIRT1 in the cortex, such as zona occludens 1 (ZO‑1), occludin, claudin‑5, SIRT1, p53 and cleaved caspase3 were investigated. mRNA expression of the p53 downstream molecules including Bcl‑associated X protein, P53 upregulated modulator of apoptosis, Noxa and BH3 interacting‑domain death agonist were also investigated. Neuronal apoptosis was also investigated by immunofluorescence. RES pretreatment reduced the mortality rate and improved neurological function, which was consistent with reduced brain water content and neuronal apoptosis; these effects were partially reversed by co‑treatment with SIR. SIRT1 may reduce the brain water content by improvement of dysfunctional BBB permeability, and protein analysis revealed that both ZO‑1, occludin and claudin‑5 may be involved, and these effects were reversed by SIRT1 inhibition. SIRT1 may also affect apoptosis post‑SAH through p53 deacetylation, and the analysis of p53 related downstream pro‑apoptotic molecules supported this hypothesis. Localization of neuron specific apoptosis revealed that SIRT1 may regulate neuronal apoptosis following SAH. SIRT1 may also ease brain edema and neuronal

Subarachnoid Hemorrhage

MedlinePlus

... risk of death was double in both the control group and espe- cially the SAH group. This is ... and smoking were more common in the SAH group than the general ... smoking and strict control of the blood pressure and cholesterol levels are ...

Protocol Based Real-Time Continuous Electroencephalography for Detecting Vasospasm in Subarachnoid Hemorrhage.

PubMed

Hong, Jeong-Ho; Bang, Jae Seung; Chung, Jin-Heon; Han, Moon-Ku

2016-03-01

A continuous electroencephalography (cEEG) can be helpful in detecting vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (SAH). We describe a patient with an aneurysmal SAH whose symptomatic vasospasm was detected promptly by using a real-time cEEG. Patient was immediately treated by intraarterial vasodilator therapy. A 50-year-old woman without any significant medical history presented with a severe bifrontal headache due to acute SAH with a ruptured aneurysm on the anterior communicating artery (Fisher grade 3). On bleed day 6, she developed a sudden onset of global aphasia and left hemiparesis preceded by cEEG changes consistent with vasospasm. A stat chemical dilator therapy was performed and she recovered without significant neurological deficits. A real-time and protocol-based cEEG can be utilized in order to avoid any delay in detection of vasospasm in aneurysmal SAH and thereby improve clinical outcomes.

A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.

PubMed

Marbacher, Serge; Andereggen, Lukas; Neuschmelting, Volker; Widmer, Hans Rudolf; von Gunten, Michael; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2012-07-15

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells. SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%. The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of risk factors and development of acute kidney injury in aneurysmal subarachnoid hemorrhage, head injury, and severe sepsis/septic shock patients during ICU treatment.

PubMed

Kamar, Ceren; Ali, Achmet; Altun, Demet; Orhun, Günseli; Sabancı, Akın; Sencer, Altay; Akıncı, İbrahim Özkan

2017-01-01

There are few studies examining development of acute kidney injury (AKI) in the various types of patients in intensive care units (ICUs). Presently described is evaluation of risk factors and development of AKI in different groups of ICU patients. Present study was performed in 3 different ICUs. Development of AKI was measured using Acute Kidney Injury Network (AKIN) classification system. Total of 300 patients who were treated in trauma, neurosurgery, or general ICU departments (due to head injury, aneurysmal subarachnoid hemorrhage [aSAH], or severe sepsis/septic shock, respectively) were assessed for incidence, risk factors, and development of AKI. AKI did not develop in aSAH patients when evaluated based on serum creatinine level; however, it was observed in 5% of aSAH patients according to volume adjusted creatinine (VACr) level. AKI developed in 76% of sepsis group, and in 20% of head injury group, based on AKIN classification, according to both serum and VACr levels. Incidence of AKI was significantly higher in sepsis group (p<0.001). Only use of vasopressor was significantly related to AKI development in sepsis and head injury groups. Mortality rate was 8%, 22%, and 42% in aSAH, head injury, and sepsis groups, respectively. AKI development and vasopressor use were significantly related to mortality in sepsis group. Despite similar characteristics and risk factors, there were fewer instances of AKI in aSAH group. Hypertension or hydration therapy used to treat vasospasm and polyuria due to cerebral salt-wasting syndrome may prevent aSAH patients from developing AKI.

[Over-expressed Bax inhibitor 1 (BI-1) inhibits apoptosis of hippocampal neurons via endoplasmic reticulum IRE1-JNK pathway in rats with subarachnoid hemorrhage].

PubMed

Liu, Jiaxin; Zhou, Shuai; Qian, Xiying; Zhang, Yueting; Zhao, Jianhua

2017-10-01

Objective To investigate the protective effect of lentivirus-mediated BI-1 overexpression on hippocampal neurons in rats with subarachnoid hemorrhage (SAH) and the relationship with endoplasmic reticulum IRE1-JNK signaling pathway. Methods The lentivirus solution of BI-1 over-expression was injected into the brain of rats 24 hours before SAH rat model was established by intravascular puncture method. At 24 hours after modeling, the brain water content and neurological score of the rats were measured. The apoptosis of hippocampal neurons was detected by TUNEL assay. Western blotting was used to detect the expressions of BI-1 protein and endoplasmic reticulum stress (ERS) marker proteins GRP78 and IRE1. ERS in hippocampal neurons of the rats with SAH was intervened by IRE1α-specific inhibitor KIRA6, and then the protein expressions of p-IRE1, p-JNK, Bax, Bcl2 and caspase-3 were detected by Western blotting. Results BI-1 over-expression improved neurobehavioral score, decreased brain water content and hippocampal neuron apoptosis rate, and also down-regulated GRP78 and IRE1 protein levels in the rats with SAH. Both the interference of KIRA6 and the over-expression of BI-1 inhibited the expressions of p-IRE1, p-JNK, Bax and caspase-3, and promoted the expression of anti-apoptotic protein Bcl2. Conclusion Over-expression of BI-1 can inhibit the apoptosis of hippocampal neurons in rats with SAH by inhibiting the activation of ERS-mediated IRE1-JNK signaling pathway, thus ultimately attenuating the early brain injury following SAH.

Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage.

PubMed

Tölli, A; Borg, J; Bellander, B-M; Johansson, F; Höybye, C

2017-02-01

Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables. Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post-injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected. A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables. Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH.

Achieving normothermia in patients with febrile subarachnoid hemorrhage: feasibility and safety of a novel intravascular cooling catheter.

PubMed

Badjatia, Neeraj; O'Donnell, Joan; Baker, John R; Huang, David; Ayata, Cenk; Greer, David M; Carter, Bob S; Ogilvy, Christopher S; McDonald, Colin T

2004-01-01

Fever is common and difficult to control in patients with subarachnoid hemorrhage (SAH). We have previously shown an inverse relationship between fever and outcome in patients with SAH. This was a prospective, single-arm, feasibility trial in which nine patients with SAH underwent temperature management using an intravascular cooling catheter (ICC) to restore and maintain 24 hours of normothermia (36.5 degrees+/-0.2 degrees C). Enrollment occurred after development of a fever of at least 38.3 degrees C within 7 days of SAH that was refractory to acetaminophen treatment. The ICC was placed at the bedside through an introducer sheath via the femoral vein into the inferior vena cava (IVC). Portable X-ray confirmed placement. Normothermia was achieved in seven of the nine patients treated (78%); it was achieved in 100% of the patients with a 14F catheter (n=4) and in 60% of the patients with a 9F catheter (n=5). The two patients not reaching normothermia were not adequately treated for shivering. All other patients reached normothermia irrespective of intubation status. Overall, normothermia was well tolerated and not discontinued because of discomfort or adverse events. Two incidences of deep vein thrombosis were diagnosis by ultrasound that were not associated with clinical sequelae, and IVC filters were placed. No unanticipated adverse events occurred. We have demonstrated that fever can be safely and effectively controlled in patients with SAH for at least 24 hours using an ICC. Future studies are needed to assess the effect of such sustained therapy on outcome in patients with SAH.

Measuring the Impact of Delayed Cerebral Ischemia on Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage-Protocol of a Swiss Nationwide Observational Study (MoCA-DCI Study).

PubMed

Stienen, Martin N; Fung, Christian; Bijlenga, Philippe; Zumofen, Daniel W; Maduri, Rodolfo; Robert, Thomas; Seule, Martin A; Marbacher, Serge; Geisseler, Olivia; Brugger, Peter; Gutbrod, Klemens; Chicherio, Christian; Monsch, Andreas U; Beaud, Valérie; Rossi, Stefania; Früh, Severin; Schmid, Nicole; Smoll, Nicolas R; Keller, Emanuela; Regli, Luca

2018-05-11

The exact relationship between delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and neuropsychological impairment remains unknown, as previous studies lacked a baseline examination after aneurysm occlusion but before the DCI-period. Neuropsychological evaluation of acutely ill patients is often applied in a busy intensive care unit (ICU), where distraction represents a bias to the obtained results. To evaluate the relationship between DCI and neuropsychological outcome after aSAH by comparing the Montreal Cognitive Assessment (MoCA) results in aSAH patients with and without DCI at 3 mo with a baseline examination before the DCI-period (part 1). To determine the reliability of the MoCA, when applied in an ICU setting (part 2). Prospective, multicenter, and observational study performed at all Swiss neurovascular centers. For part 1, n = 240 consecutive aSAH patients and for part 2, n = 50 patients with acute brain injury are recruited. Part 1: Effect size of the relationship between DCI and neuropsychological outcome (MoCA). Part 2: Reliability measures for the MoCA. The institutional review boards approved this study on July 4, 2017 under case number BASEC 2017-00103. After completion, the results will be offered to an international scientific journal for peer-reviewed publication. This study determines the exact impact of DCI on the neuropsychological outcome after aSAH, unbiased by confounding factors such as early brain injury or patient-specific characteristics. The study provides unique insights in the neuropsychological state of patients in the early period after aSAH.

Sleep Quality, Sleep EEG Pattern, Mental Well-Being and Cortisol Secretion in Patients with Ruptured Aneurysm Post-Treatment: A Comparison with Post-Surgery Meningioma Patients and Controls.

PubMed

Gerber, Markus; Colledge, Flora; Pühse, Uwe; Holsboer-Trachsler, Edith; Zimmerer, Stefan; Brand, Serge

2016-01-01

Although the chance of surviving an aneurysmal subarachnoid haemorrhage (aSAH) has increased steadily, disturbed sleep and persistent psychological complaints are frequently experienced post-ictus. To date, however, few studies have sought to determine whether physiological parameters, such as objectively measured sleep and cortisol secretion, interrelate significantly with low sleep quality and psychological complaints such as depression. Furthermore, there is little evidence as to whether post-ictal complaints differ between aSAH patients and other groups who have experienced stressful medical intervention. Data on objective and subjective sleep, sleep-related dysfunctional cognitions, psychological functioning and cortisol secretion were collected from 15 patients who had undergone medical intervention for aSAH. Data were also collected from a group of 16 individuals who had undergone surgery for a meningioma and a third group made up of 17 healthy participants. aSAH patients and meningioma patients had significantly poorer subjective sleep than healthy controls and reported more sleep-related dysfunctional cognitions and hypochondriacal beliefs. They also had a significantly higher morning cortisol response. Finally, a non-significant trend was found showing that aSAH patients and meningioma patients reported poorer psychological functioning than healthy controls. Following treatment, aSAH patients and meningioma patients experience poorer subjective sleep and some differences in objectively measured sleep, which might be attributable to increased sleep-related dysfunctional cognitions and poorer overall psychological functioning. Differences in cortisol production were also observed, suggesting that some physiological imbalances are still present post-ictus. © 2016 S. Karger AG, Basel.

Functionalized graphene oxide as a drug carrier for loading pirfenidone in treatment of subarachnoid hemorrhage.

PubMed

Yang, Lijun; Wang, Feng; Han, Haie; Yang, Liang; Zhang, Gengshen; Fan, Zhenzeng

2015-05-01

Subarachnoid hemorrhage (SAH) is a life-threatening disease that causes high morbidity and mortality. Pirfenidone is a SAH drug that prevents secondary bleeding and cerebral infarction. To improve its therapeutic efficacy, this study aimed to employ a functionalized graphene oxide nanosheet (FGO) as a drug carrier loading pirfenidone to treat SAH. The graphene oxide nanosheet was introduced with transcription activator peptide (Tat), followed by functionalization with methoxy polyethylene glycol (mPEG) and loading with pirfenidone. The pirfenidone-loaded FGO (pirfenidone-FGO) exhibits better treatment efficacy than the single pirfenidone due to more effective loading and controlled release of the drug in tissue. The introduction of Tat and mPEG onto GO nanosheet contributes to the ability to cross the blood-brain barrier and the stability in blood circulation of the drug. At lower pH values, the highly efficient release of the drug from the pirfenidone-FGO exerts effective treatment to acidic inflammatory lesion after severe SAH. Besides its treatment function, FGO is also shown as a strong near infrared absorbing material which can be applied in photoacoustic imaging, allowing rapid real-time monitoring with deep resolution of brain tissues after SAH. The treatment efficacy of pirfenidone-FGO for central nervous system injuries is further demonstrated by hematoxylin and eosin staining of coronal brain slices, as well as measurements of brain water content and blood-brain barrier permeability. Our study supports the potential of FGO in clinical application in treatment of SAH. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduction in Autophagy by (-)-Epigallocatechin-3-Gallate (EGCG): a Potential Mechanism of Prevention of Mitochondrial Dysfunction After Subarachnoid Hemorrhage.

PubMed

Chen, Ying; Huang, Liyong; Zhang, Huiyong; Diao, Xiling; Zhao, Shuyang; Zhou, Wenke

2017-01-01

Mitochondrial dysfunction and subsequent autophagy, which are common features in central nervous system (CNS) disorders, were found to contribute to neuronal cell injury after subarachnoid hemorrhage (SAH). (-)-Epigallocatechin-3-gallate (EGCG), the main biological active of tea catechin, is well known for its beneficial effects in the treatment of CNS diseases. Here, the ability of EGCG to rescue cellular injury and mitochondrial function following the improvement of autophagic flux after SAH was investigated. As expected, EGCG-protected mitochondrial function depended on the inhibition of cytosolic Ca 2+ concentration ([Ca 2+ ] i ) influx via voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca 2+ concentration ([Ca 2+ ] m ) overload via mitochondrial Ca 2+ uniporter (MCU). The attenuated [Ca 2+ ] i and [Ca 2+ ] m levels observed in the EGCG-treated group likely lessened oxyhemoglobin (OxyHb)-induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization, mitochondrial membrane permeability transition pore (mPTP) opening, reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Subsequently, EGCG can restore the disrupted autophagy flux after SAH both at the initiation and formation stages by regulating Atg5, LC3B, and Becn-1 (Beclin-1) mRNA expressions. Thus, precondition EGCG resulted in autophagosomes and more autolysosomes compared with SAH group. As a result, EGCG pre-treatment increased the neurological score and decreased cell death. This study suggested that the mitochondrial dysfunction and abnormal autophagy flux synergistically contribute to SAH pathogenesis. Thus, EGCG can be regarded as a new pharmacological agent that targets both mitochondria and altered autophagy in SAH therapy.

Case Studies in Cardiac Dysfunction After Acute Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Hamilton, Jason C.; Korn-Naveh, Lauren; Crago, Elizabeth A.

2015-01-01

Patients with acute aneurysmal subarachnoid hemorrhage (SAH) often present with more than just neurological compromise. A wide spectrum of complicating cardiopulmonary abnormalities have been documented in patients with acute SAH, presenting additional challenges to the healthcare providers who attempt to treat and stabilize these patients. The patients described in this article presented with both acute aneurysmal SAH and cardiopulmonary compromise. Education and further research on this connection is needed to provide optimal care and outcomes for this vulnerable population. Nurses play a key role in balancing the critical and diverse needs of patients presenting with these symptoms. PMID:18856247

Free recall memory performance after aneurysmal subarachnoid hemorrhage.

PubMed

Sheldon, Signy; Macdonald, R Loch; Schweizer, Tom A

2012-03-01

Memory deficits for survivors of aneurysmal subarachnoid hemorrhage (SAH) are common, however, the nature of these deficits is not well understood. In this study, 24 patients with SAH and matched control participants were asked to study six lists containing words from four different categories. For half the lists, the categories were presented together (organized lists). For the remaining lists, the related words were presented randomly to maximize the use of executive processes such as strategy and organization (unorganized lists). Across adjoining lists, there was overlap in the types of categories given, done to promote intrusions. Compared to control participants, SAH patients recalled a similar number of words for the organized lists, but significantly fewer words for the unorganized lists. SAH patients also reported more intrusions than their matched counterparts. Separating patients into anterior communicating artery ruptures (ACoA) and ruptures in other regions, there was a recall deficit only for the unorganized list for those with ACoA ruptures and deficits across both list types for other rupture locations. These results suggest that memory impairment following SAH is likely driven by impairment in the executive components of memory, particularly for those with ACoA ruptures. Such findings may help direct future cognitive-therapeutic programs.

Severe subarachnoid hemorrhage associated with cerebral venous thrombosis in early pregnancy: a case report.

PubMed

Yamamoto, Junkoh; Kakeda, Shingo; Takahashi, Mayu; Idei, Masaru; Nakano, Yoshiteru; Soejima, Yoshiteru; Saito, Takeshi; Akiba, Daisuke; Shibata, Eiji; Korogi, Yukunori; Nishizawa, Shigeru

2013-12-01

Cerebral venous thrombosis (CVT) rarely induces subarachnoid hemorrhage (SAH). During late pregnancy and puerperium, CVT is an uncommon but important cause of stroke. However, severe SAH resulting from CVT is extremely rare during early pregnancy. We report on a rare case of severe SAH due to CVT, and discuss the potential pitfalls of CVT diagnosis in early pregnancy. A 32-year-old pregnant woman (9th week of pregnancy) presented with slight head dullness. Initial magnetic resonance imaging (MRI) revealed focal, abnormal signal intensity in the left thalamus. Nine days later, the patient developed a generalized seizure and severe SAH was detected with computed tomography (CT) scan. MRI and cerebral angiography revealed a completely thrombosed superior sagittal sinus, vein of Galen, straight sinus, and right transverse sinus. Transvaginal sonography indicated a missed abortion. The day after admission, the patient presented again with a progressive loss of consciousness and signs of herniation. The patient underwent emergency decompressive craniotomy, followed by intrauterine curettage. Two months later, she made an excellent recovery except for a slight visual field defect. A rare case of severe SAH due to CVT is reported, with emphasis on the potential pitfalls of CVT diagnosis in early pregnancy. Copyright © 2013 Elsevier Inc. All rights reserved.

Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

PubMed

Mapa, Ben; Taylor, Blake E S; Appelboom, Geoffrey; Bruce, Eliza M; Claassen, Jan; Connolly, E Sander

2016-01-01

Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH. We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization. A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion. Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality. Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Nocturnal Oxygen Desaturation Index is Inversely Correlated with Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tamai, Koji; Matsuoka, Hirofumi; Suzuki, Yujiro; Yoshimatsu, Harukazu; Masuya, Daiki; Nakashima, Nariyasu; Okada, Nobuhiko; Oda, Nao; Inoue, Sayaka; Koma, Yasuko; Otsuka, Akiko

2016-01-01

The concurrent diagnosis of chronic obstructive pulmonary disease (COPD) and sleep apnoea-hypopnoea syndrome (SAHS) (overlap syndrome), can contribute to worsening respiratory symptoms, but whether the severity of COPD is associated with co-morbid SAHS is unknown. We investigated whether the severity of COPD is associated with the complication of SAHS by examination of nocturnal oximetry as an alternative to polysomnography. Patients with COPD concurrently completed nocturnal oximetry, pulmonary function tests, a COPD assessment test, an Epworth sleepiness scale and a hospital anxiety and depression scale to evaluate the severity of COPD and possible concurrent presence of SAHS. We retrospectively analysed the data to assess correlation between the oxygen desaturation index (ODI) and each clinical variables and evaluated the predictors of ODI ≥ 15. This study included 103 patients (91 males, 88%) with a mean age of 72 ± 8 years and body mass index of 22 ± 3 kg/m(2). ODI was positively correlated with FEV1, FEV1/FVC and FEV1% predicted, which meant that ODI was inversely correlated with airflow limitation. Univariate logistic regression analysis revealed that FEV1% predicted and FEV1/FVC were predictors of ODI ≥ 15. ODI is inversely correlated with airflow limitation and milder COPD patients may have co-morbid SAHS.

Neuropeptide Y - an early biomarker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

PubMed

Schebesch, Karl-Michael; Brawanski, Alexander; Bele, Sylvia; Schödel, Petra; Herbst, Andreas; Bründl, Elisabeth; Kagerbauer, Simone Maria; Martin, Jan; Lohmeier, Anette; Stoerr, Eva-Maria; Proescholdt, Martin

2013-12-01

In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. The NPY levels were significantly higher in the SAH group than in the control group (p < 0·001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p > 0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence

Comparative genomics of transcriptional regulation of methionine metabolism in proteobacteria

DOE PAGES

Leyn, Semen A.; Suvorova, Inna A.; Kholina, Tatiana D.; ...

2014-11-20

Methionine metabolism and uptake genes in Proteobacteria are controlled by a variety of RNA and DNA regulatory systems. We have applied comparative genomics to reconstruct regulons for three known transcription factors, MetJ, MetR, and SahR, and three known riboswitch motifs, SAH, SAM-SAH, and SAM_alpha, in ~200 genomes from 22 taxonomic groups of Proteobacteria. We also identified two novel regulons: a SahR-like transcription factor SamR controlling various methionine biosynthesis genes in the Xanthomonadales group, and a potential RNA regulatory element with terminator-antiterminator mechanism controlling the metX or metZ genes in beta-proteobacteria. For each analyzed regulator we identified the core, taxon-specific andmore » genome-specific regulon members. By analyzing the distribution of these regulators in bacterial genomes and by comparing their regulon contents we elucidated possible evolutionary scenarios for the regulation of the methionine metabolism genes in Proteobacteria.« less

Impact of the moon on cerebral aneurysm rupture.

PubMed

Kamp, Marcel A; Dibué, Maxine; Slotty, Philipp; Steiger, Hans-Jakob; Hänggi, Daniel

2013-08-01

Several external and internal risk factors for cerebral aneurysm rupture have been identified to date. Recently, it has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage (SAH), however, another author found no such association. Therefore, the present study investigates the influence of the lunar cycle on the incidence of aneurysmal rupture, the initial clinical presentation, and the amount of subarachnoid blood. Lunar phase and the particular day of the lunar cycle were correlated to the date of aneurysm rupture, aneurysm location, initial clinical presentation, and amount of subarachnoid blood assessed from CT scans of all patients treated for basal SAH in our department from 2003 to 2010. We found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle. The moon influences neither the incidence of aneurysmal SAH nor the grade of initial neurological deterioration or amount of subarachnoid blood.

Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia.

PubMed

Burrell, Christian; Avalon, Nicole E; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M Cristine; Freeman, William D

2016-11-01

Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.

PDO modulation of the ENSO impact on the summer South Asian high

NASA Astrophysics Data System (ADS)

Xue, Xu; Chen, Wen; Chen, Shangfeng; Feng, Juan

2018-02-01

This study investigates modulation effects of the Pacific decadal oscillation (PDO) on the impact of boreal winter El Niño-Southern Oscillation (ENSO) on the South Asian high (SAH) variability in the following summer. In the El Niño together with positive PDO (EL/+PDO) or the La Niña together with negative PDO (LA/-PDO) years, boreal winter ENSO can influence the following summer SAH activity significantly. The SAH tends to be obviously strengthened (weakened) and located further south (north) during EL/+PDO (LA/-PDO). However, in the El Niño together with negative PDO (EL/-PDO) or the La Niña together with positive PDO (LA/+PDO) years, the influence of ENSO on the SAH tends to be weak. The strength and location of SAH are close to those in the climatology of 1950-2011 during the EL/-PDO or the LA/+PDO. Further analysis indicates that the PDO could exert pronounced influence on the ENSO-SAH connection via modulating the anomalous Walker circulation and charge effect over the tropical Indian Ocean (TIO). During the EL/+PDO or LA/-PDO, the anomalous Walker circulation associated with El Niño or La Niña is stronger and lasts for a longer time than those during the EL/-PDO or LA/+PDO. This leads to stronger descending (ascending) motion over the Maritime Continent and easterly (westerly) wind anomalies over the eastern Indian Ocean in the EL/+PDO (LA/-PDO), which further exert larger effects on the surface heat fluxes and subsurface ocean dynamical heating process over the Indian Ocean. As such, the induced warm (cold) sea surface temperature anomalies over the Indian Ocean are more significant and larger in the EL/+PDO (LA/-PDO). These larger sea surface temperature anomalies over the TIO could exert a more significant influence on the tropospheric temperature via moisture adjustment, which subsequently results in stronger SAH variability in the EL/+PDO or the LA/-PDO.

Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis

PubMed Central

Powell, J; Kitchen, N; Heslin, J; Greenwood, R

2002-01-01

Objectives: To investigate (1) the prevalence of various aspects of cognitive and psychosocial dysfunction, including post-traumatic stress symptoms, over nine months after subarachnoid haemorrhage (SAH); (2) whether SAH is preceded by increased life stress; (3) to what extent adverse outcomes may be predicted from preillness life stress, early neurological impairment, age, and sex; and (4) relations between emotional and functional outcomes. Methods: 52 patients with good neurological recovery after surgery for SAH were each matched for age, sex, and occupation with a healthy control participant. SAH patients were assessed three and nine months postdischarge on measures of cognitive functioning, mood, and social functioning. Objective stressors and subjective life change during the preceding year were rated retrospectively. Controls completed measures of mood and social functioning once only. Results: Compared with controls, SAH patients showed increased mood disturbance, subtle cognitive impairment, and abnormally low independence and participation on measures of social functioning. 60% showed clinically significant post-traumatic stress symptomatology (intrusive thoughts or avoidance of reminders) at three months and 30% at nine months. Independence in activities of daily living was greatly reduced in half to a third of the sample at both three and nine months. Productive employment was below the 10th percentile of the control group for 75% of patients at three months and for 56% at nine months; this outcome could not be predicted from selected demographic, premorbid, or clinical variables but dependence on others for organisational activities was predicted by impaired prose recall. Mood at nine months was strongly predicted by prior mental health problems, poor physical health, dysphasia, and impaired prose recall at three months. There was no evidence of an abnormally high level of stressful life events in the year before SAH, although patients rated their

[Use of "the Middlesex Elderly Assessment of Mental State" scale in the assessment of cognitive functioning in patients with aneurysmal subarachnoid haemorrhage].

PubMed

Chyza, Karolina Julia; Polityńska, Barbara; Kochanowicz, Jan; Lewko, Janusz

2007-03-01

It is now well established that cognitive deficits are a frequent consequence of aneurysmal subarachnoid haemorrhage (SAH). The cognitive status in the acute phase of the illness may provide valuable prognostic information in relation to the effects of the proposed treatment and long-term functioning of the patient. A prerequisite for this task is the identification of instruments that might prove useful in the diagnosis of neuropsychological deficits in patients with SAH. For these purposes we used The Middlesex Elderly Assessment of Mental State (MEAMS) in order to assess the cognitive deficits consequent upon SAH. To assess the cognitive functioning of patients undergoing treatment for SAH of aneurysmal origin in the acute stage of the illness, using a modified form of the MEAMS. 49 patients participated in the study, none of whom had a previous history of neurological or psychiatric illness. The age of the patients ranged between 23-70 years. 35 (71%) patients received surgical treatment (clipping of the aneurysm neck) and in 14 (29%) the aneurysm was embolised. The patients were assessed on two occasions: the first on admission to the Neurosurgery department following the SAH, and on the second, following treatment to secure the aneurysm. A modified version of the MEAMS in two parallel versions was used in the assessment. The results obtained were evaluated with reference to a control group. A range of cognitive impairments was identified with the aid of the MEAMS in patients undergoing treatment for aneurysmal SAH. These included deficits in visual and auditory memory, executive, perceptual and visuo-spatial functions together with the tendency to perseverate. In those patients who underwent surgery, deficits were observed in the following areas: disorientation in relation to self, time and place; perceptual, memory and visuo-spatial impairments. The results obtained indicate that the Middlesex Elderly Assessment of Mental State, in the form used in the

Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

PubMed

Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

2016-06-01

Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atomic-level insights into metabolite recognition and specificity of the SAM-II riboswitch

PubMed Central

Doshi, Urmi; Kelley, Jennifer M.; Hamelberg, Donald

2012-01-01

Although S-adenosylhomocysteine (SAH), a metabolic by-product of S-adenosylmethionine (SAM), differs from SAM only by a single methyl group and an overall positive charge, SAH binds the SAM-II riboswitch with more than 1000-fold less affinity than SAM. Using atomistic molecular dynamics simulations, we investigated the molecular basis of such high selectivity in ligand recognition by SAM-II riboswitch. The biosynthesis of SAM exclusively generates the (S,S) stereoisomer, and (S,S)-SAM can spontaneously convert to the (R,S) form. We, therefore, also examined the effects of (R,S)-SAM binding to SAM-II and its potential biological function. We find that the unfavorable loss in entropy in SAM-II binding is greater for (S,S)- and (R,S)-SAM than SAH, which is compensated by stabilizing electrostatic interactions with the riboswitch. The positively charged sulfonium moiety on SAM acts as the crucial anchor point responsible for the formation of key ionic interactions as it fits favorably in the negatively charged binding pocket. In contrast, SAH, with its lone pair of electrons on the sulfur, experiences repulsion in the binding pocket of SAM-II and is enthalpically destabilized. In the presence of SAH, similar to the unbound riboswitch, the pseudoknot structure of SAM-II is not completely formed, thus exposing the Shine-Dalgarno sequence. Unlike SAM, this may further facilitate ribosomal assembly and translation initiation. Our analysis of the conformational ensemble sampled by SAM-II in the absence of ligands and when bound to SAM or SAH reveals that ligand binding follows a combination of conformational selection and induced-fit mechanisms. PMID:22194311

Atomic-level insights into metabolite recognition and specificity of the SAM-II riboswitch.

PubMed

Doshi, Urmi; Kelley, Jennifer M; Hamelberg, Donald

2012-02-01

Although S-adenosylhomocysteine (SAH), a metabolic by-product of S-adenosylmethionine (SAM), differs from SAM only by a single methyl group and an overall positive charge, SAH binds the SAM-II riboswitch with more than 1000-fold less affinity than SAM. Using atomistic molecular dynamics simulations, we investigated the molecular basis of such high selectivity in ligand recognition by SAM-II riboswitch. The biosynthesis of SAM exclusively generates the (S,S) stereoisomer, and (S,S)-SAM can spontaneously convert to the (R,S) form. We, therefore, also examined the effects of (R,S)-SAM binding to SAM-II and its potential biological function. We find that the unfavorable loss in entropy in SAM-II binding is greater for (S,S)- and (R,S)-SAM than SAH, which is compensated by stabilizing electrostatic interactions with the riboswitch. The positively charged sulfonium moiety on SAM acts as the crucial anchor point responsible for the formation of key ionic interactions as it fits favorably in the negatively charged binding pocket. In contrast, SAH, with its lone pair of electrons on the sulfur, experiences repulsion in the binding pocket of SAM-II and is enthalpically destabilized. In the presence of SAH, similar to the unbound riboswitch, the pseudoknot structure of SAM-II is not completely formed, thus exposing the Shine-Dalgarno sequence. Unlike SAM, this may further facilitate ribosomal assembly and translation initiation. Our analysis of the conformational ensemble sampled by SAM-II in the absence of ligands and when bound to SAM or SAH reveals that ligand binding follows a combination of conformational selection and induced-fit mechanisms.

Aneurysmal subarachnoid hemorrhage in patients under 35-years-old: a single-center experience.

PubMed

Chalouhi, Nohra; Teufack, Sonia; Chandela, Sid; Dalyai, Richard; Tjoumakaris, Stavropoula; Hasan, David M; Dumont, Aaron S; Gonzalez, L Fernando; Rosenwasser, Robert H; Jabbour, Pascal M

2013-06-01

Aneurysmal subarachnoid hemorrhage (SAH) is relatively uncommon in young adults. There is a paucity of data pertaining to the management of aneurysmal SAH in young patients, especially with endovascular therapy. We reviewed all SAH patients under the age of 35 years treated at Jefferson Hospital for Neuroscience, Philadelphia, USA, from 2004 to 2009. A total of 40 patients (15 males and 25 females) under the age of 35 were treated for aneurysmal SAH. The average patient age was 30 years (17-35 yo); 25 (62.5%) were smokers. Seventeen patients presented with a Hunt and Hess Grade I or II (42.5%), 20 with a Grade III (50%), and 3 with a Grade IV (7.5%). Thirty-two aneurysms (80%) were located in the anterior circulation and 8 (20%) in the posterior circulation. Thirty-five patients (87.5%) were treated with coil embolization versus 5 with craniotomy and clipping. The endovascular and microsurgical occlusion rates were 90.6% and 100%, respectively. There were no procedural complications with endovascular therapy. Of 35 patients undergoing endovascular treatment, 24 (68.6%) had excellent outcomes at time of discharge with a Glasgow outcome scale of 5. There were no deaths in the series. No patient experienced a rehemorrhage after endovascular treatment. Smoking, female sex, and anterior circulation aneurysms are highly prevalent in young adults with SAH. Endovascular treatment resulted in an overall favorable outcome with no rehemorrhages in patients under the age of 35 years. Our results suggest that endovascular therapy is a reasonable treatment for young patients with SAH. Copyright © 2012 Elsevier B.V. All rights reserved.

Mortality after Spontaneous Subarachnoid Hemorrhage: Causality and Validation of a Prediction Model.

PubMed

Abulhasan, Yasser B; Alabdulraheem, Najayeb; Simoneau, Gabrielle; Angle, Mark R; Teitelbaum, Jeanne

2018-04-01

To evaluate primary causes of death after spontaneous subarachnoid hemorrhage (SAH) and externally validate the HAIR score, a prognostication tool, in a single academic institution. We reviewed all patients with SAH admitted to our neuro-intensive care unit between 2010 and 2016. Univariate and multivariate logistic regressions were performed to identify predictors of in-hospital mortality. The HAIR score predictors were Hunt and Hess grade at treatment decision, age, intraventricular hemorrhage, and rebleeding within 24 hours. Validation of the HAIR score was characterized with the receiver operating curve, the area under the curve, and a calibration plot. Among 434 patients with SAH, in-hospital mortality was 14.1%. Of the 61 mortalities, 54 (88.5%) had a neurologic cause of death or withdrawal of care and 7 (11.5%) had cardiac death. Median time from SAH to death was 6 days. The main causes of death were effect of the initial hemorrhage (26.2%), rebleeding (23%) and refractory cerebral edema (19.7%). Factors significantly associated with in-hospital mortality in the multivariate analysis were age, Hunt and Hess grade, and intracerebral hemorrhage. Maximum lumen size was also a significant risk factor after aneurysmal SAH. The HAIR score had a satisfactory discriminative ability, with an area under the curve of 0.89. The in-hospital mortality is lower than in previous reports, attesting to the continuing improvement of our institutional SAH care. The major causes are the same as in previous reports. Despite a different therapeutic protocol, the HAIR score showed good discrimination and could be a useful tool for predicting mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Differences in Neuropeptide Y Secretion Between Intracerebral Hemorrhage and Aneurysmal Subarachnoid Hemorrhage.

PubMed

Schebesch, Karl-M; Bründl, Elisabeth; Schödel, Petra; Hochreiter, Andreas; Scheitzach, Judith; Bele, Sylvia; Brawanski, Alexander; Störr, Eva-M; Lohmeier, Anette; Proescholdt, Martin

2017-07-01

Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Seventy-nine patients were prospectively included: SAH patients (n=66) (historic population) and intracerebral hemorrhage patients (n=13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P<0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.

A Preliminary Observational Study of Anovulatory Uterine Bleeding After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Brown, Suzanne M; Fifield, Susan W; Pizzi, Michael A; Alejos, David; Richie, Alexa N; Dinh, Tri A; Cheshire, William P; Meek, Shon E; Freeman, William D

2017-12-01

It was observed that women with aneurysmal subarachnoid hemorrhage (aSAH) tended to have earlier menses than a typical 21- to 28-day cycle. The goal was to determine whether there is an association between aSAH and early onset of menses. All cases of aSAH in women aged 18 to 55 years who were admitted to our facility's neuroscience intensive care unit from June 1, 2011, to June 30, 2012, were reviewed. The electronic healthcare record for each of these patients was examined for documentation of menses onset, computed tomography of the head, brain aneurysm characteristics, modified Fisher score and Glasgow Coma Scale on admission, presence/absence of vasospasm, medical/surgical history, and use of medications that affect the menstrual cycle. The mean onset of menses in this study population was compared with the mean of 21 to 28 days with the 1-sample t test. During the study period, 103 patients with subarachnoid hemorrhage were admitted. Sixty-one were women, and 15 were aged 18 to 55 years. Nine of the 15 (60%) had documentation of menses occurring during their initial week of hospitalization; 1 patient had documentation of menses on hospital day 12. There is a significant difference when the mean onset of menses in our patient population is compared with the approximate normal menstrual cycle of 21 to 28 days (P < .01). Early onset of menses or abnormal uterine bleeding after SAH may occur in women with aSAH and typically within the first 7 to 10 days after intracranial aneurysm rupture. The physiologic cause of early onset of menses after aSAH, whether primary or secondary, remains unknown.

Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer.

PubMed

Parada-Huerta, E; Alvarez-Dominguez, Tp; Uribe-Escamilla, R; Rodriguez-Joya, Jf; Ponce-Medrano, Ja Diaz; Padron-Lucio, S; Alfaro-Rodriguez, A; Bandala, C

2016-01-01

Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis. On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. In Mexican patients with BCa and SAH treated with non-selective (β1- and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

PubMed

Ivanidze, J; Kesavabhotla, K; Kallas, O N; Mir, D; Baradaran, H; Gupta, A; Segal, A Z; Claassen, J; Sanelli, P C

2015-05-01

Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction. © 2015 by American Journal of Neuroradiology.

Predictors of Shunt-dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage? A Systematic Review and Meta-Analysis.

PubMed

Xie, Zhiyi; Hu, Xin; Zan, Xin; Lin, Sen; Li, Hao; You, Chao

2017-10-01

Hydrocephalus is a well-recognized complication after aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to identify predictors for shunt-dependent hydrocephalus (SDHC) after aSAH via a systematic review and meta-analysis. A systematic search was conducted using the Embase, MEDLINE, and Web of Science databases for studies pertaining to aSAH and SDHC. Risk factors were assessed by meta-analysis when they were reported by at least 2 studies. The results were presented as odd ratios or risk ratios according to the study design with the corresponding 95% confidence intervals (CI). Twenty-five studies were included. In primary analysis of 14 potential risk factors, 12 were identified as predictors of SDHC after aSAH including age ≥50 years, female gender, high Hunt-Hess grade, Glasgow Coma Scale ≤8, Fisher grade ≥3, acute hydrocephalus, external ventricular drainage insertion, intraventricular hemorrhage, postcirculation aneurysm, anterior communicating artery aneurysm, meningitis, and rebleeding. The meta-analysis based on cohort studies found a significantly increased risk for SDHC in patients with aSAH treated by coiling (risk ratio, 1.16; 95% CI, 1.05-1.29), while the meta-analysis based on case-controlled studies failed to replicate this finding (odds ratio, 1.27; 95% CI, 0.95-1.71). Several new predictors of SDHC after aSAH were identified that may assist with the early recognition and prevention of SDHC. The controversial evidence found in this study was insufficient to support the potential of neurosurgical clipping for reducing the risk of shunt dependency. Further well-designed studies are warranted to explore the effect of treatment modality on SDHC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Early release of high-mobility group box 1 (HMGB1) from neurons in experimental subarachnoid hemorrhage in vivo and in vitro

PubMed Central

2014-01-01

Background Translocation of high-mobility group box 1 (HMGB1) from nucleus could trigger inflammation. Extracellular HMGB1 up-regulates inflammatory response in sepsis as a late mediator. However, little was known about its role in subarachnoid hemorrhage-inducible inflammation, especially in the early stage. This study aims to identify whether HMGB1 translocation occurred early after SAH and also to clarify the potential role of HMGB1 in brain injury following SAH. Methods Sprague-Dawley (SD) rats were randomly divided into sham group and SAH groups at 2 h, 12 h and on day 1, day 2. SAH groups suffered experimental subarachnoid hemorrhage by injection of 0.3 ml autoblood into the pre-chiasmatic cistern. Rats injected by recombinant HMGB1(rHMGB1) solution were divided into four groups according to different time points. Cultured neurons were assigned into control group and four hemoglobin (Hb) incubated groups. Mixed glial cells were cultured and stimulated in medium from neurons incubated by Hb. HMGB1 expression is measured by western blot analysis, real-time polymerase chain reaction (PCR), immunohistochemistry and immunofluorescence. Downstream nuclear factor kappa B (NF-κB) subunit P65 and inflammatory factor Interleukin 1β (IL-1β) were measured by western blot and real-time PCR, respectively. Brain injury was evaluated by cleaved caspase-3 staining. Results Our results demonstrated HMGB1 translocation occurred as early as 2 h after experimental SAH with mRNA and protein level increased. Immunohistochemistry and immunofluorescence results indicated cytosolic HMGB1 was mainly located in neurons while translocated HMGB1 could also be found in some microglia. After subarachnoid injection of rHMGB1, NF-κB, downstream inflammatory response and cleaved caspase-3 were up-regulated in the cortex compared to the saline control group. In-vitro, after Hb incubation, HMGB1 was also rapidly released from neurons to medium. Incubation with medium from neurons up

The effects of dietary supplementation of methionine on genomic stability and p53 gene promoter methylation in rats.

PubMed

Amaral, Cátia Lira Do; Bueno, Rafaela de Barros E Lima; Burim, Regislaine Valéria; Queiroz, Regina Helena Costa; Bianchi, Maria de Lourdes Pires; Antunes, Lusânia Maria Greggi

2011-05-18

Methionine is a component of one-carbon metabolism and a precursor of S-adenosylmethionine (SAM), the methyl donor for DNA methylation. When methionine intake is high, an increase of S-adenosylmethionine (SAM) is expected. DNA methyltransferases convert SAM to S-adenosylhomocysteine (SAH). A high intracellular SAH concentration could inhibit the activity of DNA methyltransferases. Therefore, high methionine ingestion could induce DNA damage and change the methylation pattern of tumor suppressor genes. This study investigated the genotoxicity of a methionine-supplemented diet. It also investigated the diet's effects on glutathione levels, SAM and SAH concentrations and the gene methylation pattern of p53. Wistar rats received either a methionine-supplemented diet (2% methionine) or a control diet (0.3% methionine) for six weeks. The methionine-supplemented diet was neither genotoxic nor antigenotoxic to kidney cells, as assessed by the comet assay. However, the methionine-supplemented diet restored the renal glutathione depletion induced by doxorubicin. This fact may be explained by the transsulfuration pathway, which converts methionine to glutathione in the kidney. Methionine supplementation increased the renal concentration of SAH without changing the SAM/SAH ratio. This unchanged profile was also observed for DNA methylation at the promoter region of the p53 gene. Further studies are necessary to elucidate this diet's effects on genomic stability and DNA methylation. 2011 Elsevier B.V. All rights reserved.

Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?

PubMed

Gaberel, Thomas; Gakuba, Clement; Goulay, Romain; Martinez De Lizarrondo, Sara; Hanouz, Jean-Luc; Emery, Evelyne; Touze, Emmanuel; Vivien, Denis; Gauberti, Maxime

2014-10-01

The aim of the present study was to investigate the impact of different stroke subtypes on the glymphatic system using MRI. We first improved and characterized an in vivo protocol to measure the perfusion of the glymphatic system using MRI after minimally invasive injection of a gadolinium chelate within the cisterna magna. Then, the integrity of the glymphatic system was evaluated in 4 stroke models in mice including subarachnoid hemorrhage (SAH), intracerebral hemorrhage, carotid ligature, and embolic ischemic stroke. We were able to reliably evaluate the glymphatic system function using MRI. Moreover, we provided evidence that the glymphatic system was severely impaired after SAH and in the acute phase of ischemic stroke, but was not altered after carotid ligature or in case of intracerebral hemorrhage. Notably, this alteration in glymphatic perfusion reduced brain clearance rate of low-molecular-weight compounds. Interestingly, glymphatic perfusion after SAH can be improved by intracerebroventricular injection of tissue-type plasminogen activator. Moreover, spontaneous arterial recanalization was associated with restoration of the glymphatic function after embolic ischemic stroke. SAH and acute ischemic stroke significantly impair the glymphatic system perfusion. In these contexts, injection of tissue-type plasminogen activator either intracerebroventricularly to clear perivascular spaces (for SAH) or intravenously to restore arterial patency (for ischemic stroke) may improve glymphatic function. © 2014 American Heart Association, Inc.

The Relationship Between Serum Neuron-Specific Enolase Levels and Severity of Bleeding and Functional Outcomes in Patients With Nontraumatic Subarachnoid Hemorrhage.

PubMed

Tawk, Rabih G; Grewal, Sanjeet S; Heckman, Michael G; Rawal, Bhupendra; Miller, David A; Edmonston, Drucilla; Ferguson, Jennifer L; Navarro, Ramon; Ng, Lauren; Brown, Benjamin L; Meschia, James F; Freeman, William D

2016-04-01

The value of neuron-specific enolase (NSE) in predicting clinical outcomes has been investigated in a variety of neurological disorders. To investigate the associations of serum NSE with severity of bleeding and functional outcomes in patients with subarachnoid hemorrhage (SAH). We retrospectively reviewed the records of patients with SAH from June 2008 to June 2012. The severity of SAH bleeding at admission was measured radiographically with the Fisher scale and clinically with the Glasgow Coma Scale, Hunt and Hess grade, and World Federation of Neurologic Surgeons scale. Outcomes were assessed with the modified Rankin Scale at discharge. We identified 309 patients with nontraumatic SAH, and 71 had NSE testing. Median age was 54 years (range, 23-87 years), and 44% were male. In multivariable analysis, increased NSE was associated with a poorer Hunt and Hess grade (P = .003), World Federation of Neurologic Surgeons scale score (P < .001), and Glasgow Coma Scale score (P = .003) and worse outcomes (modified Rankin Scale at discharge; P = .001). There was no significant association between NSE level and Fisher grade (P = .81) in multivariable analysis. We found a significant association between higher NSE levels and poorer clinical presentations and worse outcomes. Although it is still early for any relevant clinical conclusions, our results suggest that NSE holds promise as a tool for screening patients at increased risk of poor outcomes after SAH.

Fat and neurosurgery: does obesity affect outcome after intracranial surgery?

PubMed

Schultheiss, Kim E; Jang, Yeon Gyoe; Yanowitch, Rachel N; Tolentino, Jocelyn; Curry, Daniel J; Lüders, Jürgen; Asgarzadie-Gadim, Farbod; Macdonald, R Loch

2009-02-01

Obesity has been linked to increased morbidity and mortality after some surgical procedures. The purpose of this study was to determine whether obesity affects outcome after general neurosurgery and subarachnoid hemorrhage (SAH). Three data sets were analyzed, including a retrospective review of 404 patients undergoing cranial and spinal neurosurgical procedures, a prospective collection of 100 patients with aneurysmal SAH, and data from 3567 patients with aneurysmal SAH who were entered into randomized clinical trials of tirilazad. For each data set, outcome was assessed by mortality, postoperative morbidity, and Glasgow Outcome Scale score. Prognostic factors, including body weight and body mass index, were tested for their effect on these outcomes using multivariable logistic regression. For patients undergoing general cranial and spinal neurosurgery, independent predictors of morbidity and mortality were age, American Society of Anesthesia class, disseminated malignancy, emergency surgery, and increased duration of surgery. For patients with SAH, score on the Glasgow Outcome Scale was associated with age and admission Glasgow Coma Scale score. In the tirilazad data set, multiple factors were associated with score on the Glasgow Outcome Scale, but, as with the other 2 data sets, body weight had no relationship to outcome. Obesity may have less effect on the outcome of patients with mainly cranial neurosurgical disease and aneurysmal SAH than it does on patients undergoing other types of surgery.

Usefulness of B-mode and doppler sonography for the diagnosis of severe acute viral hepatitis A.

PubMed

Shin, Sang Wook; Kim, Tae Yeob; Jeong, Woo Kyoung; Kim, Yongsoo; Kim, Jinoo; Kim, Young Hwan; Park, Hwan Cheol; Sohn, Joo Hyun

2015-01-01

To investigate B-mode and Doppler ultrasonography (US) features correlating with laboratory findings for the diagnosis of severe acute hepatitis (SAH) in patients with hepatitis A virus infection. Thirty-nine consecutive serologically proven patients were enrolled. Decreased parenchymal echotexture, periportal tracking, gallbladder wall change, and splenomegaly were assessed on B-mode images. Blood flow velocities were measured in the main portal (V(PORTAL)) and in the hepatic veins, and the hepatic venous pulsatility index was calculated. SAH was defined as high model for end-stage liver disease (MELD) score ≥ 15 with or without coagulopathy. The relationship between US features and laboratory findings was assessed, and SAH diagnosis was evaluated. Serum alanine transaminase and prothrombin time were significantly different depending on the presence of gallbladder wall change and splenomegaly (p < 0.05). V(PORTAL) was inversely correlated with MELD score (r = -0.485) and several laboratory markers. The hepatic venous waveform and hepatic venous pulsatility index were significantly correlated with MELD score. For the diagnosis of SAH, the area under the receiver operating characteristic curve of V(PORTAL) was 0.798. It reached 0.869 in the patients with typical GB change. Both B-mode and Doppler US correlated well with several laboratory variables and may be helpful to diagnose SAH in patients with hepatitis A virus infection. © 2014 Wiley Periodicals, Inc.

Ischemia modified albumin increase indicating cardiac damage after experimental subarachnoid hemorrhage

PubMed Central

2014-01-01

Background Cardiac complications are often developed after subarachnoid hemorrhage (SAH) and may cause sudden death of the patient. There are reports in the literature addressing ischemia modified albumin (IMA) as an early and useful marker in the diagnosis of ischemic heart events. The aim of this study is to evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first, second, and seventh days of experimental SAH in rats. Twenty-eight Wistar albino rats were divided into four groups each consisting of seven animals. These were classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by transclival basilar artery puncture. Blood samples were collected under anesthesia from the left ventricles of the heart using the cardiac puncture method for IMA measurement. Histopathological examinations were performed on the heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on an automatic analyser using the enzymatic method. IMA using by ACB test was detected with spectrophotometer. Results Serum IMA (p = 0.044) in seventh day of SAH were higher compared to the control group. Total injury scores of heart and lung tissue, also myocytolysis at day 7 were significantly higher than control group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001) and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA - myocytolysis (r = 0.48, p = 0.008), and between IMA – heart tissue total injury score (r = 0.41, p = 0.029) was found. Conclusion The results revealed that increased serum IMA may be related to myocardial stress after SAH. PMID:24564759

National socioeconomic indicators are associated with outcomes after aneurysmal subarachnoid hemorrhage: a hierarchical mixed-effects analysis.

PubMed

Guha, Daipayan; Ibrahim, George M; Kertzer, Joshua D; Macdonald, R Loch

2014-11-01

Although heterogeneity exists in patient outcomes following subarachnoid hemorrhage (SAH) across different centers and countries, it is unclear which factors contribute to such disparities. In this study, the authors performed a post hoc analysis of a large international database to evaluate the association between a country's socioeconomic indicators and patient outcome following aneurysmal SAH. An analysis was performed on a database of 3552 patients enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997, which included 162 neurosurgical centers in North and Central America, Australia, Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH: mortality and Glasgow Outcome Scale (GOS) score. The association between these outcomes, nation-level socioeconomic indicators (percapita gross domestic product [GDP], population-to-neurosurgeon ratio, and health care funding model), and patientlevel covariates were assessed using a hierarchical mixed-effects logistic regression analysis. Multiple previously identified patient-level covariates were significantly associated with increased mortality and worse neurological outcome, including age, intraventricular hemorrhage, and initial neurological grade. Among national-level covariates, higher per-capita GDP (p < 0.05) was associated with both reduced mortality and improved neurological outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer neurosurgical centers per population (p < 0.001), was also associated with better neurological outcome (p < 0.01). Health care funding model was not a significant predictor of either primary outcome. Higher per-capita gross GDP and population-to-neurosurgeon ratio were associated with improved outcome after aneurysmal SAH. The former result may speak to the availability of resources, while the latter may be a reflection of better outcomes with centralized care. Although patient clinical and radiographic phenotypes remain

Identification of clinical and paraclinical findings predictive for headache occurrence during spontaneous subarachnoid hemorrhage.

PubMed

Ljubisavljevic, Srdjan; Milosevic, Vuk; Stojanov, Aleksandar; Ljubisavljevic, Marina; Dunjic, Olivera; Zivkovic, Miroslava

2017-07-01

Headache is recognized as the main but unwarranted symptom of subarachnoid hemorrhage (SAH). There are no enough findings identified as predictive for headache occurrence in SAH. We evaluated the clinical and paraclinical factors predictive for headache occurrence in SAH. We retrospectively analyzed medical records of 431 consecutive non traumatic SAH patients (264 females and 167 males), ages from 19 to 91 years, presenting with headache (70.3%) and without headache (29.7%) during period of 11years. Among all tested parameters, as negative predictors for headache occurrence were recognized: patients' ages (OR 0.97 [95%CI: 0.96-0.99], p=0.025), persistence of coagulation abnormality (OR 0.23 [95%CI: 0.08-0.67], p=0.006), atrial fibrilation (OR 0.23 [95%CI: 0.09-0.59], p=0.002), chronic renal failure (OR 0.26 [95%CI: 0.09-0.76], p=0.014) and more diseases (OR 0.11 [95%CI: 0.04-0.32], p<0.0001), as higher clinical score (OR 0.94 [95%CI: 0.90-0.99], p=0.018) including positive neurological findings (OR 0.34 [95%CI: 0.21-0.55], p<0.001) and loss of consciousness (OR 0.22 [95%CI: 0.12-0.39], p<0.001) at the SAH onset, while the complaint of neck stiffness was identified as its positive predictor (OR 1.93 [95%CI: 1.19-3.10], p=0.007). Although diagnosis based solely on clinical presentation is not reliable and speculative, our findings could provide physicians with evidence to consider SAH not only in conditions of its headache occurrence but also in those with headache absence. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanism of substrate specificity in 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidases

PubMed Central

Siu, Karen K.W.; Asmus, Kyle; Zhang, Allison N.; Horvatin, Cathy; Li, Sheng; Liu, Tong; Moffatt, Barbara; Woods, Virgil L.; Howell, P. Lynne

2010-01-01

5′-Methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidase (MTAN) plays a key role in the methionine-recycling pathway of bacteria and plants. Despite extensive structural and biochemical studies, the molecular mechanism of substrate specificity for MTAN remains an outstanding question. Bacterial MTANs show comparable efficiency in hydrolyzing MTA and SAH, while the plant enzymes select preferentially for MTA, with either no or significantly reduced activity towards SAH. Bacterial and plant MTANs show significant conservation in the overall structure, and the adenine- and ribose-binding sites. The observation of a more constricted 5′-alkylthio binding site in Arabidopsis thaliana AtM-TAN1 and AtMTAN2, two plant MTAN homologues, led to the hypothesis that steric hindrance may play a role in substrate selection in plant MTANs. We show using isothermal titration calorimetry that SAH binds to both Escherichia coli MTAN (EcMTAN) and AtMTAN1 with comparable micromolar affinity. To understand why AtMTAN1 can bind but not hydrolyze SAH, we determined the structure of the protein–SAH complex at 2.2 Å resolution. The lack of catalytic activity appears to be related to the enzyme’s inability to bind the substrate in a catalytically competent manner. The role of dynamics in substrate selection was also examined by probing the amide proton exchange rates of EcMTAN and AtMTAN1 via deuterium–hydrogen exchange coupled mass spectrometry. These results correlate with the B factors of available structures and the thermodynamic parameters associated with substrate binding, and suggest a higher level of conformational flexibility in the active site of EcMTAN. Our results implicate dynamics as an important factor in substrate selection in MTAN. PMID:20554051

An experimental study of the neurophysical mechanisms of photophobia induced by subarachnoid hemorrhage.

PubMed

Aydin, Nazan; Kotan, Dilcan; Keles, Sadullah; Ondas, Osman; Aydin, Mehmet Dumlu; Baykal, Orhan; Gundogdu, Betul

2016-09-06

Photophobia is defined as a painful psychosomatic discomfort triggered by intense light flow through the pupils to the brain, but the exact mechanism through which photophobia is induced by subarachnoid hemorrhage (SAH) is not well understood. In this study, we aimed to investigate whether there was any relationship between the mydriasis induced by the degeneration of the ciliary ganglion (CG) and photophobia in instances of SAH. Five of a total of 25 rabbits were used as the intact control group; five were used in the sham-operated control group; and the remaining 15 were used as the SAH group, which was created by injecting autologous blood into their cisterna magna. All animals were examined daily for 20days to evaluate their level of photophobia, after which their brains, CGs and superior cervical ganglia (SCGs) were extracted bilaterally. The densities of normal and degenerated neurons in these ganglia were examined by stereological methods. In SAH animals with a high photophobia score, the mean pupil diameter and density of degenerated neurons density in the CG were greater than in cases with a low photophobia score (p<0.05). Further analysis revealed that the increase in the density of degenerated neurons in the CG following SAH resulted in the paralysis of the parasympathetic pathway of the pupillary muscles and mydriasis, which facilitates the excessive transfer of light to the brain and photophobia. Our findings indicate that SAH results in a high density of degenerated neurons in the CG, which induces mydriasis and is an important factor in the onset of photophobia. This phenomenon is likely due to more light energy being transferred through mydriatic pupils to the brain, resulting in vasospasm of the supplying arteries. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictors of hydrocephalus as a complication of non-traumatic subarachnoid hemorrhage: a retrospective observational cohort study in 107 patients.

PubMed

Vinas Rios, Juan Manuel; Sanchez-Aguilar, Martin; Kretschmer, Thomas; Heinen, Christian; Medina Govea, Fatima Azucena; Jose Juan, Sanchez-Rodriguez; Schmidt, Thomas

2018-01-01

The predictors of shunt dependency such as amount of subarachnoid blood, acute hydrocephalus (HC), mode of aneurysm repair, clinical grade at admission and cerebro spinal fluid (CSF) drainage in excess of 1500 ml during the 1st week after the subarachnoid hemorrhage (SAH) have been identified as predictors of shunt dependency. Therefore our main objective is to identify predictors of CSF shunt dependency following non-traumatic subarachnoid hemorrhage. We performed a retrospective study including patients from January 1st 2012 to September 30th 2014 between 16 and 89 years old and had a non-traumatic subarachnoid hemorrhage in cranial computed tomography (CCT). We excluded patients with the following characteristics: Patients who died 3 days after admittance, lesions in brainstem, previous surgical treatment in another clinic, traumatic brain injury, pregnancy and disability prior to SAH.We performed a descriptive and comparative analysis as well as a logistic regression with the variables that showed a significant difference ( p  < 0.05). Hence we identified the variables concerning HC after non traumatic SAH and its correlation. One hundred and seven clinical files of patients with non-traumatic SAH were analyzed. Twenty one (48%) later underwent shunt treatment. Shunt patients had significantly clinical and corroborated with doppler ultrasonography vasospasmus ( p  = 0.015), OR = 5.2. The amount of subarachnoidal blood according to modified Fisher grade was ( p  = 0.008) OR = 10.9. Endovascularly treated patients were less often shunted as compared with those undergoing surgical aneurysm repair ( p  = 0.004). Vasospasmus and a large amount of ventricular blood seem to be a predictor concerning hydrocephalus after non-traumatic SAH. Hence according to our results the presence of these two variables could alert the treating physician in the decision whether an early shunt implantation < 7 days after SAH should be necessary.

Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy.

PubMed

Boucher, Olivier; Dagenais, Emmanuelle; Bouthillier, Alain; Nguyen, Dang Khoa; Rouleau, Isabelle

2015-11-01

The advantage of selective amygdalohippocampectomy (SAH) over anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy (TLE) remains controversial. Because ATL is more extensive and involves the lateral and medial parts of the temporal lobe, it may be predicted that its impact on memory is more important than SAH, which involves resection of medial temporal structures only. However, several studies do not support this assumption. Possible explanations include task-specific factors such as the extent of semantic and syntactic information to be memorized and failure to control for main confounders. We compared preoperative vs. postoperative memory performance in 13 patients with SAH with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales - 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery

Frequency and magnitude of selected historical landslide events in the southern Appalachian Highlands of North Carolina and Virginia: relationships to rainfall, geological and ecohydrological controls, and effects

Treesearch

Richard M. Wooten; Anne C. Witt; Chelcy F. Miniat; Tristram C. Hales; Jennifer L. Aldred

2016-01-01

Landsliding is a recurring process in the southern Appalachian Highlands (SAH) region of the Central Hardwood Region. Debris flows, dominant among landslide processes in the SAH, are triggered when rainfall increases pore-water pressures in steep, soil-mantled slopes. Storms that trigger hundreds of debris flows occur about every 9 years and those that...

Ocular Signs Related to Overweight and Arterial Hypertension in Children: A Systematic Review

PubMed Central

Schuh, Daniela S.; Piccoli, Ângela B.; Paiani, Raquel L.; Maciel, Cristiane R; Pellanda, Lucia C; Vilela, Manuel AP

2017-01-01

Background: The ocular effects of obesity and hypertension need to be established and can be used as prognostic markers. Objective: To estimate the prevalence of ophthalmological alterations in children and adolescents who are overweight and/or have SAH. Methods: The database for this study included all observational studies (CS, cohort, case-control and “baseline” description of randomized clinical trials) with children and/or adolescents who were overweight, obese or had SAH and that measured ophthalmological alterations. Results: Comparative studies with healthy children demonstrated positive association between body adiposity with retinal venular dilation, and SAH with retinal arteriolar narrowing. Different retinal fundus cameras and computer-assisted programs to evaluate the retinal vessels, variations in the methods of analysis, adjustments, populations, were the main arguments against formal meta-analysis. The heterogeneity was too high (I2 >90%, in fixed or randomized effects), and the lack of linearity, normal distribution and homoscedasticity did not recommend meta-regression. Conclusion: Obesity and SAH show associations with ophthalmological alterations, especially with retinal vessel diameter. Lack of standardization does not allow a quantitative evaluation. PMID:29081867

Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans.

PubMed

Jorgensen, Anders; Staalsoe, Jonatan M; Simonsen, Anja H; Hasselbalch, Steen G; Høgh, Peter; Weimann, Allan; Poulsen, Henrik E; Olsen, Neils V

2018-01-01

Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1-14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (p values < .001), and exhibited a progressive further increase (to >20-fold above control levels) from day 5-14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH.

Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage

PubMed Central

2012-01-01

Background Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Methods Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. Results When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the

Relation of RhoA in Peripheral Blood Mononuclear Cells With Severity of Aneurysmal Subarachnoid Hemorrhage and Vasospasm.

PubMed

González-Montelongo, María Del Carmen; Egea-Guerrero, Juan José; Murillo-Cabezas, Francisco; González-Montelongo, Rafaela; Ruiz de Azúa-López, Zaida; Rodríguez-Rodríguez, Ana; Vilches-Arenas, Angel; Castellano, Antonio; Ureña, Juan

2018-06-01

Rho-kinase, an effector of RhoA, is associated with various cardiovascular diseases in circulating blood cells. However, the role of RhoA/Rho-kinase in peripheral blood mononuclear cells from patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) has not yet been studied in relation to the severity of this disease. Therefore, we analyzed the expression and activity of RhoA as a possible biomarker in aSAH. Twenty-four patients with aSAH and 15 healthy subjects were examined. Peripheral blood mononuclear cells were collected, and RhoA activity and expression were determined by RhoA activation assay kit (G-LISA) and enzyme-linked immunosorbent assay tests, respectively. The severity of aSAH was determined from the World Federation of Neurological Surgeon scale, and vasospasm was evaluated using clinical symptoms, arteriography, and sonography. RhoA expression was significantly increased in peripheral blood mononuclear cells from patients on days 0, 2, and 4 after aSAH versus healthy subjects ( P =0.036, 0.010, and 0.018, respectively, by U Mann-Whitney analysis). There was a significant correlation between RhoA expression and injury severity on days 2 and 4 (Spearman test, day 2: r =0.682, n=14, P =0.007; day 4: r =0.721, n=14, P =0.004). No significant correlation was observed on day 0 (day 0: r =0.131, n=6, P =0.805). Active RhoA was not significantly different in patients and healthy subjects on days 0, 2, and 4 ( P =0.243, 0.222, and 0.600, respectively) nor did it increase significantly on days 0 and 2 in patients with vasospasm versus patients without vasospasm ( P =0.064 and 0.519, respectively). In contrast, active RhoA was significantly higher on day 4 in patients who developed vasospasm versus patients without vasospasm ( P =0.028). Our preliminary results indicate that RhoA expression and activity in peripheral blood mononuclear cells might be related with aSAH severity and cerebral vasospasm. RhoA is a potential biomarker of the risks

Asymmetric and Symmetric Dimethylarginines are Markers of Delayed Cerebral Ischemia and Neurological Outcome in Patients with Subarachnoid Hemorrhage.

PubMed

Appel, Daniel; Seeberger, Miriam; Schwedhelm, Edzard; Czorlich, Patrick; Goetz, Alwin E; Böger, Rainer H; Hannemann, Juliane

2018-03-20

Delayed cerebral ischemia (DCI) is the major cause of lethality and neuronal damage in patients who survived the primary subarachnoid hemorrhage (SAH). Asymmetric and symmetric dimethylarginines (ADMA and SDMA) inhibit nitric oxide production from L-arginine via distinct mechanisms. Elevated ADMA levels are associated with vasospasm after SAH. We aimed to study the time course of ADMA and SDMA in plasma and ventricular cerebrospinal fluid (CSF) and their associations with DCI and outcome. We measured ADMA and SDMA in 34 SAH patients with an external ventricular drain at admission and on days 3, 6, 8, 12, and 15 and followed them up for clinical status and neurological outcome until 30 days post-discharge. DCI was defined as the appearance of new infarctions on cerebral computed tomography or magnetic resonance imaging. ADMA and SDMA plasma concentrations did not differ significantly at baseline between patients who suffered DCI (N = 14; 41%) and not; however, plasma ADMA reached a peak on days 8 and 15 after hemorrhage in patients with DCI (0.81-0.91 µmol/l). Baseline plasma L-arginine/ADMA ratio was significantly lower in patients with DCI (57.1 [34.3; 70.8] vs. 68.7 [55.7; 96.2]; p < 0.05). ADMA and SDMA concentrations in CSF were significantly higher in patients with DCI than without. In multivariable-adjusted linear regression models, CSF ADMA was negatively associated with the incidence of DCI (OR 0.03 [0.02-0.70]; p = 0.04), whereas CSF SDMA on the day of hemorrhage predicted poor neurological outcome until 30 days after discharge (OR 22.4 [1.21-416.02]; p = 0.04). Our study shows that ADMA and the L-arginine/ADMA ratio are associated with the incidence of DCI after SAH. By contrast, SDMA was associated with initial neuronal damage and poor neurological outcome after SAH. These data support the hypothesis that ADMA and L-arginine affect the pathophysiology of cerebral ischemia after SAH, while SDMA is a biomarker of neurological outcome after SAH.

An Evaluation of Subseasonal Intensity Variation of the South Asian High in the CMIP5 Models

NASA Astrophysics Data System (ADS)

Shang, W.; Ren, X.

2017-12-01

The South Asian High (SAH) is a vital member among the Asian summer monsoon circulations in the upper troposphere located over the Tibetan Plateau and its surrounding areas during boreal summer. This study presents an evaluation of the characteristics of SAH's subseasonal intensity variation simulated by 18 coupled models from the Coupled Model Intercomparison Project (CMIP5). The empirical orthogonal function (EOF) analysis is used on subseasonal anomalies in 100hPa geopotential height over 20°-40°N, 35°-110°E for June, July and August from 1979 to 2005. The first EOF mode from the ERA-Interim (denoted as observation) shows a monopole pattern capturing the strengthening/weakening of SAH. The power spectrum analysis of the corresponding principal component (PC1) time series shows a period about 10-30 days. In general, all the 18 coupled models can reproduce the monopole pattern and its subseasonal oscillation to a certain extent. The four well-simulated models are: ACCESS1-3, HadGEM2-CC, MRI-CGCM3 and BNU-ESM, which EOF1 show strong positive anomalies in the 100hPa geopotential height over the SAH's region and weak negative anomalies in their north side. Lead-lag regression shows that the evolution of the EOF1 from day -12 to +3 in the above four models is also reasonably simulated. In the observation, positive rainfall band moves northward from the equatorial Indian Ocean, the Bay of Bengals and the Western North Pacific to the north of Indian Peninsula, south of Tibetan Plateau and Southeast China, accompanied by the increasing intensity of SAH. In the above four models, the northward movement of anomalous rainfall band can be well reproduced. In the observation, the spatial pattern of anomalies in integrated apparent heat source and integrated apparent moisture sink resemble that of rainfall, thus corresponding to anomalous condensation heat release. The anomalous heating stimulates positive height anomalies with an anomalous anticyclonic circulation to its

Development and validation of an LC-MS/MS assay for the quantification of the trans-methylation pathway intermediates S-adenosylmethionine and S-adenosylhomocysteine in human plasma.

PubMed

Klepacki, Jacek; Brunner, Nina; Schmitz, Volker; Klawitter, Jelena; Christians, Uwe; Klawitter, Jost

2013-06-05

Although increased levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) have been implicated as markers for renal and vascular dysfunction, until now there have been no studies investigating their association with clinical post-transplant events such as organ rejection and immunosuppressant nephrotoxicity. A newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of SAM and SAH in human EDTA plasma was used for a clinical proof-of-concept pilot study. Retrospective analysis was performed using samples from a longitudinal clinical study following de novo kidney transplant patients for the first year (n=16). The ranges of reliable response were 8 to 1024 nmol/l for SAM and 16 to 1024 nmol/l for SAH. The inter-day accuracies were 96.7-103.9% and 97.9-99.3% for SAM and SAH, respectively. Inter-day imprecisions were 8.1-9.1% and 8.4-9.8%. The total assay run time was 5 min. SAM and SAH concentrations were significantly elevated in renal transplant patients preceding documented acute rejection and nephrotoxicity events when compared to healthy controls (n=8) as well as transplant patients void of allograft dysfunction (n=8). The LC-MS/MS assay will provide the basis for further large-scale clinical studies to explore these thiol metabolites as molecular markers for the management of renal transplant patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Cannabis Use and Outcomes in Patients With Aneurysmal Subarachnoid Hemorrhage.

PubMed

Behrouz, Réza; Birnbaum, Lee; Grandhi, Ramesh; Johnson, Jeremiah; Misra, Vivek; Palacio, Santiago; Seifi, Ali; Topel, Christopher; Garvin, Rachel; Caron, Jean-Louis

2016-05-01

The incidence of cannabis use in patients with aneurysmal subarachnoid hemorrhage (aSAH) and its impact on morbidity, mortality, and outcomes are unknown. Our objective was to evaluate the relationship between cannabis use and outcomes in patients with aSAH. Records of consecutive patients admitted with aSAH between 2010 and 2015 were reviewed. Clinical features and outcomes of aSAH patients with negative urine drug screen and cannabinoids-positive (CB+) were compared. Regression analyses were used to assess for associations. The study group consisted of 108 patients; 25.9% with CB+. Delayed cerebral ischemia was diagnosed in 50% of CB+ and 23.8% of urine drug screen negative patients (P=0.01). CB+ was independently associated with development of delayed cerebral ischemia (odds ratio, 2.68; 95% confidence interval, 1.03-6.99; P=0.01). A significantly higher number of CB+ than urine drug screen negative patients had poor outcome (35.7% versus 13.8%; P=0.01). In univariate analysis, CB+ was associated with the composite end point of hospital mortality/severe disability (odds ratio, 2.93; 95% confidence interval, 1.07-8.01; P=0.04). However, after adjusting for other predictors, this effect was no longer significant. We offer preliminary data that CB+ is independently associated with delayed cerebral ischemia and possibly poor outcome in patients with aSAH. Our findings add to the growing evidence on the association of cannabis with cerebrovascular risk. © 2016 American Heart Association, Inc.

Development of a diagnostic system for bilirubin detection in cerebral spinal fluid

NASA Astrophysics Data System (ADS)

Bhadri, Prashant R.; Salgaonkar, Vasant A.; Majumdar, Anindya; Morgan, Chad J.; Zuccarello, Mario; Pyne, Gail J.; Dulaney, Elizabeth; Caffery, James, Jr.; Shukla, Rakesh; Beyette, Fred R., Jr.

2004-11-01

A weakened portion of an artery in the brain leads to a medical condition known as a cerebral aneurysm. A subarachnoid hemorrhage (SAH) occurs when an aneurysm ruptures. For those individuals suspected of having a SAH, a computerized tomography (CT) scan of the brain usually demonstrates evidence of the bleeding. However, in a considerable portion of people, the CT scan is unable to detect the blood that has escaped from the blood vessel. Recent studies have indicated nearly 30% of patients with a SAH are initially misdiagnosed. For circumstances when a SAH is suspected despite a normal CT scan, physicians make the diagnosis of SAH by performing a spinal tap. A spinal tap uses a needle to sample the cerebrospinal fluid (CSF) collected from the patient"s lumbar spine. However, it is also possible for blood to be introduced into the CSF as a result of the spinal tap procedure. Therefore, an effective solution is required to help medical personnel differentiate between the blood that results from a tap and that from a ruptured aneurysm. In this paper, the development of a prototype is described which is sensitive and specific for measuring bilirubin in CSF, hemorrhagic-CSF and CSF-like solutions. To develop this instrument a combination of spectrophotometric analysis, custom data analysis software and other hardware interfaces are assembled that lay the foundation for the development of portable and user-friendly equipment suitable for assisting trained medical personnel with the diagnosis of a ruptured cerebral aneurysm.

Ischemia-modified albumin levels in cerebrovascular accidents.

PubMed

Gunduz, Abdulkadir; Turedi, Suleyman; Mentese, Ahmet; Altunayoglu, Vildan; Turan, Ibrahim; Karahan, Suleyman Caner; Topbas, Murat; Aydin, Murat; Eraydin, Ismet; Akcan, Buket

2008-10-01

Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. Mean serum IMA levels were 0.280 +/- 0.045 absorbance units (ABSU) for BI patients, 0.259 +/- 0.053 ABSU for ICH patients, 0.243 +/- 0.061 ABSU for SAH patients, and 0.172 +/- 0.045 ABSU for the control group.There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels (P b .0001). Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.

A coupled photometric assay for characterization of S-adenosyl-l-homocysteine hydrolases in the physiological hydrolytic direction.

PubMed

Kailing, Lyn L; Bertinetti, Daniela; Herberg, Friedrich W; Pavlidis, Ioannis V

2017-10-25

S-Adenosyl-l-homocysteine hydrolases (SAHases) are important metabolic enzymes and their dysregulation is associated with some severe diseases. In vivo they catalyze the hydrolysis of S-adenosyl-l-homocysteine (SAH), the by-product of methylation reactions in various organisms. SAH is a potent inhibitor of methyltransferases, thus its removal from the equilibrium is an important requirement for methylation reactions. SAH hydrolysis is also the first step in the cellular regeneration process of the methyl donor S-adenosyl-l-methionine (SAM). However, in vitro the equilibrium lies towards the synthetic direction. To enable characterization of SAHases in the physiologically relevant direction, we have developed a coupled photometric assay that shifts the equilibrium towards hydrolysis by removing the product adenosine, using a high affinity adenosine kinase (AK). This converts adenosine to AMP and thereby forms equimolar amounts of ADP, which is phosphorylated by a pyruvate kinase (PK), in turn releasing pyruvate. The readout of the assay is the consumption of NADH during the lactate dehydrogenase (LDH) catalyzed reduction of pyruvate to lactic acid. The applicability of the assay is showcased for the determination of the kinetic constants of an SAHase from Bradyrhizobium elkanii (K M,SAH 41±5μM, v max,SAH 25±1μM/min with 0.13mg/mL enzyme). This assay is a valuable tool for in vitro characterization of SAHases with biotechnological potential, and for monitoring SAHase activity in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence, epidemiology, and treatment of aneurysmal subarachnoid hemorrhage in 12 midwest communities.

PubMed

Ziemba-Davis, Mary; Bohnstedt, Bradley N; Payner, Troy D; Leipzig, Thomas J; Palmer, Erin; Cohen-Gadol, Aaron A

2014-01-01

Only 8 studies have investigated the incidence and epidemiology of aneurysmal subarachnoid hemorrhage (aSAH) in the United States. This is the first investigation in Indiana, which has some of the highest rates of tobacco smoking and obesity in the nation. The authors prospectively identified 441 consecutive patients with aSAH from 2005 to 2010 at 2 hospitals where the majority of cases are treated. Incidence calculations were based on US Census populations. Epidemiologic variables included demography; risk factors; Hunt and Hess scale; Fisher grade; number, location, and size of aneurysms; treatment type; and complications. Overall incidence was 21.8 per 100,000 population. Incidence was higher in women, increased with age, and did not vary by race. One third to half of patients were hypertensive and/or smoked cigarettes at the time of ictus. Variations by count were partially explained by Health Factor and Morbidity Rankings. Complications varied by treatment. These findings deviate from estimates that 6-16 per 100,000 people in the United States will develop aSAH and are double the incidence in a Minnesota population between 1945 and 1974. The results also deviate from the worldwide estimate of 9.0 aSAHs per 100,000 person-years. The predictive value of variations in Health Factor and Morbidity Rankings implicates the importance of future research on multivariate biopsychosocial causation of aSAH. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Spontaneous Adrenal Hemorrhage in Pregnancy: A Case Series.

PubMed

Gupta, Ankita; Minhas, Ruby; Quant, Hayley S

2017-01-01

Background . Abdominal pain during pregnancy has a broad differential diagnosis which includes spontaneous adrenal hemorrhage (SAH). There is scant literature available on optimal mode of delivery in stable patients. Cases . Patient 1 was a 35-year-old nullipara who presented at 36 weeks of gestation with left flank pain. Patient 2 was a 27-year-old multipara at 38 weeks who presented with left upper quadrant pain. Diagnosis of SAH was made by CT scan and both were managed with pain control, serial hemoglobin assessments, and abdominal exams resulting in uncomplicated vaginal deliveries. Conclusion . SAH, although rare, is an important consideration when evaluating abdominal and flank pain in pregnancy. Management options vary from conservative management to surgical intervention depending on the stability of the patient.

Spontaneous Adrenal Hemorrhage in Pregnancy: A Case Series

PubMed Central

Minhas, Ruby; Quant, Hayley S.

2017-01-01

Background. Abdominal pain during pregnancy has a broad differential diagnosis which includes spontaneous adrenal hemorrhage (SAH). There is scant literature available on optimal mode of delivery in stable patients. Cases. Patient 1 was a 35-year-old nullipara who presented at 36 weeks of gestation with left flank pain. Patient 2 was a 27-year-old multipara at 38 weeks who presented with left upper quadrant pain. Diagnosis of SAH was made by CT scan and both were managed with pain control, serial hemoglobin assessments, and abdominal exams resulting in uncomplicated vaginal deliveries. Conclusion. SAH, although rare, is an important consideration when evaluating abdominal and flank pain in pregnancy. Management options vary from conservative management to surgical intervention depending on the stability of the patient. PMID:28421152

Reporting heterogeneity in self-assessed health among elderly Europeans.

PubMed

Pfarr, Christian; Schmid, Andreas; Schneider, Udo

2012-10-05

Self-assessed health (SAH) is a frequently used measure of individuals' health status. It is also prone to reporting heterogeneity. To control for reporting heterogeneity objective measures of true health need to be included in an analysis. The topic becomes even more complex for cross-country comparisons, as many key variables tend to vary strongly across countries, influenced by cultural and institutional differences. This study aims at exploring the key drivers for reporting heterogeneity in SAH in an international context. To this end, country specific effects are accounted for and the objective health measure is concretized, distinguishing effects of mental and physical health conditions. We use panel data from the SHARE-project which provides a rich dataset on the elderly European population. To obtain distinct indicators for physical and mental health conditions two indices are constructed. Finally, to identify potential reporting heterogeneity in SAH a generalized ordered probit model is estimated. We find evidence that in addition to health behaviour, health care utilization, mental and physical health condition as well as country characteristics affect reporting behaviour. We conclude that observed and unobserved heterogeneity play an important role when analysing SAH and have to be taken into account.

Clinical Course Score (CCS): a new clinical score to evaluate efficacy of neurotrauma treatment in traumatic brain injury and subarachnoid hemorrhage.

PubMed

Brandner, Sebastian; Kellermann, Isabel; Hore, Nirjhar; Bozhkov, Yavor; Buchfelder, Michael

2015-01-01

Neurotrauma continues to represent a challenging public health issue requiring continual improvement in therapeutic approaches. As no such current system exists, we present in this study the Clinical Course Score (CCS) as a new clinical score to evaluate the efficacy of neurotrauma treatment. The CCS was calculated in neurotrauma patients to be the difference between the grade of the Glasgow Outcome Scale 6 months after discharge from our department and the grade of a 1 to 5 point reduced Glasgow Coma Scale on admission. We assessed the CCS in a total of 248 patients (196 traumatic brain injury [TBI] patients and 52 subarachnoid hemorrhage [SAH] patients) who were treated in our Department of Neurosurgery between January 2011 and December 2012. We found negative CCS grades both in mild TBI and in mild SAH patients. In patients with severe TBI or SAH, we found positive CCS grades. In SAH patients, we found higher CCS scores in younger patients compared with elderly subjects in both mild and severe cases. The CCS can be useful in evaluating different therapeutic approaches during neurotrauma therapy. This new score might improve assessment of beneficial effects of therapeutic procedures.

Aneurismal subarachnoid hemorrhage in a Chilean population, with emphasis on risk factors

PubMed Central

2011-01-01

Background Subarachnoid Hemorrhage (SAH) is caused principally by the rupture of intracranial aneurisms. Important risk factors have been described such as age, sex, hypertension (HT) and season of the year, among others. The objective is to investigate the demographic characteristics and possible risk factors in a population of Chilean patients. Methods This retrospective study was based on the analysis of 244 clinical records of patients diagnosed with aneurismal SAH who were discharged from the Instituto de Neurocirugía ASENJO in Santiago, Chile. Results The mean age of patients was 49.85 years and the male:female ratio was 1:2.7. The signs and symptoms were not different between sexes; cephalea (85.7%) was predominant, followed by loss of consciousness, vomiting/nausea and meningeal signs. Risk factors included sex, age and HT. Concordant with other reports, the incidence of SAH was greatest in spring. Conclusions The demographic characteristics and risk factors observed in patients with aneurismal SAH treated in ASENJO were comparable to those of other populations. We were not able to conclude that tobacco and alcohol consumption were risk factors for this population. PMID:22035203

Risk factors for catheter-associated urinary tract infections in critically ill patients with subarachnoid hemorrhage.

PubMed

Hagerty, Thomas; Kertesz, Louise; Schmidt, J Michael; Agarwal, Sachin; Claassen, Jan; Mayer, Stephan A; Larson, Elaine L; Shang, Jingjing

2015-02-01

Catheter-associated urinary tract infections (CAUTIs) are preventable adverse outcomes that cause increased morbidity, mortality, and financial burdens to hospitals. These are particularly prevalent in intensive care units (ICUs). Patients with subarachnoid hemorrhage (SAH) in neurological ICUs have extended lengths of stay and may be at higher risk for CAUTIs. The purpose of this study was to assess the prevalence of and risk factors for CAUTIs among patients with SAH in the neurological ICU of a large urban teaching hospital in the eastern United States. This is a retrospective analysis using the Columbia University SAH Outcomes Project data set collected between 2005 and 2012. Logistic regression is used to identify predictors of CAUTI. Catheterized adult patients (n = 242) with SAH over the 8-year period were included. The rate of CAUTIs was 20.7 per 1,000 catheter days, six times higher than the reported national average. Variables significantly associated with CAUTI were older age (odds ratio [OR] = 1.06, 95% confidence interval [CI] [1.01, 1.11]), blood sugar > 200 mg/dl (OR = 13.0, 95% CI [1.28, 107.4]), and anemia requiring transfusion (OR = 3.78, 95% CI [0.977, 14.67]). Higher CAUTI rates in this study were likely associated with prolonged catheterization. On the basis of these findings, careful assessment of the need for catheterization and increased vigilance regarding urinary catheter care in patients with SAH is indicated, particularly among those who are older, with anemia requiring transfusion and elevated blood glucose levels.

The relationship of suicide attempt history with childhood abuse and neglect, alexithymia and temperament and character dimensions of personality in substance dependents.

PubMed

Evren, Cuneyt; Evren, Bilge

2006-01-01

The aim of this study was to evaluate the prevalence of suicide in Turkish male substance dependents, and to investigate the relationship of suicide attempt history with childhood abuse and neglect, alexithymia, and temperament and character dimensions of personality. Participants were 154 consecutively admitted male substance dependents. Patients were investigated with the Childhood Abuse and Neglect Questionnaire, Toronto Alexithymia Scale (TAS-20) and Temperament and Character Inventory (TCI). Among substance-dependent patients, 28.6% was considered a group with suicide attempt history (SAH). Current age was lower and rate of being single was higher in the group with SAH. There were no significant differences between groups in terms of employment, educational status and duration of education. Rates of physical, emotional abuse and neglect, self-mutilation and being alexithymic were higher and ages at first substance use and regular substance use were lower in the group with SAH. Mean scores of "difficulty in identifying feelings" (DIF) and "difficulty in describing feelings" (DDF) subscale EOT of the TAS-20 were higher in the SAH group. Among temperament and character dimensions of the TCI, only "Self-directedness" and "Cooperativeness" were lower in SAH and there were no significant differences between groups in terms of other subscales. Age and Self-directedness score of TCI were determinants for suicide attempt. In particular, young drug users with low Self-directedness scores could be the target population in order to prevent suicidal behavior. This study also suggests that in substance-dependent patients, in the background of all suicidal behavior, childhood abuse and neglect must be evaluated.

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage

PubMed Central

2010-01-01

Background Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. Methods We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients. Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. Results The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). Conclusion We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision. Although generalizability of the model is limited due to the selected population in which it was developed, this model could eventually be used to support clinical decision making after external validation. Trial Registration International Standard Randomised Controlled Trial, Number ISRCTN49866681 PMID:20920243

Heart-fatty acid-binding and tau proteins relate to brain injury severity and long-term outcome in subarachnoid haemorrhage patients.

PubMed

Zanier, E R; Zoerle, T; Fiorini, M; Longhi, L; Cracco, L; Bersano, A; Branca, V; Benedetti, M D; De Simoni, M G; Monaco, S; Stocchetti, N

2013-09-01

Vasospasm and other secondary neurological insults may follow subarachnoid haemorrhage (SAH). Biomarkers have the potential to stratify patient risk and perhaps serve as an early warning sign of delayed ischaemic injury. Serial cerebrospinal fluid (CSF) samples were collected from 38 consecutive patients with aneurysmal SAH admitted to the neurosurgical intensive care unit. We measured heart-fatty acid-binding protein (H-FABP) and tau protein (τ) levels in the CSF to evaluate their association with brain damage, and their potential as predictors of the long-term outcome. H-FABP and τ were analysed in relation to acute clinical status, assessed by the World Federation of Neurological Surgeons (WFNS) scale, radiological findings, clinical vasospasm, and 6-month outcome. H-FABP and τ increased after SAH. H-FABP and τ were higher in patients in poor clinical status on admission (WFNS 4-5) compared with milder patients (WFNS 1-3). Elevated H-FABP and τ levels were also observed in patients with early cerebral ischaemia, defined as a CT scan hypodense lesion visible within the first 3 days after SAH. After the acute phase, H-FABP, and τ showed a delayed increase with the occurrence of clinical vasospasm. Finally, patients with the unfavourable outcome (death, vegetative state, or severe disability) had higher peak levels of both proteins compared with patients with good recovery or moderate disability. H-FABP and τ show promise as biomarkers of brain injury after SAH. They may help to identify the occurrence of vasospasm and predict the long-term outcome.

New clinical decision rule to exclude subarachnoid haemorrhage for acute headache: a prospective multicentre observational study.

PubMed

Kimura, Akio; Kobayashi, Kentaro; Yamaguchi, Hitoshi; Takahashi, Takeshi; Harada, Masahiro; Honda, Hideki; Mori, Yoshio; Hirose, Keika; Tanaka, Noriko

2016-09-09

To ensure good outcomes in the management of subarachnoid haemorrhage (SAH), accurate prediction is crucial for initial assessment of patients presenting with acute headache. We conducted this study to develop a new clinical decision rule using only objectively measurable predictors to exclude SAH, offering higher specificity than the previous Ottawa SAH Rule while maintaining comparable sensitivity. Multicentre prospective cohort study. Tertiary-care emergency departments of five general hospitals in Japan from April 2011 to March 2014. Eligible patients comprised 1781 patients aged >15 years with acute headache, excluding trauma or toxic causes and patients who presented in an unconscious state. Definitive diagnosis of SAH was based on confirmation of SAH on head CT or lumbar puncture findings of non-traumatic red blood cells or xanthochromia. A total of 1561 patients were enrolled in this study, of whom 277 showed SAH. Using these enrolled patients, we reached a rule with mainly categorical predictors used in previous reports, called the 'Ottawa-like rule', offering 100% sensitivity when using any of age ≥40 years, neck pain or stiffness, altered level of consciousness or onset during exertion. Using the 1317 patients from whom blood samples were obtained, a new rule using any of systolic blood pressure >150 mm Hg, diastolic blood pressure >90 mm Hg, blood sugar >115 mg/dL or serum potassium <3.9 mEq/L offered 100% sensitivity (95% CI 98.6% to 100%) and 14.5% specificity (12.5% to 16.9%), while the Ottawa-like rule showed the same sensitivity with a lower specificity of 8.8% (7.2% to 10.7%). While maintaining equal sensitivity, our new rule seemed to offer higher specificity than the previous rules proposed by the Ottawa group. Despite the need for blood sampling, this method can reduce unnecessary head CT in patients with acute headache. UMIN 00004871. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Anaesthetic and ICU management of aneurysmal subarachnoid haemorrhage: a survey of European practice.

PubMed

Velly, Lionel J; Bilotta, Federico; Fàbregas, Neus; Soehle, Martin; Bruder, Nicolas J; Nathanson, Michael H

2015-03-01

Many aspects of the perioperative management of aneurysmal subarachnoid haemorrhage (SAH) remain controversial. It would be useful to assess differences in the treatment of SAH in Europe to identify areas for improvement. To determine the clinical practice of physicians treating SAH and to evaluate any discrepancy between practice and published evidence. An electronic survey. Physicians identified through each national society of neuroanaesthesiology and neurocritical care. A 31-item online questionnaire was distributed by the ENIG group. Questions were designed to investigate anaesthetic management of SAH and diagnostic and treatment approaches to cerebral vasospasm. The survey was available from early October to the end of November 2012. Completed surveys were received from 268 respondents, of whom 81% replied that aneurysm treatment was conducted early (within 24 h). Sixty-five percent of centres treated more than 60% of SAH by coiling, 19% had high-volume clipping (>60% of aneurysms clipped) and 16% used both methods equally. No clear threshold for arterial blood pressure target was identified during coiling, temporary clipping or in patients without vasospasm after the aneurysm had been secured. Almost all respondents used nimodipine (97%); 21% also used statins and 20% used magnesium for prevention of vasospasm. A quarter of respondents used intra-arterial vasodilators alone, 5% used cerebral angioplasty alone and 48% used both endovascular methods to treat symptomatic vasospasm. In high-volume clipping treatment centres, 58% of respondents used endovascular methods to manage vasospasm compared with 86% at high-volume coiling treatment centres (P < 0.001). The most commonly used intra-arterial vasodilator was nimodipine (82%), but milrinone was used by 23% and papaverine by 19%. More respondents (44%) selected 'triple-H' therapy over hypertension alone (30%) to treat vasospasm. We found striking variability in the practice patterns of European

Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies.

PubMed

Höllig, Anke; Stoffel-Wagner, Birgit; Clusmann, Hans; Veldeman, Michael; Schubert, Gerrit A; Coburn, Mark

2017-01-01

Aneurysmal subarachnoid hemorrhage triggers an intense inflammatory response, which is suspected to increase the risk for secondary complications such as delayed cerebral ischemia (DCI). However, to date, the monitoring of the inflammatory response to detect secondary complications such as DCI has not become part of the clinical routine diagnostic. Here, we aim to illustrate the time courses of inflammatory parameters after aneurysmal subarachnoid hemorrhage (aSAH) and discuss the problems of inflammatory parameters as biomarkers but also their possible relevance for deeper understanding of the pathophysiology after aSAH and sophisticated planning of future studies. In this prospective cohort study, 109 patients with aSAH were initially included, n  = 28 patients had to be excluded. Serum and-if possible-cerebral spinal fluid samples ( n  = 48) were retrieved at days 1, 4, 7, 10, and 14 after aSAH. Samples were analyzed for leukocyte count and C-reactive protein (CRP) (serum samples only) as well as matrix metallopeptidase 9 (MMP9), intercellular adhesion molecule 1 (ICAM1), and leukemia inhibitory factor (LIF) [both serum and cerebrospinal fluid (CSF) samples]. Time courses of the inflammatory parameters were displayed and related to the occurrence of DCI. We illustrate the time courses of leukocyte count, CRP, MMP9, ICAM1, and LIF in patients' serum samples from the first until the 14th day after aSAH. Time courses of MMP9, ICAM1, and LIF in CSF samples are demonstrated. Furthermore, no significant difference was shown relating the time courses to the occurrence of DCI. We estimate that the wide range of the measured values hampers their interpretation and usage as a biomarker. However, understanding the inflammatory response after aSAH and generating a multicenter database may facilitate further studies: realistic sample size calculations on the basis of a multicenter database will increase the quality and clinical relevance of the acquired results.

Impaired muscle strength may contribute to fatigue in patients with aneurysmal subarachnoid hemorrhage.

PubMed

Harmsen, Wouter J; Ribbers, Gerard M; Zegers, Bart; Sneekes, Emiel M; Praet, Stephan F E; Heijenbrok-Kal, Majanka H; Khajeh, Ladbon; van Kooten, Fop; Neggers, Sebastiaan J C M M; van den Berg-Emons, Rita J

2017-03-01

Patients with aneurysmal subarachnoid hemorrhage (a-SAH) show long-term fatigue and face difficulties in resuming daily physical activities. Impaired muscle strength, especially of the lower extremity, impacts the performance of daily activities and may trigger the onset of fatigue complaints. The present study evaluated knee muscle strength and fatigue in patients with a-SAH. This study included 33 patients, 6 months after a-SAH, and 33 sex-matched and age-matched healthy controls. Isokinetic muscle strength of the knee extensors and flexors was measured at 60 and 180°/s. Maximal voluntary muscle strength was defined as peak torque and measured in Newton-meter. Fatigue was examined using the Fatigue Severity Scale. In patients with a-SAH, the maximal knee extension was 22% (60°/s) and 25% (180°/s) lower and maximal knee flexion was 33% (60°/s) and 36% (180°/s) lower compared with that of matched controls (P≤0.001). The Fatigue Severity Scale score was related to maximal knee extension (60°/s: r=-0.426, P=0.015; 180°/s: r=-0.376, P=0.034) and flexion (60°/s: r=-0.482, P=0.005; 180°/s: r=-0.344, P=0.083). The knee muscle strength was 28-47% lower in fatigued (n=13) and 11-32% lower in nonfatigued (n=20) patients; deficits were larger in fatigued patients (P<0.05), particularly when the muscle strength (peak torque) was measured at 60°/s. The present results indicate that patients with a-SAH have considerably impaired knee muscle strength, which is related to more severe fatigue. The present findings are exploratory, but showed that knee muscle strength may play a role in the severity of fatigue complaints, or vice versa. Interventions targeting fatigue after a-SAH seem necessary and may consider strengthening exercise training in order to treat a debilitating condition.

Viral erythrocytic necrosis: Chapter 2.2.7

USGS Publications Warehouse

Winton, James R.; Hershberger, Paul K.

2014-01-01

In spite of extensive efforts, the etiological agent of VEN has not been propagated in fish cell lines making its characterization difficult. However, transmission electron microscopy (TEM) of red blood cells from diseased fish convincingly demonstrates the presence of iridovirus-like particles that have been given the name erythrocytic necrosis virus (ENV). While the ENV virions in red blood cells of various species of fish from differing geographic locations may appear morphologically distinct (Smail 1982; Wolf 1988), at least one strain of ENV has now been partially sequenced, confirming it to be a member of the family Iridoviridae (Emmenegger et al. in press). However, the genetic relatedness of ENV from various fish hosts has not yet been investigated. 

Molecular epidemiology of viral hemorrhagic septicemia virus in the Great Lakes region

USGS Publications Warehouse

Winton, James; Kurath, Gael; Batts, William

2008-01-01

Viral hemorrhagic septicemia virus (VHSV) is considered by many nations and international organizations to be one of the most important viral pathogens of finfish (Office International des Epizooties 2007). For several decades following its initial characterization in the 1950s, VHSV was thought to be limited to Europe where it was regarded as an endemic pathogen of freshwater fish that was especially problematic for farmed rainbow trout, an introduced species (Wolf 1988; Smail 1999). Subsequently, it was shown that VHSV was present among many species of marine and anadromous fishes in both the Pacific and Atlantic Oceans where it has been associated with substantial mortality among both wild and cultured fish (Meyers and Winton 1995; Skall et al. 2005).

Osteogenesis imperfecta presenting as aneurysmal subarachnoid haemorrhage in a 53-year-old man

PubMed Central

Kaliaperumal, Chandrasekaran; Walsh, Tom; Balasubramanian, Chandramouli; Wyse, Gerry; Fanning, Noel; Kaar, George

2011-01-01

The authors describe a case of aneurysmal subarachnoid haemorrhage in a 53-year-old man with background of osteogenesis imperfecta (OI). CT brain revealed diffuse subarachnoid haemorrhage (SAH) and cerebral angiogram subsequently confirmed vertebral artery aneurysm rupture leading to SAH. To the authors knowledge this is the first case of vertebral artery aneurysmal SAH described in OI. A previously undiagnosed OI was confirmed by genetic analysis (COL1A1 gene mutation). This aneurysm was successfully treated by endovascular route. Post interventional treatment patient developed stroke secondary to vasospasm. Communicating hydrocephalus, which developed in the process of management, was successfully treated with ventriculo-peritoneal shunt. The aetio-pathogenesis and management of this condition is described. The authors have reviewed the literature and genetic basis of this disease. PMID:22674700

Gadolinium-Based Contrast Agent Extravasation Mimicking Subarachnoid Hemorrhage After Electroconvulsive Therapy.

PubMed

Taydas, Onur; Ogul, Hayri; Ozcan, Halil; Kantarci, Mecit

2018-06-01

Electroconvulsive therapy (ECT) is a safe method that has been applied for many years in medical treatment-resistant depression treatment. In this case report, contrast extravasation due to deterioration of the blood-brain barrier after ECT mimicking subarachnoid hemorrhage (SAH) on magnetic resonance imaging (MRI) is discussed. A 70-year-old male patient who underwent ECT presented with sulcal hyperintensities suggesting subarachnoid hemorrhage on fluid-attenuated inversion recovery sequence of MRI obtained after ECT. However, there was no evidence to suggest SAH on nonenhanced brain computed tomography. It should be kept in mind that patients may have contrast extravasation due to deterioration of the blood-brain barrier after ECT, and other alternative methods should be used for the diagnosis of SAH in these patients, not MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

Isolated abducens nerve palsy associated with subarachnoid hemorrhage: a localizing sign of ruptured posterior inferior cerebellar artery aneurysms.

PubMed

Burkhardt, Jan-Karl; Winkler, Ethan A; Lasker, George F; Yue, John K; Lawton, Michael T

2018-06-01

OBJECTIVE Compressive cranial nerve syndromes can be useful bedside clues to the diagnosis of an enlarging intracranial aneurysm and can also guide subsequent evaluation, as with an acute oculomotor nerve (cranial nerve [CN] III) palsy that is presumed to be a posterior communicating artery aneurysm and a surgical emergency until proven otherwise. The CN VI has a short cisternal segment from the pontomedullary sulcus to Dorello's canal, remote from most PICA aneurysms but in the hemodynamic pathway of a rupturing PICA aneurysm that projects toward Dorello's canal. The authors describe a cranial nerve syndrome for posterior inferior cerebellar artery (PICA) aneurysms that associates subarachnoid hemorrhage (SAH) and an isolated abducens nerve (CN VI) palsy. METHODS Clinical and radiological data from 106 surgical patients with PICA aneurysms (66 ruptured and 40 unruptured) were retrospectively reviewed. Data from a group of 174 patients with other aneurysmal SAH (aSAH) were analyzed in a similar manner to control for nonspecific effects of SAH. Univariate statistical analysis compared incidence and risk factors associated with CN VI palsy in subarachnoid hemorrhage. RESULTS Overall, 13 (4.6%) of 280 patients had CN VI palsy at presentation, and all of them had ruptured aneurysms (representing 13 [5.4%] of the 240 cases of ruptured aneurysms). CN VI palsies were observed in 12 patients with ruptured PICA aneurysms (12/66 [18.1%]) and 1 patient with other aSAH (1/174 [0.1%], p < 0.0001). PICA aneurysm location in ruptured aneurysms was an independent predictor for CN VI palsy on multivariate analysis (p = 0.001). PICA aneurysm size was not significantly different in patients with or without CN VI palsy (average size 4.4 mm and 5.2 mm, respectively). Within the PICA aneurysm cohort, modified Fisher grade (p = 0.011) and presence of a thick cisternal SAH (modified Fisher Grades 3 and 4) (p = 0.003) were predictors of CN VI palsy. In all patients with ruptured PICA

[Subarachnoid hemorrhage: epidemiology, social impact and a multidisciplinary approach].

PubMed

Ingelmo Ingelmo, I; Fàbregas Julià, N; Rama-Maceiras, P; Hernández-Palazón, J; Rubio Romero, R; Carmona Aurioles, J

2010-12-01

Cerebrovascular disease, whether ischemic or hemorrhagic, is a worldwide problem, representing personal tragedy, great social and economic consequences, and a heavy burden on the health care system. Estimated to be responsible for up to 10% of mortality in industrialized countries, cerebrovascular disease also affects individuals who are still in the workforce, with consequent loss of productive years. Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident that leads to around 5% of all strokes. SAH is most often due to trauma but may also be spontaneous, in which case the cause may be a ruptured intracranial aneurysm (80%) or arteriovenous malformation or any other abnormality of the blood or vessels (20%). Although both the diagnosis and treatment of aneurysmal SAH has improved in recent years, related morbidity and mortality remains high: 50% of patients die from the initial hemorrhage or later complications. If patients whose brain function is permanently damaged are added to the count, the percentage of cases leading to severe consequences rises to 70%. The burden of care of patients who are left incapacitated by SAH falls to the family or to private and public institutions. The economic cost is considerable and the loss of quality of life for both the patient and the family is great. Given the magnitude of this problem, the provision of adequate prophylaxis is essential; also needed are organizational models that aim to reduce mortality as well as related complications. Aneurysmal SAH is a condition which must be approached in a coordinated, multidisciplinary way both during the acute phase and throughout rehabilitation in order to lower the risk of unwanted outcomes.

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women.

PubMed

Barbosa, P R; Stabler, S P; Machado, A L K; Braga, R C; Hirata, R D C; Hirata, M H; Sampaio-Neto, L F; Allen, R H; Guerra-Shinohara, E M

2008-08-01

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

[Cerebral vasospasm and lipid peroxidation--lipid peroxides in the cerebrospinal fluid after subarachnoid hemorrhage].

PubMed

Sasaki, T; Asano, T; Takakura, K; Sano, K; Nakamura, T; Suzuki, N; Imabayashi, S; Ishikawa, Y

1982-12-01

The relationship between lipid peroxides in cerebrospinal fluid (CSF) and the occurrence of cerebral vasospasm following subarachnoid hemorrhage (SAH) was evaluated by analyzing CSF with high-performance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS). Hydroperoxy eicosatetraenoic acids (HPETEs) and hydroxy eicosatetraenoic acids (HETEs) were synthesized by the treatment of arachidonic acid with hydrogen peroxide and cupric chloride. The retention time of these HPETEs and HETEs were determined on HPLC. The position of oxydation occurred was determined after methylation, reduction and trimethyl silylation using GC-MS. Thus the elucidation of positional isomers of HPETEs and HETEs was made possible by the retention time on HPLC. The supernant of CSF after SAH was adjusted to pH 3.0 and then absorbed to octadecyl silyl silica column. The eluted fraction with 15% ethanol-water from octadecyl silyl silica column was analyzed by HPLC detecting at 238 nm. No peak was observed on HPLC at the region of HPETEs and HETEs in the CSF obtained from healthy person. In SAH patients, several peaks were recognized in accordance with the occurrence of cerebral vasospasm. One of the peaks was identified as 5-HETE by HPLC and GC-MS. In 10 SAH patients, semi-quantitative analysis of 5-HETE in the CSF was performed by measuring the height of the peak identified as 5-HETE on HPLC. The close correlation was recognized between the occurrence of cerebral vasospasm and the appearance of 5-HETE in the CSF. The results of the present study suggest that lipid peroxidation is involved in the pathogenesis of chronic vasospasm after SAH.

External Ventricular Drain and Hemorrhage in Aneurysmal Subarachnoid Hemorrhage Patients on Dual Antiplatelet Therapy: A Retrospective Cohort Study.

PubMed

Hudson, Joseph S; Prout, Benjamin S; Nagahama, Yasunori; Nakagawa, Daichi; Guerrero, Waldo R; Zanaty, Mario; Chalouhi, Nohra; Jabbour, Pascal; Dandapat, Sudeepta; Allan, Lauren; Ortega-Gutierrez, Santiago; Samaniego, Edgar A; Hasan, David

2018-04-11

Stenting and flow diversion for aneurysmal sub arachnoid hemorrhage (aSAH) require the use of dual antiplatelet therapy (DAPT). To investigate whether DAPT is associated with hemorrhagic complication following placement of external ventricular drains (EVD) in patients with aSAH. Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received DAPT for stenting or flow diversion, and patients who underwent microsurgical clipping or coiling and did not receive DAPT by way of a backward stepwise multivariate analysis. Four hundred forty-three patients were admitted for aSAH management. Two hundred ninety-eight patients required placement of an EVD. One hundred twenty patients (40%) were treated with stent-assisted coiling or flow diversion and required DAPT, while 178 patients (60%) were treated with coiling without stents or microsurgical clipping and did not receive DAPT. Forty-two (14%) cases of new hemorrhage along the EVD catheter were identified radiographically. Thirty-two of these hemorrhages occurred in patients on DAPT, while 10 occurred in patients without DAPT. After multivariate analysis, DAPT was significantly associated with radiographic hemorrhage [odds ratio: 4.92, 95% confidence interval: 2.45-9.91, P = .0001]. We did not observe an increased proportion of symptomatic hemorrhage in patients receiving DAPT (10 of 32 [31%]) vs those without (5 of 10 [50%]; P = .4508). Patients with aSAH who receive stent-assisted coiling or flow diversion are at higher risk for radiographic hemorrhage associated with EVD placement. The timing between EVD placement and DAPT initiation does not appear to be of clinical significance. Stenting and flow diversion remain viable options for aSAH patients.

Multi-wavelength spectrophotometric analysis for detection of xanthochromia in cerebrospinal fluid and accuracy for the diagnosis of subarachnoid hemorrhage.

PubMed

Smith, Andrew; Wu, Alan H B; Lynch, Kara L; Ko, Nerissa; Grenache, David G

2013-09-23

Cerebrospinal fluid (CSF) was examined for bilirubin, an important indicator for diagnosis of subarachnoid hemorrhage (SAH). A multi-wavelength (340, 415, and 460 nm) spectrophotometric assay was developed for the quantitative measurement of bilirubin in CSF, enabling the mathematical correction for absorbance of hemoglobin and proteins. Bilirubin and hemoglobin results were correlated to HPLC and a standard colorimetric assay, respectively. A subset of samples was sent for an absorbance reading at 450 nm following baseline correction. The multi-wavelength bilirubin assay was validated on 70 patients with confirmed SAH and 70 patients with neurologic symptoms who ruled out for SAH. The multi-wavelength spectrophometric assay demonstrated no interferences due to proteins (albumin) up to 30 g/l or oxyhemoglobin up to 260 mg/l. The assay limit of detection was 0.2 mg/l, linear to 20 mg/l, and CVs ranged from 1 to 6% at bilirubin concentrations of 0.84 and 2.1mg/l. The spectrophotometric assay correlated to HPLC and the colorimetric assay for bilirubin and hemoglobin, respectively. Results also correlated to the absorbance method (with removal of samples with high hemoglobin and proteins). The area under the ROC curve for diagnosis of SAH was 0.971 and 0.954 for the HPLC and spectrophotometric assay, respectively. At a cutoff of 0.2mg/l, the clinical specificity was 100% for both assays, and the clinical sensitivity was 94.3% and 88.6% for SAH for the HPLC and spectrophotometric asays, respectively. The multi-wavelength spectrophotometric assay is an objective alternative to visual inspection, HPLC, and absorbance for CSF bilirubin. Copyright © 2013 Elsevier B.V. All rights reserved.

Early Brain Injury Associated with Systemic Inflammation After Subarachnoid Hemorrhage.

PubMed

Savarraj, Jude; Parsha, Kaushik; Hergenroeder, Georgene; Ahn, Sungho; Chang, Tiffany R; Kim, Dong H; Choi, H Alex

2018-04-01

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) is defined as brain injury occurring within 72 h of aneurysmal rupture. Although EBI is the most significant predictor of outcomes after aSAH, its underlying pathophysiology is not well understood. We hypothesize that EBI after aSAH is associated with an increase in peripheral inflammation measured by cytokine expression levels and changes in associations between cytokines. aSAH patients were enrolled into a prospective observational study and were assessed for markers of EBI: global cerebral edema (GCE), subarachnoid hemorrhage early brain edema score (SEBES), and Hunt-Hess grade. Serum samples collected at ≤ 48 h of admission were analyzed using multiplex bead-based assays to determine levels of 13 pro- and anti-inflammatory cytokines. Pairwise correlation coefficients between cytokines were represented as networks. Cytokine levels and differences in correlation networks were compared between EBI groups. Of the 71 patients enrolled in the study, 17 (24%) subjects had GCE, 31 (44%) subjects had SEBES ≥ 3, and 21 (29%) had HH ≥ 4. IL-6 was elevated in groups with GCE, SEBES ≥ 3, and HH ≥ 4. MIP1β was independently associated with high-grade SEBES. Correlation network analysis suggests higher systematic inflammation in subjects with SEBES ≥ 3. EBI after SAH is associated with increased levels of specific cytokines. Peripheral levels of IL-10, IL-6, and MIP1β may be important markers of EBI. Investigating systematic correlations in addition to expression levels of individual cytokines may offer deeper insight into the underlying mechanisms related to EBI.

Predictive factors of long-term outcomes of surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

PubMed

Mathon, Bertrand; Bielle, Franck; Samson, Séverine; Plaisant, Odile; Dupont, Sophie; Bertrand, Anne; Miles, Richard; Nguyen-Michel, Vi-Huong; Lambrecq, Virginie; Calderon-Garcidueñas, Ana Laura; Duyckaerts, Charles; Carpentier, Alexandre; Baulac, Michel; Cornu, Philippe; Adam, Claude; Clemenceau, Stéphane; Navarro, Vincent

2017-08-01

The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery. Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36). With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome. The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The Association Between Spontaneous Hyperventilation, Delayed Cerebral Ischemia, and Poor Neurological Outcome in Patients with Subarachnoid Hemorrhage.

PubMed

Williamson, Craig A; Sheehan, Kyle M; Tipirneni, Renuka; Roark, Christopher D; Pandey, Aditya S; Thompson, B Gregory; Rajajee, Venkatakrishna

2015-12-01

The frequency and associations of spontaneous hyperventilation in subarachnoid hemorrhage (SAH) are unknown. Because hyperventilation decreases cerebral blood flow, it may exacerbate delayed cerebral ischemia (DCI) and worsen neurological outcome. This is a retrospective analysis of data from a prospectively collected cohort of SAH patients at an academic medical center. Spontaneous hyperventilation was defined by PaCO2 <35 mmHg and pH >7.45 and subdivided into moderate and severe groups. Clinical and demographic characteristics of patients with and without spontaneous hyperventilation were compared using χ (2) or t tests. Bivariate and multivariable logistic regression analyses were conducted to examine the association of moderate and severe hyperventilation with DCI and discharge neurological outcome. Of 207 patients, 113 (55 %) had spontaneous hyperventilation. Spontaneously hyperventilating patients had greater illness severity as measured by the Hunt-Hess, World Federation of Neurosurgical Societies (WFNS), and SAH sum scores. They were also more likely to develop the following complications: pneumonia, neurogenic myocardial injury, systemic inflammatory response syndrome (SIRS), radiographic vasospasm, DCI, and poor neurological outcome. In a multivariable logistic regression model including age, gender, WFNS, SAH sum score, pneumonia, neurogenic myocardial injury, etiology, and SIRS, only moderate [odds ratio (OR) 2.49, 95 % confidence interval (CI) 1.10-5.62] and severe (OR 3.12, 95 % CI 1.30-7.49) spontaneous hyperventilation were associated with DCI. Severe spontaneous hyperventilation (OR 4.52, 95 % CI 1.37-14.89) was also significantly associated with poor discharge outcome in multivariable logistic regression analysis. Spontaneous hyperventilation is common in SAH and is associated with DCI and poor neurological outcome.

Trends in incidence and in short term survival following a subarachnoid haemorrhage in Scotland, 1986-2005: a retrospective cohort study.

PubMed

Macpherson, Karen J; Lewsey, James D; Jhund, Pardeep S; Gillies, Michelle; Chalmers, Jim W T; Redpath, Adam; Briggs, Andrew; Walters, Matthew; Langhorne, Peter; Capewell, Simon; McMurray, John J V; MacIntyre, Kate

2011-03-29

To examine age and sex specific incidence and 30 day case fatality for subarachnoid haemorrhage (SAH) in Scotland over a 20 year period. A retrospective cohort study using routine hospital discharge data linked to death records. Between 1986 and 2005, 12,056 individuals experienced an incident SAH. Of these 10,113 (84%) survived to reach hospital. Overall age-standardised incidence rates were greater in women than men and remained relatively stable over the study period. In 2005, incidence in women was 12.8 (95% CI 11.5 to 14.2) and in men 7.9 (95% CI 6.9 to 9.1). 30 day case fatality in individuals hospitalised with SAH declined substantially, falling from 30.0% in men and 33.9% in women in 1986-1990 to 24.5% in men and 29.1% in women in 2001-2005. For both men and women, the largest reductions were observed in those aged between 40 to 59 years. After adjustment for age, socio-economic status and co-morbidity, the odds of death at 30 days in 2005 compared to odds of death in 1986 was 0.64 (0.54 to 0.76), p < 0.001 for those below 70 years, and 1.14 (0.83 to 1.56), p = 0.4 in those 70 years and above. Incidence rates for SAH remained stable between 1986 and 2005 suggesting that a better understanding of SAH risk factors and their reduction is needed. 30 day case fatality rates have declined substantially, particularly in middle-age. However, they remain high and it is important to ensure that this is not due to under-diagnosis or under-treatment.

Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage

PubMed Central

2012-01-01

Background Hydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital. Methods One hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score. Results Hydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without. Conclusions The presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization. PMID:22765765

Morphometric and ultrastructural analysis of the effect of bromocriptine and cyclosporine on the vasospastic femoral artery of rats

PubMed Central

Tokmak, Mehmet; Başocak, Kahan; Canaz, Hüseyin; Canaz, Gökhan; İplikçioğlu, Celal

2015-01-01

Vasospasm is the main causes of mortality and morbidity in patiens with subarachnoid hemorrhage (SAH). The arterial narrowing mechanism that develops after SAH is not yet fully understood but many studies showed that hypotension, neurogenic reflexes, clots in the subarachnoidal space, spasmogenic agents, humoral and celluler immunity play a role in the etiology. In this study we investigate the effects of Bromocriptine and Cyclosporine A in vasospasm secondary to SAH on rat femoral artery from ultrastructural and morphometric perspectives. 120 male Sprague-Dawley rats divided into 12 groups: Vasospasm (V), control (K), surgical control (CK) groups, vasospasm+Bromocriptine and/or Cyclosporine-A groups (VCyA, VBr, VBr+CyA), Bromocriptine and/or Cyclosporine-A control groups (CK, BK, Br+CyAK), Bromocriptine and/or Cyclosporine-A surgical control groups (BCK, CyCK, Br+CyACK). In order to create SAH model, 0, 1 cm3 blood injected into silastic sheath wrapped rat femoral artery. Bromocriptine (2 mg/kg/d) and Cyclosporine A (10 mg/kg/d) combinations applied to control, surgical control and vasospastic models. Light microscopy, transmission electron microscopy and scanning electron microscopy used during this study. Statistical evaluation of the morphometric measurement data concerning vascular wall thickness and luminal cross-sectional areas of all groups were performed using Mann-Whitney U, Wilcoxon-signed rank, and Student-t tests. Cyclosporine A, whose effects in the prevention of vasospasm have been demonstrated in previous studies. In this study we discovered that Bromocriptine demonstrated strong effects similar to Cyclosporine-A. Bromocriptine and Cyclosporine A markedly prevent the development of chronic morphologic vasospasm following SAH. The combined use of both drugs does not change this preventive effect. PMID:26770311

A comparative analysis of sex change in Labridae supports the size advantage hypothesis.

PubMed

Kazancioğlu, Erem; Alonzo, Suzanne H

2010-08-01

The size advantage hypothesis (SAH) predicts that the rate of increase in male and female fitness with size (the size advantage) drives the evolution of sequential hermaphroditism or sex change. Despite qualitative agreement between empirical patterns and SAH, only one comparative study tested SAH quantitatively. Here, we perform the first comparative analysis of sex change in Labridae, a group of hermaphroditic and dioecious (non-sex changer) fish with several model sex-changing species. We also estimate, for the first time, rates of evolutionary transitions between sex change and dioecy. Our analyses support SAH and indicate that the evolution of hermaphroditism is correlated to the size advantage. Furthermore, we find that transitions from sex change to dioecy are less likely under stronger size advantage. We cannot determine, however, how the size advantage affects transitions from dioecy to sex change. Finally, contrary to what is generally expected, we find that transitions from dioecy to sex change are more likely than transitions from sex change to dioecy. The similarity of sexual differentiation in hermaphroditic and dioecious labrids might underlie this pattern. We suggest that elucidating the developmental basis of sex change is critical to predict and explain patterns of the evolutionary history of sequential hermaphroditism.

Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage

PubMed Central

Han, Sang Myung; Wan, Hoyee; Kudo, Gen; Foltz, Warren D; Vines, Douglass C; Green, David E; Zoerle, Tommaso; Tariq, Asma; Brathwaite, Shakira; D'Abbondanza, Josephine; Ai, Jinglu; Macdonald, R Loch

2014-01-01

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation. PMID:24064494

Ehrlichia Meningitis Mimicking Aneurysmal Subarachnoid Hemorrhage: A Case Study for Medical Decision-Making Heuristics.

PubMed

Dredla, Brynn; Freeman, William D

2016-04-01

Thunderclap headache is a sudden and severe headache that can occur after an aneurysmal subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage is a medical emergency that requires prompt attention and hospitalization. Patients with thunderclap headache often undergo a noncontrast head computed tomography (CT) scan to ascertain SAH bleeding and, if the scan is negative, then undergo a lumbar puncture to look for cerebrospinal fluid (CSF) red blood cells (RBCs), which would be consistent with an aneurysmal leak. If the initial CT is negative and CSF is positive for RBCs, patients are usually admitted to the hospital for evaluation of intracranial aneurysm. We encountered a patient with thunderclap headache whose initial head CT was negative for SAH and whose CSF tested positive for RBCs. The patient was referred to our center for evaluation and management of aneurysmal SAH. However, on careful review of the patient's medical history, serum laboratory values, and spinal fluid values, the patient was diagnosed with Ehrlichia chaffeensis meningitis. While Ehrlichia meningitis is rare, it is important to recognize the clinical clues that could help avoid formal cerebral angiography, a costly and potentially unnecessary procedure. We present how this case represented a cognitive framing bias and anchoring heuristic as well as steps that medical providers can use to prevent such cognitive errors in diagnosis.

Anosmia after coiling of ruptured aneurysms: prevalence, prognosis, and risk factors.

PubMed

Bor, A Stijntje E; Niemansburg, Sophie L; Wermer, Marieke J H; Rinkel, Gabriel J E

2009-06-01

Anosmia occurs frequently in patients with subarachnoid hemorrhage (SAH) from a ruptured aneurysm treated with clipping. We analyzed prevalence, prognosis, and potential risk factors for anosmia after coiling for SAH. We interviewed all patients who resumed independent living after SAH treated with coiling between 1997 and 2007. We assessed by means of logistic regression analyses whether risk of anosmia was influenced by site of the ruptured aneurysm, neurological condition on admission, amount of extravasated blood, hydrocephalus, and treatment for hydrocephalus. Of 197 patients, 35 (18%; 95%CI:12 to 23) experienced anosmia. Anosmia had improved in 23 (66%) of them; in 20 the recovery had been complete after a median period of 6 weeks (SD +/-6.5). Intraventricular hemorrhage was a risk factor for anosmia (OR 2.4; 95%CI:1.0 to 5.9). Anterior aneurysm location (OR 1.1; 95%CI:0.5 to 2.3) and high amount of extravasated blood (OR 0.9; 95%CI:0.4 to 2.1) were not related to anosmia. Anosmia occurs after coiling in 1 of every 6 SAH patients, but has a good prognosis in most patients. The cause of anosmia after coiling for ruptured aneurysms remains elusive; severity of the initial hemorrhage or long lasting hydrocephalus may be contributing factors.

ACP Best Practice No 166

PubMed Central

Cruickshank, A

2001-01-01

After subarachnoid haemorrhage (SAH), cerebral angiography is usually performed to establish a site of bleeding, which may then be treated surgically to prevent a potentially catastrophic re-bleed. The investigation of choice in the diagnosis of SAH is computerised tomography (CT). However, because CT can miss some patients with SAH, cerebrospinal fluid (CSF) spectrophotometry should be performed in those patients with negative or equivocal CT scans or those who have presented several days after the suspected bleed. Spectrophotometry should aim to detect the presence of both oxyhaemoglobin and bilirubin because either one or both of these pigments may contribute to xanthochromia following SAH. CSF supernatant is scanned using a double beam spectrophotometer at wavelengths between 350 nm and 650 nm. Oxyhaemoglobin alone produces an absorption peak at 413–415 nm, bilirubin alone produces a broad peak at 450–460 nm, and bilirubin together with oxyhaemoglobin produce a shoulder at 450–460 nm on the downslope of the oxyhaemoglobin peak. To minimise the frequency of false positive and false negative results, a protocol has been developed, which is described. Key Words: subarachnoid haemorrhage • computerised tomography • cerebrospinal fluid • spectrophotometry • oxyhaemoglobin • bilirubin • xanthochromia PMID:11684714

Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy.

PubMed

Helmstaedter, C; Van Roost, D; Clusmann, H; Urbach, H; Elger, C E; Schramm, J

2004-02-01

Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach. To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH). 34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning. Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery. Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Pre-hemorrhage statin use and the risk of vasospasm following aneurysmal subarachnoid hemorrhage

PubMed Central

Moskowitz, Shaye I.; Ahrens, Christine; Provencio, J Javier; Chow, Michael; Rasmussen, Peter A

2010-01-01

Background and Purpose Aneurysmal subarachnoid hemorrhage (SAH) is often followed by delayed ischemic deficits attributable to cerebral vasospasm. Recent studies suggest a positive impact of statin therapy on the incidence of vasospasm. This study was designed to assess whether a history of prior use of statin therapy was associated with a lower risk of vasospasm in patients with SAH. Methods We performed a comprehensive retrospective review of patients with aneurysmal SAH between 1997 and 2004. Clinical demographics and imaging data for all patients were reviewed and a logistic regression analysis was performed to identify the predictors of cerebral vasospasm, defined as a combination of clinical signs with radiographic confirmation. Results 308 patients were included. Mean age was higher in the group receiving statins (64 +/- 12 versus 54+/- 12 years). Hunt and Hess scores and treatment modality were not significantly different between the groups. Vasospasm was observed in 31% of patients not taking a statin (n=282) versus 23% taking a statin (n=26), without achieving statistical significance. Discontinuation of the statin did not affect risk of vasospasm. Conclusions Use of a statin prior to an aneurysmal SAH trended to reduce the incidence of subsequent vasospasm, without achieving statistical significance. PMID:18423529

Crohns disease with central nervous system vasculitis causing subarachnoid hemorrhage due to aneurysm and cerebral ischemic stroke

PubMed Central

Garge, Shaileshkumar S.; Vyas, Pooja D.; Modi, Pranav D.; Ghatge, Sharad

2014-01-01

Cerebral vasculitis secondary to Crohn's disease (CD) seems to be a very rare phenomenon. We report a 39-year-old male who presented with headache, vomiting, and left-sided weakness in the known case of CD. Cross-sectional imaging (computed tomography and magnetic resonance imaging,) showed right gangliocapsular acute infarct with supraclinoid cistern subarachnoid hemorrhage (SAH). Cerebral digital substraction angiography (DSA) showed dilatation and narrowing of right distal internal carotid artery (ICA). Left ICA was chronically occluded. His inflammatory markers were significantly raised. Imaging features are suggestive of cerebral vasculitis. Arterial and venous infarcts due to thrombosis are known in CD. Our case presented with acute subarachnoid hemorrhage in supraclinoid cistern due to rupture of tiny aneurysm of perforator arteries causing SAH and infarction in right basal ganglia. Patient was treated conservatively with immunosuppression along with medical management of SAH. PMID:25506170

Crohns disease with central nervous system vasculitis causing subarachnoid hemorrhage due to aneurysm and cerebral ischemic stroke.

PubMed

Garge, Shaileshkumar S; Vyas, Pooja D; Modi, Pranav D; Ghatge, Sharad

2014-10-01

Cerebral vasculitis secondary to Crohn's disease (CD) seems to be a very rare phenomenon. We report a 39-year-old male who presented with headache, vomiting, and left-sided weakness in the known case of CD. Cross-sectional imaging (computed tomography and magnetic resonance imaging,) showed right gangliocapsular acute infarct with supraclinoid cistern subarachnoid hemorrhage (SAH). Cerebral digital substraction angiography (DSA) showed dilatation and narrowing of right distal internal carotid artery (ICA). Left ICA was chronically occluded. His inflammatory markers were significantly raised. Imaging features are suggestive of cerebral vasculitis. Arterial and venous infarcts due to thrombosis are known in CD. Our case presented with acute subarachnoid hemorrhage in supraclinoid cistern due to rupture of tiny aneurysm of perforator arteries causing SAH and infarction in right basal ganglia. Patient was treated conservatively with immunosuppression along with medical management of SAH.

Not feeling well … true or exaggerated? Self-assessed health as a leading health indicator.

PubMed

Becchetti, Leonardo; Bachelet, Maria; Riccardini, Fabiola

2018-02-01

We provide original, international evidence documenting that self-assessed health (SAH) is a leading health indicator, that is, a significant predictor of future changes in health conditions, in a large sample of Europeans aged above 50 and living in 13 different countries. We find that, after controlling for attrition bias, lagged SAH is significantly and negatively correlated with changes in the number of chronic diseases, net of the correlations with levels, and changes in sociodemographic factors and health styles, country and regional health system effects, and declared symptoms. Illness-specific estimates document that lagged SAH significantly correlates with arthritis, cholesterol, and lung diseases (and weakly so with ulcer, hypertension, and cataracts) and has a significant correlation with the probability of contracting cancer. Interpretations and policy implications of our findings are discussed in the paper. Copyright © 2017 John Wiley & Sons, Ltd.

[24-Hour blood pressure profile in patients with mild and moderate arterial hypertension and sleep apnea/hypopnea].

PubMed

Zelveian, P A; Oshchepkova, E V; Buniatian, M S; Badikov, D N; Rogoza, A N

2001-01-01

To evaluate 24-hour blood pressure (BP) profile in arterial hypertension (AH) patients (pts) with desaturation signs of sleep apnea/hypopnea syndrome (SAHS). We investigated 61 pts (44 males and 17 females) aged between 23-70 (52 +/- 2) years with mild to moderate AH. BP monitoring was performed with multisensor system TM-2425 (A&D, Japan). We assessed the following parameters: mean 24-h, awake, sleep systolic (S), diastolic (D) and pulse (P) BPs, systolic and diastolic BP loads ("normalized area under the curve"--NAUC). A normal circadian rhythm of BP was defined when nocturnal fall of SBP was > 10% and < 20%. The morning rise of BP we assessed by speed of increase of mean BP from 4 a.m. to 12 a.m. The nocturnal monitoring of arterial oxygen saturation(SaO2) was performed with pulseoximeter "NONIN 8500M" (USA). The analysis of the results was performed with the original program ARM-SaO2". The presence of SAHS was confirmed when the number of 4% desaturations were greater than 15 per hour or in the presence of group episodes of 4% desaturation below 90%. In 19 pts we revealed desaturation signs of SAHS. The comparison group included pts without SAHS (n = 42). We compared the groups regarding 24-h BP profile parameters. SAHS group had the following parameters significantly higher: mean 24-h (151.7 +/- 4.5 vs 142.9 +/- 2.4 mm Hg, p < 0.07) and sleep SBPs (142.8 +/- 5.1 vs 132.7 +/- 2.6 mm Hg, p < 0.05); mean 24-h (65.2 +/- 2.6 vs 55.9 +/- 1.9 mm Hg, p < 0.008), daytime (65.6 +/- 2.7 vs 56.6 +/- 2.0 mm Hg, p < 0.01) and sleep PBPs (64.1 +/- 2.7 vs 53.1 +/- 1.9 mm Hg, p < 0.002); 24-h (20.1 +/- 3.8 vs 12.6 +/- 1.8 mm Hg, p < 0.05) and sleep NAUC of SBP (24.6 +/- 4.4 vs 15.3 +/- 2.2 mm Hg, p < 0.03). In the group with SAHS were significantly higher the frequency of abnormal circadian rhythm of SBP (84 vs 57%, p < 0.05) and the speed of morning rise of mean BP (23.3 +/- 5.9 vs 8.5 +/- 2.8 mm Hg/h, p < 0.01). Our results suggest that pts with desaturation signs of SAHS

Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies

PubMed Central

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-01-01

In this study, we performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). EWAS for ischemic stroke was performed using 1,575 patients with this condition and 9,210 controls, and EWASs for ICH and SAH were performed using 673 patients with ICH, 265 patients with SAH and 9,158 controls. Analyses were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 41,339 or 41,332 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic or hemorrhagic stroke, respectively, was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21×10−6 was considered statistically significant. EWAS for ischemic stroke revealed that 77 SNPs were significantly associated with this condition. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension and diabetes mellitus revealed that 4 of these SNPs [rs3212335 of GABRB3 (P=0.0036; odds ratio, 1.29), rs147783135 of TMPRSS7 (P=0.0024; odds ratio, 0.37), rs2292661 of PDIA5 (P=0.0054; odds ratio, 0.35) and rs191885206 of CYP4F12 (P=0.0082; odds ratio, 2.60)] were related (P<0.01) to ischemic stroke. EWASs for ICH or SAH revealed that 48 and 12 SNPs, respectively, were significantly associated with these conditions. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension revealed that rs138533962 of STYK1 (P<1.0×10−23; odds ratio, 111.3) was significantly (P<2.60×10−4) associated with ICH and that rs117564807 of COL17A1 (P=0.0009; odds ratio, 2.23×10−8) was significantly (P<0.0010) associated with SAH. GABRB3, TMPRSS7, PDIA5 and CYP4F12 may thus be novel susceptibility loci for ischemic stroke, whereas STYK1 and COL17A1 may be such loci for ICH and SAH, respectively. PMID

Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis.

PubMed

Beez, Thomas; Steiger, Hans-Jakob; Etminan, Nima

2017-12-07

The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms

Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome

PubMed Central

Nogueira, Adriano Barreto; Nogueira, Ariel Barreto; Veiga, José Carlos Esteves; Teixeira, Manoel Jacobsen

2017-01-01

We have recently found that the temperature variability (TV) in the day–night cycle may predict the mean intracranial pressure in the following 24 h (ICP24) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP24 = 6 (4 − TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep–wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP24, and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise

Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome.

PubMed

Nogueira, Adriano Barreto; Nogueira, Ariel Barreto; Veiga, José Carlos Esteves; Teixeira, Manoel Jacobsen

2017-01-01

We have recently found that the temperature variability (TV) in the day-night cycle may predict the mean intracranial pressure in the following 24 h (ICP 24 ) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP 24  = 6 (4 - TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep-wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP 24 , and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise

Hyperacute perimesencephalic subarachnoid hemorrhage: demonstration of blood extravasation with MRI.

PubMed

Küker, W; Thiex, R; Block, F

1999-01-01

Perimesencephalic subarachnoid hemorrhage (SAH) is a benign subtype of SAH without known vascular pathology. We report a case of current subarachnoid bleeding in the vicinity of the basilar artery. The patient was on anticoagulation medication and had sustained a head injury 2 days earlier. The bleeding was documented by contrast agent extravasation in MRI. Because of the isointensity of hyperacute blood to CSF in conventional T2 sequences, FLAIR images are mandatory for diagnosis in the hyperacute state.

Wilson disease: changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease

PubMed Central

Medici, Valentina; Shibata, Noreene M.; Kharbanda, Kusum K.; LaSalle, Janine M.; Woods, Rima; Liu, Sarah; Engelberg, Jesse A.; Devaraj, Sridevi; Török, Natalie J.; Jiang, Joy X.; Havel, Peter J.; Lönnerdal, Bo; Kim, Kyoungmi; Halsted, Charles H.

2012-01-01

Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b) and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum ALT and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Conclusion: reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD. PMID:22945834

Timing of deep vein thrombosis formation after aneurysmal subarachnoid hemorrhage

PubMed Central

Liang, Conrad W.; Su, Kimmy; Liu, Jesse J.; Dogan, Aclan; Hinson, Holly E.

2015-01-01

OBJECT Deep vein thrombosis (DVT) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH). The time period of greatest risk for developing DVT after aSAH is not currently known. aSAH induces a prothrombotic state, which may contribute to DVT formation. Using repeated ultrasound screening, the hypothesis that patients would be at greatest risk for developing DVT in the subacute post-rupture period was tested. METHODS One hundred ninety-eight patients with aSAH admitted to the Oregon Health & Science University Neurosciences Intensive Care Unit between April 2008 and March 2012 were included in a retrospective analysis. Ultrasound screening was performed every 5.2 ± 3.3 days between admission and discharge. The chi-square test was used to compare DVT incidence during different time periods of interest. Patient baseline characteristics as well as stroke severity and hospital complications were evaluated in univariate and multivariate analyses. RESULTS Forty-two (21%) of 198 patients were diagnosed with DVT, and 3 (2%) of 198 patients were symptomatic. Twenty-nine (69%) of the 42 cases of DVT were first detected between Days 3 and 14, compared with 3 cases (7%) detected between Days 0 and 3 and 10 cases (24%) detected after Day 14 (p < 0.05). The postrupture 5-day window of highest risk for DVT development was between Days 5 and 9 (40%, p < 0.05). In the multivariate analysis, length of hospital stay and use of mechanical prophylaxis alone were significantly associated with DVT formation. CONCLUSIONS DVT formation most commonly occurs in the first 2 weeks following aSAH, with detection in this cohort peaking between Days 5 and 9. Chemoprophylaxis is associated with a significantly lower incidence of DVT. PMID:26162047

Impact of dexamethasone in patients with aneurysmal subarachnoid haemorrhage.

PubMed

Czorlich, P; Sauvigny, T; Ricklefs, F; Abboud, T; Nierhaus, A; Vettorazzi, E; Reuter, D A; Regelsberger, J; Westphal, M; Schmidt, N O

2017-04-01

The role of corticosteroids in the treatment of patients with aneurysmal subarachnoid haemorrhage (SAH) has remained controversial for decades. Recent studies have suggested that the administration of corticosteroids in SAH patients is associated with favourable outcomes. Given their significant adverse effects, it is essential to identify those patients who will benefit from treatment with corticosteroids. A retrospective analysis of a prospectively collected cohort (n = 306) with SAH who were treated by microsurgical clipping or endovascular intervention was performed. The role of dexamethasone administration was analysed with regard to clinical conditions and SAH-related complications. Outcome was assessed at discharge and during follow-up using the Glasgow Outcome Scale (GOS). Patients treated with dexamethasone presented with more episodes of hyperglycaemia (P < 0.001), more overall infections (P < 0.001) and more ventriculostomy-related infections (P = 0.004). Multivariate analysis demonstrated that treatment with dexamethasone was associated with an unfavourable outcome at discharge (GOS 1-3) [odds ratio (OR) 2.814, 95% confidence interval (CI) 1.440-5.497, P = 0.002]. In the subgroup of microsurgically treated patients, dexamethasone administration was associated with a favourable outcome at follow-up (OR 0.193, 95% CI 0.06-0.621, P = 0.006). A higher risk for unfavourable outcome (OR 3.382, 95% CI 1.67-6.849, P = 0.001) at discharge was observed in endovascularly treated patients who received dexamethasone but this had no impact on the outcome at follow-up. Treatment with dexamethasone seems to be associated with a risk reduction for an unfavourable outcome in those patients who underwent microsurgical clipping. Despite an increased frequency of adverse effects, glucocorticoids may have a potential benefit in this specific surgical subgroup compared to endovascularly treated SAH patients. © 2017 EAN.

A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage.

PubMed

Mohney, Nathaniel; Williamson, Craig A; Rothman, Edward; Ball, Ron; Sheehan, Kyle M; Pandey, Aditya S; Fletcher, Jeffrey J; Jacobs, Teresa L; Thompson, B Gregory; Rajajee, Venkatakrishna

2018-01-01

An inflammatory response occurs after aneurysmal subarachnoid hemorrhage (aSAH) and predicts poor outcomes. Glucocorticoids suppress inflammation and promote fluid retention. Dexamethasone is often administered after aSAH for postoperative cerebral edema and refractory headache. Our objective was to examine the impact of dexamethasone use on functional outcomes and delayed cerebral ischemia (DCI) after aSAH. Patients with aSAH admitted between 2010 and 2015 were included; the data source was a single-center subarachnoid hemorrhage registry. The intervention of interest was a dexamethasone taper used <7 days from ictus. The primary outcome was poor discharge functional outcome, with a modified Rankin Scale score >3. Other outcomes included DCI and infection. A propensity score for use of dexamethasone was calculated using a logistic regression model that included potential predictors of dexamethasone use and outcome. The impact of dexamethasone on outcomes of interest was calculated and the propensity score was controlled for. A total of 440 patients with subarachnoid hemorrhage were admitted during the study period and 309 met eligibility criteria. Dexamethasone was administered in 101 patients (33%). A total of 127 patients (41%) had a discharge modified Rankin Scale score >3, 105 (34%) developed DCI, and 94 (30%) developed an infection. After propensity score analysis, dexamethasone use was associated with a significant reduction in poor functional outcomes (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.19-0.66) but showed no significant association with DCI (OR, 0.93; 95% CI, 0.53-1.64) or infection (OR, 0.60; 95% CI, 0.34-1.06). Dexamethasone use after aSAH was associated with a reduction in poor functional outcomes at discharge but not DCI, controlling for predictors of dexamethasone use. Copyright © 2017 Elsevier Inc. All rights reserved.

Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke.

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Schmidt, Morten; Dekkers, Olaf M; Christiansen, Christian F; Pedersen, Lars; Bøtker, Hans Erik; Sørensen, Henrik T

2016-03-01

The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. © 2016 American Heart Association, Inc.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

PubMed Central

Thompson, Julie; Jones, Natasha; Al‐Khafaji, Ali; Malik, Shahid; Reich, David; Munoz, Santiago; MacNicholas, Ross; Hassanein, Tarek; Teperman, Lewis; Stein, Lance; Duarte‐Rojo, Andrés; Malik, Raza; Adhami, Talal; Asrani, Sumeet; Shah, Nikunj; Gaglio, Paul; Duddempudi, Anupama; Borg, Brian; Jalan, Rajiv; Brown, Robert; Patton, Heather; Satoskar, Rohit; Rossi, Simona; Parikh, Amay; ElSharkawy, Ahmed; Mantry, Parvez; Sher, Linda; Wolf, David; Hart, Marquis; Landis, Charles; Wigg, Alan; Habib, Shahid; McCaughan, Geoffrey; Colquhoun, Steven; Henry, Alyssa; Bedard, Patricia; Landeen, Lee; Millis, Michael; Ashley, Robert; Frank, William; Henry, Andrew; Subramanian, Ram

2018-01-01

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD. PMID:29171941

The Hijdra scale has significant prognostic value for the functional outcome of Fisher grade 3 patients with subarachnoid hemorrhage.

PubMed

Bretz, Julia S; Von Dincklage, Falk; Woitzik, Johannes; Winkler, Maren K L; Major, Sebastian; Dreier, Jens P; Bohner, Georg; Scheel, Michael

2017-09-01

Despite its high prevalence among patients with aneurysmal subarachnoid hemorrhage (aSAH) and high risk of delayed cerebral ischemia (DCI), the Fisher grade 3 category remains a poorly studied subgroup. The aim of this cohort study has been to investigate the prognostic value of the Hijdra sum scoring system for the functional outcome in patients with Fisher grade 3 aSAH, in order to improve the risk stratification within this Fisher category. Initial CT scans of 72 prospectively enrolled patients with Fisher grade 3 aSAH were analyzed, and cisternal, ventricular, and total amount of blood were graded according to the Hijdra scale. Additionally, space-occupying subarachnoid blood clots were assessed. Outcome was evaluated after 6 months. Within the subgroup of Fisher grade 3, aSAH patients with an unfavorable outcome showed a significantly larger cisternal Hijdra sum score (HSS: 21.1 ± 5.2) than patients with a favorable outcome (HSS: 17.6 ± 5.9; p = 0.009). However, both the amount of ventricular blood (p = 0.165) and space-occupying blood clots (p = 0.206) appeared to have no prognostic relevance. After adjusting for the patient's age, gender, tobacco use, clinical status at admission, and presence of intracerebral hemorrhage, the cisternal and total HSS remained the only independent parameters included in multivariate logistic regression models to predict functional outcome (p < 0.01). The cisternal Hijdra score is fairly easy to perform and the present study indicates that it has an additional predictive value for the functional outcome within the Fisher 3 category. We suggest that the Hijdra scale is a practically useful prognostic instrument for the risk evaluation after aSAH and should be applied more often in the clinical setting.

Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring.

PubMed

Khot, Vinita V; Chavan-Gautam, Preeti; Mehendale, Savita; Joshi, Sadhana R

2017-06-01

Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B 12 ) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S-adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S-adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P < .05 for both) in the preterm group as compared to the term group. S-Adenosylmethionine and SAH levels were similar in both groups, although SAM:SAH ratio was lower ( P < .05) in the preterm group as compared to the term group. The global DNA methylation levels were higher ( P < .05) in women delivering small for gestation age infants as compared to women delivering appropriate for gestation age infants at term. Our data showing lower MP in the preterm placenta may have implications for the epigenetic programming of the developing fetus.

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

PubMed

Conzen, Catharina; Albanna, Walid; Weiss, Miriam; Kürten, David; Vilser, Walthard; Kotliar, Konstantin; Zäske, Charlotte; Clusmann, Hans; Schubert, Gerrit Alexander

2018-06-01

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.

Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with the use of levetiracetam versus phenytoin after aneurysmal subarachnoid hemorrhage.

PubMed

Karamchandani, Rahul Ramesh; Fletcher, Jeffrey James; Pandey, Aditya Swarup; Rajajee, Venkatakrishna

2014-09-01

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Koenig, Matthew A

2012-06-01

The purpose of this article is to describe the modern management of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). SAH causes an inflammatory reaction to blood products in the basal cisterns of the brain, which may produce cerebral ischemia and strokes through progressive narrowing of the cerebral artery lumen. This process, known as cerebral vasospasm, is the most common cause of DCI after SAH. Untreated DCI may result in strokes, which account for a significant portion of the death and long-term disability after SAH. A number of publications, including two recent consensus statements, have clarified many best practices for defining, diagnosing, monitoring, preventing, and treating DCI. DCI is best defined as new onset of focal or global neurologic deficits or strokes not attributable to another cause. In addition to the clinical examination, radiographic studies such as transcranial Doppler ultrasonography, CT angiography, and CT perfusion may have a role in determining which patients are at high risk for developing DCI. The mainstay of prevention and treatment of DCI is maintenance of euvolemia, which can be a difficult therapeutic target to measure. Hemodynamic augmentation with induced hypertension with or without inotropic support has become the first-line treatment of DCI. The ideal method of measuring hemodynamic values and volume status in patients with DCI remains elusive. In patients who do not adequately respond to or cannot tolerate hemodynamic augmentation, endovascular therapy (intraarterial vasodilators and balloon angioplasty) is a complementary strategy. Optimal triggers for escalation and de-escalation of therapies for DCI have not been well defined. Recent guidelines and consensus statements have clarified many aspects of prevention, monitoring, and treatment of DCI after SAH. Controversies continue regarding the optimal methods for measurement of volume status, the role of invasive neuromonitoring

The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report.

PubMed

Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

2015-01-01

Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. An experimental rabbit study. The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. The mean volume of imaginary descending colons was estimated as 93 ± 12 cm(3) in the control group and 121 ± 26 cm(3) in the SS group and 176 ± 49 cm(3) in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report

PubMed Central

Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

2015-01-01

Context: Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. Aims: The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. Settings and Design: An experimental rabbit study. Materials and Methods: The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. Results: The mean volume of imaginary descending colons was estimated as 93 ± 12 cm3 in the control group and 121 ± 26 cm3 in the SS group and 176 ± 49 cm3 in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies. PMID:25972712

Trends in incidence and in short term survival following a subarachnoid haemorrhage in Scotland, 1986 - 2005: a retrospective cohort study

PubMed Central

2011-01-01

Background To examine age and sex specific incidence and 30 day case fatality for subarachnoid haemorrhage (SAH) in Scotland over a 20 year period. Methods A retrospective cohort study using routine hospital discharge data linked to death records. Results Between 1986 and 2005, 12,056 individuals experienced an incident SAH. Of these 10,113 (84%) survived to reach hospital. Overall age-standardised incidence rates were greater in women than men and remained relatively stable over the study period. In 2005, incidence in women was 12.8 (95% CI 11.5 to 14.2) and in men 7.9 (95% CI 6.9 to 9.1). 30 day case fatality in individuals hospitalised with SAH declined substantially, falling from 30.0% in men and 33.9% in women in 1986-1990 to 24.5% in men and 29.1% in women in 2001-2005. For both men and women, the largest reductions were observed in those aged between 40 to 59 years. After adjustment for age, socio-economic status and co-morbidity, the odds of death at 30 days in 2005 compared to odds of death in 1986 was 0.64 (0.54 to 0.76), p < 0.001 for those below 70 years, and 1.14 (0.83 to 1.56), p = 0.4 in those 70 years and above. Conclusions Incidence rates for SAH remained stable between 1986 and 2005 suggesting that a better understanding of SAH risk factors and their reduction is needed. 30 day case fatality rates have declined substantially, particularly in middle-age. However, they remain high and it is important to ensure that this is not due to under-diagnosis or under-treatment. PMID:21447158

Vision after trans-sylvian or temporobasal selective amygdalohippocampectomy: a prospective randomised trial.

PubMed

Delev, Daniel; Wabbels, Bettina; Schramm, Johannes; Nelles, Michael; Elger, Christian E; von Lehe, Marec; Clusmann, Hans; Grote, Alexander

2016-09-01

Selective amygdalohippocampectomy (SAH) is an accepted surgical procedure for treatment of pharmacoresistant mesial temporal lobe epilepsy, but it may lead to postoperative visual field deficits (VFDs). Here we present a prospective randomised trial comparing the postoperative VFDs after either a trans-sylvian or temporobasal approach for SAH. Forty-eight patients were randomly assigned to trans-sylvian (n = 24) or temporobasal (n = 24) SAH. Postoperative VFD were quantitatively evaluated using automated static and kinetic perimetry. In 24 cases, diffusion tensor imaging-based deterministic fibre-tracking of the optic radiation was performed. The primary endpoint was absence of postoperative VFD. The secondary endpoint was seizure outcome and driving ability. Three patients (13 %) from the trans-sylvian group showed no VFD, compared to 11 patients (46 %) from the temporobasal group without VFD (p = 0.01, RR = 3.7; CI = 1.2-11.5). Fifteen patients from each group (63 %) became completely seizure-free (ILAE1). Among those seizure-free cases, five trans-sylvian (33 %) and ten temporobasal (66 %) patients could apply for a driving licence (NNT = 3) when VFDs were considered. Although the trans-sylvian group experienced more frequent VFDs, the mean functional visual impairment showed a tendency to be less pronounced compared with the temporobasal group. DTI-based tracking of the optic radiation revealed that a lower distance of optic radiation to the temporal base correlated with increased rate of VFD in the temporobasal group. Temporobasal SAH shows significantly fewer VFDs and equal seizure-free rate compared with the trans-sylvian SAH. However, in patients in whom the optic radiation is close to the temporal base, the trans-sylvian approach may be a preferred alternative.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

PubMed

Dorhout Mees, Sanne M; Algra, Ale; Wong, George K C; Poon, Wai S; Bradford, Celia M; Saver, Jeffrey L; Starkman, Sidney; Rinkel, Gabriel J E; van den Bergh, Walter M; van Kooten, F; Dirven, C M; van Gijn, J; Vermeulen, M; Rinkel, G J E; Boet, R; Chan, M T V; Gin, T; Ng, S C P; Zee, B C Y; Al-Shahi Salman, R; Boiten, J; Kuijsten, H; Lavados, P M; van Oostenbrugge, R J; Vandertop, W P; Finfer, S; O'Connor, A; Yarad, E; Firth, R; McCallister, R; Harrington, T; Steinfort, B; Faulder, K; Assaad, N; Morgan, M; Starkman, S; Eckstein, M; Stratton, S J; Pratt, F D; Hamilton, S; Conwit, R; Liebeskind, D S; Sung, G; Kramer, I; Moreau, G; Goldweber, R; Sanossian, N

2015-11-01

Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH. © 2015 American Heart Association, Inc.

A Web-based Decision Tool to Estimate Subarachnoid Hemorrhage Risk in Emergency Department Patients

PubMed Central

Manella, Haley; Sivasankar, Shyam; Perry, Jeffrey J; Pfeil, Sam; Senyak, Josh; Shachter, Ross

2018-01-01

Subarachnoid hemorrhage (SAH) from a leaking aneurysm is a neurological emergency. SAH patients often present with headache—a common chief complaint among emergency department patients. If unrecognized, 70% of the patients with re-bleeds die and one third are left with neurological deficits. Therefore, it is critical to distinguish the signs and symptoms of SAH from benign causes of headache, perform the appropriate diagnostic tests and treat in a timely manner in order to reduce the disability and mortality associated with this condition. In patients with suspected SAH, traditional diagnostic strategies in the emergency department employ non-contrast computed tomography (CT) of the brain to detect blood in the subarachnoid space followed by lumbar puncture if there is a high clinical probability of aneurysmal bleed without any evidence of blood on CT scan. While the older generation CT scanners were less sensitive to blood detection in the subarachnoid space, recent advances in CT imaging have resulted in sensitivity approaching 100% for detection of blood in the subarachnoid space specifically within six hours of symptom onset. Therefore, the benefit of lumbar puncture is controversial when performed within the first six hours of symptom onset. Despite this, lumbar puncture is still commonly performed in the emergency department, exposing patients to unnecessary procedural risks. The objective of this research study is to develop a web-based risk calculator that estimates the risk of SAH based on time to emergency department presentation after symptom onset, physical findings and imaging characteristics with the goal of reducing unnecessary lumbar punctures in the emergency department. In this technical report, we describe the prototype calculator, the mathematical basis of the model and provide a link to the web-based prototype. In the future, we will refine the prototype, make it user-friendly to physicians, staff and patients and study its benefits in the

Influence of stroke subtype on quality of care in the Get With The Guidelines-Stroke Program.

PubMed

Smith, E E; Liang, L; Hernandez, A; Reeves, M J; Cannon, C P; Fonarow, G C; Schwamm, L H

2009-09-01

Little is known about in-hospital care for hemorrhagic stroke. We examined quality of care in intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) admissions in the national Get With The Guidelines-Stroke (GWTG-Stroke) database, and compared them to ischemic stroke (IS) or TIA admissions. Between April 1, 2003, and December 30, 2007, 905 hospitals contributed 479,284 consecutive stroke and TIA admissions. The proportions receiving each quality of care measure were calculated by dividing the total number of patients receiving the intervention by the total number of patients eligible for the intervention, excluding ineligible patients or those with contraindications to treatment. Logistic regression models were used to determine associations between measure compliance and stroke subtype, controlling for patient and hospital characteristics. Stroke subtypes were 61.7% IS, 23.8% TIA, 11.1% ICH, and 3.5% SAH. Performance on care measures was generally lower in ICH and SAH compared to IS/TIA, including guideline-recommended measures for deep venous thrombosis (DVT) prevention (for ICH) and smoking cessation (for SAH) (multivariable-adjusted p < 0.001 for all comparisons). Exceptions were that ICH patients were more likely than IS/TIA to have door-to-CT times <25 minutes (multivariable-adjusted p < 0.001) and to undergo dysphagia screening (multivariable-adjusted p < 0.001). Time spent in the GWTG-Stroke program was associated with improvements in many measures of care for ICH and SAH patients, including DVT prevention and smoking cessation therapy (multivariable-adjusted p < 0.001). Many hospital-based acute care and prevention measures are underutilized in intracerebral hemorrhage and subarachnoid hemorrhage compared to ischemic stroke /TIA. Duration of Get With The Guidelines-Stroke participation is associated with improving quality of care for hemorrhagic stroke.

Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage.

PubMed

Lopes, Katia de Paiva; Vinasco-Sandoval, Tatiana; Vialle, Ricardo Assunção; Paschoal, Fernando Mendes; Bastos, Vanessa Albuquerque P Aviz; Bor-Seng-Shu, Edson; Teixeira, Manoel Jacobsen; Yamada, Elizabeth Sumi; Pinto, Pablo; Vidal, Amanda Ferreira; Ribeiro-Dos-Santos, Arthur; Moreira, Fabiano; Santos, Sidney; Paschoal, Eric Homero Albuquerque; Ribeiro-Dos-Santos, Ândrea

2018-06-08

The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage.

PubMed

Jaja, Blessing N R; Schweizer, Tom A; Claassen, Jan; Le Roux, Peter; Mayer, Stephan A; Macdonald, R Loch

2018-06-01

Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at-risk patients. To develop and validate a risk score for convulsive seizure during acute admission for SAH. A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in-hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness-of-fit test. The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had AUC = 0.77, 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH.

Crystal Structures of the Helicobacter pylori MTAN Enzyme Reveal Specific Interactions between S-Adenosylhomocysteine and the 5'-Alkylthio Binding Subsite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, Vidhi; Ronning, Donald R.

2012-11-13

The bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzyme is a multifunctional enzyme that catalyzes the hydrolysis of the N-ribosidic bond of at least four different adenosine-based metabolites: S-adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadenosine (5'-DOA), and 6-amino-6-deoxyfutalosine. These activities place the enzyme at the hub of seven fundamental bacterial metabolic pathways: S-adenosylmethionine (SAM) utilization, polyamine biosynthesis, the purine salvage pathway, the methionine salvage pathway, the SAM radical pathways, autoinducer-2 biosynthesis, and menaquinone biosynthesis. The last pathway makes MTAN essential for Helicobacter pylori viability. Although structures of various bacterial and plant MTANs have been described, the interactions between the homocysteine moiety of SAH and themore » 5'-alkylthiol binding site of MTAN have never been resolved. We have determined crystal structures of an inactive mutant form of H. pylori MTAN bound to MTA and SAH to 1.63 and 1.20 Å, respectively. The active form of MTAN was also crystallized in the presence of SAH, allowing the determination of the structure of a ternary enzyme–product complex resolved at 1.50 Å. These structures identify interactions between the homocysteine moiety and the 5'-alkylthiol binding site of the enzyme. This information can be leveraged for the development of species-specific MTAN inhibitors that prevent the growth of H. pylori.« less

Estimated annual cost of arterial hypertension treatment in Brazil.

PubMed

Dib, Murilo W; Riera, Rachel; Ferraz, Marcos B

2010-02-01

To estimate the direct annual cost of systemic arterial hypertension (SAH) treatment in Brazil's public and private health care systems, assess its economic impact on the total health care budget, and determine its proportion of the 2005 gross domestic product (GDP). A decision tree model was used to determine direct costs based on estimated use of various resources in SAH diagnosis and care, including treatment (medication and non-medication), complementary exams, doctor visits, nutritional assessments, and emergency room visits. Estimated direct annual cost of SAH treatment was approximately US$ 398.9 million for the public health care system and US$ 272.7 million for the private system, representing 0.08% of the 2005 GDP (ranging from 0.05% to 0.16%). With total health care expenses comprising about 7.6% of Brazil's GDP, this cost represented 1.11% of overall health care costs (0.62% to 2.06%)-1.43% of total expenses for the Unified Healthcare System (Sistema Unico de Saúde, SUS) (0.79% to 2.75%) and 0.83% of expenses for the private health care system (0.47% to 1.48%). Conclusion. To guarantee public or private health care based on the principles of universality and equality, with limited available resources, efforts must be focused on educating the population on prevention and treatment compliance in diseases such as SAH that require significant health resources.

Methylenetetrahydrofolate Reductase Modulates Methyl Metabolism and Lignin Monomer Methylation in Maize.

PubMed

Wu, Zhenying; Ren, Hao; Xiong, Wangdan; Roje, Sanja; Liu, Yuchen; Su, Kunlong; Fu, Chunxiang

2018-05-30

The brown midrib2 (bm2) mutant of maize, with a modified lignin composition, contains a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. We here show that a MITE transposon insertion caused downregulation of MTHFR with accompanying decrease in 5-methyl-THF and increase in 5, 10-methylene-THF and THF in the bm2 mutant. Furthermore, MTHFR mutation did not change the content of SAM, the methyl group donor involved in the biosynthesis of guaiacyl (G) and syringyl (S) lignins, but increased the level of S-adenosyl homocysteine (SAH), the de-methylation product of SAM. Moreover, competitive inhibition of the maize caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT) enzyme activities by SAH was found, suggesting that SAH/SAM ratio rather than SAM concentration regulates the transmethylation reactions of lignin intermediates. Phenolic profiling revealed that caffeoyl alcohol glucose derivatives accumulated in the mutant, indicating impaired 3-O-methylation of monolignols. A remarkable increase in the unusual catechyl (C) lignin determined in the mutant demonstrates that MTHFR downregulation mainly affects G lignin biosynthesis, consistent with the observation that CCoAOMT is more sensitive to SAH inhibition than COMT. This study which uncovered a novel regulatory mechanism in lignin biosynthesis and may offer an effective approach to utilize lignocellulosic feedstocks in future.

Lipocalin-type prostaglandin D synthase scavenges biliverdin in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage

PubMed Central

Inui, Takashi; Mase, Mitsuhito; Shirota, Ryoko; Nagashima, Mariko; Okada, Tetsuya; Urade, Yoshihiro

2014-01-01

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is the second major protein in human cerebrospinal fluid (CSF) and belongs to the lipocalin superfamily composed of various secretory lipophilic ligand transporter proteins. However, the endogenous ligand of L-PGDS has not yet been elucidated. In this study, we purified L-PGDS from the CSF of aneurysmal subarachnoid hemorrhage (SAH) patients. Lipocalin-type PG D synthase showed absorbance spectra with major peaks at 280 and 392 nm and a minor peak at around 660 nm. The absorbance at 392 nm of L-PGDS increased from 1 to 9 days and almost disappeared at 2 months after SAH, whereas the L-PGDS activity decreased from 1 to 7 days and recovered to normal at 2 months after SAH. These results indicate that some chromophore had accumulated in the CSF after SAH and bound to L-PGDS, thus inactivating it. Matrix assisted laser desorption ionization time-of-flight mass spectrometry of L-PGDS after digestion of it with endoproteinase Lys-C revealed that L-PGDS had covalently bound biliverdin, a by-product of heme breakdown. These results suggest that L-PGDS acted as a scavenger of biliverdin, which is a molecule not found in normal CSF. This is the first report of identification of a pathophysiologically important endogenous ligand for this lipocalin superfamily protein in humans. PMID:25005874

Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

PubMed

Etminan, Nima; Macdonald, R Loch; Davis, Cara; Burton, Kevin; Steiger, Hans-Jakob; Hänggi, Daniel

2015-01-01

The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.

Korean Clinical Practice Guidelines for Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Cho, Won-Sang; Park, Sukh Que; Ko, Jun Kyeung; Kim, Dae-Won; Park, Jung Cheol; Yeon, Je Young; Chung, Seung Young; Chung, Joonho; Joo, Sung-Pil; Hwang, Gyojun; Kim, Deog Young; Chang, Won Hyuk; Choi, Kyu-Sun; Lee, Sung Ho; Sheen, Seung Hun; Kang, Hyun-Seung; Kim, Byung Moon; Bae, Hee-Joon; Oh, Chang Wan; Park, Hyeon Seon

2018-01-01

Despite advancements in treating ruptured cerebral aneurysms, an aneurysmal subarachnoid hemorrhage (aSAH) is still a grave cerebrovascular disease associated with a high rate of morbidity and mortality. Based on the literature published to date, worldwide academic and governmental committees have developed clinical practice guidelines (CPGs) to propose standards for disease management in order to achieve the best treatment outcomes for aSAHs. In 2013, the Korean Society of Cerebrovascular Surgeons issued a Korean version of the CPGs for aSAHs. The group researched all articles and major foreign CPGs published in English until December 2015 using several search engines. Based on these articles, levels of evidence and grades of recommendations were determined by our society as well as by other related Quality Control Committees from neurointervention, neurology and rehabilitation medicine. The Korean version of the CPGs for aSAHs includes risk factors, diagnosis, initial management, medical and surgical management to prevent rebleeding, management of delayed cerebral ischemia and vasospasm, treatment of hydrocephalus, treatment of medical complications and early rehabilitation. The CPGs are not the absolute standard but are the present reference as the evidence is still incomplete, each environment of clinical practice is different, and there is a high probability of variation in the current recommendations. The CPGs will be useful in the fields of clinical practice and research. PMID:29526058

Quality of internet information available to patients on websites in Portuguese.

PubMed

Del Giglio, Adriana; Abdala, Beatrice; Ogawa, Carolina; Amado, Daniel; Carter, Diego; Gomieiro, Fernanda; Salama, Fernanda; Shiroma, Marina; Del Giglio, Auro

2012-01-01

Patients and their relatives often look for information about their diseases on the internet. Diabetes mellitus (DM), systemic arterial hypertension (SAH), and acute myocardial infarction (AMI) are the most prevalent in Brazil, thus, information on these pathologies is extremely searched for on the internet. For this reason, this study attempted to evaluate the quality of information available in Portuguese on the web regarding these disorders. The first 20 websites in Portuguese for each disease through the Google® search algorithm were selected. The Discern Questionnaire (DQ) and Health on the Net (HON) were used as tools in order to evaluate the quality of information. To assess adequacy, international and Brazilian guidelines for different co-morbidities were used. When evaluating the information content available, 45%, 95%, and 85% of pages had the definition of DM, SAH, and AMI, respectively. Only 25% of the websites regarding the three co-morbidities had specific information on diagnosis and treatment. Only 15%, 20%, and 10% of the websites had HON certification, respectively. Using the DQ approach, scores higher than 50% were obtained in 70% of the DM websites, in 65% of SAH websites, and in 55% of the AMI websites. The available information in Portuguese on the internet regarding the three pathologies selected (DM, SAH, and AMI) is quite often inadequate and insufficient.

Hydrogen sulfide ameliorates subarachnoid hemorrhage-induced neuronal apoptosis via the ROS-MST1 pathway

PubMed Central

Shi, Ligen; Lei, Jianwei; Xu, Hangzhe; Zheng, Jingwei; Wang, Yan; Peng, Yucong; Yu, Jun; Zhang, Jianmin

2017-01-01

Background Hydrogen sulfide (H2S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H2S in early brain injury after subarachnoid hemorrhage (SAH). Methods One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H2S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H2S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H2S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions Exogenous NaHS, as a donor of H2S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein. PMID:29088725

Plasma 8-iso-Prostaglandin F2α, a possible prognostic marker in aneurysmal subarachnoid hemorrhage.

PubMed

Pan, De-Sheng; Yan, Min; Hassan, Muhammad; Fang, Ze-Bin; Chen, Man-Tao

2017-06-01

8-iso-Prostaglandin F2α (8-iso-PGF2α) is a potential biomarker of oxidative stress. This study clarified whether plasma 8-iso-PGF2α concentrations were affected and its underlying relevance to prognosis in aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational study, a total of 170 controls and 170 aSAH patients were enrolled. Plasma 8-iso-PGF2α concentrations were detected using an ELISA. Severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale. Clinical outcomes included 6-month mortality and poor outcome referred to as Glasgow outcome scale score of 1-3. As compared to controls, admission plasma 8-iso-PGF2α concentrations were significantly enhanced. Increased concentrations of plasma 8-iso-PGF2α correlated with WFNS scores and modified Fisher scores. 8-iso-PGF2α in plasma was an independent predictor for clinical outcomes. Under ROC curve, the predictive values of 8-iso-PGF2α concentrations resembled those of WFNS scores and modified Fisher scores for clinical outcomes. An elevation in plasma 8-iso-PGF2α concentrations is associated with the severity and poor outcome after aSAH, substantializing 8-iso-PGF2α as a potential prognostic biomarker of aSAH. Copyright © 2017. Published by Elsevier B.V.

Compared to controls, patients with ruptured aneurysm and surgical intervention show increase in symptoms of depression and lower cognitive performance, but their objective sleep is not affected.

PubMed

Brand, Serge; Zimmerer, Stefan; Kalak, Nadeem; Planta, Sandra Von; Schwenzer-Zimmerer, Katja; Müller, Andreas Albert; Zeilhofer, Hans-Florian; Holsboer-Trachsler, Edith

2015-02-01

Patients with aneurysmal subarachnoid haemorrhage (aSAH) have impaired sleep and cognitive performance together with more difficulties in social and everyday life. Hypocortisolism has also been reported. However, a study assessing all dimensions between aSAH severity, objective and subjective sleep, cortisol secretion, cognitive performance and social and everyday life has not so far been performed. The aim of the present study was therefore two-fold: (1) to assess, in a sample of patients with aSAH, objective and subjective sleep, cognitive functioning, social skills and cortisol secretion concurrently, and (2) to compare patients on these variables with a control group. Twenty-one patients (17 females; mean age: 58.80 years) with ruptured aneurysm and surgical intervention and 21 (14 females; mean age: 58.90 years) age- and gender-matched controls took part in the study. Assessments covered objective sleep-EGG recordings, subjective sleep, salivary cortisol analysis, and psychological functioning including memory performance, mood, and emotion recognition. Compared to healthy controls, patients had lower scores for verbal memory performance and emotion recognition; they also reported more marked depressive symptoms and complained of poor sleep. However, no differences were found for objective sleep or cortisol secretion. Subjective and objective sleep, cortisol secretion and psychological functioning were unrelated. Findings indicate that patients with aSAH face psychological rather than physiological issues.

Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using classification and regression tree analysis.

PubMed

Lo, Benjamin W Y; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H

2016-01-01

Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months. Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P < 0.01). A clinically useful classification tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.

Discrimination between Closely Related Cellular Metabolites by the SAM-I Riboswitch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montange, R.; Mondragon, E; van Tyne, D

2010-01-01

The SAM-I riboswitch is a cis-acting element of genetic control found in bacterial mRNAs that specifically binds S-adenosylmethionine (SAM). We previously determined the 2.9-{angstrom} X-ray crystal structure of the effector-binding domain of this RNA element, revealing details of RNA-ligand recognition. To improve this structure, variations were made to the RNA sequence to alter lattice contacts, resulting in a 0.5-{angstrom} improvement in crystallographic resolution and allowing for a more accurate refinement of the crystallographic model. The basis for SAM specificity was addressed by a structural analysis of the RNA complexed to S-adenosylhomocysteine (SAH) and sinefungin and by measuring the affinity ofmore » SAM and SAH for a series of mutants using isothermal titration calorimetry. These data illustrate the importance of two universally conserved base pairs in the RNA that form electrostatic interactions with the positively charged sulfonium group of SAM, thereby providing a basis for discrimination between SAM and SAH.« less

Management of aneurysmal subarachnoid hemorrhage.

PubMed

Etminan, N; Macdonald, R L

2017-01-01

Spontaneous subarachnoid hemorrhage (SAH) affects people with a mean age of 55 years. Although there are about 9/100 000 cases per year worldwide, the young age and high morbidity and mortality lead to loss of many years of productive life. Intracranial aneurysms account for 85% of cases. Despite this, the majority of survivors of aneurysmal SAH have cognitive deficits, mood disorders, fatigue, inability to return to work, and executive dysfunction and are often unable to return to their premorbid level of functioning. The main proven interventions to improve outcome are aneurysm repair in a timely fashion by endovascular coiling rather than neurosurgical clipping when feasible and administration of nimodipine. Management also probably is optimized by neurologic intensive care units and multidisciplinary teams. Improved diagnosis, early aneurysm repair, administration of nimodipine, and advanced neurointensive care support may be responsible for improvement in survival from SAH in the last few decades. © 2017 Elsevier B.V. All rights reserved.

Surgical Management of Dural Arteriovenous Fistula After Craniotomy: Case Report and Review of Literature.

PubMed

Pabaney, Aqueel H; Robin, Adam M; Basheer, Azam; Malik, Ghaus

2016-05-01

Development of dural arteriovenous fistula (dAVF) with cortical venous drainage at the site of previous craniotomy is a rare manifestation of nontraumatic subarachnoid hemorrhage (SAH). The authors present a case of postcraniotomy dAVF formation and discuss plausible underlying mechanisms of fistula formation and treatment options as well as review the literature. A 62-year-old man, who had undergone craniotomy 2 decades previously, presented with SAH. Workup revealed a low-flow dAVF with leptomeningeal venous drainage at the posterior margin of the craniotomy. Surgical resection of fistula was undertaken that resulted in cure. Spontaneous SAH in patients with a previous history of an intracranial procedure (e.g., craniotomy, ventriculostomy) should prompt detailed imaging evaluation. In the absence of vascular disease, meticulous review of the angiogram must be undertaken to rule out dAVF at the procedure site and it should be treated definitively. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep Apnea and Driving. Recommendations for Interpreting Spanish Regulations for Drivers.

PubMed

Terán-Santos, Joaquín; Egea Santaolalla, Carlos; Montserrat, Jose María; Masa Jiménez, Fernando; Librada Escribano, Maria Villar; Mirabet, Enrique; Valdés Rodríguez, Elena

2017-06-01

Road traffic accidents are one of the main causes of death worldwide and are clearly associated with sleepiness. Individuals with undiagnosed sleep apnea-hypopnea syndrome (SAHS) are among the population with a high risk of experiencing sleepiness at the wheel and, consequently, road traffic accidents. Treatment with continuous positive airway pressure (CPAP) has been shown to reduce the risk of accidents among drivers with SAHS. For this reason, the European Union has included this disease in the psychological and physical criteria for obtaining or renewing a driving license. To comply with this European Directive, Spain has updated its driving laws accordingly. To facilitate the implementation of the new regulations, a group of experts from various medical societies and institutions has prepared these guidelines that include questionnaires to screen for SAHS, diagnostic and therapeutic criteria, and physician's report templates. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

PubMed

Shimizu, Tomohisa; Hishikawa, Tomohito; Nishihiro, Shingo; Shinji, Yukei; Takasugi, Yuji; Haruma, Jun; Hiramatsu, Masafumi; Kawase, Hirokazu; Sato, Sachiko; Mizoue, Ryoichi; Takeda, Yoshimasa; Sugiu, Kenji; Morimatsu, Hiroshi; Date, Isao

2018-01-01

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P 50 ) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after

Fingerprinting-based metabolomic approach with LC-MS to sleep apnea and hypopnea syndrome: a pilot study.

PubMed

Ferrarini, Alessia; Rupérez, Francisco J; Erazo, Marcela; Martínez, Ma Paz; Villar-Álvarez, Felipe; Peces-Barba, Germán; González-Mangado, Nicolás; Troncoso, María F; Ruiz-Cabello, Jesús; Barbas, Coral

2013-10-01

Sleep apnea and hypopnea syndrome (SAHS) is a multicomponent disorder, with associated cardiovascular and metabolic alterations, second in order of frequency among respiratory disorders. Sleep apnea is diagnosed with an overnight sleep test called a polysomnogram, which requires having the patient in hospital. In addition, a more clear classification of patients according to mild and severe presentations would be desirable. The aim of the present study was to assess the relative metabolic changes in SAHS to identify new potential biomarkers for diagnosis, able to evaluate disease severity to establish response to therapeutic interventions and outcomes. For this purpose, metabolic fingerprinting represents a valuable strategy to monitor, in a nontargeted manner, the changes that are at the base of the pathophysiological mechanism of SAHS. Plasma samples of 33 SAHS patients were collected after polysomnography and analyzed with LC coupled to MS (LC-QTOF-MS). After data treatment and statistical analysis, signals differentiating nonsevere and severe patients were detected. Putative identification of 14 statistically significant features was obtained and changes that can be related to the episodes of hypoxia/reoxygenation (inflammation) have been highlighted. Among them, the patterns of variation of platelet activating factor and lysophospholipids, together with some compounds related to differential activity of the gut microflora (bile pigments and pipecolic acid) open new lines of research that will benefit our understanding of the alterations, offering new possibilities for adequate monitoring of the stage of the disease. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

PubMed Central

Hanafy, Khalid A.; Grobelny, Bartosz; Fernandez, Luis; Kurtz, Pedro; Connolly, ES; Mayer, Stephan A.; Schindler, Christian; Badjatia, Neeraj

2010-01-01

Objective: TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 hours and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results: Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 hours of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels (β=0.066, P<0.02), intraventricular hemorrhage (β=0.085, P<0.021), and aneurysm size >6 mm (β=0.14, p<0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. Interpretation: Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. PMID:20110094

Long-Term Causes of Death and Excess Mortality After Carotid Artery Ligation.

PubMed

Ibrahim, Tarik F; Jahromi, Behnam Rezai; Miettinen, Joonas; Raj, Rahul; Andrade-Barazarte, Hugo; Goehre, Felix; Kivisaari, Riku; Lehto, Hanna; Hernesniemi, Juha

2016-06-01

Carotid artery ligation (CAL) is used to treat large and complex intracranial aneurysms. However, little is known about long-term survival and causes of death in patients who undergo the procedure. This study was intended to evaluate if patients who have undergone CAL have long-term excess mortality and what the causes of death are. All patients were treated at Helsinki University Hospital between 1937 and 2009. Patients who had undergone CAL and survived ≥1 year after the procedure were included in the cohort. Follow-up was until death or 2015 (2711 patient-years). Causes of death were reviewed and relative survival ratios calculated using the Ederer II method and a matched population. There was 12% excess mortality in all patients 20 years after CAL and 22% after 30 years. A higher proportion of the patients who had subarachnoid hemorrhage (SAH) died during follow-up compared with unruptured patients undergoing CAL. Cardiovascular disease and cerebrovascular accident were the leading causes of death. Patients with unruptured aneurysms did not experience as much excess mortality as those who had an SAH. The higher proportion of deaths observed in ruptured patients may be partly because of long-term excess mortality conferred by the SAH itself or SAH risk factors. Although the entire population did display excess mortality compared with the general population, this may be because of shared risk factors for aneurysm development and rupture and the cause of death. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome.

PubMed

Meurice, J C; Cornette, A; Philip-Joet, F; Pepin, J L; Escourrou, P; Ingrand, P; Veale, D

2007-11-01

Quality of life (QOL) and sleepiness for patients with sleep apnea/hypopnea syndrome (SAHS) might improve with continuous positive airway pressure devices working in auto-adjust mode (autoCPAP) by allowing pressure modulations following patient needs. Clinical comparisons between devices driven by different algorithms are needed. We compared the clinical effectiveness of fixed pressure CPAP and four different autoCPAP devices by assessing compliance and QOL (36-item short-form health survey [SF-36]). SAHS patients were randomly allocated to five groups. Polysomnography (PSG) was performed to titrate the effective pressure in the constant CPAP group and evaluate residual apnea/hypopnea index (AHI) under autoCPAP. Follow-up consisted of clinical visits at three and six months by homecare technicians who assessed compliance, symptom scores and SF-36 scores. A laboratory-based PSG using the same CPAP/autoCPAP device as at home was performed at six months. Eighty-three patients (mean age 56+/-10 yrs) with mean body mass index (BMI) 30.8+/-5.3 kg/m(2) and severe SAHS (mean AHI: 52.3+/-17.8/h) were included. There were no differences in clinical symptoms or QOL scores, and similar clinical and PSG improvements were seen in all groups. CPAP use was >5 h per night, without any significant difference between groups. AutoCPAP is equally as effective as fixed CPAP for long-term home treatment in severe SAHS patients.

The evolution of invasive cerebral vasospasm treatment in patients with spontaneous subarachnoid hemorrhage and delayed cerebral ischemia-continuous selective intracarotid nimodipine therapy in awake patients without sedation.

PubMed

Paľa, Andrej; Schneider, Max; Brand, Christine; Pedro, Maria Teresa; Özpeynirci, Yigit; Schmitz, Bernd; Wirtz, Christian Rainer; Kapapa, Thomas; König, Ralph; Braun, Michael

2018-05-26

Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are major factors that limit good outcome in patients with spontaneous subarachnoid hemorrhage (SAH). Continuous therapy with intra-arterial calcium channel blockers has been introduced as a new step in the invasive treatment cascade of CV and DCI. Sedation is routinely necessary for this procedure. We report about the feasibility to apply this therapy in awake compliant patients without intubation and sedation. Out of 67 patients with invasive endovascular treatment of cerebral vasospasm due to spontaneous SAH, 5 patients underwent continuous superselective intracarotid nimodipine therapy without intubation and sedation. Complications, neurological improvement, and outcome at discharge were summarized. Very good outcome was achieved in all 5 patients. The Barthel scale was 100 and the modified Rankin scale 0-1 in all cases at discharge. We found no severe complications and excellent neurological monitoring was possible in all cases due to patients' alert status. Symptoms of DCI resolved within 24 h in all 5 cases. We could demonstrate the feasibility and safety of selective intracarotid arterial nimodipine treatment in awake, compliant patients with spontaneous SAH and symptomatic CV and DCI. Using this method, an excellent monitoring of neurological function as well as early detection of other complications is possible. It might be an important step in the risk reduction of invasive CV therapy to improve the outcome with CV and DCI after SAH in selected patients.

Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation.

PubMed

Pyne, G J; Cadoux-Hudson, T A; Clark, J F

2001-01-01

Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event. The intracellular calcium concentration has been demonstrated to rise during the vasospastic process. Calcium also stimulates oxidative metabolism as does adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP) hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP and phosphocreatine have also been demonstrated in various models of SAH mediated vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for force generation and reserves glycolytic metabolism for ion homeostasis. A decrease in oxidative metabolism during force generation would imply failing mitochondria and increased glycolytic high-energy phosphate supply. Increased oxidative metabolism would imply a decreased efficiency of the contractile apparatus or mitochondria. The aim of this study was to see if SAH CSF stimulation of porcine carotid artery oxidative metabolism was altered during force generation when compared with incremental calcium stimulation with potassium chloride depolarisation. CSF from patients (n = 10) who had subarachnoid haemorrhage stimulated force generation but with a significant 'right shift' in oxygen consumption. This 'right shift' is indicative of an increased energy cost for contractile work. These results suggest that vascular smooth muscle contractile apparatus, when stimulated by subarachnoid cerebrospinal fluid, is consuming excess adenosine triphosphate during force generation.

[A case of subarachnoid hemorrhage due to infective endocarditis by methicillin-resistant coagulase-negative staphylococcus].

PubMed

Kajikawa, Shunsuke; Oeda, Tomoko; Park, Kwiyoung; Yamamoto, Kenji; Sugiyama, Hiroshi; Sawada, Hideyuki

2017-12-27

A 77-year-old man visited our hospital with unstable gait following 2 months of anorexia. Brain MRI showed multiple infarcts; cardiac echocardiography revealed mitral-valve vegetation; and blood culture revealed methicillin-resistant coagulase-negative staphylococci. The patient was diagnosed with infective endocarditis (IE). Subarachnoid hemorrhage (SAH) developed ten days after antibiotic treatment. Intracranial aneurysm was not found. We speculated that chronic inflammation of the cerebral arterial walls by bacteria of low virulence was associated with SAH complication. The vegetation disappeared following additional gentamicin administration and the patient recovered to walk.

Preliminary Examination of Sahara 99555: Mineralogy and Experimental Studies of a New Angrite

NASA Technical Reports Server (NTRS)

Mikouchi, T.; McKay, G.; Le, L.; Mittlefehldt, D. W.

2000-01-01

A 2710 g meteorite, Sahara 99555 (Sah99), was recently recovered from the Sahara and reported to be the 5th angrite. It is the largest angrite ever found and may offer useful information to better understand the unusual petrogeneses of this rare achondrite group. It may also allow us to examine the chronological record of igneous activity in the very early solar system. We obtained a 2.6 g chip of Sah99 and here present a preliminary report of its petrology and mineralogy in conjunction with a crystallization experiment on an analogue composition.

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome.

PubMed

Nasr, Nathalie; Gaio, Rita; Czosnyka, Marek; Budohoski, Karol; Liu, Xiuyun; Donnelly, Joseph; Sykora, Marek; Kirkpatrick, Peter; Pavy-Le Traon, Anne; Haubrich, Christina; Larrue, Vincent; Smielewski, Peter

2018-07-01

Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving β-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. Forty-eight patients were included. Median age was 58 years old (36-76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS ( P =0.007), sedation ( P =0.001), World Federation of Neurosurgery score ( P =0.001), Glasgow score ( P =0.002), Fisher score ( P =0.022), and heart rate ( P =0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048-1.818; P =0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171-0.706; P =0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study. © 2018 American Heart Association, Inc.

Gutuo Jiejiu decoction improves survival of patients with severe alcoholic hepatitis: A retrospective cohort study.

PubMed

Mou, Hong-Yuan; Nie, Hong-Ming; Hu, Xiao-Yu

2017-04-28

To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH). We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed. One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients' baseline characteristics ( P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group ( P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant ( P < 0.05). No significant differences in complications and adverse effects were found

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches.

PubMed

Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha; Breaker, Ronald R

2018-03-04

Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.

Respiratory and spontaneous arousals in patients with Sleep Apnea Hypopnea Syndrome.

PubMed

Mesquita, J; Porée, F; Carrault, G; Fiz, J A; Abad, J; Jané, R

2012-01-01

Sleep in patients with Sleep Apnea-Hypopnea Syndrome (SAHS) is frequently interrupted with arousals. Increased amounts of arousals result in shortening total sleep time and repeated sleep-arousal change can result in sleep fragmentation. According to the American Sleep Disorders Association (ASDA) an arousal is a marker of sleep disruption representing a detrimental and harmful feature for sleep. The nature of arousals and its role on the regulation of the sleep process raises controversy and has sparked the debate in the last years. In this work, we analyzed and compared the EEG spectral content of respiratory and spontaneous arousals on a database of 45 SAHS subjects. A total of 3980 arousals (1996 respiratory and 1984 spontaneous) were analyzed. The results showed no differences between the spectral content of the two kinds of arousals. Our findings raise doubt as to whether these two kinds of arousals are truly triggered by different organic mechanisms. Furthermore, they may also challenge the current beliefs regarding the underestimation of the importance of spontaneous arousals and their contribution to sleep fragmentation in patients suffering from SAHS.

Spontaneous subarachnoid hemorrhage due to ruptured cavernous internal carotid artery aneurysm after medical prolactinoma treatment.

PubMed

Khalsa, Siri Sahib; Hollon, Todd C; Shastri, Ravi; Trobe, Jonathan D; Gemmete, Joseph J; Pandey, Aditya S

2017-03-01

Aneurysms of the cavernous segment of the internal carotid artery (ICA) are believed to have a low risk of subarachnoid haemorrhage (SAH), given the confines of the dural rings and the anterior clinoid process. The risk may be greater when the bony and dural protection has been eroded. We report a case of spontaneous SAH from rupture of a cavernous ICA aneurysm in a patient whose large prolactinoma had markedly decreased in size as the result of cabergoline treatment. After passing a balloon test occlusion, the patient underwent successful endovascular vessel deconstruction. This case suggests that an eroding skull base lesion may distort normal anterior cranial base anatomy and allow communication between the cavernous ICA and subarachnoid space. The potential for SAH due to cavernous ICA aneurysm rupture should be recognised in patients with previous pituitary or other skull base lesions adjacent to the cavernous sinus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

PubMed

Krewer, Carmen; Schneider, Manfred; Schneider, Harald Jörn; Kreitschmann-Andermahr, Ilonka; Buchfelder, Michael; Faust, Michael; Berg, Christian; Wallaschofski, Henri; Renner, Caroline; Uhl, Eberhard; Koenig, Eberhard; Jordan, Martina; Stalla, Günter Karl; Kopczak, Anna

2016-08-15

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

Detection and quantification of microRNA in cerebral microdialysate.

PubMed

Bache, Søren; Rasmussen, Rune; Rossing, Maria; Hammer, Niels Risør; Juhler, Marianne; Friis-Hansen, Lennart; Nielsen, Finn Cilius; Møller, Kirsten

2015-05-07

Secondary brain injury accounts for a major part of the morbidity and mortality in patients with spontaneous aneurysmal subarachnoid hemorrhage (SAH), but the pathogenesis and pathophysiology remain controversial. MicroRNAs (miRNAs) are important posttranscriptional regulators of complementary mRNA targets and have been implicated in the pathophysiology of other types of acute brain injury. Cerebral microdialysis is a promising tool to investigate these mechanisms. We hypothesized that miRNAs would be present in human cerebral microdialysate. RNA was extracted and miRNA profiles were established using high throughput real-time quantification PCR on the following material: 1) Microdialysate sampled in vitro from A) a solution of total RNA extracted from human brain, B) cerebrospinal fluid (CSF) from a neurologically healthy patient, and C) a patient with SAH; and 2) cerebral microdialysate and CSF sampled in vivo from two patients with SAH. MiRNAs were categorized according to their relative recovery (RR) and a pathway analysis was performed for miRNAs exhibiting a high RR in vivo. Seventy-one of the 160 miRNAs detected in CSF were also found in in vivo microdialysate from SAH patients. Furthermore specific miRNAs consistently exhibited either a high or low RR in both in vitro and in vivo microdialysate. Analysis of repeatability showed lower analytical variation in microdialysate than in CSF. MiRNAs are detectable in cerebral microdialysate; a large group of miRNAs consistently showed a high RR in cerebral microdialysate. Measurement of cerebral interstitial miRNA concentrations may aid in the investigation of secondary brain injury in neurocritical conditions.

A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.

PubMed

Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee H

2013-01-28

We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

PubMed

Wendling, Anne-Sophie; Steinhoff, Bernhard J; Bodin, Frédéric; Staack, Anke M; Zentner, Josef; Scholly, Julia; Valenti, Maria-Paula; Schulze-Bonhage, Andreas; Hirsch, Edouard

2015-03-01

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently. Copyright © 2015 Elsevier B.V. All rights reserved.

The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms.

PubMed

Reynolds, Matthew R; Buckley, Robert T; Indrakanti, Santoshi S; Turkmani, Ali H; Oh, Gerald; Crobeddu, Emanuela; Fargen, Kyle M; El Ahmadieh, Tarek Y; Naidech, Andrew M; Amin-Hanjani, Sepideh; Lanzino, Giuseppe; Hoh, Brian L; Bendok, Bernard R; Zipfel, Gregory J

2015-10-01

Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients

Ventilation practices in subarachnoid hemorrhage: a cohort study exploring the use of lung protective ventilation.

PubMed

Marhong, Jonathan D; Ferguson, Niall D; Singh, Jeffrey M

2014-10-01

Acute respiratory distress syndrome (ARDS) is common following aneurysmal subarachnoid hemorrhage (SAH), but the influence of mechanical ventilator settings on its development is unclear. We sought to determine adherence to lung protective thresholds in ventilated patients with SAH and describe the association between ventilator settings and subsequent development of ARDS. We conducted a retrospective cohort study of consecutive patients receiving mechanical ventilation within 72 h of SAH at a single academic center. Ventilator settings and blood gas data were collected twice daily for the first 7 days of ventilation along with ICU and hospital outcomes. Lung protective ventilation was defined as follows: tidal volume ≤8 mL/kg of predicted body weight, positive end-expiratory pressure (PEEP) ≥5 cm H(2)O, and peak or plateau pressure ≤30 cm H(2)O. The development of ARDS was ascertained retrospectively by PaO(2)/FiO(2) ≤300 with new bilateral lung opacities on chest X-ray within one day of hypoxemia. We identified 62 patients who underwent early mechanical ventilation following SAH. PS and Continuous Positive Airway Pressure were common ventilator modes with a median tidal volume of 7.8 mL/kg [interquartile range 6.8-8.8], median peak pressure of 14 cm H(2)O [IQR 12-17], and median PEEP of 5 cm H(2)O [IQR 5-6]. Adherence to tidal volumes ≤8 mL/kg was seen in 64 % of all observations and peak pressures <30 cm H(2)O were 94 % of all observations. All three lung protective criteria were seen in 58 % of all observations. Thirty-one patients (50 %) were determined to have ARDS. ARDS patients were more frequently ventilated with a peak pressure >30 cm H(2)O (11.3 % of ARDS ventilation days vs. 0 % of non-ARDS ventilation days; p < 0.01). Initial tidal volume was not associated with subsequent development of ARDS in univariate (p = 0.6) or multivariate analysis (p = 0.49). Only the number of ARDS risk factors was independently associated with the development of

Viral hemorrhagic septicemia

USGS Publications Warehouse

Batts, William N.; Winton, James R.

2012-01-01

Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

Dietary practices among individuals with diabetes and hypertension are similar to those of healthy people: a population-based study.

PubMed

Ozcariz, Silvia G I; Bernardo, Carla de O; Cembranel, Francieli; Peres, Marco A; González-Chica, David A

2015-05-10

Currently, diabetes mellitus (DM) and systemic arterial hypertension (SAH) are among the top five global risks for mortality. Among the modifiable factors, careful dietary practice is one of the essential elements for the control of NCDs, since these diseases are often the result of unhealthy lifestyles. Thus, this study aimed to assess the frequency of dietary practices among adult males and females with DM and/or SAH, and compare whether or not they are more frequent than in healthy adults, through a population-based study conducted in the city of Florianópolis, southern Brazil. Cross-sectional population-based study, using as exposure self-reported DM and/or SAH status. Dietary practices were assessed using a semiquantitative food consumption questionnaire. The following were considered as adequate: regular intake (≥ 6 times/week) of fruit and vegetables, daily intake of fruit (≥ 3 times/day) and vegetables (≥ 2 times/day), intake lower than 2 times/week of meat fat, fried foods, and soda. Bivariate and adjusted analysis for sociodemographic variables were conducted using Poisson regression, stratified by gender. Florianópolis, southern Brazil, 2009. Representative sample of 20 to 59 year-old adults (n=1720). A total of 16.6% participants were diagnosed with DM and/or SAH. The most frequently consumed unhealthy foods were fried food (51.0%, 95% CI: 48.8-53.5) and soda (57.9% 95%CI: 55.5-60.2). Of healthy foods, fruit was the less consumed on a daily basis (11.1% 95%CI 9.6-12.5). In general, women showed better dietary practices than men. In adjusted analysis none of dietary practices was more frequent among diabetic and/or hypertensive adults compared with healthy individuals, regardless of gender. No differences were found between healthy and unhealthy adults, when the number of dietary practices was assessed. The frequency of dietary practices was low and did not differ between individuals with or without DM and/or SAH. It is fundamental to reinforce

The Synergistic Priming Effect of Exogenous Salicylic Acid and H2O2 on Chilling Tolerance Enhancement during Maize (Zea mays L.) Seed Germination

PubMed Central

Li, Zhan; Xu, Jungui; Gao, Yue; Wang, Chun; Guo, Genyuan; Luo, Ying; Huang, Yutao; Hu, Weimin; Sheteiwy, Mohamed S.; Guan, Yajing; Hu, Jin

2017-01-01

Chilling stress is an important constraint for maize seedling establishment in the field. To examine the role of salicylic acid (SA) and hydrogen peroxide (H2O2) in response to chilling stress, we investigated the effects of seed priming with SA, H2O2, and SA+H2O2 combination on maize resistance under chilling stress (13°C). Priming with SA, H2O2, and especially SA+H2O2 shortened seed germination time and enhanced seed vigor and seedling growth as compared with hydropriming and non-priming treatments under low temperature. Meanwhile, SA+H2O2 priming notably increased the endogenous H2O2 and SA content, antioxidant enzymes activities and their corresponding genes ZmPAL, ZmSOD4, ZmAPX2, ZmCAT2, and ZmGR expression levels. The α-amylase activity was enhanced to mobilize starch to supply metabolites such as soluble sugar and energy for seed germination under chilling stress. In addition, the SA+H2O2 combination positively up-regulated expressions of gibberellic acid (GA) biosynthesis genes ZmGA20ox1 and ZmGA3ox2, and down-regulated GA catabolism gene ZmGA2ox1 expression; while it promoted GA signaling transduction genes expressions of ZmGID1 and ZmGID2 and decreased the level of seed germination inhibitor gene ZmRGL2. The abscisic acid (ABA) catabolism gene ZmCYP707A2 and the expressions of ZmCPK11 and ZmSnRK2.1 encoding response receptors in ABA signaling pathway were all up-regulated. These results strongly suggested that priming with SA and H2O2 synergistically promoted hormones metabolism and signal transduction, and enhanced energy supply and antioxidant enzymes activities under chilling stress, which were closely relevant with chilling injury alleviation and chilling-tolerance improvement in maize seed. Highlights:Seed germination and seedling growth were significantly improved under chilling stress by priming with SA+H2O2 combination, which was closely relevant with the change of reactive oxygen species, metabolites and energy supply, hormones metabolism and

Neuropsychological function after endovascular and neurosurgical treatment of subarachnoid hemorrhage: a systematic review and meta-analysis.

PubMed

Egeto, Peter; Loch Macdonald, R; Ornstein, Tisha J; Schweizer, Tom A

2018-03-01

OBJECTIVE Subarachnoid hemorrhage (SAH) is treated with either surgical clipping or endovascular coiling, though the latter is the preferred treatment method given its more favorable functional outcomes. However, neuropsychological functioning after treatment is rarely taken into account. In this meta-analysis, the authors synthesized relevant data from the literature and compared neuropsychological functioning in patients after coiling and clipping of SAH. They hypothesized that the coiled patients would outperform the clipped patients; that group differences would be greater with higher posterior circulation rupture rates, in older patients, and in more recent publications; that group differences would be smaller with greater rates of middle cerebral artery (MCA) rupture; and that anterior communicating artery (ACoA) rupture rates would not influence effect sizes. METHODS The MEDLINE, Embase, and PsycINFO databases were searched for clinical studies that compared neuropsychological functioning after either endovascular coiling or surgical clipping for SAH. Hedge's g and 95% confidence intervals were calculated using random effects models. Patients who had undergone coiling or clipping were compared on test performance in 8 neuropsychological domains: executive functions, language, attention/processing speed, verbal memory, visual memory, spatial memory, visuospatial functions, and intelligence. Patients were also compared with healthy controls, and meta-regressions were used to explore the relation between effect sizes and publication year, delay between treatment and neuropsychological testing, mean patient age, and rates of posterior circulation, ACoA, and MCA ruptures. RESULTS Thirteen studies with 396 clipped cases, 314 coiled cases, and 169 healthy controls were included in the study. The coil-treated patients outperformed the clip-treated patients on executive function (g = 0.17, 95% CI 0.08-0.25) and language tests (g = 0.23, 95% CI 0.07-0.39), and all

Prediction of Mortality in Patients with Isolated Traumatic Subarachnoid Hemorrhage Using a Decision Tree Classifier: A Retrospective Analysis Based on a Trauma Registry System.

PubMed

Rau, Cheng-Shyuan; Wu, Shao-Chun; Chien, Peng-Chen; Kuo, Pao-Jen; Chen, Yi-Chun; Hsieh, Hsiao-Yun; Hsieh, Ching-Hua

2017-11-22

Background: In contrast to patients with traumatic subarachnoid hemorrhage (tSAH) in the presence of other types of intracranial hemorrhage, the prognosis of patients with isolated tSAH is good. The incidence of mortality in these patients ranges from 0-2.5%. However, few data or predictive models are available for the identification of patients with a high mortality risk. In this study, we aimed to construct a model for mortality prediction using a decision tree (DT) algorithm, along with data obtained from a population-based trauma registry, in a Level 1 trauma center. Methods: Five hundred and forty-five patients with isolated tSAH, including 533 patients who survived and 12 who died, between January 2009 and December 2016, were allocated to training ( n = 377) or test ( n = 168) sets. Using the data on demographics and injury characteristics, as well as laboratory data of the patients, classification and regression tree (CART) analysis was performed based on the Gini impurity index, using the rpart function in the rpart package in R. Results: In this established DT model, three nodes (head Abbreviated Injury Scale (AIS) score ≤4, creatinine (Cr) <1.4 mg/dL, and age <76 years) were identified as important determinative variables in the prediction of mortality. Of the patients with isolated tSAH, 60% of those with a head AIS >4 died, as did the 57% of those with an AIS score ≤4, but Cr ≥1.4 and age ≥76 years. All patients who did not meet the above-mentioned criteria survived. With all the variables in the model, the DT achieved an accuracy of 97.9% (sensitivity of 90.9% and specificity of 98.1%) and 97.7% (sensitivity of 100% and specificity of 97.7%), for the training set and test set, respectively. Conclusions: The study established a DT model with three nodes (head AIS score ≤4, Cr <1.4, and age <76 years) to predict fatal outcomes in patients with isolated tSAH. The proposed decision-making algorithm may help identify patients with a high risk of

Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid Hemorrhage: Choroidal Artery Vasospasm-Related Ependymal Cell Degeneration and Aqueductal Stenosis-First Experimental Study.

PubMed

Yolas, Coskun; Ozdemir, Nuriye Guzin; Kanat, Ayhan; Aydin, Mehmet Dumlu; Keles, Papatya; Kepoglu, Umit; Aydin, Nazan; Gundogdu, Cemal

2016-06-01

Hydrocephalus is a serious complication of subarachnoid hemorrhage (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH. Although various etiologic theories have been put forward, choroidal artery vasospasm-related ependymal desquamation and subependymal basal membrane rupture as mechanisms of aqueductal stenosis have not been suggested in the literature. This study was conducted on 26 hybrid rabbits. Five rabbits were placed in a control group, 5 were placed in a sham group, and the remaining rabbits (n = 16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH group died. The other 21 animals were decapitated after the 4-week follow-up period. Choroidal artery changes resulting from vasospasm, aqueduct volume, ependymal cell density, and Evans index values of brain ventricles were obtained and compared statistically. Mean aqueduct volume was 1.137 mm(3) ± 0.096, normal ependymal cell density was 4560/mm(2) ± 745, and Evans index was 0.32 ± 0.05 in control animals (n = 5); these values were 1.247 mm(3) ± 0.112, 3568/mm(2) ± 612, and 0.34 ± 0.15 in sham animals (n = 5); 1.676 mm(3) ± 0.123, 2923/mm(2) ± 591, and 0.43 ± 0.09 in animals without aqueductal stenosis (n = 5); and 0.650 mm(3) ± 0.011, 1234/mm(2) ± 498, and 0.60 ± 0.18 in animals with severe aqueductal stenosis (n = 6). The choroidal vasospasm index values were 1.160 ± 0.040 in the control group, 1.150 ± 0.175 in the sham group, 1.760 ± 0.125 in the nonstenotic group, and 2.262 ± 0.160 in the stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and choroidal artery vasospasm index values were statistically significantly different between groups (P < 0.05). Ependymal cell desquamation and subependymal basal membrane destruction related to choroidal artery vasospasm may lead to aqueductal stenosis and hydrocephalus after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2

SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases.

PubMed

Zhang, Jing; Zheng, Yujun George

2016-03-18

S-Adenosyl-L-methionine (SAM) is a sulfonium molecule with a structural hybrid of methionine and adenosine. As the second largest cofactor in the human body, its major function is to serve as methyl donor for SAM-dependent methyltransferases (MTases). The resultant transmethylation of biomolecules constitutes a significant biochemical mechanism in epigenetic regulation, cellular signaling, and metabolite degradation. Recently, numerous SAM analogs have been developed as synthetic cofactors to transfer the activated groups on MTase substrates for downstream ligation and identification. Meanwhile, new compounds built upon or derived from the SAM scaffold have been designed and tested as selective inhibitors for important MTase targets. Here, we summarized the recent development and application of SAM analogs as chemical biology tools for MTases.

Health Care Costs of Spontaneous Aneurysmal Subarachnoid Hemorrhage for Rehabilitation, Home Care, and In-Hospital Treatment for the First Year.

PubMed

Ridwan, Sami; Urbach, Horst; Greschus, Susanne; von Hagen, Johanna; Esche, Jonas; Boström, Azize

2017-01-01

Given the young age of onset and high probability of long-term disability after subarachnoid hemorrhage (SAH), the financial impact is expected to be substantial. Our primary objective was to highlight subsequent treatment costs after the acute in-hospital stay, including rehabilitation and home care, compared with costs for ischemic stroke. The study included 101 patients (median age 52 years, 70 women) with aneurysmal SAH treated from July 2007 to April 2009. In-hospital costs were calculated using German diagnosis related groups. Rehabilitation costs depended on rehabilitation phase/grade and daily rate. Level of severity of care requirements determined the costs for home care. Of patients, 54% received coiling and 46% received clipping. The clipping group included more poor-grade patients than the coiling group (P = 0.039); 23 patients died. Of 78 surviving patients, 70 received rehabilitation treatment (68 in Germany). Mean rehabilitation costs were €16,030 per patient. Patients in the clipping group generated higher rehabilitation costs and longer treatment periods in rehabilitation facilities (P = 0.001 for costs [€20,290 vs. €11,771] and P = 0.011 for duration (54.4 days vs. 40.5 days). Of surviving patients, 32% needed home care, of whom 52% required constant care. Multivariate regression analysis identified longer intensive care unit stay and poor Hunt and Hess grade as independent predictors of higher costs. Aneurysmal SAH prevalently affects working individuals with long-term occupational disability necessitating long-term medical rehabilitation for most patients and subsequent nursing care in one third of survivors. Overall, SAH treatment generates far higher costs than reported for ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural tube defects induced by folate deficiency in mutant curly tail (Grhl3) embryos are associated with alteration in folate one-carbon metabolism but are unlikely to result from diminished methylation

PubMed Central

De Castro, Sandra CP; Leung, Kit-yi; Savery, Dawn; Burren, Katie; Rozen, Rima; Copp, Andrew J.; Greene, Nicholas D.E.

2013-01-01

Background Folate one-carbon metabolism has been implicated as a determinant of susceptibility to neural tube defects (NTDs), owing to the preventive effect of maternal folic acid supplementation and the higher risk associated with markers of diminished folate status. Methods Folate one-carbon metabolism was compared in curly tail (ct/ct) and genetically matched congenic (+ct/+ct) mouse strains using the deoxyuridine suppression test in embryonic fibroblast cells and by quantifying s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH) in embryos using liquid chromatography tandem mass spectrometry. A possible genetic interaction between curly tail and a null allele of 5,10-methylenetetrahydrofolate reductase (MTHFR) was investigated by generation of compound mutant embryos. Results There was no deficit in thymidylate biosynthesis in ct/ct cells but incorporation of exogenous thymidine was lower than in +ct/+ct cells. In +ct/+ct embryos the SAM/SAH ratio was diminished by dietary folate deficiency and normalised by folic acid or myor-inositol treatment, in association with prevention of NTDs. In contrast, folate deficiency caused a significant increase in SAM/SAH ratio in ct/ct embryos. Loss of MTHFR function in curly tail embryos significantly reduced the SAM/SAH ratio but did not cause cranial NTDs or alter the frequency of caudal NTDs. Conclusions Curly tail fibroblasts and embryos, in which Grhl3 expression is reduced, display alterations in one-carbon metabolism, particularly in the response to folate deficiency, compared with genetically-matched congenic controls in which Grhl3 is unaffected. However, unlike folate deficiency, diminished methylation potential appears to be insufficient to cause cranial NTDs in the curly tail strain, and neither does it increase the frequency of caudal NTDs. PMID:20589880

Duration of Agitation, Fluctuations of Consciousness, and Associations with Outcome in Patients with Subarachnoid Hemorrhage.

PubMed

Reznik, Michael E; Mahta, Ali; Schmidt, J Michael; Frey, Hans-Peter; Park, Soojin; Roh, David J; Agarwal, Sachin; Claassen, Jan

2018-01-08

Agitation is common after subarachnoid hemorrhage (SAH) and may be independently associated with outcomes. We sought to determine whether the duration of agitation and fluctuating consciousness were also associated with outcomes in patients with SAH. We identified all patients with positive Richmond Agitation Sedation Scale (RASS) scores from a prospective observational cohort of patients with SAH from 2011 to 2015. Total duration of agitation was extrapolated for each patient using available RASS scores, and 24-h mean and standard deviation (SD) of RASS scores were calculated for each patient. We also calculated each patient's duration of substantial fluctuation of consciousness, defined as the number of days with 24-h RASS SD > 1. Patients were stratified by 3-month outcome using the modified Rankin scale, and associations with outcome were assessed via logistic regression. There were 98 patients with at least one positive RASS score, with median total duration of agitation 8 h (interquartile range [IQR] 4-18), and median duration of substantially fluctuating consciousness 2 days (IQR 1-3). Unfavorable 3-month outcome was significantly associated with a longer duration of fluctuating consciousness (odds ratio [OR] per day, 1.51; 95% confidence interval [CI], 1.04-2.20; p = 0.031), but a briefer duration of agitation (OR per hour, 0.94; 95% CI, 0.89-0.99; p = 0.031). Though a longer duration of fluctuating consciousness was associated with worse outcomes in our cohort, total duration of agitation was not, and may have had the opposite effect. Our findings should therefore challenge the intensity with which agitation is often treated in SAH patients.

Predictors of work status and quality of life 9-13 years after aneurysmal subarachnoid hemorrahage.

PubMed

Vilkki, Juhani; Juvela, Seppo; Malmivaara, Kirsi; Siironen, Jari; Hernesniemi, Juha

2012-08-01

Aneurysmal subarachnoid hemorrhage (SAH) causes long-term psychosocial impairments even in patients who regain functional independence. Little is known about predictors of these impairments. We studied how early clinical data and neuropsychological results predict work status and health-related quality of life (HRQoL) 9-13 years after SAH. One hundred one patients performed a neuropsychological test battery and returned their self-rating and partner's rating of a psychosocial impairment questionnaire approximately 1 year after SAH. These data were analyzed for association to the patients' work status and self-rated HRQoL approximately 10 years later. Age inversely, lower levels of self-rated impairments, employment and higher levels of education at the first follow-up independently predicted employment at the long-term follow-up. Although most cognitive test results were significantly associated with employment status at the long-term follow-up, they were of limited additional value as predictors of work status. The best predictor combination for long-term high HRQoL was good performance in a face recognition test and lower levels of self-rated impairments at the first follow-up as well as male sex. Problems in usual activities at the long-term follow-up were predicted by poor results in the face recognition and in a word list-learning task. Questionnaire ratings of patients' psychosocial impairments 1 year after SAH give important information for the long-term prediction of their work status and HRQoL. In the long run, patients' unemployment becomes strongly associated with higher age, while their performance of usual activities can be predicted with learning and memory results.

Efficacy of Early Rehabilitation After Surgical Repair of Acute Aneurysmal Subarachnoid Hemorrhage: Outcomes After Verticalization on Days 2-5 Versus Day 12 Post-Bleeding.

PubMed

Milovanovic, Andjela; Grujicic, Danica; Bogosavljevic, Vojislav; Jokovic, Milos; Mujovic, Natasa; Markovic, Ivana Petronic

2017-01-01

To develop a specific rehabilitation protocol for patients who have undergone surgical repair of acute aneurysmal subarachnoid hemorrhage (aSAH), and to determine the time at which verticalization should be initiated after aSAH. Sixty-five patients who underwent acute-term surgery for aSAH and early rehabilitation were evaluated in groups: Group 1 (n=34) started verticalization on days 2-5 post-bleeding whereas Group 2 (n=31) started verticalization approximately day 12 post-bleeding. All patients were monitored for early complications, vasospasm and ischemia. Assessments of motor status, depression and anxiety (using Zung scales), and cognitive status (using the Mini-Mental State Examination (MMSE)) were conducted at discharge and at 1 and 3 months post-surgery. At discharge, Group 1 had a significantly higher proportion of patients with ischemia than Group 2 (p=0.004). Group 1 had a higher proportion of patients with hemiparesis than Group 2 three months post-surgery (p=0.015). Group 1 patients scored significantly higher on the Zung depression scale than Group 2 patients at 1 month (p=0.005) and 3 months post-surgery (p=0.001; the same applies to the Zung anxiety scale (p=0.006 and p=0.000, respectively). Group 2 patients scored significantly higher on the MMSE than those in Group 1 at discharge (p=0.040) and 1 month post-surgery (p=0.025). Early verticalization had no effect with respect to preventing early postoperative complications in this patient group. Once a patient has undergone acute surgical repair of aSAH, it is safe and preferred that rehabilitation be initiated immediately postsurgery. However, verticalization should not start prior to day 12 post-bleeding.

Resumption of work after aneurysmal subarachnoid hemorrhage in middle-aged Japanese patients.

PubMed

Nishino, A; Sakurai, Y; Tsuji, I; Arai, H; Uenohara, H; Suzuki, S; Li, J H

1999-01-01

Previous reports on the results of treatment for aneurysmal subarachnoid hemorrhage (SAH) have been based only on activities of daily living after discharge, whereas resumption of work has received insufficient attention. Most Japanese work under a lifetime employment system, and it is best for those who have recovered from SAH to return to work for their previous employer. The present study was conducted to determine the extent to which discharged patients who have suffered an SAH resume their former occupations in Japan, focusing on those between 40 and 49 years of age, who usually have a strong desire to return to work. The participants consisted of 193 patients with SAH. Based on the results of telephone interviews or written questionnaires, their work status at 1 year after onset was analyzed. The work resumption rates for patients with Hunt and Kosnik neurological Grades 1 or 2 on admission were higher than for those with Grades 3 or 4 (p = 0.015) and lower for patients with basilar artery aneurysms than for those with aneurysms at other sites (p = 0.028). With regard to premorbid occupation, the work resumption rates were high (80%) for professionals and engineers, many of whom were public servants, or teachers at junior or senior high schools. The resumption rates were also high for primary industry workers (80%), but lowest (20%) for professional drivers (p = 0.04-0.001). The work resumption rate was lower for women than for men (p = 0.01). These findings indicate that resumption of work is determined not only by medical factors, but also by social factors including gender, type of occupation, employment system, and socioeconomic background.

Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study.

PubMed

Ulvi, Hızır; Demir, Recep; Aygül, Recep; Kotan, Dilcan; Calik, Muhammet; Aydin, Mehmet Dumlu

2013-12-30

Phrenic nerves have important roles on the management of respiration rhythm. Diaphragm paralysis is possible in phrenic nerve roots ischemia in subarachnoid hemorrhage (SAH). We examined whether there is a relationship between phrenic nerve root ischemia and respiratory disturbances in SAH. This study was conducted on 5 healthy control and 14 rabbits with experimentally induced SAH by injecting autologous blood into their cisterna magna. Animals were followed up via monitors for detecting the heart and respiration rhythms for 20 days and then decapitaed by humanely. Normal and degenerated neuron densities of phrenic nerve root at the level of C4 dorsal root ganglia (C4DRG) were estimated by Stereological methods. Between the mean numerical density of degenerated neurons of C4DRG and respiratory rate/minute of groups were compared statistically. Phrenic nerve roots, artery and diaphragm muscles degeneration was detected in respiratory arrest developed animals. The mean neuronal density of C4DRG was 13272 ±1201/mm3 with a mean respiration rate of 23 ±4/min in the control group. The mean degenerated neuron density was 2.240 ±450/mm(3) and respiration rhythm was 31 ±6/min in survivors. But, the mean degenerated neuron density was 5850 ±650/mm(3) and mean respiration rhythm was 34 ±7/min in respiratory arrest developed animals (n = 7). A linear relationship was noticed between the degenerated neuron density of C4DRG and respiraton rate (r = -0.758; p < 0.001). Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature.

Homocysteine regulates fatty acid and lipid metabolism in yeast.

PubMed

Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O; Wolinski, Heimo; Rechberger, Gerald N; Tehlivets, Oksana

2018-04-13

S -Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S -adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Homocysteine regulates fatty acid and lipid metabolism in yeast

PubMed Central

Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O.; Wolinski, Heimo; Rechberger, Gerald N.; Tehlivets, Oksana

2018-01-01

S-Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S-adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. PMID:29414770

Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm.

PubMed

Duman, Enes; Karakoç, Fatma; Pinar, H Ulas; Dogan, Rafi; Fırat, Ali; Yıldırım, Erkan

2017-12-01

Background Cerebral vasospasm (CV) is a major cause of delayed morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Various cerebral protectants have been tested in patients with aneurysmal SAH. We aimed to research the success rate of treatment of CV via intra-arterial milrinone injection and aggressive pharmacological therapy for refractory CV. Methods A total of 25 consecutive patients who received intra-arterial milrinone and nimodipine treatment for CV following SAH between 2014 and 2017 were included in the study. Patients who underwent surgical clipping were excluded. Refractory vasospasm was defined as patients with CV refractory to therapies requiring ≥3 endovascular interventions. Overall, six patients had refractory CV. Long-term neurological outcome was assessed 6-18 months after SAH using a modified Rankin score and Barthel index. Results The median modified Rankin scores were 1 (min: 0, max: 3) and Barthel index scores were 85 (min: 70, max: 100) From each vasospastic territory maximal 10-16 mg milrinone was given to patients; a maximum of 24 mg milrinone was given to each patient in a session and a maximum of 42 mg milrinone was given to a patient in a day. Both milrinone and nimodipine were given to three patients. There was a large vessel diameter increase after milrinone and nimodipine injections. No patient died due to CV; only one patient had motor dysfunction on the right lower extremity. Conclusion Higher doses of milrinone can be used effectively to control refractory CV. For exceptional patients with refractory CV, high dose intra-arterial nimodipine and milrinone infusion can be used as a rescue therapy.

Incidence of hemorrhagic stroke in black Caribbean, black African, and white populations: the South London stroke register, 1995-2004.

PubMed

Smeeton, Nigel C; Heuschmann, Peter U; Rudd, Anthony G; McEvoy, Andrew W; Kitchen, Neil D; Sarker, Shah Jalal; Wolfe, Charles D A

2007-12-01

Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. First-ever stroke patients were drawn from a prospective community stroke register based in a multiethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression. Between 1995 and 2004, 566 incident stroke patients were registered: 395 PICHs and 171 SAHs. For PICH, age- and sex-adjusted IRRs were higher in BAs (IRR, 2.80; 95% CI, 2.00 to 3.91) than in BCs (IRR, 1.46; 95% CI, 1.07 to 1.99) and were particularly pronounced for patients age 0 to 64 years: IRR=3.95 (95% CI, 2.65 to 5.87) in BAs and 2.38 (95% CI, 1.50 to 3.80) in BCs. For those <65 years, prestroke hypertension was more prevalent in BAs and BCs (P=0.049). For SAH, the IRR was higher in BCs (IRR; 1.62; 95% CI, 1.05 to 2.48) than in BAs (IRR, 0.80; 95% CI, 0.43 to 1.46). The higher incidence of PICH observed in BCs and BAs could be explained by prestroke hypertension being more common among young blacks. The different incidences of SAH in BCs and BAs suggest that the baseline risk of stroke for distinct black ethnic groups is not homogeneous.

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.

PubMed

von der Brelie, Christian; Subai, Alexander; Limperger, Verena; Rohde, Veit; Dempfle, Astrid; Boström, Azize

2018-04-01

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

Neonatal arterial hypertension in nephro-urological malformations in a tertiary care hospital.

PubMed

Lanzarini, V V; Furusawa, E A; Sadeck, L; Leone, C R; Vaz, F A C; Koch, V H

2006-09-01

An increase in the survival of neonates with antenatal diagnosis of malformations was achieved by the recent technical advances in neonatal intensive care units. The aim of this article is to describe the experience with neonatal arterial hypertension, in newborns with nephro-urological malformations, in a tertiary care referral Nursery, in a period of 4 years. Newborn medical records from the Nursery Annex to the Maternity of Hospital das Clinicas, School of Medicine, University of Sao Paulo, with the diagnosis of nephro-urological malformations and systemic arterial hypertension (SAH) at hospital discharge, in a period from January 1999 to January 2003, were retrospectively analysed. Among 10.278 live newborns in the studied period, 15 (0.15%) newborns were compatible with our inclusion criteria. Of these 15 newborns, 12 (80%) were male and three were premature (20%). In relation to aetiology, 13 (87%) showed urological malformations, 1 (6%) chronic renal insufficiency secondary to kidney dysplasia and one (6%) autosomal recessive polycystic kidney disease. SAH control was achieved with monotherapy in eight patients (53%), five patients (33%) needed an association of two drugs (calcium-channel blocker and angiotensin converting enzyme (ACE) inhibitor), one child used three types of antihypertensive drugs (calcium-channel blocker, ACE inhibitor and hydrochlorothiazide) for pressoric control and one child's blood pressure (BP) was controlled exclusively by peritoneal dialysis. The incidence of nephro-urological malformations in our service during the studied period was 0.89%. SAH incidence among these newborns was 19%. Our data reinforce previous studies pointing to the necessity to consider children with nephro-urological malformations as a risk group for SAH, who should have the BP evaluated since the neonatal period.

Prognosis of patients in coma after acute subdural hematoma due to ruptured intracranial aneurysm.

PubMed

Torné, Ramon; Rodríguez-Hernández, Ana; Romero-Chala, Fabián; Arikan, Fuat; Vilalta, Jordi; Sahuquillo, Juan

2016-04-01

Acute subdural hematomas (aSDH) secondary to intracranial aneurysm rupture are rare. Most patients present with coma and their functional prognosis has been classically considered to be very poor. Previous studies mixed good-grade and poor-grade patients and reported variable outcomes. We reviewed our experience by focusing on patients in coma only and hypothesized that aSDH might worsen initial mortality but not long-term functional outcome. Between 2005 and 2013, 440 subarachnoid hemorrhage (SAH) patients were admitted to our center. Nineteen (4.3%) were found to have an associated aSDH and 13 (2.9%) of these presented with coma. Their prospectively collected clinical and outcome data were reviewed and compared with that of 104 SAH patients without aSDH who presented with coma during the same period. Median aSDH thickness was 10mm. Four patients presented with an associated aneurysmal cortical laceration and only one had good recovery. Overall, we observed good long-term outcomes in both SAH patients in coma with aSDH and those without aSDH (38.5% versus 26.4%). Associated aSDH does not appear to indicate a poorer long-term functional prognosis in SAH patients presenting with coma. Anisocoria and brain herniation are observed in patients with aSDH thicknesses that are smaller than those observed in trauma patients. Despite a high initial mortality, early surgery to remove the aSDH results in a good outcome in over 60% of survivors. Aneurysmal cortical laceration appears to be an independent entity which shows a poorer prognosis than other types of aneurysmal aSDH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of treatment modality on in-hospital outcome in patients with subarachnoid hemorrhage: a nationwide study in Japan (J-ASPECT Study).

PubMed

Kurogi, Ryota; Kada, Akiko; Nishimura, Kunihiro; Kamitani, Satoru; Nishimura, Ataru; Sayama, Tetsuro; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Hagihara, Akihito; Iihara, Koji

2018-05-01

OBJECTIVE Although heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities. METHODS They analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis. RESULTS Patients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3-6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate. CONCLUSIONS Despite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.

Antioxidant status and alpha1-antiproteinase activity in subarachnoid hemorrhage patients.

PubMed

Marzatico, F; Gaetani, P; Tartara, F; Bertorelli, L; Feletti, F; Adinolfi, D; Tancioni, F; Rodriguez y Baena, R

1998-01-01

The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Gathier, C S; van den Bergh, W M; Slooter, A J C

2014-04-01

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Incidence of Hospitalized Stroke in the Czech Republic: The National Registry of Hospitalized Patients.

PubMed

Sedova, Petra; Brown, Robert D; Zvolsky, Miroslav; Kadlecova, Pavla; Bryndziar, Tomas; Kubelka, Tomáš; Weiss, Viktor; Volný, Ondřej; Bednarik, Josef; Mikulik, Robert

2017-05-01

Contemporary stroke incidence data are not available in some countries and regions, including in Eastern Europe. Based on previous validation of the accuracy of the National Registry of Hospitalized Patients (NRHOSP), we report the incidence of hospitalized stroke in the Czech Republic (CR) using the NRHOSP. The results of the prior validation study assessing the accuracy of coding of stroke diagnoses in the NRHOSP were applied, and we calculated (1) the overall incidence of hospitalized stroke and (2) the incidence rates of hospitalized stroke for the three main stroke types: cerebral infarction (International Classification of Diseases Tenth Revision, CI I63), subarachnoid hemorrhage (SAH I60), and intracerebral hemorrhage (ICH I61). We calculated the average annual age- and sex-standardized incidence. The overall incidence of hospitalized stroke was 241 out of 100,000 individuals. The incidence of hospitalized stroke for the main stroke types was 8.2 cases in SAH, 29.5 in ICH, and 211 in CI per 100,000 individuals. The standardized annual stroke incidence adjusted to the 2000 World Health Organization population for overall stroke incidence of hospitalized stroke was 131 per 100,000 individuals. Standardized stroke incidence for stroke subtypes was 5.7 cases in SAH, 16.7 in ICH, and 113 in CI per 100,000 individuals. These studies provide an initial assessment of the burden of stroke in this part of the world. The estimates of hospitalized stroke in the CR and Eastern Europe suggest that ICH is about three times more common than SAH, and hemorrhagic stroke makes up about 18% of strokes. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Aneurysmal subarachnoid hemorrhage causes injury of the ascending reticular activating system: relation to consciousness.

PubMed

Jang, S H; Kim, H S

2015-04-01

Little is known about the pathogenetic mechanism of impaired consciousness following subarachnoid hemorrhage. Using diffusion tensor imaging, we attempted to investigate the presence of injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei, and the relation between this injury and consciousness level in patients with SAH. We recruited 24 consecutive patients with spontaneous SAH following aneurysmal rupture and 21 healthy control subjects. Consciousness level was rated by using the Glasgow Coma Scale. Using diffusion tensor tractography, we reconstructed the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei. Values of fractional anisotropy, apparent diffusion coefficient, and tract number of the ascending reticular activating system were measured. A significant difference in the tract number was observed between the patient and control groups (P < .05); however, there was no significant difference in terms of fractional anisotropy and apparent diffusion coefficient values (P > .05). In addition, regarding the tract number of the patient group, the Glasgow Coma Scale showed strong positive correlations with the tract number on the more affected side (r = 0.890, P < .05), the less affected side (r = 0.798, P < .05), and both sides (r = 0.919, P < .05), respectively. We found injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the thalamus in patients with SAH. In addition, we observed a close association between injury of the lower portion of the ascending reticular activating system and impaired consciousness in patients with SAH. © 2015 by American Journal of Neuroradiology.

[Cerebral vasospasm after subarachnoid hemorrhage].

PubMed

Milojević, T M; Baljozović, B V; Rakić, M Lj; Nestorović, B D; Dostanić, M M; Milaković, B D; Kojić, Z Z; Repac, N R; Cvrkota, I S

2008-01-01

Cerebral vasospasm causes permanent neurolological deficit or death occurance in 13% of clinical cases. Peak frequency is from 8-10th day after SAH. The purpose of this study is factor analysis that may have influence on vasospasm development , as well as predictor determination. The study is prospective and analysis 192 patients treated in Institute of Neurosurgery, Clinical Centre of Serbia, Belgrade. The majority of patients were admitted in hospital in first four days after SAH, and 184 had GCS over 7. Univariate methods of factor analysis were used, and for significance of predictors influence testing multivariante regression analysis was used. Vasospasm occurred in 22,40% of all cases. No relationships have been found between sex, age, previous hypertension, timing of surgery, appearance of hydrocephalus and intracerebral hematoma, hypertermia or mean arterial blood pressure, with occurrence of cerebral vasospasm. Factors with significantly associated with the occurance of vasospasm were: hearth disease, hypernatriemia, Hct, clinical grade on admission as well as preoperative clinical grade and Fisher CT scan grade. In the first four days after SAH, Fisher scan grade, preoperative clinical grade and Hct, appeared as predictors. After four days, clinical grade on admission and hypernatiemia, showed as poredictors.

The impact of hypopituitarism on function and performance in subjects with recent history of traumatic brain injury and aneurysmal subarachnoid haemorrhage.

PubMed

Srinivasan, Lakshmi; Roberts, Brian; Bushnik, Tamara; Englander, Jeffrey; Spain, David A; Steinberg, Gary K; Ren, Li; Sandel, M Elizabeth; Al-Lawati, Zahraa; Teraoka, Jeffrey; Hoffman, Andrew R; Katznelson, Laurence

2009-07-01

To correlate deficient pituitary function with life satisfaction and functional performance in subjects with a recent history of traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cross-sectional study. Eighteen subjects with TBI and 16 subjects with SAH underwent pituitary hormonal and functional assessments 5-12 months following the event. Adrenal reserve was assessed with a 1 mcg cosyntropin stimulation test and growth hormone deficiency (GHD) was diagnosed by insufficient GH response to GHRH-Arginine stimulation. Assessments of life satisfaction and performance-function included the Satisfaction with Life Scale (SWLS), Craig Handicap Assessment and Reporting Technique (CHART) and the Mayo Portland Adaptability Inventory-4 (MPAI-4). Hypopituitarism was present in 20 (58.8%) subjects, including 50% with adrenal insufficiency. Hypothyroidism correlated with worse performance on SWLS and CHART measures. GHD was associated with poorer performance on CHART and MPAI-4 scale. In this series of subjects with history of TBI and SAH, hypothyroidism and GHD were associated with diminished life satisfaction and performance-function on multiple assessments. Further studies are necessary to determine the appropriate testing of adrenal reserve in this population and to determine the benefit of pituitary hormone replacement therapy on function following brain injury.

Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis.

PubMed

Ganesan, Murali; Feng, Dan; Barton, Ryan W; Thomes, Paul G; McVicker, Benita L; Tuma, Dean J; Osna, Natalia A; Kharbanda, Kusum K

2016-11-01

Alcohol-induced reduction in the hepatocellular S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio impairs the activities of many SAM-dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT-mediated reactions consume as much as 40% of all the SAM-derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions. For these studies, male Wistar rats were pair-fed the Lieber-DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed. We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol-induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH-fed rats was also not normalized or SAM levels spared when these rats were fed the creatine-supplemented EtOH diet. However, a >10-fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine-supplemented diets. Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high-fat-diet-induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis. Copyright © 2016 by the Research Society on Alcoholism.

Agitation After Subarachnoid Hemorrhage: A Frequent Omen of Hospital Complications Associated with Worse Outcomes.

PubMed

Reznik, Michael E; Schmidt, J Michael; Mahta, Ali; Agarwal, Sachin; Roh, David J; Park, Soojin; Frey, Hans Peter; Claassen, Jan

2017-06-01

Agitated delirium is frequent following acute brain injury, but data are limited in patients with subarachnoid hemorrhage (SAH). We examined incidence, risk factors, and consequences of agitation in these patients in a single-center retrospective study. We identified all patients treated with antipsychotics or dexmedetomidine from a prospective observational cohort of patients with spontaneous SAH. Agitation was confirmed by chart review. Outcomes were assessed at 12 months using the modified Rankin Scale (mRS), Telephone Interview for Cognitive Status (TICS), and Lawton IADL (Instrumental Activities of Daily Living) scores. Independent predictors were identified using logistic regression. From 309 SAH patients admitted between January 2011 and December 2015, 52 (17 %) developed agitation, frequently in the first 72 h (50 %) and in patients with Hunt-Hess grades 3-4 (12 % of grades 1-2, 28 % of grades 3-4, 8 % of grade 5). There was also a significant association between agitation and a history of cocaine use or prior psychiatric diagnosis. Agitated patients were more likely to develop multiple hospital complications; and in half of these patients, complications were diagnosed within 24 h of agitation onset. Agitation was associated with IADL impairment at 12 months (Lawton >8; p = 0.03, OR 2.7, 95 % CI, 1.1-6.8) in non-comatose patients (Hunt-Hess 1-4), but not with functional outcome (mRS >3), cognitive impairment (TICS ≤30), or ICU/hospital length of stay after controlling for other predictors. Agitation occurs frequently after SAH, especially in non-comatose patients with higher clinical grades. It is associated with the development of multiple hospital complications and may have an independent impact on long-term outcomes.

Agitation after subarachnoid hemorrhage: a frequent omen of hospital complications associated with worse outcomes

PubMed Central

Reznik, Michael E.; Schmidt, J. Michael; Mahta, Ali; Agarwal, Sachin; Roh, David J.; Park, Soojin; Frey, Hans Peter; Claassen, Jan

2017-01-01

Purpose Agitated delirium is frequent following acute brain injury, but data are limited in patients with subarachnoid hemorrhage (SAH). We examined incidence, risk factors, and consequences of agitation in these patients in a single-center retrospective study. Methods We identified all patients treated with antipsychotics or dexmedetomidine from a prospective observational cohort of patients with spontaneous SAH. Agitation was confirmed by chart review. Outcomes were assessed at 12 months using the modified Rankin Scale (mRS), Telephone Interview for Cognitive Status (TICS), and Lawton-IADL (Instrumental Activities of Daily Living) score. Independent predictors were identified using logistic regression. Results From 309 SAH patients admitted between 1/2011 and 12/2015, 52 (17%) developed agitation, frequently in the first 72 hours (50%) and in patients with Hunt-Hess grades 3–4 (12% of grades 1–2, 28% of grades 3–4, 8% of grade 5). There was also a significant association between agitation and a history of cocaine use or prior psychiatric diagnosis. Agitated patients were more likely to develop multiple hospital complications, and in half of these patients complications were diagnosed within 24 hours of agitation onset. Agitation was associated with IADL impairment at 12 months (Lawton >8; p = 0.03, OR 2.7, 95% CI 1.1–6.8) in non-comatose patients (Hunt-Hess 1–4), but not with functional outcome (mRS >3), cognitive impairment (TICS ≤30), or ICU/hospital length of stay after controlling for other predictors. Conclusion Agitation occurs frequently after SAH, especially in non-comatose patients with higher clinical grades. It is associated with the development of multiple hospital complications, and may have an independent impact on long-term outcomes. PMID:28008563

Cost-effectiveness of digital subtraction angiography in the setting of computed tomographic angiography negative subarachnoid hemorrhage.

PubMed

Jethwa, Pinakin R; Punia, Vineet; Patel, Tapan D; Duffis, E Jesus; Gandhi, Chirag D; Prestigiacomo, Charles J

2013-04-01

Recent studies have documented the high sensitivity of computed tomography angiography (CTA) in detecting a ruptured aneurysm in the presence of acute subarachnoid hemorrhage (SAH). The practice of digital subtraction angiography (DSA) when CTA does not reveal an aneurysm has thus been called into question. We examined this dilemma from a cost-effectiveness perspective by using current decision analysis techniques. A decision tree was created with the use of TreeAge Pro Suite 2012; in 1 arm, a CTA-negative SAH was followed up with DSA; in the other arm, patients were observed without further imaging. Based on literature review, costs and utilities were assigned to each potential outcome. Base-case and sensitivity analyses were performed to determine the cost-effectiveness of each strategy. A Monte Carlo simulation was then conducted by sampling each variable over a plausible distribution to evaluate the robustness of the model. With the use of a negative predictive value of 95.7% for CTA, observation was found to be the most cost-effective strategy ($6737/Quality Adjusted Life Year [QALY] vs $8460/QALY) in the base-case analysis. One-way sensitivity analysis demonstrated that DSA became the more cost-effective option if the negative predictive value of CTA fell below 93.72%. The Monte Carlo simulation produced an incremental cost-effectiveness ratio of $83 083/QALY. At the conventional willingness-to-pay threshold of $50 000/QALY, observation was the more cost-effective strategy in 83.6% of simulations. The decision to perform a DSA in CTA-negative SAH depends strongly on the sensitivity of CTA, and therefore must be evaluated at each center treating these types of patients. Given the high sensitivity of CTA reported in the current literature, performing DSA on all patients with CTA negative SAH may not be cost-effective at every institution.

Medically induced hypertension, hypervolaemia and haemodilution for the treatment and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage: systematic review.

PubMed

Loan, James J M; Wiggins, Anthony N; Brennan, Paul M

2018-01-17

Arterial vasospasm is a major cause of death and long-term disability following subarachnoid haemorrhage (SAH). The use of medically induced hypertension, hypervolaemia and/or haemodilution is widely practiced for prophylaxis and treatment of vasospasm following SAH. We aimed to determine if the quality of available research is adequate to inform use of haemodynamic management strategies to prevent or treat vasospasm following SAH. Individual searches of the following databases were conducted: The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and cohort studies comparing any element or combination thereof: medically induced hypertension, hypervolaemia, and haemodilution were included. Data were extracted using standardised proformas and risk of bias assessed using a domain-based risk of bias assessment tool. 348 study reports were identified by our literature search. Eight studies were included, three of which examined both volume expansion and medically induced hypertension. Three randomised clinical trials and two cohort studies examining prophylactic volume expansion were included. Two trials of prophylactic medically induced hypertension and two cohort studies were included. One trial and one cohort study of medically induced hypertension for treatment of established vasospasm was included. These trials demonstrated no significant difference in any of the clinical outcome measures studied. No trials of blood transfusion were included. There is currently insufficient evidence to determine the efficacy or non-efficacy of intravenous volume expansion, medically induced hypertension or blood transfusion for the treatment or prophylaxis of vasospasm following SAH. All of these approaches have been associated with adverse events, of unclear incidence. The current evidence base therefore cannot be used to reliably inform clinical practice. This is a

A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Young, Julia M; Morgan, Benjamin R; Mišić, Bratislav; Schweizer, Tom A; Ibrahim, George M; Macdonald, R Loch

2015-12-01

Individuals who have aneurysmal subarachnoid hemorrhages (SAHs) experience decreased health-related qualities of life (HRQoLs) that persist after the primary insult. To identify clinical variables that concurrently associate with HRQoL outcomes by using a partial least-squares approach, which has the distinct advantage of explaining multidimensional variance where predictor variables may be highly collinear. Data collected from the CONSCIOUS-1 trial was used to extract 29 clinical variables including SAH presentation, hospital procedures, and demographic information in addition to 5 HRQoL outcome variables for 256 individuals. A partial least-squares analysis was performed by calculating a heterogeneous correlation matrix and applying singular value decomposition to determine components that best represent the correlations between the 2 sets of variables. Bootstrapping was used to estimate statistical significance. The first 2 components accounting for 81.6% and 7.8% of the total variance revealed significant associations between clinical predictors and HRQoL outcomes. The first component identified associations between disability in self-care with longer durations of critical care stay, invasive intracranial monitoring, ventricular drain time, poorer clinical grade on presentation, greater amounts of cerebral spinal fluid drainage, and a history of hypertension. The second component identified associations between disability due to pain and discomfort as well as anxiety and depression with greater body mass index, abnormal heart rate, longer durations of deep sedation and critical care, and higher World Federation of Neurosurgical Societies and Hijdra scores. By applying a data-driven, multivariate approach, we identified robust associations between SAH clinical presentations and HRQoL outcomes. EQ-VAS, EuroQoL visual analog scaleHRQoL, health-related quality of lifeICU, intensive care unitIVH, intraventricular hemorrhagePLS, partial least squaresSAH, subarachnoid

Terson syndrome in aneurysmal subarachnoid hemorrhage-its relation to intracranial pressure, admission factors, and clinical outcome.

PubMed

Joswig, Holger; Epprecht, Lorenz; Valmaggia, Christophe; Leschka, Sebastian; Hildebrandt, Gerhard; Fournier, Jean-Yves; Stienen, Martin Nikolaus

2016-06-01

A large number of reports have not been able to clarify the pathophysiology of Terson syndrome (TS) in aneurysmal subarachnoid hemorrhage (aSAH). Prospective single-center study on aSAH patients. Fundoscopic and radiological signs of TS were assessed. The opening intracranial pressure (ICP) in patients who required a ventriculostomy was recorded with a manometer. Six out of 36 included patients had TS (16.7 %), which was associated with unfavorable admission scores. Twenty-nine patients (80.5 %) required ventriculostomy; TS was associated with higher ICP (median, 40 vs. 15 cm cmH2O, p = .003); all patients with TS had pathological ICP values of >20 cmH2O. Patients with a ruptured aneurysm of the anterior cerebral artery complex were ten times as likely to suffer from TS (OR 10.0, 95 % CI 1.03-97.50). Detection of TS on CT had a sensitivity of 50 %, a specificity of 98.4 %, a positive predictive value of 83.3 %, and a negative predictive value of 92.4 %. Mortality was 45 times as high in patients with TS (OR 45.0, 95 % CI 3.86-524.7) and neurologic morbidity up until 3 months post-aSAH was significantly higher in patients with TS (mRS 4-6; 100 vs. 17 %; p = .001). Our findings demonstrate an association between raised ICP and the incidence of TS. TS should be ruled out in aSAH patients presenting comatose or with raised ICP to ensure upfront ophthalmological follow-up. In alert patients without visual complaints and a TS-negative CT scan, the likelihood for the presence of TS is very low.

Subarachnoid haemorrhage guidelines and clinical practice: a cross-sectional study of emergency department consultants' and neurospecialists' views and risk tolerances.

PubMed

Lansley, J; Selai, C; Krishnan, A S; Lobotesis, K; Jäger, H R

2016-09-15

To establish if emergency medicine and neuroscience specialist consultants have different risk tolerances for investigation of suspected spontaneous subarachnoid haemorrhage (SAH), and to establish if their risk-benefit appraisals concur with current guidelines. 4 major neuroscience centres in London. 58 consultants in emergency medicine and neuroscience specialities (neurology, neurosurgery and neuroradiology) participated in an anonymous survey. The primary outcome measure was the highest stated acceptable risk of missing SAH in the neurologically intact patient presenting with sudden onset headache. Secondary outcome measures included agreement with guideline recommendations, risk/benefit appraisal and required performance of diagnostic tests, including lumbar puncture. Emergency department clinicians accepted almost 3 times the risk of a missed SAH diagnosis compared with the neuroscience specialists (2.8% vs 1.1%; p=0.02), were more likely to accept a higher risk of missed diagnosis for the benefit of a non-invasive test (p=0.04) and were more likely to disagree with current published guidelines stipulating the need for LP in all CT-negative cases (p=0.001). Divergence from recognised procedures for SAH investigation is often criticised and attributed to a lack of knowledge of guidelines. This study indicates that divergence from guidelines may be explained by alternative risk-benefit appraisals made by doctors with their patients. Guideline recommendations may gain wider acceptance if they accommodate the requirements of the doctors and patients using them. Further study of clinical risk tolerance may help explain patterns of diagnostic test use and other variations in healthcare delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Subarachnoid Hemorrhage and Readmissions: National Rates, Causes, Risk Factors, and Outcomes in 16,001 Hospitalized Patients.

PubMed

Rumalla, Kavelin; Smith, Kyle A; Arnold, Paul M; Mittal, Manoj K

2018-02-01

The acute complications of aneurysmal subarachnoid hemorrhage (aSAH) often lead to readmissions, which are linked to hospital reimbursement. The national rates, causes, risk factors, and outcomes associated with 30-day and 90-day readmission after aSAH have not previously been reported. The Nationwide Readmissions Database was queried from January to September 2013 for all patients (age ≥18 years) with a diagnosis of aSAH. Data points included demographics, comorbidities, complications, and discharge outcomes. Causes and risk factors for 30-day and 90-day readmission were identified in univariate and multivariable analysis. In 12,777 patients discharged alive after hospitalization for aSAH, 962 (7.5%) were readmitted within 30 days and 2153 (16.7%) within 90 days. Common causes of readmission included stroke, hydrocephalus, septicemia, and headache. At 30-day and 90-day readmission, 39.7% and 51.2% of patients with diagnosis of hydrocephalus underwent ventriculoperitoneal shunt placement, respectively. In multivariable analysis, cannabis use and diabetes were predictors of both 30-day and 90-day readmission and older patients were uniquely susceptible to 30-day readmissions. Risk factors for 90-day readmission included Medicare insurance, hypothyroidism, initial discharge to skilled nursing facility, and several index complications including bowel obstruction, gastrostomy, acute lung injury, and cerebral edema. Average cost and length of stay were calculated at 30-day ($16.647, 7.1 days) and 90-day readmission ($17,926, 6.7 days). Mortality was 2.8% within 30 days and 3.8% within 90 days. Many readmissions occur outside the 30-day follow-up period in patients subarachnoid hemorrhage and possess unique risk factors, which may help identify high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice.

PubMed

Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse; Bromley, Susan; García Rodríguez, Luis A

2017-11-28

To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom. A cohort of new users of low-dose aspirin (75-300 mg; n = 199,079) aged 40-84 years and a 1:1 matched cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95% confidence intervals (CIs) were calculated for current low-dose aspirin use (0-7 days before the index date [ICB date for cases, random date for controls]); reference group was never used. There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH], and n = 385 for subarachnoid hemorrhage [SAH]). RRs (95% CI) were 0.98 (0.84-1.13) for all ICB, 0.98 (0.80-1.20) for ICH, 1.23 (0.95-1.59) for SDH, and 0.77 (0.58-1.01) for SAH. No duration of use or dose-response association was apparent. RRs (95% CI) for ≥1 year of low-dose aspirin use were 0.90 (0.72-1.13) for ICH, 1.20 (0.91-1.57) for SDH, and 0.69 (0.50-0.94) for SAH. Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year. © 2017 American Academy of Neurology.

A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Human, Theresa; Diringer, Michael N; Allen, Michelle; Zipfel, Gregory J; Chicoine, Michael; Dacey, Ralph; Dhar, Rajat

2018-04-01

Seizures occur in 10-20% of patients with subarachnoid hemorrhage (SAH), predominantly in the acute phase. However, anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis. The objective of this study was to compare brief versus extended seizure prophylaxis after aneurysmal SAH. We performed a prospective, single-center, randomized, open-label trial of a brief (3-day) course of levetiracetam (LEV) versus extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome. Eighty-four SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in three (9%) of 35 in the brief LEV group versus one (2%) of 49 in the extended group (p = 0.2). Ten (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on computed tomography (CT) scans (adjusted OR 12.5, 95% CI 1.2-122, p = 0.03). Good functional outcome (mRS 0-2) was more likely in the brief LEV group (83 vs. 61%, p = 0.04). This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment.

Arterial injuries after penetrating brain injury in civilians: risk factors on admission head computed tomography.

PubMed

Bodanapally, Uttam K; Saksobhavivat, Nitima; Shanmuganathan, Kathirkamanathan; Aarabi, Bizhan; Roy, Ashis K

2015-01-01

The object of this study was to determine the specific CT findings of the injury profile in penetrating brain injury (PBI) that are risk factors related to intracranial arterial injuries. The authors retrospectively evaluated admission head CTs and accompanying digital subtraction angiography (DSA) studies from patients with penetrating trauma to the head in the period between January 2005 and December 2012. Two authors reviewed the CT images to determine the presence or absence of 30 injury profile variables and quantified selected variables. The CT characteristics in patients with and without arterial injuries were compared using univariate analysis, multivariate analysis, and receiver operating characteristic (ROC) curve analysis to determine the respective risk factors, independent predictors, and optimal threshold values for the continuous variables. Fifty-five patients were eligible for study inclusion. The risk factors for an intracranial arterial injury on univariate analysis were an entry wound over the frontobasal-temporal regions, a bihemispheric wound trajectory, a wound trajectory in proximity to the circle of Willis (COW), a subarachnoid hemorrhage (SAH), a higher SAH score, an intraventricular hemorrhage (IVH), and a higher IVH score. A trajectory in proximity to the COW was the best predictor of injury (OR 6.8 and p = 0.005 for all penetrating brain injuries [PBIs]; OR 13.3 and p = 0.001 for gunshot wounds [GSWs]). Significant quantitative variables were higher SAH and IVH scores. An SAH score of 3 (area under the ROC curve [AUC] for all PBIs 0.72; AUC for GSWs 0.71) and an IVH score of 3 (AUC for all PBIs 0.65; AUC for GSWs 0.65) could be used as threshold values to suggest an arterial injury. The risk factors identified may help radiologists suggest the possibility of arterial injury and prioritize neurointerventional consultation and potential DSA studies.

The Role of Post-Resuscitation Electrocardiogram in Patients With ST-Segment Changes in the Immediate Post-Cardiac Arrest Period.

PubMed

Kim, Youn-Jung; Min, Sun-Yang; Lee, Dong Hun; Lee, Byung Kook; Jeung, Kyung Woon; Lee, Hui Jai; Shin, Jonghwan; Ko, Byuk Sung; Ahn, Shin; Nam, Gi-Byoung; Lim, Kyoung Soo; Kim, Won Young

2017-03-13

The authors aimed to evaluate the role of post-resuscitation electrocardiogram (ECG) in patients showing significant ST-segment changes on the initial ECG and to provide useful diagnostic indicators for physicians to determine in which out-of-hospital cardiac arrest (OHCA) patients brain computed tomography (CT) should be performed before emergency coronary angiography. The usefulness of immediate brain CT and ECG for all resuscitated patients with nontraumatic OHCA remains controversial. Between January 2010 and December 2014, 1,088 consecutive adult nontraumatic patients with return of spontaneous circulation who visited the emergency department of 3 tertiary care hospitals were enrolled. After excluding 245 patients with obvious extracardiac causes, 200 patients were finally included. The patients were categorized into 2 groups: those with ST-segment changes with spontaneous subarachnoid hemorrhage (SAH) (n = 50) and those with OHCA of suspected cardiac origin group (n = 150). The combination of 4 ECG characteristics including narrow QRS (<120 ms), atrial fibrillation, prolonged QTc interval (≥460 ms), and ≥4 ST-segment depressions had a 66.0% sensitivity, 80.0% specificity, 52.4% positive predictive value, and 87.6% negative predictive value for predicting SAH. The area under the receiver-operating characteristic curves in the post-resuscitation ECG findings was 0.816 for SAH. SAH was observed in a substantial number of OHCA survivors (25.0%) with significant ST-segment changes on post-resuscitation ECG. Resuscitated patients with narrow QRS complex and any 2 ECG findings of atrial fibrillation, QTc interval prolongation, or ≥4 ST-segment depressions may help identify patients who need brain CT as the next diagnostic work-up. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Hospital care for stroke patients in the Valencian Region using the basic minimum data set from the International Classification of Diseases, 9th revision, clinical modification].

PubMed

Geffner-Sclarsky, D

To determine the load and characteristics of cerebrovascular diseases (CVD) admitted in the hospital network throughout the Valencian Region. The paper reports on an analysis of the information included in the basic minimum data set (BMDS) from the 26 hospitals run by the Valencian Regional Ministry of Health in the year 2001. Patients that were selected were those whose main diagnosis was codes C.430 to C.437, according to the International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM). A total of 10,558 patients with CVD were discharged, which accounts for 2.6% of admissions and 3% of hospital stays. The mean age of the series was 71.03 years -standard deviation (SD): 9- and 94.8% were admitted as emergencies. By diagnoses, 3% (319) were subarachnoid haemorrhages (SAH; C.430); 13.4% (1,412) were cerebral haemorrhages (ICH; C.431); 18.5% (1,956) were transient ischemic attacks (TIA; C.435); 49.5% (5,225) were cases of cerebral infarction (CI; C.434 and C.436); and 15.6% involved other vascular processes (C.433 and C.437). Mortality rates were 30.1% in SAH; 33.9% in ICH; 11.7% in CI; and 2.7% in TIA. Mean number of days in hospital: SAH 17.4 (SD: 15); ICH 13.1 (SD: 11.8); CI 9.9 (SD: 6.4) and in cases of TIA 7.2 (SD: 4). The percentages of survivors who were discharged home were 78.9 % in SAH, 83.2% in ICH and 91.9% in the case of CI. In all, 51.3% (5,413 patients) were discharged by neurological units. In spite of possible insufficiencies analysed in this work, the use of the BMDS provides valuable epidemiological information that is very useful for health care management.

Changes in the level of cardiac troponine and disorders in pulmonary gas exchange as predictors of short- and long-term outcomes of patients with aneurysm subarachnoid haemorrhage.

PubMed

Burzyńska, Małgorzata; Uryga, Agnieszka; Kasprowicz, Magdalena; Kędziora, Jarosław; Szewczyk, Ewa; Woźniak, Jowita; Jarmundowicz, Włodzimierz; Kübler, Andrzej

2017-12-01

Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO 2 /FiO 2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO 2 /FiO 2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.

Subtypes and case-fatality rates of stroke: a hospital-based stroke registry in Taiwan (SCAN-IV).

PubMed

Jeng, J S; Lee, T K; Chang, Y C; Huang, Z S; Ng, S K; Chen, R C; Yip, P K

1998-04-01

Stroke data bank can afford important information regarding risk factors, pathogenesis, prognosis, etc. By means of hospital-based stroke registry, we investigated the risk factors and case-fatality rates in different types of stroke and transient ischemic attack (TIA) patients at the National Taiwan University Hospital in 1995. After excluding ineligible patients, 995 patients aged 1-98 years (575 men and 420 women) were recruited. Men predominated in all age groups for stroke and TIA in general except for cerebral hemorrhage (CH) in patients aged < 35 years and subarachnoid hemorrhage (SAH) in patients aged > or = 45 years. Of these, 676 (67.9%), 41 (4.1%), 228 (22.9%) and 50 (5%) patients were classified in the categories of cerebral infarction (CI), TIA, CH and SAH, respectively. The CI/CH ratio was 2.96. Hypertension remained one of the most important risk factors for CI, CH and TIA patients. Severe extracranial carotid artery stenosis (> or = 50%) was found in 12% of the CI patients and 27% of the TIA patients, but not found in the CH and SAH patients. Of these patients, the 30-day case-fatality rate was 10.9%, highest in SAH (30%), followed by CH (24.1%) and CI (5.6%). There were 41 in-hospital stroke patients who had significantly higher case-fatality rates than the other stroke patients (P<0.001 for all stroke, CI and CH patients by chi2 test). As compared to the previous stroke registries in Taiwan, there is a secular trend of increasing CI/CH ratios. These findings in Taiwan were compared with those in other populations, including other Asian, Caucasian and black populations. The CI/CH ratios in Asian populations, including Chinese, Japanese and Korean, were much lower than those in Caucasian and black populations. Dietary, environmental and genetic factors probably play important roles in these differences.

In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA.

PubMed

Vergis, Nikhil; Atkinson, Stephen R; Knapp, Suzanne; Maurice, James; Allison, Michael; Austin, Andrew; Forrest, Ewan H; Masson, Steven; McCune, Anne; Patch, David; Richardson, Paul; Gleeson, Dermot; Ryder, Stephen D; Wright, Mark; Thursz, Mark R

2017-04-01

Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. We analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 × 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P = .084), infection during treatment (P = .20), or infection after treatment (P = .27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.27-2.92; P = .002). There was no association between prednisolone therapy

Transtracheal oxygen and positive airway pressure: A salvage technique in overlap syndrome.

PubMed

Biscardi, Frank Hugo; Rubio, Edmundo Raul

2014-01-01

The coexistence of sleep apnea-hypopnea syndrome (SAHS) with chronic obstructive pulmonary disease (COPD) occurs commonly. This so called overlap syndrome leads to more profound hypoxemia, hypercapnic respiratory failure, and pulmonary hypertension than each of these conditions independently. Not infrequently, these patients show profound hypoxemia, despite optimal continuous positive airway pressure (CPAP) therapy for their SAHS. We report a case where CPAP therapy with additional in-line oxygen supplementation failed to accomplish adequate oxygenation. Adding transtracheal oxygen therapy (TTOT) to CPAP therapy provided better results. We review the literature on transtracheal oxygen therapy and how this technique may play a significant role in these complicated patients with overlap syndrome, obviating the need for more invasive procedures, such as tracheostomy.

A Beginner's Guide to Science Project Competitions in Indiana.

ERIC Educational Resources Information Center

Zeck, Patricia Arnett

2000-01-01

Describes a regional science fair in Indiana. Presents guidelines for organization and registration, rules and regulations, display and presentation, science fair advancement opportunities, and other competitions. (SAH)

Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet.

PubMed

Igolnikov, Alexander C; Green, Richard M

2006-03-01

The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypothesized that phosphatidylethanolamine-N-methyl transferase (PEMT) up-regulation is a consequence of MCD diet administration, and is important for the pathogenesis of steatohepatitis in this model. However, the effect of decreased phosphatidylcholine secretion and modulation of PEMT on the development of diet-induced steatohepatitis in Mdr2 (+/-) mice has not been explored. Thus, the purpose of the study is to examine the effects of the MCD diet on Mdr2 (+/-) mice. Mdr2 (+/-) and Mdr2 (+/+) mice were treated with an MCD or control diet for up to 30 days, and the severity of steatohepatitis, PEMT activity and hepatic S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) levels were measured. Serum ALT levels, hepatic inflammation, and PEMT activity were significantly lower, and hepatic SAM:SAH ratios were significantly higher in Mdr2 (+/-) mice at 7 and 30 days on the MCD diet. Mdr2 (+/-) mice have diminished susceptibility to MCD diet-induced NASH, which is associated with a relative decrease in PEMT activity and increased SAM:SAH ratios.

Effective use of sertraline for pathological laughing after severe vasospasm due to aneurysmal subarachnoid hemorrhage: case report.

PubMed

Takeuchi, Hayato; Iwamoto, Kazuhide; Mukai, Mao; Fujita, Tomoaki; Tsujino, Hitoshi; Iwamoto, Yoshihiro

2014-01-01

Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing.

Effective Use of Sertraline for Pathological Laughing after Severe Vasospasm Due to Aneurysmal Subarachnoid Hemorrhage: Case Report

PubMed Central

TAKEUCHI, Hayato; IWAMOTO, Kazuhide; MUKAI, Mao; FUJITA, Tomoaki; TSUJINO, Hitoshi; IWAMOTO, Yoshihiro

2014-01-01

Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing. PMID:24201096

Crystal structure of norcoclaurine-6-O-methyltransferase, a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids.

PubMed

Robin, Adeline Y; Giustini, Cécile; Graindorge, Matthieu; Matringe, Michel; Dumas, Renaud

2016-09-01

Growing pharmaceutical interest in benzylisoquinoline alkaloids (BIA) coupled with their chemical complexity make metabolic engineering of microbes to create alternative platforms of production an increasingly attractive proposition. However, precise knowledge of rate-limiting enzymes and negative feedback inhibition by end-products of BIA metabolism is of paramount importance for this emerging field of synthetic biology. In this work we report the structural characterization of (S)-norcoclaurine-6-O-methyltransferase (6OMT), a key rate-limiting step enzyme involved in the synthesis of reticuline, the final intermediate to be shared between the different end-products of BIA metabolism, such as morphine, papaverine, berberine and sanguinarine. Four different crystal structures of the enzyme from Thalictrum flavum (Tf 6OMT) were solved: the apoenzyme, the complex with S-adenosyl-l-homocysteine (SAH), the complexe with SAH and the substrate and the complex with SAH and a feedback inhibitor, sanguinarine. The Tf 6OMT structural study provides a molecular understanding of its substrate specificity, active site structure and reaction mechanism. This study also clarifies the inhibition of Tf 6OMT by previously suggested feedback inhibitors. It reveals its high and time-dependent sensitivity toward sanguinarine. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Clinical Outcome Prediction in Aneurysmal Subarachnoid Hemorrhage Using Bayesian Neural Networks with Fuzzy Logic Inferences

PubMed Central

Lo, Benjamin W. Y.; Macdonald, R. Loch; Baker, Andrew; Levine, Mitchell A. H.

2013-01-01

Objective. The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH). Methods. The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients). Results. Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters. Discussion. This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication. PMID:23690884

Administration of hypertonic (3%) sodium chloride/acetate in hyponatremic patients with symptomatic vasospasm following subarachnoid hemorrhage.

PubMed

Suarez, J I; Qureshi, A I; Parekh, P D; Razumovsky, A; Tamargo, R J; Bhardwaj, A; Ulatowski, J A

1999-07-01

A retrospective study was carried out to evaluate the effect of hypertonic (3%) saline chloride/acetate on various hemodynamic parameters in mildly hyponatremic patients with symptomatic vasospasm following aneurysmal subarachnoid hemorrhage (SAH). We identified 29 hyponatremic (serum sodium < 135 mEq/L) patients who received hypertonic (3%) sodium chloride/acetate as a continuous infusion. Administration of hypertonic (3%) sodium chloride/acetate resulted in higher central venous pressures and positive fluid balance, with a concomitant increase in serum sodium and chloride concentrations without metabolic acidosis. There were no changes in mean cerebral blood flow velocities after infusion of hypertonic (3%) sodium chloride/acetate. We found no reports of congestive heart failure, pulmonary edema, metabolic acidosis, coagulopathy, intracranial hemorrhages, or central pontine myelinolysis in any of these patients. We conclude that hypertonic (3%) sodium chloride/acetate can be administered to patients with mild hyponatremia in the setting of symptomatic vasospasm following SAH without untoward effects. Sample size and limitations of a retrospective analysis preclude conclusions about safety and efficacy of hypertonic (3%) sodium chloride/acetate administration in this patient population. However, our results support justification for a prospective, randomized, double-blind trial of hypertonic (3%) sodium chloride/acetate versus normal saline in patients with symptomatic vasospasm following SAH.

Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension

PubMed Central

de Oliveira, Lucas Felipe; Almeida, Thalles Ramos; Ribeiro Machado, Marcus Paulo; Cuba, Marilia Beatriz; Alves, Angélica Cristina; da Silva, Marcos Vinícius; Rodrigues Júnior, Virmondes; Dias da Silva, Valdo José

2015-01-01

Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH. PMID:26300922

Transsylvian selective amygdalohippocampectomy in children with hippocampal sclerosis: seizure, intellectual and memory outcome.

PubMed

Beaton, Anne E; Durnford, Andrew; Heffer-Rahn, Phillip E; Kirkham, Fenella; Griffin, Angela; Gray, William P; Gray, W L S

2012-11-01

This study investigates the efficacy of transylvian selective amygdalohippocampectomy (TS SAH) in children with medically intractable epilepsy due to unilateral hippocampal sclerosis. Post-surgical seizure control, intellectual and memory outcomes are examined. This study reports on pre- and post-surgical clinical data from 10 patients who underwent TS SAH between 2002 and 2010 after 24 months follow-up. Pre- and post-operative change in seizure frequency, AED use, intellect and memory are compared. At 12 months and 24 months post-surgery, 9/10 (90%) and 7/8 (87.5%) patients respectively, were seizure free (Engel I). No patients were classed as Engel III or IV. No significant improvement or decline at a group level was found on measures of intellect or verbal or visual memory. One hundred per cent improved or remained within 1 SD of their pre-operatives score on verbal and perceptual reasoning learning and reasoning measures. Significant improvement was found post-operatively for both immediate and delayed facial memory. Our findings of good post-surgical seizure control and favourable cognitive outcome provides evidence against previous findings that SAH in children may not be effective. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Deaths from stroke in US young adults, 1989-2009.

PubMed

Poisson, Sharon N; Glidden, David; Johnston, S Claiborne; Fullerton, Heather J

2014-12-02

To determine what the trends in stroke mortality have been over 2 decades in young adults. In this cohort study, we analyzed death certificate data for ischemic and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) in adults aged 20-44 in the United States for 1989 through 2009, covering approximately 2.2 billion person-years. Poisson regression was used to calculate and compare time trend data between groups and to compare trends in young adults to those in adults over age 45. Mortality from stroke in young adults declined by 35% over the study period, with reductions in all 3 stroke subtypes (ischemic stroke decreased by 15%, ICH by 47%, and SAH by 50%). Black race was a risk factor for all 3 stroke subtypes (relative risk 2.4 for ischemic stroke, 4.0 for ICH, and 2.1 for SAH), but declines in all stroke subtypes were more dramatic in black compared to white participants (p < 0.001 for all stroke subtypes). Although hospitalizations for stroke in young patients have been increasing, the apparent decrease in mortality rates and in racial disparities suggests that recognition and treatment in this group may be improving. © 2014 American Academy of Neurology.

Deaths from stroke in US young adults, 1989–2009

PubMed Central

Glidden, David; Johnston, S. Claiborne; Fullerton, Heather J.

2014-01-01

Objective: To determine what the trends in stroke mortality have been over 2 decades in young adults. Methods: In this cohort study, we analyzed death certificate data for ischemic and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) in adults aged 20–44 in the United States for 1989 through 2009, covering approximately 2.2 billion person-years. Poisson regression was used to calculate and compare time trend data between groups and to compare trends in young adults to those in adults over age 45. Results: Mortality from stroke in young adults declined by 35% over the study period, with reductions in all 3 stroke subtypes (ischemic stroke decreased by 15%, ICH by 47%, and SAH by 50%). Black race was a risk factor for all 3 stroke subtypes (relative risk 2.4 for ischemic stroke, 4.0 for ICH, and 2.1 for SAH), but declines in all stroke subtypes were more dramatic in black compared to white participants (p < 0.001 for all stroke subtypes). Conclusions: Although hospitalizations for stroke in young patients have been increasing, the apparent decrease in mortality rates and in racial disparities suggests that recognition and treatment in this group may be improving. PMID:25361783

Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

PubMed

Kim, J A; Rosenthal, E S; Biswal, S; Zafar, S; Shenoy, A V; O'Connor, K L; Bechek, S C; Valdery Moura, J; Shafi, M M; Patel, A B; Cash, S S; Westover, M B

2017-06-01

To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Killer Pigments in Bacteria: An Ecological Nightmare.

ERIC Educational Resources Information Center

Benathen, Isaiah A.; Saccardi, Marion

2000-01-01

Describes an alternative to teaching ecology by using bacteria to test competitor survival. Students observe a time-dependent selective killing of other unrelated bacteria by Pseudomonas aeruginosa. (SAH)

Computer-Assisted Diagnosis of the Sleep Apnea-Hypopnea Syndrome: A Review

PubMed Central

Alvarez-Estevez, Diego; Moret-Bonillo, Vicente

2015-01-01

Automatic diagnosis of the Sleep Apnea-Hypopnea Syndrome (SAHS) has become an important area of research due to the growing interest in the field of sleep medicine and the costs associated with its manual diagnosis. The increment and heterogeneity of the different techniques, however, make it somewhat difficult to adequately follow the recent developments. A literature review within the area of computer-assisted diagnosis of SAHS has been performed comprising the last 15 years of research in the field. Screening approaches, methods for the detection and classification of respiratory events, comprehensive diagnostic systems, and an outline of current commercial approaches are reviewed. An overview of the different methods is presented together with validation analysis and critical discussion of the current state of the art. PMID:26266052

Small Molecule Inhibitors That Selectively Block Dengue Virus Methyltransferase*

PubMed Central

Lim, Siew Pheng; Sonntag, Louis Sebastian; Noble, Christian; Nilar, Shahul H.; Ng, Ru Hui; Zou, Gang; Monaghan, Paul; Chung, Ka Yan; Dong, Hongping; Liu, Boping; Bodenreider, Christophe; Lee, Gladys; Ding, Mei; Chan, Wai Ling; Wang, Gang; Jian, Yap Li; Chao, Alexander Theodore; Lescar, Julien; Yin, Zheng; Vedananda, T. R.; Keller, Thomas H.; Shi, Pei-Yong

2011-01-01

Crystal structure analysis of Flavivirus methyltransferases uncovered a flavivirus-conserved cavity located next to the binding site for its cofactor, S-adenosyl-methionine (SAM). Chemical derivatization of S-adenosyl-homocysteine (SAH), the product inhibitor of the methylation reaction, with substituents that extend into the identified cavity, generated inhibitors that showed improved and selective activity against dengue virus methyltransferase (MTase), but not related human enzymes. Crystal structure of dengue virus MTase with a bound SAH derivative revealed that its N6-substituent bound in this cavity and induced conformation changes in residues lining the pocket. These findings demonstrate that one of the major hurdles for the development of methyltransferase-based therapeutics, namely selectivity for disease-related methyltransferases, can be overcome. PMID:21147775

Neuroscience and the fallacies of functionalism.

PubMed

Reddy, William M

2010-01-01

Smail's "On Deep History and the Brain" is rightly critical of the functionalist fallacies that have plagued evolutionary theory, sociobiology, and evolutionary psychology. However, his attempt to improve on these efforts relies on functional explanations that themselves oversimplify the lessons of neuroscience. In addition, like explanations in evolutionary psychology, they are highly speculative and cannot be confirmed or disproved by evidence. Neuroscience research is too diverse to yield a single picture of brain functioning. Some recent developments in neuroscience research, however, do suggest that cognitive processing provides a kind of “operating system” that can support a great diversity of cultural material. These developments include evidence of “top-down” processing in motor control, in visual processing, in speech recognition, and in “emotion regulation.” The constraints that such a system may place on cultural learning and transmission are worth investigating. At the same time, historians are well advised to remain wary of the pitfalls of functionalism.

Experiments with Corn To Demonstrate Plant Growth and Development.

ERIC Educational Resources Information Center

Haldeman, Janice H.; Gray, Margarit S.

2000-01-01

Explores using corn seeds to demonstrate plant growth and development. This experiment allows students to formulate hypotheses, observe and record information, and practice mathematics. Presents background information, materials, procedures, and observations. (SAH)

Teaching the Mathematics of Radioactive Dating.

ERIC Educational Resources Information Center

Shea, James H.

2001-01-01

Describes a method used to teach the concept of radiometric dating using mathematical equations. Explores the lack of information in textbooks on how to solve radiometric dating problems using mathematical concepts. (SAH)

Student Science Teachers' Accounts of a Well-Remembered Event about Classroom Management.

ERIC Educational Resources Information Center

Zuckerman, June Trop

2000-01-01

Discusses how 36 student science teachers described and responded to one of their own classroom management problems. Based on student teachers' written accounts of a well-remembered event about classroom management. (SAH)

Cabbage Patch Chemistry.

ERIC Educational Resources Information Center

Journal of Chemical Education, 2000

2000-01-01

This activity takes students through the process of fermentation. Requires an entire month for the full reaction to take place. The reaction, catalyzed by bacterial enzymes, produces lactic acid from glucose. (SAH)

Investigating Wound Healing in Plant Cells: This Spud's for You!

ERIC Educational Resources Information Center

Thomson, Norm

2000-01-01

Presents classroom inquiry-based investigations to investigate wound healing in plant tissues and cells. Students create their own research problems and the investigations can be related to the National Science Standards. (SAH)

"True" posterior communicating aneurysms: Three cases, three strategies.

PubMed

Nery, Breno; Araujo, Ricardo; Burjaili, Bruno; Smith, Timothy R; Rodrigues, Jose Carlos; Silva, Marcelo Nery

2016-01-01

The authors provide a review of true aneurysms of the posterior communicating artery (PCoA). Three cases admitted in our hospital are presented and discussed as follows. First patient is a 51-year-old female presenting with a Fisher II, Hunt-Hess III (headache and confusion) subarachnoid hemorrhage (SAH) from a ruptured true aneurysm of the right PCoA. She underwent a successful ipsilateral pterional craniotomy for aneurysm clipping and was discharged on postoperative day 4 without neurological deficit. Second patient is a 53-year-old female with a Fisher I, Hunt-Hess III (headache, mild hemiparesis) SAH and multiple aneurisms, one from left ophthalmic carotid artery and one (true) from right PCoA. These lesions were approached and successfully treated by a single pterional craniotomy on the left side. The patient was discharged 4 days after surgery, with complete recovery of muscle strength during follow-up. Third patient is a 69-year-old male with a Fisher III, Hunt-Hess III (headache and confusion) SAH, from a true PCoA on the right. He had a left subclavian artery occlusion with flow theft from the right vertebral artery to the left vertebral artery. The patient underwent endovascular treatment with angioplasty and stent placement on the left subclavian artery that resulted in aneurysm occlusion. In conclusion, despite their seldom occurrence, true PCoA aneurysms can be successfully treated with different strategies.

[Genetic dissection of intracranial aneurysm].

PubMed

Onda, Hideaki; Yoneyama, Taku; Akagawa, Hiroyuki; Kasuya, Hidetoshi

2008-11-01

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm (IA) is a devastating condition with high mortality and morbidity. Genetic as well as environment factors play important roles in the pathogenesis of SAH and IAs. We review the present knowledge on the genetic factors responsible for SAH or IAs. Linkage analysis and association study are used for genetic dissection. Genome-wide linkage analyses have specified several genetic loci for IAs and 6 loci (1p34-36, 7q11, 11q24-25, 14q22-31, 19q13, and Xp22) have been replicated in different populations. Numerous functional and/or positional candidate genes for IAs have been investigated by case-control association studies. The results of genetic association studies are modest because of small sample sizes. To date, no specific genes have been identified as responsible for IA development or rupture. Recent, large-scale genome-wide association (GWA) studies have revealed consistent and replicable genetic markers of several complex diseases such as coronary artery disease and type 2 diabetes. Although, thus far, no GWA studies have been performed for IAs, such a study may accomplish the breakthrough of genetic dissection of IAs. The identification of susceptible genes might lead to the understanding of the mechanism of IA formation or rupture and to novel therapeutic strategies.

ε-Aminocaproic acid in angiographically negative subarachnoid hemorrhage patients is safe: a retrospective review of 83 consecutive patients.

PubMed

Hui, Ferdinand K; Schuette, Albert J; Lieber, Michael; Spiotta, Alejandro M; Moskowitz, Shaye I; Barrow, Daniel L; Cawley, C Michael

2012-03-01

ε-Aminocaproic acid (EACA) has been used to reduce the rate of cerebral aneurysm rerupture before definitive treatment. In centers administering EACA to patients with a subarachnoid hemorrhage (SAH), patients eventually diagnosed with angiographically negative subarachnoid hemorrhage (ANSAH) may also initially receive EACA, perhaps placing them at increased risk for ischemic complications. To evaluate the effect of short-term EACA on outcomes and secondary measures in patients with ANSAH. We conducted a retrospective study of 454 consecutive SAH patients over a 2-year period under a current protocol for EACA use. Patients were excluded if a source for the SAH was discovered, yielding a total of 83 ANSAH patients. The patients were assigned to groups that did or did not receive EACA. The primary end points of the study were ischemic complications, pulmonary emboli, vasospasm, ventriculoperitoneal shunting rates, and outcomes. Statistical analysis yielded no significant difference between the 2 arms with respect to any of the end points: vasospasm (P = .65), deep vein thrombosis (P = .51), pulmonary embolism (P = 1.0), stroke (P = 1.0), myocardial infarction (P = 1.0), and ventriculoperitoneal shunt (P = .57). There was no statistically significant outcome difference using the modified Rankin Scale (P = .30). Short-term (<72 hour) application of EACA does not result in an increase in adverse events in patients with ANSAH.

Early Predictors of Fever in Patients with Aneurysmal Subarachnoid Hemorrhage.

PubMed

Rocha Ferreira da Silva, Ivan; Rodriguez de Freitas, Gabriel

2016-12-01

Fever is commonly observed in patients who have had aneurysmal subarachnoid hemorrhage (SAH), and it has been associated with the occurrence of delayed cerebral ischemia and worse outcomes in previous studies. Frequently, fever is not the result of bacterial infections, and distinction between infection-related fever and fever secondary to brain injury (also referred as central fever) can be challenging. The current study aimed to identify risk factors on admission for the development of central fever in patients with SAH. Databank analysis was performed using information from demographic data (age, gender), imaging (transcranial Doppler ultrasound, computed tomography, and cerebral angiogram), laboratory (white blood cell count, hemoglobin, renal function, and electrolytes), and clinical assessment (Hunt-Hess and modified Fisher scales on admission, occurrence of fever). A multivariate logistic regression model was created. Of 55 patients, 32 developed fever during the first 7 days of hospital stay (58%). None of the patients had identifiable bacterial infections during their first week in the neurocritical care unit. Hunt-Hess scale >2 and leukocytosis on admission were associated to the development of central fever, even after correction in a logistic regression model. Leukocytosis and a poor neurologic examination on admission might help predict which subset of patients with SAH are at higher risk of developing central fever early in their hospital stay. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

PubMed

Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

2017-04-15

Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebral haemodynamics in patients with hydrocephalus after subarachnoid haemorrhage due to ruptured aneurysm.

PubMed

Chang, Chia-Cheng; Kuwana, Nobumasa; Ito, Susumu; Yokoyama, Takaakira; Kanno, Hiroshi; Yamamoto, Isao

2003-01-01

Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may be reduced in patients with normal pressure hydrocephalus (NPH) after subarachnoid haemorrhage (SAH). However, little is known about brain circulation in asymptomatic patients with ventriculomegaly after SAH. This study investigated CBF and CVR in symptomatic and asymptomatic patients with ventriculomegaly to clarify the mechanism of NPH. CBF and CVR were investigated in 48 patients with ventriculomegaly after SAH due to ruptured aneurysm. Mean CBF of the whole brain was measured by first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after administration of 500 mg acetazolamide. Thirty patients with NPH who responded to shunting had significantly ( P<0.01) reduced mean CBF and CVR compared with normal controls. Fourteen asymptomatic patients with ventriculomegaly showed significant ( P<0.01) reduction in CVR but no difference in mean CBF. Four symptomatic patients who did not respond to shunting showed significantly ( P<0.01) reduced mean CBF but had preserved CVR. Postoperative mean CBF and CVR increased significantly ( P<0.01) in 21 patients who responded to shunting, but showed no significant change in four symptomatic patients who did not respond to shunting. Reduction of CBF superimposed on pre-existing impairment of CVR may be an essential step in the mechanism responsible for the manifestation of symptoms of NPH.

Adding Math to Biology.

ERIC Educational Resources Information Center

Texley, Juliana

2001-01-01

Describes a teaching method in which students learn about evolutionary biology through the use of mathematics. Uses the concept of biostatistics, the mathematical analysis of the variation in nature, to understand evolution. (SAH)

The Silent Revolution Continues.

ERIC Educational Resources Information Center

Perlin, John

2001-01-01

Discusses the reliability and versatility of using photovoltaics whereby solar cells convert sunlight directly into electricity. The growing concern of global warming promises to transform photovoltaics into a major energy producer. (Author/SAH)

Inflammation, negative nitrogen balance, and outcome after aneurysmal subarachnoid hemorrhage.

PubMed

Badjatia, Neeraj; Monahan, Aimee; Carpenter, Amanda; Zimmerman, Jacqueline; Schmidt, J Michael; Claassen, Jan; Connolly, E Sander; Mayer, Stephan A; Karmally, Wahida; Seres, David

2015-02-17

To analyze the impact of inflammation and negative nitrogen balance (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH). This was a prospective observational study of SAH patients admitted between May 2008 and June 2012. Measurements of C-reactive protein (CRP), transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were performed over 4 preset time periods during the first 14 postbleed days (PBD) in addition to daily caloric intake. Factors associated with REE and NBAL were analyzed with multivariable linear regression. Hospital-acquired infections (HAI) were tracked daily for time-to-event analyses. Poor outcome at 3 months was defined as a modified Rankin Scale score ≥ 4 and assessed by multivariable logistic regression. There were 229 patients with an average age of 55 ± 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001), higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 ± 3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p = 0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at 3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p < 0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p = 0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p = 0.04). Negative NBAL after SAH is influenced by inflammation and associated with an increased risk of HAI and poor outcome. Underfeeding and systemic inflammation are potential modifiable risk factors for negative NBAL and poor outcome after SAH. © 2015 American Academy of Neurology.

Folate and Cobalamin Modify Associations between S-adenosylmethionine and Methylated Arsenic Metabolites in Arsenic-Exposed Bangladeshi Adults123

PubMed Central

Howe, Caitlin G.; Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Ilievski, Vesna; Slavkovich, Vesna; Alam, Shafiul; Siddique, Abu B.; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Chronic exposure to inorganic arsenic (InAs) through drinking water is a major problem worldwide. InAs undergoes hepatic methylation to form mono- and dimethyl arsenical species (MMA and DMA, respectively), facilitating arsenic elimination. Both reactions are catalyzed by arsenic (+3 oxidation state) methyltransferase (AS3MT) using S-adenosylmethionine (SAM) as the methyl donor, yielding the methylated product and S-adenosylhomocysteine (SAH), a potent product-inhibitor of AS3MT. SAM biosynthesis depends on folate- and cobalamin-dependent one-carbon metabolism. With the use of samples from 353 participants in the Folate and Oxidative Stress Study, our objective was to test the hypotheses that blood SAM and SAH concentrations are associated with arsenic methylation and that these associations differ by folate and cobalamin nutritional status. Blood SAM and SAH were measured by HPLC. Arsenic metabolites in blood and urine were measured by HPLC coupled to dynamic reaction cell inductively coupled plasma MS. In linear regression analyses, SAH was not associated with any of the arsenic metabolites. However, log(SAM) was negatively associated with log(% urinary InAs) (β: −0.11; 95% CI: −0.19, −0.02; P = 0.01), and folate and cobalamin nutritional status significantly modified associations between SAM and percentage of blood MMA (%bMMA) and percentage of blood DMA (%bDMA) (P = 0.02 and P = 0.01, respectively). In folate- and cobalamin-deficient individuals, log(SAM) was positively associated with %bMMA (β: 6.96; 95% CI: 1.86, 12.05; P < 0.01) and negatively associated with %bDMA (β: −6.19; 95% CI: −12.71, 0.32; P = 0.06). These findings suggest that when exposure to InAs is high, and methyl groups are limiting, SAM is used primarily for MMA synthesis rather than for DMA synthesis, contributing additional evidence that nutritional status may explain some of the interindividual differences in arsenic metabolism and, consequently, susceptibility to arsenic

Tonic-Clonic Activity at Subarachnoid Hemorrhage Onset: Impact on Complications and Outcome

PubMed Central

De Marchis, Gian Marco; Pugin, Deborah; Lantigua, Hector; Zammit, Christopher; Tadi, Prasanna; Schmidt, J. Michael; Falo, M. Cristina; Agarwal, Sachin; Mayer, Stephan A.; Claassen, Jan

2013-01-01

Objective Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital complications, including seizures, remains unclear. One study associated onset TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no other studies have confirmed this relationship. This study aims to assess the impact of onset TCA on in-hospital complications, poor functional outcome, mortality, and epilepsy at 3 months. Methods Analysis of a prospective study cohort of 1479 SAH patients admitted to Columbia University Medical Center between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified based on accounts of emergency care providers or family witnesses. Results TCA at onset was described in 170 patients (11%). Patients with onset TCA were younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%, P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral blood than those without onset TCA (all, P<0.001). After adjusting for known confounders, onset TCA was significantly associated with in-hospital seizures (OR 3.80, 95%-CI: 2.43–5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06–2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21–2.58, P = 0.003). At 3 months, however, onset TCA was not associated with poor functional outcome, mortality, and epilepsy after adjusting for age, admission clinical grade, and cisternal blood volume. Conclusions Onset TCA is not a rare event as it complicates 11% of cases of SAH. New and clinically relevant findings are the association of onset TCA with in-hospital seizures, pneumonia and delayed cerebral ischemia. Despite the increased risk of in-hospital complications, onset TCA is not associated with disability, mortality, and epilepsy at 3 months. PMID:23951155

Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

PubMed

Fan, Lin-Feng; He, Ping-You; Peng, Yu-Cong; Du, Qing-Hua; Ma, Yi-Jun; Jin, Jian-Xiang; Xu, Hang-Zhe; Li, Jian-Ru; Wang, Zhi-Jiang; Cao, Sheng-Long; Li, Tao; Yan, Feng; Gu, Chi; Wang, Lin; Chen, Gao

2017-11-01

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression

Dobutamine-induced high cardiac index did not prevent vasospasm in subarachnoid hemorrhage patients: a randomized controlled pilot study.

PubMed

Rondeau, Nelly; Cinotti, Raphaël; Rozec, Bertrand; Roquilly, Antoine; Floch, Hervé; Groleau, Nicolas; Michel, Patrick; Asehnoune, Karim; Blanloeil, Yvonnick

2012-10-01

Prevention of vasospasm is a challenging issue in subarachnoid hemorrhage (SAH) patients and the objective is to compare high dobutamine-induced cardiac index (CI) and high norepinephrine-induced hypertension for the prevention of vasospasm in SAH patients. Single center, single blind, controlled randomized study. Patients hospitalized in intensive care unit (ICU) for a moderate to severe SAH (WFNS grade ≥2) were randomized to receive dobutamine to reach a 25 % increase in cardiac index or norepinephrine to reach a mean arterial pressure ≥100 mmHg. Norepinephrine could be used in the dobutamine group to maintain a cerebral pressure perfusion ≥60 mmHg. Primary endpoint was the incidence of angiographic vasospasm in the first 14 days in the ICU setting, which was upheld by a cerebral arteriography. Secondary endpoints were the incidence of delayed ischemic deficits, duration of mechanical ventilation, and ICU length of stay (LOS). During the 3-year study, 41 patients were randomized. Six patients were excluded--3 because of consent withdrawal and 3 who did not receive the assigned treatment. Respectively, 17 and 18 patients in the dobutamine and the norepinephrine group were kept in analysis. Five (28 %) patients in the dobutamine group and 5 (27 %) patients in the norepinephrine group developed vasospasm in ICU (p = 1). Seven (41 %) patients presented a delayed ischemic deficit in the dobutamine group and 9 (50 %) in the norepinephrine group (p = 0.24). Duration of mechanical ventilation was 8 [0.5-11.5] days in the dobutamine group and 19 [2.7-23] days in the norepinephrine group (p = 0.01). ICU LOS was 11 [6-15] days in the dobutamine group and 21 [9-28] days in the norepinephrine group (p = 0.01). As compared to norepinephrine-induced hypertension, dobutamine-induced high CI did not reduce the rate of vasospasm in SAH patients. Dobutamine may reduce durations of mechanical ventilation and ICU LOS.

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

PubMed Central

2013-01-01

Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

The association between weather conditions and stroke admissions in Turkey

NASA Astrophysics Data System (ADS)

Çevik, Yunsur; Doğan, Nurettin Özgür; Daş, Murat; Ahmedali, Asliddin; Kul, Seval; Bayram, Hasan

2015-07-01

Although several factors such as cigarette smoking, blood pressure, diabetes, obesity, hypercholesterolemia, physical inactivity and dietary factors have been well documented to increase the risk for stroke, there are conflicting data about the role of meteorological variables in the etiology of stroke. We conducted a retrospective study to investigate the association between weather patterns, including daily temperature, humidity, wind speed, and air pressure, and stroke admissions to the Emergency Department of Atatürk Training and Research Hospital in Ankara, Turkey, between January 2009 and April 2010. Generalized additive models with logistic link function were used to investigate the relationship between predictors and days with and without stroke admission at lags 0-4. A total of 373 stroke patients were admitted to the emergency department (ED) between January 2009 and April 2010. Of patients, 297 had ischemic stroke (IS), 34 hemorrhagic stroke (HS), and 42 subarachnoidal hemorrhage (SAH). Although we did not find any association between overall admissions due to stroke and meteorological parameters, univariable analysis indicated that there were significantly more SAH cases on days with lower daily mean temperatures of 8.79 ± 8.75 °C as compared to relatively mild days with higher temperatures (mean temperature = 11.89 ± 7.94 °C, p = 0.021). The multivariable analysis demonstrated that admissions due to SAH increased on days with lower daily mean temperatures for the same day (lag 0; odds ratio (OR) [95 % confidence interval (95 % CI)] = 0.93 [0.89-0.98], p = 0.004) and lag 1 (OR [95 % CI] =0.76 [0.67-0.86], p = 0.001). Furthermore, the wind speed at both lag 1 (OR [95 % CI] = 1.63 [1.27-2.09], p = 0.001) and lag 3 (OR [95 % CI] = 1.43 [1.12-1.81], p = 0.004) increased admissions due to HS, respectively. In conclusion, our study demonstrated that there was an association between ED admissions due to SAH and HS and weather conditions suggesting that

Inflammation, negative nitrogen balance, and outcome after aneurysmal subarachnoid hemorrhage

PubMed Central

Monahan, Aimee; Carpenter, Amanda; Zimmerman, Jacqueline; Schmidt, J. Michael; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.; Karmally, Wahida; Seres, David

2015-01-01

Objective: To analyze the impact of inflammation and negative nitrogen balance (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH). Methods: This was a prospective observational study of SAH patients admitted between May 2008 and June 2012. Measurements of C-reactive protein (CRP), transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were performed over 4 preset time periods during the first 14 postbleed days (PBD) in addition to daily caloric intake. Factors associated with REE and NBAL were analyzed with multivariable linear regression. Hospital-acquired infections (HAI) were tracked daily for time-to-event analyses. Poor outcome at 3 months was defined as a modified Rankin Scale score ≥4 and assessed by multivariable logistic regression. Results: There were 229 patients with an average age of 55 ± 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001), higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 ± 3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p = 0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at 3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p < 0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p = 0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p = 0.04). Conclusions: Negative NBAL after SAH is influenced by inflammation and associated with an increased risk of HAI and poor outcome. Underfeeding and systemic inflammation are potential modifiable risk factors for negative NBAL and poor outcome after SAH. PMID:25596503

Springtails in the Classroom: Collembola as Model Organisms for Inquiry-based Laboratories.

ERIC Educational Resources Information Center

Moore, John C.; Tripp, Bradley B.; Simpson, Rod T.; Coleman, David C.

2000-01-01

Advocates the use of springtails (Collembola) in the K-12 classroom as a model invertebrate that can easily be reared and manipulated to demonstrate key concepts in biology. Describes experimental procedures using springtails. (SAH)

Variations of pituitary function over time after brain injuries: the lesson from a prospective study.

PubMed

Giordano, Giulio; Aimaretti, Gianluca; Ghigo, Ezio

2005-01-01

Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH) are conditions at high risk to develop hypopituitarism as pointed out by many papers in scientific literature. But most of the papers were referred to retrospective evaluations, not considering the possible evolution of the pituitary function over time. Aim of our studies was to clarify whether pituitary deficiencies and normal pituitary function recorded at short term follow-up (3 months), would improve or worsen, respectively, at long term (12 months after the brain injury). In a multicenter study protocol, in patients who suffered TBI (n = 70; 50 Males, 20 Females; age 39.31 +/- 2.4 years; BMI 23.8 +/- 0.4 kg/m(2)) or SAH (n = 32; 12M, 20F; age: 51.9 +/- 2.2 year; BMI: 24.7 +/- 0.6 kg/m(2)) we tested 3 and 12 months after the pathological events the pituitary function. In TBI patients, the 3 month evaluation had shown some degree of hypopituitarism in 32.8% and the 12 months retesting demonstrated some degree of hypopituitarism in 22.7%. Total hypopituitarism was always confirmed at 12 months while Multiple and Isolated deficits recorded at 3 months was confirmed in nearly 25% only of the patients. On the other hand, in 5.5% of TBI with normal pituitary function at 3 months Isolated deficits were recorded at 12 months testing. Moreover, in 13.3% of TBI with Isolated deficit at 3 months Multiple hypopituitarism was demonstrated at 12 months retesting. In SAH patients, the 3 months evaluation had shown some degree of hypopituitarism in 46.8% and the 12 month retesting demonstrated some degree of hypopituitarism in 37.5%. No multiple hypopituitarism recorded at 3 months was confirmed at 12 months, but 2 patients with isolated deficits at 3 months showed multiple hypopituitarism at 12 month retesting. At 12 as well as at 3 months, both in TBI and SAH patients, the most common deficit was severe GHD (>20%) followed by secondary hypogonadism and then hypoadrenalism and hypothyroidism. In all, in patients

Effects of decompressive craniectomy on functional outcomes and death in poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

PubMed

Alotaibi, Naif M; Elkarim, Ghassan Awad; Samuel, Nardin; Ayling, Oliver G S; Guha, Daipayan; Fallah, Aria; Aldakkan, Abdulrahman; Jaja, Blessing N R; de Oliveira Manoel, Airton Leonardo; Ibrahim, George M; Macdonald, R Loch

2017-12-01

OBJECTIVE Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH. METHODS A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1-3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5-8) or unfavorable outcome (mRS Scores 4-6, GOS Scores 1-3, GOSE Scores 1-4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model. RESULTS Fifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%-69%) and for death was 27.8% (95% CI 21%-35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%-64%] vs 74.4% [95% CI 43%-91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1-3 months after discharge among patients who did not undergo DC (OR 0.58 [95% CI 0.27-1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.

PubMed

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi

2006-03-01

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.

Meteorology Online.

ERIC Educational Resources Information Center

Kahl, Jonathan D. W.

2001-01-01

Describes an activity to learn about meteorology and weather using the internet. Discusses the National Weather Service (NWS) internet site www.weather.gov. Students examine maximum and minimum daily temperatures, wind speed, and direction. (SAH)

The Antimicrobial Properties of Red Algae. The Fight of Your Life: Battling Bacteria.

ERIC Educational Resources Information Center

Case, Christine L.; Warner, Michael

2001-01-01

Describes a research project in which a professor and a student collaborated in the screening of macroscopic algae for antimicrobial properties. Includes background information, materials and methods, results, and a discussion of the experiment. (SAH)

Learning from Landfills.

ERIC Educational Resources Information Center

Galus, Pamela

2000-01-01

Describes a project in which students developed an all-class laboratory activity called "The Decomposition of Organic and Inorganic Substances in a Landfill". Explores what conditions are necessary to facilitate decomposition in a landfill. (SAH)

Switch On Student Interest.

ERIC Educational Resources Information Center

Nelson, Jane B.

2000-01-01

Describes a set of laboratory activities in which students construct a model for the relationship between potential difference (measured in volts) and current (measured in amperes) in a DC circuit with a single resistor. (SAH)

Heat and Kinetic Theory in 19th-Century Physics Textbooks: The Case of Spain.

ERIC Educational Resources Information Center

Vaquero, Jose M.; Santos, Andres

2001-01-01

Presents an analysis of the contents of 19th century Spanish textbooks. These textbooks are centered on imponderable fluids, the concept of energy, the mechanical theory of heat, and the kinetic theory of gases. (SAH)

Dealing with Behavioral Problems: Rules of Comportment in the Science Lecture.

ERIC Educational Resources Information Center

Druger, Marvin

2001-01-01

Highlights some ways that instructors of large lecture classes can effectively deal with such issues as inappropriate talking; tardiness; leaving early; sleeping, eating, or drinking during class; listening to music; or simply being discourteous. (SAH)

Presenting Science in a Video-Delivered, Web-based Format: Comparing Learning Settings To Get the Most Out of Teaching.

ERIC Educational Resources Information Center

Urven, Lance E.; Yin, L. Roger; Eshelman, Bruce D.; Bak, John D.

2000-01-01

Describes a high school course entitled "Science Technology in Society". High school students use live video presentations and world wide web courseware. Concludes that distance learning students performed as well as traditionally instructed students. (SAH)

The Bird.

ERIC Educational Resources Information Center

Hannon, Jean

2001-01-01

Students use a dead bird to learn about bird life, anatomy, and death. Students examine a bird body and discuss what happened to the bird. Uses outdoor education as a resource for learning about animals. (SAH)

Fishing for Seeds.

ERIC Educational Resources Information Center

Science and Children, 2001

2001-01-01

Describes a method to collect seeds that are dispersed from weeds while avoiding some outdoor hazards such as rough terrain or animals. Describes a plan for creating a weed fishing pole and includes a materials list. (SAH)

Variations in the Prevalence of Risk Factors for Coronary Artery Disease in Rio Grande do Sul-Brazil: A Comparative Analysis between 2002 and 2014

PubMed Central

Gus, Iseu; Ribeiro, Rodrigo Antonini; Kato, Sérgio; Bastos, Juliano; Medina, Claudio; Zazlavsky, Claudio; Portal, Vera Lucia; Timmers, Rita; Markoski, Melissa Medeiros; Gottschall, Carlos Antônio Mascia

2015-01-01

Background Due to the importance of coronary artery disease (CAD), continuous investigation of the risk factors (RFs) is needed. Objective To evaluate the prevalence of RFs for CAD in cities in Rio Grande do Sul State, and compare it with that reported in a similar study conducted in the same cities in 2002. Methods Cross-sectional study on 1,056 healthy adults, investigating the prevalence and absolute and relative frequencies of the following RFs for CAD: obesity, systemic arterial hypertension (SAH), dyslipidemias, smoking, sedentary lifestyle, diabetes mellitus, and family history, as well as age and sex. Data was collected in 19 cities, host of the Offices of the Regional Coordinators of Health, as in the 2002 study. Results Twenty-six percent of the sample consisted of older adults and 57% were women. The prevalence of sedentary lifestyle was 44%, history family 50%, smoking 23%, overweight/obesity 68%, dyslipidemia (high cholesterol levels) 43%, SAH 40%, and diabetes 11%. When compared to the 2002 study, the prevalence of active smoking and sedentary behavior decreased, whereas the prevalence of hypertension, dyslipidemia and obesity increased. Obesity is the most prevalent RF in women, and SAH the most prevalent in men. Conclusions The prevalence of RFs for CAD in Rio Grande do Sul State remains high. Hypertension, obesity and dyslipidemia are still prevalent and require major prevention programs. Smoking and physical inactivity have decreased in the state, suggesting the efficacy of related campaigns. PMID:26761368

Cognition and adjustment after late and early operation for ruptured aneurysm.

PubMed

Sonesson, B; Ljunggren, B; Säveland, H; Brandt, L

1987-09-01

Does early aneurysm operation, while lowering the overall management mortality, result in an unacceptable morbidity in terms of increased cognitive disturbances and psychosocial maladjustment? The present study evaluates quality of life, degree of cognitive dysfunction, and adjustment of 93 patients with satisfactory neurological recoveries after operations for ruptured supratentorial aneurysms. All patients had been in neurological Grades I to III (Hunt and Hess) after subarachnoid hemorrhage (SAH). Fifty-five patients were operated upon during the acute state, i.e., within 72 hours after bleeding (early surgery = ES), and 38 patients had been subjected to late surgery (LS), i.e., were operated on 9 days or more after SAH. Each patient was subjected to a clinical interview and a comprehensive neuropsychological investigation. The time interval between SAH and assessment varied between 12 and 103 months (mean, 56 months). The results confirm that there are indication of cognitive malfunctioning and psychosocial disturbances of varying severity and distribution in patients who have undergone LS. The pattern and distribution of sequelae after LS did not differ substantially from that in patients subjected to ES. The results offer strong support to the concept that remaining disturbances in cognition are mainly related to the impact of the initial hemorrhage per se. In patients with anterior communicating artery aneurysms, a larger decrease in tempo and perceptual vigilance was noted, suggesting that the subfrontal midline structures are particularly involved in processes demanding flexibility, attention, and capacity to adapt to novel demands in a perceptual situation.

Reduced CBF recovery detected by longitudinal 3D-SSP SPECT analyses predicts outcome of postoperative patients after subarachnoid haemorrhage.

PubMed

Mutoh, Tatsushi; Totsune, Tomoko; Takenaka, Shunsuke; Tatewaki, Yasuko; Nakagawa, Manabu; Suarez, Jose I; Taki, Yasuyuki; Ishikawa, Tatsuya

2018-02-01

The aim of this study was to evaluate the impact of cerebral blood flow (CBF) recovery obtained from brain single-photon emission computed tomography (SPECT) images on postoperative outcome after aneurysmal subarachnoid haemorrhage (SAH). Twenty-nine patients who had undergone surgical clipping for ruptured anterior communicating artery aneurysms were analyzed prospectively. Routine measurements of CBF were performed using technetium-99 m hexamethyl propyleneamine oxine SPECT on days 4 and 14 after SAH. Regional voxel data analyzed by three dimensional stereotactic surface projection (3D-SSP) were compared between patients and age-matched normal database (NDB). In 3D-SSP analysis of all patients, cortical hypoperfusion around the surgical site in bilateral frontal lobes was evident on day 4 (P < .05 vs NDB), which was improved significantly on day 14. However, the recovery was less complete in patients with poor clinical grades (P < .05) and presenting symptoms attributable to delayed cerebral ischaemia (DCI) (P < .05) than those without. Multivariate analysis showed that patients with mild to moderate CBF recovery (relative Z-score differences of <4) (P = .014; odds ratio, 2.5; 95% confidence interval, 1.93-3.31) was independently associated with poor functional outcome at 3 months. We conclude that reduced CBF recovery detected by serial 3D-SSP SPECT image analyses can be a potential predictor of poor prognosis in postoperative patients after SAH. © 2017 John Wiley & Sons Australia, Ltd.

Variations in the Prevalence of Risk Factors for Coronary Artery Disease in Rio Grande do Sul-Brazil: A Comparative Analysis between 2002 and 2014.

PubMed

Gus, Iseu; Ribeiro, Rodrigo Antonini; Kato, Sérgio; Bastos, Juliano; Medina, Claudio; Zazlavsky, Claudio; Portal, Vera Lucia; Timmers, Rita; Markoski, Melissa Medeiros; Gottschall, Carlos Antônio Mascia

2015-12-01

Due to the importance of coronary artery disease (CAD), continuous investigation of the risk factors (RFs) is needed. To evaluate the prevalence of RFs for CAD in cities in Rio Grande do Sul State, and compare it with that reported in a similar study conducted in the same cities in 2002. Cross-sectional study on 1,056 healthy adults, investigating the prevalence and absolute and relative frequencies of the following RFs for CAD: obesity, systemic arterial hypertension (SAH), dyslipidemias, smoking, sedentary lifestyle, diabetes mellitus, and family history, as well as age and sex. Data was collected in 19 cities, host of the Offices of the Regional Coordinators of Health, as in the 2002 study. Twenty-six percent of the sample consisted of older adults and 57% were women. The prevalence of sedentary lifestyle was 44%, history family 50%, smoking 23%, overweight/obesity 68%, dyslipidemia (high cholesterol levels) 43%, SAH 40%, and diabetes 11%. When compared to the 2002 study, the prevalence of active smoking and sedentary behavior decreased, whereas the prevalence of hypertension, dyslipidemia and obesity increased. Obesity is the most prevalent RF in women, and SAH the most prevalent in men. The prevalence of RFs for CAD in Rio Grande do Sul State remains high. Hypertension, obesity and dyslipidemia are still prevalent and require major prevention programs. Smoking and physical inactivity have decreased in the state, suggesting the efficacy of related campaigns.

Effect of stress hyperglycemia and intensive rehabilitation therapy in non-diabetic hemorrhagic stroke: Korean Stroke Cohort for Functioning and Rehabilitation.

PubMed

Yoon, J A; Kim, D Y; Sohn, M K; Lee, J; Lee, S-G; Lee, Y-S; Han, E Y; Joo, M C; Oh, G-J; Han, J; Lee, S W; Park, M; Chang, W H; Shin, Y-I; Kim, Y-H

2016-11-01

We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke. © 2016 EAN.

Newton and Colour: The Complex Interplay of Theory and Experiment.

ERIC Educational Resources Information Center

Martins, Roberto De Andrade; Silva, Cibelle Celestino

2001-01-01

Elucidates some aspects of Newton's theory of light and colors, specifically as presented in his first optical paper in 1672. Analyzes Newton's main experiments intended to show that light is a mixture of rays with different refrangibilities. (SAH)

Habitat Sweet Habitat.

ERIC Educational Resources Information Center

Aram, Roberta J.; Whitson, Sherry; Dieckhoff, Rosemarie

2001-01-01

Describes a successful simulation that explores animal camouflage and the fundamental idea that organisms depend on their environment. Uses a story from a basal reader to facilitate student learning; however, other trade books could also be used. (SAH)

Supplemental nutrition assistance program participation and health: Evidence from low-income individuals in Tennessee

USDA-ARS?s Scientific Manuscript database

We investigate the factors that contribute to participation in the Supplemental Nutrition Assistance Program (SNAP), and the effects of such participation on self-assessed health (SAH). An endogenous switching ordered probability model is developed with alternative error distributional assumptions, ...

Plant Tissue Culture in a Bag.

ERIC Educational Resources Information Center

Beck, Mike

2000-01-01

Describes the use of an oven bag as a sterile chamber for culture initiation and tissue transfer. Plant tissue culture is an ideal tool for introducing students to plants, cloning, and experimental design. Includes materials, methods, discussion, and conclusion sections. (SAH)

75 FR 57859 - Specially Adapted Housing and Special Home Adaptation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... Home Adaptation AGENCY: Department of Veterans Affairs. ACTION: Final rule. SUMMARY: The Department of... specially adapted housing and special home adaptation grants. This final rule incorporates certain... regulations pertaining to eligibility for specially adapted housing (SAH) grants and special home adaptation...

Animal Watching: Outdoors and In.

ERIC Educational Resources Information Center

McLure, John W.

2001-01-01

Describes using domesticated, wild, or feral animals to teach students about nature and animal behavior. Connections can be made with psychology, economics, genetics, history, art, and other disciplines. The study of animal behavior provides opportunities for harmless student experimentation. (SAH)

Comparing counselling models for the hazardous use of alcohol at the Swedish National Alcohol Helpline: study protocol for a randomised controlled trial.

PubMed

Säfsten, Eleonor; Forsell, Yvonne; Ramstedt, Mats; Galanti, Maria Rosaria

2017-06-06

Hazardous and harmful consumption of alcohol is a leading cause of preventable disease and premature deaths. Modifying the amount and pattern of risky alcohol consumption conveys substantial benefits to individuals and to society at large. Telephone helplines provide a feasible alternative to face-to-face counselling in order to increase the reach of brief interventions aiming at modifying the hazardous and harmful use of alcohol. However, there is a lack of studies on the implementation and evaluation of population-based telephone services for the prevention and treatment of alcohol misuse. A randomised controlled trial was designed to compare a brief, structured intervention to usual care within the Swedish National Alcohol Helpline (SAH), concerning their effectiveness on decreasing the hazardous use of alcohol. Between May 2015 and December 2017, about 300 callers are to be individually randomised with a 1:1 ratio to a brief, structured intervention (n = 150) or to usual care (n = 150). The brief, structured intervention consists of the delivery of a self-help booklet followed by one proactive call from SAH counsellors to monitor and give feedback about the client's progression. Callers assigned to usual care receive telephone counselling according to existing practice, i.e., motivational interviewing in a tailored and client-driven combination of proactive and reactive calls. The primary outcome is defined as a change from a higher to a lower AUDIT risk-level category between baseline and follow-up. General linear modeling will be used to calculate risk ratios of the outcome events. The primary analysis will follow an intention-to-treat (ITT) approach. The trial is designed to evaluate the effectiveness in decreasing the hazardous and harmful consumption of alcohol of a brief, structured intervention compared to usual care when delivered at the SAH. The results of the study will be used locally to improve the effectiveness of the service provided at