Science.gov

Sample records for spinal subarachnoid hemorrhage

  1. Subarachnoid hemorrhage

    MedlinePlus

    ... injury leading to subarachnoid hemorrhage is motor vehicle crashes. Risks include: Aneurysm in other blood vessels Fibromuscular ... lumbar puncture ( spinal tap ) may be done. Other tests that may be done include: Cerebral angiography of ...

  2. Subarachnoid hemorrhage

    MedlinePlus

    ... malformation (AVM) Bleeding disorder Bleeding from a cerebral aneurysm Head injury Unknown cause (idiopathic) Use of blood ... subarachnoid hemorrhage is motor vehicle crashes. Risks include: Aneurysm in other blood vessels Fibromuscular dysplasia (FMD) and ...

  3. Spinal axis imaging in non-aneurysmal subarachnoid hemorrhage: a prospective cohort study.

    PubMed

    Germans, Menno R; Coert, Bert A; Majoie, Charles B L M; van den Berg, René; Verbaan, Dagmar; Vandertop, W Peter

    2014-11-01

    In 15 % of all spontaneous subarachnoid hemorrhages (SAH), no intracranial vascular pathology is found. Those non-aneurysmal hemorrhages are categorized into perimesencephalic SAH (PMSAH) and non-perimesencephalic SAH (NPSAH). Searching for spinal pathology might reveal a cause for the hemorrhage in some patients. Our goal was to assess the yield of magnetic resonance (MR) imaging of the complete spinal axis in search for a spinal origin in non-aneurysmal SAH. In a prospective, observational study at a tertiary SAH referral center, we assessed clinical and radiological characteristics of patients who consecutively presented with spontaneous non-aneurysmal SAH, diagnosed by computed tomography (CT) or lumbar puncture, and negative CT angiography and digital subtraction angiography (DSA). Eligible patients were enrolled for investigation of the complete spinal axis by standard T1- and T2-weighted MR-imaging. Ninety-seven non-aneurysmal SAH patients were included in the study. Baseline characteristics were comparable between PMSAH and NPSAH patients. DSA and spinal MR-imaging were performed in 95 and 91 % of patients, respectively. This revealed one lumbar ependymoma in a 43-year-old male who was diagnosed by LP (yield 1 %). No spinal origin for the SAH was found in 51 PMSAH patients. The yield of MR-imaging of the complete spinal axis in spontaneous non-aneurysmal SAH patients is low. Routine radiological investigation of the spinal axis in non-aneurysmal SAH patients is therefore not recommended. PMID:25182702

  4. Solitary ruptured aneurysm of the spinal artery of adamkiewicz with subarachnoid hemorrhage.

    PubMed

    Son, Seong; Lee, Sang-Gu; Park, Cheol-Wan

    2013-07-01

    Spinal subarachnoid hemorrhage (SAH) due to solitary spinal aneurysm is extremely rare. A 45-year-old female patient visited the emergency department with severe headache and back pain. Imaging studies showed cerebral SAH in parietal lobe and spinal SAH in thoracolumbar level. Spinal angiography revealed a small pearl and string-like aneurysm of the Adamkiewicz artery at the T12 level. One month after onset, her back pain aggravated, and follow-up imaging study showed arachnoiditis. Two months after onset, her symptoms improved, and follow-up imaging study showed resolution of SAH. The present case of spinal SAH due to rupture of dissecting aneurysm of the Adamkiewicz artery underwent subsequent spontaneous resolution, indicating that the wait-and-see strategy may provide adequate treatment option. PMID:24044082

  5. Subarachnoid Hemorrhage

    MedlinePlus

    ... can result from the rupture of an intracranial aneurysm — a weakened, dilated area of a blood vessel ... blood vessels in the brain even after the aneurysm that caused the hemorrhage is treated. Most of ...

  6. Spontaneous resolution of an isolated cervical anterior spinal artery aneurysm after subarachnoid hemorrhage

    PubMed Central

    Pahl, Felix Hendrik; de Oliveira, Matheus Fernandes; Rotta, Marcus Alexandre Cavalcanti; Dias, Guilherme Marcos Soares; Rezende, André Luiz; Rotta, José Marcus

    2014-01-01

    Background: Isolated cervical anterior spinal artery aneurysms are extremely rare. Subarachnoid hemorrhage (SAH) secondary to such lesions have been described only in six cases to the best of our knowledge. Case Description: We describe an unusual clinical picture of SAH due to rupture of anterior spinal artery aneurysm in a patient with previous normal angiogram. Due to the location of the aneurysm and clinical status of the patient, conservative management was proposed, and she was discharged to further follow-up. Monthly routine angiograms revealed resolution of the aneurysm 90 days after bleeding, which was highly suggestive of vascular dissection. Conclusion: We highlight the need to consider these aneurysms in the differential diagnosis of SAH, especially when occurring in the posterior fossa and when angiography findings are inconclusive. PMID:25317354

  7. Successfully Treated Isolated Posterior Spinal Artery Aneurysm Causing Intracranial Subarachnoid Hemorrhage: Case Report

    PubMed Central

    HORIO, Yoshinobu; KATSUTA, Toshiro; SAMURA, Kazuhiro; WAKUTA, Naoki; FUKUDA, Kenji; HIGASHI, Toshio; INOUE, Tooru

    2015-01-01

    There are very few published reports of rupture of an isolated posterior spinal artery (PSA) aneurysm, and consequently the optimal therapeutic strategy is debatable. An 84-year-old man presented with sudden onset of restlessness and disorientation. Neuroradiological imaging showed an intracranial subarachnoid hemorrhage (SAH) with no visible intracranial vascular lesion. Spinal magnetic resonance imaging (MRI) detected a localized subarachnoid hematoma at Th10–11. Both contrast-enhanced spinal computed tomography and enhanced MRI and magnetic resonance angiography revealed an area of enhancement within the hematoma. Superselective angiography of the left Th12 intercostal artery demonstrated a faintly enhanced spot in the venous phase. Thirteen days after the onset of symptoms, a small fusiform aneurysm situated on the radiculopial artery was resected. The patient's postoperative course was uneventful and he was eventually discharged in an ambulatory condition. To our knowledge, this 84-year-old man is the oldest reported case of surgical management of a ruptured isolated PSA aneurysm. This case illustrates both the validity and efficacy of this therapeutic approach. PMID:26522607

  8. Subarachnoid Hemorrhage: An Update.

    PubMed

    Dority, Jeremy S; Oldham, Jeffrey S

    2016-09-01

    Subarachnoid hemorrhage (SAH) is a debilitating, although uncommon, type of stroke with high morbidity, mortality, and economic impact. Modern 30-day mortality is as high as 40%, and about 50% of survivors have permanent disability. Care at high-volume centers with dedicated neurointensive care units is recommended. Euvolemia, not hypervolemia, should be targeted, and the aneurysm should be secured early. Neither statin therapy nor magnesium infusions should be initiated for delayed cerebral ischemia. Cerebral vasospasm is just one component of delayed cerebral edema. Hyponatremia is common in subarachnoid hemorrhage and is associated with longer length of stay, but not increased mortality. PMID:27521199

  9. Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    D'Souza, Stanlies

    2015-07-01

    Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome. PMID:25272066

  10. Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    2015-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome. PMID:25272066

  11. Symptomatic Tarlov Cyst Following Spontaneous Subarachnoid Hemorrhage

    PubMed Central

    Kong, Woo Keun; Hong, Seung-Koan

    2011-01-01

    Most of Tarlov or perineurial cysts remain asymptomatic throughout the patient's life. The pathogenesis is still unclear. Hemorrhage has been suggested as one of the possible causes and trauma with resultant hemorrhage into subarachnoid space has been suggested as an origin of these cysts. However, Tarlov cysts related to spontaneous subarachnoid hemorrhage has not been reported. The authors report a case of Tarlov cyst which was symptomatic following spontaneous subarachnoid hemorrhage. PMID:22053232

  12. Use of cervical spinal cord stimulation in treatment and prevention of arterial vasospasm after aneurysmal subarachnoid hemorrhage. Technical details.

    PubMed

    Slavin, K V; Vannemreddy, P S S V; Goellner, E; Alaraj, A M; Aydin, S; Eboli, P; Mlinarevich, N; Watson, K S; Walters, L E; Amin-Hanjani, S; Deveshwar, R; Aletich, V; Charbel, F T

    2011-03-29

    Based on past laboratory and anecdotal clinical experience, we hypothesized that prolonged cervical spinal cord stimulation (SCS) in the acute settings of aneurysmal subarachnoid hemorrhage (aSAH) would be both safe and feasible, and that 2-week stimulation will reduce incidence of cerebral arterial vasospasm. The goal of our clinical study was to establish feasibility and safety of cervical SCS in a small group of selected aSAH patients. Single-arm non-randomized prospective study of cSCS in aSAH patients involved percutaneous implantation of 8-contact electrode in 12 consecutive aSAH patients that satisfied strict inclusion criteria. The electrode insertion was performed immediately upon surgical or endovascular securing of the ruptured aneurysm while the patient was still under general anesthesia. Patients were stimulated for 14 consecutive days or until discharge. There were no complications related to the electrode insertion or to SCS during the study and no long-term side effects of SCS during 1-year follow-up. There was 1 unrelated death and two electrode pullouts. This article summarizes technical details of SCS electrode insertion and the stimulation parameters used in the research study. Our study of SCS for prevention of vasospasm after aSAH conclusively shows both safety and feasibility of this promising treatment approach. Despite high level of acuity in aSAH patients, impaired level of consciousness, frequent patient re-positioning, need in multiple tests and variety of monitors, SCS electrodes may be safely implanted and maintained for the two-week period. Long-term follow up shows no adverse effects of cervical SCS in this patient category. PMID:24059581

  13. Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.

    PubMed

    Pinnamaneni, Sowmya; Dutta, Tanya; Melcer, Joshua; Aronow, Wilbert S

    2015-01-01

    Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes. PMID:25606704

  14. 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

  15. Ehrlichia Meningitis Mimicking Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Dredla, Brynn

    2015-01-01

    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. PMID:27053985

  16. [Subarachnoid hematoma and spinal anesthesia].

    PubMed

    Dupeyrat, A; Dequiré, P M; Mérouani, A; Moullier, P; Eid, G

    1990-01-01

    Two cases of spinal subarachnoid haematoma occurring after spinal anaesthesia are reported. In the first case, lumbar puncture was attempted three times in a 81-year-old man; spinal anaesthesia trial was than abandoned, and the patient given a general anaesthetic. He was given prophylactic calcium heparinate soon after surgery. On the fourth day, the patient became paraparetic. Radioculography revealed a blockage between T10 and L3. Laminectomy was performed to remove the haematoma, but the patient recovered motor activity only very partially. The second case was a 67-year-old man, in whom spinal anaesthesia was easily carried out. He was also given prophylactic calcium heparinate soon after surgery. On the fourth postoperative day, pulmonary embolism was suspected. Heparin treatment was then started. Twelve hours later, lumbar and bilateral buttock pain occurred, which later spread to the neck. On the eighth day, the patient had neck stiffness and two seizures. Emergency laminectomy was carried out, which revealed a subarachnoid haematoma spreading to a level higher than T6 and below L1, with no flow of cerebrospinal fluid, and a non pulsatile spinal cord. Surgery was stopped. The patient died on the following day. Both these cases are similar to those previously reported and point out the role played by anticoagulants. Because early diagnosis of spinal cord compression is difficult, the prognosis is poor, especially in case of paraplegia. PMID:2278424

  17. Spinal subarachnoid haematoma after spinal anaesthesia: case report.

    PubMed

    Vidal, Marion; Strzelecki, Antoine; Houadec, Mireille; Krikken, Isabelle Ranz; Danielli, Antoine; Souza Neto, Edmundo Pereira de

    2016-01-01

    Subarachnoid haematoma after spinal anaesthesia is known to be very rare. In the majority of these cases, spinal anaesthesia was difficult to perform and/or unsuccessful; other risk factors included antiplatelet or anticoagulation therapy, and direct spinal cord trauma. We report a case of subarachnoid haematoma after spinal anaesthesia in a young patient without risk factors. PMID:27591468

  18. The clinical significance of small subarachnoid hemorrhages.

    PubMed

    Albertine, Paul; Borofsky, Samuel; Brown, Derek; Patel, Smita; Lee, Woojin; Caputy, Anthony; Taheri, M Reza

    2016-06-01

    With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests

  19. [Diagnostic challenges of aneurysmal subarachnoid hemorrhage].

    PubMed

    Vehviläinen, Juho; Niemelä, Mika; Korja, Miikka

    2016-01-01

    Diagostic approach to aneurysmal subarachnoid hemorrhage (aSAH) is based on computer tomography (CT) imaging, although a lumbar puncture and subsequent cerebrospinal fluid analysis is sometimes necessary. Identification of the ruptured aneurysm is done using angiography. Despite of modern imaging techniques, diagnostic definition of aSAH is still occasionally challenging. We describe three cases in which the diagnosis of aSAH has been delayed, in spite of positive imaging or lumbar puncture findings. PMID:27089620

  20. Jugular Foramen Arteriovenous Shunt with Subarachnoid Hemorrhage

    PubMed Central

    Rodesch, G.; Comoy, J.; Hurth, M.; Lasjaunias, P.

    1991-01-01

    The authors report the case of a 37-year-old man with an extracerebral arteriovenous fistula at the skull base, revealed by subarachnoid and intraventricular hemorrhage. The malformation was fed by the neuromeningeal trunk of the ascending pharyngeal artery and drained into left laterobulbar veins. Embolization with bucrylate was performed and occluded totally the shunting zone. A 1-year follow-up angiogram confirmed the good stability of the result, the patient being asymptomatic. This case emphasizes the quality of results that can be obtained with bucrylate in arterioverious fistulas presenting with hemorrhage. It confirms that the external carotid artery must be studied when dealing with intracranial hemorrhage. On the other hand, magnetic resonance imaging and angiography may depict vascular abnormalities but do not always indicate the shunting area, thus the pathologic type of the malformation. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 5p136-b PMID:17170835

  1. [Continuous EEG monitoring for aneurysmal subarachnoid hemorrhage].

    PubMed

    Pugin, D; Vulliemoz, S; Bijlenga, P; Gasche, Y

    2014-12-10

    Subarachnoid hemorrhage (SAH) still carries a high morbidity and mortality, despite improvement in surgical and medical management. Seizures and delayed cerebral ischemia (DCI) secondary to vasospasm or cortical spreading depression are frequent after SAH. Continuous EEG allows early detection of non-convulsive seizures or delayed cerebral ischemia and may become a promissing tool in the monitoring of SAH patients. However, its use in clinical practice is still limited because many resources are required for recording and analyzing continuous EEG. Moreover, we require more data to confirm the relationship between aggressive treatment of non-convulsive seizure or delayed cerebral ischemia triggered by continuous EEG and outcome. PMID:25632630

  2. Magnesium sulfate administration in subarachnoid hemorrhage.

    PubMed

    Suarez, Jose I

    2011-09-01

    Magnesium offers theoretic vascular and neuroprotective benefits for patients with subarachnoid hemorrhage. An electronic literature search was conducted to identify original research studies describing intravenous magnesium treatment in patients with SAH published in English between January 1990 and October 2010. Seventeen articles were identified and reviewed, including one phase III randomized-controlled clinical trial and six phase II randomized-controlled trials. Study quality was low for most of the included studies, with the phase III trial considered to be of moderate quality. Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial. PMID:21748496

  3. Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non-perimesencephalic

    PubMed Central

    Coelho, Luís Guilherme Bastos Silva Aguiar; Costa, José Manuel Dias; Silva, Elsa Irene Peixoto Azevedo

    2016-01-01

    Objective To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Methods The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Results Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 ± 10.3 months). Conclusion Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources. PMID:27410409

  4. Surgical management of aneurysmal subarachnoid hemorrhage.

    PubMed

    Colby, Geoffrey P; Coon, Alexander L; Tamargo, Rafael J

    2010-04-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a common and often devastating condition that requires prompt neurosurgical evaluation and intervention. Modern management of aSAH involves a multidisciplinary team of subspecialists, including vascular neurosurgeons, neurocritical care specialists and, frequently, neurointerventional radiologists. This team is responsible for stabilizing the patient on presentation, diagnosing the offending ruptured aneurysm, securing the aneurysm, and managing the patient through a typically prolonged and complicated hospital course. Surgical intervention has remained a definitive treatment for ruptured cerebral aneurysms since the early 1900s. Over the subsequent decades, many innovations in microsurgical technique, adjuvant maneuvers, and intraoperative and perioperative medical therapies have advanced the care of patients with aSAH. This report focuses on the modern surgical management of patients with aSAH. Following a brief historical perspective on the origin of aneurysm surgery, the topics discussed include the timing of surgical intervention after aSAH, commonly used surgical approaches and craniotomies, fenestration of the lamina terminalis, intraoperative neurophysiological monitoring, intraoperative digital subtraction and fluorescent angiography, temporary clipping, deep hypothermic cardiopulmonary bypass, management of acute hydrocephalus, cerebral revascularization, and novel clip configurations and microsurgical techniques. Many of the topics highlighted in this report represent some of the more debated techniques in vascular neurosurgery. The popularity of such techniques is constantly evolving as new studies are performed and data about their utility become available. PMID:20380967

  5. Post-traumatic subarachnoid hemorrhage: A review.

    PubMed

    Modi, Nikhilkumar J; Agrawal, Manish; Sinha, Virendra Deo

    2016-01-01

    Head injury has been the leading cause of death and disability in people younger than 40 years and the incidence is rising continuously. Anticipation of the pathological consequences of post-traumatic subarachnoid hemorrhage (tSAH) and an outcome-oriented management are very important in these cases. To encounter the complications pertaining to traumatic brain injury (TBI) and tSAH, various classifications have been proposed and goal-oriented screening strategies have been offered. The role of serial computed tomography (CT) scans, perfusion studies, transcranial Doppler, magnetic resonance imaging (MRI), and angiographic studies as diagnostic tools, has been described. Recently, MRI fluid-attenuated inversion recovery (FLAIR), gradient reversal echo (GRE), and susceptibility weighted imaging (SWI) have emerged as excellent complimentary MRI sequences, and the authors of this article have evaluated their role in the diagnosis and prognostication of patients with tSAH. Numerous studies have been conducted on the various complications associated with tSAH such as vasospasm, hydrocephalus, and electrolyte disturbances and their management. This article discusses these aspects of tSAH and their management nuances. PMID:26954974

  6. Reversible cerebral vasoconstriction syndrome and nonaneurysmal subarachnoid hemorrhage

    PubMed Central

    Barboza, Miguel A; Maud, Alberto; Rodriguez, Gustavo J

    2014-01-01

    Background Reversible cerebral vasoconstriction syndrome was first described by Call, Fleming, and colleagues. Clinically this entity presents acutely, with severe waxing and waning headaches (“thunderclap”), and occasional fluctuating neurological signs. Case presentation We present four subsequent cases of patients with severe thunderclap headache and brain tomography with evidence of subarachnoid hemorrhage. The brain angiogram showed no aneurysm but intracranial vasculopathy consistent with multiple areas of stenosis and dilatation (angiographic beading) in different territories. Conclusion Neurologists should be aware of Call Fleming syndrome presenting with severe headache and associated convexity subarachnoid hemorrhage. After other diagnoses are excluded, patients can be reassured about favorable prognosis with symptomatic management. Abbreviations RCVS Reversible cerebral vasoconstriction syndrome CT Computed tomography SAH Subarachnoid hemorrhage MR Magnetic resonance CTA Computed tomography angiography MRA Magnetic resonance angiography PMID:25132905

  7. The distribution of intravenous nicardipine in rat brain after subarachnoid hemorrhage

    SciTech Connect

    Tsukahara, T.; Arista, A.; Kassell, N.F. )

    1989-09-01

    The distribution of intravenously injected nicardipine in rat brain was investigated, as well as the influence of subarachnoid hemorrhage on its distribution. Autoradiographic studies demonstrated the accumulation of {sup 3}H-nicardipine only in the ventricles and subarachnoid spaces around pial vessels in normal brains. Thirty minutes after subarachnoid hemorrhage, the concentration of {sup 3}H-nicardipine was higher in the ventricles and in the subarachnoid space than that found in normal brains. It is concluded that nicardipine penetrates into the subarachnoid spaces and ventricles from pial vessels and/or choroid plexus, and that subarachnoid hemorrhage increases the penetration of nicardipine from vessels into the subarachnoid space.

  8. Acute management of poor condition subarachnoid hemorrhage patients

    PubMed Central

    Eleftherios, Archavlis; Carvi y Nievas, Mario Nazareno

    2007-01-01

    Poor condition subarachnoid hemorrhage (SAH) patients present a high mortality and morbidity. In this study, we reviewed the acute interventional (surgical and endovascular) management of 109 SAH-poor condition patients, who were treated as early as logistically possible after confirming stable circulation parameters. Patients over the age of 70 years, without clinical response to painful stimulation were excluded. We recognized at least 3 different postinterventional therapeutic approaches: (1) Norm- or hypovolemic, normotensive hemodilution in 30 patients with space-occupying intracranial hematomas as well as in 31 cases with acute cerebro-spinal-fluid obstruction. (2) Normovolemic, hypertensive hemodilution after unilateral decompressive craniotomy in 23 surgical- and 2 endovascular-treated patients with focalized space occupying lesions and reduced cerebral perfusion. (3) Hypovolemic, normo-, or hypertensive hemodilution after bilateral decompressive craniotomy in 23 cases with massive brain-swelling. We observed a reduced mortality (21%). The overall late outcome was favorable in 56% and unfavorable in 23%. Selective aggressive treatment adapted to increase the cerebral perfusion, seems to be an effective therapy to improve the survival and outcome of several poor condition SAH-patients. PMID:18200827

  9. Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review

    PubMed Central

    Lucke-Wold, Brandon P.; Logsdon, Aric F.; Manoranjan, Branavan; Turner, Ryan C.; McConnell, Evan; Vates, George Edward; Huber, Jason D.; Rosen, Charles L.; Simard, J. Marc

    2016-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials. PMID:27049383

  10. Thoracolumbar spinal vascular malformation as a rare cause of isolated intraventricular hemorrhage.

    PubMed

    Marlin, Evan S; Entwistle, John J; Arnold, Michael A; Pierson, Christopher R; Governale, Lance S

    2014-07-01

    Spinal vascular malformations are rare vascular lesions that most frequently present with back pain, radiculopathy, and/or myelopathy. Neurological decline is typically secondary to progressive radiculopathy, myelopathy, venous thrombosis, and stroke. Few case reports have described thoracolumbar spinal vascular malformations that present with both subarachnoid and intraventricular hemorrhage. This is the first reported case of a thoracolumbar spinal vascular malformation presenting with isolated intraventricular hemorrhage on initial imaging followed by acute and fatal rehemorrhage. PMID:24784978

  11. Subarachnoid hemorrhage as the initial presentation of cerebral venous thrombosis.

    PubMed

    Kato, Yuji; Takeda, Hidetaka; Furuya, Daisuke; Nagoya, Harumitsu; Deguchi, Ichiro; Fukuoka, Takuya; Tanahashi, Norio

    2010-01-01

    Cerebral venous thrombosis presenting as subarachnoid hemorrhage (SAH) is very rare. We present a woman with thrombosis of the superior sagittal, straight, transverse and sigmoid sinuses who presented with SAH in the right temporal sulcus and bilateral cerebellar sulci. Brain perfusion CT demonstrated a delay of the mean transit time and high cerebral blood volume around the right posterior temporal lobe and cerebellum. These findings were compatible with venous congestion and they suggest the possibility that extension of the dural sinus thrombosis into the superficial veins caused localized venous hypertension with dilatation of the thin, fragile-walled cortical veins which eventually ruptured into the subarachnoid space. PMID:20190485

  12. [A case of Churg-Strauss syndrome with subarachnoid hemorrhage].

    PubMed

    Ito, Miiko; Kato, Naoki; Su, Ching-Chan; Kayama, Takamasa

    2014-03-01

    Churg-Strauss syndrome (CSS) is a vasculitis syndromes and is only rarely complicated by subarachnoid hemorrhage. In the current report, we describe a case of CSS with subarachnoid hemorrhage, which showed a favorable outcome following conservative treatment. A 68-year-old man with CSS on maintenance steroid therapy underwent MRI/A during tinnitus aggravation, and showed dilation of the left middle cerebral artery and stenosis of the peripheral area of the right vertebral artery. After 2 months, he presented sudden pain in the occipitocervical area, and CT revealed subarachnoid hemorrhage. Intracranial 3D CT-A and MRI/A showed the development of a protrusion at the base of the left anterior cerebral artery. Although both findings suggested cerebral artery dissection, the source of hemorrhage could not be identified. The 2009 Japanese Guidelines for the Management of Stroke recommends early diagnosis and treatment of hemorrhagic cerebral artery dissection because of the high risk of re-bleeding. However, considering the risks of vasculitis aggravation, development of systemic complications, and recurrence, conservative treatment was selected. In addition, owing to the risk of complications associated with the frequent use of iodinated contrast agents and angiography procedures, patient was followed up using MRI. His course was favorable, and he was discharged despite mild right abducens paralysis. When patients with hemorrhagic cerebral artery dissection have a history of allergic diseases, CCS should be considered; conservative treatment consisting of rest, strict blood pressure control, and steroid therapy may be the most appropriate option for certain patients. PMID:24607952

  13. Brain Metastasis of Pleural Mesothelioma after a Subarachnoid Hemorrhage.

    PubMed

    Hirooka, Aya; Tamiya, Akihiro; Kanazu, Masaki; Nonaka, Junichi; Yonezawa, Taiji; Asami, Kazuhiro; Atagi, Shinji

    2016-01-01

    Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm induced by asbestos exposure. Brain metastases from MPM are extremely rare, with most such cases diagnosed only at the time of autopsy. This report describes what we believe to be the first case of MPM metastasizing to the brain after a subarachnoid hemorrhage, as well as the subsequent surgical removal of the brain metastasis. PMID:27041164

  14. Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection: is early surgical exploration warranted?

    PubMed

    Alexiades, Nikita G; Ellis, Jason A; Meyers, Philip M; Connolly, E Sander

    2016-06-01

    The natural history of spontaneous cerebral artery dissection and thrombosis remains uncertain. Concurrent subarachnoid hemorrhage further complicates the therapeutic approach. Thus the best strategy for managing patients with acute vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we present a case of spontaneous posterior inferior cerebellar artery dissection presenting with subarachnoid hemorrhage and acute thrombosis. Although the patient was initially managed conservatively, angiographic follow-up demonstrated recanalization of the diseased vessel, necessitating definitive treatment. Thus we propose that angiographic follow-up is necessary in the management of patients with subarachnoid hemorrhage in association with apparent vessel thrombosis. PMID:25987592

  15. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    PubMed

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation. PMID:26342279

  16. Encephalic hemodynamic phases in subarachnoid hemorrhage: how to improve the protective effect in patient prognoses

    PubMed Central

    de Lima Oliveira, Marcelo; de Azevedo, Daniel Silva; de Azevedo, Milena Krajnyk; de Carvalho Nogueira, Ricardo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2015-01-01

    Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses. PMID:26109948

  17. 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

  18. Current strategies for the management of aneurysmal subarachnoid hemorrhage.

    PubMed

    Solomon, R A; Fink, M E

    1987-07-01

    Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm represents a major health issue. Although most people who experience an aneurysmal SAH survive to be admitted to a hospital, less than one third of these patients ever return to their premorbid status. Clearly, morbidity of this magnitude demands reevaluation of the clinical approach to this problem. This article reviews the natural history of aneurysmal SAH, and examines the current therapeutic strategies that have been suggested to improve the outcome. Careful evaluation of the existing data suggests that early aneurysm surgery and aggressive postoperative volume expansion therapy constitute the best presently available approach to patients with ruptured intracranial aneurysms. PMID:3297009

  19. 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. PMID:27053985

  20. Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage.

    PubMed

    Hamming, Arend M; Wermer, Marieke Jh; Umesh Rudrapatna, S; Lanier, Christian; van Os, Hine Ja; van den Bergh, Walter M; Ferrari, Michel D; van der Toorn, Annette; van den Maagdenberg, Arn Mjm; Stowe, Ann M; Dijkhuizen, Rick M

    2016-07-01

    Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T2-weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233 mm(3)) than in the no-SD group (29 ± 54 mm(3)) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage. PMID:26661246

  1. 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

  2. Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage.

    PubMed

    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

  3. Relationship between Postmenopausal Estrogen Deficiency and Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Tabuchi, Sadaharu

    2015-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) is one of the most severe forms of stroke, which results from the rupture of a cerebral aneurysm. SAH is the only type of stroke with a female predominance, suggesting that reproductive factors may play a significant role in the etiology. Estrogen has important effects on vascular physiology and pathophysiology of cerebral aneurysm and SAH and, thus, potential therapeutic implications. There have been growing bodies of epidemiological and experimental studies which support the hypothesis of a significant relationship between estrogen deficiency and cerebral aneurysm formation with subsequent SAH. This hypothesis is the focus of this review as well as possible pathology-based therapeutics with regard to aspects of molecular pathophysiology, especially related to women's health. PMID:26538819

  4. Referral pattern of patients with aneurysmal subarachnoid hemorrhage.

    PubMed

    Schievink, W I; van der Werf, D J; Hageman, L M; Dreissen, J J

    1988-05-01

    The referral pattern of 334 patients admitted to a neurosurgical clinic with aneurysmal subarachnoid hemorrhage (SAH) was analyzed. Forty-nine percent of the patients were admitted after the day following the SAH. Failure of patients to seek prompt medical care was a cause of delay in 29 patients and of physician diagnostic errors in 95 patients. Common misdiagnoses included migraine, mental exhaustion, sinusitis, and influenza. A delay at the referring hospital was observed in 97 patients. Early intervention is important for the optimal management of patients with SAH. Educating the public, medical students, and physicians about the signs and symptoms of SAH and the importance of prompt therapy is likely to improve overall outcome after aneurysmal rupture. PMID:3363473

  5. 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. PMID:26872422

  6. Subarachnoid hemorrhage from intracranial aneurysms during pregnancy and the puerperium.

    PubMed

    Kataoka, Hiroharu; Miyoshi, Takekazu; Neki, Reiko; Yoshimatsu, Jun; Ishibashi-Ueda, Hatsue; Iihara, Koji

    2013-01-01

    Subarachnoid hemorrhage (SAH) due to the rupture of an intracranial aneurysm (IA) is a rare but serious complication of pregnancy and is responsible for important morbidity and mortality during pregnancy. This study reviewed reports of ruptured IA during pregnancy and the puerperium, and our own cases of ruptured IA in pregnant women. Hemorrhage occurred predominantly during the third trimester of pregnancy, when maternal cardiac output and blood volume increase and reach maximum. Physiological and hormonal changes in pregnancy are likely to affect the risk of IA rupture. Ruptured IAs during pregnancy should be managed based on neurosurgical considerations, and the obstetrical management of women with ruptured IAs should be decided according to the severity of SAH and the gestational age. Emergent cesarean section followed by clipping or coiling of aneurysms is indicated if the maternal condition and the gestational age allow such interventions. Although SAH during pregnancy can result in disastrous outcomes, the necessity of intracranial screening for high-risk pregnant women is still controversial. PMID:23979051

  7. Effect of Aneurysmal Subarachnoid Hemorrhage on Word Generation

    PubMed Central

    Ladowski, Daniella; Qian, Winnie; Kapadia, Anish N.; Macdonald, R. Loch; Schweizer, Tom A.

    2014-01-01

    Background. Aneurysmal subarachnoid hemorrhage (aSAH) survivors commonly exhibit impairment on phonemic and semantic fluency tests; however, it is unclear which of the contributing cognitive processes are compromised in aSAH patients. One method of disentangling these processes is to compare initial word production, which is a rapid, semiautomatic, frontal-executive process, and late phase word production, which is dependent on more effortful retrieval and lexical size and requires a more distributed neural network. Methods. Seventy-two individuals with aSAH and twenty-five control subjects were tested on a cognitive battery including the phonemic and semantic fluency task. Demographic and clinical information was also collected. Results. Compared to control subjects, patients with aSAH were treated by clipping and those with multiple aneurysms were impaired across the duration of the phonemic test. Among patients treated by coiling, those with anterior communicating artery aneurysms or a neurological complication (intraventricular hemorrhage, vasospasm, and edema) showed worse output only in the last 45 seconds of the phonemic test. Patients performed comparably to control subjects on the semantic test. Conclusions. These results support a “diffuse damage” hypothesis of aSAH, indicated by late phase phonemic fluency impairment. Overall, the phonemic and semantic tests represent a viable, rapid clinical screening tool in the postoperative assessment of patients with aSAH. PMID:24803729

  8. Behavioral deficits following experimental subarachnoid hemorrhage in the rat.

    PubMed

    Germanò, A F; Dixon, C E; d'Avella, D; Hayes, R L; Tomasello, F

    1994-06-01

    To characterize some of the short-term and long-term functional consequences of subarachnoid hemorrhage (SAH) in rats, we employed a battery of well-characterized tests for assessment of acute and chronic behavioral and neurologic performances. Three groups of 10 rats (blood injected, mock CSF injected and sham-operated controls) were studied. During the acute stage, simple nonpostural somatomotor reflexes (pinna and corneal reflexes), simple postural responses (paw flexion, tail flexion, and head support), startle response, and postural functions (righting reflex) did not differ significantly between the experimental groups. Assessments of body weight, beam walking ability, and beam balancing revealed significant disturbances in blood-injected rats. This work demonstrates that this single-hemorrhage rodent model of SAH is associated with the induction of enduring neurologic and behavioral deficits. Because of the significant interspecies difference, a direct extrapolation of our results to humans may not be appropriate. However, we suggest that the observed behavioral and neurologic changes may parallel those seen in humans after SAH. Results reported here further confirm the rat model of SAH as a viable laboratory instrument for the study of the pathophysiology of SAH and provide normative values for the evaluation of new treatment modalities. PMID:7996588

  9. Diagnosis and Management of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Marupudi, Neena I.; Mittal, Sandeep

    2015-01-01

    Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase the risk of morbidity and mortality. We review recent literature on hyponatremia in subarachnoid hemorrhage and present currently recommended protocols for diagnosis and management. PMID:25937938

  10. Leptomeningeal transthyretin-type amyloidosis presenting as acute hydrocephalus and subarachnoid hemorrhage.

    PubMed

    Bevers, Matthew B; McGuone, Declan; Jerath, Nivedita U; Musolino, Patricia L

    2016-07-01

    We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage. PMID:26896372

  11. Clinical Neurochemistry of Subarachnoid Hemorrhage: Toward Predicting Individual Outcomes via Biomarkers of Brain Energy Metabolism.

    PubMed

    Tholance, Yannick; Barcelos, Gleicy; Dailler, Frederic; Perret-Liaudet, Armand; Renaud, Bernard

    2015-12-16

    The functional outcome of patients with subarachnoid hemorrhage is difficult to predict at the individual level. The monitoring of brain energy metabolism has proven to be useful in improving the pathophysiological understanding of subarachnoid hemorrhage. Nonetheless, brain energy monitoring has not yet clearly been included in official guidelines for the management of subarachnoid hemorrhage patients, likely because previous studies compared only biological data between two groups of patients (unfavorable vs favorable outcomes) and did not determine decision thresholds that could be useful in clinical practice. Therefore, this Viewpoint discusses recent findings suggesting that monitoring biomarkers of brain energy metabolism at the level of individuals can be used to predict the outcomes of subarachnoid hemorrhage patients. Indeed, by taking into account specific neurochemical patterns obtained by local or global monitoring of brain energy metabolism, it may become possible to predict routinely, and with sufficient sensitivity and specificity, the individual outcomes of subarachnoid hemorrhage patients. Moreover, combining both local and global monitoring improves the overall performance of individual outcome prediction. Such a combined neurochemical monitoring approach may become, after prospective clinical validation, an important component in the management of subarachnoid hemorrhage patients to adapt individualized therapeutic interventions. PMID:26595414

  12. [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. PMID:21298906

  13. Incidence and Mortality of Spontaneous Subarachnoid Hemorrhage in Martinique

    PubMed Central

    Mehdaoui, Hossein; Hamlat, Abderrahmane; Piotin, Michel; Banydeen, Rishika; Mejdoubi, Mehdi

    2016-01-01

    Background Incidence of spontaneous subarachnoid hemorrhages (SAH) varies wildly across the world and seems to be low in Central and South America (4.2 per 100 000 person-years; CI 95%; 3.1–5.7). The objective of our study was to describe the characteristics of SAH and to estimate its incidence and severity in Martinique, a small French island located in the Caribbean Sea. Methods Due to its insular nature and small captive population, Martinique is ideal for the setting up of population-based epidemiological studies with good exhaustiveness. Our study, spanning a 7 year period (2007–2013), consisted of retrospective case ascertainment with multiple overlapping methods. Crude incidence and 30 day case-fatality rates for SAH among the Martinican population were computed for the study period. Incidence and disease severity was also analyzed according to age, gender and aneurysm presence. World age-standardized incidence rates were also calculated. Results A total of 121 patients had a SAH during the study period, with a higher frequency of female cases (71.1% versus 28.9%, p<0.001). Patient mean age was 57.1 years (median = 55 [46–66]). An aneurysmal origin was found in 96 SAH cases (79.3%). Crude annual incidence was 4.36 per 100 000 person-years (CI 95% 2.30–6.42). World age-standardized incidence was 3.29 per 100 000 person-years (CI 95% 1.74–4.84). During the 30 days following SAH diagnosis, 29 patients died (case fatality rate: 24% (CI 95% 16.4–31.6)). Conclusions The incidence of spontaneous subarachnoid hemorrhage in Martinique is much lower than in other parts of the world and similar to countries in Central and South America. These results are possibly related to environmental factors and most particularly to a low rate of smoking in the Martinican population. Thirty-day case-fatality rate is similar to what is observed in developed countries. PMID:27213614

  14. Migrating lumbar intrathecal catheter fragment associated with intracranial subarachnoid hemorrhage.

    PubMed

    Hnenny, Luke; Sabry, Hatem A; Raskin, Jeffrey S; Liu, Jesse J; Roundy, Neil E; Dogan, Aclan

    2015-01-01

    Intrathecal catheter placement into the lumbar cistern has varied indications, including drug delivery and CSF diversion. These Silastic catheters are elastic and durable; however, catheter-associated malfunctions are well reported in the literature. Fractured catheters are managed with some variability, but entirely intradural retained fragments are often managed conservatively with observation. The authors describe a case of a 70-year-old man with an implanted intrathecal morphine pump for failed back surgery syndrome who presented to an outside hospital with a history of headache, neck pain, nausea, and photophobia of 3 days' duration. He also described mild weakness and intermittent numbness of both legs. Unenhanced head CT demonstrated subarachnoid hemorrhage (SAH). A right C-5 hemilaminectomy was performed. This case is unique in that there was no indication that the lumbar intrathecal catheter had fractured prior to the patient's presentation with SAH. This case demonstrates that intrathecal catheter fragments are mobile and can precipitate intracranial morbidity. Extrication of known fragments is safe and should be attempted to prevent further neurosurgical morbidity. PMID:25360531

  15. Brain Volume Determination in Subarachnoid Hemorrhage Using Rats.

    PubMed

    Lekic, Tim; Hardy, Maurice; Fujii, Mutsumi; McBride, Devin W; Zhang, John H

    2016-01-01

    Brain edema is routinely measured using the wet-dry method. Volume, however, is the sum total of all cerebral tissues, including water. Therefore, volumetric change following injury may not be adequately quantified using percentage of edema. We thus tested the hypothesis that dried brains can be reconstituted with water and then re-measured to determine the actual volume. Subarachnoid hemorrhage (SAH) was induced by endovascular perforation in adult male Sprague-Dawley rats (n = 30). Animals were euthanized at 24 and 72 h after evaluation of neurobehavior for determination of brain water content. Dried brains were thereafter reconstituted with equal parts of water (lost from brain edema) and centrifuged to remove air bubbles. The total volume was quantified using hydrostatic (underwater) physics principles that 1 ml water (mass) = 1 cm(3) (volume). The amount of additional water needed to reach a preset level marked on 2-ml test tubes was added to that lost from brain edema, and from the brain itself, to determine the final volume. SAH significantly increased both brain water and volume while worsening neurological function in affected rats. Volumetric measurements demonstrated significant brain swelling after SAH, in addition to the brain edema approach. This modification of the "wet-dry" method permits brain volume determination using valuable post hoc dried brain tissue. PMID:26463930

  16. 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. PMID:26669277

  17. 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

  18. Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

    PubMed Central

    Kikkawa, Yuichiro; Matsuo, Satoshi; Kurogi, Ryota; Nakamizo, Akira; Mizoguchi, Masahiro; Sasaki, Tomio

    2014-01-01

    Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits. Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC) preincubated with relaxin, myosin light chain phosphorylation (MLC) was investigated with immunoblotting after endothelin-1 stimulation. Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC. Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm. PMID:25133183

  19. Aneurysmal Subarachnoid Hemorrhage Models: Do They Need a Fix?

    PubMed Central

    Sehba, Fatima A.; Pluta, Ryszard M.

    2013-01-01

    The discovery of tissue plasminogen activator to treat acute stroke is a success story of research on preventing brain injury following transient cerebral ischemia (TGI). That this discovery depended upon development of embolic animal model reiterates that proper stroke modeling is the key to develop new treatments. In contrast to TGI, despite extensive research, prevention or treatment of brain injury following aneurysmal subarachnoid hemorrhage (aSAH) has not been achieved. A lack of adequate aSAH disease model may have contributed to this failure. TGI is an important component of aSAH and shares mechanism of injury with it. We hypothesized that modifying aSAH model using experience acquired from TGI modeling may facilitate development of treatment for aSAH and its complications. This review focuses on similarities and dissimilarities between TGI and aSAH, discusses the existing TGI and aSAH animal models, and presents a modified aSAH model which effectively mimics the disease and has a potential of becoming a better resource for studying the brain injury mechanisms and developing a treatment. PMID:23878760

  20. Botulinum toxin a treatment of cricopharyngeal dysphagia after subarachnoid hemorrhage.

    PubMed

    Krause, Eike; Schirra, Jörg; Gürkov, Robert

    2008-12-01

    Elevated muscular tone associated with spastic syndromes can cause excessive contractility at the upper esophageal sphincter and impede swallowing. A 47-year-old male patient with spasticity predominantly of the lower extremities after a subarachnoid hemorrhage suffered from severe dysphagia and chronic salivary aspiration. He was dependent on a cuffed tracheostomy tube and a percutaneous enterogastric feeding tube. Barium swallow and esophageal manometry revealed cricopharyngeal spasm, while laryngeal elevation and pharyngeal contractility were well preserved. We endoscopically injected 180 MU botulinum toxin A into the cricopharyngeus muscle. Two days post injection, swallowing function had improved and oral nutrition was possible. This improvement lasted for six weeks. After another injection 8 weeks later, an undesired diffusion into the hypopharynx occurred and manometry showed diminished contractility without amelioration of dysphagia. Botulinum toxin therapy of cricopharyngeal spasm improves swallowing function in a subgroup of patients with spastic syndromes. The therapeutic effect is of limited duration. Toxin diffusion into the pharynx should be avoided. Manometry is useful in planning and monitoring the therapy. PMID:18437465

  1. Noninvasive Intracranial Pressure Determination in Patients with Subarachnoid Hemorrhage.

    PubMed

    Noraky, James; Verghese, George C; Searls, David E; Lioutas, Vasileios A; Sonni, Shruti; Thomas, Ajith; Heldt, Thomas

    2016-01-01

    Intracranial pressure (ICP) should ideally be measured in many conditions affecting the brain. The invasiveness and associated risks of the measurement modalities in current clinical practice restrict ICP monitoring to a small subset of patients whose diagnosis and treatment could benefit from ICP measurement. To expand validation of a previously proposed model-based approach to continuous, noninvasive, calibration-free, and patient-specific estimation of ICP to patients with subarachnoid hemorrhage (SAH), we made waveform recordings of cerebral blood flow velocity in several major cerebral arteries during routine, clinically indicated transcranial Doppler examinations for vasospasm, along with time-locked waveform recordings of radial artery blood pressure (APB), and ICP was measured via an intraventricular drain catheter. We also recorded the locations to which ICP and ABP were calibrated, to account for a possible hydrostatic pressure difference between measured ABP and the ABP value at a major cerebral vessel. We analyzed 21 data records from five patients and were able to identify 28 data windows from the middle cerebral artery that were of sufficient data quality for the ICP estimation approach. Across these windows, we obtained a mean estimation error of -0.7 mmHg and a standard deviation of the error of 4.0 mmHg. Our estimates show a low bias and reduced variability compared with those we have reported before. PMID:27165879

  2. Neuroprotective Effect of Radix Trichosanthis Saponins on Subarachnoid Hemorrhage

    PubMed Central

    Chen, Ying; Sun, Haiyan; Huang, Liyong; Li, Juxiang; Zhou, Wenke; Chang, Jingling

    2015-01-01

    Redox homeostasis has been implicated in subarachnoid hemorrhage (SAH). As a result, antioxidants and/or free radical scavengers have become an important therapeutic modality. Considering that radix trichosanthis (RT) saponins exhibited strong antioxidant ability both in vivo and in vitro, the present study aimed to reveal whether the neuroprotective activities of RT saponins were mediated by p38/p53 signal pathway after SAH. An established SAH model was used and superoxide dismutase (SOD), malondialdehyde (MDA), induced nitric oxide synthase (iNOS), nitric oxide (NO), lactate dehydrogenase (LDH), p-p38, and p53 activation were detected after 48 h of SAH. The results showed that RT saponins inhibited iNOS expression to restore NO to basal level. Moreover, compared with Cu/Zn-SOD, RT saponins (2 mg/kg/d dosage) significantly increased Mn-SOD activity after SAH. Accompanied with lowered NO and elevated SOD, decreased p38 phosphorylation and p53 activities were observed, especially for RT saponins at 2 mg/kg/d dosage. In this setting, the neurological outcome was also improved with less neuronal cells damage after RT saponins pretreatment. Our findings demonstrated the beneficial effects of RT saponins in enhancing neuroprotective effects by deducing iNOS activity, normalizing SOD level, and inhibiting p-p38 and p53 expression, hence offering significant therapeutic implications for SAH. PMID:26089937

  3. Fatal subarachnoid hemorrhage caused by Aspergillus arteritis without angiographic abnormalities.

    PubMed

    Miki, Yasuo; Tomiyama, Masahiko; Haga, Rie; Nishijima, Haruo; Suzuki, Chieko; Nishijima, Michiharu; Midorikawa, Hiroshi; Sannohe, Seiya; Kurotaki, Hidekachi; Wakabayashi, Koichi; Baba, Masayuki

    2012-10-01

    No source of bleeding is detected by angiogram in 15-20% of patients with nonaneurysmal subarachnoid hemorrhage (SAH). This negative angiographic finding might suggest a benign prognosis. We describe a case of fatal SAH caused by Aspergillus arteritis without formation of fusiform dilatation or aneurysms. A 76-year-old man with a 2-month history of progressive visual loss due to pachymeningitis around the optic nerves suffered from SAH in the bilateral sylvian fissures. Repetitive serum galactomannan assay and angiography showed no abnormality. Post mortem examination revealed marked proliferation of Aspergillus in the granulomas of the frontal base dura mater. In addition, major trunks and several branches of the bilateral middle cerebral arteries were invaded by Aspergillus hyphae, which destroyed the walls in the absence of dilatation and aneurysms. Invasive aspergillosis of the CNS often forms a mycotic aneurysm. However, four autopsy cases of nonaneurysmal SAH due to invasive aspergillosis have been reported. The present case is the second autopsy case of Aspergillus arteritis without angiographic abnormality, resulting in fatal SAH. Aggressive and continuous antifungal therapy is absolutely necessary in suspected cases of invasive aspergillosis of the CNS, even if angiography is negative and therapeutic markers of aspergillosis are normal. PMID:22239342

  4. Stem Cells as a Potential Adjunctive Therapy in Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Ghonim, Hesham T.; Shah, Sumedh S.; Thompson, John W.; Ambekar, Sudheer; Peterson, Eric C.; Elhammady, Mohamed Samy

    2016-01-01

    BACKGROUND Despite advances in the management of subarachnoid hemorrhage, a considerable proportion of patients are still left with severe and disabling long-term consequences. Unfortunately, there are limited therapeutic options to counteract the sequelae following the initial insult. The role of stem cells has been studied in the treatment of various diseases. The goal of this study was to provide a literature review regarding the potential advantages of stem-cell therapy to counteract or minimize the sequelae of aneurysmal subarachnoid hemorrhage. METHODS PubMed, Google Scholar, and ClinicalTrials.gov searches were conducted to incorporate pertinent studies that discussed stem cell use in the management of subarachnoid hemorrhage. Included articles were subjected to data extraction for the synthesis of the efficacy of stem-cell therapy. RESULTS Four preclinical studies with 181 animal model subjects (44 mice, 137 rats) were incorporated in our review. Endovascular punctures (65%) and blood injections in subarachnoid spaces (17%) were used to induce hemorrhage models. Stem cells were administered intravenously (3.0 × 106 cells) or intranasally (1.5 × 106 cells). According to literature, mesenchymal cell therapy significantly (p<0.05) induces stem-cell migration to lesion sites, decreases associated neural apoptosis and inflammation, improves ultrastructural integrity of cerebral tissue, and aids in improving sensorimotor function post subarachnoid hemorrhage. CONCLUSION Stem cells, particularly mesenchymal stem cells, have shown promising cellular, morphological, and functional benefits in animal models suffering from induced subarachnoid hemorrhages. However, further studies are warranted to elucidate the full effects of stem-cell therapy for aneurysmal subarachnoid hemorrhage. PMID:26958151

  5. The Importance of Early Brain Injury after Subarachnoid Hemorrhage

    PubMed Central

    Sehba, Fatima A.; Hou, Jack; Pluta, Ryszard M.; Zhang, John H.

    2012-01-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH. PMID:22414893

  6. NONCONVULSIVE SEIZURES IN SUBARACHNOID HEMORRHAGE LINK INFLAMMATION AND OUTCOME

    PubMed Central

    Claassen, Jan; Albers, David; Schmidt, J. Michael; De Marchis, Gian Marco; Pugin, Deborah; Falo, Christina Maria; Mayer, Stephan A.; Cremers, Serge; Agarwal, Sachin; Elkind, Mitchell SV; Connolly, E. Sander; Dukic, Vanja; Hripcsak, George; Badjatia, Neeraj

    2014-01-01

    Objective Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury but mechanisms that cause NCSz are controversial. Pro-inflammatory states are common after many brain injuries and inflammatory mediated changes in blood-brain-barrier permeability have experimentally been linked to seizures. Methods In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome,SIRS) and laboratory markers of inflammation (tumor necrosis factor receptor 1,TNF-R1; high sensitivity C-reactive protein,hsCRP). Logistic regression, cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. Results Among 479 SAH patients, 53(11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (OR1.9 per point increase in SIRS; 95%-CI1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR1.2 per 20 point hsCRP increase [95%-CI1.1-1.4]; OR2.5 per 100 point TNF-R1 increase [95%-CI2.1-2.9]). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. Interpretation In-hospital NCSz were independently associated with a pro-inflammatory state following SAH reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and this effect is at least in part mediated through in-hospital NCSz. PMID:24771589

  7. Age-associated vasospasm in aneurysmal subarachnoid hemorrhage.

    PubMed

    Kale, Sushant P; Edgell, Randall C; Alshekhlee, Amer; Borhani Haghighi, Afshin; Sweeny, Justin; Felton, Jason; Kitchener, Jacob; Vora, Nirav; Bieneman, Bruce K; Cruz-Flores, Salvador; Abdulrauf, Saleem

    2013-01-01

    The relationship between age and vasospasm caused by subarachnoid hemorrhage (SAH) is controversial. We evaluated this relationship in a contemporary sample from a single institution. In a retrospective study design, we included patients with SAH caused by ruptured intracranial aneurysms. All patients underwent an evaluation that included head imaging, cerebral angiography, and treatment for the underlying aneurysm. Vasospasm was classified as absent, any vasospasm, or symptomatic vasospasm. Age was classified into 2 categories with a cutoff of 50 years, and also was stratified by decade. All patients had received preventative and therapeutic measures for vasospasm. Logistic regression analysis was used to assess the association between age and the occurrence of vasospasm. A total of 108 patients were included in this analysis, 67 of whom were age ≥50 years. The older patients had a higher incidence of vascular risk factors, and the younger patients had a higher incidence of smoking and illicit substance abuse. The mean age of the patients with any vasospasm (n = 41) was 48.51 ± 11.23 years, compared with 59.67 ± 13.30 years in those without vasospasm (P < .0001). Adjusted analysis found a greater risk of vasospasm in the younger patients compared with the older patients (odds ratio, 5.83; 95% confidence interval, 2.41-14.12 for any vasospasm; odds ratio, 2.66; 95% confidence interval, 1.008-7.052 for symptomatic vasospasm). This risk of vasospasm decreased with advanced age (P < .0001). Our findings suggest that patients age <50 years are at 5-fold greater risk of any vasospasm compared with older patients, and that age-adjusted prevention protocols may need to be considered. PMID:21719308

  8. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage

    PubMed Central

    Nyberg, Christoffer; Karlsson, Torbjörn; Hillered, Lars; Stridsberg, Mats; Ronne Engström, Elisabeth

    2016-01-01

    Introduction In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems. Methods A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed. Results Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased. Conclusions The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult. PMID:27007694

  9. Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia.

    PubMed

    Sokolov, Arseny A; Husain, Shakir; Sztajzel, Roman; Croquelois, Alexandre; Lobrinus, Johannes A; Thaler, David; Städler, Claudio; Hungerbühler, Hansjörg; Caso, Valeria; Rinkel, Gabriel J; Michel, Patrik

    2016-07-01

    Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5-14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (χ = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2-264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (χ = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials. PMID:27399083

  10. Recombinant Osteopontin in Cerebral Vasospasm After Subarachnoid Hemorrhage

    PubMed Central

    Suzuki, Hidenori; Hasegawa, Yu; Chen, Wanqiu; Kanamaru, Kenji; Zhang, John H.

    2010-01-01

    Objective Osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein, has been reported to be protective against ischemic lesions, but effects of OPN on vascular functions have not been investigated. The aim of this study was to assess whether recombinant OPN (r-OPN) could prevent cerebral vasospasm after subarachnoid hemorrhage (SAH) in rats. Methods r-OPN was administered intraventricularly to rats undergoing SAH by the endovascular perforation, and its protective effects were evaluated by measuring the diameter of cerebral arteries and neurobehavioral testing. Western blotting and immunofluorescence were performed to explore the underlying mechanisms. An integrin receptor antagonist GRGDSP or mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1 small interfering RNA (siRNA) was also administered to r-OPN-treated SAH rats, and those effects were evaluated. Results Pre-SAH administration of r-OPN prevented vasospasm and neurological impairments at 24–72 hours post-SAH. r-OPN enhanced an endogenous MAPK inhibitor, MKP-1, and suppressed the phosphorylation of MAPKs, caldesmon and heat shock protein 27 in the spastic cerebral arteries at 24 hours post-SAH. Immunofluorescence revealed that MKP-1 was induced in the arterial smooth muscle layer. GRGDSP prevented r-OPN-induced MKP-1 upregulation, and MKP-1 siRNA abolished both MAPK inactivation and anti-vasospastic effects by r-OPN. Post-SAH r-OPN treatment also prevented vasospasm. Interpretation r-OPN induced MKP-1 in the spastic cerebral arteries via binding to L-arginyl-glycyl-L-aspartate-dependent integrin receptors and prevented vasospasm after SAH. Therapeutic induction of MKP-1 may be a novel approach for the prevention and treatment of cerebral vasospasm. PMID:21031580

  11. Causes of 30-day readmission after aneurysmal subarachnoid hemorrhage.

    PubMed

    Greenberg, Jacob K; Washington, Chad W; Guniganti, Ridhima; Dacey, Ralph G; Derdeyn, Colin P; Zipfel, Gregory J

    2016-03-01

    OBJECT Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care. METHODS The authors retrospectively reviewed the medical records of all patients who received surgical orendovas-cular treatment for aneurysmal SAH at Barnes-Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization. RESULTS Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3-17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming. CONCLUSIONS Most readmissions after aneurysmal SAH relate to late consequences of

  12. Isolated Cranial Nerve-III Palsy Secondary to Perimesencephalic Subarachnoid Hemorrhage

    PubMed Central

    Abbatemarco, Justin R.

    2016-01-01

    We describe isolated cranial nerve-III palsy as a rare clinical finding in a patient with perimesencephalic subarachnoid hemorrhage. In this unusual case, the patient presented with complete cranial nerve-III palsy including ptosis and pupillary involvement. Initial studies revealed subarachnoid hemorrhage in the perimesencephalic, prepontine, and interpeduncular cisterns. Angiographic studies were negative for an intracranial aneurysm. The patient's neurological deficits improved with no residual deficits on follow-up several months after initial presentation. Our case report supports the notion that patients with perimesencephalic subarachnoid hemorrhage have an excellent prognosis. Our report further adds a case of isolated cranial nerve-III palsy as a rare initial presentation of this type of bleeding, adding to the limited body of the literature. PMID:26949557

  13. A multicenter prospective cohort study of volume management after subarachnoid hemorrhage: circulatory characteristics of pulmonary edema after subarachnoid hemorrhage.

    PubMed

    Obata, Yoshiki; Takeda, Junichi; Sato, Yohei; Ishikura, Hiroyasu; Matsui, Toru; Isotani, Eiji

    2016-08-01

    OBJECT Subarachnoid hemorrhage (SAH) is often accompanied by pulmonary complications, which may lead to poor outcomes and death. This study investigated the incidence and cause of pulmonary edema in patients with SAH by using hemodynamic monitoring with PiCCO-plus pulse contour analysis. METHODS A total of 204 patients with SAH were included in a multicenter prospective cohort study to investigate hemodynamic changes after surgical clipping or coil embolization of ruptured cerebral aneurysms by using a PiCCO-plus device. Changes in various hemodynamic parameters after SAH were analyzed statistically. RESULTS Fifty-two patients (25.5%) developed pulmonary edema. Patients with pulmonary edema (PE group) were significantly older than those without pulmonary edema (non-PE group) (p = 0.017). The mean extravascular lung water index was significantly higher in the PE group than in the non-PE group throughout the study period. The pulmonary vascular permeability index (PVPI) was significantly higher in the PE group than in the non-PE group on Day 6 (p = 0.029) and Day 10 (p = 0.011). The cardiac index of the PE group was significantly decreased biphasically on Days 2 and 10 compared with that of the non-PE group. In the early phase (Days 1-5 after SAH), the daily water balance of the PE group was slightly positive. In the delayed phase (Days 6-14 after SAH), the serum C-reactive protein level and the global end-diastolic volume index were significantly higher in the PE group than in the non-PE group, whereas the PVPI tended to be higher in the PE group. CONCLUSIONS Pulmonary edema that occurs in the early and delayed phases after SAH is caused by cardiac failure and inflammatory (i.e., noncardiogenic) conditions, respectively. Measurement of the extravascular lung water index, cardiac index, and PVPI by PiCCO-plus monitoring is useful for identifying pulmonary edema in patients with SAH. PMID:26613172

  14. An uncommon initial presentation of snake bite-subarachnoid hemorrhage: A case report with literature review

    PubMed Central

    Roy, Manoj Kumar; Dutta, Joydip; Chatterjee, Apratim; Sarkar, Anup; Roy, Koushik; Agarwal, Rakhesh; Lahiri, Durjoy; Biswas, Amrito; Mondal, Anupam; Maity, Pranab; Mukhopadhyay, Jotideb

    2015-01-01

    Snake bites are very common in India, particularly in West Bengal. Snake bite can cause various hematological, neuromyopathical complications. It can be very fatal if not detected and treated early. Timely intervention can save the patient. We are reporting a case of hematotoxic Russell viper snake bite presented with subarachnoid hemorrhage. Patient was successfully treated with antivenom serum (AVS) along with other conservative management. Subarachnoid hemorrhage as an initial presentation in viper bite is very rare and we discuss the case with proper literature review. PMID:26425018

  15. Accumulation of intimal platelets in cerebral arteries following experimental subarachnoid hemorrhage in cats

    SciTech Connect

    Haining, J.L.; Clower, B.R.; Honma, Y.; Smith, R.R.

    1988-07-01

    From 2 hours to 23 days following experimental subarachnoid hemorrhage, the accumulation of indium-111-labeled platelets on the intimal surface of the middle cerebral artery was studied in 23 cats. Subarachnoid hemorrhage was produced by transorbital rupture of the right middle cerebral artery. Of the 23 cats, 17 exhibited right middle cerebral artery/left middle cerebral artery radioactivity ratios of greater than 1.25. When these results were compared with those of 12 control cats, 0.001 less than p less than 0.005 (chi2 test). Thus, the results from the control and experimental groups are significantly different and indicate early (after 2 hours) preferential accumulation of intimal platelets in the ruptured right middle cerebral artery compared with the unruptured left middle cerebral artery and new platelet deposition continuing for up to 23 days. However, the experimental group did not reveal a clear pattern for platelet accumulation following subarachnoid hemorrhage. There was no simple correlation between the magnitude of the radioactivity ratios and the time after hemorrhage when the cats were killed although the ratios for 2 hours to 7 days seemed greater than those for 8 to 23 days. Assuming the pivotal role of platelets in the angiopathy of subarachnoid hemorrhage, the administration of antiplatelet agents as soon as possible following its occurrence may be of value.

  16. Prognosis Predicting Score for Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Duan, Guoli; Yang, Pengfei; Li, Qiang; Zuo, Qiao; Zhang, Lei; Hong, Bo; Xu, Yi; Zhao, Wenyuan; Liu, Jianmin; Huang, Qinghai

    2016-01-01

    Abstract The elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) have a greater risk of poor clinical outcome after endovascular treatment (EVT) than younger patients do. Hence, it is necessary to explore which factors are associated with poor outcome and develop a predictive score specifically for elderly patients with aSAH receiving EVT. The aim of this study was to develop and validate a predictive score for 1-year outcomes in individual elderly patients with aSAH underwent EVT. In this 10-year prospective study, 520 consecutive aSAH elderly (age ≥ 60 years) patients underwent EVT in a single center were included. The risk factors, periprocedural, and 1-year follow-up data of all patients were entered in a specific prospective database. The modified Rankin scale was used for evaluating clinical outcome. To optimize the model's predictive capacity, the original matrix was randomly divided in 2 submatrices (learning and testing). The predictive score was developed using Arabic numerals for all variables based on the variable coefficients (β) of multivariable logistic regression analysis in the learning set and the predictive performance evaluation was assessed in the testing set. The risk classes were constructed using classification criteria based on sensitivity and specificity. The poor outcome rate at 1 year was 26.15%. Six risk factors, including age, hypertension, Hunt–Hess scale, Fisher scale, aneurysm location, and periprocedural complications, were independently associated with poor outcome and assembled the Changhai score. The discriminative power analysis with the area under the receiver operating characteristic curve (AUC) of the Changhai score was statistically significant (0.864, 0.824–0.904, P < 0.001). The sensitivity and specificity of the Changhai score were 82.07% and 78.06%, respectively. Our study indicated that age, hypertension, Hunt–Hess scale, Fisher scale, aneurysm location, and periprocedural complications were

  17. Changes in the Metabolism of Sphingolipids after Subarachnoid Hemorrhage

    PubMed Central

    Testai, Fernando D; Xu, Hao-Liang; Kilkus, John; Suryadevara, Vidyani; Gorshkova, Irina; Berdyshev, Evgeny; Pelligrino, Dale A; Dawson, Dawson

    2014-01-01

    Background We previously described that ceramide (Cer), a mediator of cell death, increases in the cerebrospinal fluid (CSF) of subarachnoid hemorrhage (SAH) patients. This study investigated the alterations of biochemical pathways involved in Cer homeostasis in SAH. Methods Cer, dihydroceramide (DHC), sphingosine-1-phosphate (S1P) and the activities of acid sphingomyelinase (ASMase), neutral sphingomyelinase (NSMase), sphingomyelinase synthase (SMS), S1P-lyase, and glucosylceramide synthase (GCS) were determined in the CSF of SAH subjects and in brain homogenate of SAH rats. Results Compared to controls (n=8), SAH patients (n=26) had higher ASMase activity (10.0±3.5 IF/µl.min vs. 15.0±4.6 IF/µl.min; p=0.009) and elevated levels of Cer (11.4±8.8 pmol/ml vs. 33.3±48.3 pmol/ml; p=0.001) and DHC (1.3±1.1 pmol/ml vs. 3.8±3.4 pmol/ml; p=0.001) in the CSF. The activities of GCS, NSMase, and SMS in the CSF were undetectable. Brain homogenates from SAH animals had increased ASMase activity (control: 9.7±1.2 IF/µg.min; SAH: 16.8±1.6 IF/µg.min; p<0.05) and Cer levels (control: 3422±26 fmol/nmol of total lipid P; SAH: 7073±2467 fmol/nmol of total lipid P; p<0.05) compared to controls. In addition, SAH was associated with a reduction of 60% in S1P levels, a 40% increase in S1P-lyase activity, and a 2-fold increase in the activity of GCS but similar NSMase and SMS activities than controls. Conclusions Our results show an activation of ASMase, S1P-lyase, and GCS resulting in a shift in the production of protective (S1P) in favor of deleterious (Cer) sphingolipids after SAH. Additional studies are needed to determine the effect of modulators of the pathways here described in the outcome of SAH. PMID:25597763

  18. Changes in the metabolism of sphingolipids after subarachnoid hemorrhage.

    PubMed

    Testai, Fernando D; Xu, Hao-Liang; Kilkus, John; Suryadevara, Vidyani; Gorshkova, Irina; Berdyshev, Evgeny; Pelligrino, Dale A; Dawson, Glyn

    2015-05-01

    We previously described how ceramide (Cer), a mediator of cell death, increases in the cerebrospinal fluid (CSF) of subarachnoid hemorrhage (SAH) patients. This study investigates the alterations of biochemical pathways involved in Cer homeostasis in SAH. Cer, dihydroceramide (DHC), sphingosine-1-phosphate (S1P), and the activities of acid sphingomyelinase (ASMase), neutral sphingomyelinase (NSMase), sphingomyelinase synthase (SMS), S1P-lyase, and glucosylceramide synthase (GCS) were determined in the CSF of SAH subjects and in brain homogenate of SAH rats. Compared with controls (n = 8), SAH patients (n = 26) had higher ASMase activity (10.0 ± 3.5 IF/µl· min vs. 15.0 ± 4.6 IF/µl • min; P = 0.009) and elevated levels of Cer (11.4 ± 8.8 pmol/ml vs. 33.3 ± 48.3 pmol/ml; P = 0.001) and DHC (1.3 ± 1.1 pmol/ml vs. 3.8 ± 3.4 pmol/ml; P = 0.001) in the CSF. The activities of GCS, NSMase, and SMS in the CSF were undetectable. Brain homogenates from SAH animals had increased ASMase activity (control: 9.7 ± 1.2 IF/µg • min; SAH: 16.8 ± 1.6 IF/µg • min; P < 0.05) and Cer levels (control: 3,422 ± 26 fmol/nmol of total lipid P; SAH: 7,073 ± 2,467 fmol/nmol of total lipid P; P < 0.05) compared with controls. In addition, SAH was associated with a reduction of 60% in S1P levels, a 40% increase in S1P-lyase activity, and a twofold increase in the activity of GCS. In comparison, NSMase and SMS activities were similar to controls and SMS activities similar to controls. In conclusion, our results show an activation of ASMase, S1P-lyase, and GCS resulting in a shift in the production of protective (S1P) in favor of deleterious (Cer) sphingolipids after SAH. Additional studies are needed to determine the effect of modulators of the pathways described here in SAH. PMID:25597763

  19. Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) Trial

    PubMed Central

    Budohoski, Karol; Smith, Christopher; Hutchinson, Peter J.; Kirkpatrick, Peter J.

    2015-01-01

    BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome. ABBREVIATIONS: ALP, alkaline phosphatase ALT, alanine aminotransferase CK, creatine kinase CRP, C-reactive protein EVD, external ventricular drainage ICH GCP, International Conference on Harmonisation guidelines for good clinical practice mRS, modified Rankin Scale SAH, subarachnoid hemorrhage STASH, Simvastatin in

  20. Cerebral amyloid angiopathy-related atraumatic convexal subarachnoid hemorrhage: an ARIA before the tsunami

    PubMed Central

    Martínez-Lizana, Eva; Carmona-Iragui, María; Alcolea, Daniel; Gómez-Choco, Manuel; Vilaplana, Eduard; Sánchez-Saudinós, María B; Clarimón, Jordi; Hernández-Guillamon, Mar; Munuera, Josep; Gelpi, Ellen; Gómez-Anson, Beatriz; de Juan-Delago, Manel; Delgado-Mederos, Raquel; Montaner, Joan; Ois, Angel; Amaro, Sergi; Blesa, Rafael; Martí-Fàbregas, Joan; Lleó, Alberto; Fortea, Juan

    2015-01-01

    Atraumatic convexal subarachnoid hemorrhage (cSAH) in elderly patients is a rare entity that has been associated with cerebral amyloid angiopathy (CAA) and intracerebral hematomas (ICH). To characterize this entity and to study these associations, 22 patients over 60 with cSAH were included in a multicenter ambispective cohort study. Clinical data, magnetic resonance imaging (MRI) studies, APOE genotyping, and cerebrospinal fluid (CSF) biomarkers were evaluated. Results were compared with data from healthy controls (HC), non-cSAH CAA patients (CAAo), and Alzheimer disease patients. Convexal subarachnoid hemorrhage presented with transient sensory or motor symptoms. At follow-up (median 30.7 months), 5 patients had died, 6 survivors showed functional disability (modified Rankins Scale (mRS)>2), and 12 cognitive impairment. Four patients had prior ICH and six had an ICH during follow-up. CSF-Aß40 and Aß42 levels were lower in cSAH and CAAo compared with HC. Convexal subarachnoid hemorrhage presented an APOE-ɛ2 overrepresentation and CAAo had an APOE-ɛ4 overrepresentation. On MRI, all patients fulfilled CAA-modified Boston criteria and 9 showed cortical ischemia in the surrounding cortex or the vicinity of superficial siderosis. The neuropathologic study, available in one patient, showed severe CAA and advanced Alzheimer-type pathology. Convexal subarachnoid hemorrhage in the elderly is associated with cognitive impairment and lobar ICH occurrence. Our findings support the existence of an underlying CAA pathology. PMID:25735919

  1. [Bacillus cereus sepsis and subarachnoid hemorrhage following consolidation chemotherapy for acute myelogenous leukemia].

    PubMed

    Kawatani, Eri; Kishikawa, Yuki; Sankoda, Chikahiro; Kuwahara, Nobuo; Mori, Daisuke; Osoegawa, Kouichi; Matsuishi, Eijo; Gondo, Hisashi

    2009-04-01

    A 64-year-old man with acute myelogenous leukemia (FAB classification, M7) in remission received consolidation chemotherapy with mitoxantrone/cytosine arabinoside. WBC counts decreased to 0/microl on day 14, and fever (39.3 degrees C) and epigastralgia developed on day 15. Cefozopran was instituted for febrile neutropenia; however, on day 16, he was found to be in cardiac arrest. CT scan on day 16 revealed subarachnoid hemorrhage. Gram-positive rods were isolated from blood cultures on day 15, and were later identified as B.cereus. He recovered transiently, but eventually died on day 19. Postmortem examination demonstrated many colonies of B. cereus in the cerebrum, cerebellum, lung, and liver. Hepatocyte necrosis was also observed in the liver. Bacterial aneurysms or septic emboli were not identified in the arachnoid vessels, but necrosis of cerebral vessels was prominent, which was considered to be the cause of subarachnoid hemorrhage. Fatal subarachnoid hemorrhage has been reported to be associated with B. cereus sepsis, which developed at nadir following chemotherapy for leukemia patients. Because of the aggressive clinical course of B. cereus sepsis, including the risk for subarachnoid hemorrhage, early treatment with effective antibiotics for B. cereus sepsis would be important in the management of leukemia patients after chemotherapy. PMID:19404024

  2. Fatal subarachnoid hemorrhage associated with internal carotid artery dissection resulting from whiplash trauma.

    PubMed

    Uhrenholt, Lars; Freeman, Michael D; Webb, Alexandra L; Pedersen, Michael; Boel, Lene Warner Thorup

    2015-12-01

    Spinal injury following inertial loading of the head and neck (whiplash) is a common sequel of low speed traffic crashes. A variety of non-musculoskeletal injuries have been described in association with injury to the spine following whiplash trauma, including traumatic brain injury, vestibular derangement, and cranial nerve injury, among others. Vascular injuries in the head and neck have, however, only rarely been described. We present the case of a middle-aged male who sustained an ultimately fatal injury that resulted from injury to the internal carotid artery (ICA) and intracerebral vascular structures following a hard braking maneuver, with no direct head- or neck contact with the vehicular interior. Based on this unusual mechanism of injury we reviewed hospital data from the United States nationwide inpatient database (NIS) to assess the frequency of similar injuries reportedly resulting from traffic crashes. The post-mortem examination revealed a left internal carotid artery dissection associated with subarachnoid hemorrhage (SAH). Based on the close temporal association, the absent prior history, and the plausibility of the injury mechanism, the injury was attributed to the braking maneuver. An analysis of NIS data demonstrated that the prevalence of subarachnoid hemorrhage is significantly higher when there is a traumatic etiology, and higher yet when the trauma is a traffic crash (odds ratio 3.3 and 4.3, respectively). The presented case, together with the hospital inpatient data analysis, indicate that although SAH in combination with ICA dissection is relatively rare, it is substantially more probable following a traffic crash. In a clinical or forensic setting the inference that magnitude of a trauma was low should not serve as a basis for either excluding a cervical artery dissection from a differential diagnosis, or for excluding the trauma as a cause of a diagnosed dissection. This case report illustrates a rare fatal outcome of inertial load to

  3. The Effects of Vasospasm and Re-Bleeding on the Outcome of Patients with Subarachnoid Hemorrhage from Ruptured Intracranial Aneurysm.

    PubMed

    Filipce, Venko; Caparoski, Aleksandar

    2015-01-01

    Vasospasm and re-bleeding after subarachnoid hemorrhage from ruptured intracranial aneurysm are devastating complication that can severely affect the outcome of the patients. We are presenting a series of total number of 224 patients treated and operated at our Department due to subarachnoid hemorrhage, out of which certain number developed vasospasm and re-bleeding. We are evaluating the effect of these complications on the outcome of the patients according to the Glasgow Outcome Scale at the day of discharge. In our experience both vasospasm and ReSAH can significantly influence the outcome of patients with subarachnoid hemorrhage from ruptured intracranial aneurysm. PMID:27442399

  4. High frequency of spinal involvement in patients with basal subarachnoid neurocysticercosis

    PubMed Central

    Callacondo, D.; Garcia, H.H.; Gonzales, I.; Escalante, D.; Gilman, Robert H.; Tsang, Victor C.W.; Gonzalez, Armando; Lopez, Maria T.; Gavidia, Cesar M.; Martinez, Manuel; Alvarado, Manuel; Porras, Miguel; Saavedra, Herbert; Rodriguez, Silvia; Verastegui, Manuela; Mayta, Holger; Herrera, Genaro; Lescano, Andres G.; Zimic, Mirko; Gonzalvez, Guillermo; Moyano, Luz M.; Ayvar, Viterbo; Diaz, Andre

    2012-01-01

    Objective: To determine the frequency of spinal neurocysticercosis (NCC) in patients with basal subarachnoid NCC compared with that in individuals with viable limited intraparenchymal NCC (≤20 live cysts in the brain). Methods: We performed a prospective observational case-control study of patients with NCC involving the basal cisterns or patients with only limited intraparenchymal NCC. All patients underwent MRI examinations of the brain and the entire spinal cord to assess spinal involvement. Results: Twenty-seven patients with limited intraparenchymal NCC, and 28 patients with basal subarachnoid NCC were included in the study. Spinal involvement was found in 17 patients with basal subarachnoid NCC and in only one patient with limited intraparenchymal NCC (odds ratio 40.18, 95% confidence interval 4.74–340.31; p < 0.0001). All patients had extramedullary (intradural) spinal NCC, and the lumbosacral region was the most frequently involved (89%). Patients with extensive spinal NCC more frequently had ventriculoperitoneal shunt placement (7 of 7 vs 3 of 11; p = 0.004) and tended to have a longer duration of neurologic symptoms than those with regional involvement (72 months vs 24 months; p = 0.062). Conclusions: The spinal subarachnoid space is commonly involved in patients with basal subarachnoid NCC, compared with those with only intraparenchymal brain cysts. Spinal cord involvement probably explains serious late complications including chronic meningitis and gait disorders that were described before the introduction of antiparasitic therapy. MRI of the spine should be performed in basal subarachnoid disease to document spinal involvement, prevent complications, and monitor for recurrent disease. PMID:22517102

  5. Monotherapy with stenting in subarachnoid hemorrhage (SAH) after middle cerebral artery dissection.

    PubMed

    Puri, Ajit S; Gounis, Matthew J; Massari, Francesco; Howk, Mary; Weaver, John; Wakhloo, Ajay K

    2016-04-01

    Isolated middle cerebral artery dissection is a rare clinical entity, with descriptions limited to a few case reports and case series. Symptomatic dissection in the anterior circulation can present as an ischemic stroke in a young population; however, it is rarely associated with subarachnoid hemorrhage. We describe a young patient who presented with acute headache from a subarachnoid hemorrhage that was ultimately determined to be due to a vascular dissection in the middle cerebral artery. The initial angiogram showed vascular irregularities in this area with stenosis. Repeat imaging 4 days after presentation identified a pseudoaneurysm proximal to the stenosis. The patient was successfully treated with a self-expanding nitinol stent and followed up with serial angiography during postoperative recovery in the hospital; additional angiograms were performed approximately 1 and 6 months after treatment. Serial angiograms demonstrated incremental healing of the dissection. The patient was discharged and remains neurologically intact at the 6-month follow-up. PMID:25854687

  6. Spontaneous nontraumatic subarachnoid hemorrhage without cerebrovascular malformations in a maintenance hemodialysis patient

    PubMed Central

    Jayasurya, R.; Murugesan, N.; Kumar, R.; Dubey, A. K.; Priyamvada, P. S.; Swaminathan, R. P.; Parameswaran, S.

    2015-01-01

    Nontraumatic subarachnoid hemorrhage (SAH) in a dialysis patient is an uncommon occurrence and is often associated with high mortality. We report for the first time in India, a case of spontaneous nontraumatic, nonaneurysmal SAH without any cerebrovascular malformation in a maintenance hemodialysis patient, following a session of hemodialysis. The dialysis prescription needs to be modified in these patients, in order to prevent worsening of cerebral edema and progression of hemorrhage. Where available, continuous forms of renal replacement therapies, with regional anticoagulation seem to be the best option for such patients, till neurologic stabilization is achieved. PMID:26628800

  7. A case of subarachnoid hemorrhage revealed by an acute coronary syndrome (ACS).

    PubMed

    Hatim, Abdedaim; El Otmani, Wafae; Houssa, Mehdi Ait; Atmani, Noureddine; Moutakiallah, Younes; Haimeur, Charqui; Drissi, Mohammed

    2015-01-01

    The subarachnoid hemorrhage (SAH) is definitely the best descriptive model of the interaction between cardiovascular system and cerebral damage. The underlying mechanism of cardiovascular alterations after SAH is linked to the adrenergic discharge related to aneurysm rupture. Cardiac and pulmonary complications are common after severe brain injury, especially the aneurismal subarachnoid hemorrhage. Acute neurogenic pulmonary edema is not exceptional; it may occur in 20% of cases and commonly follows a severe subarachnoid hemorrhage. Severe myocardial damage with cardiogenic shock may possibly reveal the SAH (3% of cases) and mislead to wrong diagnosis of ACS with dramatic therapeutic consequences. The contribution of CT and cerebral angiography is essential for diagnosis and treatment. Surgical or endovascular treatment depends on location, size and shape of the aneurysm, on patient's age, neurological status and existence of concomitant diseases. We report the case of a 58 years old patient, with a past medical history of diabetes and hypertension, admitted for acute pulmonary edema with cardiogenic shock. This case illustrates an unusual presentation of aneurismal SAH in a patient presenting with an acute coronary syndrome. PMID:26309459

  8. Transient ST elevation and left ventricular asynergy associated with normal coronary artery and Tc-99m PYP Myocardial Infarct Scan in subarachnoid hemorrhage.

    PubMed

    Chang, P C; Lee, S H; Hung, H F; Kaun, P; Cheng, J J

    1998-01-31

    A 72-year-old woman who presented with transient electrocardiographic ST segment elevation and left ventricular asynergy in an acute phase of subarachnoid hemorrhage was found to have normal coronary angiogram and normal Tc-99m PYP myocardial infarct scan. These findings suggested that noninvasive Tc-99m PYP myocardial infarct scan could substitute coronary angiogram for differentiating wall motion and electrocardiographic abnormalities secondary to subarachnoid hemorrhage from those caused by coronary artery disease in patients with subarachnoid hemorrhage. PMID:9510495

  9. Assessment of Basilar Artery Reactivity in Stroke and Subarachnoid Hemorrhage Using Wire Myograph.

    PubMed

    Ghantous, Crystal M; Azrak, Zeina; Rahman, Farah Abdel; Itani, Hana A; Zeidan, Asad

    2016-01-01

    Blood flow regulation of normal cerebral arteries is a critical and important factor to supply the brain tissue with nutrients and oxygen. Stroke insult results in a disruption or reduction in cerebral arteries' blood flow with subsequent brain tissue damage. Hemorrhagic stroke is one type of stroke and accounts for about 13 % of all of stroke insults. In this type of stroke, the cerebral artery breaks open and causes bleeding in or surrounding the brain. Subsequently, this bleeding causes blood vessels to constrict in a process called vasospasm, in which the vessels narrow and impede the blood flow to brain tissue. Hemorrhagic stroke is the major cause of prolonged constriction of cerebral arteries. This leads to partial brain damage and sometimes death in patients with aneurysmal subarachnoid hemorrhage. Among the key delicate techniques to assess small blood vessel functionality is the wire myograph, which can be utilized in several cerebral injury models including stroke. The wire myograph is a device that provides information about the reactivity, stiffness, and elasticity of small blood vessels under isometric conditions. In this book chapter, we describe the techniques involved in wire myography assessment and the different measures and parameters recorded; we describe the utility of this technique in evaluating the effects of subarachnoid hemorrhage on basilar artery sensitivity to different agonists. PMID:27604742

  10. Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

    PubMed

    Chung, David Y; Oka, Fumiaki; Ayata, Cenk

    2016-06-01

    Delayed cerebral ischemia is the most feared cause of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggests that delayed cerebral ischemia represents multiple concurrent and synergistic mechanisms, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SDs) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. We now know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. In this review, we discuss the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage, or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression in subarachnoid hemorrhage and other forms of acute brain injury. PMID:27258442

  11. Arachnoid cell involvement in the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage*

    PubMed Central

    Xin, Zhao-liang; Wu, Xiao-kang; Xu, Jian-rong; Li, Xi

    2010-01-01

    Objective: To assess if arachnoid cells have the capability to present antigen and activate T-lymphocytes after stimulation by bloody cerebrospinal fluid (CSF), and to illuminate the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage (SAH). Methods: Arachnoid cells were cultured, characterized, and examined by immunofluorescence for the basal expression of human leukocyte antigen-DR (HLA-DR). Expression of HLA-DR, after co-culturing arachnoid cells in vitro with bloody CSF, was investigated by immunofluorescence and flow cytometry (FCM). The variation of arachnoid cells’ ultrastructure was observed by transmission electron microscope (TEM). Arachnoid cells were co-cultured with peripheral blood mononuclear cells (PBMCs). The content of soluble interleukin-2 receptor (sIL-2r) in culture medium was detected by enzyme-linked immunosorbent assay (ELISA). Results: (1) Arachnoid cells were successfully cultured for many passages. The immunofluorescent staining was positive for HLA-DR in over 95% of the human arachnoid cells. The punctate HLA-DR was distributed in cytoplasm and not in the karyon. (2) After co-culturing arachnoid cells in vitro with bloody CSF, numerous particles with strong fluorescence appeared in the cytoplasm on Day 6. On Day 8, the quantity of particles and fluorescent intensity were maximal. FCM showed that the percentage of HLA-DR expressing cells was (2.5±0.4)% at the first 5 d, increasing to (60.8±3.6)% on Day 7. (3) After co-culturing arachnoid cells in vitro with bloody CSF, many lysosome and secondary lysosome particles were present in the cytoplasm. Hyperplasia of rough endoplasmic reticulum and enlarged cysts were observed, with numerous phagocytizing vesicles also observed at the edge of the arachnoid cells. (4) Arachnoid cells stimulated by bloody CSF were co-cultured in vitro with PBMCs. The content of sIL-2r in the culture medium, having been maintained at around 1.30 ng/ml during

  12. Copeptin as a Marker for Severity and Prognosis of Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Fung, Christian; De Marchis, Gian Marco; Katan, Mira; Seiler, Marleen; Arnold, Marcel; Gralla, Jan; Raabe, Andreas; Beck, Jürgen

    2013-01-01

    Background Grading of patients with aneurysmal subarachnoid hemorrhage (aSAH) is often confounded by seizure, hydrocephalus or sedation and the prediction of prognosis remains difficult. Recently, copeptin has been identified as a serum marker for outcomes in acute ischemic stroke and intracerebral hemorrhage (ICH). We investigated whether copeptin might serve as a marker for severity and prognosis in aSAH. Methods Eighteen consecutive patients with aSAH had plasma copeptin levels measured with a validated chemiluminescence sandwich immunoassay. The primary endpoint was the association of copeptin levels at admission with the World Federation of Neurological Surgeons (WFNS) grade score after resuscitation. Levels of copeptin were compared across clinical and radiological scores as well as between patients with ICH, intraventricular hemorrhage, hydrocephalus, vasospasm and ischemia. Results Copeptin levels were significantly associated with the severity of aSAH measured by WFNS grade (P = 0.006), the amount of subarachnoid blood (P = 0.03) and the occurrence of ICH (P = 0.02). There was also a trend between copeptin levels and functional clinical outcome at 6-months (P = 0.054). No other clinical outcomes showed any statistically significant association. Conclusions Copeptin may indicate clinical severity of the initial bleeding and may therefore help in guiding treatment decisions in the setting of aSAH. These initial results show that copeptin might also have prognostic value for clinical outcome in aSAH. PMID:23326397

  13. Subarachnoid hemorrhage caused by an undifferentiated sarcoma of the sellar region

    PubMed Central

    Ganaha, Tsukasa; Inamasu, Joji; Oheda, Motoki; Hasegawa, Mitsuhiro; Hirose, Yuichi; Abe, Masato

    2016-01-01

    Background: It is rare for patients with pituitary apoplexy to exhibit concomitant subarachnoid hemorrhage (SAH). Only a handful of patients with pituitary apoplexy have developed such hemorrhagic complications, and histopathological examination revealed pituitary adenoma as the cause of SAH. Case Report: A previously healthy 35-year-old woman was brought to our institution after complaining of severe headache and left monocular blindness. Brain computed tomography showed a diffuse SAH with a central low density. Subsequently, the brain magnetic resonance imaging revealed an intrasellar mass with heterogeneous contrast enhancement. The patient was presumptively diagnosed with SAH secondary to hemorrhagic pituitary adenoma and underwent transcranial surgery to remove both the tumor and subarachnoid clot. A histological evaluation of the surgical specimen revealed malignant cells with strong predilection for vascular invasion. Following immunohistochemical evaluation, the tumor was negative for the majority of tumor markers and was positive only for vimentin and p53; thus, a diagnosis of undifferentiated sarcoma was established. Conclusions: This case was informative in the respect that tumors other than pituitary adenoma should be included in the differential diagnosis of patients with pituitary apoplexy. PMID:27500006

  14. [A case of HELLP syndrome resulting in eclampsia with non-aneurysmal subarachnoid hemorrhage].

    PubMed

    Yoshikane, Tsutomu; Miyazaki, Takeshi; Aoki, Showa; Kambara, Mizuki; Hagiwara, Shinya; Miyazaki, Kohji; Akiyama, Yasuhiko

    2013-02-01

    It is known that hemorrhagic stroke at the perinatal period are caused by specifics conditions like eclampsia as well as by the existing abnormal vessels. We treated a case of HELLP syndrome resulting in eclampsia with non-aneurysmal, convexity subarachnoid hemorrhage. A 34-year-old female, who had been pointed out to have a high level of urinal protein at the 37th week, was seen in the emergency department because of severe headache, vomiting and respiratory discomfort. Her systolic blood pressure was over 190mmHg, and caesarean section was selected. On the way to the operating room, she had a generalized convulsion with loss of consciousness. The delivery was carried out. The CT immediately after the caesarean section revealed faint and localized subarachnoid hemorrhage in the bilateral convexity areas. Additionally, the FLAIR image of MRI demonstrated increased intensity in the bilateral cerebellar hemispheres, basal ganglion and subcortical area, suggesting vasogenic edema. The patient had a good clinical course and the abnormal signal of MRI also recovered by treatment with oral iron and zinc. Here, we report a speculation for the mechanism of this case and precautions against stroke in the perinatal period. PMID:23378389

  15. Dysregulation of oxygen hemodynamic responses to synaptic train stimulation in a rat hippocampal model of subarachnoid hemorrhage.

    PubMed

    Galeffi, Francesca; Degan, Simone; Britz, Gavin; Turner, Dennis A

    2016-04-01

    We investigated microvascular reactivity to synaptic train stimulation after induction of subarachnoid hemorrhage in adult rats, analyzing tissue oxygen levels [pO2] in intact hippocampus. In control rats, hippocampal pO2averaged 11.4 mm Hg whereas hemodynamic responses averaged 13.1 mm Hg (to a 25 s train). After subarachnoid hemorrhage (at 2 days), we recorded a dramatic elevation in baseline pO2in the hippocampus (to 68.4 mm Hg) accompanied by inverted pO2responses to synaptic train stimulation (-9.46 mm Hg). These significant changes in baseline hippocampal pO2and inverted pO2responses after subarachnoid hemorrhage indicate severe alterations of neurovascular coupling and neuronal viability. PMID:26721394

  16. Biomarkers as outcome predictors in subarachnoid hemorrhage – a systematic review

    PubMed Central

    Hong, Caron M.; Tosun, Cigdem; Kurland, David B.; Gerzanich, Volodymyr; Schreibman, David; Simard, J. Marc

    2015-01-01

    Context Subarachnoid hemorrhage (SAH) has a high fatality rate and many suffer from delayed neurological deficits. Biomarkers may aid in the identification of high-risk patients, guide treatment/management and improve outcome. Objective The aim of this review was to summarize biomarkers of SAH associated with outcome. Methods An electronic database query was completed, including an additional review of reference lists to include all potential human studies. Results A total of 298 articles were identified; 112 were reviewed; 55 studies were included. Conclusion This review details biomarkers of SAH that correlate with outcome. It provides the basis for research investigating their possible translation into the management of SAH patients. PMID:24499240

  17. Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage After Lumboperitoneal Shunt for Fulminant Idiopathic Intracranial Hypertension.

    PubMed

    Fok, Anthony; Chandra, Ronil V; Gutman, Matthew; Ligtermoet, Matthew; Seneviratne, Udaya; Kempster, Peter

    2016-06-01

    A 33-year-old woman presented with severe visual loss from fulminant idiopathic intracranial hypertension. Her lumbar puncture opening pressure was 97 cm H2O. Soon after lumboperitoneal shunt surgery, she had a generalized tonic-clonic seizure. Magnetic resonance imaging demonstrated frontal subarachnoid hemorrhage (SAH) and neuroimaging findings consistent with posterior reversible encephalopathy syndrome (PRES). We hypothesize that an abrupt drop in intracranial pressure after lumboperitoneal shunting led to maladjustment of cerebral vascular autoregulation, which caused SAH and PRES. PMID:26919070

  18. Rare anatomical variations of persistent trigeminal artery in two patients with non-aneurysmal subarachnoid hemorrhage.

    PubMed

    Samaniego, Edgar A; Dabus, Guilherme; Andreone, Vincenzo; Linfante, Italo

    2011-09-01

    Carotid-basilar anastomoses are remnants of the fetal circulation and although rare, they may become symptomatic and should be recognized during cerebral angiography. Two patients are described with non-aneurysmal subarachnoid hemorrhage and persistent trigeminal arteries (PTA) found on cerebral angiography. In the first patient, the PTA ended in the anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery. The second patient had a PTA terminating in the AICA and superior cerebellar artery. These rare anatomical PTA variants should be recognized on cerebral angiography. PMID:21990842

  19. A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Hänggi, Daniel; Etminan, Nima; Steiger, Hans Jakob; Johnson, Mark; Peet, M Melissa; Tice, Tom; Burton, Kevin; Hudson, Bruce; Turner, Michele; Stella, Angela; Heshmati, Parissa; Davis, Cara; Faleck, Herbert J; Macdonald, R Loch

    2016-04-01

    Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine-PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612-1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine-PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments. PMID:26935204

  20. High Risk for Seizures Following Subarachnoid Hemorrhage Regardless of Referral Bias

    PubMed Central

    O’Connor, Kathryn L.; Westover, M. Brandon; Phillips, Michael T.; Iftimia, Nicolae A.; Buckley, Deidre A.; Ogilvy, Christopher S.; Shafi, Mouhsin M.

    2016-01-01

    Background To investigate the frequency, predictors, and clinical impact of electrographic seizures in patients with high clinical or radiologic grade non-traumatic subarachnoid hemorrhage (SAH), independent of referral bias. Methods We compared rates of electrographic seizures and associated clinical variables and outcomes in patients with high clinical or radiologic grade non-traumatic SAH. Rates of electrographic seizure detection before and after institution of a guideline which made continuous EEG monitoring routine in this population were compared. Results Electrographic seizures occurred in 17.6 % of patients monitored expressly because of clinically suspected subclinical seizures. In unselected patients, seizures still occurred in 9.6 % of all cases, and in 8.6 % of cases in which there was no a priori suspicion of seizures. The first seizure detected occurred 5.4 (IQR 2.9–7.3) days after onset of subarachnoid hemorrhage with three of eight patients (37.5 %) having the first recorded seizure more than 48 h following EEG initiation, and 2/8 (25 %) at more than 72 h following EEG initiation. High clinical grade was associated with poor outcome at time of hospital discharge; electrographic seizures were not associated with poor outcome. Conclusions Electrographic seizures occur at a relatively high rate in patients with non-traumatic SAH even after accounting for referral bias. The prolonged time to the first detected seizure in this cohort may reflect dynamic clinical features unique to the SAH population. PMID:24723663

  1. A case of cerebral aneurysm rupture and subarachnoid hemorrhage associated with air travel.

    PubMed

    Cui, Victoria; Kouliev, Timur; Wood, Jason

    2014-01-01

    During air travel, passengers are exposed to unique conditions such as rapid ascent and descent that can trigger significant physiological changes. In addition, the cabins of commercial aircraft are only partially pressured to 552-632 mmHg or the equivalent terrestrial altitudes of 1,500-2,500 m (5,000-8,000 feet) above sea level. While studies in high-altitude medicine have shown that all individuals experience some degree of hypoxia, cerebral edema, and increased cerebral blood flow, the neurological effects that accompany these changes are otherwise poorly understood. In this study, we report a case of acute subarachnoid hemorrhage from a ruptured cerebral aneurysm associated with travel on commercial aircraft. We then review relevant cases of neurological incidents with possible air travel-related etiology and discuss the physiological factors that may have contributed to the patient's acute subarachnoid hemorrhage. In the future, this report may serve as reference for more detailed and conservative medical guidelines and recommendations regarding air travel. PMID:27147875

  2. Erythropoietin for the Treatment of Subarachnoid Hemorrhage: A Feasible Ingredient for a Successful Medical Recipe

    PubMed Central

    Grasso, Giovanni; Tomasello, Giovanni; Noto, Marcello; Alafaci, Concetta; Cappello, Francesco

    2015-01-01

    Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been investigated intensively. A number of pathological processes have been identified in the pathogenesis of vasospasm, including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. To date, the current therapeutic interventions remain ineffective as they are limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO) has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is administered systemically. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the current review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrhage. PMID:26581085

  3. Luminal platelet aggregates in functional deficits in parenchymal vessels after subarachnoid hemorrhage

    PubMed Central

    Friedrich, Victor; Flores, Rowena; Muller, Artur; Sehba, Fatima A.

    2010-01-01

    The pathophysiology of early ischemic injury after aneurysmal subarachnoid hemorrhage (SAH) is not understood. This study examined the acute effect of endovascular puncture-induced SAH on parenchymal vessel function in rat, using intravascular fluorescent tracers to assess flow and vascular permeability and immunostaining to assess structural integrity and to visualize platelet aggregates. In sham-operated animals, vessels were well filled with tracer administered 10 seconds before sacrifice, and parenchymal escape of tracer was rare. At ten minutes and 3 hours after hemorrhage, patches of poor vascular filling were distributed throughout the forebrain. Close examination of these regions revealed short segments of narrowed diameter along many profiles. Most vascular profiles with reduced perfusion contained platelet aggregates and in addition showed focal loss of collagen IV, a principal component of basal lamina. In contrast, vessels were well filled at 24 hours post-hemorrhage, indicating that vascular perfusion had recovered. Parenchymal escape of intravascular tracer was detected at 10 minutes post-hemorrhage and later as plumes of fluorescence emanating into parenchyma from restricted microvascular foci. These data demonstrate that parenchymal microvessels are compromised in function by 10 minutes after SAH and identify focal microvascular constriction and local accumulation of luminal platelet aggregates as potential initiators of that compromise. PMID:20654597

  4. Neuropsychological assessments in patients with aneurysmal subarachnoid hemorrhage, perimesencephalic SAH, and incidental aneurysms.

    PubMed

    Krajewski, Kara; Dombek, Susanne; Martens, Tobias; Köppen, Johannes; Westphal, Manfred; Regelsberger, Jan

    2014-01-01

    Subarachnoid hemorrhage (SAH) is known to be associated with long-term cognitive deficits. Neurosurgical manipulation on the brain itself has been reported to have influence on neuropsychological sequelae. The following is a comparative study on perimesencephalic and aneurysmal subarachnoid hemorrhage patients as well as elective aneurysm patients that was carried out to determine the isolated and combined impact of surgical manipulation and hemorrhage, respectively, on long-term neuropsychological outcome. Inclusion criteria were good neurological recovery at discharge (modified Rankin Scale 0 or 1) without focal neurological deficit. Standardized psychological testing covered attention, memory, executive functions, and mood. Thirteen aneurysmal SAH patients, 15 patients undergoing elective clipping, and 14 patients with perimesencephalic SAH were analyzed. Standardized neuropsychological testing and social/professional history questionnaires were performed 2 years (mean) after discharge. Memory impairment and slower cognitive processing were found in the aneurysmal and perimesencephalic SAH groups, while elective aneurysm patients showed signs of impaired attention. However, compared with norm data for age-matched healthy controls, all groups showed no significant test results. In contrast, signs of clinical depression were seen in 9/42 patients, 45 % of all patients complained of stress disorders and 55 % of patients were unable to work in their previous professions. Nearly normal neuropsychological test results on long-term follow-up in SAH patients were unexpected. However, a 50 % rate of unemployment accompanied with stress disorders and depression manifests insufficient social and workplace reintegration. Therefore, even more specific rehabilitation programs are required following inpatient treatment to attain full recovery. PMID:23949148

  5. Subarachnoid Hemorrhage

    MedlinePlus

    ... Volunteer Support TeamCindy Upcoming Events Past Events Support Canada Online Store About Us BAF at a Glance Board of Directors / Staff Medical Advisory Board Sponsors Publications BAF Newsletters Annual Reports News Public Service Announcements Press Releases Blog Administrative Tax ...

  6. Subarachnoid Hemorrhage

    MedlinePlus

    ... The Christopher C. Getch, MD Chair of Research Carol W. Harvey Memorial Chair of Research The Karen ... The Christopher C. Getch, MD Chair of Research Carol W. Harvey Memorial Chair of Research The Karen ...

  7. Subarachnoid Hemorrhage

    MedlinePlus

    ... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2016 - The Internet Stroke Center. All rights reserved. The information contained ...

  8. Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space.

    SciTech Connect

    Stockman, Harlan Wheelock

    2005-01-01

    The lattice Boltzmann method is used to model oscillatory flow in the spinal subarachnoid space. The effect of obstacles such as trabeculae, nerve bundles, and ligaments on fluid velocity profiles appears to be small, when the flow is averaged over the length of a vertebra. Averaged fluid flow in complex models is little different from flow in corresponding elliptical annular cavities. However, the obstacles stir the flow locally and may be more significant in studies of tracer dispersion.

  9. Chronic basilar artery dissection with an associated symptomatic aneurysm presenting with massive subarachnoid hemorrhage.

    PubMed

    Cohen, José E; Moscovici, Samuel; Rajz, Gustavo; Vargas, Andres; Itshayek, Eyal

    2016-08-01

    Basilar artery dissection (BAD) is a rare condition with a worse prognosis than a dissection limited to the vertebral artery. We report a rare case of chronic BAD with an associated symptomatic aneurysm presenting with massive subarachnoid hemorrhage (SAH) in a 54-year-old woman. The diagnosis of acute BAD could only be made retrospectively, based on clinical and neuroradiological studies from a hospital admission 10months earlier. Angiography performed after her SAH showed unequivocal signs of imperfect healing; she was either post-recanalization of a complete occlusion or post-dissection. Residual multi-channel intraluminal defects led to the development of a small aneurysm, which was responsible for the massive hemorrhage. The occurrence of an associated aneurysm, and wall disease, but not an intraluminal process, reinforces the diagnosis of dissection. The patient was fully recovered at 90day follow-up. This case reinforces the need for long-term neuroradiological surveillance after non-hemorrhagic intracranial dissections to detect the development of de novo aneurysms. PMID:26960262

  10. Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats

    PubMed Central

    2012-01-01

    Background Anesthesia is indispensable for in vivo research but has the intrinsic potential to alter study results. The aim of the current study was to investigate the impact of three common anesthesia protocols on physiological parameters and outcome following the most common experimental model for subarachnoid hemorrhage (SAH), endovascular perforation. Methods Sprague-Dawley rats (n = 38) were randomly assigned to (1) chloral hydrate, (2) isoflurane or (3) midazolam/medetomidine/fentanyl (MMF) anesthesia. Arterial blood gases, intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), and regional cerebral blood flow (rCBF) were monitored before and for 3 hours after SAH. Brain water content, mortality and rate of secondary bleeding were also evaluated. Results Under baseline conditions isoflurane anesthesia resulted in deterioration of respiratory parameters (arterial pCO2 and pO2) and increased brain water content. After SAH, isoflurane and chloral hydrate were associated with reduced MAP, incomplete recovery of post-hemorrhagic rCBF (23 ± 13% and 87 ± 18% of baseline, respectively) and a high anesthesia-related mortality (17 and 50%, respectively). Anesthesia with MMF provided stable hemodynamics (MAP between 100-110 mmHg), high post-hemorrhagic rCBF values, and a high rate of re-bleedings (> 50%), a phenomenon often observed after SAH in humans. Conclusion Based on these findings we recommend anesthesia with MMF for the endovascular perforation model of SAH. PMID:22414527

  11. The relationship of subarachnoid hemorrhage and the need for postoperative shunting.

    PubMed

    Vale, F L; Bradley, E L; Fisher, W S

    1997-03-01

    The incidence of chronic hydrocephalus requiring shunting after aneurysmal subarachnoid hemorrhage (SAH) is not precisely known. The authors investigated whether the need for ventriculoperitoneal (VP) shunting can be predicted by initial Hunt and Hess grade or Fisher computerized tomography score. One hundred eight patients who presented with SAH and underwent 116 surgical procedures for aneurysm clipping were evaluated retrospectively to determine the incidence of chronic hydrocephalus. Chronic hydrocephalus was defined as clinically and radiographically demonstrated hydrocephalus that lasted 2 weeks or longer after the original hemorrhage and that required shunting. All SAH patients were managed in a similar fashion with induced hypervolemia, relative hemodilution, and hypertension complemented by a course of calcium channel blockers. The majority of patients underwent perioperative extracranial ventricular drainage to allow intraoperative brain relaxation and to assist intracranial pressure management. The overall mortality rate of the study group was 17%. Of the surviving patients, 20% underwent VP shunt placement secondary to chronic hydrocephalus. There were no statistically significant relationships between chronic hydrocephalus and patient age or gender, aneurysm type and size, or use of a perioperative drain. There was a high clinical correlation between chronic hydrocephalus and admission Hunt and Hess grades and Fisher grades (p < 0.05). All of the patients who survived a second bleeding episode and almost 46% of the patients who presented with intraventricular hemorrhage required placement of a VP shunt. The authors present predictive tables of chronic hydrocephalus based on the patient's admission Hunt and Hess grade and Fisher classification. PMID:9046303

  12. Role of unphosphorylated transcription factor STAT3 in late cerebral ischemia after subarachnoid hemorrhage

    PubMed Central

    Samraj, Ajoy K; Müller, Anne H; Grell, Anne-Sofie; Edvinsson, Lars

    2014-01-01

    Molecular mechanisms behind increased cerebral vasospasm and local inflammation in late cerebral ischemia after subarachnoid hemorrhage (SAH) are poorly elucidated. Using system biology tools and experimental SAH models, we have identified signal transducer and activator of transcription 3 (STAT3) transcription factor as a possible major regulatory molecule. On the basis of the presence of transcription factor binding sequence in the promoters of differentially regulated genes (significant enrichment PE: 6 × 105) and the consistent expression of STAT3 (mRNA, P=0.0159 and Protein, P=0.0467), we hypothesize that unphosphorylated STAT3 may directly DNA bind and probably affect the genes that are involved in inflammation and late cerebral ischemia to influence the pathologic progression of SAH. PMID:24517975

  13. Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage

    PubMed Central

    Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J. Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E. Sander; Kleinberg, Samantha

    2016-01-01

    High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology. PMID:27123582

  14. Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome

    PubMed Central

    Nanba, Takamasa; Kashimura, Hiroshi; Saura, Hiroaki; Takeda, Masaru

    2016-01-01

    Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID:27365964

  15. Carotid rete mirabile associated with subarachnoid hemorrhage from intracranial aneurysm: A case report and systematic review

    PubMed Central

    Yamaki, Vitor Nagai; Júnior, Fernando Mendes Paschoal; Piske, Ronie Leo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2015-01-01

    Carotid rete mirabile (CRM) is a rare physiological vascular network in humans that is most often found in Eastern populations. This paper describes a CRM associated with an aneurysmal subarachnoid hemorrhage (aSAH) and discusses the details of the patient’s treatment. A 28-year-old woman was admitted to our service with clinical signs and symptoms of a spontaneous aSAH. Computed tomography revealed a diffuse and extensive SAH (Fisher group IV), while an angiogram showed an abnormal collateral network in the right carotid system and a hypoplastic aspect to the internal carotid artery (ICA) on the same side. In addition, a saccular aneurysm with a diameter of 9.5 mm was present in the ophthalmic segment of the left ICA. This case is extremely uncommon. To avoid rebleeding in the patient, we successfully treated the patient by clipping the aneurysmal lesion. No procedure was performed for the CRM. PMID:25934776

  16. 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.

  17. A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

    PubMed Central

    Yu, Yong-Peng; Chi, Xiang-Lin; Liu, Li-Jun

    2014-01-01

    Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH. PMID:24707204

  18. Concurrence of Aneurysmal Subarachnoid Hemorrhage and Stanford Type A Acute Aortic Dissection.

    PubMed

    Inamasu, Joji; Suzuki, Takeya; Wakako, Akira; Sadato, Akiyo; Hirose, Yuichi

    2016-06-01

    We report a rare case of concurrent aneurysmal subarachnoid hemorrhage (SAH) and acute aortic dissection (AAD). A 38-year-old man visited our hospital complaining of severe headache, and brain computed tomography (CT) revealed the presence of SAH. Thoracic to neck computed tomography angiography (CTA), performed in addition to brain CTA, suggested a tear in the aortic arch, and subsequent CT aortography established the diagnosis of Stanford type A AAD. The AAD in our patient, who reported no episodes of chest or back pain, was detected incidentally by thoracic to neck CTA. The imaging study has rarely been indicated for SAH except that it provides additional anatomical information in patients for whom extracranial-intracranial bypass surgery or endovascular treatment is considered. Nevertheless, our experience may highlight additional diagnostic value of thoracic to neck CTA in SAH patients. PMID:27083068

  19. Acute subarachnoid hemorrhage in posterior condylar canal dural arteriovenous fistula: imaging features with endovascular management

    PubMed Central

    Mondel, Prabath Kumar; Saraf, Rashmi; Limaye, Uday S

    2014-01-01

    A 43-year-old man presented with acute subarachnoid hemorrhage. He was investigated and found to have a rare posterior condylar canal dural arteriovenous fistula (DAVF). DAVFs of the posterior condylar canal are rare. Venous drainage of the DAVF was through a long, tortuous, and aneurysmal bridging vein. We describe the clinical presentation, cross sectional imaging, angiographic features, and endovascular management of this patient. The patient was treated by transarterial embolization of the fistula through the ascending pharyngeal artery. This is the first report of an acutely bled posterior condylar canal DAVF treated by transarterial Onyx embolization with balloon protection in the vertebral artery. The patient recovered without any neurological deficit and had an excellent outcome. On 6 month follow-up angiogram, there was stable occlusion of the dural fistula. PMID:24990846

  20. Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome.

    PubMed

    Nanba, Takamasa; Kashimura, Hiroshi; Saura, Hiroaki; Takeda, Masaru

    2016-01-01

    Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID:27365964

  1. 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

  2. Compressive Cervicothoracic Adhesive Arachnoiditis following Aneurysmal Subarachnoid Hemorrhage: A Case Report and Literature Review.

    PubMed

    Rahmathulla, Gazanfar; Kamian, Kambiz

    2014-08-01

    We present the case of a 55-year-old woman with diffuse adhesive arachnoiditis in the posterior fossa and cervicothoracic spine following posterior inferior cerebellar artery aneurysmal subarachnoid hemorrhage (SAH). She underwent aneurysm clipping with subsequent gradual neurologic decline associated with sensory disturbances, gait ataxia, and spastic paraparesis. Magnetic resonance imaging revealed diffuse adhesive arachnoiditis in the posterior fossa and cervicothoracic spine, syringobulbia, and multiple arachnoid cysts in the cervicothoracic spine along with syringohydromyelia. Early surgical intervention with microlysis of the adhesions and duraplasty at the clinically relevant levels resulted in clinical improvement. Although adhesive arachnoiditis, secondary arachnoid cysts, and cerebrospinal fluid flow abnormalities resulting in syrinx are rare following aneurysmal SAH, early recognition and appropriate intervention lead to good clinical outcomes. PMID:25083391

  3. [Japanese Guidelines for the Management of Stroke 2015: overview of the chapter on Subarachnoid Hemorrhage].

    PubMed

    Ishihara, Hideyuki; Suzuki, Michiyasu

    2016-04-01

    After an interval of 6 years, the Japanese Guidelines for the Management of Stroke were revised in 2015 in accordance with recent advances in clinical knowledge. The chapter on subarachnoid hemorrhage includes new and revised recommendations for diagnosis, treatment selection, and management of vasospasm. The chapter on diagnosis recommends re-examination of vascular images at regular intervals in cases in which cerebral aneurysm was not detected on the first examination. The section dealing with treatment selection for cerebral aneurysmal emphasizes that the method for aneurysm obliteration should be selected based on consultation with both surgical and endovascular specialists. The role of triple-H therapy(i.e., induced hypertension, hypervolemia, and hemodilution) has changed from a preventive measure to a treatment option for symptomatic cerebral vasospasm. PMID:27333759

  4. Transpulmonary Thermodilution-Based Management of Neurogenic Pulmonary Edema After Subarachnoid Hemorrhage.

    PubMed

    Mutoh, Tatsushi; Kazumata, Ken; Ueyama-Mutoh, Tomoko; Taki, Yasuyuki; Ishikawa, Tatsuya

    2015-11-01

    Neurogenic pulmonary edema (NPE) is a potentially catastrophic but treatable systemic event after subarachnoid hemorrhage (SAH). The development of NPE most frequently occurs immediately after SAH, and the severity is usually self-limiting. Despite extensive research efforts and a breadth of collective clinical experience, accurate diagnosis of NPE can be difficult, and effective hemodynamic treatment options are limited. Recently, a bedside transpulmonary thermodilution device has been introduced that traces physiological patterns consistent with current theories regarding the mechanism (hydrostatic or permeability PE) of NPE. This article provides an overview of the clinical usefulness of the advanced technique for use in the neurointensive care unit for the diagnosis and management of post-SAH NPE. PMID:26517502

  5. Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.

    PubMed

    Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Kleinberg, Samantha

    2016-01-01

    High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology. PMID:27123582

  6. Risk Factors for Rebleeding of Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis

    PubMed Central

    Tang, Chao; Zhang, Tian-Song; Zhou, Liang-Fu

    2014-01-01

    Background Rebleeding is a serious complication of aneurysmal subarachnoid hemorrhaging. To date, there are conflicting data regarding the factors contributing to rebleeding and their significance. Methods A systematic review of PubMed and Embase databases was conducted for studies pertaining to aneurysmal subarachnoid hemorrhage (aSAH) and rebleeding in order to assess the associated risk factors. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated from fourteen studies comprised of a total of 5693 patients that met the inclusion criteria. Results Higher rebleeding rates were observed < 6 h after the initial aSAH (OR  = 3.22, 95% CI  = 1.46–7.12), and were associated with high systolic blood pressure (OR  = 1.93, 95% CI  = 1.31–2.83), poor Hunt-Hess grade (III–IV) (OR  = 3.43, 95% CI  = 2.33–5.05), intracerebral or intraventricular hematomas (OR  = 1.65, 95% CI  = 1.33–2.05), posterior circulation aneurysms (OR  = 2.15, 95% CI  = 1.32–3.49), and aneurysms >10 mm in size (OR  = 1.70, 95% CI  = 1.35–2.14). Conclusions Aneurysmal rebleeding occurs more frequently within the first 6 hours after the initial aSAH. Risk factors associated with rebleeding include high systolic pressure, the presence of an intracerebral or intraventricular hematoma, poor Hunt-Hess grade (III-IV), aneurysms in the posterior circulation, and an aneurysm >10 mm in size. PMID:24911172

  7. Protective effects of perfluorooctyl-bromide nanoparticles on early brain injuries following subarachnoid hemorrhage in rats

    PubMed Central

    Zhang, Huan; Xu, Rui; Xie, Fei; Xu, Wei; Zeng, Meng-Fei; Wang, Xin; Zhu, Ji

    2015-01-01

    To investigate the protective effects of perfluorooctyl-bromide (PFOB) nanoparticles on early brain injury (EBI) following subarachnoid hemorrhage (SAH), a total of 120 rats were randomly assigned to the following groups: Sham operation group (n = 40), SAH group (n = 40), and SAH + PFOB group (n = 40). Endovascular perforation was performed to induce subarachnoid hemorrhage. Brain water content was measured 24 h after surgery. Meanwhile, morphological changes in the rat hippocampal CA1 region were examined using light and transmission electron microscopy. The rate of neuronal apoptosis in rat hippocampal CA1 region was determined using TUNEL assay. Protein and mRNA expression levels of Caspase-3, Bax, and Bcl-2 were measured using western blot and RT-PCR assays 12, 24, 48, and 72 h after surgery. Compared to the SAH group, the SAH + PFOB group had significantly lower brain water content (P<0.01), with alleviated morphological abnormalities in HE-stained neurons and significantly decreased neurons with karyopyknosis and hyperchromatism in the hippocampal CA1 region. Electron microscopy revealed reduction of neuronal apoptosis, alleviation of glial cell swelling, and mitigation of perivascular edema in the hippocampal region. Immunohistochemical analysis showed that the expression of apoptosis-related factors Caspase-3 and Bax was significantly reduced, while that of the anti-apoptotic factor Bcl-2 was significantly increased. TUNEL staining showed that neuronal apoptosis was significantly reduced in the hippocampal CA1 region (P<0.01). RT-PCR and Western-blot data indicated that expressions of Caspase-3 and Bax were both significantly reduced, while bcl-2 expression was increased significantly at 12, 24, 48, and 72 h after SAH (P<0.01). Together, our data support that PFOB nanoparticles with high oxygen content could counteract ischemia and hypoxia, block neuronal apoptotic pathways, reduce neuronal apoptosis, and therefore, achieve neuroprotective effects in EBI

  8. Association of apolipoprotein E polymorphisms with cerebral vasospasm after spontaneous subarachnoid hemorrhage.

    PubMed

    Wu, Hai-tao; Zhang, Xiao-dong; Su, Hai; Jiang, Yong; Zhou, Shuai; Sun, Xiao-chuan

    2011-01-01

    Cerebral vasospasm (CVS) is the main complication of spontaneous subarachnoid hemorrhage (SAH), severely affecting clinical outcome of patients with SAH. Apolipoprotein E gene (APOE) is associated with prognosis of spontaneous subarachnoid hemorrhage (SAH), and APOEε4 allele is reported to be apt to CVS after SAH. The current study aimed to investigate the association of APOE polymorphisms with CVS after SAH. One hundred and eighty-five patients with spontaneous SAH were recruited in the study. APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CVS was judged by Transcranial Doppler sonography (TCD) combined with patients' condition. χ2-test and logistic regression analysis were done by SPSS (version 11.5). The distributions of APOE genotypes and alleles matched Hardy-Weinberg Law. In 185 patients, 21 of 32 (65.7%) patients with APOEε4 allele showed CVS, which was significantly different from those without APOE ε4 allele (56 of 153 patients, 36.6%, P=0.022). However, neither the presence of ε2 nor ε3 was significantly different from those absent of it (P>0.05). Logistic regression analysis demonstrated that ApoEε4 allele was a risk factor (OR=2.842. 95% CI 1.072-6.124. P=0.019) to predispose to CVS after adjusting for age, sex, hypertension or not, hyperlipemia or not, Fisher grade, and Hunt-Hess grade after SAH. Our finding suggests that the patients with APOEε4 allele predispose to CVS after spontaneous SAH. PMID:21116929

  9. Astrocyte Ca2+ Signaling Drives Inversion of Neurovascular Coupling after Subarachnoid Hemorrhage

    PubMed Central

    Pappas, Anthony C.; Koide, Masayo

    2015-01-01

    Physiologically, neurovascular coupling (NVC) matches focal increases in neuronal activity with local arteriolar dilation. Astrocytes participate in NVC by sensing increased neurotransmission and releasing vasoactive agents (e.g., K+) from perivascular endfeet surrounding parenchymal arterioles. Previously, we demonstrated an increase in the amplitude of spontaneous Ca2+ events in astrocyte endfeet and inversion of NVC from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage (SAH) model rats. However, the role of spontaneous astrocyte Ca2+ signaling in determining the polarity of the NVC response remains unclear. Here, we used two-photon imaging of Fluo-4-loaded rat brain slices to determine whether altered endfoot Ca2+ signaling underlies SAH-induced inversion of NVC. We report a time-dependent emergence of endfoot high-amplitude Ca2+ signals (eHACSs) after SAH that were not observed in endfeet from unoperated animals. Furthermore, the percentage of endfeet with eHACSs varied with time and paralleled the development of inversion of NVC. Endfeet with eHACSs were present only around arterioles exhibiting inversion of NVC. Importantly, depletion of intracellular Ca2+ stores using cyclopiazonic acid abolished SAH-induced eHACSs and restored arteriolar dilation in SAH brain slices to two mediators of NVC (a rise in endfoot Ca2+ and elevation of extracellular K+). These data indicate a causal link between SAH-induced eHACSs and inversion of NVC. Ultrastructural examination using transmission electron microscopy indicated that a similar proportion of endfeet exhibiting eHACSs also exhibited asymmetrical enlargement. Our results demonstrate that subarachnoid blood causes a delayed increase in the amplitude of spontaneous intracellular Ca2+ release events leading to inversion of NVC. SIGNIFICANCE STATEMENT Aneurysmal subarachnoid hemorrhage (SAH)—strokes involving cerebral aneurysm rupture and release of blood onto the brain surface

  10. Astrocyte Ca2+ Signaling Drives Inversion of Neurovascular Coupling after Subarachnoid Hemorrhage.

    PubMed

    Pappas, Anthony C; Koide, Masayo; Wellman, George C

    2015-09-30

    Physiologically, neurovascular coupling (NVC) matches focal increases in neuronal activity with local arteriolar dilation. Astrocytes participate in NVC by sensing increased neurotransmission and releasing vasoactive agents (e.g., K(+)) from perivascular endfeet surrounding parenchymal arterioles. Previously, we demonstrated an increase in the amplitude of spontaneous Ca(2+) events in astrocyte endfeet and inversion of NVC from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage (SAH) model rats. However, the role of spontaneous astrocyte Ca(2+) signaling in determining the polarity of the NVC response remains unclear. Here, we used two-photon imaging of Fluo-4-loaded rat brain slices to determine whether altered endfoot Ca(2+) signaling underlies SAH-induced inversion of NVC. We report a time-dependent emergence of endfoot high-amplitude Ca(2+) signals (eHACSs) after SAH that were not observed in endfeet from unoperated animals. Furthermore, the percentage of endfeet with eHACSs varied with time and paralleled the development of inversion of NVC. Endfeet with eHACSs were present only around arterioles exhibiting inversion of NVC. Importantly, depletion of intracellular Ca(2+) stores using cyclopiazonic acid abolished SAH-induced eHACSs and restored arteriolar dilation in SAH brain slices to two mediators of NVC (a rise in endfoot Ca(2+) and elevation of extracellular K(+)). These data indicate a causal link between SAH-induced eHACSs and inversion of NVC. Ultrastructural examination using transmission electron microscopy indicated that a similar proportion of endfeet exhibiting eHACSs also exhibited asymmetrical enlargement. Our results demonstrate that subarachnoid blood causes a delayed increase in the amplitude of spontaneous intracellular Ca(2+) release events leading to inversion of NVC. Significance statement: Aneurysmal subarachnoid hemorrhage (SAH)--strokes involving cerebral aneurysm rupture and release of blood onto the

  11. Deaths from cerebrovascular diseases correlated to month of birth: elevated risk of death from subarachnoid hemorrhage among summer-born

    NASA Astrophysics Data System (ADS)

    Nonaka, K.; Imaizumi, Y.

    It has been suggested that maternal nutrition, and fetal and infant growth have an important effect on the risk of cardiovascular disease in adult life. We investigated the population-based distribution of deaths from cerebrovascular diseases (ICD9 codes 430, 431, or 434) in Japan in 1986-1994 as a function of birth month, by examining death-certificate records. For a total of 853 981 people born in the years 1900-1959, the distribution of the number of deaths according to the month of birth was compared with the distribution expected from the monthly numbers of all births for each sex and for the corresponding birth decade. For those born between 1920 and 1949, there were significant discrepancies between the actual numbers of deaths from subarachnoid hemorrhage (ICD9 430) and the numbers expected, and these differences were related to the month of birth. Those born in summer, June-September, consistently had an elevated risk of death, particularly men, where the excess risk was 8%-23%. This tendency was also observed, less distinctly but significantly, for deaths from intracerebral hemorrhage (ICD9 431), but was not observed for those dying from occlusion of the cerebral arteries (ICD9 434). The observation that the risk of dying from subarachnoid hemorrhage was more than 10% higher among those born in the summer implies that at least one in ten deaths from subarachnoid hemorrhage has its origin at a perinatal stage. Although variations in hypertension in later life, which could possibly be ''programmed'' during the intra-uterine stages, could be an explanation for this observation, the disease-specific nature of the observation suggests the involvement of aneurysm formation, which is a predominant cause of subarachnoid hemorrhage.

  12. Impact of electrolyte imbalances on the outcome of aneurysmal subarachnoid hemorrhage: A prospective study

    PubMed Central

    Alimohamadi, Maysam; Saghafinia, Masoud; Alikhani, Fariba; Danial, Zohreh; Shirani, Mohamad; Amirjamshidi, Abbas

    2016-01-01

    Background: Electrolyte disturbances are frequently observed during the acute and subacute period after subarachnoid hemorrhage (SAH) and may potentially worsen therapeutic outcome. This study was conducted to determine the pattern of electrolyte disturbance in the acute and subacute phase after SAH and their effect on the long-term outcome of the patients. Materials and Methods: Fifty-three patients were prospectively enrolled. The standards of care for all patients were uniformly performed. The serum levels of electrolytes (sodium, potassium and magnesium) were determined with measurements obtained on admission, 3–5 and 7–10 days after SAH. Radiographic intensity of hemorrhage (Fisher's scale), and the clinical grading (World Federation of Neurosurgical Societies grade) were documented in the first visit. The outcomes were evaluated using Glasgow outcome scale at 3 months after discharge. Results: Hyponatremia was the most common electrolyte imbalance among the patients but did not worsen the outcome. Although less common, hypernatremia in the subacute phase was significantly associated with poor outcome. Both hypokalemia and hypomagnesemia were predictive of poor outcomes. Conclusions: Because electrolyte abnormalities can adversely affect the outcome, the serum levels of electrolytes should be closely monitored with serial measurements and treated properly in patients with aneurysmal SAH. PMID:26889275

  13. Mouse genetic background is associated with variation in secondary complications after subarachnoid hemorrhage.

    PubMed

    D'Abbondanza, Josephine A; Lass, Elliot; Ai, Jinglu; Loch Macdonald, R

    2015-01-01

    Spontaneous subarachnoid hemorrhage (SAH) is a form of hemorrhagic stroke that accounts for approximately 7 % of all strokes worldwide and is associated with mortality in approximately 35 % of cases and morbidity in many of the survivors. Studies have suggested that genetic variations may affect the pathophysiology of SAH. The goal of this study was to investigate the effect of mouse genetic background on brain injury and large artery vasospasm after SAH. SAH was induced in seven inbred strains of mice, and the degree of large artery vasospasm and brain injury was assessed. After 48 h, SAH mice showed a significant reduction in middle cerebral artery diameter and increased neuronal injury in the cerebral cortex compared with sham-operated controls. Mouse strains also demonstrated variable degrees of vasospasm and brain injury. This data suggests that different genetic factors influence how much brain injury and vasospasm occur after SAH. Future investigations may provide insight into the causes of these differences between strains and into which genetic contributors may be responsible for vasospasm and brain injury after SAH. PMID:25366595

  14. Plasma Estrogen Levels Are Associated With Severity of Injury and Outcomes After Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Crago, Elizabeth A.; Sherwood, Paula R.; Bender, Catherine; Balzer, Jeffrey; Ren, Dianxu; Poloyac, Samuel M.

    2015-01-01

    Background Biochemical mediators alter cerebral perfusion and have been implicated in delayed cerebral ischemia (DCI) and poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Estrogens (estrone [E1] and estradiol [E2]) are mediators with neuroprotective properties that could play a role in DCI. This study explored associations between plasma estrogen levels and outcomes following aSAH. Methods Plasma samples from 1–4, 4–6, and 7–10 days after hemorrhage from 99 adult aSAH patients were analyzed for estrogen levels using liquid chromatography tandem mass spectrometry. DCI was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. Outcomes were assessed using the Modified Rankin Scale at 3 and 12 months after hemorrhage. Statistical analysis included correlation, regression, and group-based trajectory. Results Higher E1 and E2 levels were associated with higher Hunt and Hess grade (E1, p = .01; E2, p = .03), the presence of DCI (E1, p = .02; E2, p = .02), and poor 3-month outcomes (E1, p = .002; E2, p = .002). Trajectory analysis identified distinct populations over time for E1 (61 % E1 high) and E2 {68% E2 high). Patients in higher trajectory groups had higher Fisher grades (E1, p = .008; E2, p = .01), more frequent DCI (E1, p = .04; E2, p = .08), and worse 3-month outcomes (E1, p = .01; E2, p = .004) than low groups. Conclusions These results provide the first clinical evidence that plasma El and E2 concentrations are associated with severity of injury and outcomes after aSAH. PMID:25548393

  15. Evaluation of a filament perforation model for mouse subarachnoid hemorrhage using 7.0 Tesla MRI.

    PubMed

    Muroi, Carl; Kashiwagi, Yuto; Rokugawa, Takemi; Tonomura, Misato; Obata, Atsushi; Nevzati, Edin; Tsuboi, Akio; Okuchi, Kazuo; Mishima, Kenichi; Abe, Kohji; Fujioka, Masayuki

    2016-06-01

    The filament perforation model (FPM) in mice is becoming increasingly popular to elucidate the molecular pathogenesis of neuronal injury after subarachnoid hemorrhage (SAH). We evaluated brain MRI in a mouse FPM. A total of 28 male C57Bl/6J mice were used. Seventeen animals underwent SAH induction by FPM. In two animals, transient middle cerebral artery occlusion (MCAo) was induced. Nine mice served as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2(∗)-weighted images (T2*WI) and apparent diffusion coefficient maps were acquired at day 0 and at various time points following SAH (range: day 1-6 after SAH). Cerebral blood flow (CBF) analysis by (14)C-iodoamphetamine ((14)C-IMP) autoradiography was conducted in nine animals. Hemorrhage could be best confirmed using T2*WI. The degree of hemorrhage varied. All animals evaluated for ⩾2days were hydrocephalic, which was best seen on T2WI. T2-hyperintensity of the corpus callosum and external capsule, indicating white matter (WM) injury, was present after SAH. Ventricle and WM injury volumes were statistically significantly higher at day 3 compared to day 0. Territorial ischemia was detectable in MCAo but not in SAH. Markedly hypointense cortical veins were visible in the hyperacute and delayed phase after SAH on T2*WI. The (14)C-IMP analysis indicated decreased CBF after SAH. MRI is feasible and useful in evaluating pathophysiological changes over time. T2*WI seems best for SAH detection and grading. The chronological change of hydrocephalus and WM injury could be analyzed. T2*WI illustrated specific signal changes of cortical veins, possibly caused by increased oxygen extraction fraction due to decreased CBF. PMID:27021225

  16. Hyperbaric oxygen therapy fails to reduce hydrocephalus formation following subarachnoid hemorrhage in rats

    PubMed Central

    2014-01-01

    Background & purpose Approximately 40% of hemorrhagic stroke survivors develop hydrocephalus. Hyperbaric oxygen (HBO) has been shown to be anti-inflammation following experimental stroke; however, its effect upon post-hemorrhagic hydrocephalus formation is not known. The objective of this study is to investigate whether HBO therapy can effectively reduce hydrocephalus formation and improve neurobehavioral functions in a rat model of subarachnoid hemorrhage (SAH). Method Thirty-eight male Sprague–Dawley rats (300-320 g) rats survived for 21 days from SAH by endovascular perforation or sham surgery were used. At 24 hours after SAH, HBO (3 atmospheres absolute) or normobaric oxygen (NBO) administrated for 1 hour once daily for a total of 7 days. Wire hanging and rotarod testing were conducted at 14 days after SAH, and cognitive functions were evaluated via the Morris water maze, between day 17 to day 21 after surgery. At day 21, rats were sacrificed and cerebroventricular volumes were measured histologically. Results Hydrocephalus exacerbated neurological deficits after SAH, and HBO multiple treatment tendentially improved the neurobehavioral functions. Spatial learning and memory deficits were noticed after SAH, and rats with hydrocephalus showed worse learning and memory abilities and HBO treatment showed a minor improvement. In the SAH group (room air) 4 rats showed an increased ventricular volume at day 21 after SAH-induction (n = 10). HBO or NBO therapy did not alter the occurrence of hydrocephalus after SAH, as 4 rats in each of these groups showed an increased ventricular volume (n = 10 per group). Conclusion Multiple HBO therapy does not ameliorate hydrocephalus formation in a rat model of SAH; however, HBO tendentially improved the neurological functions and spatial learning and memory abilities in rats with hydrocephalus. PMID:25132956

  17. 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. PMID:25506170

  18. Loss of long-term potentiation in the hippocampus after experimental subarachnoid hemorrhage in rats.

    PubMed

    Tariq, A; Ai, J; Chen, G; Sabri, M; Jeon, H; Shang, X; Macdonald, R L

    2010-01-20

    Survivors of aneurysmal subarachnoid hemorrhage (SAH) often suffer from cognitive impairment such as memory loss. However, the underlying mechanisms of these impairments are not known. Long-term potentiation (LTP) of synapses in the hippocampus is generally regarded as a molecular substrate of memory. The purpose of this study was to examine the effect of SAH on LTP in the hippocampal Schaffer collateral (CA3-CA1) pathway in a rat model of SAH. We found SAH caused significant vasospasm of the middle cerebral artery (MCA) compared to saline injected or sham controls (P<0.001). Basic neurotransmission quantified as excitatory post synaptic and spike response from animals with SAH were significantly decreased as compared to naive controls (P<0.05). However, sham operated and saline injected controls showed similar amplitude as naive controls. This suggests that reduction in basic neurotransmission is due to blood in the subarachnoid space. Similarly, analysis of LTP demonstrated that naive, sham and saline controls have a 92+/-16%, 69+/-27% and 71+/-14% increase over the baseline in the average spike amplitude following high frequency stimulation (HFS), respectively. This indicates the presence of LTP (P<0.05). In contrast, the spike amplitude in animals of SAH returned to baseline level within 60 min post HFS indicating the absence of LTP. We conclude that SAH caused vasospasm of the MCA that was associated with disrupted basic neurotransmission and plasticity at CA3-CA1 synapses. These changes might be accountable for the memory loss in humans with SAH. PMID:19854243

  19. Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates

    PubMed Central

    Fathi, Ali Reza; Pluta, Ryszard M.; Bakhtian, Kamran D.; Qi, Meng; Lonser, Russell R.

    2016-01-01

    Object Subarachnoid hemorrhage (SAH)-induced vasospasm is a significant underlying cause of aneurysm rupture-related morbidity and death. While long-term intravenous infusion of sodium nitrite (NaNO2) can prevent cerebral vasospasm after SAH, it is not known if the intravenous administration of this compound can reverse established SAH-induced vasospasm. To determine if the intravenous infusion of NaNO2 can reverse established vasospasm, the authors infused primates with the compound after SAH-induced vasospasm was established. Methods Subarachnoid hemorrhage–induced vasospasm was created in 14 cynomolgus macaques via subarachnoid implantation of a 5-ml blood clot. On Day 7 after clot implantation, animals were randomized to either control (saline infusion, 5 monkeys) or treatment groups (intravenous NaNO2 infusion at 300 μg/kg/hr for 3 hours [7 monkeys] or 8 hours [2 monkeys]). Arteriographic vessel diameter was blindly analyzed to determine the degree of vasospasm before, during, and after treatment. Nitric oxide metabolites (nitrite, nitrate, and S-nitrosothiols) were measured in whole blood and CSF. Results Moderate-to-severe vasospasm was present in all animals before treatment (control, 36.2% ± 8.8% [mean ± SD]; treatment, 45.5% ± 12.5%; p = 0.9). While saline infusion did not reduce vasospasm, NaNO2 infusion significantly reduced the degree of vasospasm (26.9% ± 7.6%; p = 0.008). Reversal of the vasospasm lasted more than 2 hours after cessation of the infusion and could be maintained with a prolonged infusion. Nitrite (peak value, 3.7 ± 2.1 μmol/L), nitrate (18.2 ± 5.3 μmol/L), and S-nitrosothiols (33.4 ± 11.4 nmol/L) increased significantly in whole blood, and nitrite increased significantly in CSF. Conclusions These findings indicate that the intravenous infusion of NaNO2 can reverse SAH-induced vasospasm in primates. Further, these findings indicate that a similar treatment paradigm could be useful in reversing cerebral vasospasm after

  20. Single Phase Dual-energy CT Angiography: One-stop-shop Tool for Evaluating Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang

    2016-01-01

    Aneurysmal subarachnoid hemorrhages have extremely high case fatality in clinic. Early and rapid identifications of ruptured intracranial aneurysms seem to be especially important. Here we evaluate clinical value of single phase contrast-enhanced dual-energy CT angiograph (DE-CTA) as a one-stop-shop tool in detecting aneurysmal subarachnoid hemorrhage. One hundred and five patients who underwent true non-enhanced CT (TNCT), contrast-enhanced DE-CTA and digital subtraction angiography (DSA) were included. Image quality and detectability of intracranial hemorrhage were evaluated and compared between virtual non-enhanced CT (VNCT) images reconstructed from DE-CTA and TNCT. There was no statistical difference in image quality (P > 0.05) between VNCT and TNCT. The agreement of VNCT and TNCT in detecting intracranial hemorrhage reached 98.1% on a per-patient basis. With DSA as reference standard, sensitivity and specificity on a per-patient were 98.3% and 97.9% for DE-CTA in intracranial aneurysm detection. Effective dose of DE-CTA was reduced by 75.0% compared to conventional digital subtraction CTA. Thus, single phase contrast-enhanced DE-CTA is optimal reliable one-stop-shop tool for detecting intracranial hemorrhage with VNCT and intracranial aneurysms with DE-CTA with substantial radiation dose reduction compared with conventional digital subtraction CTA. PMID:27222163

  1. Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

    PubMed Central

    LIN, CHENG; ZHAO, YUANLI; WAN, GANG; ZHU, ANLIN; WANG, HAO

    2016-01-01

    The aim of the current study was to observe the effects of simvastatin and taurine on delayed cerebral vasospasm (DCVS) following experimental subarachnoid hemorrhage (SAH) in rabbits. A total of 48 New Zealand white rabbits were allocated at random into four groups (control, SAH, SAH + simvastatin and SAH + taurine groups; n=12 each). The rabbit model of DCVS was established using a double hemorrhage method, which involved injecting autologous arterial blood into the cisterna magna in the SAH groups. The SAH + simvastatin group was administered oral simvastatin (5 mg/kg) daily between days 0–6. The SAH + taurine group was administered oral taurine (50 mg/kg) daily between days 0–6. Starch (50 mg/kg) was administered orally to the animals in the other two groups (control and SAH groups). The control group were not subjected to any other injections or treatment. The internal diameter and internal diameter/wall thickness of the basilar artery (BA) were measured. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were determined using immunohistochemical and quantitative polymerase chain reaction methods following the sacrifice of all animals on day 7. The activity of nuclear factor (NF)-κB in the BA was also measured using an electrophoretic mobility shift assay. The BA walls in the SAH + simvastatin and SAH + taurine groups exhibited reduced narrowing and corrugation of the tunica elastica interna compared with the SAH group. At the protein and cDNA levels, it was found that cerebral vasospasm of the BA in the SAH + simvastatin and SAH + taurine groups was alleviated, as indicated by the reduced expression of TNF-α, IL-1β, IL-6 and NF-κB compared with the SAH group (P<0.05). In conclusion, simvastatin and taurine reduced DCVS following SAH in rabbits, which suggests that these compounds may exert anti-inflammatory effects. PMID:27073449

  2. Current Status of Endovascular Treatment for Vasospasm following Subarachnoid Hemorrhage: Analysis of JR-NET2

    PubMed Central

    HAYASHI, Kentaro; HIRAO, Tomohito; SAKAI, Nobuyuki; NAGATA, Izumi

    2014-01-01

    Endovascular treatments are employed for cerebral vasospasm following subarachnoid hemorrhage, which is not responded to the medical treatments. However, the effect or complication of the treatments is not known well. Here, we analyzed the data of Japanese Registry of Neuroendovascular Therapy 2 (JRNET2) and revealed current status of the endovascular treatment for the cerebral vasospasm. JR-NET2 is conducted from January 1, 2007 to December 31, 2009. Information on the clinical status, imaging studies, treatment methods, the results of treatment, and status 30 days later were recorded. Totally 645 treatments for 480 patients (mean age, 59.4 years; 72.7% woman) were included. Factors related to the neurological improvement and treatment related complications were statistically analyzed. Treatments for ruptured cerebral aneurysm were direct surgery for 366 cases and endovascular treatment for 253 cases. The timing of the endovascular treatment for the cerebral vasospasm was within 3 hours in 209 cases, 3–6 hours in 158 cases, and more than 6 hours in 158 cases. Intra-arterial vasodilator was employed for the 495 cases and percutaneous transluminal angioplasty for 140 cases. Neurological improvement was observed in 372 cases and radiological improvement was seen in 623 cases. The treatment related complication occurred in 20 cases (3.1%), including 6 cases of intracranial hemorrhage, 5 cases of cerebral ischemia, a case of puncture site trouble, and 8 cases of others. Statistical analysis showed early treatment was related to the neurological improvement. Current status of endovascular treatment for cerebral vasospasm was revealed. Endovascular treatment was effective for vasospasm especially was performed early. PMID:24257541

  3. Human cerebrospinal fluid microRNA: temporal changes following subarachnoid hemorrhage.

    PubMed

    Powers, Ciarán J; Dickerson, Ryan; Zhang, Stacey W; Rink, Cameron; Roy, Sashwati; Sen, Chandan K

    2016-05-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of hemorrhagic stroke with 30-day mortality between 33 and 45%. Delayed cerebral ischemia (DCI) is the chief cause of morbidity and mortality in patients who survive the initial aSAH. DCI accounts for almost 50% of deaths in patients surviving to treatment of the ruptured aneurysm. The mechanisms for brain injury after aSAH and the brain's response to this injury are not fully understood in humans. MicroRNAs (miRs) are 22- to 25-nucleotide single-stranded RNA molecules that inhibit the expression of specific messenger RNA targets. In this work, miR profiling of human cerebrospinal fluid from eight patients after aSAH was performed daily for 10 days with the goal of identifying changes in miR abundance. Using the nanoString nCounter Expression Assay, we identified two specific clusters of miR that were differentially regulated over time. Quantitative RT-PCR was performed on select miRs from each cluster. The first cluster contained miRs known to be present in blood and decreased in abundance over time. miRs in this group include miR-92a and let-7b. The second cluster contained several poorly characterized miRs that increased in abundance over time. miRs in this group included miR-491. This second cluster of miRs may be released into the CSF by the brain itself as a result of the initial SAH. Temporal changes in the abundance of specific miRs in human CSF after aSAH may provide novel insight into the role of miRs in brain injury and the brain's response. PMID:26945012

  4. Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

    PubMed Central

    Kooijman, Elke; Nijboer, Cora H.; van Velthoven, Cindy T. J.; Mol, Wouter; Dijkhuizen, Rick M.; Kesecioglu, Jozef; Heijnen, Cobi J.

    2014-01-01

    Subarachnoid hemorrhage (SAH) represents a considerable health problem with an incidence of 6–7 per 100.000 individuals per year in Western society. We investigated the long-term consequences of SAH on behavior, neuroinflammation and gray- and white-matter damage using an endovascular puncture model in Wistar rats. Rats were divided into a mild or severe SAH group based on their acute neurological score at 24 h post-SAH. The degree of hemorrhage determined in post-mortem brains at 48 h strongly correlated with the acute neurological score. Severe SAH induced increased TNF-α, IL-1β, IL-10, MCP-1, MIP2, CINC-1 mRNA expression and cortical neutrophil influx at 48 h post-insult. Neuroinflammation after SAH was very long-lasting and still present at day 21 as determined by Iba-1 staining (microglia/macrophages) and GFAP (astrocytes). Long-term neuroinflammation was strongly associated with the degree of severity of SAH. Cerebral damage to gray- and white-matter was visualized by immunohistochemistry for MAP2 and MBP at 21 days after SAH. Severe SAH induced significant gray- and white-matter damage. MAP2 loss at day 21 correlated significantly with the acute neurological score determined at 24 h post-SAH. Sensorimotor behavior, determined by the adhesive removal task and von Frey test, was affected after severe SAH at day 21. In conclusion, we are the first to show that SAH induces ongoing cortical inflammation. Moreover, SAH induces mainly cortical long-term brain damage, which is associated with long-term sensorimotor damage. PMID:24603553

  5. The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

    PubMed Central

    2014-01-01

    Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed. SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH. Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult. PMID:24386932

  6. Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using classification and regression tree analysis

    PubMed Central

    Lo, Benjamin W. Y.; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R. Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A. H.

    2016-01-01

    Background: 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). Methods: 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. Results: 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). Conclusions: 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. PMID:27512607

  7. Astragaloside IV Alleviates Early Brain Injury Following Experimental Subarachnoid Hemorrhage in Rats

    PubMed Central

    Shao, Anwen; Guo, Songxue; Tu, Sheng; Ammar, Al-baadani; Tang, Junjia; Hong, Yuan; Wu, Haijian; Zhang, Jianmin

    2014-01-01

    Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti-apoptotic effects. PMID:25136262

  8. CSF and Serum Biomarkers Focusing on Cerebral Vasospasm and Ischemia after Subarachnoid Hemorrhage

    PubMed Central

    Jung, Carla S.; Lange, Bettina; Zimmermann, Michael; Seifert, Volker

    2013-01-01

    Delayed cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) remain severe complications after subarachnoid hemorrhage (SAH). Although focal changes in cerebral metabolism indicating ischemia are detectable by microdialysis, routinely used biomarkers are missing. We therefore sought to evaluate a panel of possible global markers in serum and cerebrospinal fluid (CSF) of patients after SAH. CSF and serum of SAH patients were analyzed retrospectively. In CSF, levels of inhibitory, excitatory, and structural amino acids were detected by high-performance liquid chromatography (HPLC). In serum, neuron-specific enolase (NSE) and S100B level were measured and examined in conjunction with CVS and DCI. CVS was detected by arteriography, and ischemic lesions were assessed by computed tomography (CT) scans. All CSF amino acids were altered after SAH. CSF glutamate, glutamine, glycine, and histidine were significantly correlated with arteriographic CVS. CSF glutamate and serum S100B were significantly correlated with ischemic events after SAH; however, NSE did not correlate neither with ischemia nor with vasospasm. Glutamate, glutamine, glycine, and histidine might be used in CSF as markers for CVS. Glutamate also indicates ischemia. Serum S100B, but not NSE, is a suitable marker for ischemia. These results need to be validated in larger prospective cohorts. PMID:23509668

  9. Protective effect 3,4-dihydroxyphenylethanol in subarachnoid hemorrhage provoked oxidative neuropathy

    PubMed Central

    Zhong, Yu-Wen; Wu, Juan; Hu, Hua-Long; Li, Wei-Xin; Zhong, Yong

    2016-01-01

    Clinical studies have indicated that early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with fatal outcomes. Oxidative stress and brain edema are the characteristic pathological events in occurrence EBI following SAH. The present study aimed to examine the effect of 3,4-dihydroxyphenylethanol (DOPET) against SAH-induced EBI, and to demonstrate whether the effect is associated with its potent free radical scavenging property. SAH was induced in rats using an endovascular perforation technique, and 24 h later the rats displayed diminished neurological scores and brain edema. Furthermore, elevated malondialdehyde (an index of lipid peroxidation) and depleted levels of antioxidants were observed in the rat cerebral cortex tissue. Quantitative polymerase chain reaction analysis indicated the upregulated mRNA expression of the apoptotic markers caspase-3 and −9 in the cerebral cortex. Furthermore, the protein expression levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly upregulated in SAH-induced rats. By constrast, treatment with DOPET significantly attenuated EBI by reducing brain edema, elevation of antioxidant status, inhibition of apoptosis and inflammation. In this context, DOPET may be a potent agent in the treatment of EBI following SAH, as a result of its free radical scavenging capacity. PMID:27588109

  10. [Subarachnoid hemorrhage complicated with different manifestations of transient abnormal left ventricular wall motion: two case reports].

    PubMed

    Inoue, Fumitaka; Tsuzuki, Takashi; Thoma, Yoshiki; Shiono, Shigeru; Tabuse, Hisayuki; Hoshida, Thoru; Saito, Yoshihiko

    2006-05-01

    Two patients with subarachnoid hemorrhage presented with transient abnormal left ventricular wall motion. Case 1 was a 56-year-old man. Electrocardiography showed ST segment elevation in leads I, II, II, aVL, aVF, V3-V6. Echocardiography showed localized left ventricular hypokinesis around the apical area (takotsubo-like cardiomyopathy). Ejection fraction was 20% (1st hospital day). Troponin T was positive. Case 2 was a 48-year-old woman. Electrocardiography showed ST segment elevation in leads I, aVL, V2-V6 and ST segment depression in leads II, III, aVF, V1. Echocardiography showed diffuse left ventricular hypokinesis. Ejection fraction was 21% (1st hospital day). Troponin T was positive. These two patients had no history of cardiac disease, and coronary angiography showed no stenosis or obstruction. Catecholamine was given for 1 day(Case 1) and for about 2 weeks (Case 2). Pimobendane was given to Case 2. Ejection fraction was 57% in Case 1 (2nd hospital day) and 33% (6th hospital day), 43% (7th hospital day)and 58% (16th hospital day)in Case 2. The recovery period of left ventricular abnormal wall motion and the medication period were longer in Case 2 showing diffuse hypokinesis than in Case 1 showing takotsubo-like cardiomyopathy. PMID:16764331

  11. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

    PubMed Central

    Østergaard, Leif; Aamand, Rasmus; Karabegovic, Sanja; Tietze, Anna; Blicher, Jakob Udby; Mikkelsen, Irene Klærke; Iversen, Nina Kerting; Secher, Niels; Engedal, Thorbjørn Søndergaard; Anzabi, Mariam; Jimenez, Eugenio Gutierrez; Cai, Changsi; Koch, Klaus Ulrik; Næss-Schmidt, Erhard Trillingsgaard; Obel, Annette; Juul, Niels; Rasmussen, Mads; Sørensen, Jens Christian Hedemann

    2013-01-01

    The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions. PMID:24064495

  12. Attention and executive functions in microsurgically treated patients after subarachnoid hemorrhage

    PubMed Central

    Koso, Maida; Dizdarevic, Kemal

    2015-01-01

    Objectives: This research aimed to assess attention and executive functions in subarachnoid hemorrhage (SAH) patients. Methods: The prospective, controlled, longitudinal study was conducted. There were two groups of patients (SAH and lumbar microdiscectomy groups), and all of them were operated on by a single neurosurgeon (KD) in the same institution. Preoperatively, SAH patients were in the Hunt-Hess Grade I and II. They did not develop any focal neurological deficit or hydrocephalus postoperatively. The patients were tested in 2-time points: 15 and 45 days after microsurgery with a battery of tests and questioners consisting of the Trail Making Test, the Sustained Attention to Response Task, the Hayling Sentence Completion Test, The Attention/Concentration test of Attention, the Wechsler Adult Intelligence Scale (verbal part). Results between groups were compared (sex, age; years of education and verbal IQ). Results: It was found the presence of lower attention and executive function test scores in the SAH group of patients with a trend of improving during the time. Conclusion: The detailed neuropsychological assessment of operated patients who sustained SAH and were without the focal neurological deficit postoperatively, showed declination in their attention and executive function with a trend of cognitive recovery as time passes by. PMID:26425152

  13. Trends in the use of pulmonary artery catheterization in the aneurysmal subarachnoid hemorrhage population.

    PubMed

    Inouye, S; Jin, D; Cen, S; Nguyen, P; Renda, N; Amar, A P; Mack, W J; Kim-Tenser, M A

    2016-09-01

    Use of the pulmonary artery catheter (PAC) has been controversial since the late 1980s. Multi-center observational and randomized controlled trials (RCTs) have concluded that PACs fail to decrease mortality. Subsequently, studies have looked for a decline in PAC use that corresponds to the literature and have indeed found that it exists. However, none to date have looked primarily at trends in the aneurysmal subarachnoid hemorrhage (aSAH) population. This study uses the Nationwide Inpatient Sample (NIS) from 2000-2010 to identify trends in PAC use among patients with aSAH. Trend analysis was assessed using a multivariable regression model with a calculation of slope of PAC frequency over time for pre-2005 and post-2005. Trends in mortality and routine discharge were also assessed for the same time period. 363,096 SAH patients were extrapolated using survey weights, of whom 6,988 had a PAC. Over time, PAC use declined, with a significant downward shift in the year 2005. Analyses also showed a decrease in mortality over the same time period. Our results show that PAC use among patients with aSAH decreased from 2000 to 2010. Similar to other studies, the decline appears to be temporally related to RCTs that showed a lack of benefit from PAC. Studies such as these have the potential to influence clinical practice through illumination of shifting opinions and approaches. PMID:27068011

  14. Protein expression levels in the medullary visceral zone of rats with subarachnoid hemorrhage.

    PubMed

    Sun, L H; Xing, L F; Zhang, G H; Pan, S Y

    2015-01-01

    We investigated protein expression in the medullary visceral zone (MVZ) of rats with multiple-organ dysfunction syndrome (MODS) caused by subarachnoid hemorrhage (SAH) to discuss the possible regulatory mechanism of the MVZ in the course of SAH-induced MODS. A SAH-induced MODS model was established in rats by injecting arterial blood into the Willis' circle. Protein expression in the MVZ was analyzed by immunohistochemistry assay. Protein expression in the MVZ peaked 24-36 h after SAH, and was significantly higher than in the control and sham operation groups. Organs at each time point exhibited inflammatory injuries to varying degrees after SAH, which reached a maximum at 24-36 h. Incidences of systemic inflammatory response syndrome and MODS were 100 and 71.67%, respectively, after SAH. There is a consistency between MVZ protein expression and inflammatory changes in each organ after SAH. This prompts the suggestion that the MVZ may be one of the direct regulative centers in SAH-induced MODS, and may be involved in the functional regulation of the surrounding organs after SAH. PMID:26345815

  15. Intravenous Flat-Detector Computed Tomography Angiography for Symptomatic Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Jeon, Jin Pyeong; Sheen, Seung Hun; Cho, Yong-Jun

    2014-01-01

    The study evaluated the diagnostic accuracy of intravenous flat-detector computed tomography (IV FDCT) angiography in assessing hemodynamically significant cerebral vasospasm in patients with subarachnoid hemorrhage (SAH) with digital subtraction angiography (DSA) as the reference. DSA and IV FDCT were conducted concurrently in patients suspected of having symptomatic cerebral vasospasm postoperatively. The presence and severity of vasospasm were estimated according to location (proximal versus distal). Vasospasm >50% was defined as having hemodynamic significance. Vasospasms <30% were excluded from this analysis to avoid spectrum bias. Twenty-nine patients (311 vessel segments) were measured. The intra- and interobserver agreements were excellent for depicting vasospasm (k = 0.84 and 0.74, resp.). IV FDCT showed a sensitivity of 95.7%, specificity of 92.3%, positive predictive value of 93.6%, and negative predictive value of 94.7% for detecting vasospasm (>50%) with DSA as the reference. Bland-Altman plots revealed good agreement of assessing vasospasm between the two tests. The discrepancy of vasospasm severity was more noted in the distal location with high-severity. However, it was not statistically significant (Spearman's rank test; r = 0.15, P = 0.35). Therefore, IV FDCT could be a feasible noninvasive test to evaluate suspected significant vasospasm in SAH. PMID:25383367

  16. 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

  17. TREATMENT OF A CEREBRAL DISSECTING ANEURYSM IN ANTERIOR CIRCULATION: REPORT OF 11 SUBARACHNOID HEMORRHAGE CASES

    PubMed Central

    OYAMA, HIROFUMI; KITO, AKIRA; MAKI, HIDEKI; HATTORI, KENICHI; NODA, TOMOYUKI; WADA, KENTARO

    2012-01-01

    ABSTRACT This report presents 8 cases of internal carotid artery aneurysms, 1 case of a middle cerebral artery aneurysm, and 2 cases of anterior cerebral artery aneurysms, together with a discussion of the treatment of aneurysms in anterior circulation. All cases showed subarachnoid hemorrhage. Two of the 8 internal carotid artery aneurysms were trapped with a low-flow bypass; however, both patients died of an immediate hemodynamic infarction or vasospasm-induced infarction. Five of the 8 internal carotid artery aneurysms were trapped after revascularization with high flow bypass. Four of those patients were self-supporting at discharge, but one patient was discharged in a vegetative state due to the sacrifice of arterial branches which were included in the dissecting portion. One case of the dissecting aneurysm in the M2 portion of the middle cerebral artery was trapped after low-flow bypass. This patient was self-supporting at discharge. In 2 cases of anterior cerebral artery aneurysms, the lesions were first wrapped with Bemsheets, and then the aneurysmal clip was applied on the wrapped dome. Trapping following high-flow bypass is the best method for treating a dissecting aneurysm in the internal carotid artery. Trapping also can be used to treat a dissecting aneurysm of the middle cerebral artery, after low-flow bypass. Clipping on the wrapped aneurysm can also be performed successfully in the anterior cerebral artery aneurysm. PMID:23092105

  18. Massive Cerebrospinal Fluid Replacement Reduces Delayed Cerebral Vasospasm After Embolization of Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Geng, Liming; Ma, Fei; Liu, Yun; Mu, Yanchun; Zou, Zhongmin

    2016-01-01

    Background Delayed cerebral vasospasm (DCVS) following aneurismal subarachnoid hemorrhage (SAH) is a leading cause of poor prognosis and death in SAH patients. Effective management to reduce DCVS is needed. A prospective controlled trial was conducted to determine if massive cerebrospinal fluid (CSF) replacement (CR) could reduce DCVS occurrence and improve the clinical outcome after aneurysmal SAH treated with endovascular coiling. Material/Methods Patients treated with endovascular coiling after aneurysmal SAH were randomly divided into a control group receiving regular therapy alone (C group, n=42) and a CSF replacement group receiving an additional massive CSF replacement with saline (CR group, n=45). CSF examination, head CT, DCVS occurrence, cerebral infarction incidence, Glasgow Outcome Scale prognostic score, and 1-month mortality were recorded. Results The occurrence of DCVS was 30.9% in the C group and 4.4% in the CR group (P<0.005). The cerebral infarction incidences in the C and CR groups were 19.0% and 2.2% (P<0.05), respectively, 1 month after the treatments. Mortality was not significantly different between the 2 groups during the follow-up period. Conclusions Massive CR after embolization surgery for aneurysmal SAH can significantly reduce DCVS occurrence and effectively improve the outcomes. PMID:27394187

  19. Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

    PubMed Central

    Schallner, Nils; Pandit, Rambhau; LeBlanc, Robert; Thomas, Ajith J.; Ogilvy, Christopher S.; Zuckerbraun, Brian S.; Gallo, David; Otterbein, Leo E.; Hanafy, Khalid A.

    2015-01-01

    Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms. PMID:26011640

  20. Differential effects of activity and climate on onset of subarachnoid hemorrhage.

    PubMed

    Kawai, K; Nonaka, K; Suzuki, H; Kirino, T; Tamura, A

    2001-05-01

    Conflicting findings of the effect of climate on onset of subarachnoid hemorrhage (SAH) may result from the influence of strenuous activities which can trigger aneurysmal rupture independent of climatological factors. The effect of climate and patient activities on onset of SAH were analyzed. The clinical records of 786 consecutive patients with aneurysmal SAH admitted to our hospital for 10 years were reviewed. Activities at onset were categorized according to the intensity of strain at onset. Seasonal variation, circannual cyclic trend, and association with 90 meteorological factors were examined in each category and the results were compared between categories. Bimonthly occurrence in the light strain group showed a significant seasonal variation and cyclic trend with two peaks in early spring and fall, whereas no significant trend was detected in the overall patients and in the heavy strain group. The significant meteorological factors were global solar radiation, sunshine hours, changes in mean and minimum temperature and mean vapor pressure from the previous day, and minimum pressure in the previous 7 days. Lower global solar radiation in the light strain group was associated with onset with the lowest p value (p = 0.0046). No factors were significant in the heavy strain group. There is some evidence of the possible influence of climatological factors on onset of SAH without strenuous activity. Strenuous activity seems to affect onset more strongly, which masks any effect of climate. PMID:11396302

  1. Clinical experience with nimodipine in the prophylaxis of neurological deficits after subarachnoid hemorrhage.

    PubMed

    Kazner, E; Sprung, C; Adelt, D; Ammerer, H P; Karnick, R; Baumann, H; Böker, D K; Grotenhuis, J A; Jaksche, H; Istaitih, A R

    1985-05-01

    The efficacy and tolerability of the dihydropyridine calcium antagonist nimodipine (BAY e 9736) in the prophylaxis of ischemic neurological deficits after subarachnoid hemorrhage were investigated in 171 patients in an open, prospective, multicenter study. 68 of the patients had to be excluded from the efficacy assessment as they had failed to satisfy important inclusion criteria. The efficacy assessment was based on 104 patients of Hunt and Hess grades I-III. In 86 patients the ruptured aneurysm was clipped before or during the nimodipine therapy, while 18 patients did not undergo surgery owing to failure to detect an aneurysm, continuous deterioration of the clinical condition, or for other reasons. At the end of the nimodipine treatment 74 of the patients (71%) were completely free from symptoms or had only very slight neurological deficits. There were 10 patients (10%) with moderate and 10 with a severe disablement, 4 patients were apallic, and 6 (6%) died during the nimodipine treatment. In 4 patients (3.8%) cerebral vasospasm was the sole cause of severe neurological deficits or death, while in a further 3 patients (2.7%) vasospasm and other serious complications were responsible for poor outcome. 22 of the 171 patients (12.9%) died during or shortly after nimodipine therapy. Rebleeding occurred during nimodipine therapy in 7 of the 143 preoperatively treated cases (4.9%). PMID:4010865

  2. Caspase-1 inhibitor Prevents Neurogenic Pulmonary Edema after Subarachnoid Hemorrhage in Mice

    PubMed Central

    Suzuki, Hidenori; Sozen, Takumi; Hasegawa, Yu; Chen, Wanqiu; Zhang, John H.

    2009-01-01

    Background and Purpose We examined the effects of a caspase-1 inhibitor, N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK), on neurogenic pulmonary edema (NPE) in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice. Methods Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10mg/kg) and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1β, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens (ZO)-1, MMP zymography, TUNEL staining and immunostaining were performed on the lung at 24 hours post-SAH. Results Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1β and caspase-3 and the number of TUNEL-positive pulmonary endothelial cells, preventing NPE. Another antiapoptotic drug Z-VAD-FMK also reduced NPE. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, ZO-1 levels and MMP activity. Conclusions We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and NPE after SAH in mice. PMID:19875734

  3. Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage.

    PubMed

    Zhang, Dingding; Zhang, Huasheng; Hao, Shuangying; Yan, Huiying; Zhang, Zihuan; Hu, Yangchun; Zhuang, Zong; Li, Wei; Zhou, Mengliang; Li, Kuanyu; Hang, Chunhua

    2016-06-15

    A growing body of evidence demonstrates that Akt may serve as a therapeutic target for treatment of early brain injury following subarachnoid hemorrhage (SAH). The purpose of the current study was to evaluate the neuroprotective effect of Akt specific activator SC79 in an experimental rat model of SAH. SAH was induced by injecting 300 μL of blood into the prechiasmatic cistern. Intracerebroventricular (ICV) injection of SC79 (30 min post-SAH) induced the p-Akt (Ser473) expression in a dose-dependent manner. A single ICV dose treatment of SC79 (100 μg/rat) significantly increased the expression of Bcl-2 and p-GSK-3β (Ser9), decreased the protein levels of Bax, cytoplasm cytochrome c, and cleaved caspase-3, indicating the antiapoptotic effect of SC79. As a result, the number of apoptotic cells was reduced 24 h post SAH. Moreover, SC79 treatment alleviated SAH-induced oxidative stress, restored mitochondrial morphology, and improved neurological deficits. Strikingly, treatment of SC79 provided a beneficial outcome against neurologic deficit with a therapeutic window of at least 4 h post SAH by ICV injection and 30 min post SAH by intraperitoneal injection. Collectively, SC79 exerts its neuroprotective effect likely through the dual activities of antioxidation and antiapoptosis. These data provide a basic platform to consider SC79 as a novel therapeutic agent for treatment of SAH. PMID:26983552

  4. Role of Mitochondrial Calcium Uniporter in Early Brain Injury After Experimental Subarachnoid Hemorrhage.

    PubMed

    Yan, Huiying; Zhang, Dingding; Hao, Shuangying; Li, Kuanyu; Hang, Chun-Hua

    2015-12-01

    Previous studies have shown that mitochondrial Ca(2+) is undertaken by mitochondrial calcium uniporter (MCU), and its accumulation is associated with the development of many diseases. However, little was known about the role of MCU in early brain injury (EBI) after subarachnoid hemorrhage (SAH). MCU can be opened by spermine under a physiological condition and inhibited by ruthenium red (RR). Herein, we investigated the effects of RR and spermine to reveal the role of MCU in SAH animal model. The data obtained with biochemical and histological assays showed that mitochondrial Ca(2+) concentration was significantly increased in the temporal cortex of rats 1, 2, and 3 days after SAH, consistent with constant high levels of cellular Ca(2+) concentration. In agreement with the observation in the acute phase, SAH rats showed an obvious increase of reactive oxygen species (ROS) level and decrease of ATP production. Blockage of MCU prevented Ca(2+) accumulation, abated the level of oxidative stress, and improved the energy supply. Translocation of cytochrome c, increased cleaved caspase-3, and a large amount of apoptotic cells after SAH were reversed by RR administration. Surprisingly, exogenous spermine did not increase cellular Ca(2+) concentration, but lessened the Ca(2+) accumulation after SAH to benefit the rats. Taken together, our results demonstrated that blockage of MCU or prevention of Ca(2+) accumulation after SAH is essential in EBI after SAH. These findings suggest that MCU is considered to be a therapeutic target for patients suffering from SAH. PMID:25370932

  5. Roller coaster-associated subarachnoid hemorrhage--report of 2 cases.

    PubMed

    Rutsch, Sebastian; Niesen, Wolf-Dirk; Meckel, Stephan; Reinhard, Matthias

    2012-04-15

    The most common neurological injuries associated with roller coaster rides are subdural hematoma and cervical artery dissection. We report two cases of roller-coaster associated subarachnoid hemorrhage (SAH). A 40-year-old healthy man developed a strong, holocephalic headache during a roller coaster ride. SAH Hunt & Hess grade II and Fisher grade 3 was diagnosed. An underlying aneurysm of the anterior communicating artery was successfully treated with coil embolization. A 41-year-old female (smoker, otherwise healthy) experienced a sudden, strong headache and diplopia during a roller coaster ride. A perimesencephalic SAH (Hunt & Hess grade II, Fisher grade 3) was disclosed by a CT scan. No aneurysm was detected on angiography. Both patients were discharged without neurological disability. In conclusion, SAH is a rare but relevant differential diagnosis in cases of acute headache during roller coaster rides. Both aneurysmal and non-aneurysmal perimesencephalic SAH can occur. A combination of mechanical factors and excessive blood pressure rises in vulnerable persons is discussed. PMID:22177088

  6. 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. PMID:25819362

  7. Altered Resting-State Connectivity within Executive Networks after Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Maher, Monica; Churchill, Nathan W.; de Oliveira Manoel, Airton Leonardo; Graham, Simon J.; Macdonald, R. Loch; Schweizer, Tom A.

    2015-01-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant mortality rates, and most survivors experience significant cognitive deficits across multiple domains, including executive function. It is critical to determine the neural basis for executive deficits in aSAH, in order to better understand and improve patient outcomes. This study is the first examination of resting-state functional Magnetic Resonance Imaging in a group of aSAH patients, used to characterize changes in functional connectivity of the frontoparietal network. We scanned 14 aSAH patients and 14 healthy controls, and divided patients into “impaired” and “unimpaired” groups based on a composite executive function score. Impaired patients exhibited significantly lower quality of life and neuropsychological impairment relative to controls, across multiple domains. Seed-based functional connectivity analysis demonstrated that unimpaired patients were not significantly different from controls, but impaired patients had increased frontoparietal connectivity. Patients evidenced increased frontoparietal connectivity as a function of decreased executive function and decreased mood (i.e. quality of life). In addition, T1 morphometric analysis demonstrated that these changes are not attributable to local cortical atrophy among aSAH patients. These results establish significant, reliable changes in the endogenous brain dynamics of aSAH patients, that are related to cognitive and mood outcomes. PMID:26172281

  8. N-acetylcysteine suppresses oxidative stress in experimental rats with subarachnoid hemorrhage.

    PubMed

    Lu, Hua; Zhang, Dong-Mei; Chen, Hui-Ling; Lin, Yi-Xing; Hang, Chun-Hua; Yin, Hong-Xia; Shi, Ji-Xin

    2009-05-01

    The neuroprotective effect of N-acetylcysteine (NAC), a sulfhydryl-containing antioxidant, on experimentally induced subarachnoid hemorrhage (SAH) in rats was assessed. NAC was administered to rats after the induction of SAH. Neurological deficits and brain edema were investigated. The activity of antioxidant defense enzymes, copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), were measured in the brain cortex by spectrophotometer. The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. We found that NAC markedly reversed the SAH-induced neurological deficit and brain edema. We further investigated the mechanism involved in the neuroprotective effects of NAC on rat brain tissue and found that NAC significantly increased CuZn-SOD and GSH-Px activity and decreased MDA content in the SAH brain. NAC has the potential to be a novel therapeutic strategy for the treatment of SAH, and its neuroprotective effect may be partly mediated via enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation. PMID:19264484

  9. Early ischemic lesions following subarachnoid hemorrhage: common cold remedy as precipitating factor?

    PubMed

    Genonceaux, Sandrine; Cosnard, Guy; Van De Wyngaert, Françoise; Hantson, Philippe

    2011-03-01

    A 46-year-old woman presented with tetraplegia contrasting with a relatively preserved consciousness following aneurysmal subarachnoid hemorrhage (SAH). Multiple ischemic lesions were detected by magnetic resonance imaging (MRI), in the absence of vasospasm or signs of increased intracranial pressure. During the weeks before SAH, the patient had repeatedly used a nasal decongestant containing phenylephrine. After coiling of the aneurysm harboured by the right posterior cerebral artery, symptomatic vasospasm developed in the territory of the right middle cerebral artery and required aggressive therapy by intra-arterial infusion of milrinone followed by continuous intravenous administration. Follow-up MRI did not reveal new ischemic lesions. Echocardiography had demonstrated the presence of a patent foramen ovale. At 3 months follow-up, a major motor deficit persisted with akinetic mutism. The mechanisms of multiple early infarction following aneurysmal SAH are still debated, as vasospasm is usually not seen on the first imaging. Among precipitating factors of microvascular vasospasm, vasoactive substances like phenylephrine, may play a significant role. PMID:21510236

  10. Importance of accessory outflow pathways in hydrocephalus after experimental subarachnoid hemorrhage

    SciTech Connect

    Griebel, R.W.; Black, P.M.; Pile-Spellman, J.; Strauss, H.W.

    1989-02-01

    This study evaluated the changes in pathways of cerebrospinal fluid (CSF) outflow that accompanied acute and compensated hydrocephalus in the rabbit. Intraventricularly injected 99mTc antimony sulfide was used as a tracer of outflow pathways, and specified structures were counted 12 to 24 hours after injection. Fifteen rabbits were divided into three groups: 1) an acutely hydrocephalic group in which 3 cisternal injections of blood were followed by a study of CSF pressure, ventricular size, and CSF outflow pathways 1 week after the last injection; 2) a control group treated according to the same protocol, except that sterile saline was injected instead of blood; and 3) a chronic group also treated according to the same protocol but in which the animals were maintained an average of 4 weeks after the last blood injection. Ventricular size was measured by computed digitation and expressed as an area ratio of ventricle to brain (VBR). In control animals, 11.8% of the injected colloid dosage was found in cranial perineural lymphatic channels, and 4.8% appeared in the spinal cord. The mean CSF pressure was 149 +/- 20.2 mm H20 (mean +/- SE) and the mean VBR was 0.040 +/- 0.003. In animals evaluated 1 week after subarachnoid injection, accessory cranial perineural lymphatic outflow decreased significantly to 3.4%, and spinal cord activity increased to 9.8% (P less than 0.05, two-tailed t-test). These animals were hydrocephalic and had CSF pressure of 247 +/- 25.1 mm H20 (mean +/- SE) and VBR of 0.083 +/- 0.009.

  11. Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage.

    PubMed

    Chang, Tiffany R; Kowalski, Robert G; Carhuapoma, J Ricardo; Tamargo, Rafael J; Naval, Neeraj S

    2016-03-01

    OBJECT Seizures are relatively common after aneurysmal subarachnoid hemorrhage (aSAH). Seizure prophylaxis is controversial and is often based on risk stratification; middle cerebral artery (MCA) aneurysms, associated intracerebral hemorrhage (ICH), poor neurological grade, increased clot thickness, and cerebral infarction are considered highest risk for seizures. The purpose of this study was to evaluate the impact of recent cocaine use on seizure incidence following aSAH. METHODS Prospectively collected data from aSAH patients admitted to 2 institutional neuroscience critical care units between 1991 and 2009 were reviewed. The authors analyzed factors that potentially affected the incidence of seizures, including patient demographic characteristics, poor clinical grade (Hunt and Hess Grade IV or V), medical comorbidities, associated ICH, intraventricular hemorrhage (IVH), hydrocephalus, aneurysm location, surgical clipping and cocaine use. They further studied the impact of these factors on "early" and "late" seizures (defined, respectively, as occurring before and after clipping/coiling). RESULTS Of 1134 aSAH patients studied, 182 (16%) had seizures; 81 patients (7.1%) had early and 127 (11.2%) late seizures, with 26 having both. The seizure rate was significantly higher in cocaine users (37 [26%] of 142 patients) than in non-cocaine users (151 [15.2%] of 992 patients, p = 0.001). Eighteen cocaine-positive patients (12.7%) had early seizures compared with 6.6% of cocaine-negative patients (p = 0.003); 27 cocaine users (19%) had late seizures compared with 10.5% non-cocaine users (p = 0.001). Factors that showed a significant association with increased risk for seizure (early or late) on univariate analysis included younger age (< 40 years) (p = 0.009), poor clinical grade (p = 0.029), associated ICH (p = 0.007), and MCA aneurysm location (p < 0.001); surgical clipping was associated with late seizures (p = 0.004). Following multivariate analysis, age < 40 years

  12. Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature.

    PubMed

    Lee, Sang-Hyo; Park, David Jaehyun; Jeun, Sin-Soo

    2016-04-01

    Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery. PMID:27195260

  13. Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature

    PubMed Central

    Lee, Sang-Hyo; Jeun, Sin-Soo

    2016-01-01

    Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery. PMID:27195260

  14. Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage.

    PubMed

    Tsai, Yi-Da; Hsu, Chin-Wang; Hsu, Chia-Ching; Liao, Wen-I; Chen, Sy-Jou

    2016-03-01

    Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease. PMID:26275629

  15. Long-Term Outcomes for Different Forms of Stress Cardiomyopathy After Surgical Treatment for Subarachnoid Hemorrhage

    PubMed Central

    Bihorac, Azra; Ozrazgat-Baslanti, Tezcan; Mahanna, Elizabeth; Malik, Seemab; White, Peggy; Sorensen, Matthew; Fahy, Brenda G.; Petersen, John W

    2016-01-01

    Background Stress-induced cardiomyopathy (SCM) after subarachnoid hemorrhage (SAH) includes predominant apical or basal regional left ventricular dysfunction (RLVD) with concomitant changes in electrocardiogram or increase in cardiac enzymes. We hypothesized that difference in outcome is associated with the type of RLVD after SAH. Methods We studied a single-center retrospective cohort of SAH patients hospitalized between 2000 and 2010 with follow-up until 2013. We classified patients who had an echocardiogram for clinically indicated reasons according to the predominate location of RLVD as classic SCM-apical form and variant SCM-basal form. A Cox proportional hazard model and logistic regression were used to estimate risk for death and hospital complications associated with different RLVD, after adjustment for propensity to undergo echocardiography given clinical characteristics on admission. Results Among 715 SAH patients 28% (200/715) had an echocardiogram for clinical evidence of cardiac dysfunction during hospitalization, the most common being acute LV dysfunction, suspected acute ischemic event, changes in electrocardiogram and cardiac enzymes and arrhythmia. SCM was present in 59 patients (8% of all cohort and 30% of patients with echocardiogram, respectively) with similar distribution of SCM-basal (25/59) and SCM-Apical forms (34/59). SAH patients who had an echocardiogram for clinically indicated reasons had a significantly decreased risk-adjusted long-term survival compared to those without an echocardiogram, regardless of the presence of RLVD. SCM-basal was associated with cardiac complications (OR 6.1, 99% CI 1.8–20.2) and severe sepsis (OR 5.3 99% CI 1.6–17.2). Conclusions SAH patients with echocardiogram for a clinically indicated reason have a decreased long-term survival, regardless of the presence of RLVD. The association between severe sepsis and SCM-basal warrants future studies to determine their potential synergistic effect on LV systolic

  16. Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice.

    PubMed

    Liu, Lei; Fujimoto, Masashi; Kawakita, Fumihiro; Nakano, Fumi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-09-01

    The role of vascular endothelial growth factor (VEGF) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The aim of this study was to investigate effects of anti-VEGF therapy on EBI after SAH. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or two dosages (0.2 and 1 μg) of anti-VEGF antibody were randomly administrated by an intracerebroventricular injection. Neuroscore, brain water content, immunoglobulin G staining, and Western blotting were performed to evaluate EBI at 24-48 h. To confirm the role of VEGF, anti-VEGF receptor (VEGFR)-2 (a major receptor of VEGF) antibody was intracerebroventricularly administered and the effects on EBI were evaluated at 24 h. A higher dose, but not a lower dose, of anti-VEGF antibody significantly ameliorated post-SAH neurological impairments and brain edema at 24-48 h post-SAH. Post-SAH blood-brain barrier disruption was also inhibited by anti-VEGF antibody. The protective effects of anti-VEGF antibody were associated with the inhibition of post-SAH induction of VEGF, VEGFR-2, phosphorylated VEGFR-2, interleukin-1β and a matricellular protein tenascin-C (TNC). Anti-VEGFR-2 antibody also suppressed post-SAH neurological impairments and brain edema associated with VEGFR-2 inactivation and TNC downregulation. These findings demonstrated that VEGF causes post-SAH EBI via VEGFR-2 and TNC and that anti-VEGF therapy is effective for post-SAH EBI. PMID:26289408

  17. Relationship between sympathetic nervous activity and inflammatory response after subarachnoid hemorrhage in a perforating canine model.

    PubMed

    Gao, Cheng; Liu, Xiangzhen; Shi, Huaizhang; Xu, Shancai; Ji, Zhiyong; Wang, Chunlei; Wu, Pei; Liu, Zhen; Zhao, Shiguang

    2009-05-11

    The objective of the present study was to evaluate the correlation between sympathetic nerve activation and inflammatory response in the acute stage of subarachnoid hemorrhage (SAH) in a canine perforating model. SAH was induced by perforation of the basilar artery with the use of a microcatheter via the femoral artery in 20 mongrel dogs. Hemodynamic parameters and intracranial pressure were recorded, and blood sample for C3a, C5b-9, IL-6, IL-8 and noradrenaline kinetic determination were measured at 0, 5, 15, 30, 60, 120, and 180 min after SAH. Noradrenaline (pg/mL) increased abruptly from 104+/-59 to 2010+/-918 at 5 min after SAH. C3a and C5b-9 reached peak values at 15 min and IL-6 and IL-8 reached peak values at 30 min after SAH, respectively. The peak values of C3a and C5b-9 correlated positively with the peak value of noradrenaline (r=0.743 and r=0.753, respectively). The peak values of IL-6 and IL-8 also correlated positively with the peak values of noradrenaline (r=0.603 and r=0.681, respectively).These results suggest that a pronounced activation of the sympathetic nervous system and the inflammatory response occurs in acute stage of SAH. Significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and immune response are quantitatively linked in early stage after SAH. The exact mechanisms underlying this phenomenon deserved further investigations. PMID:19217831

  18. Role of Endothelin-1 in Human Aneurysmal Subarachnoid Hemorrhage: Associations with Vasospasm and Delayed Cerebral Ischemia

    PubMed Central

    Thampatty, Bhavani P.; Sherwood, Paula R.; Gallek, Matthew J.; Crago, Elizabeth A.; Ren, Dianxu; Hricik, Allison J.; Kuo, Chien-Wen J.; Klamerus, Megan M.; Alexander, Sheila A.; Bender, Catherine M.; Hoffman, Leslie A.; Horowitz, Michael B.; Kassam, Amin B.; Poloyac, Samuel M.

    2011-01-01

    Background Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI. Methods Patients with aSAH were consented (n = 106). Cerebral vasospasm was determined by angiography. DCI was determined by transcranial Doppler (TCD) results and/or angiogram results with corresponding clinical deterioration. CSF ET-1 levels over 14 days after the initial insult was quantified by ELISA. ET-1 analysis included a group-based trajectory analysis and ET-1 exposure rate during 24, 48, and 72 h prior to, as well as 72 h post angiography, or clinical deterioration. Results Trajectory analysis revealed two distinct groups of subjects with 56% of patients in the low ET-1 trajectory group (mean at day 1 = 0.31 pg/ml; SE = 0.04; mean at day 14 = 0.41 pg/ml; SE = 0.15) and 44% of patients in the high ET-1 trajectory group (mean at day 1 = 0.65 pg/ml; SE = 0.08; mean at day 14 = 0.61 pg/ml; SE = 0.06). Furthermore, we observed that ET-1 exposure rate 72 h before angiography and clinical spasm was a significant predictor of both angiographic vasospasm and DCI, whereas, ET-1 exposure after angiography and clinical spasm was not associated with either angiographic vasospasm or DCI. Conclusion Based on these results we conclude that ET-1 concentrations are elevated in a sub-group of patients and that the acute (72 h prior to angiography and clinical neurological deterioration), but not chronic, elevations in CSF ET-1 concentrations are indicative of the pathogenic alterations of vasospasm and DCI in aSAH patients. PMID:21286855

  19. Systolic Blood Pressure Variability is a Novel Risk Factor for Rebleeding in Acute Subarachnoid Hemorrhage

    PubMed Central

    Lin, Qing-Song; Ping-Chen; Lin, Yuan-Xiang; Lin, Zhang-Ya; Yu, Liang-Hong; Dai, Lin-Sun; Kang, De-Zhi

    2016-01-01

    Abstract Rebleeding of an aneurysm is a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Whereas numerous studies have demonstrated predictors of rebleeding and effect of systolic blood pressure variability (SBPV) on stroke, few data on the association between SBPV and rebleeding. Here, we sought to identify the effect of SBPV on rebleeding in acute aneurysmal SAH. Case–control study. From January 2010 to June 2015, 612 patients with aneurysmal SAH were enrolled in our tertiary care medical center. Main outcome measures: Consecutive patients with acute (<3 days from ictus) aneurismal rebleeding or repair or death were retrospectively included. Antihypertensive therapy based on a predefined standardized protocol was prescribed to lower and maintain SBP between 120 and 160 mm Hg. SBP was measured hourly until a censoring event occurred. SBPV was determined as standard deviation (SD) and successive variation (SV). Binary logistic regression was used to assess the association between SBPV and rebleeding. Rebleeding occurred in 61 (10.0%) of the 612 patients. We identified 47 acute rebleeding as cases and 382 early repair or early death as controls. On binary logistic regression analysis, rebleeding was associated with the SD of SBP (odds ratio [OR], 1.254; 95% confidence interval [CI], 1.131–1.391; P < 0.001) and the SV of SBP (OR, 1.131; 95% CI, 1.039–1.231; P = 0.004). No significant difference was seen between rebleeding and mean systolic blood pressure (MSBP). SBPV is associated with increased rates of acute aneurysmal rebleeding. Further prospective research is warranted to confirm that SBP stability prevents acute aneurysm rebleeding. PMID:26986118

  20. Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study.

    PubMed

    De Micheli, E; Pinna, G; Alfieri, A; Caramia, G; Bianchi, L; Colivicchi, M A; Della Corte, L; Bricolo, A

    2000-01-01

    Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage

  1. Cholesterol as a Risk Factor for Subarachnoid Hemorrhage: A Systematic Review

    PubMed Central

    Lindbohm, Joni Valdemar; Kaprio, Jaakko; Korja, Miikka

    2016-01-01

    Background The role played by total cholesterol (TC) in risk for subarachnoid hemorrhage (SAH) is unclear because studies report both high and low TC each as a risk factor. We performed a systematic review to clarify associations between lipid profile and SAH. Methods Our literature search comprised Pubmed, Scopus, and Cochrane Library databases with no language, publication year, or study type limitations. The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) checklist guided our reporting. Data forms adapted from the Critical Appraisal Skills Program (CASP), and Cochrane Collaboration guidelines provided a platform for risk-of-bias evaluation. We used a random effects model to calculate pooled estimates and assessed heterogeneity with I2-statistics. Results Of the final 21 studies reviewed, 12 were prospective and 9 retrospective. All studies assessed TC, four assessed HDL, and none LDL in risk for SAH. Heterogeneity among all, retrospective, and Asian studies was high (I2 = 79.5%, I2 = 89.0%, and I2 = 84.3%) and considerable in prospective (I2 = 46.0%). We therefore focused on qualitative analysis and found that only two studies had a low risk of bias. According to these studies high TC increases risk for SAH in men, whereas the role of HDL remained unclear. Conclusion The low-risk-of-bias studies suggest that elevated TC levels elevate risk for SAH in men. Due to the high prevalence of hypercholesterolemia, population attributable risk (PAR) of hypercholesterolemia may exceed the PARs of smoking and hypertension in men. Apart from diabetes and obesity, the risk-factor profile of SAH seems to resemble that of other cerebrovascular diseases, at least in men. PMID:27077917

  2. Retinal Vessel Analysis (RVA) in the Context of Subarachnoid Hemorrhage - A Proof of Concept Study

    PubMed Central

    Weiss, Miriam; Clusmann, Hans; Fuest, Matthias; Mueller, Marguerite; Brockmann, Marc Alexander; Vilser, Walthard; Schmidt-Trucksäss, Arno; Hoellig, Anke; Seiz, Marcel; Thomé, Claudius; Kotliar, Konstantin; Schubert, Gerrit Alexander

    2016-01-01

    Background Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. Methods In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. Results Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. Conclusion RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort. PMID:27388619

  3. Serum lipid profile spectrum and delayed cerebral ischemia following subarachnoid hemorrhage: Is there a relation?

    PubMed Central

    Dhandapani, Sivashanmugam; Aggarwal, Ashish; Srinivasan, Anirudh; Meena, Rajesh; Gaudihalli, Sachin; Singh, Harnarayan; Dhandapani, Manju; Mukherjee, Kanchan K.; Gupta, Sunil K.

    2015-01-01

    Background: Serum lipid abnormalities are known to be important risk factors for vascular disorders. However, their role in delayed cerebral ischemia (DCI), the major cause of morbidity after subarachnoid hemorrhage (SAH) remains unclear. This study was an attempt to evaluate the spectrum of lipid profile changes in SAH compared to matched controls, and their relation with the occurrence of DCI. Methods: Admission serum lipid profile levels were measured in patients of SAH and prospectively studied in relation to various factors and clinical development of DCI. Results: Serum triglyceride (TG) levels were significantly lower among SAH patients compared to matched controls (mean [±standard deviation (SD)] mg/dL: 117.3 [±50.4] vs. 172.8 [±89.1], P = 0.002), probably because of energy consumption due to hypermetabolic response. Patients who developed DCI had significantly higher TG levels compared to those who did not develop DCI (mean [±SD] mg/dL: 142.1 [±56] vs. 111.9 [±54], P = 0.05). DCI was noted in 62% of patients with TG >150 mg/dL, compared to 22% among the rest (P = 0.01). Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and lipoprotein (a) neither showed a significant difference between SAH and controls and nor any significant association with DCI. Multivariate analysis using binary logistic regression adjusting for the effects of age, sex, systemic disease, World Federation of Neurosurgical Societies grade, Fisher grade, and clipping/coiling, revealed higher TG levels to have significant independent association with DCI (P = 0.01). Conclusions: Higher serum TG levels appear to be significantly associated with DCI while other lipid parameters did not show any significant association. This may be due to their association with remnant cholesterol or free fatty acid-induced lipid peroxidation. PMID:26664869

  4. Whole Blood Gene Expression Profiles of Patients with a Past Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    van ’t Hof, Femke N. G.; Ruigrok, Ynte M.; Medic, Jelena; Sanjabi, Bahram; van der Vlies, Pieter; Rinkel, Gabriel J. E.; Veldink, Jan H.

    2015-01-01

    Background The pathogenesis of development and rupture of intracranial aneurysms (IA) is largely unknown. Also, screening for IA to prevent aneurysmal subarachnoid hemorrhage (aSAH) is inefficient, as disease markers are lacking. We investigated gene expression profiles in blood of previous aSAH patients, who are still at risk for future IA, aiming to gain insight into the pathogenesis of IA and aSAH, and to make a first step towards improvement of aSAH risk prediction. Methods and Results We collected peripheral blood of 119 patients with aSAH at least two years prior, and 118 controls. We determined gene expression profiles using Illumina HumanHT-12v4 BeadChips. After quality control, we divided the dataset in a discovery (2/3) and replication set (1/3), identified differentially expressed genes, and applied (co-)differential co-expression to identify disease-related gene networks. No genes with a significant (false-discovery rate <5%) differential expression were observed. We detected one gene network with significant differential co-expression, but did not find biologically meaningful gene networks related to a history of aSAH. Next, we applied prediction analysis of microarrays to find a gene set that optimally predicts absence or presence of a history of aSAH. We found no gene sets with a correct disease state prediction higher than 40%. Conclusions No gene expression differences were present in blood of previous aSAH patients compared to controls, besides one differentially co-expressed gene network without a clear relevant biological function. Our findings suggest that gene expression profiles, as detected in blood of previous aSAH patients, do not reveal the pathogenesis of IA and aSAH, and cannot be used for aSAH risk prediction. PMID:26439625

  5. Blockage of mitochondrial calcium uniporter prevents iron accumulation in a model of experimental subarachnoid hemorrhage

    SciTech Connect

    Yan, Huiying; Hao, Shuangying; Sun, Xiaoyan; Zhang, Dingding; Gao, Xin; Yu, Zhuang; Li, Kuanyu; Hang, Chun-Hua

    2015-01-24

    Highlights: • Iron accumulation was involved in the acute phase following SAH. • Blockage of MCU could attenuate cellular iron accumulation following SAH. • Blockage of MCU could decrease ROS generation and improve cell energy supply following SAH. • Blockage of MCU could alleviate apoptosis and brain injury following SAH. - Abstract: Previous studies have shown that iron accumulation is involved in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH) and chelation of iron reduced mortality and oxidative DNA damage. We previously reported that blockage of mitochondrial calcium uniporter (MCU) provided benefit in the early brain injury after experimental SAH. This study was undertaken to identify whether blockage of MCU could ameliorate iron accumulation-associated brain injury following SAH. Therefore, we used two reagents ruthenium red (RR) and spermine (Sper) to inhibit MCU. Sprague–Dawley (SD) rats were randomly divided into four groups including sham, SAH, SAH + RR, and SAH + Sper. Biochemical analysis and histological assays were performed. The results confirmed the iron accumulation in temporal lobe after SAH. Interestingly, blockage of MCU dramatically reduced the iron accumulation in this area. The mechanism was revealed that inhibition of MCU reversed the down-regulation of iron regulatory protein (IRP) 1/2 and increase of ferritin. Iron–sulfur cluster dependent-aconitase activity was partially conserved when MCU was blocked. In consistence with this and previous report, ROS levels were notably reduced and ATP supply was rescued; levels of cleaved caspase-3 dropped; and integrity of neurons in temporal lobe was protected. Taken together, our results indicated that blockage of MCU could alleviate iron accumulation and the associated injury following SAH. These findings suggest that the alteration of calcium and iron homeostasis be coupled and MCU be considered to be a therapeutic target for patients suffering from SAH.

  6. Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats.

    PubMed

    Cui, Yonghua; Duan, Xiaochun; Li, Haiying; Dang, Baoqi; Yin, Jia; Wang, Yang; Gao, Anju; Yu, Zhengquan; Chen, Gang

    2016-08-01

    Increasing studies have demonstrated the neuroprotective effect of hydrogen sulfide (H2S) in central nervous system (CNS) diseases. However, the potential application value of H2S in the therapy of subarachnoid hemorrhage (SAH) is still not well known. This study was to investigate the potential effect of H2S on early brain injury (EBI) induced by SAH and explore the underlying mechanisms. The role of sodium hydrosulfide (NaHS), a donor of H2S, in SAH-induced EBI, was investigated in both in vivo and in vitro. A prechiasmatic cistern single injection model was used to produce experimental SAH in vivo. In vitro, cultured primary rat cortical neurons and human umbilical vein endothelial cells (HUVECs) were exposed to OxyHb at concentration of 10 μM to mimic SAH. Endogenous production of H2S in the brain was significantly inhibited by SAH. The protein levels of the predominant H2S-generating enzymes in the brain, including cystathionineb-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3MST), were also correspondingly reduced by SAH, while treatment with NaHS restored H2S production and the expressions of CBS and 3MST. More importantly, NaHS treatment could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, brain cell apoptosis, inflammatory response, and cerebral vasospasm) after SAH. In vitro, H2S protects neurons and endothelial function by functioning as an antioxidant and antiapoptotic mediator. Our results suggest that NaSH as an exogenous H2S donor could significantly reduce EBI induced by SAH. PMID:26111628

  7. [Changes in regional and local brain circulation in patients with subarachnoid hemorrhage due to ruptured aneurysm].

    PubMed

    Nemati, M N; Dietz, H

    1995-01-01

    It is well known that cerebral blood flow (CBF) is altered corresponding to the severity of the subarachnoid hemorrhage (SAH) in different extents. The extent of CBF reduction and its regional accentuation is regarded as a pathophysiological correlation of clinical conditions. Therefore, we agree that CBF of patients in grade IV+V (Hunt and Hess) are clearly lower than in grade I+II. There are quite different results in grade III. Disturbance of consciousness and/or neurological deficits, as described in the definition of grade III, can be a consequence of different kinds of CBF changes. 45 Xe-CT studies were performed on 19 patients (mean age 44 +/- 14 years) after SAH. 8 patients were of grade I+II, 7 of grade III, and 4 patients of grade IV+V. The studies were performed preoperatively, at a time of clinical change, and before discharge. The evaluation of flow-maps was done by measuring 15 regions per hemisphere. Mean CBF data were evaluated in each area. To show the CBF differences between both hemispheres within each group of patients, a difference index (%) was calculated. The results demonstrated a mean CBF reduction in nearly all regions from grade I+II to grade III up to grade IV+V. The mean CBF reduction between grade I+II and grade III was 10% for gray and 20% for white matter (p < 0.05). On the other hand the difference index of gray matter in grade III with 17% is significantly higher than in grade I+II. For the white matter there was no significant side difference. Our findings demonstrate a visually evaluable pattern of CBF corresponding to grade I+II, grade III, and grade I+V. Intention of this study was to show a correlation between clinical conditions of patients after SAH and the CBF changes by the use of Xe-CT method. PMID:8867355

  8. Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats

    PubMed Central

    Suzuki, Hidenori; Ayer, Robert; Sugawara, Takashi; Chen, Wanqiu; Sozen, Takumi; Hasegawa, Yu; Kanamaru, Kenji; Zhang, John H.

    2009-01-01

    Objective Accumulated evidence suggests that the primary cause of poor outcome after subarachnoid hemorrhage (SAH) is not only cerebral arterial narrowing, but also early brain injury (EBI). Our objective was to determine the effect of recombinant osteopontin (r-OPN), a pleiotropic extracellular matrix glycoprotein, on post-SAH EBI in rats. Design Controlled in vivo laboratory study. Setting Animal research laboratory. Subjects One hundred seventy-seven male adult Sprague-Dawley rats, 300–370g. Interventions The endovascular perforation model of SAH was produced. SAH or sham-operated rats were treated with an equal volume (1μL) of pre-SAH intracerebroventricular administration of two dosages (0.02 and 0.1μg) of r-OPN, albumin or vehicle. Body weight, neurological scores, brain edema and blood-brain barrier (BBB) disruption were evaluated, and Western blot analyses were performed to determine the effect of r-OPN on matrix metalloproteinase (MMP)-9, substrates of MMP-9 (zona occludens [ZO]-1, laminin), tissue inhibitor of MMP (TIMP)-1, inflammation (interleukin-1β), and nuclear factor (NF)-κ B signaling pathways. Measurements and Main Results Treatment with r-OPN prevented a significant loss in body weight, neurological impairment, brain edema, and BBB disruption after SAH. These effects were associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, the maintenance of TIMP-1, and the consequent preservation of the cerebral microvessel basal lamina protein laminin, and the tight junction protein ZO-1. Conclusions These results demonstrate that r-OPN treatment is effective for post-SAH EBI. PMID:19851092

  9. Correlation between angiographic transit times and neurological status on admission in patients with aneurysmal subarachnoid hemorrhage.

    PubMed

    Ivanov, Alexander; Linninger, Andreas; Hsu, Chih-Yang; Amin-Hanjani, Sepideh; Aletich, Victor A; Charbel, Fady T; Alaraj, Ali

    2016-04-01

    OBJECT The use of digital subtraction angiography (DSA) for semiquantitative cerebral blood flow(CBF) assessment is a new technique. The aim of this study was to determine whether patients with aneurysmal subarachnoid hemorrhage (aSAH) with higher Hunt and Hess grades also had higher angiographic contrast transit times (TTs) than patients with lower grades. METHODS A cohort of 30 patients with aSAH and 10 patients without aSAH was included. Relevant clinical information was collected. A method to measure DSA TTs by color-coding reconstructions from DSA contrast-intensity images was applied. Regions of interest (ROIs) were chosen over major cerebral vessels. The estimated TTs included time-to-peak from 0% to 100% (TTP0-100), TTP from 25% to 100% (TTP25-100), and TT from 100% to 10% (TT100-10) contrast intensities. Statistical analysis was used to compare TTs between Group A (Hunt and Hess Grade I-II), Group B (Hunt and Hess Grade III-IV), and the control group. The correlation coefficient was calculated between different ROIs in aSAH groups. RESULTS There was no difference in demographic factors between Group A (n = 10), Group B (n = 20), and the control group (n = 10). There was a strong correlation in all TTs between ROIs in the middle cerebral artery (M1, M2) and anterior cerebral artery (A1, A2). There was a statistically significant difference between Groups A and B in all TT parameters for ROIs. TT100-10 values in the control group were significantly lower than the values in Group B. CONCLUSIONS The DSA TTs showed significant correlation with Hunt and Hess grades. TT delays appear to be independent of increased intracranial pressure and may be an indicator of decreased CBF in patients with a higher Hunt and Hess grade. This method may serve as an indirect technique to assess relative CBF in the angiography suite. PMID:26452118

  10. Personalized Medicine in Cerebrovascular Neurosurgery: Precision Neurosurgical Management of Cerebral Aneurysms and Subarachnoid Hemorrhage

    PubMed Central

    Achrol, Achal Singh; Steinberg, Gary K.

    2016-01-01

    Cerebral aneurysms are common vascular lesions. Little is known about the pathogenesis of these lesions and the process by which they destabilize and progress to rupture. Treatment decisions are motivated by a desire to prevent rupture and the devastating morbidity and mortality associated with resulting subarachnoid hemorrhage (SAH). For patients presenting with SAH, urgent intervention is required to stabilize the lesion and prevent re-rupture. Those patients fortunate enough to survive a presenting SAH and subsequent securing of their aneurysm must still face a spectrum of secondary sequelae, which can include cerebral vasospasm, delayed ischemia, seizures, cerebral edema, hydrocephalus, and endocrinologic and catecholamine-induced systemic dysfunction in cardiac, pulmonary, and renal systems. Increased focus on understanding the pathophysiology and molecular characteristics of these secondary processes will enable the development of targeted therapeutics and novel diagnostics for improved patient selection in personalized medicine trials for SAH. In unruptured cerebral aneurysms, treatment decisions are less clear and currently based solely on treating larger lesions, using rigid aneurysm size cutoffs generalized from recent studies that are the subject of ongoing controversy. Further compounding this controversy is the fact that the vast majority of aneurysms that come to clinical attention at the time of a hemorrhagic presentation are of smaller size, suggesting that small aneurysms are indeed not benign lesions. As such, patient-specific biomarkers that better predict which aneurysms represent high-risk lesions that warrant clinical intervention are of vital importance. Recent advancements in genomic and proteomic technologies have enabled the identification of molecular characteristics that may prove useful in tracking aneurysm growth and progression and identifying targets for prophylactic therapeutic interventions. Novel quantitative neuroimaging

  11. 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

  12. [Unilateral Posterior Reversible Encephalopathy Syndrome after Ventriculo-Peritoneal Shunt for Normal Pressure Hydrocephalus Following Subarachnoid Hemorrhage: A Case Report].

    PubMed

    Sato, Hiroyuki; Koizumi, Takayuki; Sato, Daisuke; Endo, Shin; Kato, Syunichi

    2016-06-01

    The patient, a 79-year-old man, experienced a Hunt & Kosnik grade IV subarachnoid hemorrhage, presenting with sudden-onset coma and severe left hemiplegia. We performed cranial clipping surgery for a ruptured aneurysm on the right middle cerebral artery the same day. Post-operative recovery proceeded smoothly, with gradual improvements in disturbed consciousness and left hemiplegia. Three weeks post-operation, CT revealed low-density areas in the right frontal and temporal lobe, believed to be due to subarachnoid hemorrhage, as well as hydrocephaly. We then performed a lumbo-peritoneal (L-P) shunt for the hydrocephaly. Two months later, the patient experienced shunt occlusion, and we performed a ventriculo-peritoneal (V-P) shunt revision (pressure: 6 cm H(2)O). Headaches, severe decline in cognitive function, and worsened left hemiplegia were observed seven weeks post-shunt revision. Cranial CT revealed widespread low-density areas in right posterior cerebral white matter. We suspected unilateral posterior reversible encephalopathy syndrome (PRES) after performing cranial MRI and cerebral angiography. Increasing the set pressure of the shunt improved the symptoms and radiographic findings. PRES is typically bilateral, and unilateral incidents are rare. This is the first report of unilateral PRES secondary to shunt operation. Its unilaterality appears to have been caused by unilateral brain damage or adhesions to the brain surface from the subarachnoid cerebral hemorrhage. Overdrainage post-shunt can also induce PRES. Diagnosis of PRES is more difficult in unilateral cases;practitioners must keep PRES in mind as a rare complication post-shunt operation. PMID:27270150

  13. Safety and Efficacy of Transluminal Balloon Angioplasty Using a Compliant Balloon for Severe Cerebral Vasospasm after an Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Choi, Beom Jin; Lee, Jae Il; Ko, Jun Kyeung; Park, Hwa Seung; Choi, Chang Hwa

    2011-01-01

    Objective Vasospasm of cerebral vessels remains a major source of morbidity and mortality after an aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to evaluate the safety and efficacy of transluminal balloon angioplasty (TBA) for SAH-induced vasospasm. Methods Eleven patients with an angiographically confirmed significant vasospasm (>50% vessel narrowing and clinical deterioration) were studied. A total of 54 vessel segments with significant vasospasm were treated by TBA. Digital subtraction angiography was used to confirm the presence of vasospasm, and TBA was performed to dilate vasospastic arteries. Medical and angiographic reports were reviewed to determine technical efficacy and for procedural complications. Results TBA using Hyper-Glide or Hyper-Form balloons (MicroTherapeutics, Irvine, CA) was successfully accomplished in 88.9% vasospastic segments (48 of 54), namely, in the distal internal carotid artery (100%, n=7), the middle cerebral artery (100%), including the M1 (n=10), M2 (n=10), and M3 segments (n=4), in the vertebral artery (100%, n=2), basilar artery (100%, n=1), and in the anterior cerebral artery (ACA), including the A1 (66%), A2 (66%), and A3 segments (100%). Vessel diameters significantly increased after TBA. There were no cases of vessel rupture or thromboembolic complications. GCS at one day after TBA showed an improvement in all patients except one. Conclusion This study suggests that TBA using Hyper-Glide or Hyper-Form balloons is a safe and effective treatment for subarachnoid hemorrhage-induced cerebral vasospasm. PMID:21556235

  14. Femoral access in 100 consecutive subarachnoid hemorrhage patients: the "craniotomy" of endovascular neurosurgery

    PubMed Central

    2010-01-01

    Background Femoral access is a fundamental element of catheter-based cerebral angiography. Knowledge of location of the common femoral artery (CFA) bifurcation is important as the risk of retroperitoneal bleeding is increased if the puncture is superior to the inguinal ligament and there is an increased risk of thrombosis and arteriovenous fistula formation if the puncture is distal into branch vessels. We sought to characterize the location of the CFA bifurcation along with the presence of significant atherosclerosis or iliac tortuosity in a contemporary series of subarachnoid hemorrhage (SAH) patients. Findings The records of a prospective single-center aneurysm database were reviewed to identify 100 consecutive SAH patients. Using an oblique femoral arteriogram, the presence of significant atherosclerosis, iliac tortuosity, and the CFA bifurcation were assessed. The CFA bifurcation was graded according to its position with respect to the femoral head: below (grade 1), lower half (grade 2), and above the upper half (grade 3). We found a CFA bifurcation grade 1 in 50 patients (50%, mean age 51.2 years), grade 2 in 40 patients (40%, mean age 55.5 years), and grade 3 in 10 patients (10%, mean age 58.2 years). Whereas 30 of 90 patients with CFA grades I or II were male (33%), only 10% with grade 3 were male (1 of 10, p = 0.12). Mean age for significant atherosclerosis was 65.5 +/- 2.6 years versus 50.9 +/- 1.6 years (p < 0.001) without, and iliac tortuosity was 64.9 +/- 2.4 years versus 50.3 +/- 1.6 years (p < 0.001) without. Conclusions Although a requisite element of endovascular treatment in SAH patients, femoral access can be complicated by a high common femoral artery bifurcation and the presence of atherosclerotic disease and/or iliac artery tortuosity. In this study, we found a grade 3 (above the femoral head) CFA bifurcation in 10% patients, with 90% of these patients being female. We also found the presence of atherosclerotic disease and iliac tortuosity to

  15. Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients.

    PubMed

    Wu, Wei; Guan, Yi; Zhao, Gang; Fu, Xi-Jia; Guo, Tie-Zhu; Liu, Yue-Ting; Ren, Xin-Liang; Wang, Wei; Liu, Han-Rui; Li, Yun-Qian

    2016-07-01

    The present study investigated the correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in cerebrospinal fluid (CSF) and subarachnoid hemorrhage (SAH) progression. A meta-analysis was further conducted from pooled data to analyze the clinical value of IL-6 and TNF-α in SAH diagnosis. In our case-control study, a total of 57 SAH patients were assigned to two groups, CVS group (n = 27) and non-CVS group (n = 30), based on the presence of cerebral vasospasm (CVS). In addition, 65 healthy subjects were enrolled as controls. IL-6 and TNF-α levels in CSF were measured in all the study subjects by enzyme-linked immunosorbent assay (ELISA). For meta-analysis, an exhaustive literature search was conducted to identify relevant published articles and strict inclusion and exclusion criteria were applied to select studies for the present meta-analysis. Data extracted from these studies was analyzed using STATA 12.0 software. IL-6 and TNF-α levels in CSF of SAH patients were markedly higher than those of healthy controls (all P < 0.001). Further, CVS patients showed elevated IL-6 and TNF-α levels in CSF compared to non-CVS patients (all P < 0.001). The increase in IL-6 and TNF-α levels in CSF correlated with the increasing disease severity, based on Hunt-Hess grade, in SAH patients (all P < 0.05). Our meta-analysis also confirmed that IL-6 and TNF-α CSF levels were markedly higher in SAH patients compared to healthy controls (all P < 0.001). Ethnicity-stratified analysis showed that both IL-6 and TNF-α CSF levels were elevated in Asian SAH patients, compared to their healthy counterparts (all P < 0.05). The TNF-α CSF levels were significantly higher in Caucasian SAH patients (P < 0.001), but the IL-6 CSF levels showed no such differences compared to the healthy controls (P = 0.219). Subgroup analysis based on the presence of CVS showed that both IL-6 and TNF-α CSF levels were markedly higher in CVS

  16. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    NASA Astrophysics Data System (ADS)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  17. Adrenoceptor Polymorphisms and the Risk of Cardiac Injury and Dysfunction After Subarachnoid Hemorrhage

    PubMed Central

    Zaroff, Jonathan G.; Pawlikowska, Ludmila; Miss, Jacob C.; Yarlagadda, Sirisha; Ha, Connie; Achrol, Achal; Kwok, Pui-Yan; McCulloch, Charles E.; Lawton, Michael T.; Ko, Nerissa; Smith, Wade; Young, William L.

    2015-01-01

    Background and Purpose Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) and may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would be associated with an increased risk of cardiac injury. Methods This was a prospective cohort study. The primary outcome variables were the serum level of cardiac troponin I (cTi, abnormal if >1.0 µg/L) and the left ventricular ejection fraction (LVEF, abnormal if <50%). Six adrenoceptor polymorphisms were genotyped: β1AR Arg389Gly, β1AR Ser49Gly, β2AR Gly16Arg, β2AR Gln27Glu, β2AR Thr164Ile, and α2AR del322–325. The effect of each polymorphism on the risk of developing cardiac abnormalities was quantified using multivariable logistic regression. Results The study included 182 patients. The CC genotype (Arg/Arg) of β1AR Arg389Gly (odds ratio [OR] 3.4, P=0.030) and the CC genotype (Gln/Gln) of β2AR Gln27Glu (OR 3.1, P=0.032) were predictive of cTi release. The presence of the α2AR deletion was predictive of reduced LVEF (OR 4.2, P=0.023). The combination of the β1AR 389 CC and the β2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, P=0.012). The combination of the β1AR 389 CC and the α2AR deletion genotypes resulted in a marked increase in the odds of developing a reduced LVEF (OR 10.3, P=0.033). Conclusions Genetic polymorphisms of the adrenoceptors are associated with an increased risk of cardiac abnormalities after SAH. These data support the hypothesis that cardiac dysfunction after SAH is a form of neurocardiogenic injury. PMID:16728691

  18. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage

    PubMed Central

    Dhar, Rajat; Zazulia, Allyson R; Videen, Tom O; Zipfel, Gregory J; Derdeyn, Colin P; Diringer, Michael N

    2009-01-01

    Background Anemia is common after subarachnoid hemorrhage (SAH) and may exacerbate the reduction in oxygen delivery (DO2) underlying delayed cerebral ischemia (DCI). The association between lower hemoglobin and worse outcome, including more cerebral infarcts, supports a role for red blood cell (RBC) transfusion to correct anemia. However, the cerebral response to transfusion remains uncertain, as higher hemoglobin may increase viscosity and further impair cerebral blood flow (CBF) in the setting of vasospasm. Methods Eight patients with aneurysmal SAH and hemoglobin < 10 g/dl were studied with 15O-PET before and after transfusion of 1 unit of RBCs. Paired t-tests were used to analyze the change in global and regional CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) after transfusion. DO2 was calculated from CBF and arterial oxygen content (CaO2). CBF, CMRO2 and DO2 are reported in ml/100g/min. Results Transfusion resulted in a 15% rise in hemoglobin (8.7±0.8 to 10.0±1.0 g/dl) and CaO2 (11.8±1.0 to 13.6±1.1 ml/dL, both p < 0.001). Global CBF remained stable (40.5±8.1 to 41.6±9.9), resulting in an 18% rise in DO2 from 4.8±1.1 to 5.7±1.4 (p = 0.017). This was associated with a fall in OEF from 0.49±0.11 to 0.41±0.11 (p = 0.11) and stable CMRO2. Rise in DO2 was greater (28%) in regions with oligemia (low DO2 and OEF≥0.5) at baseline, but was attenuated (10%) within territories exhibiting angiographic vasospasm, where CBF fell 7%. Conclusions Transfusion of RBCs to anemic patients with SAH resulted in a significant rise in cerebral DO2 without lowering global CBF. This was associated with reduced OEF, which may improve tolerance of vulnerable brain regions to further impairments of CBF. Further studies are needed to confirm the benefit of transfusion on DCI and balance this against potential systemic and cerebral risks. PMID:19628806

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

    PubMed

    Murthy, Santosh B; Moradiya, Yogesh; Shah, Shreyansh; Naval, Neeraj S

    2014-12-01

    Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007-2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p<0.001), predominantly male (53.3% versus 38.5%, p<0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p<0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p<0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p<0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27-1.61, p<0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69-0.87, p<0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted. PMID:24998859

  20. Optimal Contrast of Cerebral Dual-Energy Computed Tomography Angiography in Patients With Spontaneous Subarachnoid Hemorrhage

    PubMed Central

    Wang, Dan; Zhang, Qiaowei; Hu, Hongjie; Zhang, Wenming; Chen, Renbiao; Zee, Chi S.; Yu, Risheng

    2016-01-01

    Objective The aim of this study was to investigate the image quality of cerebral dual-energy computed tomography (CT) angiography using a nonlinear image blending technique as compared with the conventional linear blending method in patients with spontaneous subarachnoid hemorrhage (SAH). Methods A retrospective review of 30 consecutive spontaneous SAH patients who underwent a dual-source, dual-energy (80 kV and Sn140 kV mode) cerebral CT angiography was performed with permission from hospital ethical committee. Optimized images using nonlinear blending method were generated and compared with the 0.6 linear blending images by evaluating cerebral artery enhancement, attenuation of SAH, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), respectively. Two neuroradiologists independently assessed subjective vessel visualization per segment using a 5-point scale. Results The nonlinear blending images showed higher cerebral artery enhancement (307.24 ± 58.04 Hounsfield unit [HU]), lower attenuation of SAH (67.07 ± 6.79 HU), and image noise (7.18 ± 1.20 HU), thus achieving better SNR (43.92 ± 11.14) and CNR (34.34 ± 10.25), compared with those of linear blending images (235.47 ± 46.45 HU for cerebral artery enhancement, 70.00 ± 6.41 HU for attenuation of SAH, 8.39 ± 1.25 HU for image noise, 28.86 ± 8.43 for SNR, and 20.37 ± 7.74 for CNR) (all P < 0.01). The segmental scorings of the nonlinear blending image (31.6% segments with a score of 5, 57.4% segments with a score of 4, 11% segments with a score of 3) ranged significantly higher than those of linear blending images (11.5% segments with a score of 5, 77.5% segments with a score of 4, 11% segments with a score of 3) (P < 0.01). The interobserver agreement was good (κ = 0.762), and intraobserver agreement was excellent for both observers (κ = 0.844 and 0.858, respectively). Conclusions The nonlinear image blending technique improved vessel visualization of cerebral dual-energy CT

  1. Neuroimaging characteristics of ruptured aneurysm as predictors of outcome after aneurysmal subarachnoid hemorrhage: pooled analyses of the SAHIT cohort.

    PubMed

    Jaja, Blessing N R; Lingsma, Hester; Steyerberg, Ewout W; Schweizer, Tom A; Thorpe, Kevin E; Macdonald, R Loch

    2016-06-01

    OBJECT Neuroimaging characteristics of ruptured aneurysms are important to guide treatment selection, and they have been studied for their value as outcome predictors following aneurysmal subarachnoid hemorrhage (SAH). Despite multiple studies, the prognostic value of aneurysm diameter, location, and extravasated SAH clot on computed tomography scan remains debatable. The authors aimed to more precisely ascertain the relation of these factors to outcome. METHODS The data sets of studies included in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository were analyzed including data on ruptured aneurysm location and diameter (7 studies, n = 9125) and on subarachnoid clot graded on the Fisher scale (8 studies; n = 9452) for the relation to outcome on the Glasgow Outcome Scale (GOS) at 3 months. Prognostic strength was quantified by fitting proportional odds logistic regression models. Univariable odds ratios (ORs) were pooled across studies using random effects models. Multivariable analyses were adjusted for fixed effect of study, age, neurological status on admission, other neuroimaging factors, and treatment modality. The neuroimaging predictors were assessed for their added incremental predictive value measured as partial R(2). RESULTS Spline plots indicated outcomes were worse at extremes of aneurysm size, i.e., less than 4 or greater than 9 mm. In between, aneurysm size had no effect on outcome (OR 1.03, 95% CI 0.98-1.09 for 9 mm vs 4 mm, i.e., 75th vs 25th percentile), except in those who were treated conservatively (OR 1.17, 95% CI 1.02-1.35). Compared with anterior cerebral artery aneurysms, posterior circulation aneurysms tended to result in slightly poorer outcome in patients who underwent endovascular coil embolization (OR 1.13, 95% CI 0.82-1.57) or surgical clipping (OR 1.32, 95% CI 1.10-1.57); the relation was statistically significant only in the latter. Fisher CT subarachnoid clot burden was related to outcome in a gradient manner. Each

  2. Turner syndrome with spinal hemorrhage due to vascular malformation

    PubMed Central

    Yu, Min Kyung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Kim, Duk Hee; Kim, Ho-Seong

    2015-01-01

    Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS. PMID:26817012

  3. Magnetic Resonance Imaging Detects and Predicts Early Brain Injury after Subarachnoid Hemorrhage in a Canine Experimental Model

    PubMed Central

    Jadhav, Vikram; Sugawara, Takashi; Zhang, John; Jacobson, Paul

    2008-01-01

    Abstract The canine double hemorrhage model is an established model to study cerebral vasospasm, the late sequelae of subarachnoid hemorrhage (SAH). The present study uses magnetic resonance imaging (MRI) to examine the recently reported early brain injury after SAH. Double hemorrhage SAH modeling was obtained by injecting 0.5 mL/kg of autologous arterial blood into the cisterna magna of five adult mongrel dogs on day 0 and day 2, followed by imaging at day 2 and day 7 using a 4.7-Tesla (T) scanner. White matter (WM) showed a remarkable increase in T2 values at day 2 which resolved by day 7, whereas gray matter (GM) T2 values did not resolve. The apparent diffusion coefficient (ADC) values progressively increased in both WM and GM after SAH, suggestive of a transition from vasogenic to cytotoxic edema. Ventricular volume also increased dramatically. Prominent neuronal injury with Nissl's staining was seen in the cortical GM and in the periventricular tissue. Multimodal MRI reveals acute changes in the brain after SAH and can be used to non-invasively study early brain injury and normal pressure hydrocephalus post-SAH. MR can also predict tissue histopathology and may be useful for assessing pharmacological treatments designed to ameliorate SAH. PMID:18729770

  4. Time course of the diameter of the major cerebral arteries after subarachnoid hemorrhage using corrosion cast technique.

    PubMed

    Ono, Shigeki; Date, Isao; Onoda, Keisuke; Ohmoto, Takashi

    2003-06-01

    In this report, we examined whether corrosion cast method is also applicable for the measurement and estimation of the rat major arteries in which subarachnoid hemorrhage (SAH) is produced. Additionally, we have examined the diameters of the rat major arteries following SAH. A total of 0.3 ml autologous blood was injected into the cisterna magna of male Sprague-Dawley rats for the SAH model. A perfusion of a semi-polymerized casting medium was performed, 10 min, 30 min, 1 h, 4 h, 8 h, 1 day, 2 days, 3 days, 5 days, and 7 days after SAH. The brains were corroded in a 10% NaOH solution. The BA and the other major arteries were then measured using scanning electron microscopy (SEM). Macroscopic observation and hematoxylin-eosin (HE) staining were also performed. Using the corrosion cast method, the biphasic contractile response was observed in the BA; 8.3% and 11.6% contractions were observed 30 min and 1 day after SAH, respectively. In addition, there was almost no smooth muscle or adventitial thickening in the chronic stage. In contrast, the dilative response was observed in the internal carotid artery and middle cerebral artery 10 min after SAH. Macroscopic findings and HE staining revealed that the extensive basal subarachnoid hematoma had almost disappeared by day 2. These results indicate that in this model, the minimal spasm, which occurs one day after SAH, can be explained by the small capacity of the rat subarachnoid space and the rapid cerebrospinal fluid washout around major vessels at the cerebral base. Moreover, the present data also show the compensatory dilatation in the ICA and MCA in the early stage after SAH. PMID:12870265

  5. Subarachnoid hemorrhage in the rat: cerebral blood flow and glucose metabolism during the late phase of cerebral vasospasm

    SciTech Connect

    Delgado, T.J.; Arbab, M.A.; Diemer, N.H.; Svendgaard, N.A.

    1986-10-01

    A double-isotope technique for the simultaneous measurement of CBF and CMRglu was applied to a subarachnoid hemorrhage (SAH) model in the rat. Cisternal injection of 0.07 ml blood caused a rather uniform 20% reduction in CBF together with an increase in glucose utilization of 30% during the late phase of vasospasm. In one-third of the SAH animals, there were focal areas where the flow was lowered to 30% of the control values and the glucose uptake increased to approximately 250% of control. We suggest that blood in the subarachnoid space via a neural mechanism induces the global flow and metabolic changes, and that the foci are caused by vasospasm superimposed on the global flow and metabolic changes. In the double-isotope autoradiographic technique, (/sup 14/C)iodoantipyrine and (/sup 3/H)deoxyglucose were used for CBF and CMRglu measurements, respectively, in the same animal. In half of the sections, the (/sup 14/C)iodoantipyrine was extracted using 2,2-dimethoxypropane before the section was placed on a /sup 3/H- and /sup 14/C-sensitive film. The other sections were placed on x-ray film with an emulsion insensitive to /sup 3/H. The validity of the double-isotope method was tested by comparing the data with those obtained in animals receiving a single isotope. The CBF and metabolic values obtained in the two groups were similar.

  6. The Effectiveness of Lumbar Cerebrospinal Fluid Drainage to Reduce the Cerebral Vasospasm after Surgical Clipping for Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Park, Soojeong; Yang, Narae

    2015-01-01

    Objective Removal of blood from subarachnoid space with a lumbar drainage (LD) may decrease development of cerebral vasospasm. We evaluated the effectiveness of a LD for a clinical vasospasm and outcomes after clipping of aneurysmal subarachnoid hemorrhage (SAH). Methods Between July 2008 and July 2013, 234 patients were included in this study. The LD group consisted of 126 patients, 108 patients in the non LD group. We investigated outcomes as follow : 1) clinical vasospasm, 2) angioplasty, 3) cerebral infarction, 4) Glasgow outcome scale (GOS) score at discharge, 5) GOS score at 6-month follow-up, and 6) mortality. Results Clinical vasospasm occurred in 19% of the LD group and 42% of the non LD group (p<0.001). Angioplasty was performed in 17% of the LD group and 38% of the non LD group (p=0.001). Cerebral infarctions were detected in 29% and 54% of each group respectively (p<0.001). The proportion of GOS score 5 at 6 month follow-up in the LD group was 69%, and it was 58% in the non LD group (p=0.001). Mortality rate showed 5% and 10% in each group respectively. But, there was no difference in shunt between the two groups. Conclusion LD after aneurysmal SAH shows marked reduction of clinical vasospasm and need for angioplasty. With this technique we have shown favorable GOS score at 6 month follow-up. PMID:25810855

  7. Global emergency medicine journal club: social media responses to the January 2014 online emergency medicine journal club on subarachnoid hemorrhage.

    PubMed

    Chan, Teresa M; Rosenberg, Hans; Lin, Michelle

    2014-07-01

    From January 20 to 24, 2014, Annals continued a successful collaboration with an academic Web site, Academic Life in Emergency Medicine (ALiEM), to host another Global Emergency Medicine Journal Club session featuring the 2013 Journal of the American Medical Association article "Clinical Decision Rules to Rule Out Subarachnoid Hemorrhage for Acute Headache" by Perry et al. This online journal club used the power of rapid Twitter conversations, a live videocast with the authors, and more detailed discussions hosted on the ALiEM Web site's comment section. There were more than 1,431 individuals from 501 cities in 59 countries who viewed the blog post. During this 5-day event, 28 comments (average word count 153 words) and 206 tweets were made. This summary article details the community discussion, shared insights, and analytic data generated during this novel, multiplatform approach. PMID:24951414

  8. Subarachnoid hemorrhage caused by Aspergillus aneurysm as a complication of transcranial biopsy of an orbital apex lesion--case report.

    PubMed

    Okada, Y; Shima, T; Nishida, M; Yamane, K; Yoshida, A

    1998-07-01

    A 62-year-old male complaining of unilateral visual disturbance and pain in the involved eye had a small mass at the right orbital apex which was identified as an Aspergillus granuloma by transcranial biopsy. One month later, the patient became comatose because of fatal subarachnoid hemorrhage due to a newly developed aneurysm. Autopsy showed a ruptured aneurysm on the right internal carotid-posterior communicating artery. Histological examination demonstrated prominent Aspergillus invasion of the arterial wall. Aspergillus infection must be taken into consideration in patients with orbital apex syndrome, which may lead to serious cerebrovascular consequences. If sino-orbital lesions are detected by neuroimaging techniques, biopsy using an extradural approach should be performed to obtain a definitive diagnosis. PMID:9745252

  9. The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage

    PubMed Central

    2013-01-01

    Background Although microglia and the Toll-like receptor (TLR) pathway have long been thought to play a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), thus far only correlations have been made. In this study, we attempted to solidify the relationship between microglia and the TLR pathway using depletion and genetic knockouts, respectively. Methods Subarachnoid hemorrhage was induced in TLR4−/−, TRIF−/−, MyD88−/− and wild type C57BL/6 mice by injecting 60 μl of autologous blood near the mesencephalon; animals were euthanized 1 to 15 days after SAH for immunohistochemical analysis to detect microglia or apoptotic cells. Lastly, microglial depletion was performed by intracerebroventricular injection of clodronate liposomes. Results On post operative day (POD) 7 (early phase SAH), neuronal apoptosis was largely TLR4-MyD88-dependent and microglial-dependent. By POD 15 (late phase SAH), neuronal apoptosis was characterized by TLR4- toll receptor associated activator of interferon (TRIF)-dependence and microglial-independence. Similarly, vasospasm was also characterized by an early and late phase with MyD88 and TRIF dependence, respectively. Lastly, microglia seem to be both necessary and sufficient to cause vasospasm in both the early and late phases of SAH in our model. Conclusion Our results suggest that SAH pathology could have different phases. These results could explain why therapies tailored to aSAH patients have failed for the most part. Perhaps a novel strategy utilizing immunotherapies that target Toll like receptor signaling and microglia at different points in the patient’s hospital course could improve outcomes. PMID:23849248

  10. Direct communication of the spinal subarachnoid space with the rat dorsal root ganglia.

    PubMed

    Joukal, Marek; Klusáková, Ilona; Dubový, Petr

    2016-05-01

    The anatomical position of the subarachnoid space (SAS) in relation to dorsal root ganglia (DRG) and penetration of tracer from the SAS into DRG were investigated. We used intrathecal injection of methylene blue to visualize the anatomical position of the SAS in relation to DRG and immunostaining of dipeptidyl peptidase IV (DPP-IV) for detecting arachnoid limiting the SAS. Intrathecal administration of fluorescent-conjugated dextran (fluoro-emerald; FE) was used to demonstrate direct communication between the SAS and DRG. Intrathecal injection of methylene blue and DPP-IV immunostaining revealed that SAS delimited by the arachnoid was extended up to the capsule of DRG in a fold-like recess that may reach approximately half of the DRG length. The arachnoid was found in direct contact to the neuronal body-rich area in the angle between dorsal root and DRG as well as between spinal nerve roots at DRG. Particles of FE were found in the cells of DRG capsule, satellite glial cells, interstitial space, as well as in small and medium-sized neurons after intrathecal injection. Penetration of FE from the SAS into the DRG induced an immune reaction expressed by colocalization of FE and immunofluorescence indicating antigen-presenting cells (MHC-II+), activated (ED1+) and resident (ED2+) macrophages, and activation of satellite glial cells (GFAP+). Penetration of lumbar-injected FE into the cervical DRG was greater than that into the lumbar DRG after intrathecal injection of FE into the cisterna magna. Our results demonstrate direct communication between DRG and cerebrospinal fluid in the SAS that can create another pathway for possible propagation of inflammatory and signaling molecules from DRG primary affected by peripheral nerve injury into DRG of remote spinal segments. PMID:26844624

  11. Cultured human chromaffin cells grafted in spinal subarachnoid space relieves allodynia in a pain rat model

    PubMed Central

    Jeon, Younghoon; Baek, Woon Yi; Chung, Seung Hyun; Shin, Nari; Kim, Hye Rim

    2011-01-01

    Background Implantation of xenogenic chromaffin cells into the spinal subarachnoid space can produce analgesia in neuropathic pain models. However, transplantation of xenogeneic chromaffin cell has a potential risk of viral or bacterial infections from animals to humans including encephalopathy due to prion transmission. The aim of this study was to investigate the possibility of developing a homogeneic source of therapeutic chromaffin cells. Methods Anti-allodynic effects of human chromaffin cells (HCCs) were evaluated in a neuropathic pain model in rats induced by chronic constriction injury of the sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were intrathecally implanted into rats (n = 10), while empty capsules were intrathecally implanted as a control (n = 8). Levels of norepinephrine from encapsulated HCCs before and after nicotinic stimulation were measured. We then perfomed a behavior test (cold allodynia) with acetone. In addition, to assess the potential contribution to pain reduction of opioid peptides released from the HCCs, all animals were injected with naloxone. Results The concentration of norepinephrine after nicotine stimulation was significantly increased compared to basal levels. Intrathecal implantation of encapsulated HCCs, significantly reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05). Fifteen minutes after the injection of naloxone, cold allodynia significantly decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in control animals was unaltered. Conclusions From these results, it appears that HCCs have a possibility as an analgesic source for transplants delivering pain-reducing neuroactive substances. PMID:21716909

  12. 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

    2016-01-01

    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. PMID:27277584

  13. Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid hemorrhage

    PubMed Central

    Kokkoris, Stelios; Andrews, Peter; Webb, David J.

    2012-01-01

    Calcitonin gene-related peptide (CGRP) is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G protein-coupled receptor called calcitonin receptor-like receptor (CLR), a single transmembrane protein called receptor activity-modifying protein (RAMP), and an additional protein that is required for Gas coupling, known as receptor component protein (RCP). Several mechanisms involved in CGRP-mediated relaxation have been identified. These include nitric oxide (NO)-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid hemorrhage (SAH) is associated with cerebral vasoconstriction that occurs several days after the hemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: (a) the pathophysiology of delayed ischemic neurologic deficit after SAH (b) the basics of the CGRP receptor structure, signal transduction, and vasodilatation mechanisms and (c) the studies that have been conducted so far using CGRP in both animals and humans with SAH. PMID:23162536

  14. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

    PubMed

    Dong, Yushu; Fan, Chongxi; Hu, Wei; Jiang, Shuai; Ma, Zhiqiang; Yan, Xiaolong; Deng, Chao; Di, Shouyin; Xin, Zhenlong; Wu, Guiling; Yang, Yang; Reiter, Russel J; Liang, Guobiao

    2016-04-01

    Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis. PMID:26639408

  15. Effect of subarachnoid hemorrhage on contractile responses and noradrenaline release evoked in cat cerebral arteries by histamine

    SciTech Connect

    Lobato, R.D.; Marin, J.; Salaices, M.; Rico, M.L.; Sanchez, C.F.

    1981-10-01

    This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the contractile responses and the noradrenaline release evoked in cat cerebral arteries by histamine. The dose-dependent vasoconstriction induced by histamine on the cerebral arteries of normal cats was significantly reduced by diphenhydramine and phentolamine. When SAH was produced 3 and 7 days before the experiment, the histamine-induced vasoconstriction also decreased. Thereafter, a tendency to normalization in the contractile vascular responses was observed such that in 15 days after the hemorrhage it was not significantly different from that found in controls animals. The decrease in the contractile responses to histamine provoked by SAH was similar to that seen after pretreatment with intracisternal injections of 6-hydroxydopamine. The amount of radioactivity released by histamine following preincubation with /sup 3/H-noradrenaline from the cerebral arteries of cats exposed to SAH 3, 7, and 15 days before the experiment was significantly reduced when compared with controls. Moreover, the basal level of tritium release and the radioactivity retained at the end of the experiment were also decreased after SAH. Results indicate histamine releases noradrenaline from cat cerebral arteries, and SAH produce a transient denervation of the perivascular adrenergic nerve endings, which explained by the impairment of the indirect adrenergic mechanism involved in the overall contractile response elicited by this amine in cerebral arteries. Histamine does not seem to play a significant role in the production of the cerebral vasospasm occurring after SAH.

  16. Mammalian target of rapamycin (mTOR) inhibition reduces cerebral vasospasm following a subarachnoid hemorrhage injury in canines.

    PubMed

    Zhang, Weiguang; Khatibi, Nikan H; Yamaguchi-Okada, Mitsuo; Yan, Junhao; Chen, Chunhua; Hu, Qin; Meng, Haiwei; Han, Hongbin; Liu, Shuwei; Zhou, Changman

    2012-02-01

    Mammalian target of rapamycin (mTOR) pathway is a serine/threonine protein kinase that plays a vital role in regulating growth, proliferation, survival, and protein synthesis among cells. In the present study, we investigated the role of the mTOR pathway following subarachnoid hemorrhage brain injury--specifically investigating its ability to mediate the activation of cerebral vasospasm. Additionally, we investigated whether key signaling pathway molecules such as the mTOR, P70S6K1, and 4E-BP1 play a role in the process. Thirty dogs were randomly divided into 5 groups: sham, SAH (subarachnoid hemorrhage), SAH+DMSO (dimethyl sulfoxide), SAH+Rapamycin and SAH+AZD8055. An established canine double-hemorrhage model of SAH was used by injecting autologous arterial blood into the cisterna magna on days 0 and 2. Angiography was performed at days 0 and 7. Clinical behavior, histology, immunohistochemistry, and Western blot of mTOR, P70S6K1, 4E-BP1 and PCNA (proliferating cell nuclear antigen) in the basilar arteries were examined. In the SAH and SAH+DMSO groups, severe angiographic vasospasm was obtained (34.3±19.8%, 38.4±10.3) compared with that in Sham (93.9±5.0%) respectively. mTOR, P70S6K1, 4E-BP1 and PCNA increased in the sample of spastic basilar arteries (p<0.05). In the SAH+RAPA and SAH+AZD8055 groups, Rapamycin and AZD8055 attenuated angiographic vasospasm (62.3±15.9% and 65.2±10.3%) while improving appetite and activity scores (p<0.05) on days 5 through 7. Rapamycin and AZD8055 significantly reduced the level and expression of mTOR, P70S6K1, 4E-BP1 and PCNA (p<0.05). In conclusion, our study suggests that the mTOR molecular signaling pathway plays a significant role in cerebral vasospasm following SAH, and that inhibition of the mTOR pathway has the potential to become an attractive strategy to treat vasospasm following SAH. PMID:22177999

  17. Protein therapy using heme-oxygenase-1 fused to a polyarginine transduction domain attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

    PubMed

    Ogawa, Tomoyuki; Hänggi, Daniel; Wu, Yumei; Michiue, Hiroyuki; Tomizawa, Kazuhito; Ono, Shigeki; Matsui, Hideki; Date, Isao; Steiger, Hans-Jakob

    2011-11-01

    A sequence of 11 consecutive arginine residues (11R) is one of the best protein transduction domains for introducing proteins into cell membranes. Heme-oxygenase-1 (HO-1) is involved in heme catabolism and reduces the contractile effect of hemoglobin after subarachnoid hemorrhage (SAH). Therefore, we constructed 11R-fused HO-1 protein to achieve successful transduction of the protein into the cerebral arteries and examined the therapeutic effect of the 11R-HO-1 protein for cerebral vasospasm (CV) after SAH. We injected the 11R-HO-1 protein into the cisterna magna of male rats and, several hours after the injection, performed immunofluorescence staining and western blotting analysis of the rat basilar arteries (BAs) to determine transduction efficacy. We also assessed intraarterial HO-1 activity as cGMP (cyclic guanosine 3', 5'-cyclic monophosphate) accumulation in SAH and determined whether protein transduction of 11R-HO-1 quantified the therapeutic effect in a rat double-hemorrhage model of SAH. The BAs expressed significantly more HO-1 in the group injected with 11R-HO-1 (3.56±0.54 (11R-HO-1) versus control (saline)), and transduction of 11R-HO-1 resulted in higher activity (>3.25-fold) in rat BAs with SAH. Moreover, the results of the rat double-hemorrhage model showed that the 11R-HO-1 protein significantly attenuated CV after SAH (317.59±23.48 μm (11R-HO-1) versus 270.08±14.66 μm (11R-fused enhanced green fluorescent protein), 252.05±13.95 μm (saline), P<0.01). PMID:21654696

  18. Intracranial Vasospasm without Intracranial Hemorrhage due to Acute Spontaneous Spinal Subdural Hematoma

    PubMed Central

    Oh, Jung-Hwan; Jwa, Seung-Joo; Yang, Tae Ki; Lee, Chang Sub; Oh, Kyungmi

    2015-01-01

    Spontaneous spinal subdural hematoma (SDH) is very rare. Furthermore, intracranial vasospasm (ICVS) associated with spinal hemorrhage has been very rarely reported. We present an ICVS case without intracranial hemorrhage following SDH. A 41-year-old woman was admitted to our hospital with a complaint of severe headache. Multiple intracranial vasospasms were noted on a brain CT angiogram and transfemoral cerebral angiography. However, intracranial hemorrhage was not revealed by brain MRI or CT. On day 3 after admission, weakness of both legs and urinary incontinence developed. Spine MRI showed C7~T6 spinal cord compression due to hyperacute stage of SDH. After hematoma evacuation, her symptoms gradually improved. We suggest that spinal cord evaluation should be considered in patients with headache who have ICVS, although intracranial hemorrhage would not be visible in brain images. PMID:26713084

  19. Recurrent Meningitis and Subarachnoid Hemorrhage Due to Salmonella in an HIV+ Patient: Case Report and Mini-Review of the Literature

    PubMed Central

    Belloso, Waldo H; Romano, Marina; Greco, Graciela S; Davey, Richard T; Perelsztein, Ariel G; Sánchez, Marisa L; Ajzenszlos, Martín R; Otegui, Inés M

    2011-01-01

    Meningitis due to non-typhi salmonella is infrequent in HIV-positive adults. We report a case of a patient with >300 CD4+ cells/mm3 who presented with five episodes of recurrent meningitis, focal subarachnoid hemorrhage and cerebral vasculitis ultimately attributed to Salmonella choleraesuis infection. Even within the cART era invasive salmonellosis can occur in unusual ways in HIV-infected patients. PMID:21772932

  20. The influence of coughing on cerebrospinal fluid pressure in an in vitro syringomyelia model with spinal subarachnoid space stenosis

    PubMed Central

    2009-01-01

    Background The influence of coughing, on the biomechanical environment in the spinal subarachnoid space (SAS) in the presence of a cerebrospinal fluid flow stenosis, is thought to be an important etiological factor in craniospinal disorders, including syringomyelia (SM), Chiari I malformation, and hydrocephalus. The aim of this study was to investigate SAS and syrinx pressures during simulated coughing using in vitro models and to provide information for the understanding of the craniospinal fluid system dynamics to help develop better computational models. Methods Four in vitro models were constructed to be simplified representations of: 1) non-communicating SM with spinal SAS stenosis; 2) non-communicating SM due to spinal SAS stenosis with a distensible spinal column; 3) non-communicating SM post surgical removal of a spinal SAS stenosis; and 4) a spinal SAS stenosis due to spinal trauma. All of the models had a flexible spinal cord. To simulate coughing conditions, an abrupt CSF pressure pulse (~ 5 ms) was imposed at the caudal end of the spinal SAS by a computer-controlled pump. Pressure measurements were obtained at 4 cm intervals along the spinal SAS and syrinx using catheter tip transducers. Results Pressure measurements during a simulated cough, showed that removal of the stenosis was a key factor in reducing pressure gradients in the spinal SAS. The presence of a stenosis resulted in a caudocranial pressure drop in the SAS, whereas pressure within the syrinx cavity varied little caudocranially. A stenosis in the SAS caused the syrinx to balloon outward at the rostral end and be compressed at the caudal end. A >90% SAS stenosis did not result in a significant Venturi effect. Increasing compliance of the spinal column reduced forces acting on the spinal cord. The presence of a syrinx in the cord when there was a stenosis in the SAS, reduced pressure forces in the SAS. Longitudinal pressure dissociation acted to suck fluid and tissue caudocranially in the

  1. Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy.

    PubMed

    Vuong, Shawn M; Jeong, William J; Morales, Humberto; Abruzzo, Todd A

    2016-10-01

    Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail. PMID:27616317

  2. Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats.

    PubMed

    Tan, Guanping; Liu, Liu; He, Zhaohui; Sun, Jiujun; Xing, Wenli; Sun, Xiaochuan

    2016-07-01

    Early brain injury (EBI) is a major cause of mortality from subarachnoid hemorrhage (SAH). We aimed to study the pathophysiology of EBI and explore the role of hepcidin, a protein involved in iron homeostatic regulation, and its downstream proteins. One hundred and thirty-two male Sprague-Dawley rats were assigned into groups (n = 24/group): sham, SAH, SAH + hepcidin, SAH + hepcidin-targeting small interfering ribonucleic acid (siRNA), and SAH + scramble siRNA. Three hepcidin-targeting siRNAs and one scramble siRNA for hepcidin were injected 24 h before hemorrhage induction, and hepcidin protein was injected 30 min before induction. The rats were neurologically evaluated at 24 h and euthanized at 72 h. Hepcidin, ferroportin-1, and ceruloplasmin protein expression were measured by immunohistochemistry and Western blotting. Brain water content, blood-brain barrier (BBB) leakage, non-heme tissue iron and Garcia scale were evaluated. Hepcidin expression increased in the cerebral cortex and hippocampus after experimental SAH (P < 0.05 compared to sham), while ferroportin-1 and ceruloplasmin decreased (P < 0.05). Hepcidin injection lowered the expression of ferroportin-1 and ceruloplasmin further but siRNA reduced the levels of hepcidin (P < 0.05 compared to SAH) resulting in recovery of ferroportin-1 and ceruloplasmin levels. Apoptosis was increased in SAH rats compared to sham (P < 0.05) and increased slightly more by hepcidin, but decreased by siRNA (P < 0.05 compared to SAH). SAH rats had lower neurological scores, high brain water content, BBB permeability, and non-heme tissue iron (P < 0.05). In conclusion, downregulation of ferroportin-1 and ceruloplasmin caused by hepcidin enhanced iron-dependent oxidative damage and may be the potential mechanism of SAH. PMID:27250827

  3. Does isolated traumatic subarachnoid hemorrhage merit a lower intensity level of observation than other traumatic brain injury?

    PubMed

    Phelan, Herb A; Richter, Adam A; Scott, William W; Pruitt, Jeffrey H; Madden, Christopher J; Rickert, Kim L; Wolf, Steven E

    2014-10-15

    Evidence is emerging that isolated traumatic subarachnoid hemorrhage (ITSAH) may be a milder form of traumatic brain injury (TBI). If true, ITSAH may not benefit from intensive care unit (ICU) admission, which would, in turn, decrease resource utilization. We conducted a retrospective review of all TBI admissions to our institution between February 2010 and November 2012 to compare the presentation and clinical course of subjects with ITSAH to all other TBI. We then performed descriptive statistics on the subset of ITSAH subjects presenting with a Glasgow Coma Score (GCS) of 13-15. Of 698 subjects, 102 had ITSAH and 596 had any other intracranial hemorrhage pattern. Compared to all other TBI, ITSAH had significantly lower injury severity scores (p<0.0001), lower head abbreviated injury scores (p<0.0001), higher emergency department GCS (p<0.0001), shorter ICU stays (p=0.007), higher discharge GCS (p=0.005), lower mortality (p=0.003), and significantly fewer head computed tomography scans (p<0.0001). Of those ITSAH subjects presenting with a GCS of 13-15 (n=77), none underwent placement of an intracranial monitor or craniotomy. One subject (1.3%) demonstrated a change in exam (worsened headache and dizziness) concomitant with a progression of his intracranial injury. His symptoms resolved with readmission to the ICU and continued observation. Our results suggest that ITSAH are less-severe brain injuries than other TBI. ITSAH patients with GCS scores of 13-15 demonstrate low rates of clinical progression, and when progression occurs, it resolves without further intervention. This subset of TBI patients does not appear to benefit from ICU admission. PMID:24926612

  4. Association between S100B Levels and Long-Term Outcome after Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Pooled Analysis

    PubMed Central

    Lai, Pui Man Rosalind; Du, Rose

    2016-01-01

    S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer’s Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (padj = 3.1 x 10−4) and worse GOS outcome (padj = 5.5 x 10−11). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome. PMID:27007976

  5. [The relationship between aneurysmal subarachnoid hemorrhage and meteorological parameters based on a series of 236 French patients].

    PubMed

    Rué, M; Camiade, E; Jecko, V; Bauduer, F; Vignes, J-R

    2014-10-01

    Subarachnoid hemorrhage (SAH) is a sudden and potentially severe event with mortality rates ranging between 24 and 30 % depending on the initial clinical condition. Studies have attempted to assess the possible influence of meteorological parameters on the occurrence of SAH. However, this idea remains very controversial and the results vary widely from one study to another. Our study is the second largest French series, and first performed in a homogeneous series of patients. The aim of our study was to attempt to establish a relationship between the weather (i.e.) temperature variations and daily variations of atmospheric pressure in the days before the onset of SAH and the same day and the occurrence of non-traumatic SAH in a homogeneous population of 236 patients from a single center, over a period of 7 years (2002 to 2008). This retrospective study does not suggest any relationship between the occurrence of SAH and meteorological data studied. Moreover, no relationship was observed between mean changes in temperature or pressure and the occurrence of SAH, that the day of the bleeding or the days preceding the SAH. However, a female predominance was observed and a relatively high mortality rate of 18.3 %. The distribution of the occurrence of an SAH was random. As it seems impossible to provide logistics and organization of care for non-traumatic SAH, the care system must remain vigilant throughout the year. PMID:24856315

  6. Medical Management of Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage: A Review of Current and Emerging Therapeutic Interventions

    PubMed Central

    Adamczyk, Peter; Amar, Arun Paul; Mack, William J.

    2013-01-01

    Cerebral vasospasm is a major source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Evidence suggests a multifactorial etiology and this concept remains supported by the assortment of therapeutic modalities under investigation. The authors provide an updated review of the literature for previous and recent clinical trials evaluating medical treatments in patients with cerebral vasospasm secondary to aSAH. Currently, the strongest evidence supports use of prophylactic oral nimodipine and initiation of triple-H therapy for patients in cerebral vasospasm. Other agents presented in this report include magnesium, statins, endothelin receptor antagonists, nitric oxide promoters, free radical scavengers, thromboxane inhibitors, thrombolysis, anti-inflammatory agents and neuroprotectants. Although promising data is beginning to emerge for several treatments, few prospective randomized clinical trials are presently available. Additionally, future investigational efforts will need to resolve discrepant definitions and outcome measures for cerebral vasospasm in order to permit adequate study comparisons. Until then, definitive recommendations cannot be made regarding the safety and efficacy for each of these therapeutic strategies and medical management practices will continue to be implemented in a wide-ranging manner. PMID:23691312

  7. 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. PMID:27423593

  8. Detection of Neuroinflammation in a Rat Model of Subarachnoid Hemorrhage Using [18F]DPA-714 PET Imaging.

    PubMed

    Thomas, Clément; Vercouillie, Johnny; Doméné, Aurélie; Tauber, Clovis; Kassiou, Michael; Guilloteau, Denis; Destrieux, Christophe; Sérrière, Sophie; Chalon, Sylvie

    2016-01-01

    Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinflammation related to microglial activation was correlated with the degree of bleeding. We used the rat filament model and evaluated (at 48 hours postsurgery) the intensity of neuroinflammation using positron emission tomography (PET) imaging with the 18-kDa translocator protein (TSPO) tracer [(18)F]DPA-714, quantitative autoradiography with [(3)H]PK-11195, and SAH grade by postmortem brain picture. High SAH grades were strongly and positively correlated with in vivo PET imaging of TSPO in the cortex and striatum. In addition, a positive correlation was found in the cortex in TSPO, with densities determined by imaging and autoradiographic approaches. Qualitative immunofluorescence studies indicated that overexpression of TSPO was linked to astrocytic/microglial activation. In this model, PET imaging of TSPO using [(18)F]DPA-714 appeared to be a relevant index of the degree of bleeding, indicating that this imaging method could be used in human patients to improve the management of patients with SAH. PMID:27118758

  9. Hemoglobin induced NO/cGMP suppression Deteriorate Microcirculation via Pericyte Phenotype Transformation after Subarachnoid Hemorrhage in Rats

    PubMed Central

    Li, Qiang; Chen, Yujie; Li, Bo; Luo, Chunxia; Zuo, Shilun; Liu, Xin; Zhang, John H.; Ruan, Huaizhen; Feng, Hua

    2016-01-01

    Subarachnoid hemorrhage (SAH) usually results from ruptured aneurysm, but how leaked hemoglobin regulates the microcirculation in the pathophysiology of early brain injury after SAH is still unclear. In the present study, we sought to investigate the role and possible mechanism of hemoglobin induced pericyte phenotype transformation in the regulation of microcirculation after SAH. Endovascular perforation SAH rat model, brain slices and cultured pericytes were used, and intervened with endothelial nitric oxide synthase (eNOS) antagonist L-NNA and its agonist scutellarin, hemoglobin, DETA/NO (nitric oxide(NO) donor), PITO (NO scavenger), 8-Br-cGMP (cGMP analog). We found modulating eNOS regulated pericyte α-SMA phenotype transformation, microcirculation, and neurological function in SAH rats. Modulating eNOS also affected eNOS expression, eNOS activity and NO availability after SAH. In addition, we showed hemoglobins penetrated into brain parenchyma after SAH. And hemoglobins significantly reduced the microvessel diameters at pericyte sites, due to the effects of hemoglobin inducing α-SMA expressions in cultured pericytes and brain slices via inhibiting NO/cGMP pathway. In conclusion, pericyte α-SMA phenotype mediates acute microvessel constriction after SAH possibly by hemoglobin suppressing NO/cGMP signaling pathway. Therefore, by targeting the eNOS and pericyte α-SMA phenotype, our present data may shed new light on the management of SAH patients. PMID:26911739

  10. Changes in trace elements of cerebrospinal fluid after subarachnoid hemorrhage, and effects of trace elements on vasospasm

    NASA Astrophysics Data System (ADS)

    Sato, N.; Kuroda, K.; Suzuki, M.; Ogawa, A.; Sera, K.

    1999-04-01

    Various causal factors have been proposed for cerebral vasospasm after subarachnoid hemorrhage (SAH), such as serotonin, acetylcholine, angiotensin, thrombin and thromboxane A2. However, none of them explain the whole pathomechanism of vasospasm. To evaluate the role of trace elements on vasospasm, we have examined these sequential changes in the cerebrospinal fluid (CSF) after SAH by PIXE, and have investigated the relation between trace elements and vasospasm. We obtained the CSF samples from cisternal drainage in patients with SAH who underwent radical surgery within 48 h from the onset. The drainage was placed into basal cisterns at the end of the operation. Three sampling times (3-5, 7-9 and 12-14 days from the onset) has been scheduled because vasospasm is likely to occur from day 4 to day 14 after the onset. In this study, we focused on the levels of Mg, Ca, Mn, Al, Zn, P, Pb, Sr, Br, Co, Cu, Si, Ti, Mn,Co, Cu, Zn, Br, Sr, Mo and Pb, and we found a significantly lower level of Mg in the CSF of patients with vasospasm on days 7-9 after the onset. These results suggest that Mg in the CSF may ameliorate vasoconstriction due to Ca in the pathomechanism of vasospasm.

  11. Use of Intra-aortic- Balloon Pump Counterpulsation in Patients with Symptomatic Vasospasm Following Subarachnoid Hemorrhage and Neurogenic Stress Cardiomyopathy

    PubMed Central

    Al-Mufti, Fawaz; Morris, Nicholas; Lahiri, Shouri; Roth, William; Witsch, Jens; Machado, Iona; Agarwal, Sachin; Park, Soojin; Meyers, Philip M.; Connolly, E. Sander; Claassen, Jan

    2016-01-01

    Introduction Intra-aortic counterpulsation balloon pumps (IABPs) have been widely used to augment hemodynamics in critically ill patients with cardiogenic shock and have recently been proposed as a management strategy for subarachnoid hemorrhage (SAH) patients with neurogenic stress cardiomyopathy (NSC). Prior case series have described the use of IABP as a means to manage cardiogenic shock in this patient population; however, we sought to describe our experience with IABP as a means to wean vasopressor requirement while augmenting hemodynamics and maintaining pressures at goal. Methods Five patients were identified from a single center, prospective, observational cohort study that received an IABP for the management of ischemia related to cerebral vasospasm in the setting of NSC. We evaluated all cases for efficacy of IABP in reducing vasopressor requirement, and complications. Results Vasopressor requirements were reduced by a mean of 50% (range 25–65%) following IABPs placement within 24–48 h. There were no significant complications from IABPs. Out of the five patients, the outcome in three cases was favorable (mRS≤1). Two patients suffered delayed cerebral ischemia (DCI), one patient passed away due to severe sepsis, and one patient was left with severe disability. Only one patient required anticoagulation and that was for a preexisting deep venous thrombosis. Conclusion The use of IABPs may be beneficial as an adjunctive therapy in SAH patients with concomitant symptomatic vasospasm and NSC. PMID:27403221

  12. Expression of high-mobility group box-1 (HMGB1) in the basilar artery after experimental subarachnoid hemorrhage.

    PubMed

    Zhao, Xu Dong; Mao, Hai Yan; Lv, Jing; Lu, Xiao Jie

    2016-05-01

    It has been suggested that inflammatory damage may be involved in the pathogenesis of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). High-mobility group box-1 protein (HMGB1) has been identified as a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. However, little is known about the role of HMGB1 in SAH-induced cerebrovascular inflammation. In this study, 48 male rats were assigned randomly to four groups: a control group, or SAH day 3, day 5, or day 7 groups. The animals in SAH day 3, day 5, and day 7 groups were subjected to injection of autologous blood into the cisterna magna twice, on day 0 and day 2, and were killed on days 3, 5, and 7, respectively. Cross-sectional area of the basilar artery was measured and the HMGB1 expression was assessed by immunohistochemistry and western blot analysis. The mRNA level of HMGB1 was also determined by reverse transcription polymerase chain reaction. The basilar arteries exhibited vasospasm after SAH which was most severe on day 3 and 5. Elevated expression of HMGB1 was detected after SAH and was highest on day 3 and 5. HMGB1 is increasingly expressed in parallel to the development of CVS in this rat experimental model of SAH. These results suggest that HMGB1 may be related to the CVS observed after SAH and HMGB1 may play a key role in the inflammatory response in CVS after SAH. PMID:26765765

  13. 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

  14. Induced hypertension for the treatment of cerebral ischemia after subarachnoid hemorrhage. Direct effect on cerebral blood flow

    SciTech Connect

    Muizelaar, J.P.; Becker, D.P.

    1986-04-01

    The best treatment for symptomatic cerebral ischemia from presumed vasospasm after aneurysmal subarachnoid hemorrhage remains a matter of controversy. A direct effect of any treatment modality on regional cerebral blood flow has never been documented. In a series of 43 patients operated on for ruptured anterior circulation aneurysms, five patients (11.6%) developed clinical signs of cerebral ischemia postoperatively. In four of those patients, the diagnosis of vasospasm was made with measurements of cerebral blood flow (133Xe inhalation or intravenous injection, 10-16 detectors, cerebral blood flow infinity). Treatment with induced arterial hypertension with phenylephrine was instituted. Hemodilution was instituted in one patient; the other three patients already had hematocrits in the range of 33. Within 1 hour, the cerebral blood flow measurement was repeated to document the effect of treatment. The average pretreatment hemispherical blood flow on the operated side was 18.8 mL/100 g per minute, on the contralateral side 21.0 mL/100 g per minute. With treatment these flows increased to 30.8 and 35.8 mL/100 g per minute, respectively. There was also an immediate and obvious positive clinical effect in all patients. The role of measurement of cerebral blood flow in the clinical management of vasospasm is discussed. We stress the theoretical and practical advances of measurements of cerebral blood flow over cerebral angiography, especially in comatose patients.

  15. Norrin protected Blood Brain Barrier via Frizzled 4/β-catenin Pathway after Subarachnoid Hemorrhage in Rats

    PubMed Central

    Chen, Yujie; Zhang, Yang; Tang, Junjia; Liu, Fei; Hu, Qin; Luo, Chunxia; Tang, Jiping; Feng, Hua; Zhang, John H

    2014-01-01

    Background and Purpose Norrin and its receptor Frizzled 4 have important roles in the blood-brain barrier (BBB) development. This study is to investigate a potential role and mechanism of Norrin/Frizzled 4 on protecting BBB integrity after subarachnoid hemorrhage (SAH). Methods One hundred and seventy-eight male Sprague-Dawley rats were used. SAH model was induced by endovascular perforation. Frizzled 4 small interfering RNA (siRNA) was injected intracerebroventricularly 48 hours before SAH. Norrin was administrated intracerebroventricularly 3 hours after SAH. SAH grade, neurologic scores, brain water content, Evans blue extravasation, western blots and immunofluorescence were employed to study the mechanisms of Norrin and its receptor regulation protein TSPAN12, as well as neurological outcome. Results Endogenous Norrin and TSPAN12 expression were increased after SAH, and Norrin was colocalizated with astrocytes marker GFAP in cortex. Exogenous Norrin treatment significantly alleviated neurobehavioral dysfunction, reduced brain water content and Evans blue extravasation, promoted β-catenin nuclear translocation and increased Occludin, VE-Cadherin and ZO-1 expressions. These effects were abolished by Frizzled 4 siRNA pretreated before SAH. Conclusions Norrin protected BBB integrity and improved neurological outcome after SAH, and the action of Norrin seemed mediated by Frizzled 4 receptor activation which promoted β-catenin nuclear translocation, which then enhanced Occludin, VE-Cadherin and ZO-1 expression. Norrin might have potential to protect BBB after SAH. PMID:25550365

  16. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Zhang, Zong-yong; Sun, Bao-liang; Yang, Ming-feng; Li, Da-wei; Fang, Jie; Zhang, Shuai

    2015-03-01

    Carnosine (β-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models. PMID:25179154

  17. Spatial and Temporal Morphological Changes in the Subarachnoid Space after Graded Spinal Cord Contusion in the Rat

    PubMed Central

    Reyes-Alva, Horacio J.; Franco-Bourland, Rebecca E.; Martinez-Cruz, Angelina; Grijalva, Israel; Madrazo, Ignacio

    2013-01-01

    Abstract Spontaneous repair or treatment-induced recovery after spinal cord injury (SCI) is very limited and might be related to extramedullary alterations that have only briefly been documented. Here we report on the morphological changes of the spinal subarachnoid space (SAS) in a clinically relevant model of SCI. Anesthetized rats were subjected either to mild or severe spinal cord contusion at T9. Spine blocks from the site of injury and adjacent segments were harvested at acute (1 h and 1 day [d]), subacute (3 and 7 d), and chronic (1 and 3 months) stages post-injury. Histopathology and morphometry at each decalcified vertebral level were assessed. At acute and subacute stages, reduction of SAS lumen was observed after both mild and severe injuries. Acutely, after severe injuries, SAS occlusion was associated mainly with cord swelling and subarachnoid hematomas; a trend for dural sac constriction was observed for mild injuries. At 7 d, cord swelling diminished in both instances, but dural sac constriction increased for severe injuries. At early stages, in the epicenter and vicinity, histopathology revealed compression of neurovascular elements within the SAS, which was more intense in severe than in mild injuries. In the chronic stage, SAS lumen increased notably, mostly from cord atrophy, despite dural sac constriction. Myelograms complemented observations made on SAS lumen permeability. Post-traumatic arachnoiditis occurred mainly in animals with severe injury. In conclusion, early extramedullary SAS changes described here might be expected to produce alterations in cerebrospinal fluid (CSF) dynamics and cord blood perfusion, thereby contributing to the pathophysiology of SCI and becoming novel targets for treatment. PMID:23472674

  18. Inhibition of cerebrovascular raf activation attenuates cerebral blood flow and prevents upregulation of contractile receptors after subarachnoid hemorrhage

    PubMed Central

    2011-01-01

    Background Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH. Results Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ETB, 5-HT1B and AT1 receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score. Conclusion These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy. PMID:22032648

  19. Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature

    PubMed Central

    Dabus, Guilherme; Nogueira, Raul G.

    2013-01-01

    Objectives Cerebral vasospasm is one of the leading causes of morbi-mortality following aneurysmal subarachnoid hemorrhage. The aim of this article is to discuss the current status of vasospasm therapy with emphasis on endovascular treatment. Methods A comprehensive review of the literature obtained by a PubMed search. The most relevant articles related to medical, endovascular and alternative therapies were selected for discussion. Results Current accepted medical options include the oral nimodipine and ‘triple-H’ therapy (hypertension, hypervolemia and hemodilution). Nimodipine remains the only modality proven to reduce the incidence of infarction. Although widely used, ‘triple-H’ therapy has not been demonstrated to significantly change overall outcome after cerebral vasospasm. Indeed, both induced hypervolemia and hemodilution may have deleterious effects, and more recent physiologic data favor normovolemia with induced hypertension or optimization of cardiac output. Endovascular options include percutaneous transluminal balloon angioplasty (PTA) and intra-arterial (IA) infusion of vasodilators. Multiple case reports and case series have been encountered in the literature using different drug regimens with diverse mechanisms of action. Compared with PTA, IA drug infusion has the advantages of distal penetration and a better safety profile. Its main disadvantages are the more frequent need for repeat treatments and its systemic hemodynamic repercussions. Alternative options using intraventricular/cisternal drug therapy and flow augmentation strategies have also shown possible benefits; however, their use is not yet as well established. Conclusion Blood pressure or cardiac output optimization should be the mainstay of hyperdynamic therapy. Endovascular treatment appears to have a positive impact on neurological outcome compared with the natural history of the disease. The role of intraventricular therapy and flow augmentation strategies in association

  20. Induction of autophagy by cystatin C: a potential mechanism for prevention of cerebral vasospasm after experimental subarachnoid hemorrhage

    PubMed Central

    2013-01-01

    Background Studies have demonstrated that autophagy pathways are activated in the brain after experimental subarachnoid hemorrhage (SAH) and this may play a protective role in early brain injury. However, the contribution of autophagy in the pathogenesis of cerebral vasospasm (CVS) following SAH, and whether up-regulated autophagy may contribute to aggravate or release CVS, remain unknown. Cystatin C (CysC) is a cysteine protease inhibitor that induces autophagy under conditions of neuronal challenge. This study investigated the expression of autophagy proteins in the walls of basilar arteries (BA), and the effects of CysC on CVS and autophagy pathways following experimental SAH in rats. Methods All SAH animals were subjected to injection of 0.3 mL fresh arterial, non-heparinized blood into the cisterna magna. Fifty rats were assigned randomly to five groups: control group (n = 10), SAH group (n = 10), SAH + vehicle group (n = 10), SAH + low dose of CysC group (n = 10), and SAH + high dose of CysC group (n = 10). We measured proteins by western blot analysis, CVS by H&E staining method, morphological changes by electron microscopy, and recorded neuro-behavior scores. Results Microtubule-associated protein light chain-3, an autophagosome biomarker, and beclin-1, a Bcl-2-interacting protein required for autophagy, were significantly increased in the BA wall 48 h after SAH. In the CysC-handled group, the degree of CVS, measured as the inner BA perimeter and BA wall thickness, was significantly ameliorated in comparison with vehicle-treated SAH rats. This effect paralleled the intensity of autophagy in the BA wall induced by CysC. Conclusions These results suggest that the autophagy pathway is activated in the BA wall after SAH and CysC-induced autophagy may play a beneficial role in preventing SAH-induced CVS. PMID:23816364

  1. The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage

    PubMed Central

    Kopczak, Anna; Krewer, Carmen; Schneider, Manfred; Kreitschmann-Andermahr, Ilonka; Schneider, Harald Jörn; Stalla, Günter Karl

    2015-01-01

    Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH) in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1) patients with lowered basal laboratory values; (2) patients with lowered basal laboratory values or the need for hormone replacement therapy; (3) diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients), lowered estradiol (14.3% of female patients) and lowered insulin-like growth factor I (IGF-I) values (12.1%) were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians’ diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery) were predominantly observed for the somatotropic axis (12.5%), the gonadotropic axis in women (11.1%) and the corticotropic axis (10.6%). Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004). In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4) values) to 94.6% (prolactin values). PMID:26703585

  2. Expression and cell distribution of SENP3 in the cerebral cortex after experimental subarachnoid hemorrhage in rats: a pilot study.

    PubMed

    Yang, Yi-qing; Li, Hua; Zhang, Xiangsheng; Wang, Chun-xi; Sun, Qing; Li, Song; Li, Weide; Li, Wei; Ding, Ke; Liu, Ming; Yu, Zhuang; Hang, Chun-hua

    2015-04-01

    Subarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. Small ubiquitin-like modifier (SUMO)-specific proteases 3 (SENP3), a member of the SUMO-specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO-2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its role potential role in SAH. A total of 95 Sprague-Dawley rats were randomly divided into sham group and SAH groups at 6, 12, 24, 48 h, day 3, day 5, and day 7. SAH groups suffered experimental SAH by injection with 0.3 ml nonheparinized autoblood into the prechiasmatic cistern. SENP3 expression is surveyed by western blot analysis, real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence. The levels of cleavage caspase-3 were determined by western blot and immunohistochemistry. SENP3 protein expression was significantly up-regulated after SAH which peaked at 24 h; however, the mRNA expression of SENP3 remained unchanged. Meanwhile, the level of cleaved caspase-3 was also increased after SAH. There is a highly positive correlation between cleavage caspase-3 and SENP3 in protein level. Immunofluorescent results showed that the expression of SENP3 was increased in neurons, rather than astrocytes nor microglia. Our findings indicated a possible role of SENP3 in the pathogenesis of early brain injury mediated by apoptosis following SAH. PMID:25423917

  3. The spectrum of management practices in nontraumatic subarachnoid hemorrhage: A survey of high-volume centers in the United States

    PubMed Central

    Tomycz, Luke; Shekhawat, Nakul; Forbes, Jonathan; Ghiassi, Mayshan; Ghiassi, Mahan; Lockney, Dennis; Velez, Dennis; Mericle, Robert

    2011-01-01

    Background: There is a considerable variety of management practices for nontraumatic subarachnoid hemorrhage (ntSAH) across high-volume centers in the United States. We sought to design a survey which would highlight areas of controversy in the modern management of ntSAH and identify specific areas of interest fo further study. Methods: A questionnaire on management practices in ntSAH was formulated using a popular web-based survey tool (SurveyMonkey™, Palo Alto, CA) and sent to endovascular neurointerventionists and cerebrovascular surgeons who manage a high volume of these patients annually. Two-hundred questionnaires were delivered electronically, and after a period of 2 months, the questionnaire was resent to nonresponders. Results: Seventy-three physicians responded, representing a cross-section of academic and other high-volume centers of excellence from around the country. On average, the responding interventionists in this survey each manage approximately 100 patients with ntSAH annually. Over 57% reported using steroids to treat this patient population. Approximately 18% of the respondents use intrathecal thrombolytics in ntSAH. Over 90% of responding physicians administer nimodipine to all patients with ntSAH. Over 40% selectively administer antiepileptic drugs to patients with ntSAH. Several additional questions were posed regarding the methods of detecting and treating vasospasm, as well as the indications for CSF diversion in patients with ntSAH further demonstrating the great diversity in management. Conclusion: This survey illustrates the astonishing variety of treatment practices for patients with ntSAH and underscores the need for further study. PMID:21748042

  4. Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice.

    PubMed

    Fujimoto, Masashi; Shiba, Masato; Kawakita, Fumihiro; Liu, Lei; Shimojo, Naoshi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-06-01

    OBJECT Tenascin-C (TNC), a matricellular protein, is induced in the brain following subarachnoid hemorrhage (SAH). The authors investigated if TNC causes brain edema and blood-brain barrier (BBB) disruption following experimental SAH. METHODS C57BL/6 wild-type (WT) or TNC knockout (TNKO) mice were subjected to SAH by endovascular puncture. Ninety-seven mice were randomly allocated to WT sham-operated (n = 16), TNKO sham-operated (n = 16), WT SAH (n = 34), and TNKO SAH (n = 31) groups. Mice were examined by means of neuroscore and brain water content 24-48 hours post-SAH; and Evans blue dye extravasation and Western blotting of TNC, matrix metalloproteinase (MMP)-9, and zona occludens (ZO)-1 at 24 hours post-SAH. As a separate study, 16 mice were randomized to WT sham-operated, TNKO sham-operated, WT SAH, and TNKO SAH groups (n = 4 in each group), and activation of mitogen-activated protein kinases (MAPKs) was immunohistochemically evaluated at 24 hours post-SAH. Moreover, 40 TNKO mice randomly received an intracerebroventricular injection of TNC or phosphate-buffered saline, and effects of exogenous TNC on brain edema and BBB disruption following SAH were studied. RESULTS Deficiency of endogenous TNC prevented neurological impairments, brain edema formation, and BBB disruption following SAH; it was also associated with the inhibition of both MMP-9 induction and ZO-1 degradation. Endogenous TNC deficiency also inhibited post-SAH MAPK activation in brain capillary endothelial cells. Exogenous TNC treatment abolished the neuroprotective effects shown in TNKO mice with SAH. CONCLUSIONS Tenascin-C may be an important mediator in the development of brain edema and BBB disruption following SAH, mechanisms for which may involve MAPK-mediated MMP-9 induction and ZO-1 degradation. TNC could be a molecular target against which to develop new therapies for SAH-induced brain injuries. PMID:26473781

  5. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

    PubMed Central

    Zhang, Xiang-Sheng; Li, Wei; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Liu, Jing-Peng; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway. PMID:27529233

  6. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway.

    PubMed

    Zhang, Xiang-Sheng; Li, Wei; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Liu, Jing-Peng; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway. PMID:27529233

  7. Mechanisms of Osteopontin-Induced Stabilization of Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Rats

    PubMed Central

    Suzuki, Hidenori; Hasegawa, Yu; Kanamaru, Kenji; Zhang, John H.

    2010-01-01

    Background and Purpose Osteopontin (OPN) is an inducible multifunctional extracellular matrix protein that may be protective against blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). However, the protective mechanisms remain unclear. Methods We produced the endovascular perforation model of SAH in rats and studied the time course of OPN induction in brains using Western blotting and immunofluorescence (n=50). Then, 34 rats were randomly assigned to sham (n=3), sham+OPN small interfering RNA (siRNA; n=3), SAH+negative control siRNA (n=14) and SAH+OPN siRNA (n=14) groups, and 109 rats to sham+vehicle (n=17), sham+recombinant OPN (r-OPN; n=17), SAH+vehicle (n=33), SAH+r-OPN (n=31) and SAH+r-OPN+GRGDSP (L-arginyl-glycyl-L-aspartate motif-containing hexapeptide; n=11) groups. Effects of OPN siRNA or r-OPN on BBB disruption and the related proteins were studied. Results OPN was significantly induced in the reactive astrocytes and capillary endothelial cells, peaking at 72 hours post-SAH, during the recovery phase of BBB disruption. Blockage of endogenous OPN induction exacerbated BBB disruption associated with reduction of angiopoietin-1 and mitogen-activated protein kinase (MAPK) phosphatase-1 (an endogenous MAPK inhibitor), activation of MAPKs and induction of vascular endothelial growth factor (VEGF)-A at 72 hours post-SAH, while r-OPN treatment improved it associated with MKP-1 induction, MAPK inactivation and VEGF-A reduction, which was blocked by GRGDSP at 24 hours post-SAH. VEGF-B and angiopoietin-2 levels were unchanged. Conclusions OPN may increase MKP-1 that inactivates MAPKs, upstream and downstream of VEGF-A, via binding to L-arginyl-glycyl-L-aspartate-dependent integrin receptors, suggesting a novel mechanism of OPN-induced post-SAH BBB protection. PMID:20616319

  8. Minocycline Improves Functional Outcomes, Memory Deficits, and Histopathology after Endovascular Perforation-Induced Subarachnoid Hemorrhage in Rats

    PubMed Central

    Sherchan, Prativa; Lekic, Tim; Suzuki, Hidenori; Hasegawa, Yu; Rolland, William; Duris, Kamil; Zhan, Yan; Tang, Jiping

    2011-01-01

    Abstract Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation. The aim of this study was to use minocycline, a known neuroprotectant agent, to evaluate the long-term benefits in terms of neurobehavior and neuropathology after experimental SAH in rats, and to determine which neurobehavioral test would be effective for long-term evaluation. SAH was induced by endovascular perforation in adult male Sprague-Dawley rats (n=118). The animals were treated with intraperitoneal injection of minocycline (45 mg/kg or 135 mg/kg) or vehicle 1 h after SAH induction. In the short-term, animals were euthanized at 24 and 72 h for evaluation of neurobehavior, brain water content, and matrix metalloproteinase (MMP) activity. In the long-term, neurobehavior was evaluated at days 21–28 post-SAH, and histopathological analysis was done at day 28. High-dose but not low-dose minocycline reduced brain water content at 24 h, and therefore only the high-dose regimen was used for further evaluation, which reduced MMP-9 activity at 24 h. Further, high-dose minocycline improved spatial memory and attenuated neuronal loss in the hippocampus and cortex. The rotarod, T-maze, and water maze tests, but not the inclined plane test, detected neurobehavioral deficits in SAH rats at days 21–28. This study demonstrates that minocycline attenuates long-term functional and morphological outcomes after endovascular perforation-induced SAH. Long-term neurobehavioral assessments using the rotarod, T-maze, and water maze tests could be useful to evaluate the efficacy of therapeutic intervention after experimental SAH. PMID:22013966

  9. Genetic markers in the EET metabolic pathway are associated with outcomes in patients with aneurysmal subarachnoid hemorrhage

    PubMed Central

    Donnelly, Mark K; Conley, Yvette P; Crago, Elizabeth A; Ren, Dianxu; Sherwood, Paula R; Balzer, Jeffery R; Poloyac, Samuel M

    2015-01-01

    Preclinical studies show that epoxyeicosatrienoic acids (EETs) regulate cerebrovascular tone and protect against cerebral ischemia. We investigated the relationship between polymorphic genes involved in EET biosynthesis/metabolism, cytochrome P450 (CYP) eicosanoid levels, and outcomes in 363 patients with aneurysmal subarachnoid hemorrhage (aSAH). Epoxyeicosatrienoic acids and dihydroxyeicosatetraenoic acid (DHET) cerebrospinal fluid (CSF) levels, as well as acute outcomes defined by delayed cerebral ischemia (DCI) or clinical neurologic deterioration (CND), were assessed over 14 days. Long-term outcomes were defined by Modified Rankin Scale (MRS) at 3 and 12 months. CYP2C8*4 allele carriers had 44% and 36% lower mean EET and DHET CSF levels (P=0.003 and P=0.007) and were 2.2- and 2.5-fold more likely to develop DCI and CND (P=0.039 and P=0.041), respectively. EPHX2 55Arg, CYP2J2*7, CYP2C8*1B, and CYP2C8 g.36785A allele carriers had lower EET and DHET CSF levels. CYP2C8 g.25369T and CYP2C8 g.36755A allele carriers had higher EET levels. Patients with CYP2C8*2C and EPHX2 404del variants had worse long-term outcomes while those with EPHX2 287Gln, CYP2J2*7, and CYP2C9 g.816G variants had favorable outcomes. Epoxyeicosatrienoic acid levels were associated with Fisher grade and unfavorable 3-month outcomes. Dihydroxyeicosatetraenoic acids were not associated with outcomes. No associations passed Bonferroni multiple testing correction. These are the first clinical data demonstrating the association between the EET biosynthesis/metabolic pathway and the pathophysiology of aSAH. PMID:25388680

  10. Identification of specific age groups with a high risk for developing cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

    PubMed

    Malinova, Vesna; Schatlo, Bawarjan; Voit, Martin; Suntheim, Patricia; Rohde, Veit; Mielke, Dorothee

    2016-07-01

    The impact of age on the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a matter of ongoing discussion. The aim of this study was to identify age groups with a higher risk for developing vasospasm, delayed ischemic neurological deficit (DIND), or delayed infarction (DI) and to identify a cut-off age for a better risk stratification. We defined six age groups (<30, 30-39, 40-49, 50-59, 60-69, and >70 years). ROC analysis was performed to determine a cutoff age with the highest positive predictive value (PPV) for developing vasospasm, defined as a blood-flow-velocity-increase >120 cm/s in transcranial-Doppler-sonography (TCD). Multivariate binary-logistic-regression-analysis was then performed to evaluate differences in the incidence of cerebral vasospasm, DIND, and DI among the different age groups. A total of 753 patients were included in the study. The highest incidence (70 %) of TCD-vasospasm was found in patients between 30 and 39 years of age. The cutoff age with the highest PPV (65 %) for developing TCD-vasospasm was 38 years. Multivariate analysis revealed that age <38 years (OR 3.6; CI 95 % 2.1-6.1; p < 0.001) best predicted vasospasm, followed by the need for cerebrospinal fluid drainage (OR 1.5; CI 95 % 1.0-2.3; p = 0.04). However, lower age did not correlate with higher rates of DIND or infarcts. The overall vasospasm-incidence after aSAH is age-dependent and highest in the age group <38 years. Surprisingly, the higher incidence in the younger age group does not translate into a higher rate of DIND/DI. This finding may hint towards age-related biological factors influencing the association between arterial narrowing and cerebral ischemia. PMID:26940102