... snapping feeling in the head. Other symptoms: Decreased consciousness and alertness Eye discomfort in bright light ( photophobia ) ... time, the outlook is much worse. Changes in consciousness and alertness due to a subarachnoid hemorrhage may ...
Hassan, Ali; Ahmad, Bakhtiar; Ahmed, Zahoor; Al-Quliti, Khalid W.
Ruptured cerebral aneurysm is the most common cause of spontaneous subarachnoid hemorrhage (SAH). Rarely cerebral venous sinus thrombosis (CVST) may present initially as acute SAH, and clinically mimics aneurysmal bleed. We report 2 cases of CVST who presented with severe headache associated with neck pain and focal seizures. Non-contrast brain CT showed SAH, involving the sulci of the convexity of hemisphere (cSAH) without involving the basal cisterns. Both patients received treatment with anticoagulants and improved. Awareness of this unusual presentation of CVST is important for early diagnosis and treatment. The purpose of this paper is to emphasize the inclusion of vascular neuroimaging like MRI with venography or CT venography in the diagnostic workup of SAH, especially in a patient with strong clinical suspicion of CVST or in a patient where neuroimaging showed cSAH. PMID:25630784
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.
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
Kim, Tae Jin; Koh, Eun Jung
Very rarely, spinal subarachnoid hemorrhage (SSAH) can occur without any direct spinal injury in patients with traumatic intracranial SAH. A-59-year-old male with traumatic intracranial subarachnoid hemorrhage (SAH) presented with pain and numbness in his buttock and thigh two days after trauma. Pain and numbness rapidly worsened and perianal numbness and voiding difficulty began on the next day. Magnetic resonance imaging showed intraspinal hemorrhage in the lumbosacral region. The cauda equina was displaced and compressed. Emergent laminectomy and drainage of hemorrhage were performed and SSAH was found intraoperatively. The symptoms were relieved immediately after the surgery. Patients with traumatic intracranial hemorrhage who present with delayed pain or neurological deficits should be evaluated for intraspinal hemorrhage promptly, even when the patients had no history of direct spinal injury and had no apparent symptoms related to the spinal injury in the initial period of trauma. PMID:27857928
Kong, Woo Keun; Cho, Keun-Tae; Hong, Seung-Koan
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.
Kong, Woo Keun; Hong, Seung-Koan
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
Rosenberg, G A; Herz, D A; Leeds, N; Strully, K
Two patients with Meckel's Cave meningiomas were initially hospitalized as a result of subarachnoid hemorrhage. Four-vessel angiography was necessary to exclude other causes of bleeding while demonstrating these lesions. Apoplectic presentation in both cases led to early diagnosis and successful surgical therapy. A review of the literature reveals subarachnoid hemorrhage to be a rarity in association with meningiomas. The two patients currently reported are believed to be the only examples on record of hemorrhagic meningiomas arising from the region of Meckel's Cave.
Macdonald, Robert Loch; Leung, Ming; Tice, Tom
Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.
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
Macdonald, R Loch; Cusimano, Michael D; Etminan, Nima; Hanggi, Daniel; Hasan, David; Ilodigwe, Don; Jaja, Blessing; Lantigua, Hector; Le Roux, Peter; Lo, Benjamin; Louffat-Olivares, Ada; Mayer, Stephan; Molyneux, Andrew; Quinn, Audrey; Schweizer, Tom A; Schenk, Thomas; Spears, Julian; Todd, Michael; Torner, James; Vergouwen, Mervyn D I; Wong, George K C
The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over the past 25 years. This improvement may be due to early aneurysm repair by endovascular or open means, use of nimodipine, and better critical care management. Despite this improvement, mortality remains at about 40%, and many survivors have permanent neurologic, cognitive, and neuropsychologic deficits. Randomized clinical trials have tested pharmacologic therapies, but few have been successful. There are numerous explanations for the failure of these trials, including ineffective interventions, inadequate sample size, treatment side effects, and insensitive or inappropriate outcome measures. Outcome often is evaluated on a good-bad dichotomous scale that was developed for traumatic brain injury 40 years ago. To address these issues, we established the Subarachnoid Hemorrhage International Trialists (SAHIT) data repository. The primary aim of the SAHIT data repository is to provide a unique resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase III trials in aneurysmal SAH. With this aim in mind, we convened a multinational investigator meeting to explore merging individual patient data from multiple clinical trials and observational databases of patients with SAH and to create an agreement under which such a group of investigators could submit data and collaborate. We welcome collaboration with other investigators.
Guppy, Kern H; Silverthorn, James W; Akins, Paul T
Intrathecal spinal catheters (lumbar drains) are indicated for several medical and surgical conditions. In neurosurgical procedures, they are used to reduce intracranial and intrathecal pressures by diverting CSF. They have also been placed for therapeutic access to administer drugs, and more recently, vascular surgeons have used them to improve spinal cord perfusion during the treatment of thoracic aortic aneurysms. Insertion of these lumbar drains is not without attendant complications. One complication is the shearing of the distal end of the catheter with a resultant retained fragment. The authors report the case of a 65-year-old man who presented with a subarachnoid hemorrhage due to the migration of a retained lumbar drain that sheared off during its removal. To the best of the authors' knowledge, this is the first case of rostral migration of a retained intrathecal catheter causing subarachnoid hemorrhage. The authors review the literature on retained intrathecal spinal catheters, and their findings support either early removal of easily accessible catheters or close monitoring with serial imaging.
Lovelock, C.E.; Rinkel, G.J.E.; Rothwell, P.M.
Background: Treatment of aneurysmal subarachnoid hemorrhage (SAH) has changed substantially over the last 25 years but there is a lack of reliable population-based data on whether case-fatality or functional outcomes have improved. Methods: We determined changes in the standardized incidence and outcome of SAH in the same population between 1981 and 1986 (Oxford Community Stroke Project) and 2002 and 2008 (Oxford Vascular Study). In a meta-analysis with other population-based studies, we used linear regression to determine time trends in outcome. Results: There were no reductions in incidence of SAH (RR = 0.79, 95% confidence interval [CI] 0.48–1.29, p = 0.34) and in 30-day case-fatality (RR = 0.67, 95% CI 0.39–1.13, p = 0.14) in the Oxford Vascular Study vs Oxford Community Stroke Project, but there was a decrease in overall mortality (RR = 0.47, 0.23–0.97, p = 0.04). Following adjustment for age and baseline SAH severity, patients surviving to hospital had reduced risk of death or dependency (modified Rankin score > 3) at 12 months in the Oxford Vascular Study (RR = 0.51, 0.29–0.88, p = 0.01). Among 32 studies covering 39 study periods from 1980 to 2005, 7 studied time trends within single populations. Unadjusted case-fatality fell by 0.9% per annum (0.3–1.5, p = 0.007) in a meta-analysis of data from all studies, and by 0.9% per annum (0.2–1.6%, p = 0.01) within the 7 population studies. Conclusion: Mortality due to subarachnoid hemorrhage fell by about 50% in our study population over the last 2 decades, due mainly to improved outcomes in cases surviving to reach hospital. This improvement is consistent with a significant decrease in case-fatality over the last 25 years in our pooled analysis of other similar population-based studies. GLOSSARY CI = confidence interval; mRS = modified Rankin score; OCSP = Oxford Community Stroke Project; OXVASC = Oxford Vascular Study; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies
Zheng, Vera Zhiyuan; Wong, George Kwok Chu
Subarachnoid hemorrhage (SAH) is an important cause of stroke mortality and morbidity, especially in the young stroke population. Recent evidences indicate that neuroinflammation plays a critical role in both early brain injury and the delayed brain deterioration after SAH, including cellular and molecular components. Cerebral vasospasm (CV) can lead to death after SAH and independently correlated with poor outcome. Neuroinflammation is evidenced to contribute to the etiology of vasospasm. Besides, systemic inflammatory response syndrome (SIRS) commonly occurs in the SAH patients, with the presence of non-infectious fever and systematic complications. In this review, we summarize the evidences that indicate the prominent role of inflammation in the pathophysiology of SAH. That may provide the potential implications on diagnostic and therapeutic strategies.
Brice, Roanne G.; Brice, Alejandro
This second article of a two-part case study focuses on the experiences of a patient and his spouse (caregiver) when a neurological trauma occurs. It is the personal account when A.B. survived a vertebral artery aneurysm and hemorrhage resulting in a subarachnoid hemorrhage. It is also an in-depth post-trauma account from two speech-language…
Kerro, Ali; Woods, Timothy; Chang, Jason J
"Stunned myocardium," characterized by reversible left ventricular dysfunction, was first described via animal models using transient coronary artery occlusion. However, this phenomenon has also been noted with neurologic pathologies and collectively been labeled "neurogenic stunned myocardium" (NSM). Neurogenic stunned myocardium resulting from subarachnoid hemorrhage (SAH) is a challenging pathology due to its diagnostic uncertainty. Traditional diagnostic criteria for NSM after SAH focus on electrocardiographic and echocardiographic abnormalities and troponemia. However, tremendous heterogeneity still exists. Traditional pathophysiological mechanisms for NSM encompassed hypothalamic and myocardial perivascular lesions. More recently, research on pathophysiology has centered on myocardial microvascular dysfunction and genetic polymorphisms. Catecholamine surging as a mechanism has also gained attention with particular focus placed on the role of adrenergic blockade in both the prehospital and acute settings. Management remains largely supportive with case reports acknowledging the utility of inotropes such as dobutamine and milrinone and intra-aortic balloon pump when NSM is accompanied by cardiogenic shock. Neurogenic stunned myocardium that follows SAH can result in many complications such as arrhythmias, pulmonary edema, and prolonged intubation, which can negatively impact long-term recovery from SAH and increase morbidity and mortality. This necessitates the need to accurately diagnose and treat NSM.
Saracen, A; Kotwica, Z; Woźniak-Kosek, A; Kasprzak, P
Neurogenic pulmonary edema (NPE) is observed in cerebral injuries and has an impact on treatment results, being a predictor of fatal prognosis. In this study we retrospectively reviewed medical records of 250 consecutive patients with aneurysmal subarachnoid hemorrhage (SAH) for the frequency and treatment results of NPE. The following factors were taken under consideration: clinical status, aneurysm location, presence of NPE, intracranial pressure (ICP), and mortality. All patients had plain- and angio-computer tomography performed. NPE developed most frequently in case of the aneurysm located in the anterior communicating artery. The patients with grades I-III of SAH, according to the World Federation of Neurosurgeons staging, were immediately operated on, while those with poor grades IV and V had only an ICP sensor's implantation procedure performed. A hundred and eighty five patients (74.4 %) were admitted with grades I to III and 32 patients (12.8 %) were with grade IV and V each. NPE was not observed in SAH patients with grade I to III, but it developed in nine patients with grade IV and 11 patients with grade V. Of the 20 patients with NPE, 19 died. Of the 44 poor grade patients (grades IV-V) without NPE, 20 died. All poor grade patients had elevated ICP in a range of 24-56 mmHg. The patients with NPE had a greater ICP than those without NPE. Gender and age had no influence on the occurrence of NPE. We conclude that the development of neurogenic pulmonary edema in SAH patients with poor grades is a fatal prognostic as it about doubles the death rate to almost hundred percent.
Albano, Beatrice; Del Sette, Massimo; Roccatagliata, Luca; Gandolfo, Carlo; Primavera, Alberto
Reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of disorders characterized by prolonged, but reversible vasoconstriction of the cerebral arteries, usually associated with acute-onset, severe, recurrent headaches, with or without additional neurological signs and symptoms. Various complications of this condition have been observed, such as cortical subarachnoid hemorrhages (cSAH), intracerebral hemorrhages, reversible posterior leukoencephalopathy, ischaemic strokes and transient ischaemic attacks. It is important to include RCVS in thunderclap headache differential diagnosis and among non-aneurismatic subarachnoid hemorrhage causes. In the past years, thanks to the major diffusion of new diagnostic tools such as magnetic resonance, computed tomography and digital subtraction angiography, RCVS have been demonstrated to be more frequent than previously thought. We report an illustrative case of a woman affected by a small cSAH, associated to RCVS, after elective triplet cesarean delivery. To our knowledge, this is the first case of cSAH associated to RCVS after a triplet pregnancy.
Brice, Alejandro E.; Brice, Roanne G.; Wallace, Sarah E.
Subarachnoid hemorrhages (SAHs) are a serious medical emergency, as 30% to 50% of all SAHs can result in death. Personal accounts and case studies are an important aspect of evidence-based practice. This first article of two presents a review of AB's (patient) condition immediately following an SAH in the intensive care and immediately post…
Wang, Kuo-Chuan; Tang, Sung-Chun; Lee, Jing-Er; Li, Yu-I; Huang, Yi-Shuian; Yang, Wei-Shiung; Jeng, Jiann-Shing; Arumugam, Thiruma V; Tu, Yong-Kwang
We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.
Rama-Maceiras, P; Fàbregas Julià, N; Ingelmo Ingelmo, I; Hernández-Palazón, J
The high rates of morbidity and mortality after subarachnoid hemorrhage due to spontaneous rupture of an intracranial aneurysm are mainly the result of neurologic complications. Sixty years after cerebral vasospasm was first described, this problem remains unsolved in spite of its highly adverse effect on prognosis after aneurysmatic rupture. Treatment is somewhat empirical, given that uncertainties remain in our understanding of the pathophysiology of this vascular complication, which involves structural and biochemical changes in the endothelium and smooth muscle of vessels. Vasospasm that is refractory to treatment leads to cerebral infarction. Prophylaxis, early diagnosis, and adequate treatment of neurologic complications are key elements in the management of vasospasm if neurologic damage, lengthy hospital stays, and increased use of health care resources are to be avoided. New approaches to early treatment of cerebral lesions and cortical ischemia in cases of subarachnoid hemorrhage due to aneurysm rupture should lead to more effective, specific management.
Choi, Jae Young; Cha, Seung Heon; Cho, Won Ho; Ko, Jun Kyeung
The authors describe a case of communicating hydrocephalus accompanied by an arachnoid cyst in an aneurismal subarachnoid hemorrhage. A 69-year-old female was referred to our clinic due to the sudden onset of a headache. A head computed tomography scan demonstrated an arachnoid cyst in the right middle fossa with a mass effect and diffuse subarachnoid hemorrhage. Digital subtraction angiography then revealed a left internal carotid-posterior communicating artery aneurysm. The neck of the aneurysm was clipped successfully and the post-operative period was uneventful. However, two months after discharge, the patient reported that her mental status had declined over previous weeks. A cranial computed tomography scan revealed an interval increase in the size of the ventricle and arachnoid cyst causing a midline shift. Simultaneous navigation guided ventriculoperitoneal shunt and cystoperitoneal shunt placement resulted in remarkable radiological and clinical improvements.
Hamilton, Jason C.; Korn-Naveh, Lauren; Crago, Elizabeth A.
Patients with acute aneurysmal subarachnoid hemorrhage (SAH) often present with more than just neurological compromise. A wide spectrum of complicating cardiopulmonary abnormalities have been documented in patients with acute SAH, presenting additional challenges to the healthcare providers who attempt to treat and stabilize these patients. The patients described in this article presented with both acute aneurysmal SAH and cardiopulmonary compromise. Education and further research on this connection is needed to provide optimal care and outcomes for this vulnerable population. Nurses play a key role in balancing the critical and diverse needs of patients presenting with these symptoms. PMID:18856247
Yasar Tekelioglu, Umit; Demirhan, Abdullah; Akkaya, Akcan; Gurel, Kamil; Ocak, Tarik; Duran, Arif; Kocoglu, Hasan
We report a case of a 33-year-old woman who developed severe brain edema and pseudo-subarachnoid hemorrhage (SAH) at 36-hour follow-up after successful cardiopulmonary resuscitation for anaphylactic shock as a result of a bee sting. The patient died on the sixth day of the follow-up due to multiple organ failure and brain herniation. Our case suggests that the SAH-like findings on computed tomography scanning were not a new complication ("real" SAH) arising from the bee sting; rather, it was a pseudo-SAH related to prolonged cardiopulmonary resuscitation).
Attia, Mohammed Sabri; Loch Macdonald, R
Subarachnoid hemorrhage (SAH) remains one of the most morbid subtypes of stroke around the world and has been the focus of hemorrhagic stroke research for longer than five decades. Animal models have been instrumental in shaping the progress and advancement of SAH research, particularly models that allow for transgenic manipulation. The anterior circulation mouse model provides the research community with a rodent model that depicts very similar clinical findings of SAH; from the location of the hemorrhages to the secondary complications that arise after the hemorrhagic insult. The model allows for the recreation of clinically relevant findings such as large vessel vasospasm, oxidative stress, microcirculatory spasm and microthrombosis, and delayed neuronal injury - all of which appear in human cases of SAH. The model is also not technically demanding, is highly reproducible, and allows for an array of transgenic manipulation, which is essential for mechanistic investigations of the pathogenesis of SAH. The anterior circulation mouse model of SAH is one of a few models that are currently used in mice, and provides the research community with a relatively easy, reliable, and clinically relevant model of SAH - one that could be effectively be used to test for early brain injury (EBI) and delayed neurological injury after SAH.
Kamiya, K; Kuyama, H; Symon, L
A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.
Jeon, Hyojin; Ai, Jinglu; Sabri, Mohamed; Tariq, Asma; Shang, Xueyuan; Chen, Gang; Macdonald, R Loch
About 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment. PMID:19706182
Palade, C.; Ciurea, Alexandru V.; Nica, D. A.; Savu, R.; Moisa, Horatiu Alexandru
Programmed cell death is crucial for the correct development of the organism and the clearance of harmful cells like tumor cells or autoreactive immune cells. Apoptosis is initiated by the activation of cell death receptors and in most cases it is associated with the activation of the cysteine proteases, which lead to apoptotic cell death. Cells shrink, chromatin clumps and forms a large, sharply demarcated, crescent-shaped or round mass; the nucleus condenses, apoptotic bodies are formed and eventually dead cells are engulfed by a neighboring cell or cleared by phagocytosis. The authors have summarized the most important data concerning apoptosis in subarachnoid hemorrhage that have been issued in the medical literature in the last 20 years. PMID:24049554
Luo, Jinqi; Reis, Cesar; Manaenko, Anatol
Hydrocephalus (HCP) is a common complication in patients with subarachnoid hemorrhage. In this review, we summarize the advanced research on HCP and discuss the understanding of the molecular originators of HCP and the development of diagnoses and remedies of HCP after SAH. It has been reported that inflammation, apoptosis, autophagy, and oxidative stress are the important causes of HCP, and well-known molecules including transforming growth factor, matrix metalloproteinases, and iron terminally lead to fibrosis and blockage of HCP. Potential medicines for HCP are still in preclinical status, and surgery is the most prevalent and efficient therapy, despite respective risks of different surgical methods, including lamina terminalis fenestration, ventricle-peritoneal shunting, and lumbar-peritoneal shunting. HCP remains an ailment that cannot be ignored and even with various solutions the medical community is still trying to understand and settle why and how it develops and accordingly improve the prognosis of these patients with HCP. PMID:28373987
Chang, Melody M.; Raval, Ronak N.; Southerland, Jessie J.; Adewumi, Dare A.; Bahjri, Khaled A.; Samuel, Rajeev K.; Woods, Rafeek O.; Ajayi, Olaide O.; Lee, Bryan S.; Hsu, Frank P. K.; Applegate II, Richard L.; Dorotta, Ihab R.
Background: Aneurysmal subarachnoid hemorrhages are frequently complicated by hypertension and neurogenic myocardial stunning. Beta blockers may be used for management of these complications. We sought to investigate sympathetic nervous system modulation by beta blockers and their effect on radiographic vasospasm, delayed cerebral infarction, discharge destination and death. Methods: Retrospective chart review of 218 adults admitted to the ICU between 8/2004 and 9/2010 was performed. Groups were identified relevant to beta blockade: 77 were never beta blocked (No/No), 123 received post-admission beta blockers (No/Yes), and 18 were continued on their home beta blockers (Yes/Yes). Records were analyzed for baseline characteristics and the development of vasospasm, delayed cerebral infarction, discharge destination and death, expressed as adjusted odds ratio. Results: Of the 218 patients 145 patients developed vasospasm, 47 consequently infarcted, and 53 died or required care in a long-term facility. When compared to No/No patients, No/Yes patients had significantly increased vasospasm (OR 2.11 (1.06-4.16)). However, these patients also had significantly fewer deaths or need for long term care (OR 0.17 (0.05-0.64)), with decreased tendency for infarcts (OR 0.70 (0.32-1.55)). When compared to No/No patients, Yes/Yes patients demonstrated a trend toward increased vasospasm (OR 1.61 (0.50-5.29)) that led to infarction (OR 1.51 (0.44-5.13)), but with decreased mortality or need for long term care in a facility (OR 0.13 (0.01-1.30)). Conclusion: Post-admission beta blockade in aneurysmal subarachnoid hemorrhage patients was associated with increased incidence of vasospasm. However, despite the increased occurrence of vasospasm, beta blockers were associated with improved discharge characteristics and fewer deaths. PMID:28217182
Nogueira, Ariel B.; Esteves Veiga, José C.; Teixeira, Manoel J.
BACKGROUND: Stroke, including subarachnoid hemorrhage (SAH), is one of the leading causes of morbidity and mortality worldwide. The mortality rate of poor-grade SAH ranges from 34% to 52%. In an attempt to improve SAH outcomes, clinical research on multimodality monitoring has been performed, as has basic science research on inflammation and neuroregeneration (which can occur due to injury-induced neurogenesis). Nevertheless, the current literature does not focus on the integrated study of these fields. Multimodality monitoring corresponds to physiological data obtained during clinical management by both noninvasive and invasive methods. Regarding inflammation and neuroregeneration, evidence suggests that, in all types of stroke, a proinflammatory phase and an anti-inflammatory phase occur consecutively; these phases affect neurogenesis, which is also influenced by other pathophysiological features of stroke, such as ischemia, seizures, and spreading depression. OBJECTIVE: To assess whether injury-induced neurogenesis is a prognostic factor in poor-grade SAH that can be monitored and modulated. METHODS: We propose a protocol for multimodality monitoring-guided hypothermia in poor-grade SAH in which cellular and molecular markers of inflammation and neuroregeneration can be monitored in parallel with clinical and multimodal data. EXPECTED OUTCOMES: This study may reveal correlations between markers of inflammation and neurogenesis in blood and cerebrospinal fluid, based on clinical and multimodality monitoring parameters. DISCUSSION: This protocol has the potential to lead to new therapies for acute, diffuse, and severe brain diseases. ABBREVIATIONS: BBB, blood-brain barrier CPP, cerebral perfusion pressure EEG, electroencephalography ICP, intracranial pressure IL, interleukin MCA, middle cerebral artery SAH, subarachnoid hemorrhage SD, spreading depression SGZ, subgranular zone SVZ, subventricular zone TCD, transcranial Doppler PMID:25050583
Choi, H. Alex; Edwards, Nancy; Chang, Tiffany; Sladen, Robert N.
Despite significant regional and risk factor-related variations, the overall mortality rate in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) remains high. Compared to ischemic stroke, which is typically irreversible, hemorrhagic stroke tends to carry a higher mortality, but patients who do survive have less disability. Technologies to monitor and treat complications of SAH have advanced considerably in recent years, but good long-term functional outcome still depends on prompt diagnosis, early aggressive management, and avoidance of premature withdrawal of support. Endovascular procedures and open craniotomy to secure a ruptured aneurysm represent some of the numerous critical steps required to achieve the best possible result. In this review, we have attempted to provide a contemporary, evidence-based outline of the perioperative critical care management of patients with SAH. This is a challenging and potentially fatal disease with a wide spectrum of severity and complications and an often protracted course. The dynamic nature of this illness, especially in its most severe forms, requires considerable flexibility in clinician management, especially given the panoply of available treatment modalities. Judicious hemodynamic monitoring and adaptive therapy are essential to respond to the fluctuating nature of cerebral vasospasm and the varying oxygen demands of the injured brain that may readily induce acute or delayed cerebral ischemia. PMID:25237442
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
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.
Tholance, Yannick; Barcelos, Gleicy; Dailler, Frederic; Perret-Liaudet, Armand; Renaud, Bernard
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.
Ingelmo Ingelmo, I; Fàbregas Julià, N; Rama-Maceiras, P; Hernández-Palazón, J; Rubio Romero, R; Carmona Aurioles, J
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.
Bhat, Abdul Rashid; AfzalWani, Mohammed; Kirmani, Altaf R.
Context: Kashmir, a snow bound and mountain locked valley, is populated by about 7 million ethnic and non-migratory Kashmiris who have specific dietary and social habits than rest of the world. The neurological disorders are common in Kashmiri population. Aims: To study the prevalence and outcome of spontaneous intracranial subarachnoid hemorrhage (SAH) in Kashmir compared withother parts of the world. Settings and Design: A retrospective and hospital based study from 1982 to 2010 in the single and only Neurosurgical Centre of the State of Jammu and Kashmir. Materials and Methods: A hospital based study, in which, information concerning all Kashmiri patients was collected from the case sheets, patient files, discharge certificates, death certificates, and telephonic conversations with the help of Medical Records Department and Central Admission Register of Sher–i-Kashmir Institute of Medical Sciences, Kashmir India. Statistical Analysis: Analysis of variance and students T-test were used at occasions. Results: Incidence of SAH in Kashmiris is about 13/100,000 persons per year. SAH comprises 31.02% of total strokes and aneurysmal ruptures are cause of 54.35% SAHs. The female suffers 1.78 times more than the male. Total mortality of 36.60% was recorded against a good recovery of 14.99%. The familial SAHs and multiple aneurysms were also common. Intra-operative finding of larger aneurysmal size than recorded on pre-operative computed tomography (CT) angiogram of same patients was noteworthy. In 493 patients of SAH, the angiography revealed 705 aneurysms. Conclusion: Spontaneous intracranial subarachnoid hemorrhage, due to aneurysmal rupture, is common in Kashmir, with worst outcome. Food habits like “salt-tea twice a day”, group-smoking of wet tobacco like “Jejeer”, winter season, female gender, hypertension, and inhalation of “Kangri” smoke are special risk factorsof SAH, in Kashmiris. The plain CT brain and CT angiography are best diagnostic tools. The
Ghonim, Hesham T.; Shah, Sumedh S.; Thompson, John W.; Ambekar, Sudheer; Peterson, Eric C.; Elhammady, Mohamed Samy
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
Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, John H.
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
van der Bilt, Ivo A C; Vendeville, Jean-Paul; van de Hoef, Tim P; Begieneman, Mark P V; Lagrand, Wim K; Kros, Johan M; Wilde, Arthur A M; Rinkel, Gabriel J E; Niessen, Hans W M
Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls. Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.
Advanced age is a recognized risk factor in patients with SAH. A strong correlation has been found between advanced age and impairment of consciousness at admission, presence of thick subarachnoid clot, intraventricular hemorrhage and acute hydrocephalus. Thus suggesting a more severe disease in elderly. Moreover the incidence of rebleeding increases with advancing age. As to the results of surgery a linear correlation between age and outcome has been found in most of series and it is difficult to identify a critical age. However the rate of patients with a poor outcome is significantly higher when an age cut off 60-65 years is considered. Significant improvements have been obtained in the last 30 years in elderly but mortality rate still remains at high level: in the order of 20% in the patients 60-70 years old. For patients over 70 years only results from single series are available and these suggest favourable results in very selected cases. The introduction of GDC coil in the treatment of cerebral aneurysms has changed the management of most SAH patients and particularly of the older ones. The guidelines of current management of such patients followed at the Niguarda Hospital of Milan are presented. Age is one of the four "factors" taken into consideration for a selection of treatment (surgery or coil).
MAIMAITILI, AISHA; MAIMAITILI, MIJITI; REXIDAN, AIKEREMU; LU, JUNYI; AJIMU, KUERBAN; CHENG, XIAOJIANG; LUO, KUN; SAILIKE, DUISHANBAI; LIU, YUAN; KAHEERMAN, KADEER; TANG, CHANGJIU; ZHANG, TINGRONG
The aim of this study was to investigate the changes in serum pituitary hormone levels and the mechanism of hyponatremia in aneurysmal subarachnoid hemorrhage (SAH). Nuclear medical tests and serum electrolyte monitoring were performed in 49 aneurysmal SAH cases and 10 healthy volunteers. The levels of serum pituitary hormones were significantly higher in the SAH patients compared with the control group on days 1–3 and 7–9 after SAH onset (P<0.05). The peak value occurred on days 7–9. The rate of hyponatremia was 49.0% in the 49 SAH patients. The incidence of severe hyponatremia was significantly higher in Fisher grades III–IV and Hunt-Hess grades III–IV compared with Fisher grades I–II and Hunt-Hess grades I–II, respectively (P<0.05). There was no correlation between the site of aneurysm and the rate of hyponatremia. The incidence of symptomatic cerebral vasospasm was significantly higher in the hyponatremia group and Fisher grades III–IV compared with the normal serum sodium group and Fisher grades I–II, respectively. Serum pituitary hormone levels were positively correlated with blood loss and disease severity in patients with aneurysmal SAH. Hyponatremia may be considered an important indicator of SAH. SAH patients are likely to benefit from intense monitoring and regulation of serum sodium. PMID:23837049
Song, Seung-Yoon; Park, Jong-Tae; Kang, Sung-Don
An intracranial saccular aneurysm is uncommonly diagnosed in a patient with closed head trauma. We herein present a patient with delayed rebleeding of a cerebral aneurysm misdiagnosed as traumatic subarachnoid hemorrhage (SAH). A 26-year-old female visited our emergency department because of headache after a motorcycle accident. Brain computed tomography (CT) showed a right-side dominant SAH in Sylvian fissure. Although traumatic SAH was strongly suggested because of the history of head trauma, we performed a CT angiogram to exclude any vascular abnormalities. The CT angiogram showed no vascular abnormality. She was discharged after conservative treatment. One day after discharge, she returned to the emergency department because of mental deterioration. Brain CT showed diffuse SAH, which was dominant in the right Sylvian fissure. The CT angiogram revealed a right middle cerebral artery bifurcation aneurysm. During operation, a non-traumatic true saccular aneurysm was found. The patient recovered fully after successful clipping of the aneurysm and was discharged without neurologic deficit. Normal findings on a CT angiogram do not always exclude aneurysmal SAH. Follow-up vascular study should be considered in trauma patients who are highly suspicious of aneurysmal rupture. PMID:27847770
Wellman, George C.; Koide, Masayo
Summary Intracerebral or parenchymal arterioles play an important role in the regulation of both global and regional blood flow within the brain. Brain cortex lacks significant collateral sources of blood and are thus at risk if blood flow through parenchymal arterioles is restricted. Increasingly, evidence is accumulating that abnormal parenchymal arteriolar constriction contributes to the development of neurological deficits caused by subarachnoid hemorrhage (SAH). For example, parenchymal arterioles isolated from SAH model rats exhibit enhanced constriction in response to increased intravascular pressure. This increased pressure-dependent constriction or myogenic tone would result in a shift in the cerebral autoregulatory response and decreased cerebral perfusion. Here, we summarize our current knowledge regarding cellular mechanisms contributing to enhanced contractility of parenchymal arteriolar myocytes following SAH. Our studies demonstrate SAH-induced membrane potential depolarization involving altered K+ homeostasis leads to enhanced voltage-dependent Ca2+ channel activity, increased smooth muscle cytosolic Ca2+ and parenchymal arteriolar constriction. In summary, emerging evidence demonstrates that SAH can profoundly affect parenchymal arteriolar tone promoting decreased cortical blood flow and compromised neuronal viability. PMID:22890665
Sehba, Fatima A.; Pluta, Ryszard M.
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
Koide, Masayo; Sukhotinsky, Inna; Ayata, Cenk; Wellman, George C.
Aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences on brain function including profound effects on communication between neurons and the vasculature leading to cerebral ischemia. Physiologically, neurovascular coupling represents a focal increase in cerebral blood flow to meet increased metabolic demand of neurons within active regions of the brain. Neurovascular coupling is an ongoing process involving coordinated activity of the neurovascular unit—neurons, astrocytes, and parenchymal arterioles. Neuronal activity can also influence cerebral blood flow on a larger scale. Spreading depolarizations (SD) are self-propagating waves of neuronal depolarization and are observed during migraine, traumatic brain injury, and stroke. Typically, SD is associated with increased cerebral blood flow. Emerging evidence indicates that SAH causes inversion of neurovascular communication on both the local and global level. In contrast to other events causing SD, SAH-induced SD decreases rather than increases cerebral blood flow. Further, at the level of the neurovascular unit, SAH causes an inversion of neurovascular coupling from vasodilation to vasoconstriction. Global ischemia can also adversely affect the neurovascular response. Here, we summarize current knowledge regarding the impact of SAH and global ischemia on neurovascular communication. A mechanistic understanding of these events should provide novel strategies to treat these neurovascular disorders. PMID:23577279
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
Abstract 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 (χ2 = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ2 = 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 (χ2 = 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
Nyberg, Christoffer; Karlsson, Torbjörn; Hillered, Lars; Stridsberg, Mats; Ronne Engström, Elisabeth
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
Passier, Patricia E C A; Visser-Meily, Johanna M A; Rinkel, Gabriel J E; Lindeman, Eline; Post, Marcel W M
This study was conducted to investigate life satisfaction and employment status after aneurysmal subarachnoid hemorrhage (SAH) and to explain the associations between life satisfaction and demographic, disease-related, psychological, and personality characteristics. Subjects with SAH (n = 141) living at home 2-4 years after the SAH responded to a mailed questionnaire. Outcomes were life satisfaction, as measured with the Life Satisfaction Questionnaire 9 (LiSat-9), and employment status. Determinants in multiple regression analysis were demographic and SAH characteristics, subjective complaints (eg, mood disorder, fatigue, cognitive complaints), and personality characteristics (eg, neuroticism, passive coping style). Of the 141 subjects, 64 (46.7%) had a Glasgow Outcome Scale score of V (good outcome) at discharge. Mean subject age was 51.4 ± 12.3 years, and mean time after SAH was 36.1 ± 7.9 months. Of the 88 subjects who were working at the time of the SAH, 54 (61.4%) returned to work, but only 31 (35.2%) resumed their work completely. The subjects were least satisfied with their vocational situation (51.9% satisfied) and sexual life (51.7%) and were most satisfied with their relationships (75.2%-88.7%) and self-care ability (88.6%). Age (β value = 0.17), return to work after SAH (0.19), disability at hospital discharge (0.25), worsened mood (-0.37), and passive coping (-0.25) together accounted for 47.2% of the life satisfaction scores. Our data indicate that return to work is a major issue for individuals who survive an SAH. Not returning to work, disability, depression, and passive coping are associated with reduced life satisfaction. Thus, vocational reintegration after SAH merits more attention during rehabilitation.
Claassen, Jan; Perotte, Adler; Albers, David; Kleinberg, Samantha; Schmidt, J. Michael; Tu, Bin; Badjatia, Neeraj; Lantigua, Hector; Hirsch, Lawrence J.; Mayer, Stephan A.; Connolly, E. Sander; Hripcsak, George
Objective Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood. Methods We analyzed intracortical EEG and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury. Results Intracortical seizures were seen in 38% of patients and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (P=0.001), blood pressure (P<0.001), and respiratory rate (P<0.001). There were trends for rising cerebral perfusion pressure (P=0.03) and intracranial pressure (P =0.06) seen after seizure onset. Intracortical seizure associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (P=0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs. 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively). Interpretation We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in regional cerebral blood flow. These real-world physiologic observations may permit more successful translation of laboratory research to the bedside. PMID:23813945
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
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
Obata, Yoshiki; Takeda, Junichi; Sato, Yohei; Ishikura, Hiroyasu; Matsui, Toru; Isotani, Eiji
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.
Haining, J.L.; Clower, B.R.; Honma, Y.; Smith, R.R.
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.
Walcott, Brian P; Berkhemer, Olvert A; Leslie-Mazwi, Thabele M; Chandra, Ronil V; Ogilvy, Christopher S; Yoo, Albert J
Vertebrovertebral fistulae are rare vascular malformations that uncommonly can rupture to present clinically as intracranial subarachnoid hemorrhage. We report a 69-year-old man presenting following spontaneous apoplectic collapse. Initial workup revealed diffuse, intracranial subarachnoid hemorrhage, intraventricular hemorrhage and hydrocephalus. However, the etiology was not apparent on CT angiography of the head. Catheter-based angiography was performed, demonstrating a single-hole, high-flow vertebrovertebral fistula, arising from the V2 segment and decompressing into both cervical and skull base venous structures. Definitive treatment consisted of endovascular fistula obliteration with a combination of coil and liquid embolic material. The patient made a full neurological recovery. High cervical and skull base fistulae are rare causes of intracranial hemorrhage; endovascular treatment is effective at disconnection of the arteriovenous shunt.
Kamp, Marcel A.; Dibué, Maxine; Schneider, Toni; Steiger, Hans-Jakob; Hänggi, Daniel
Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. Furthermore, expression patterns and function of ion channels appear to differ between main and small peripheral vessels, which may be key in understanding mechanisms behind subarachnoid hemorrhage-induced vasospasm. Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed. PMID:23251831
Kawatani, Eri; Kishikawa, Yuki; Sankoda, Chikahiro; Kuwahara, Nobuo; Mori, Daisuke; Osoegawa, Kouichi; Matsuishi, Eijo; Gondo, Hisashi
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.
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
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
Dennis, G. C.; Welch, B.; Cole, A. N.; Mendoza, R.; Morgan, J.; Epps, J.; Bernard, E.; St Louis, P.
The clinical outcome of patients following subarachnoid hemorrhage is complicated by delayed cerebral ischemia and contributing factors such as hypertension. To observe the impact of hypertension and delayed cerebral ischemia on the outcome of a predominantly African-American cohort following subarachnoid hemorrhage, both retrospective (n = 42) and prospective (n = 21) studies were conducted. In the total pool (n = 63), the mean age was 49.7 years (range: 17 to 80) with a preponderance of female patients (70%). Aneurysm formation was significant in the region of the posterior communicating artery. Of the patients reviewed, 73.8% had preexisting hypertension and 45.9% developed delayed cerebral ischemia. Approximately 89% of the patients who suffered from delayed cerebral ischemia had hypertension. Results failed to display any significant beneficial association between the use of the calcium channel blocker nimodipine and delayed cerebral ischemia. Use of the antifibrinolytic drug aminocaproic acid demonstrated a worse patient outcome. It is not recommended that aminocaproic acid be used in this population. Subsequently, due to the proportional occurrence of delayed cerebral ischemia in hypertensive patients following subarachnoid hemorrhage, it is suggested that prophylactic surgical management of unruptured intracranial aneurysms be considered in hypertensive patients. Further study is needed to discern the association between hypertension, delayed cerebral ischemia, and stroke in patients following subarachnoid hemorrhage. PMID:9046763
Filipce, Venko; Caparoski, Aleksandar
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.
Forget, Patrice; Goffette, Pierre; van de Wyngaert, Françoise; Raftopoulos, Christian; Hantson, Philippe
A 34-year-old woman with a previous history of severe headache ("thunderclap") was admitted with a diagnosis of aneurysmal subarachnoid hemorrhage (SAH). The patient developed symptomatic vasospasm on day 5 that resolved rapidly after having increased arterial blood pressure. She experienced also short-lasting excruciating headache. On day 12, while velocities had normalised, as revealed by transcranial Doppler (TCD), for more than 48 h, she developed aphasia and right hemiplegia associated with diffuse segmental vasospasm on the left middle cerebral artery. Intra-arterial infusion of vasodilatory agents was required. Recurrence of symptomatic vasospasm was noted on day 25, with a great number of territories involved as shown in the cerebral angiogram. A second intra-arterial treatment was needed. The patient complained of multiple episodes of extremely severe headache ("thunderclap"), with also transient dysarthria and hemiparesia on day 30. She was discharged on day 38 after full recovery. The clinical and TCD/radiological findings were consistent with a reversible cerebral vasoconstriction syndrome overlapping SAH related symptomatic vasospasm.
Caner, Basak; Hou, Jack; Altay, Orhan; Fujii, Mutsumi; Zhang, John H
Subarachnoid hemorrhage is a devastating disease that can be difficult to manage. Not only is the initial bleeding and rebleeding associated with high mortality, but a large fraction of patients also develop a delayed neurological deficit even when the aneurysm was successfully secured with clipping or coiling. Past research effort has traditionally been focused on vasospasm, which was conceived to be the sole factor for delayed neurological deficit. The failure of anti-vasospastic drugs to improve outcome in clinical trials has brought into focus the significance of early brain injury. The immediate events associated with subarachnoid hemorrhage, including increased intracranial pressure, decreased cerebral blood flow and global ischemia initiate a cascade of pathological changes that occur before the onset of delayed vasospasm. These pathological changes in the very early stage of the hemorrhage propagate and cause blood-brain barrier disruption, inflammation, oxidative stress and cell death. Focusing only on the treatment of vasospasm with complete disregard for early brain injury is insufficient for the management of subarachnoid hemorrhage. Instead, a therapeutic intervention has to aim at stopping the molecular cascades of early brain injury that may lead to long-term deficits in addition to vasospasm. We review the pathological mechanisms of early brain injury, which may reveal new therapeutic avenues that can be exploited to serve as combination therapy with anti-vasospasm medications in the future.
Thanabalasundaram, Gopiga; Hernández-Durán, Silvia; Leslie-Mazwi, Thabele; Ogilvy, Christopher S
Cerebral hyperperfusion syndrome is a well-recognized and potentially fatal complication of carotid revascularization. However, the occurrence of non-aneurysmal subarachnoid hemorrhage as a manifestation of cerebral hyperperfusion syndrome post-carotid endarterectomy is uncommon. We report a case of a patient who presented with headache following carotid endarterectomy for a critically occluded common carotid artery. This progressed to deteriorating consciousness and seizures. Investigations revealed a left cortical non-aneurysmal subarachnoid hemorrhage. Non-aneurysmal subarachnoid hemorrhage is a rare post-operative complication of carotid endarterectomy. Immediate management with aggressive blood pressure control is key to prevent permanent neurological deficits. Cerebral hyperperfusion syndrome (CHS) after carotid revascularization procedures is an uncommon and potentially fatal complication. Pathophysiologically it is attributed to impaired autoregulatory mechanisms and results in disruption of cerebral hemodynamics with increased regional cerebral blood flow (Cardiol Rev 20:84-89, 2012; J Vasc Surg 49:1060-1068, 2009). The condition is characterized by throbbing ipsilateral frontotemporal or periorbital headache. Other symptoms include vomiting, confusion, macular edema, focal motor seizures with frequent secondary generalization, focal neurological deficits, and intraparenchymal or subarachnoid hemorrhage (SAH) (Lancet Neurol 4:877-888, 2005). The incidence of CHS varies from 0.2% to 18.9% after carotid endarterectomy (CEA), with a typical reported incidence of less than 3% in larger studies (Cardiol Rev 20:84-89, 2012; Neurosurg 107:1130-1136, 2007). Uncontrolled hypertension, an arterially isolated cerebral hemisphere, and contralateral carotid occlusion are the main risk factors (Lancet Neurol 4:877-888, 2005; J Neurol Neurosurg Psychiatry 83:543-550, 2012). We present a case of non-aneurysmal SAH after CEA, with focus on its presentation, risk factors
Hara, Naoto; Mukuno, Kazuo; Ohtaka, Hironori; Shimizu, Kimiya
Two clinical cases in which ischemic optic neuropathy (ION) occurred after subarachnoid hemorrhage (SAH) are reported. Hemorrhage in the proximity of the optic chiasm was confirmed in 2 cases following rupture of an anterior communicating artery aneurysm. Optic disk atrophy with excavation and permanent visual field defect (altitudinal superior hemianopia) occurred in both cases. ION seems to occur in association with the optic nerve coincidental with the hyperdensity side of SAH on head CT scan. The incidence of ION appears to be attributable to an insufficient blood supply to arteries distributed in the posterior part of the optic nerve as a result of SAH.
Jayasurya, R.; Murugesan, N.; Kumar, R.; Dubey, A. K.; Priyamvada, P. S.; Swaminathan, R. P.; Parameswaran, S.
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
Alcalá-Cerra, Gabriel; Gutiérrez Paternina, Juan J.; Buendía de Ávila, María E.; Preciado Mesa, Edgar I.; Barrios, Rubén Sabogal; Niño-Hernández, Lucía M.; Jaramillo, Keith Suárez
Background: Trends in management of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms among neurosurgeons is very variable and had not been previously described in any Latin American country. This study was conducted to determine the preferences of Colombian neurosurgeons in pharmacologic, surgical, and endovascular management of patients with aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms. Methods: A survey-based descriptive study was performed in a sample of members from the Colombian Association of Neurosurgery. Questions about pharmacologic, surgical, and endovascular management of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysm were carried out. We calculated the mean and the standard deviation of the results obtained from the continuous variables. The results of the categorical variables are presented as percentages. Results: The preference of medication with poor clinical evidence, such as magnesium sulfate, aspirin, statins, and anti-fibrinolytics was lower than 10%. The use of intravenous nimodipine and systemic glucocorticoids was as high as 31%. The availability of endovascular therapy was 69%. The indication for treatment of patients with unruptured intracranial aneurysms that required intervention was less than 13.8%. In patients with ruptured or unruptured intracranial aneurysms, coiling was the preferred method for exclusion. Conclusions: Reported compliance of evidence-based clinical guidelines was similar to that described in developed countries, and even better. However, there is little agreement in treating patients with unruptured intracranial aneurysms. For other issues, the conducts reported by Colombian neurosurgeons are in accordance with the current guidelines. PMID:22059120
Sivakumar, Walavan; Ravindra, Vijay M; Cutler, Aaron; Couldwell, William T
Although most patients with intracranial hypotension typically present with headaches, the rest of the clinical spectrum is characteristically non-specific and often quite variable. In a patient with concurrent pathologies that can produce a similar clinical picture, a high index of suspicion must be maintained to achieve the correct diagnosis. The authors report a patient with intracranial hypotension in the setting of concurrent perineural cyst rupture and subarachnoid hemorrhage. A 63-year-old woman with a family history of ruptured intracranial aneurysms presented after a sudden thunderclap headache and was found to have diffuse subarachnoid hemorrhage. Imaging revealed anterior communicating and superior hypophyseal artery aneurysms. Following the uneventful clipping of both aneurysms, the patient experienced a delayed return to her neurological baseline. After it was noted that the patient had an improved neurological examination when she was placed supine, further investigation confirmed intracranial hypotension from perineural cyst rupture. The patient improved and returned to her neurological baseline after undergoing a high-volume blood patch and remained neurologically intact at postoperative follow-up. Although intracranial hypotension is known to be commonly associated with cerebrospinal fluid leak, its causal and temporal relationship with subarachnoid hemorrhage has yet to be elucidated.
Kertzscher, Ulrich; Schneider, Torsten; Goubergrits, Leonid; Affeld, Klaus; Hänggi, Daniel; Spuler, Andreas
Background Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters. Methodology/Principal Findings A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies) on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force. Conclusions/Significance From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space. PMID:22870243
neuroradiology for a four vessel cerebral angiogram. While CT and MR angiography have a high sensitivity and specificity in intracranial aneurysm ...hemorrhage have multiple intracranial aneurysms (13). Patent aneurysms are seen as a contrast filled outpouching from the vessel wall on angiography...also helpful signs of aneurysm rupture, particularly in those patients with multiple aneurysms . Risk factors for development of intracranial aneurysms
Walcott, Brian P; Patel, Anoop P; Stapleton, Christopher J; Trivedi, Rikin A; Young, Adam M H; Ogilvy, Christopher S
Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00]=16.33, p=0.005), angiogenin (F [1.00,7.00]=7.65, p=0.028), apolipoprotein A-IV (F [1.00,7.00]=6.308, p=0.040), granulocyte colony-stimulating factor (F [1.00,7.00]=9.08, p=0.020), macrophage-stimulating protein (F [1.00,7.00]=24.21, p=0.002), tetranectin (F [1.00,7.00]=5.46, p<0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00]=6.94, p=0.034), and significantly increased for vitronectin (F [1.00,7.00]=5.79, p=0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration.
Rowland, Matthew J.; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W.; Westbrook, Jon; Warnaby, Catherine E.; Pattinson, Kyle T. S.
Objectives: Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed “early brain injury,” with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Design: Unblinded pilot study testing response to drug intervention. Setting: Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Patients: Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41–69 yr]; 11 women). Interventions: IV sodium nitrite (10 μg/kg/min) for 1 hour. Measurements and Main Results: Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p < 0.0001) but an overall decrease in the alpha/delta frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to –31%) (p = 0.006, multivariate analysis accounting for major confounds). Conclusions: Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient’s susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage. PMID:27441898
Rama-Maceiras, P; Fàbregas Julià, N; Ingelmo Ingelmo, I; Hernández-Palazón, J
Systemic complications secondary to subarachnoid hemorrhage from an aneurysm are common (40%) and the mortality attributable to them (23%) is comparable to mortality from the primary lesion, rebleeding, or vasospasm. Although nonneurologic medical complications are avoidable, they worsen the prognosis, lengthen the hospital stay, and generate additional costs. The prevention, early detection, and appropriate treatment of systemic complications will be essential for managing the individual patient's case. Treatment should cover major symptoms (headache, nausea, and dizziness) and ambient noise should be reduced, all with the aim of achieving excellence and improving the patient's perception of quality of care.
Avdagic, Selma Sijercic; Brkic, Harun; Avdagic, Harun; Smajic, Jasmina; Hodzic, Samir
Background: One of the complications aneurysms subarachnoid hemorrhage is the development of vasospasm, which is the leading cause of disability and death from ruptured cerebral aneurysm. Aim: To evaluate the significance of previous comorbidities on early outcome of patients with subarachnoid hemorrhage caused by rupture of a cerebral aneurysm in the prevention of vasospasm. Patients and methods: The study had prospective character in which included 50 patients, whose diagnosed with SAH caused by the rupture of a brain aneurysm in the period from 2011to 2013. Two groups of patients were formed. Group I: patients in addition to the standard initial treatment and “3H therapy” administered nimodipine at a dose of 15-30 mg / kg bw / h (3-10 ml) for the duration of the initial treatment. Group II: patients in addition to the standard initial treatment and “3H therapy” administered with MgSO4 at a dose of 12 grams in 500 ml of 0.9% NaCl / 24 h during the initial treatment. Results: Two-thirds of the patients (68%) from both groups had a good outcome measured with values according to GOS scales, GOS IV and V. The poorer outcome, GOS III had 20% patients, the GOS II was at 2% and GOS I within 10% of patients. If we analyze the impact of comorbidity on the outcome, it shows that there is a significant relationship between the presence of comorbidity and outcomes. The patients without comorbidity (83.30%) had a good outcome (GOS IV and V), the same outcome was observed (59.4%) with comorbidities, which has a statistically significant difference (p = 0.04). Patients without diabetes (32%) had a good outcome (GOS IV and V), while the percentage of patients with diabetes less frequent (2%) with a good outcome, a statistically significant difference (p = 0.009). Conclusion: The outcome of treatment 30 days after the subarachnoid hemorrhage analyzed values WFNS and GOS, is not dependent on the method of prevention and treatment of vasospasm. Most concomitant diseases in
Nakajima, Hanako; Okada, Hiroshi; Hirose, Kazuki; Murakami, Toru; Shiotsu, Yayoi; Kadono, Mayuko; Inoue, Mamoru; Hasegawa, Goji
Hyponatremia is a common finding after subarachnoid hemorrhaging (SAH) and can be caused by either cerebral salt-wasting syndrome (CSWS) or syndrome of inappropriate antidiuretic hormone (SIADH). Distinguishing between these two entities can be difficult because they have similar manifestations, including hyponatremia, serum hypo-osmolality, and high urine osmolality. We herein report the case of a 60-year-old man who suffered from SAH complicated by hyponatremia. During his initial hospitalization, he was diagnosed with CSWS. He was readmitted one week later with hyponatremia and was diagnosed with SIADH. This is the first report of SAH causing CSWS followed by SIADH. These two different sources of hyponatremia require different treatments.
Dredla, Brynn; Freeman, William D
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.
Zhou, James; Agarwal, Nitin; Hamilton, D Kojo; Koltz, Michael T
The study of intracranial aneurysms has grown at an astounding rate since Sir Charles Symond's association of hemorrhage within the subarachnoid space to intracranial aneurysms in 1923. These associations led to the first surgical treatment of an intracranial aneurysm with wrapping by Norman Dott in 1931, and shortly thereafter, clip ligation by Walter Dandy in 1938. Surgical outcomes were improved by the introduction of the operative microscope in the 1960s and perioperative care utilizing induced hypertension, hypovolemia, and hemodilution ("HHH therapy"). Recent monumental advancements, such as coil embolization in 1990 by Guglielmi, have continued to advance the field forward. The authors hope to highlight some of the most seminal and influential works. Herein, we utilize the technique of citation analysis to assemble a list of the 100 most influential works pertaining to aneurysmal subarachnoid hemorrhage published between the years 1900 and 2015 to honor these individuals and to provide guidance to current and future researchers in the field. We additionally calculate the effects of author, journal, topic, and study design on the overall influence of publications in this field.
Ray, Wilson Z; Krisht, Khaled M; Schabel, Alex; Schmidt, Richard H
Background Context Isolated spinal artery aneurysms not associated with vascular malformations are exceedingly rare. Purpose To present a rare case of subarachnoid hemorrhage after thoracic radiculomedullary artery pseudoaneurysm rupture in a patient who abused synthetic cannabinoids and methamphetamines. Study Design Case report. Methods A 41-year-old man with a history of polysubstance abuse presented with acute-onset headache, back pain, and transient bilateral lower-extremity numbness. He reported daily use of the synthetic cannabinoid "Spice." He denied use of other illegal drugs, but laboratory testing was positive for methamphetamines. Magnetic resonance imaging showed a focal hematoma at T2-3, and spinal angiography was negative for vascular abnormalities; however, a follow-up angiogram 6 days later revealed interval development of an irregular dilation of the left T3 radiculomedullary artery originating from the left supreme intercostal artery. Results Surgical trapping and resection of the lesion yielded a good clinical outcome. Conclusions Although two previous case reports have described patients with thoracic radiculomedullary pseudoaneurysm causing spinal subarachnoid hemorrhage (SAH), this is the first reported case associated with synthetic cannabinoids and methamphetamine abuse. Although this diagnosis is exceptionally rare, clinical presentation of SAH with associated back pain and lower-extremity symptoms warrants an aggressive imaging workup. Even in the setting of negative angiography, repeat cerebral and spinal angiograms may be necessary to identify a potentially treatable cause of spinal SAH.
Cetas, J S; Lee, D R; Alkayed, N J; Wang, R; Iliff, J J; Heinricher, M M
Symptomatic ischemia following aneurysmal subarachnoid hemorrhage (SAH) is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits, and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the CNS to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental SAH in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABA(A) receptor agonist and antagonist was used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade SAH. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.
Objective To investigate the characteristics and risk factors of dysphagia with the Videofluoroscopic Dysphagia Scale (VDS) using a videofluoroscopic swallowing study (VFSS) in patients with ruptured aneurysmal subarachnoid hemorrhage (aSAH). Methods Data of 64 patients presenting with first-ever ruptured aSAH were analyzed. Characteristics of dysphagia were evaluated using VFSS and all subjects were divided into a high (>47) and low risk group (≤47) by the VDS score. Clinical and functional parameters were assessed by medical records including demographics, hypertension and diabetes mellitus (DM), the Glasgow Coma Scale (GCS), the Hunt and Hess scale, endotracheal intubation, acute management modalities, as well as Korean version of the Mini-Mental Status Examination (K-MMSE) and Korean version of Modified Barthel Index (K-MBI). Radiologic factors identified the amount of hemorrhage, ventricular rupture, and aneurysmal location. Results About a half of the subjects showed oral phase abnormalities and the oral transit time was delayed in 46.8% of the patients. The pharyngeal transit time was also prolonged in 39.0% of the subjects and the proportion of penetration and aspiration observed was 46.8%. The parameters-GCS score (p=0.048), hemorrhagic volume (p=0.028), presence of intraventricular hemorrhage (p=0.038), and K-MMSE (p=0.007)-were predisposing factors for dysphagia in patients with aSAH. Conclusion Abnormalities in the oral phase were more prominent in patients with aSAH than in those with other types of stroke. The risk factors associated with dysphagia persisting over 6 months after stroke onset were the initial GCS, hemorrhage volume, presence of intraventricular hemorrhage, and cognitive status as measured by the K-MMSE. PMID:28119832
Suzuki, S; Ito, O; Sayama, T; Yamaguchi, S; Goto, K; Sasaki, T
We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.
... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2017 - The Internet Stroke Center. All rights reserved. The information contained ...
... Neurology ª 2013 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. that vascular risk ... e57 ª 2013 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. PATIENT PAGE Section ...
... of Research The Southern NH & Merrimack Valley Awareness Train Chair of Research TeamCindy Alcatraz Chair of Research ... of Research The Southern NH & Merrimack Valley Awareness Train Chair of Research TeamCindy Alcatraz Chair of Research ...
Matsuda, Ryosuke; Hironaka, Yasuo; Takeshima, Yasuhiro; Park, Young-Su; Nakase, Hiroyuki
The authors report the rare case of a 58-year-old man with segmental arterial mediolysis (SAM) with associated intracranial and intraabdominal aneurysms, who suffered subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm. This disease primarily involves the intraabdominal arterial system, resulting in intraabdominal and retroperitoneal hemorrhage in most cases. The patient presented with severe headache and vomiting. The CT scans of the head revealed SAH. Cerebral angiography revealed 3 aneurysms: 1 in the right distal anterior cerebral artery (ACA), 1 in the distal portion of the A(1) segment of the right ACA, and 1 in the left vertebral artery. The patient had a history of multiple intraabdominal aneurysms involving the splenic, gastroepiploic, gastroduodenal, and bilateral renal arteries. He underwent a right frontotemporal craniotomy and fibrin coating of the dissecting aneurysm in the distal portion of the A(1) segment of the right ACA, which was the cause of the hemorrhage. Follow-up revealed no significant changes in the residual intracranial and intraabdominal aneurysms. An SAH due to SAM with associated multiple intraabdominal aneurysms is extremely rare. The authors describe their particular case and review the literature pertaining to SAM with associated intracranial and intraabdominal aneurysms.
Germans, Menno R; Coert, Bert A; Majoie, Charles B L M; van den Berg, René; Verbaan, Dagmar; Vandertop, W Peter
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.
Cohen, José E; Moscovici, Samuel; Rajz, Gustavo; Vargas, Andres; Itshayek, Eyal
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.
Nakaoka, Mitsuo; Ohbayashi, Naohiko; Yahara, Kaita; Nabika, Shinya
Carotid artery stenting (CAS) has a fatal complication of intracranial hemorrhage (ICH) associated with cerebral hyperperfusion syndrome (CHS), i.e. brain hemorrhage and subarachnoid hemorrhage (SAH). Although SAH accounts for a small percentage of these patients, it is difficult to make a differential diagnosis of this syndrome from CHS without ICH because the clinical presentations resemble each other. Furthermore, not only does the cause of SAH following CAS remain unclear but also the role of controlling postoperative blood pressure is not detected in preventing ICH after CAS. Herein, we report a case of SAH following CAS and review previous literature to discuss the mechanism and the management of this fatal complication. A 78-year-old woman with a history of arteriosclerotic obliteration and myocardial infarction was referred to our department for intervention to asymptomatic severe stenosis of the right internal carotid artery. We performed CAS under local anesthesia. Although her blood pressure was controlled to normotension during the procedure, the patient complained of headache following predilation. Postoperative emergent non-contrast computed tomography revealed SAH with leakage of contrast medium occupying the right sylvian fissure. We continued strict blood pressure control, and the patient was discharged without any neurological deficit. A well-opened lumen of the stent was recognized three months later at the outpatient visit. Strict control of intraoperative and postoperative blood pressure may improve the outcome of SAH following CAS though the role in preventing ICH after CAS is unclear. PMID:26184053
Rahmathulla, Gazanfar; Kamian, Kambiz
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
Rahmathulla, Gazanfar; Kamian, Kambiz
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.
Al Yassin, Altaib; Ouyang, Bichun; Temes, Richard
Although survival has dramatically improved following aneurysmal subarachnoid hemorrhage (aSAH), the reasons for persistent high rates of unemployment in this population remain unknown. Retrospective review for medical records of patients with aSAH admitted to Rush University Medical Center was undertaken. Multivariate logistic regression models were used to test the association of either depression or anxiety with the 6-month employment status. Among the 29 patients who developed depression or anxiety, 86.2% were unemployed at 6 months following their aSAH. After controlling for confounding factors, anxiety and depression were significantly associated with higher 6-month unemployment rates (odds ratio [OR]=0.08, 95% confidence interval [CI]=0.02-0.3, p=0.0002). Depression and anxiety are common following aSAH and are associated with increased unemployment rates 6 months post aSAH.
Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.
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.
Fandino, J; Fathi, A R; Graupner, T; Jacob, S; Landolt, H
Cerebral vasospasm is still the most important cause of death and disability after rupture of intracranial aneurysms. The therapeutic strategies in the treatment of subarachnoid hemorrhage induced vasospasm vasospasm include four groups: 1) prevention of vasospasm; 2) reversion of vasospasm; 3) improvement of cerebral perfusion; and 4) neuroprotection and rescue therapies. Recent experimental studies allowed the design of phase II clinical studies which demonstrated positive results with medications and compounds such as statins (simvastatin and pravastatin) and endothelin-1 receptor antagonists (clasozentan). Moreover, experimental and clinical evidences showed the advantages of early cerebrospinal fluid drainage, intrathecal administration of NO-donors, effects of Ca2+ protein kinase inhibitor (Fasudil) and catecholamines on the cerebral vessels. This review article summarizes the stage of investigation of these medications and therapeutic strategies which will be relevant in the treatment of cerebral vasospasm.
Kochar, P.S.; Morrish, W.F.; Hudon, M.E.; Wong, J.H.; Goyal, M.
Summary Aneurysms of the lenticulostriatal perforating arteries are rare and either involve the middle cerebral artery-perforator junction or are located distally in basal ganglia. We describe a rare ruptured fusiform lenticulostriatal perforating artery aneurysm arising from a proximal M2 MCA branch, discerned on superselective microcatheter angiography, presenting solely with subarachnoid hemorrhage (SAH). A 50-year-old previously healthy man presented with diffuse SAH and negative CT angiogram. Cerebral angiogram demonstrated a 2 mm fusiform aneurysm presumably arising from the right lateral lenticulostriate perforator but the exact origin of the perforator was unclear. Superselective angiography was required to precisely delineate the aneurysm and its vessel of origin and directly influenced treatment planning (surgical trapping). Superselective microcatheter angiography provides both an option for endovascular therapy as well as more accurate delineation for surgical planning for these rare aneurysms. PMID:20977857
Yamaki, Vitor Nagai; Júnior, Fernando Mendes Paschoal; Piske, Ronie Leo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson
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
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
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
Zhang, Huan; Xu, Rui; Xie, Fei; Xu, Wei; Zeng, Meng-Fei; Wang, Xin; Zhu, Ji
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
Pappas, Anthony C; Koide, Masayo; Wellman, George C
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
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.
Abel, Taylor J.; Howard, Matthew A.; Menezes, Arnold
Syringomyelia resulting from arachnoiditis secondary to aneurysmal subarachnoid hemorrhage (SAH) is an extremely rare clinical entity with few cases reported in the literature. The presentation, management, and pathogenesis of syringomyelia in this setting is poorly understood. We describe the presentation, radiology, management, and outcomes in two patients with syringomyelia resulting from arachnoiditis secondary to aneurysmal SAH and review the literature on this rare condition. Case number 1 was treated successfully with syrinx-subarachnoid shunt after extensive lysis of adhesions. Case number 2 was treated with syringoperitoneal shunt. Both patients had radiographic decreased syrinx size postoperatively. These patients add to the small literature on syringomyelia occurring secondary to SAH-associated arachnoiditis. The radiographic outcomes demonstrate that in the appropriately selected patient, syrinx-subarachnoid or syringoperitoneal shunting are viable options. PMID:25013348
Grasso, Giovanni; Alafaci, Concetta; Macdonald, R. Loch
Background: Aneurysmal subarachnoid hemorrhage (SAH) accounts for 5% of strokes and carries a poor prognosis. It affects around 6 cases per 100,000 patient years occurring at a relatively young age. Methods: Common risk factors are the same as for stroke, and only in a minority of the cases, genetic factors can be found. The overall mortality ranges from 32% to 67%, with 10–20% of patients with long-term dependence due to brain damage. An explosive headache is the most common reported symptom, although a wide spectrum of clinical disturbances can be the presenting symptoms. Brain computed tomography (CT) allow the diagnosis of SAH. The subsequent CT angiography (CTA) or digital subtraction angiography (DSA) can detect vascular malformations such as aneurysms. Non-aneurysmal SAH is observed in 10% of the cases. In patients surviving the initial aneurysmal bleeding, re-hemorrhage and acute hydrocephalus can affect the prognosis. Results: Although occlusion of an aneurysm by surgical clipping or endovascular procedure effectively prevents rebleeding, cerebral vasospasm and the resulting cerebral ischemia occurring after SAH are still responsible for the considerable morbidity and mortality related to such a pathology. A significant amount of experimental and clinical research has been conducted to find ways in preventing these complications without sound results. Conclusions: Even though no single pharmacological agent or treatment protocol has been identified, the main therapeutic interventions remain ineffective and limited to the manipulation of systemic blood pressure, alteration of blood volume or viscosity, and control of arterial dioxide tension. PMID:28217390
Cerebral blood flow (CBF) was measured in 90 patients who underwent early aneurysmal clipping after subarachnoid hemorrhage (SAH). Measurements were made by a noninvasive, two-dimensional method involving intravenous injection of 133Xe. Patients of Hunt and Hess grades I and II exhibited normal to slightly subnormal CBF, without significant changes, during the study period. Grades III-V patients had almost normal CBF in the early postoperative period, but their CBF gradually decreased, becoming significantly low after day 31. It is noteworthy that in grades IV and V patients, CBF was abnormally high in the acute stage, relative to their poor neurological condition; these patients were considered to have the "global luxury perfusion syndrome." The syndrome was not uncommon in patients with severe SAH. Possible causative or contributory factors are attempts to surgically reduce intracranial pressure, which leads to increased cerebral perfusion pressure, and concomitant global dysautoregulation. In patients with this syndrome, maneuvers intended to increase CBF should be avoided, as they may aggravate brain swelling or cause hemorrhagic events. Positron emission tomographic studies will provide more accurate and useful information concerning the management of SAH patients.
Bittel, Brennen; Husmann, Kathrin
Introduction: We present a case report in a patient with severe, recurrent, thunderclap with computed tomography (CT) evidence of subarachnoid blood and negative work-up for aneurysm. This case is an example of Call-Fleming syndrome with subarachnoid hemorrhage in which transcranial Doppler (TCD) was used for monitoring of cerebral vasoconstriction when angiography did not evidence vasoconstriction. We will review Call-Fleming syndrome and the utility of transcranial doppler imaging to assess cerebral vasoconstriction. Methods: A review of the current literature regarding diagnostics, treatment, and morbidity in Call-Fleming (reversible cerebral vasoconstriction syndrome) as well as a review of the data using transcranial color-coded sonography and transcranial doppler imaging to assess vasospasm in these cases. Results: The patient underwent computed tomography angiography (CTA) and venography (CTV), catheter angiography, lumbar puncture, and vasculitis work-up which were all negative. His magnetic resonance imaging (MRI) showed T2 weighted and fluid attenuation inversion recovery (FLAIR) hyper-intensities in the posterior frontal lobes as well as subarachnoid blood along bilateral occipital convexities. TCDs were obtained which showed elevated mean velocities. Conclusion: The use of bedside transcranial doppler imaging is a non-invasive means of assessing vasospasm in Call-Fleming syndrome; even in cases where angiography is negative. Determining the degree of vasospasm based on the data in subarachnoid hemorrhage, we are able to predict a patient’s risk of complications related to vasospasm including reversible posterior leukoencephalopathy and ischemic events. PMID:22518264
Garge, Shaileshkumar S.; Vyas, Pooja D.; Modi, Pranav D.; Ghatge, Sharad
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
Akutsu, Nobuyuki; Hosoda, Kohkichi; Ohta, Kohei; Tanaka, Hirotomo; Taniguchi, Masaaki; Kohmura, Eiji
We report an unusual case of subarachnoid hemorrhage caused by intraoperative rupture of an intracavernous carotid artery aneurysm coexisting with a prolactinoma. A 58-year-old man presenting with diplopia was found to have a left intracavernous carotid artery aneurysm encased by a suprasellar tumor on magnetic resonance imaging. His serum prolactin level was 5036 ng/mL. Proximal ligation of the left internal carotid artery with a superficial temporal artery to middle cerebral artery anastomosis was scheduled. Because the patient's diplopia had deteriorated, we started him on cabergoline at a dose of 0.25 mg once a week. One month after administration of cabergoline, the diplopia was improved to some extent and serum prolactin was decreased to 290 ng/ml. Six weeks after starting the cabergoline, the patient underwent a left frontotemporal craniotomy to treat the aneurysm. When the dura mater was opened, abnormal brain swelling and obvious subarachnoid hemorrhage were observed. Postoperative computed tomography demonstrated a thick subarachnoid hemorrhage. This case suggests that medical therapy for a pituitary adenoma should be started after treatment for a coexisting intracavernous aneurysm is completed. PMID:25083394
Akutsu, Nobuyuki; Hosoda, Kohkichi; Ohta, Kohei; Tanaka, Hirotomo; Taniguchi, Masaaki; Kohmura, Eiji
We report an unusual case of subarachnoid hemorrhage caused by intraoperative rupture of an intracavernous carotid artery aneurysm coexisting with a prolactinoma. A 58-year-old man presenting with diplopia was found to have a left intracavernous carotid artery aneurysm encased by a suprasellar tumor on magnetic resonance imaging. His serum prolactin level was 5036 ng/mL. Proximal ligation of the left internal carotid artery with a superficial temporal artery to middle cerebral artery anastomosis was scheduled. Because the patient's diplopia had deteriorated, we started him on cabergoline at a dose of 0.25 mg once a week. One month after administration of cabergoline, the diplopia was improved to some extent and serum prolactin was decreased to 290 ng/ml. Six weeks after starting the cabergoline, the patient underwent a left frontotemporal craniotomy to treat the aneurysm. When the dura mater was opened, abnormal brain swelling and obvious subarachnoid hemorrhage were observed. Postoperative computed tomography demonstrated a thick subarachnoid hemorrhage. This case suggests that medical therapy for a pituitary adenoma should be started after treatment for a coexisting intracavernous aneurysm is completed.
Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang
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.
Lessen, Samantha; Keene, Adam
Aneurysmal subarachnoid hemorrhage (SAH) is associated with high mortality. The initial hemorrhage causes death in approximately 25% of patients, with most subsequent mortality being attributable to delayed cerebral ischemia (DCI). Delayed cerebral ischemia generally occurs on post-bleed days 4 through 20, with the incidence peaking at day 8. Because of the risks of DCI, patients with SAH are usually monitored in an intensive care unit (ICU) for 14 to 21 days. Unfortunately, prolonged ICU admissions are expensive and are associated with well-documented risks to patients. We hypothesized that a subset of patients who are at low risk of DCI should be safe to transfer out of the ICU early. All patients admitted to Montefiore Medical Center from 2008 to 2013 with grade I SAH who had their aneurysms successfully protected, had an uncomplicated postoperative course, and had no clinical or ultrasonographic evidence of DCI after day 8 were retrospectively studied. The primary outcome was clinical or ultrasonographic evidence of the development of DCI after day 8. Secondary outcomes included length of ICU and hospital stay and hospital mortality. Forty patients who met the above-mentioned criteria were identified. Of these, only 1 (2.5%) developed ultrasonographic evidence of DCI after day 8 but required no intervention. The mean length of stay in the ICU was until post-bleed day 13, and the mean hospital length of stay was until post-bleed day 14. The in-hospital mortality was 0 of 40. Thus, we identified a low-risk subset of patients with grade I SAH who may be candidates for early transfer out of the ICU. PMID:26740854
Talavera, J O; Wacher, N H; Laredo, F; Halabe, J; Rosales, V; Madrazo, I; Lifshitz, A
Clinical diagnosis of subarachnoid hemorrhage (SAH) is frequently misdiagnosed with intracerebral hemorrhage (ICH) or cerebral infarction (CI), which delays appropriate referral. This study was undertaken to create a clinical index to select, among stroke patients, those with the highest probability of having a SAH. Clinical data of patients with acute stroke were evaluated with the X2 and the Fisher exact test; a p value < 0.05 was considered significant. Significant variables were included in a "log-lineal regression analysis" where those with an odds ratio (OR) 95% confidence limits not including the unit were considered to construct an index using the odds ratio coefficient (C). The results indicated that of 197 records which were included, 22 cases of SAH and 175 of ICH or CI were demonstrated. Kappa coefficients for observer variation in clinical data retrieval was 0.91. After "log-lineal regression analysis" was carried out the following variables were significant: neck stiffness (C = 3, OR = 21); lack of focal neurologic signs (C = 2, OR = 6.88); and age < or = 60 years (C = 1.5, OR = 4.35). A fourth variable, seizures (C = 1, OR = 3.25), was marginally significant (p = 0.07), but added predictive value to the index. The positive predictive values of the sum of the coefficients were: 0 = 0%; 1-2 = 3%; 2.5-3.5 = 21%; 4-5 = 40%; 6.5 = 75%; 7.5 = 100%. In conclusion, when a stroke patient shows neck stiffness, or any combination of young age, lack of focal neurologic signs or seizures (a score > or = 2.5, the index has a 91% sensitivity and 82% specificity), he/she must be referred to a tertiary care center.
Lee, Chu-I; Chou, An-Kuo; Lin, Ching-Chih; Chou, Chia-Hua; Loh, Joon-Khim; Lieu, Ann-Shung; Wang, Chih-Jen; Huang, Chi-Ying F; Howng, Shen-Long; Hong, Yi-Ren
Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and γ-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.
Alexander, Sheila; Poloyac, Samuel; Hoffman, Leslie; Gallek, Matthew; Dianxu Ren; Balzer, Jeffrey; Kassam, Amin; Conley, Yvette
Aneurysmal subarachnoid hemorrhage (SAH) is a hemorrhagic stroke subtype with a poor recovery profile. Cerebral vasospasm (CV), a narrowing of the cerebral vasculature, significantly contributes to the poor recovery profile. Variation in the endothelial nitric oxide (NO) synthase (eNOS) gene has been implicated in CV and outcome after SAH. The purpose of this project was to explore the potential association between three eNOS tagging single nucleotide polymorphisms (SNPs) and recovery from SAH. We included 195 participants with a diagnosis of SAH and DNA and 6-month outcome data available but without preexisting neurologic disease/deficit. Genotyping was performed using an ABI Prism 7000 Sequence Detection System and TaqMan assays. CV was verified by cerebral angiogram independently read by a neurosurgeon on 118 participants. Modified Rankin Scores (MRS) and Glasgow Outcome Scale (GOS) scores were collected 6 months posthemorrhage. Data were analyzed using descriptive statistics, analysis of variance (ANOVA) and chi-square analysis as appropriate. The sample was primarily female (n=147; 75.4%) and White (n=178; 91.3%) with a mean age of 54.6 years. Of the participants with CV data, 56 (47.5%) developed CV within 14 days of SAH. None of the SNPs individually were associated with CV presence; however, a combination of the three variant SNPs was significantly associated with CV (p=.017). Only one SNP (rs1799983, variant allele) was associated with worse 6-month GOS scores (p<.001) and MRS (p<.001). These data indicate that the eNOS gene plays a role in the response to SAH, which may be explained by an influence on CV.
Ni, Wei; Gu, Yuxiang
Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage. PMID:28249040
Rutsch, Sebastian; Niesen, Wolf-Dirk; Meckel, Stephan; Reinhard, Matthias
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.
Starke, Robert M.; Kim, Grace H.; Komotar, Ricardo J.; Hickman, Zachary L.; Black, Eric M.; Rosales, Maritza B.; Kellner, Christopher P.; Hahn, David K.; Otten, Marc L.; Edwards, John; Wang, Tao; Russo, James J.; Mayer, Stephan A.; Connolly, E. Sander
Summary Vasospasm is a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Studies have demonstrated a link between single nucleotide polymorphisms (SNP) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio for symptomatic vasospasm in patients with one T allele was 3.3 (95% CI 1.1–10.0, p=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI 1.3–9.6, p=0.013, TT OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI 1.3–9.5, p=0.016, TT OR 12.0). Patients with the T allele of the eNOS gene are more likely have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome. PMID:18319732
Nakae, Yoshiharu; Kudo, Yosuke; Yamamoto, Ryoo; Johkura, Ken
A pseudo-subarachnoid hemorrhage (pseudo-SAH) is a brain computed tomography (CT) finding that is seen as high-density areas along the basal cisterns, the sylvian vallecula/fissure, the tentorium cerebella, or the cortical sulci, although no SAH is found upon lumbar puncture or at autopsy. There is one report of cryptococcal meningitis presenting as pseudo-SAH, but the explanatory pathology is unknown. A 68-year-old woman with headache, fever, decreased hearing, and decreased vision was admitted to our hospital. Cerebrospinal fluid India ink staining was positive, and culture yielded Cryptococcus neoformans. Cryptococcus meningitis was diagnosed. Head CT and magnetic resonance imaging (MRI) showed no abnormality upon admission, but 1 month later, head CT showed iso- to high-density areas within the sulci, and fluid-attenuated inversion recovery MRI showed high signal intensity within the convexity sulci resembling an SAH. These areas were enhanced by gadolinium on T1-weighted images. Lumber puncture produced no evidence of bleeding. Biopsy of the left frontal lobe sulci was performed, and histopathological study revealed inflammation and granulation with capsules of C. neoformans. The inflammation and granulation at the convexity sulci induced by the C. neoformans infection explained the pseudo-SAH in this case. Physicians should be aware that cryptococcal meningitis-induced inflammation and granulation at the sulci can present as pseudo-SAH on CT and MRI.
Hayek, Muhammad Ali; Roth, Christian; Kaestner, Stefanie; Deinsberger, Wolfgang
Background The indication for and the timing of a permanent shunt operation in patients following acute hydrocephalus (HC) after subarachnoid hemorrhage (SAH) remains controversial because risk factors for chronic HC fail to predict permanent shunt dependency. The amount of cerebrospinal fluid (CSF) drained via an external ventricular drain (EVD) may predict shunt dependency. Methods We conducted a retrospective study of our HC database from January 2006 to December 2011. All patients receiving an EVD due to acute HC after SAH were analyzed. The daily amount of drained CSF was documented until the EVD was removed or converted to a permanent shunt either immediately or during a follow-up period of 6 months. Results A total of 139 patients (48 male, 91 female; mean age: 57 ± 14 years) were eligible for the study. Mean duration of EVD was 16 ± 10 days (range: 4-60 days). A permanent shunt was necessary in 32% of cases (n = 45). The mean daily CSF volume was 139 ± 17 mL (range: 15-460 mL). Using repeated-measures analysis of variance, there was a significant difference of daily drained CSF volumes between both the groups in the first 15 days after the EVD. Conclusion Our results suggest that the daily amount of external CSF drainage volume in the acute state of SAH might influence the development of HC.
Ishizaka, Shunsuke; Hayashi, Kentaro; Otsuka, Munehiro; Fukuda, Shuji; Tsunoda, Keishi; Ushijima, Ryujiro; Kitagawa, Naoki; Suyama, Kazuhiko; Nagata, Izumi
A 66-year-old woman with primary Sjogren syndrome developed syringomyelia following two episodes of subarachnoid hemorrhage (SAH) due to the rupture of basilar artery aneurysms. Gait disturbance and abnormal sensation with pain over the foot and abdomen appeared 3 years after the last SAH. Magnetic resonance (MR) imaging revealed a syringomyelia throughout the thoracic cord, from the T2 to T11 levels. In addition, the thoracic cord was compressed by multiple arachnoid cysts in the ventral side of spinal cord. Computed tomography myelography revealed complete block of cerebrospinal fluid (CSF) flow at the T7 level. Surgery for microlysis of the adhesions and restoration of the CSF flow pathway was performed. Postoperatively, leg motor function slowly improved and she could walk unaided. However, abdominal paresthesia was persisted. Postoperative MR imaging revealed diminished size of the syrinxes. We should recognize syringomyelia and arachnoid cysts due to adhesive arachnoiditis as a late complication of SAH. Microlysis of the adhesions focusing on the lesion thought to be the cause of the symptoms is one of the choices to treat massive syringomyelia and arachnoid cysts associated with arachnoiditis following SAH.
Purpose Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional—an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other’s expression. Methods This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6–72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. Results It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. Conclusions Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction. PMID:28043115
Koyanagi, Masaomi; Fukuda, Hitoshi; Lo, Benjamin; Uezato, Minami; Kurosaki, Yoshitaka; Sadamasa, Nobutake; Handa, Akira; Chin, Masaki; Yamagata, Sen
OBJECTIVE Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI. METHODS The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables. RESULTS After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups. CONCLUSIONS In propensity score-matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.
Boluijt, Jacoline; Meijers, Joost C M; Rinkel, Gabriel J E; Vergouwen, Mervyn D I
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic parameters that can be used for the prediction or diagnosis of DCI, or that inform on the pathogenesis of DCI and may serve as treatment targets. We included 24 studies that fulfilled predefined criteria and described 39 biomarkers. Only one study fulfilled predefined criteria for high quality. Since no parameter on admission was associated with DCI and in none of the included studies blood was drawn at the time of clinical deterioration, none of the studied parameters can presently be used for the prediction or diagnosis of DCI. Regarding the pathogenesis of DCI, it was shown that compared with patients without DCI those with DCI had higher levels of von Willebrand factor and platelet activating factor in plasma 5 to 9 days after aSAH, membrane tissue factor in cerebrospinal fluid 5 to 9 days after aSAH, and D-dimer in plasma 11 to 14 days after aSAH. Confirmation in high-quality studies is needed to investigate whether these parameters can serve as targets for new intervention studies.
Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc
Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.
Genonceaux, Sandrine; Cosnard, Guy; Van De Wyngaert, Françoise; Hantson, Philippe
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.
Ayer, Robert; Chen, Wanqiu; Sugawara, Takashi; Suzuki, Hidenori; Zhang, John H.
Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380g. Octanol (260.46mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 hour after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 hours after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH induced apoptosis. Despites previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study. PMID:20018179
Lee, Wen-Di; Wang, Kuo-Chuan; Tsai, Yi-Fen; Chou, Pin-Chun; Tsai, Li-Kai; Chien, Chung-Liang
Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days 5 and 7 post SAH. Furthermore, treatment of cultured rat fetal NSCs with the CSF collected from rats on days 5 and 7 post SAH enhanced their proliferation, differentiation, and migration. Enzyme-linked immunosorbent assay (ELISA) of the CSF detected a marked increase in the concentration of brain-derived neurotrophic factor (BDNF). Treating the cultured NSCs with recombinant BDNF (at the same concentration as that in the CSF) or with CSF from SAH rats, directly, stimulated proliferation, differentiation, and migration to a similar extent. BDNF expression was upregulated in the SVZ of rats on days 5 and 7 post SAH, and BDNF release occurred from NSCs, astrocytes, and microglia in the SVZ. These results indicate that SAH triggers the expression of BDNF, which promotes the proliferation, differentiation, and migration of NSCs in the SVZ after SAH. PMID:27832087
Schallner, Nils; Pandit, Rambhau; LeBlanc, Robert; Thomas, Ajith J.; Ogilvy, Christopher S.; Zuckerbraun, Brian S.; Gallo, David; Otterbein, Leo E.; Hanafy, Khalid A.
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
Rosenbaum, Benjamin P; Weil, Robert J
Aneurysmal subarachnoid hemorrhage (SAH) is a common condition treated by neurosurgeons. The inherent variability in the incidence and presentation of ruptured cerebral aneurysms has been investigated in association with seasonality, circadian rhythm, lunar cycle, and climate factors. We aimed to identify an association between solar activity (solar flux and sunspots) and the incidence of aneurysmal SAH, all of which appear to behave in periodic fashions over long time periods. The Nationwide Inpatient Sample (NIS) provided longitudinal, retrospective data on patients hospitalized with SAH in the United States, from 1988 to 2010, who underwent aneurysmal clipping or coiling. Solar activity and SAH incidence data were modeled with the cosinor methodology and a 10-year periodic cycle length. The NIS database contained 32,281 matching hospitalizations from 1988 to 2010. The acrophase (time point in the cycle of highest amplitude) for solar flux and for sunspots were coincident. The acrophase for aneurysmal SAH incidence was out of phase with solar activity determined by non-overlapping 95% confidence intervals (CIs). Aneurysmal SAH incidence peaks appear to be delayed behind solar activity peaks by 64 months (95% CI; 56-73 months) when using a modeled 10-year periodic cycle. Solar activity (solar flux and sunspots) appears to be associated with the incidence of aneurysmal SAH. As solar activity reaches a relative maximum, the incidence of aneurysmal SAH reaches a relative minimum. These observations may help identify future trends in aneurysmal SAH on a population basis.
Li, Mingchang; Wang, Wei; Mai, Haojian; Zhang, Xinmu; Wang, Jian; Gao, Yufeng; Wang, Yuefei; Deng, Gang; Gao, Ling; Zhou, Shuanhu; Chen, Qianxue; Wang, Xin
Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology. In addition, western blot analyses show obviously decreased expression of active caspase-3 in methazolamide-treated SAH mice comparing with vehicle-treated SAH animals. Furthermore, methazolamide effectively inhibits ROS production in PCNs induced by blood exposure or hemoglobin insult. However, methazolamide has no protective effects in morality, fluctuation of cerebral blood flow, SAH grade, and cerebral vasospasm of SAH mice. Given methazolamide, a potent carbonic anhydrase inhibitor, can penetrate the blood–brain barrier and has been used in clinic in the treatment of ocular conditions, it provides potential as a novel therapy for SAH. PMID:27731352
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
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
Kao, Lily; Al-Lawati, Zahraa; Vavao, Joli; Steinberg, Gary K; Katznelson, Laurence
Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l(-1)) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l(-1)) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 +/- 1.9 vs. 9.6 +/- 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.
Kojima, Jun; Katayama, Yoichi; Moro, Nobuhiro; Kawai, Hiroyuki; Yoneko, Maki; Mori, Tatsuro
Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. Therefore, it is important to determine the mechanism of CSW. The purpose of this study was to evaluate whether the rat SAH model exhibits CSW and to investigate the relationship between CSW and natriuretic peptides. A SAH model was produced in 24 rats by perforating a cerebral artery with a nylon thread up through the common carotid artery. To evaluate CSW, urine was cumulatively collected from SAH onset to 12 hours and sodium (Na) excretion was analyzed. Body weight and hematocrit were analyzed before and after SAH onset. Concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in plasma were also analyzed. Urine volume and total Na excretion of SAH rats were significantly higher than those of sham rats (p<0.05). Body weight of SAH rats significantly decreased and hematocrit significantly increased (p < 0.05). ANP concentration was significantly decreased in SAH rats (p<0.05). However, BNP concentrations did not change. This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.
Li, Yanjiang; Yang, Heng; Ni, Wei; Gu, Yuxiang
Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.
Nichols, Linda Jayne; Gall, Seana; Stirling, Christine
An aneurysmal subarachnoid hemorrhage (aSAH) carries a high disability burden. The true impact of rurality as a predictor of outcome severity is unknown. Our aim is to clarify the relationship between the proposed explanations of regional and rural health disparities linked to severity of outcome following an aSAH. An initial literature search identified limited data directly linking geographical location, rurality, rural vulnerability, and aSAH. A further search noting parallels with ischemic stroke and acute myocardial infarct literature presented a number of diverse and interrelated predictors. This a priori knowledge informed the development of a conceptual framework that proposes the relationship between rurality and severity of outcome following an aSAH utilizing structural equation modeling. The presented conceptual framework explores a number of system, environmental, and modifiable risk factors. Socioeconomic characteristics, modifiable risk factors, and timely treatment that were identified as predictors of severity of outcome following an aSAH and within each of these defined predictors a number of contributing specific individual predictors are proposed. There are considerable gaps in the current knowledge pertaining to the impact of rurality on the severity of outcome following an aSAH. Absent from the literature is any investigation of the cumulative impact and multiplicity of risk factors associated with rurality. The proposed conceptual framework hypothesizes a number of relationships between both individual level and system level predictors, acknowledging that intervening predictors may mediate the effect of one variable on another.
Zhong, Yu-Wen; Wu, Juan; Hu, Hua-Long; Li, Wei-Xin; Zhong, Yong
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
Azurmendi, Leire; Degos, Vincent; Tiberti, Natalia; Kapandji, Natacha; Sanchez, Paola; Sarrafzadeh, Asita; Puybasset, Louis; Turck, Natacha; Sanchez, Jean-Charles
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high rates of mortality and morbidity. Nosocomial infections, such as pneumonia or urinary tract infections, are among the main causes of worsening outcomes and death. The aim of this study was to discover a biomarker to predict infection in aSAH patients. For this purpose, the plasma of infected and noninfected patients was compared using quantitative mass spectrometry. The most interesting differentially expressed proteins were selected for validation by immunoassays on plasma samples taken from patients (n = 81) over 10 days of hospitalization. Predictive performances were established using Mann-Whitney U tests and receiver operating characteristic curves. Quantitative proteomics identified 17 significantly regulated proteins. Of these, levels of serum amyloid A (SAA) were significantly higher in infected patients (p < 0.007). ELISA confirmed that the concentrations were significantly higher (p < 0.002) already at hospital admission in patients who subsequently developed an infection during their hospitalization, (AUC of 76%) for a cutoff value of 90.9 μg/mL. Our data suggested that measuring SAA could be an efficient means of detecting patients susceptible of developing an infection during hospitalization after an aSAH. Its predictive capacity could lead to earlier antibiotherapy, improved patient management, and potentially better long-term outcomes.
Schallner, Nils; Pandit, Rambhau; LeBlanc, Robert; Thomas, Ajith J; Ogilvy, Christopher S; Zuckerbraun, Brian S; Gallo, David; Otterbein, Leo E; Hanafy, Khalid A
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.
Lilla, Nadine; Füllgraf, Hannah; Stetter, Christian; Köhler, Stefan; Ernestus, Ralf-Ingo; Westermaier, Thomas
Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism. Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA. Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls. Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage. PMID:28261039
Geng, Liming; Ma, Fei; Liu, Yun; Mu, Yanchun; Zou, Zhongmin
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 AND 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.
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
Egashira, Yusuke; Hua, Ya; Keep, Richard F; Iwama, Toru; Xi, Guohua
We reported previously that subarachnoid hemorrhage (SAH) causes acute white matter injury in mice. In this study, we investigated lipocalin 2 (LCN2) mediated blood-brain barrier (BBB) disruption in white matter, which may lead to subsequent injury. SAH was induced by endovascular perforation in wild-type (WT) and LCN2-knockout (LCN2(-/-)) mice. Sham mice underwent the same procedure without perforation. Mice underwent magnetic resonance imaging (MRI) 24 h after SAH to confirm the development of T2-hyperintensity in white matter. Western blotting and immunohistochemistry were performed to elucidate the mechanisms of LCN2-mediated white matter injury and BBB disruption. It was confirmed that LCN2 expression was significantly increased in white matter of WT mice after SAH by Western blotting (versus sham; p < 0.05). Immunohistochemistry showed that LCN2 receptor 24p3R was expressed in oligodendrocytes, astrocytes, endothelial cells, and pericytes in the white matter. In WT mice with SAH, albumin leakage along the white matter was prominently observed and was consistent with T2-hyperintensity on MRI. As with our previous report, LCN2(-/-) mice scarcely developed T2-hyperintensity on MRI or albumin leakage in white matter. Our results suggest that BBB leakage occurs in white matter after SAH and that LCN2 contributes to SAH-induced BBB disruption.
Gangemi, Michelangelo; Cavallo, Luigi Maria; Di Somma, Alberto; Mazzucco, Grazia Marina; Bono, Paolo Sebastiano; Ghetti, Giovanni; Zambon, Giampaolo
Background Chronic shunt-dependent hydrocephalus is a complication of aneurysmal subarachnoid hemorrhage (aSAH). Its incidence and risk factors have been described while the hydrocephalus onset in terms of days after treatment (microsurgical or endovascular) has not been yet analyzed. Materials and Methods 45 patients, treated for aSAH in 4 Italian Neurosurgical Departments, were retrospectively analyzed. It was calculated the time that elapses between treatment and hydrocephalus onset in 36 patients. Results Of the 45 shunted patients, 15 (33.3%) were included in the microsurgical group (group A) and 30 (66.6%) were in the endovascular one (group B). There was no difference of the hydrocephalus onset between the two groups (24,1 days, group A vs. 27,7 days, group B). The presence of intracerebral hematoma (ICH) caused a delay in the hydrocephalus onset after endovascular treatment in terms of 11,5 days compared to microsurgical group as well the absence of vasospasm determined a delay of 13,7 days (not statistically significant). Conclusion No difference in terms of hydrocephalus onset after microsurgical or endovascular treatment has been demonstrated. Only the presence of ICH or the absence of vasospasm can cause a slight delay in the time of hydrocephalus onset in the endovascular series (not statistically significant). Long-term follow-up studies involving higher numbers of subjects are needed to better demonstrate this issue. PMID:24809036
Sun, L H; Xing, L F; Zhang, G H; Pan, S Y
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.
Nichols, Linda Jayne; Gall, Seana; Stirling, Christine
An aneurysmal subarachnoid hemorrhage (aSAH) carries a high disability burden. The true impact of rurality as a predictor of outcome severity is unknown. Our aim is to clarify the relationship between the proposed explanations of regional and rural health disparities linked to severity of outcome following an aSAH. An initial literature search identified limited data directly linking geographical location, rurality, rural vulnerability, and aSAH. A further search noting parallels with ischemic stroke and acute myocardial infarct literature presented a number of diverse and interrelated predictors. This a priori knowledge informed the development of a conceptual framework that proposes the relationship between rurality and severity of outcome following an aSAH utilizing structural equation modeling. The presented conceptual framework explores a number of system, environmental, and modifiable risk factors. Socioeconomic characteristics, modifiable risk factors, and timely treatment that were identified as predictors of severity of outcome following an aSAH and within each of these defined predictors a number of contributing specific individual predictors are proposed. There are considerable gaps in the current knowledge pertaining to the impact of rurality on the severity of outcome following an aSAH. Absent from the literature is any investigation of the cumulative impact and multiplicity of risk factors associated with rurality. The proposed conceptual framework hypothesizes a number of relationships between both individual level and system level predictors, acknowledging that intervening predictors may mediate the effect of one variable on another. PMID:27695237
Yan, Hui; Chen, Yujie; Li, Lingyong; Jiang, Jiaode; Wu, Guangyong; Zuo, Yuchun; Zhang, John H; Feng, Hua; Yan, Xiaoxin; Liu, Fei
Chronic hydrocephalus is one of the severe complications after subarachnoid hemorrhage (SAH). However, there is no efficient treatment for the prevention of chronic hydrocephalus, partially due to poor understanding of underlying pathogenesis, subarachnoid fibrosis. Transforming growth factor-β1(TGF-β1) is a potent fibrogenic factor implicated in wide range of fibrotic diseases. To investigate whether decorin, a natural antagonist for TGF-β1, protects against subarachnoid fibrosis and chronic hydrocephalus after SAH, two-hemorrhage-injection SAH model was conducted in 6-week-old rats. Recombinant human decorin(rhDecorin) (30ug/2ul) was administered before blood injection and on the 10th day after SAH. TGF-β1, p-Smad2/3, connective tissue growth factor (CTGF), collagen I and pro-collagen I c-terminal propeptide were assessed via western blotting, enzyme-linked immunosorbent assay, radioimmunoassay and immunofluorescence. And neurobehavioral tests and Morris water maze were employed to evaluate long-term neurological functions after SAH. We found that SAH induced heightened activation of TGF-β1/Smad/CTGF axis, presenting as a two peak response of TGF-β1 in cerebrospinal fluid, elevation of TGF-β1, p-Smad2/3, CTGF, collagen I in brain parenchyma and pro-collagen I c-terminal propeptide in cerebrospinal fluid, and increased lateral ventricle index. rhDecorin treatment effectively inhibited up-regulation of TGF-β1, p-Smad2/3, CTGF, collagen I and pro-collagen I c-terminal propeptide after SAH. Moreover, rhDecorin treatment significantly reduced lateral ventricular index and incidence of chronic hydrocephalus after SAH. Importantly, rhDecorin improved neurocognitive deficits after SAH. In conclusion, rhDecorin suppresses extracellular matrix accumulation and following subarachnoid fibrosis via inhibiting TGF-β1/Smad/CTGF pathway, preventing development of hydrocephalus and attenuating long-term neurocognitive defects after SAH.
Nakagawa, Manabu; Mutoh, Tatsushi; Takenaka, Shunsuke; Mutoh, Tomoko; Totsune, Tomoko; Taki, Yasuyuki; Ishikawa, Tatsuya
Background Delayed cerebral ischemia (DCI) is one of the main causes of poor outcomes after subarachnoid hemorrhage (SAH). The early identification of DCI by noninvasive imaging modalities would provide valuable information of therapeutic intervention for improving the patient outcomes. We aimed to describe the clinical features of cerebral blood flow (CBF) data obtained from the single-photon emission computed tomography (SPECT) during the risk period for DCI after SAH. Material/Methods Clinical data from 94 SAH patients who underwent surgical clipping of anterior circulation aneurysms were reviewed retrospectively. 99mTc-HMPAO SPECT images were visually and semiquantitatively analyzed on days 7 and 14 after SAH. Results In all cases, the areas of hypoperfusion were found in the middle cerebral artery territories. By contrast, the areas of mild hyperperfusion were always detected on the surgical side, the prevalence which increased from days 7 (n=28; 30%) to 14 (n=48; 51%) without neurological defects. Univariate analysis revealed that the hyperperfusion on day 14 had a significant relationship with functional outcome at 3 months (P=0.04). Multivariate analysis including age, clinical SAH grade, DCI, and hyperperfusion on day 14 showed that DCI (P=0.004; odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02–0.48) and hyperperfusion on day 14 (P=0.002; OR, 2.44; 95% CI, 1.40–4.29) were independently associated with functional outcome at 3 months. Conclusions Delayed mild hyperperfusion around the surgical site can predict good prognosis after SAH, although it may hinder the CBF diagnosis of focal ischemia attributable to DCI. PMID:28093563
Tarnoki, Adam D.; Türker, Acar; Tarnoki, David L.; İyisoy, Mehmet S; Szilagyi, Blanka K.; Duong, Hoang; Miskolczi, Laszlo
Aim To assess impacts of different weather conditions on hospitalizations of patients with ischemic strokes and subarachnoid hemorrhages (SAH) in South Florida. Methods Diagnostic data of patients with spontaneous SAH and strokes were recorded between June 2010 and July 2013. Daily synchronous forecast charts were collected from the National Weather Service and the whole data were matched prospectively. The incidence rate ratio (IRR) was calculated. Results Increased incidence rate of ischemic stroke was consistent with the daily lowest and highest air pressure (IRR 1.03, P = 0.128 and IRR 0.98, P = 0.380, respectively), highest air temperature (IRR 0.99, P = 0.375), and presence of hurricanes or storms (IRR 0.65, P = 0.054). Increased incidence of SAH cases was consistent with daily lowest and highest air pressure (IRR 0.87, P < 0.001 and IRR 1.08, P = 0.019, respectively) and highest air temperature (IRR 0.98, P < 0.001). Presence of hurricanes and/or tropical storms did not influence the frequency of SAH. We found no relationship between the presence of fronts and the admissions for ischemic stroke or SAH. Conclusion Higher number of ischemic stroke and SAH cases can be expected with the daily lowest and highest air pressure, highest air temperature. Presence of hurricanes or tropical storms increased the risk of ischemic stroke but not the SAH. These findings can help to develop preventive health plans for cerebrovascular diseases. PMID:28252876
Al-Mufti, Fawaz; Roh, David; Lahiri, Shouri; Meyers, Emma; Witsch, Jens; Frey, Hans-Peter; Dangayach, Neha; Falo, Cristina; Mayer, Stephan A; Agarwal, Sachin; Park, Soojin; Meyers, Philip M; Sander Connolly, E; Claassen, Jan; Michael Schmidt, J
OBJECTIVE The clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome. METHODS The authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up. RESULTS The cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0-3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4-1.6, p = 0.5). CONCLUSIONS UEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.
Foreman, Paul M; Chua, Michelle; Harrigan, Mark R; Fisher, Winfield S; Vyas, Nilesh A; Lipsky, Robert H; Walters, Beverly C; Tubbs, R Shane; Shoja, Mohammadali M; Griessenauer, Christoph J
OBJECTIVE Delayed cerebral ischemia (DCI) is a recognized complication of aneurysmal subarachnoid hemorrhage (aSAH) that contributes to poor outcome. This study seeks to determine the effect of nosocomial infection on the incidence of DCI and patient outcome. METHODS An exploratory analysis was performed on 156 patients with aSAH enrolled in the Cerebral Aneurysm Renin Angiotensin System study. Clinical and radiographic data were analyzed with univariate analysis to detect risk factors for the development of DCI and poor outcome. Multivariate logistic regression was performed to identify independent predictors of DCI. RESULTS One hundred fifty-three patients with aSAH were included. DCI was identified in 32 patients (20.9%). Nosocomial infection (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.09-11.2, p = 0.04), ventriculitis (OR 25.3, 95% CI 1.39-458.7, p = 0.03), aneurysm re-rupture (OR 7.55, 95% CI 1.02-55.7, p = 0.05), and clinical vasospasm (OR 43.4, 95% CI 13.1-143.4, p < 0.01) were independently associated with the development of DCI. Diagnosis of nosocomial infection preceded the diagnosis of DCI in 15 (71.4%) of 21 patients. Patients diagnosed with nosocomial infection experienced significantly worse outcomes as measured by the modified Rankin Scale score at discharge and 1 year (p < 0.01 and p = 0.03, respectively). CONCLUSIONS Nosocomial infection is independently associated with DCI. This association is hypothesized to be partly causative through the exacerbation of systemic inflammation leading to thrombosis and subsequent ischemia.
De Micheli, E; Pinna, G; Alfieri, A; Caramia, G; Bianchi, L; Colivicchi, M A; Della Corte, L; Bricolo, A
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.
Izumihara, Akifumi; Shimoji, Takashi; Uesugi, Masashi; Fujisawa, Hirosuke; Suzuko, Michiyasu; Ie, Tomoji
The aim of this study was to analyze epidemiological and clinical data of patients with aneurysmal subarachnoid hemorrhage (SAH) in the Yaeyama islands, an isolated subtropical region of Japan. A total of 94 patients (31 men and 63 women, mean age 57.3 years) were diagnosed as having non-traumatic SAH during a 13-year period from 1989 to 2002. The age-and sex-adjusted annual incidence rate of SAH was 17.4 per 100,000 population. The incidence of SAH was the highest in August. Seventy-nine patients were hospitalized within 24 hours after onset of SAH. Seventeen patients were transferred by helicopter. The Hunt and Kosnik grade was I in 29 patients (30.9%). The CT Fisher group was 3 in 42 patients (44.7%). Ruptured aneurysm was detected in 78 patients (saccular type in 70 patients, small size in 49 patients, and internal carotid artery in 28 patients). Rebleeding occurred in 20 patients (21.3%). Symptomatic vasospasm occurred in 26 patients (27.7%). Acute and chronic hydrocephalus occurred in 25 (26.6%) and 22 (23.4%) patients respectively. A total of 120 neurosurgical operations were performed in 70 patients (operation for ruptured aneurysm in 62, early operation in 39). A total of 42 operative complications occurred in 29 patients. Fifty-one patients (54.3%) had a good outcome. The number of full-time neurosurgeons did not influence the performance of neurosurgical operation and outcome. In conclusion, epidemiologically, the high incidence of SAH in August is unusual. Patients with aneurysmal SAH in the Yaeyama islands have common clinical characteristics and undergo standard neurosurgical treatment.
Zhang, Xiang-Sheng; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Jiang, Tian-Wei; Li, Wei; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua
Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH. PMID:27735947
Background Hyponatremia occurring as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome is a common complication in patients with subarachnoid hemorrhage (SAH). The efficacy and safety of urea as treatment for SIADH-induced hyponatremia has not been reported in this population. Methods This is a retrospective analysis of all patients admitted to our department for nontraumatic SAH between January 2003 and December 2008 (n = 368). All patients with SIADH-induced hyponatremia (plasma sodium < 135 mEq/L, urine sodium > 20 mEq/L, and osmolality > 200 mOsm/kg; absence of overt dehydration or hypovolemia; no peripheral edema or renal failure; no history of adrenal or thyroid disease) routinely received urea per os when hyponatremia was associated with clinical deterioration or remained less than 130 mEq/L despite saline solution administration. Results Forty-two patients developed SIADH and were treated with urea. Urea was started after a median of 7 (IQR, 5–10) days and given orally at doses of 15–30 g tid or qid for a median of 5 (IQR, 3–7) days. The median plasma sodium increase over the first day of treatment was 3 (IQR, 1–6) mEq/L. Hyponatremia was corrected in all patients, with median times to Na+ >130 and >135 mEq/L of 1 (IQR, 1–2) and 3 (IQR, 2–4) days, respectively. Urea was well tolerated, and no adverse effects were reported. Conclusions Oral urea is an effective and well-tolerated treatment for SIADH-induced hyponatremia in SAH patients. PMID:22647340
Souza, Moysés Loiola Ponte de
Cognitive deficits caused by subarachnoid hemorrhage (SAH) after rupture of cerebral aneurysms are common, as approximately half of patients have severe, or at least striking, declines in one or more functions of the cognitive domain. The Fisher Scale is associated with the development of vasospasm and thus with the final performance of the patient after SAH. The association of this scale with language disorders in the period preceding the treatment has not been reported yet in the literature. Associate the presence of language deficits with varying degrees of the Fisher Scale in patients with SAH in the period preceding the treatment of aneurysm, as well as compare the various degrees of this scale, identifying the Fisher Scale degrees more associated with the decline of language. The database of 185 preoperative evaluations of language was studied, through the Montreal Toulouse Protocol Alpha version and verbal fluency through CERAD battery, of patients of Hospital da Restauração with aneurysmal SAH. The data relating to the Fisher Scale, the location of the aneurysm, the age and the gender of patients were obtained through review of medical records. Patients were divided according to the Fisher Scale (Fisher I, II, III or IV) and compared with a control group of individuals considered normal. Disorders in language and verbal fluency in patients with SAH in the preoperative period were evidenced. The classification of the patients according to the Fisher Scale allowed to identify differences between the sub-groups and to conclude that patients with bulkier bleeding (Fisher III and IV) have larger declines in the analyzed functions.
Background Cardiac complications are often developed after subarachnoid hemorrhage (SAH) and may cause sudden death of the patient. There are reports in the literature addressing ischemia modified albumin (IMA) as an early and useful marker in the diagnosis of ischemic heart events. The aim of this study is to evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first, second, and seventh days of experimental SAH in rats. Twenty-eight Wistar albino rats were divided into four groups each consisting of seven animals. These were classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by transclival basilar artery puncture. Blood samples were collected under anesthesia from the left ventricles of the heart using the cardiac puncture method for IMA measurement. Histopathological examinations were performed on the heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on an automatic analyser using the enzymatic method. IMA using by ACB test was detected with spectrophotometer. Results Serum IMA (p = 0.044) in seventh day of SAH were higher compared to the control group. Total injury scores of heart and lung tissue, also myocytolysis at day 7 were significantly higher than control group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001) and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA - myocytolysis (r = 0.48, p = 0.008), and between IMA – heart tissue total injury score (r = 0.41, p = 0.029) was found. Conclusion The results revealed that increased serum IMA may be related to myocardial stress after SAH. PMID:24564759
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
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
Fukuda, Hitoshi; Lo, Benjamin; Yamamoto, Yu; Handa, Akira; Yamamoto, Yoshiharu; Kurosaki, Yoshitaka; Yamagata, Sen
OBJECTIVE Plasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes. METHODS A total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. RESULTS D-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer. CONCLUSIONS Elevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.
Bekelis, Kimon; Gottlieb, Daniel J; Su, Yin; Lanzino, Giuseppe; Lawton, Michael T; MacKenzie, Todd A
OBJECTIVE The impact of treatment method-surgical clipping or endovascular coiling-on the cost of care for patients with aneurysmal subarachnoid hemorrhage (SAH) is debated. Here, the authors investigated the association between treatment method and long-term Medicare expenditures in elderly patients with aneurysmal SAH. METHODS The authors performed a cohort study of 100% of the Medicare fee-for-service claims data for elderly patients who had undergone treatment for ruptured cerebral aneurysms in the period from 2007 to 2012. To control for measured confounding, the authors used propensity score-adjusted multivariable regression analysis with mixed effects to account for clustering at the hospital referral region (HRR) level. An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method. RESULTS During the study period, 3210 patients underwent treatment for ruptured cerebral aneurysms and met the inclusion criteria. Of these patients, 1206 (37.6%) had surgical clipping and 2004 (62.4%) had endovascular coiling. The median total Medicare expenditures in the 1st year after admission for SAH were $113,000 (IQR $77,500-$182,000) for surgical clipping and $103,000 (IQR $72,900-$159,000) for endovascular coiling. When the authors adjusted for unmeasured confounders by using an instrumental variable analysis, clipping was associated with increased 1-year Medicare expenditures by $19,577 (95% CI $4492-$34,663). CONCLUSIONS In a cohort of Medicare patients with aneurysmal SAH, after controlling for unmeasured confounding, surgical clipping was associated with increased 1-year expenditures in comparison with endovascular coiling.
Zhang, Li; Li, Zhen; Feng, Dongxia; Shen, Haitao; Tian, Xiaodi; Li, Haiying; Wang, Zhong; Chen, Gang
Oxidative stress is responsible for a poor prognosis of subarachnoid hemorrhage (SAH) patients. Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in central nervous system (CNS). Here, we investigated the role of Nox4 and whether there was a synergistic effect of Nox2 and Nox4 in SAH-induced EBI. Clinical brain biopsies of four patients with traumatic brain injury (TBI) and perihematomal brain tissue from six subjects with SAH were examined. Gp91ds-tat (a specific inhibitor of Nox2), GKT137831 (a specific inhibitor of Nox4), and apocynin (a non-specific Nox inhibitor) were used to test the role of Nox2 and Nox4. The protein levels of Nox2 and Nox4 were elevated in rat neurons and astrocytes at 12 h after SAH, and in cultured brain microvascular endothelial cells at 24 h after exposure to OxyHb. Similarly, there were higher Nox2 and Nox4 protein levels in perihematomal neurons and astrocytes in SAH patients than that in brain tissue from subjects with TBI. In SAH rat model, gp91ds-tat and GKT137831 could reduce SAH-induced neuronal death and degeneration, whereas apocynin did not induce a more intense neuroprotection. Consistently, in in vitro SAH model, siRNA-mediated silencing of Nox2 and Nox4 suppressed the OxyHb-induced neuronal apoptosis, whereas Nox2 and Nox4 co-knockdown also did not show a remarkable overlay effect. In conclusion, Nox4 should contribute to the pathological processes in SAH-induced EBI, and there was not an overlay effect of Nox2 inhibition and Nox4 inhibition on preventing SAH-induced EBI.
Sakamaki, Tsuyako; Hara, Motohiko; Kayaba, Kazunori; Kotani, Kazuhiko; Ishikawa, Shizukiyo
Background Previous studies on the association between coffee consumption and subarachnoid hemorrhage (SAH) have provided inconsistent results. We examine the risk of SAH from coffee consumption in a Japanese population. Methods Our analyses were based on the Jichi Medical School Cohort Study, a large-scale population-based prospective cohort study. A total of 9941 participants (3868 men and 6073 women; mean age 55 years) with no history of cardiovascular disease or carcinoma were examined. Participants were asked to choose one of five options to indicate their daily coffee consumption: none, less than 1 cup a day, 1–2 cups a day, 3–4 cups a day, or 5 or more cups a day. The incidence of SAH was assessed independently by a diagnostic committee. Cox proportional hazards models were used to calculate hazard ratios (HRs) and their 95% confidence intervals (CI) after adjustment for age and sex (HR1) and for additional potential confounders (HR2). Results During 10.7 years of follow-up, SAH occurred in 47 participants. When compared with the participants who consumed less than 1 cup of coffee a day, the HR of SAH was significantly higher in the group who consumed 5 or more cups a day in both models (HR1 4.49; 95% CI, 1.44–14.00; HR2 3.79; 95% CI, 1.19–12.05). Conclusions The present community-based cohort study showed that heavy coffee consumption was associated with an increased incidence of SAH after adjusting for age, sex, and multiple potential cardiovascular confounders. PMID:26460383
De Marchis, Gian Marco; Pugin, Deborah; Meyers, Emma; Velasquez, Angela; Suwatcharangkoon, Sureerat; Park, Soojin; Falo, M. Cristina; Agarwal, Sachin; Mayer, Stephan; Schmidt, J. Michael; Connolly, E. Sander
Objective: To assess the relationship between seizure burden on continuous EEG (cEEG) and functional as well as cognitive outcome 3 months after subarachnoid hemorrhage (SAH). Methods: The study included all consecutive patients with a spontaneous SAH admitted to the Columbia University Medical Center Neurological Intensive Care Unit and monitored with cEEG between 1996 and 2013. Seizure burden was defined as the duration, in hours, of seizures on cEEG. Cognitive outcomes were measured with the Telephone Interview for Cognitive Status (TICS, ranging from 0 to 51, indicating poor to good global mental status). Results: Overall, 402 patients with SAH were included with a median age of 58 years (interquartile range [IQR] 46–68 years). The median duration of cEEG monitoring was 96 hours (IQR 48–155 hours). Seizures were recorded in 50 patients (12%), in whom the median seizure burden was 6 hours (IQR 1–13 hours). At 3 months, in multivariate analysis, seizure burden was associated with unfavorable functional and cognitive outcome. Every hour of seizure on cEEG was associated with an odds ratio of 1.10 (95% confidence interval [CI] 1.01–1.21, p = 0.04) to 3-month disability and mortality, and the TICS-score decreased, on average, by 0.16 points (adjusted coefficient −0.19, 95% CI −0.33 to −0.05, p = 0.01). Conclusion: In this study, after adjusting for established predictors, seizure burden was associated with functional outcome and cognitive impairment 3 months after SAH. PMID:26701381
Yan, Huiying; Hao, Shuangying; Sun, Xiaoyan; Zhang, Dingding; Gao, Xin; Yu, Zhuang; Li, Kuanyu; Hang, Chun-Hua
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.
Kim, Sang Yong; Kim, Seong Min; Park, Moon Sun; Kim, Han Kyu; Park, Ki Seok
Objective The purpose of the study is to determine the effectiveness and safety of nicardipine infusion for controlling blood pressure in patients with subarachnoid hemorrhage (SAH). Methods We prospectively evaluated 52 patients with SAH and treated with nicardipine infusion for blood pressure control in a 29 months period. The mean blood pressure of pre-injection, bolus injection and continuous injection period were compared. This study evaluated the effectiveness of nicardipine for each Fisher grade, for different dose of continuous nicardipine infusion, and for the subgroups of systolic blood pressure. Results The blood pressure measurement showed that the mean systolic blood pressure / diastolic blood pressure (SBP/DBP) in continuous injection period (120.9/63.0 mmHg) was significantly lower than pre-injection period (145.6/80.3 mmHg) and bolus injection period (134.2/71.3 mmHg), and these were statistically significant (p < 0.001). In each subgroups of Fisher grade and different dose, SBP/DBP also decreased after the use of nicardipine. These were statistically significant (p < 0.05), but there was no significant difference in effectiveness between subgroups (p > 0.05). Furthermore, controlling blood pressure was more effective when injecting higher dose of nicardipine in higher SBP group rather than injecting lower dose in lower SBP group, and it also was statistically significant (p < 0.05). During the infusion, hypotension and cardiogenic problems were transiently combined in five cases. However, patients recovered without any complications. Conclusion Nicardipine is an effective and safe agent for controlling acutely elevated blood pressure after SAH. A more systemic study with larger patients population will provide significant results and will bring solid evidence on effectiveness of nicardipine in SAH. PMID:23210033
Kumar, Monisha; Cao, Wenjing; McDaniel, Jenny K.; Pham, Huy P.; Raju, Dheeraj; Nawalinski, Kelsey; Frangos, Suzanne; Kung, David; Zager, Eric E.; Kasner, Scott E.; Levine, Joshua M.; Zheng, X. Long
Summary Background Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Objective To determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Methods 40 consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Results Mean age of SAH patients was 52.4 years (26–84 years) and 30 (75%) were women. 12/40 (30%) had a high Hunt and Hess grade (IV–V) and 25 (62.5%) were treated with coil embolization. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. Conclusions The relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome. PMID:28102428
Shimada, Kenji; Furukawa, Hajime; Wada, Kosuke; Wei, Yuan; Tada, Yoshiteru; Kuwabara, Atsushi; Shikata, Fumiaki; Kanematsu, Yasuhisa; Lawton, Michael T; Kitazato, Keiko T; Nagahiro, Shinji; Hashimoto, Tomoki
Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-α and interleukin-1β in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner. PMID:25757758
Schmidt, J. Michael; Sow, Daby; Crimmins, Michael; Albers, David; Agarwal, Sachin; Claassen, Jan; Connolly, E. Sander; Elkind, Mitchell S. V.; Hripcsak, George; Mayer, Stephan A.
Introduction We sought to determine if monitoring heart rate variability (HRV) would enable preclinical detection of secondary complications after subarachnoid hemorrhage (SAH). Methods We studied 236 SAH patients admitted within the first 48 hours of bleed onset, discharged after SAH day 5, and had continuous electrocardiogram records available. The diagnosis and date of onset of infections and DCI events were prospectively adjudicated and documented by the clinical team. Continuous ECG was collected at 240 Hz using a high-resolution data acquisition system. The Tompkins Hamilton algorithm was used to identify R-R intervals excluding ectopic and abnormal beats. Time, frequency, and regularity domain calculations of HRV were generated over the first 48 hours of ICU admission and 24 hours prior to the onset of each patient's first complication, or SAH day 6 for control patients. Clinical prediction rules to identify infection and DCI events were developed using bootstrap aggregation and cost sensitive meta-classifiers. Results The combined infection and DCI model predicted events 24 hours prior to clinical onset with high sensitivity (87%) and moderate specificity (66%), and was more sensitive than models that predicted either infection or DCI. Models including clinical and HRV variables together substantially improved diagnostic accuracy (AUC 0.83) compared to models with only HRV variables (AUC 0.61). Conclusions Changes in HRV after SAH reflect both delayed ischemic and infectious complications. Incorporation of concurrent disease severity measures substantially improves prediction compared to using HRV alone. Further research is needed to refine and prospectively evaluate real-time bedside HRV monitoring after SAH. PMID:24610353
Culyer, Virginia; McDonough, Erin; Lindsell, Christopher J; Alwell, Kathleen; Moomaw, Charles J; Kissela, Brett M; Flaherty, Matthew L; Khatri, Pooja; Woo, Daniel; Ferioli, Simona; Broderick, Joseph P; Kleindorfer, Dawn; Adeoye, Opeolu
Elevated blood pressure is common in patients with acute subarachnoid hemorrhage (SAH). American Heart Association guidelines do not specify a blood pressure target, but limited data suggest that systolic blood pressure (SBP)≥160 mmHg is associated with increased risk of rebleeding and neurologic decline. In a population-based study, we determined the frequency of antihypertensive therapy in emergency department (ED) patients with SAH and the proportion of those patients with SBP≥160 mmHg who received this therapy. In 2005, nontraumatic SAH cases were retrospectively ascertained at 16 hospitals in our region by screening for International Classification of Diseases Ninth Revision diagnostic codes 430-436. Blood pressure was recorded at ED presentation and also before and after any treatment with antihypertensives. Hypotension was defined as SBP<100 mmHg. The Mann-Whitney U test and χ2 test were used for comparisons. Our cohort comprised 82 patients with SAH presenting to an ED; 4 patients were excluded. The median age of the included patients was 54 years, 74.4% were female, 29.5% were black, and 31 (39.7%) had SBP≥160 mmHg. Antihypertensive therapy was given to 22 of 31 patients (70.9%) with SBP≥160 mmHg and to 4 of 47 patients (8.5%) with SBP<160 mmHg. No patients became hypotensive after receiving treatment. Age, sex, Glascow Coma Scale score, and National Institutes of Health Stroke Scale score were similar between treated and untreated patients. In the absence of definitive evidence, current blood pressure management in local EDs appears reasonable. Further studies of blood pressure management in acute SAH are warranted.
Plata-Bello, Julio; Modroño, Cristián; Acosta-López, Silvia; Pérez-Martín, Yaiza; Marcano, Francisco; García-Marín, Víctor; González-Mora, José Luis
Nearly 20 % of patients who suffer a subarachnoid hemorrhage (SAH) still display cognitive impairment even a year after follow-up. Visuospatial and visuoperceptive domains may be impaired in this cognitive impairment and may not have been fully studied in these patients. Furthermore, these cognitively impaired domains have been associated with activity in the so-called mirror neuron system (MNS). The aim of the study is to analyze the pattern of brain activity with an MNS task-based functional magnetic resonance imaging (fMRI) study in SAH patients. A complete neuropsychological assessment and fMRI study (with observation and execution conditions) were performed in patients with a history of SAH registered in the database of the Hospital Universitario de Canarias and a healthy control group. The patients had to meet all the following inclusion criteria for the study (less than 50 years old; SAH with a Fisher score 1-3; no vasospasm or ischemia; minimum follow-up of one year). Twelve SAH patients were studied. Three of which displayed visuospatial/visuoperceptive impairment. fMRI study showed the presence of higher activity in MNS regions in these patients than in patients with normal visuospatial/visuoperceptive functions. Furthermore, there was a negative correlation between the test scores and brain activity in premotor regions of the studied patients. SAH patients with visuospatial/visuoperceptive impairment have greater activity in the MNS regions. This finding may be associated with a subcortical dysfunction, leading to a disruption of neural activity and less efficient behavior of this brain network.
Placek, Michal M; Wachel, Pawel; Czosnyka, Marek; Soehle, Martin; Smielewski, Peter; Kasprowicz, Magdalena
We investigated changes of time-frequency (TF) complexity, in terms of Rényi entropy and a measure of concentration, of middle cerebral blood flow velocity (CBFV) and arterial blood pressure in relation to the development of cerebral vasospasm in 15 patients after aneurysmal subarachnoid hemorrhage. Interhemispheric differences in the period of no vasospasm and vasospasm were also compared. Results show reduced complexity of TF representations of CBFV on the side of aneurysm before vasospasm was identified. This potentially can serve as an early-warning indicator of future derangement of cerebral circulation.
Shimizu, S; Endo, M; Kan, S; Kitahara, T; Ohwada, T; Fujii, K
Four patients with supratentorial mass lesions (two chronic subdural hematomas, one acute epidural hematoma, and one acute subdural hematoma) showed hyperdense sylvian cisterns on computed tomography (CT). Association of subarachnoid hemorrhage was suspected initially, but was excluded by intraoperative observation or postoperative lumbar puncture. CT showed disappearance of the hyperdense areas just after evacuation of the mass lesions. The hyperdense areas are probably a result of the partial volume phenomenon or concentrations of calcium deposits rather than abnormally high hematocrit levels, which were not found in these patients.
Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T
Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.
Hayashi, Shigeto; Takeda, Naoya; Komura, Eiji
A 30-year-old woman suffered cerebellar hemorrhage during the delivery of her first child. She had undergone surgical removal of a symptomatic cerebellar hemangioblastoma 6 years previously. Neuroradiological examinations indicated recurrent hemangioblastoma, confirmed by histological examination of the surgical specimen. She was discharged with no neurological deficit. Hemangioblastomas are benign tumors that are curable with surgical removal, but can grow during pregnancy. Women of reproductive age who have been treated for hemangioblastoma need careful long-term follow up, even if they show no signs of lesion recurrence.
Shuaib, Umar Ashfaq; Kate, Mahesh; Homik, Joanne; Jerrakathil, Thomas
Aneurysmal subarachnoid haemorrhage (SAH) is rarely associated with Takayasu's arteritis (TA). The present report describes a 21-year-old woman with recurrent SAH and TA. In addition, she also had recurrent spells of postural weakness in the bilateral lower limb occurring at the same time. Sequential CT of the head and MRI showed bilateral cortical SAH. Vascular imaging with MR angiogram and CT angiogram showed bilateral subclavian arteries and left common carotid artery occlusion with multiple hypertrophied collaterals vessels in the neck. There was no evidence of aneurysms in the intracranial vasculature in the conventional angiogram. The CT angiogram of the aorta showed severe stenosis of the abdominal aorta above the renal arteries. The patient was treated with immunomodulatory therapy and had a favourable outcome without further recurrence at end of 1 year of follow-up. A review of the literature showed 21cases with aneurysmal SAH and three cases non-aneurysmal SAH in patients with TA have been reported. Various factors are responsible for the reorganisation of the intracranial of the arteries in patients with chronic vasculitis in the presence of extracranial stenosis and occlusion, which could possibly explain the SAH in absence of aneurysm in patients with TA. PMID:23771963
SATOMI, Junichiro; HADEISHI, Hiromu; YOSHIDA, Yasuji; SUZUKI, Akifumi; NAGAHIRO, Shinji
Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) are likely to die due to irreversible acute-stage primary brain damage. However, the mechanism(s) and pathology responsible for their high mortality rate remain unclear. We report our findings on the brains of individuals who died in the acute stage of SAH. An autopsy was performed on the brains of 11 SAH patients (World Federation of Neurosurgical Societies grade 5) who died within 3 days of admission and who did not receive respiratory assistance. All brains were free of intracranial hematoma and hydrocephalus; all harbored ruptured aneurysms. In all brains, multiple infarcts with perifocal edema were scattered throughout the cortex and subcortical white matter of the whole brain. Infarcts with a patchy – were more often seen than infarcts with a wedge-shaped pattern. Microscopic examination revealed multiple areas with cytotoxic edema and neuronal death indicative of acute ischemic changes. Edema and congestion were more obvious in areas where the subarachnoid clot tightly adhered to the pia mater. Pathologically, the brains of deceased patients with acute poor-grade SAH were characterized by edema and multifocal infarcts spread throughout the whole brain; they were thought to be attributable to venous ischemia. Diffuse disturbance in venous drainage attributable to an abrupt increase in the intracranial pressure and focal disturbances due to tight adhesion of the subarachnoid clot to the pia mater, may contribute strongly to irreversible brain damage in the acute stage of SAH. PMID:27357086
Cai, Jing; Cao, Shenglong; Chen, Jingyin; Yan, Feng; Chen, Gao; Dai, Yuying
This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague-Dawley rats (n=72) by endovascular perforation. Progesterone (8 mg/kg or 16 mg/kg) was administered to rats at 1, 6, and 12h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24h after experimental SAH. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH.
Background Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Methods Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. Results When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the
Karic, Tanja; Røe, Cecilie; Nordenmark, Tonje Haug; Becker, Frank; Sorteberg, Wilhelm; Sorteberg, Angelika
OBJECTIVE Early rehabilitation is effective in an array of acute neurological disorders but it is not established as part of treatment guidelines after aneurysmal subarachnoid hemorrhage (aSAH). This may in part be due to the fear of aggravating the development of cerebral vasospasm, which is the most feared complication of aSAH. The aim of this study was to evaluate the effect of early rehabilitation and mobilization on complications during the acute phase and within 90 days after aSAH. METHODS This was a prospective, interventional study that included patients with aSAH at the neuro-intermediate ward after aneurysm repair. The control group received standard treatment, whereas the early rehab group underwent early rehabilitation and mobilization in addition to standard treatment. Clinical and radiological characteristics of patients with aSAH, progression in mobilization, and treatment variables were registered. The frequency and severity of cerebral vasospasm, cerebral infarction acquired in conjunction with the aSAH, and acute and chronic hydrocephalus, as well as pulmonary and thromboembolic complications, were compared between the 2 groups. RESULTS Clinical and radiological characteristics of patients with aSAH were similar between the groups. The early rehab group was mobilized beginning on the first day after aneurysm repair. The significantly quicker and higher degree of mobilization in the early rehab group did not increase complications. Clinical cerebral vasospasm was not as frequent in the early rehab group and it also tended to be less severe. Each step of mobilization achieved during the first 4 days after aneurysm repair reduced the risk of severe vasospasm by 30%. Acute and chronic hydrocephalus were similar in both groups, but there was a tendency toward earlier shunt implantation among patients in the control group. Pulmonary infections, thromboembolic events, and death before discharge or within 90 days after the ictus were similar between the 2
Platz, Johannes; Güresir, Erdem; Wagner, Marlies; Seifert, Volker; Konczalla, Juergen
OBJECTIVE Delayed cerebral ischemia (DCI) has a major impact on the outcome of patients suffering from aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to assess the influence of an additional intracerebral hematoma (ICH) on the occurrence of DCI. METHODS The authors conducted a single-center retrospective analysis of cases of SAH involving patients treated between 2006 and 2011. Patients who died or were transferred to another institution within 10 days after SAH without the occurrence of DCI were excluded from the analysis. RESULTS Additional ICH was present in 123 (24.4%) of 504 included patients (66.7% female). ICH was classified as frontal in 72 patients, temporal in 24, and perisylvian in 27. DCI occurred in 183 patients (36.3%). A total of 59 (32.2%) of these 183 patients presented with additional ICH, compared with 64 (19.9%) of the 321 without DCI (p = 0.002). In addition, DCI was detected significantly more frequently in patients with higher World Federation of Neurosurgical Societies (WFNS) grades. The authors compared the original and modified Fisher Scales with respect to the occurrence of DCI. The modified Fisher Scale (mFS) was superior to the original Fisher Scale (oFS) in predicting DCI. Furthermore, they suggest a new classification based on the mFS, which demonstrates the impact of additional ICH on the occurrence of DCI. After the different scales were corrected for age, sex, WFNS score, and aneurysm site, the oFS no longer was predictive for the occurrence of DCI, while the new scale demonstrated a superior capacity for prediction as compared with the mFS. CONCLUSIONS Additional ICH was associated with an increased risk of DCI in this study. Furthermore, adding the presence or absence of ICH to the mFS improved the identification of patients at the highest risk for the development of DCI. Thus, a simple adjustment of the mFS might help to identify patients at high risk for DCI.
Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling
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
Qian, Cong; Yu, Xiaobo; Chen, Jingyin; Gu, Chi; Wang, Lin; Chen, Gao; Dai, Yuying
Abstract Background and objectives: Vasospasm-related injury such as delayed ischemic neurological defect (DIND) or cerebral infarction is an important prognostic factor for aneurismal subarachnoid hemorrhage (SAH). Whether cerebrospinal fluid (CSF) drainage can achieve a better outcome in aneurismal SAH patients after coiling or clipping remains the subject of debate. Here, we report a meta-analysis of the related available literature to assess the effect of continuous CSF drainage on clinical outcomes in patients with aneurismal SAH. Methods: Case-control studies regarding the association between aneurismal SAH and CSF drainage were systematically identified through online databases (PubMed, Web of Science, Elsevier Science Direct, and Springer Link). Inclusion and exclusion criteria were defined for the eligible studies. The fixed-effects model was performed when homogeneity was indicated. Alternatively, the random-effects model was utilized. Results: This meta-analysis included 11 studies. Continuous CSF drainage obviously improved patients’ long-term outcome (odds ratio [OR] of 2.86, 95% confidence interval [CI], 1.37–5.98, P < 0.01). CSF drainage also reduced angiographic vasospasm (OR of 0.35, 95% CI, 0.23–0.51, P < 0.01), symptomatic vasospasm (OR of 0.32, 95% CI, 0.32–0.43, P < 0.01), and DIND (OR of 0.48, 95% CI, 0.25–0.91, P = 0.03), but there was no significant difference between the CSF drainage group and the no CSF drainage group on shunt-dependent hydrocephalus (SDHC) prevention (OR of 1.04, 95% CI, 0.52–2.07, P = 0.91). Further analysis on lumbar drainage (LD) and external ventricular drainage (EVD) indicated that LD had a better outcome (OR of 3.11, 95% CI, 1.18–8.23, P = 0.02), whereas no significant difference in vasospasm-related injury was detected between the groups (OR of 1.13, 95% CI, 0.54–2.37, P = 0.75). Conclusion: Continuous CSF drainage is an effective treatment for aneurismal SAH patients; lumbar drainage
Kopczak, Anna; Kilimann, Ingo; von Rosen, Friedrich; Krewer, Carmen; Schneider, Harald Jörn; Stalla, Günter Karl; Schneider, Manfred
We performed a screening on patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) to determine the prevalence of post-traumatic hypopituitarism in neurorehabilitation in a cross-sectional, observational single-center study. In addition, the therapeutic consequences of our screening were analyzed retrospectively. From February 2006 to August 2009, patients between 18 and 65 years (n=509) with the diagnosis of TBI (n=340) or SAH (n=169) were screened within two weeks of admittance to neurorehabilitation as clinical routine. Blood was drawn to determine fasting cortisol, free thyroxine (fT4), prolactin, testosterone or estradiol, and insulin-like growth factor I (IGF-I). Patients with abnormalities in the screening or clinical signs of hypopituitarism received further stimulation tests: growth hormone releasing hormone -L-arginine-test and adrenocorticotrophic hormone (ACTH)-test (n=36); ACTH-test alone (n=26); or insulin tolerance test (n=56). In our screening of 509 patients, 28.5% showed lowered values in at least one hormone of the hypothalamus-pituitary axis and 4.5% in two or more axes. The most common disturbance was a decrease of testosterone in 40.7% of all men (in the following 13/131 men were given substitution therapy). Low fT4 was detected in 5.9% (n=3 were given substitution therapy). Low IGF-I was detected in 5.8%, low cortisol in 1.4%, and low prolactin in 0.2%; none were given substitution therapy. Further stimulation tests revealed growth hormone deficiency in 20.7% (n=19/92) and hypocortisolism in 23.7% (n=28/118). Laboratory values possibly indicating hypopituitarism (33%) were common but did not always implicate post-traumatic hypopituitarism. Laboratory values possibly indicating hypopituitarism were common in our screening but most patients were clinically not diagnosed as pituitary insufficient and did not receive hormone replacement therapy. A routine screening of all patients in neurorehabilitation without considering
Liu, Junhui; Chen, Qianxue
Vasospasm is one of the most common complications after aneurysmal subarachnoid hemorrhage.Statins have been proven to be effective to reduce the incidence of vasospasm both in experimental subarachnoid hemorrhage and several clinical trials before. This meta-analysis aimed to investigate the efficacy of statins for patients with aneurysmal subarachnoid hemorrhage. We made strict search strategies to select the randomized controlled trial and observational studies published up to December 20th 2014. Outcomes of interest were cerebral vasospasm, delayed cerebral ischemia and poor outcome. Data analyses of RCTs and observational studies were made separately. Finally six randomized clinical trial and eight observational studies were included in this meta-analysis. There were in total 1031 patients in six RCTs with 504 patients received statins and 527 patients in placebo group. 561 patients with statins compared with 1579 patients in no statin-use group were finally included in 8 observational studies. Outcomes included in this meta-analysis (cerebral vasospasm, DIC and poor outcome) all indicated no statistical significance between two groups both in RCTs and observational studies. No benefits of statins-use for patients with aneurysmal subarachnoid hemorrhage were observed in both RCTs and observational studies, which was quite different from the results of several previous meta-analysis. PMID:26221259
Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage])
Etminan, Nima; Aldrich, Francois; Steiger, Hans Jakob; Mayer, Stephan A.; Diringer, Michael N.; Hoh, Brian L.; Mocco, J; Faleck, Herbert J.; Macdonald, R. Loch
Background and Purpose— We conducted a randomized, open-label, phase 1/2a, dose-escalation study of intraventricular sustained-release nimodipine (EG-1962) to determine safety, tolerability, pharmacokinetics, and clinical effects in aneurysmal subarachnoid hemorrhage. Methods— Subjects with aneurysmal subarachnoid hemorrhage repaired by clipping or coiling were randomized to EG-1962 or enteral nimodipine. Subjects were World Federation of Neurological Surgeons grade 2 to 4 and had an external ventricular drain. Cohorts of 12 subjects received 100 to 1200 mg EG-1962 (9 per cohort) or enteral nimodipine (3 per cohort). The primary objective was to determine the maximum tolerated dose. Results— Fifty-four subjects in North America were randomized to EG-1962, and 18 subjects were randomized to enteral nimodipine. The maximum tolerated dose was 800 mg. One serious adverse event related to EG-1962 (400 mg) and 2 EG-1962 dose-limiting toxicities were without clinical sequelae. There was no EG-1962-related hypotension compared with 17% (3/18) with enteral nimodipine. Favorable outcome at 90 days on the extended Glasgow outcome scale occurred in 27/45 (60%, 95% confidence interval 46%–74%) EG-1962 subjects (5/9 with 100, 6/9 with 200, 7/9 with 400, 4/9 with 600, and 5/9 with 800 mg) and 5/18 (28%, 95% confidence interval 7%–48%, relative risk reduction of unfavorable outcome; 1.45, 95% confidence interval 1.04–2.03; P=0.027) enteral nimodipine subjects. EG-1962 reduced delayed cerebral ischemia (14/45 [31%] EG-1962 versus 11/18 [61%] enteral nimodipine) and rescue therapy (11/45 [24%] versus 10/18 [56%]). Conclusions— EG-1962 was safe and tolerable to 800 mg, and in this, aneurysmal subarachnoid hemorrhage population was associated with reduced delayed cerebral ischemia and rescue therapy. Overall, the rate of favorable clinical outcome was greater in the EG-1962-treated group. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique
Li, Minghua; Zhu, Yueqi; Song, Hongmei; Gu, Binxian; Lu, Haitao; Li, Yuehua; Tan, Huaqiao; Cheng, Yingsheng
Purpose To evaluate the diagnostic accuracy of aneurysm detection and the fidelity of morphologic characterization of three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography at 3.0 T in patients with a Glasgow coma score of 15 and noncontrast material-enhanced computed tomography (CT) findings that showed acute nontraumatic subarachnoid hemorrhage. Materials and Methods The institutional review board approved this prospective study, and patients provided informed consent. A total of 277 patients who had not experienced trauma but in whom nonenhanced CT showed subarachnoid hemorrhage, who had a Glasgow coma score of 15, and who underwent both 3D TOF MR angiography and digital subtraction angiography (DSA) (the reference standard) were included. Three observers who were blinded to clinical and DSA results independently analyzed all 3D TOF MR angiographic data sets. The receiver operating characteristic curve was applied to analysis of the detection of aneurysms with 3D TOF MR angiography by using patient- and aneurysm-based evaluations. Multivariate logistic regression analysis was performed to identify aneurysm-specific variables, including size, shape (daughter sac/lobulation/margin), neck width (wide if > 4 mm or if fundus-to-neck ratio was < 2), and relation to adjacent artery, that significantly affected morphologic assessment with 3D TOF MR angiography. Results Aneurysms were depicted with DSA in 225 patients. In patient- and aneurysm-based evaluations, respectively, 3D TOF MR angiography yielded accuracies of 96.8% (268 of 277) and 96.6% (309 of 320), sensitivities of 98.2% (219 of 223) and 98.1% (260 of 265), specificities of 91% (49 of 54) and 89% (49 of 55), positive predictive values of 97.8% (219 of 224) and 97.7% (260 of 266), and negative predictive values of 92% (49 of 53) and 91% (49 of 54). Accuracy of display of morphologic features was 92.5% (236 of 255) for size, 86.3% (220 of 255) for neck width, 94.5% for shape (241 of
Rowland, Matthew J; Garry, Payashi; Westbrook, Jon; Corkill, Rufus; Antoniades, Chrystalina A; Pattinson, Kyle T S
OBJECTIVE Delayed cerebral ischemia (DCI) causing cerebral infarction remains a significant cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Early brain injury in the first 72 hours following rupture is likely to play a key role in the pathophysiology underlying DCI but remains difficult to quantify objectively. Current diagnostic modalities are based on the concept of vasoconstriction causing cerebral ischemia and infarction and are either invasive or have a steep learning curve and user variability. The authors sought to determine whether saccadic eye movements are impaired following aSAH and whether this measurement in the acute period is associated with the likelihood of developing DCI. METHODS As part of a prospective, observational cohort study, 24 male and female patients (mean age 53 years old, range 31-70 years old) were recruited. Inclusion criteria included presentation with World Federation of Neurosurgical Societies (WFNS) Grades 1 or 2 ("good grade") aSAH on admission and endovascular treatment within 72 hours of aneurysmal rupture. DCI and DCI-related cerebral infarction were defined according to consensus guidelines. Saccadometry data were collected at 3 time points in patients: in the first 72 hours, between Days 5 and 10, and at 3 months after aSAH. Data from 10 healthy controls was collected on 1 occasion for comparison. RESULTS Age-adjusted saccadic latency in patients was significantly prolonged in the first 72 hours following aSAH when compared with controls (188.7 msec [95% CI 176.9-202.2 msec] vs 160.7 msec [95% CI 145.6-179.4 msec], respectively; p = 0.0054, t-test). By 3 months after aSAH, there was no significant difference in median saccadic latency compared with controls (188.7 msec [95% CI 176.9-202.2 msec] vs 180.0 msec [95% CI 165.1-197.8 msec], respectively; p = 0.4175, t-test). Patients diagnosed with cerebral infarction due to DCI had a significantly higher age-adjusted saccadic latency in the
Xiong, Ye; Wang, Xue-Min; Zhong, Ming; Li, Ze-Qun; Wang, Zhi; Tian, Zuo-Fu; Zheng, Kuang; Tan, Xian-Xi
The aim of the present study was to evaluate the expression levels of caveolin-1 in the basilar artery following delayed cerebral vasospasm (DCVS) in a rat model of subarachnoid hemorrhage (SAH), in order to investigate the association between caveolin-1 and DCVS, and its potential as a treatment for DCVS of SAH. A total of 150 Sprague Dawley rats were randomly allocated into blank, saline and SAH groups. The SAH and saline groups were subdivided into days 3, 5, 7 and 14 following the establishment of the model. The murine model of SAH was established by double injection of autologous arterial blood into the cisterna magana and DCVS was detected using Bederson neurological severity scores. Hematoxylin and eosin (HE) staining was used to observe the inner perimeter of the basilar artery pipe and variations in the thickness of the basilar artery wall. Alterations in the levels of caveolin-1 protein in the basilar artery were measured using immunofluorescence and western blot analysis; whereas alterations in the mRNA expression levels of caveolin-1 were detected by reverse transcription-quantitative polymerase chain reaction. In the present study, 15 mice succumbed to SAH-induced DCVS in the day 3 (n=3), 5 (n=5) and 7 (n=2) groups. No mortality was observed in the blank control and saline groups during the process of observation in the SAH group, All mice in the SAH groups exhibited Bederson neurological severity scores ≥1; whereas no neurological impairment was detected in the blank and normal saline groups, demonstrating the success of the model. HE staining was used to assess vasospasm and the results demonstrated that the inner perimeter of the basal artery pipe decreased at day 3 in the SAH group; whereas values peaked in the day 7 group. The thickness of the basal artery wall significantly increased (P<0.05), as compared with the blank and saline groups, in which no significant alterations in the wall thickness and the inner perimeter of the basal artery pipe
Ono, Shigeki; Date, Isao; Onoda, Keisuke; Ohmoto, Takashi
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.
Park, Soojeong; Yang, Narae
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
Nakagawa, K; Hirai, K; Aoyagi, M; Yamamoto, K; Hirakawa, K; Katayama, Y
Endothelial cell dysfunction may contribute to cerebral vasospasm and aggravation of ischemic brain damage following subarachnoid hemorrhage (SAH). It has been suggested that oxyhemoglobin derived from subarachnoid blood clots might be a prime candidate for cerebral vasospasm. In this study, cisternal bloody cerebrospinal fluid (bCSF) was collected from SAH patients four and seven days after aneurysmal rupture, and the effects of bCSF on the cell growth and intracellular calcium ion ([Ca2+]i) dynamics were investigated in cultured human umbilical vein endothelial cells. CSF collected from patients undergoing other intracranial surgeries was used as a control. Pre-treatment with bCSF4 significantly facilitated cell proliferation and DNA synthesis in the cultured endothelial cells, and significantly enhanced histamine-induced [Ca2+]i increase, while acute treatment of the bCSF elicited no [Ca2+]i change. Pre-treatment with interleukin-1 beta showed a similar significant enhancement of the histamine-induced [Ca2+]i response, while pre-treatment with high concentrations of serum or interleukin-6 did not change the [Ca2+]i response. It is concluded that bCSF collected from SAH patients contains some substances which enhance endothelial cell proliferation and sensitivity to inflammatory mediator.
Chan, Teresa M; Rosenberg, Hans; Lin, Michelle
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.
Li, Tao; Zhang, Jie; Liu, Rong-Yao; Lian, Zhi-Gang; Chen, Xiao-Lin; Ma, Li; Sun, Hao-Min; Zhao, Yuan-Li
Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.
Zhang, Zong-Yong; Yang, Ming-Feng; Wang, Tao; Li, Da-Wei; Liu, Yun-Lin; Zhang, Jin-Hui; Sun, Bao-Liang
Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The aim of this study was to assess whether cysteamine prevents post-SAH oxidative stress injury via its antioxidative and anti-apoptotic effects. It was observed that intraperitoneal administration of cysteamine (20 mg/kg/day) could significantly alleviate EBI (including neurobehavioral deficits, brain edema, blood-brain barrier permeability, and cortical neuron apoptosis) after SAH in rats. Meanwhile, cysteamine treatment reduced post-SAH elevated the reactive oxygen species level, the concentration of malondialdehyde, 3-nitrotyrosine, and 8-hydroxydeoxyguanosine and increased the glutathione peroxidase enzymatic activity, the concentration of glutathione and brain-derived neurotrophic factor in brain cortex at 48 h after SAH. These results indicated that administration of cysteamine may ameliorate EBI and provide neuroprotection after SAH in rat models.
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
Yan, Feng; Cao, Shenglong; Li, Jianru; Dixon, Brandon; Yu, Xiaobo; Chen, Jingyin; Gu, Chi; Lin, Wang; Chen, Gao
Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Endoplasmic reticulum (ER) stress was reported to have a vital role in the pathophysiology of neuronal apoptosis in the brain. The present study was designed to investigate the potential effects of ER stress and its downstream signals in early brain injury after SAH. One hundred thirty-four rats were subjected to an endovascular perforation model of SAH. The RNA-activated protein kinase-like ER kinase (PERK) inhibitor GSK2606414 and the Akt inhibitor MK2206 were injected intracerebroventricularly. SAH grade, neurologic scores, and brain water content were measured 72 h after subarachnoid hemorrhage. Expression of PERK and its downstream signals, Akt, Bcl-2, Bax, and cleaved caspase-3, were examined using Western blot analysis. Specific cell types that expressed PERK were detected with double immunofluorescence staining. Neuronal cell death was demonstrated with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). Our results showed that the expression of p-PERK and its downstream targets, p-eIF2α and ATF4, increased after SAH and peaked at 72 h after SAH. PERK was expressed mostly in neurons. The inhibition of PERK with GSK2606414 reduced p-PERK, p-eIF2α, and ATF4 expression. Furthermore, GSK2606414 treatment increased p-Akt levels and the Bcl-2/Bax ratio as well as decreased cleaved caspase-3 expression and neuronal death, thereby improving neurological deficits at 72 h after SAH. The selective Akt inhibitor MK2206 abolished the beneficial effects of GSK2606414. PERK, the major transducer of ER stress, is involved in neuronal apoptosis after SAH. The inhibition of PERK reduces early brain injury via Akt-related anti-apoptosis pathways. PERK may serve as a promising target for future therapeutic intervention.
Khalsa, Siri Sahib; Hollon, Todd C; Shastri, Ravi; Trobe, Jonathan D; Gemmete, Joseph J; Pandey, Aditya S
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.
Bandeira, A.; Ribeiro, C.; Reis, J.
Summary There are currently no consensus criteria to define the dosage of intra-arterial Nimodipine to be used to obtain permanent remission of vasospasm secondary to subarachnoid haemorrhage. The purpose of this paper is to establish a mathematical relation between the number of vessels affected by this kind of vasospasm and the Nimodipine dose that must be used for intra-arterial angioplasty to obtain permanent remission of the vasospasm. PMID:20566112
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
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.
Lobato, R.D.; Marin, J.; Salaices, M.; Rico, M.L.; Sanchez, C.F.
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.
Westermaier, Thomas; Jauss, Alina; Eriskat, Jörg; Kunze, Ekkehard; Roosen, Klaus
Present knowledge about hemodynamic and metabolic changes after subarachnoid hemorrhage (SAH) originates from neuromonitoring usually starting with aneurysm surgery and animal studies that have been focusing on the first 1 to 3 h after SAH. Most patients, however, are referred to treatment several hours after the insult. We examined the course of hemodynamic parameters, cerebral blood flow, and tissue oxygenation (ptiO2) in the first 6 h after experimental SAH. Sixteen Sprague-Dawley rats were subjected to SAH using the endovascular filament model or served as controls (n=8). Bilateral local cortical blood flow, intracranial pressure, cerebral perfusion pressure, and ptiO2 were followed for 6 h after SAH. After induction of SAH, local cortical blood flow rapidly declined to 22% of baseline and returned to 80% after 6 h. The decline of local cortical blood flow markedly exceeded the decline of cerebral perfusion pressure. ptiO2 declined to 57%, recovered after 2 h, and reached > or =140% of baseline after 6 h. Acute vasoconstriction after SAH is indicated by the marked discrepancy of cerebral perfusion pressure and local cortical blood flow. The excess tissue oxygenation several hours after SAH suggests disturbed oxygen utilization and cerebral metabolic depression. Aside from the sudden increase of intracranial pressure at the time of hemorrhage and delayed cerebral vasospasm, the occurrence of acute vasoconstriction and disturbed oxygen utilization may be additional factors contributing to secondary brain damage after SAH.
Cornejo, Rodrigo; Romero, Carlos; Ugalde, Diego; Bustos, Patricio; Diaz, Gonzalo; Galvez, Ricardo; Llanos, Osvaldo; Tobar, Eduardo
We report the successful treatment of two patients with aneurismal subarachnoid hemorrhage complicated by severe respiratory failure and refractory septic shock using simultaneous prone position ventilation and high-volume hemofiltration. These rescue therapies allowed the patients to overcome the critical situation without associated complications and with no detrimental effects on the intracranial and cerebral perfusion pressures. Prone position ventilation is now an accepted therapy for severe acute respiratory distress syndrome, and high-volume hemofiltration is a non-conventional hemodynamic support that has several potential mechanisms for improving septic shock. In this manuscript, we briefly review these therapies and the related evidence. When other conventional treatments are insufficient for providing safe limits of oxygenation and perfusion as part of basic neuroprotective care in subarachnoid hemorrhage patients, these rescue therapies should be considered on a case-by-case basis by an experienced critical care team. PMID:25028955
Tan, Guanping; Liu, Liu; He, Zhaohui; Sun, Jiujun; Xing, Wenli; Sun, Xiaochuan
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.
Introduction Elevated brain potassium levels ([K+]) are associated with neuronal damage in experimental models. The role of brain extracellular [K+] in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) and its association with hemorrhage load, metabolic dysfunction and outcome has not been studied so far. Methods Cerebral microdialysis (CMD) samples from 28 poor grade aSAH patients were analyzed for CMD [K+] for 12 consecutive days after ictus, and time-matched to brain metabolic and hemodynamic parameters as well as corresponding plasma [K+]. Statistical analysis was performed using a generalized estimating equation with an autoregressive function to handle repeated observations of an individual patient. Results CMD [K+] did not correlate with plasma [K+] (Spearman’s ρ = 0.114, P = 0.109). Higher CMD [K+] was associated with the presence of intracerebral hematoma on admission head computed tomography, CMD lactate/pyruvate ratio >40 and CMD lactate >4 mmol/L (P < 0.05). In vitro retrodialysis data suggest that high CMD [K+] was of brain cellular origin. Higher CMD [K+] was significantly associated with poor 3-month outcome, even after adjusting for age and disease severity (P < 0.01). Conclusions The results of this pilot study suggest that brain extracellular [K+] may serve as a biomarker for brain tissue injury in poor-grade aSAH patients. Further studies are needed to elucidate the relevance of brain interstitial K+ levels in the pathophysiology of secondary brain injury after aSAH. PMID:24920041
Phelan, Herb A; Richter, Adam A; Scott, William W; Pruitt, Jeffrey H; Madden, Christopher J; Rickert, Kim L; Wolf, Steven E
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.
Asahi, Takashi; Kashiwazaki, Daina; Koh, Masaki; Matsumura, Nobuhisa; Kuroda, Satoshi
Typically, intrathecal baclofen therapy(ITB)for spasticity is continuously required because the spasticity can recur if the ITB is stopped. Thus, an infusion pump for the ITB is permanently implanted. Some sporadic cases exhibiting remarkable improvements in their spasticity and consciousness disturbances have been reported after implanting the ITB pump. We experienced a rare case involving removal of the ITB pump after the spasticity resolved and the consciousness disturbances markedly improved. A 15-year-old girl developed a subarachnoid hemorrhage due to rupture of an aneurysm in the right anterior cerebral artery. Her initial Glasgow Coma Scale score was 4(E1V1M2). Trapping of the aneurysm and decompression craniotomy were performed. Subsequently, she underwent a tracheotomy, and a percutaneous gastrostomy(PEG)tube was implanted because of persistent consciousness disturbances. Cranioplasty and lumbar-peritoneal shunt for normal pressure hydrocephalus were performed after 1 month. An ITB pump was implanted to improve the spasticity observed mainly in the lower extremities 61 days after hemorrhage onset. Right hemiparesis remained due to Kernohan's notch. After transfer to the rehabilitation hospital, her consciousness disturbances and spasticity remarkably improved(1.9 to 1.0 and 3.5 to 1.0 on the Ashworth scale for the upper and lower extremities, respectively). The tracheostomy and PEG tubes were removed, and the baclofen dose was gradually reduced. She was completely off baclofen after 7 months, and she was discharged with a short leg brace and a cane for walking. The baclofen pump was then removed. In this case, temporary ITB improved the spasticity and consciousness disturbances.
Gao, Cheng; Yu, Hongwei; Yan, Cong; Zhao, Wenyang; Liu, Yao; Zhang, Dongdong; Li, Jingwei; Liu, Nan
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins. The results showed that XIAP was significantly up-regulated in the cortex and hippocampus and that XIAP was mainly expressed in neuronal cells following SAH. The inhibition of endogenous XIAP aggravated blood-brain barrier disruption, neurological deficits and brain edema. Recombinant XIAP preserved the blood-brain barrier, improved the neurological scores and ameliorated brain edema. Recombinant XIAP treatment also decreased the expression of cleaved caspase-3, caspase-8 and caspase-9, whereas there was no effect on the expression of p53, apoptosis-inducing factor or cytochrome c. These results show that XIAP acts as an endogenous neuroprotective and anti-apoptotic agent following SAH. The effects of XIAP on early brain injury was associated with the inhibition of the caspase-dependent apoptosis pathway.
Sugawara, Takashi; Ayer, Robert; Jadhav, Vikram; Chen, Wanqiu; Tsubokawa, Tamiji; Zhang, John H.
The mechanisms involved in simvastatin-mediated attenuation of cerebral vasospasm after subarachnoid hemorrhage (SAH) are unclear. We investigated the role of the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway and endothelial nitric oxide synthase (eNOS) in the cerebral vasculature in statin-mediated attenuation of cerebral vasospasm using wortmannin, an irreversible pharmacological PI3K inhibitor, and a rat SAH endovascular perforation model. Simvastatin was administered intraperitoneally in two dosages (1 mg/kg and 20 mg/kg) at 0.5, 24, and 48 hr after SAH and histological parameters of ipsilateral intracranial carotid artery (ICA) were assessed at 24 and 72 hr. SAH significantly decreased ICA diameter and perimeter while increasing wall thickness at both 24 and 72 hr. High-dosage simvastatin prevented the reduction of ICA diameter and perimeter following SAH, whereas both high and low dosages reduced wall thickness significantly at 24 and 72 hr. The effects of simvastatin were significantly reversed by wortmannin. High-dosage simvastatin increased pAkt and peNOS (phosphorylated forms) levels without increasing Akt and eNOS expression compared with the SAH group and also improved neurological deficits at 24 and 72 hr. Simvastatin did not affect protein levels by itself compared with untreated sham group. The present study elucidates the critical role of the PI3K activation leading to phosphorylation of Akt and eNOS in simvastatin-mediated attenuation of cerebral vasospasm after SAH. PMID:18683242
Silasi, Gergely; Colbourne, Frederick
The endovascular perforation model of subarachnoid hemorrhage (SAH) is a commonly used model in rats as it is performed without a craniotomy and accurately mimics the physiological effects of SAH in humans. The long-term behavioural profile of the model, however, has not been characterized. Given that humans often have cognitive deficits following SAH, we set out to characterize the behavioural profile as well as the spontaneous temperature changes of rats following intraluminal perforation. Rats were pre-trained on three motor tasks (tapered beam, limb-use asymmetry and the horizontal ladder tasks) prior to receiving a SAH. The animals were then assessed on post-surgical days 3, 7, 14 and 21 on these tasks. At the completion of motor testing, the rats were assessed on a moving platform version of the Morris water task. Despite significant mortality (33%), SAH did not result in lasting motor deficits on any of the tasks examined. However, the SAH group did show a minor cognitive impairment in the Morris water task. In addition, SAH produced a slight, but significant elevation in body temperature (vs. sham operated rats) despite an acute decrease in general home cage activity. The majority of the animals did not have any observable infarcts and the SAH did not significantly affect cortical thickness. In summary, the endovascular perforation model of SAH results in no lasting motor deficits and only minor cognitive impairment in survivors, which alone would be difficult to evaluate in neuroprotection or rehabilitation studies.
Frontera, Jennifer A
Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH). Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included. Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically. Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.
Foreman, Paul M; Chua, Michelle H; Harrigan, Mark R; Fisher, Winfield S; Tubbs, R Shane; Shoja, Mohammadali M; Griessenauer, Christoph J
OBJECTIVE Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) occurs in approximately 30% of patients. The Practical Risk Chart was developed to predict DCI based on admission characteristics; the authors seek to externally validate and critically appraise this prediction tool. METHODS A prospective cohort of aSAH patients was used to externally validate the previously published Practical Risk Chart. The model consists of 4 variables: clinical condition on admission, amount of cisternal and intraventricular blood on CT, and age. External validity was assessed using logistic regression. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS In a cohort of 125 patients with aSAH, the Practical Risk Chart adequately predicted DCI, with an AUC of 0.66 (95% CI 0.55-0.77). Clinical grade on admission and amount of intracranial blood on CT were the strongest predictors of DCI and clinical vasospasm. The best-fit model used a combination of the Hunt and Hess grade and the modified Fisher scale to yield an AUC of 0.76 (95% CI 0.675-0.85) and 0.70 (95% CI 0.602-0.8) for the prediction of DCI and clinical vasospasm, respectively. CONCLUSIONS The Practical Risk Chart adequately predicts the risk of DCI following aSAH. However, the best-fit model represents a simpler stratification scheme, using only the Hunt and Hess grade and the modified Fisher scale, and produces a comparable AUC.
Cremers, Charlotte H P; van der Schaaf, Irene C; Wensink, Emerens; Greving, Jacoba P; Rinkel, Gabriel J E; Velthuis, Birgitta K; Vergouwen, Mervyn D I
Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed, Embase, and Cochrane databases to identify studies on the relationship between CTP and DCI. Eleven studies totaling 570 patients were included. On admission, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP) did not differ between patients who did and did not develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage (SAH)), DCI was associated with a decreased CBF (pooled mean difference -11.9 mL/100 g per minute (95% confidence interval (CI): -15.2 to -8.6)) and an increased MTT (pooled mean difference 1.5 seconds (0.9-2.2)). Cerebral blood volume did not differ and TTP was rarely reported. Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.
Suzuki, Hidenori; Shiba, Masato; Nakatsuka, Yoshinari; Nakano, Fumi; Nishikawa, Hirofumi
Recent investigations have shown that many factors may cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). To find new potential contributors to DCI, this retrospective study compared gas data in the cerebrospinal fluid (CSF) between patients with and without DCI. The subjects were 61 consecutive patients with SAH classified as Fisher group III on admission computed tomography scans, whose aneurysms were obliterated by clipping or coiling within 24 h post-SAH. Thirty-three patients were treated with CSF drainage. CSF samples were chronologically obtained from CSF drains or lumbar taps. Patients with DCI were more frequently treated with CSF drainage, especially cisternal drainage, and were associated with significantly higher pH and lower partial pressure of carbon dioxide (PCO2) in the CSF compared with patients without DCI, although CSF concentrations of bicarbonate ion as well as arterial blood gas data were not different between the two groups. Total hemoglobin concentrations in the drained or tapped CSF were higher in patients with no DCI compared with patients with DCI at any sampling time, suggesting that CSF hemoglobin was not efficiently removed in patients with DCI. This study revealed higher CSF pH and lower CSF PCO2 as new potential contributors to the development of DCI, which might result from inappropriate CSF drainage that failed to remove clot and acid metabolites in it efficiently. Both of the disturbed CSF gas and inappropriate CSF drainage may cause constriction of the arteries and arterioles, leading to DCI.
Laban, Kamil G; Vergouwen, Mervyn DI; Dijkhuizen, Rick M; Sena, Emily S; Macleod, Malcolm R; Rinkel, Gabriel JE; van der Worp, H Bart
In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients. PMID:25944590
Gao, Cheng; Yu, Hongwei; Yan, Cong; Zhao, Wenyang; Liu, Yao; Zhang, Dongdong; Li, Jingwei; Liu, Nan
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins. The results showed that XIAP was significantly up-regulated in the cortex and hippocampus and that XIAP was mainly expressed in neuronal cells following SAH. The inhibition of endogenous XIAP aggravated blood-brain barrier disruption, neurological deficits and brain edema. Recombinant XIAP preserved the blood-brain barrier, improved the neurological scores and ameliorated brain edema. Recombinant XIAP treatment also decreased the expression of cleaved caspase-3, caspase-8 and caspase-9, whereas there was no effect on the expression of p53, apoptosis-inducing factor or cytochrome c. These results show that XIAP acts as an endogenous neuroprotective and anti-apoptotic agent following SAH. The effects of XIAP on early brain injury was associated with the inhibition of the caspase-dependent apoptosis pathway. PMID:28327595
Nakagawa, Ichiro; Kurokawa, Shinichiro; Takayama, Katsutoshi; Wada, Takeshi; Nakase, Hiroyuki
Cerebral salt wasting syndrome (CSWS) in patients with aneurysmal subarachnoid hemorrhage (SAH) is considered to correlate with delayed ischemic neurological deficits (DIND) induced by cerebral vasospasm; however, its exact mechanism is still not well-known. The purpose of the present study is to evaluate the relationship between hyponatremia caused by CSWS and the increase of the urinary sodium excretion in early phase following SAH. Fifty-four patients with SAH were divided into 2 groups, normonatremia group and hyponatremia group which suffered hyponatremia after SAH. The hyponatremia group comprise 14 patients (26%) in whom the hyponatremia developed of the SAH. In this group, the serum level of sodium significantly decreased 7 days after SAH and then gradually normalised. Further, excretion of sodium in the urine tended to increase 3 days after SAH and significantly increased 7 days after SAH. In conclusion, the increased urinary sodium excretion in the early phase of SAH would serve as a predictive factor for CSWS after SAH. We consider that it is important to start sodium and fluid supplementation and inhibit natriuresis by fludrocortisone acetate administration before hyponatremia occurs in order to prevention delayed ischemic neurological deficits in SAH patients.
Enomoto, Yukiko; Yoshimura, Shinichi; Yamada, Kiyofumi; Iwama, Toru
The incidence of convulsion and associated factors were retrospectively analyzed in 23 patients with symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH) who underwent a total of 31 intra-arterial infusion of fasudil hydrochloride (IAFH) procedures in 49 vessels. Fasudil hydrochloride was administered by superselective infusion via a microcatheter positioned at the proximal portion of the affected artery. Thirteen procedures were performed by manually controlled infusion of 30-75 mg fasudil hydrochloride (1.2-3.75 mg/ml) for approximately 10 minutes. Eighteen procedures were performed by continuous infusion of 60 mg fasudil hydrochloride (1.2 mg/ml) by infusion pump at a constant rate of 3 mg/min. Neurological improvement was observed after 18 of 22 procedures in patients with neurological deterioration due to vasospasm. Convulsion during IAFH developed in 4 patients, all treated by manual infusion (p < 0.05). The manual infusion method (p < 0.05) and infusion rate greater than 3 mg/min (p < 0.01) were significantly associated with the incidence of convulsion during IAFH. IAFH was effective for treating cerebral vasospasm following aneurysmal SAH. IAFH at a constant rate of 3 mg/min delivered by infusion pump improved the symptoms of cerebral vasospasm and prevented convulsions during IAFH.
Shiratori, Tohru; Sato, Atsushi; Fukuzawa, Masao; Kondo, Naoko; Tanno, Shogo
Dextran is a colloid effective for volume expansion; however, a possible side effect of its use is anaphylaxis. Dextran-induced anaphylactoid reaction (DIAR) is a rare but severe complication, with a small dose of dextran solution sufficient to induce anaphylaxis. An 86-year-old female who underwent clipping for a ruptured cerebral aneurysm was admitted to the intensive care unit. Prophylactic hypertension-hypervolemia-hemodilution therapy was induced for cerebral vasospasm following a subarachnoid hemorrhage. The patient went into severe shock after administration of dextran for volume expansion, and dextran administration was immediately discontinued. The volume administered at that time was only 0.8 mL at the most. After fluid resuscitation with a crystalloid solution, circulatory status began to recover. However, cerebral vasospasm occurred and the patient's neurological condition deteriorated. Five weeks after the shock, she was diagnosed with hypersensitivity to dextran by a skin test. When severe hypotension occurs after dextran administration, appropriate treatments for shock should be performed immediately with discontinuation of dextran solution. Although colloid administration is recommended in some guidelines and researches, it is necessary to consider concerning the indication for volume expansion as well as the risk of colloid administration. PMID:26171255
Xu, Jie; Xu, Zhen; Yan, Ai
Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH. Furthermore, AE1-329 obviously reduced the number of activated microglia and the mRNA and protein levels of pro-inflammatory cytokines, and increased Ser1177 phosphorylated endothelial nitric oxide synthase (Ser1177 p-eNOS). Moreover, AE1-329 significantly reduced the number of TUNEL-positive cells and active caspase-3 in cortex after SAH. The EP4 selective antagonist AE3-208 was also administrated and the opposite effects were achieved. Our results indicate that activation of EP4 protects brain from EBI through downregulating neuroinflammation reaction after SAH.
This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH. PMID:28337226
Su, Shao-Hua; Xu, Wei; Hai, Jian; Wu, Yi-Fang; Yu, Fei
Aneurysmal subarachnoid hemorrhage (aSAH)-induced cerebral vasospasm and delayed ischemic neurological deficit (DIND) are the major causes of morbidity and mortality in patients with aSAH. The effects of statins-use for patients with aSAH remain controversial. Here,a total of 249 patients from six randomized controlled trials(RCTs) were subjected to meta-analysis. No significant decrease was found in the incidence of vasospasm(RR, 0.80; 95% CI, 0.54–1.17), with substantial heterogeneity (I2 = 49%, P = 0.08), which was verified by the further sensitivity analysis and subgroup meta-analysis. Furthermore, no significant difference was presented in the incidence of poor neurological outcome(RR, 0.94; 95% CI, 0.77–1.16), and potential side effects(RR, 2.49; 95% CI, 0.75–8.33). Nevertheless, significant difference was reported in the occurrence of DIND(RR, 0.58; 95% CI, 0.37–0.92) and mortality(RR, 0.30; 95% CI, 0.14–0.64). At present, although statins-use in the patients with aSAH should not be considered standard care at present, statins-use may have the potential effects in the prevention of mortality in patients with aSAH. PMID:24763190
Sato, N.; Kuroda, K.; Suzuki, M.; Ogawa, A.; Sera, K.
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.
Shimoda, Masami; Hoshikawa, Kaori; Shiramizu, Hideki; Oda, Shinri; Matsumae, Mitsunori
The diagnostic efficacy of fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging and computed tomography (CT) for acute subarachnoid hemorrhage (SAH) were compared and the problems with diagnosis were investigated in 81 patients with aneurysmal SAH within 24 hours after onset who underwent FLAIR imaging and CT on admission. The number of hematomas in the cisterns and ventricles were evaluated by clot scores. In addition, the frequency of undetected hematomas was calculated for the cisterns and ventricles. Clot scores were significantly higher for FLAIR imaging than for CT in the lateral sylvian, quadrigeminal, and convexity cisterns. On the other hand, clot scores were significantly higher for CT than for FLAIR imaging in the interhemispheric and medial sylvian cisterns. The overall frequency of undetected SAH was 2% for FLAIR imaging and 14% for CT. With the exception of the interhemispheric and medial sylvian cisterns, the frequency of undetected SAH was higher for CT than for FLAIR imaging. In this study, FLAIR imaging was more sensitive than CT for the detection of acute SAH within 24 hours after onset. However, the diagnostic efficacy of FLAIR imaging was reduced in comparatively tight cisterns.
Lim, Seung Hoon; Lee, Seung Hwan; Koh, Jun Seok
Objective Intracranial ruptured vertebral artery dissecting aneurysms (VADAns) are associated with high morbidity and mortality when left untreated due to the high likelihood of rebleeding. The present study aimed to establish an endovascular therapeutic strategy that focuses specifically on the angioarchitecture of ruptured VADAns. Methods Twenty-three patients with ruptured VADAn received endovascular treatment (EVT) over 7 years. The patient group included 14 women (60.9%) and 9 men (39.1%) between the ages of 39 and 72 years (mean age 54.2 years). Clinical data and radiologic findings were retrospectively analyzed. Results Four patients had aneurysms on the dominant vertebral artery. Fourteen (61%) aneurysms were located distal to the posterior inferior cerebellar artery (PICA). Six (26%) patients had an extracranial origin of the PICA on the ruptured VA, and 2 patients (9%) had bilateral VADAns. Eighteen patients (78%) were treated with internal coil trapping. Two patients (9%) required an adjunctive bypass procedure. Seven patients (30%) required stent-supported endovascular procedures. Two patients experienced intra-procedural rupture during EVT, one of which was associated with a focal medullary infarction. Two patients (9%) exhibited recanalization of the VADAn during follow-up, which required additional coiling. No recurrent hemorrhage was observed during the follow-up period. Conclusion EVT of ruptured VADAns based on angioarchitecture is a feasible and effective armamentarium to prevent fatal hemorrhage recurrence with an acceptable low risk of procedural complications. Clinical outcomes depend mainly on the pre-procedural clinical state of the patient. Radiologic follow-up is necessary to prevent hemorrhage recurrence after EVT. PMID:26539258
Griebel, R.W.; Black, P.M.; Pile-Spellman, J.; Strauss, H.W.
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.
Kuruppu, Sanjaya; Chou, Sherry H.-Y.; Feske, Steven K.; Suh, Sarah; Hanchapola, Iresha; Lo, Eng H.; Ning, MingMing; Smith, A. Ian
Endothelin converting Enzyme-1 (ECE-1) is essential for the production of Endothelin-1 (ET-1), which is associated with vasospasm following subarachnoid hemorrhage (SAH). We have previously demonstrated the presence of a catalytically active soluble form of ECE-1 in the media of endothelial cells. We aimed to determine if this form of ECE-1 exists in vivo, in cerebrospinal fluid (CSF) of SAH patients. We examined CSF taken from SAH subjects for the presence of soluble ECE-1 using a bradykinin based quenched fluorescent substrate assay. We obtained further confirmation by characterizing the CSF mediated cleavage products of BigET-1 and BigET18–34 (6 μg/ml) using mass spectrometry. The specificity of cleavage was confirmed using the ECE-1 inhibitor CGS35066 5nmol/L. SAH CSF samples had mean ECE-1 activity of 0.127 ± 0.037 μmols of substrate cleaved/μl of CSF/24 h. The C-terminal peptides generated upon the cleavage of BigET-1 and BigET18–34 were detected 48 h after incubation of these substrates with CSF. Cleavage of these substrates was inhibited by CGS35066. Results of Western blots also produced strong evidence for the presence of truncated soluble ECE-1 in CSF. These results strongly suggest the presence of a truncated but catalytically active form of ECE-1 in the CSF of SAH subjects. Further studies are necessary to determine the biological significance of soluble ECE-1 in CSF of SAH subjects, including an association with vasospasm after SAH. PMID:23816989
Background Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders that occur owing to the abnormalities in type 1 collagen, and is characterized by increased bone fragility and other extraskeletal manifestations. We report the case of a patient who was diagnosed with OI following subarachnoid hemorrhage (SAH) secondary to a ruptured saccular intracranial aneurysm (IA). Case Presentation A 37-year-old woman was referred to our hospital because of sudden headache and vomiting. She was diagnosed with SAH (World Federation of Neurosurgical Society grade 2) owing to an aneurysm of the middle cerebral artery. She then underwent surgical clipping of the aneurysm successfully. She had blue sclerae, a history of several fractures of the extremities, and a family history of bone fragility and blue sclerae in her son. According to these findings, she was diagnosed with OI type 1. We performed genetic analysis for a single nucleotide G/C polymorphism (SNP) of exon 28 of the gene encoding for alpha-2 polypeptide of collagen 1, which is a potential risk factor for IA. However, this SNP was not detected in this patient or in five normal control subjects. Other genetic analyses did not reveal any mutations of the COL1A1 or COL1A2 gene. The cerebrovascular system is less frequently involved in OI. OI is associated with increased vascular weakness owing to collagen deficiency in and around the blood vessels. SAH secondary to a ruptured IA with OI has been reported in only six cases. Conclusion The patient followed a good clinical course after surgery. It remains controversial whether IAs are caused by OI or IAs are coincidentally complicated with OI. PMID:25056440
Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee
OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.
Kamp, Marcel A; Lieshout, Jasper H van; Dibué-Adjei, Maxine; Weber, Jasmin K; Schneider, Toni; Restin, Tanja; Fischer, Igor; Steiger, Hans-Jakob
Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology.
Watanabe, Akihiro; Tagami, Takashi; Yokobori, Shoji; Matsumoto, Gaku; Igarashi, Yutaka; Suzuki, Go; Onda, Hidetaka; Fuse, Akira; Yokota, Hiroyuki
Predictive variables of delayed cerebral ischemia (DCI) and pulmonary edema following subarachnoid hemorrhage (SAH) remain unknown. We aimed to determine associations between transpulmonary thermodilution-derived variables and DCI and pulmonary edema occurrence after SAH. We reviewed 34 consecutive SAH patients monitored by the PiCCO system. Six patients developed DCI at 7 days after SAH on average; 28 did not (non-DCI). We compared the variable measures for 1 day before DCI occurred (DCI day -1) in the DCI group and 6 days after SAH (non-DCI day -1) in the non-DCI group for control. The mean value of the global end-diastolic volume index (GEDI) for DCI day -1 was lower than that for non-DCI day -1 (676 ± 65 vs. 872 ± 85 mL/m, P = 0.04). Central venous pressure (CVP) was not significantly different (7.8 ± 3.1 vs. 9.4 ± 1.9 cm H2O, P = 0.45). At day -1 for both DCI and non-DCI, 11 patients (32%) had pulmonary edema. Global end-diastolic volume index was significantly higher in patients with pulmonary edema than in those without this condition (947 ± 126 vs. 766 ± 81 mL/m, P = 0.02); CVP was not significantly different (8.7 ± 2.8 vs. 9.2 ± 2.1 cm H2O, P = 0.78). Although significant correlation was found between extravascular lung water (EVLW) measures and GEDI (r = 0.58, P = 0.001), EVLW and CVP were not correlated (r = 0.03, P = 0.88). Thus, GEDI might be associated with DCI occurrence and EVLW accumulation after SAH.
Okada, Takeshi; Suzuki, Hidenori
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor (NF)-κB signaling among TLR4 signaling pathways as to the development of early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κB and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.
Xu, Haoliang; Testai, Fernando D; Valyi-Nagy, Tibor; N Pavuluri, Mani; Zhai, Fengguo; Nanegrungsunk, Danop; Paisansathan, Chanannait; Pelligrino, Dale A
Our previous findings indicated that in rats subjected to subarachnoid hemorrhage (SAH), suppression of post-SAH neuroinflammation via vascular adhesion protein-1 (VAP-1) blockade provides significant neuroprotection. We and others have reported that neuroinflammation contributes to cerebral microvascular impairment. Thus, in the present study, we tested the hypotheses that: (1) treatment with LJP-1586, a selective VAP-1 blocker, prevents SAH-associated pial arteriolar dilating dysfunction; and (2) the vasculoprotective effect of LJP-1586 arises from inhibiting SAH-elicited neutrophil recruitment. We utilized an endovascular perforation model of SAH. Rats subjected to SAH were either treated with LJP-1586 or rendered neutropenic via anti-neutrophil-antibody treatment. Findings from these groups were compared to their respective control groups. At 48 h post-SAH, rats were evaluated for neurobehavioral function, pial venular leukocyte trafficking, and pial arteriolar reactivity to topically-applied acetylcholine (ACh) and S-nitroso-N-acetyl penicillamine (SNAP). Pial arteriolar responses decreased at 48 h post-SAH. However, in the presence of LJP-1586, those responses were significantly preserved. Neutrophil-depletion yielded a substantial suppression of SAH-associated leukocyte adhesion and infiltration. This was accompanied by a significant preservation of pial arteriolar dilating function, suggesting a direct link between neutrophil recruitment and the loss of cerebral microvascular reactivity. Moreover, neutrophil depletion also was associated with significant protection of neurobehavioral function. The present findings suggest that attenuating SAH-linked elevation in neutrophil trafficking will protect against the development of microvascular dysfunction and subsequent neurological impairment.
Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki
Early brain injury/ischemia (EBI) is a serious complication early after subarachnoid hemorrhage (SAH) that contributes to development of delayed cerebral ischemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5h after SAH induction was monitored with Doppler-echocardiography. MRI-continuous arterial spin labeling was used for quantitative CBF measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P <0.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P <0.05). The neuroprotective effects afforded by MIL or Control were attenuated by HIF inhibition (P <0.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. This article is protected by copyright. All rights reserved.
Fujimoto, Masashi; Shiba, Masato; Kawakita, Fumihiro; Liu, Lei; Shimojo, Naoshi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori
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.
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
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
Dong, Yushu; Li, Yue; Feng, Dayun; Wang, Julei; Wen, Hua; Liu, Debao; Zhao, Dandan; Liu, Haiying; Gao, Guodong; Yin, Zhongmin; Qin, Huaizhou
Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of cellular adaptation to hypoxia and has been proposed as a potent therapeutic target for cerebral ischemia. However, research on the expression and effects of HIF-1α in subarachnoid hemorrhage (SAH) is limited. The aim of the present study was to investigate the expression of HIF-1α in the hippocampus and its possible protective effect against hippocampal apoptosis and cognitive dysfunction in a rat model of SAH. Seventy-two Sprague-Dawley (SD) rats were randomly divided into the sham group, the SAH+vehicle group, and the SAH+YC-1 group. Immunohistochemical staining and western blotting analyses revealed that the expression of HIF-1α and its downstream effectors, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and glucose transporter 1 (GLUT1), increased in the hippocampus 48h after the induction of SAH. YC-1 blocked this upregulation. The number of active caspase-3-positive cells and the expression of active caspase-3 in the hippocampus significantly increased in the YC-1 group relative to the vehicle group. A cell death assay further revealed that DNA fragmentation was significantly increased at 48h in the YC-1 group compared with the vehicle group. In Morris water maze (MWM) tests, the YC-1 group showed increased escape latency times and distances as well as reduced time spent and distance traveled in the target quadrant. These results indicate that hippocampal apoptosis increased and cognitive function deteriorated when HIF-1α was inhibited, suggesting that HIF-1α has a neuroprotective effect in SAH and may represent an effective therapeutic target.
Hu, Quan; Li, Tong; Wang, Lingxiao; Xie, Yunkai; Liu, Song; Bai, Xuemei; Zhang, Tiantian; Bo, Shishi; Xin, Danqing; Xue, Hao; Li, Gang; Wang, Zhen
The sonic hedgehog (Shh) signaling pathway plays a fundamental role in the central nervous system (CNS) development, but its effects on neural cell survival and brain repair after subarachnoid hemorrhage (SAH) has not been well-investigated. The present study was undertaken to evaluate the influence of an agonist of the Shh co-receptor Smoothened (Smo), purmorphamine (PUR), on early brain injury (EBI) as well as the underlying mechanisms after SAH. PUR was administered via an intraperitoneal injection with a dose of 0.5, 1, and 5 mg/kg at 2, 6, 24, and 46 h after SAH in rat model. The results showed that PUR treatment significantly ameliorated brain edema, improved neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex (PFC), associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. PUR also promoted phospho-ERK levels. Additionally, PUR treatment markedly decreased MDA concentration accompanied with the elevation in the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in PFC. Notably, PUR treatment significantly reversed the changes of Shh pathway mediators containing Patched, Gli1, and Shh by SAH insult, and the neuroprotection of PUR on SAH was blocked by Smo antagonist cyclopamine. These results indicated that PUR exerts neuroprotection against SAH-evoked injury in rats, mediated in part by anti-apoptotic and anti-oxidant mechanism, up-regulating phospho-ERK levels, mediating Shh signaling molecules in the PFC. PMID:28149272
Fujii, Mutsumi; Sherchan, Prativa; Krafft, Paul R; Rolland, William B; Soejima, Yoshiteru; Zhang, John H
Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. Peripheral leukocytes can infiltrate the injured brain, thereby aggravating BBB leakage and neuroinflammation. Thus, anti-inflammatory pharmacotherapies may ameliorate EBI and provide neuroprotection after SAH. Cannabinoid type 2 receptor (CB2R) agonism has been shown to reduce neuroinflammation; however, the precise protective mechanisms remain to be elucidated. This study aimed to evaluate whether the selective CB2R agonist, JWH133 can ameliorate EBI by reducing brain-infiltrated leukocytes after SAH. Adult male Sprague-Dawley rats were randomly assigned to the following groups: sham-operated, SAH with vehicle, SAH with JWH133 (1.0mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0mg/kg). SAH was induced by endovascular perforation, and JWH133 was administered 1h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24h after surgery. JWH133 improved neurological scores and reduced brain water content; however, SR144528 reversed these treatment effects. JWH133 reduced Evans blue dye extravasation after SAH. Furthermore, JWH133 treatment significantly increased TGF-β1 expression and prevented an SAH-induced increase in E-selectin and myeloperoxidase. Lastly, SAH resulted in a decreased expression of the tight junction protein zonula occludens-1 (ZO-1); however, JWH133 treatment increased the ZO-1 expression. We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-β1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH.
Azurmendi, Leire; Degos, Vincent; Tiberti, Natalia; Kapandji, Natacha; Sanchez-Peña, Paola; Sarrafzadeh, Asita; Puybasset, Louis; Turck, Natacha; Sanchez, Jean-Charles
OBJECT Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high rates of mortality and morbidity. The main predictor for the poor outcome is the World Federation of Neurosurgical Societies (WFNS) scale. However, this scale does not take into account proinflammatory events, such as infection occurring after the aSAH, which could modify the long-term status of patients. The aim of this study was to evaluate neopterin as an inflammatory biomarker for outcome and infection prediction in aSAH patients. METHODS Plasma concentrations of neopterin were measured in 61 aSAH patients (22 male and 39 female; mean age [± SD] 52.8 ± 11.8 years) using a commercial ELISA kit. Samples were collected daily for 10 days. Outcome at 12 months was determined using the Glasgow Outcome Scale (GOS) and dichotomized as poor (GOS score 1, 2, or 3) or good (GOS score 4 or 5). Infection was determined by the presence of a positive bacterial culture. RESULTS Patients with poor outcome at 12 months had higher concentrations of neopterin than patients with good outcome. In the same way, patients who had an infection during the hospitalization had significantly higher concentrations of neopterin than patients without infection (p = 0.001). Moreover, neopterin concentrations were significantly (p < 0.008) elevated in infected patients 2 days before infection detection and antibiotic therapy. CONCLUSIONS Neopterin is an efficient outcome predictor after aSAH. Furthermore, it is able to differentiate between infected and uninfected patients as early as 2 days before clinical signs of infection, facilitating earlier antibiotic therapy and better management.
Lin, Chun Fu; Hsu, Sanford P. C.; Lin, Chung Jung; Guo, Wan Yuo; Liao, Chih Hsiang; Chu, Wei Fa; Hung, Sheng Che; Shih, Yang Shin; Lin, Yen Tzu
Purpose We sought to imitate angiographic cerebral circulation time (CCT) and create a similar index from baseline CT perfusion (CTP) to better predict vasospasm in patients with subarachnoid hemorrhage (SAH). Methods Forty-one SAH patients with available DSA and CTP were retrospectively included. The vasospasm group was comprised of patients with deterioration in conscious functioning and newly developed luminal narrowing; remaining cases were classified as the control group. The angiography CCT (XA-CCT) was defined as the difference in TTP (time to peak) between the selected arterial ROIs and the superior sagittal sinus (SSS). Four arterial ROIs were selected to generate four corresponding XA-CCTs: the right and left anterior cerebral arteries (XA-CCTRA2 and XA-CCTLA2) and right- and left-middle cerebral arteries (XA-CCTRM2 and XA-CCTLM2). The CCTs from CTP (CT-CCT) were defined as the differences in TTP from the corresponding arterial ROIs and the SSS. Correlations of the different CCTs were calculated and diagnostic accuracy in predicting vasospasm was evaluated. Results Intra-class correlations ranged from 0.96 to 0.98. The correlations of XA-CCTRA2, XA-CCTRM2, XA-CCTLA2, and XA-CCTLM2 with the corresponding CT-CCTs were 0.64, 0.65, 0.53, and 0.68, respectively. All CCTs were significantly prolonged in the vasospasm group (5.8–6.4 s) except for XA-CCTLA2. CT-CCTA2 of 5.62 was the optimal cut-off value for detecting vasospasm with a sensitivity of 84.2% and specificity 82.4% Conclusion CT-CCTs can be used to interpret cerebral flow without deconvolution algorithms, and outperform both MTT and TTP in predicting vasospasm risk. This finding may help facilitate management of patients with SAH. PMID:26986626
Kohama, Misaki; Sugiyama, Shinichiro; Sato, Kenichi; Endo, Hidenori; Niizuma, Kuniyasu; Endo, Toshiki; Ohta, Makoto; Matsumoto, Yasushi; Fujimura, Miki; Tominaga, Teiji
Background Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. Methods This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. Results Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. Conclusions In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients. PMID:27665361
Migdal, Victoria L.; Wu, W. Kelly; Long, Drew; McNaughton, Candace D.; Ward, Michael J.; Self, Wesley H.
Objective To compare the risks and benefits of lumbar puncture (LP) to evaluate for subarachnoid hemorrhage (SAH) after a normal head computed tomography (CT) scan. Methods This was an observational study of adult emergency department (ED) patients at a single hospital who presented with headache and underwent LP after a normal head CT to evaluate for SAH. LP results classified as indicating a SAH included: xanthochromia in cerebrospinal fluid (CSF); or red blood cells in the final tube of CSF with an aneurysm or arteriovenous malformation on cerebral angiography. An LP-related complication was defined as hospitalization or a return visit due to symptoms attributed to the LP. Proportions of the study patients who had SAH diagnosed by LP and who experienced an LP-related complication were compared. Results The study included 302 patients, including 2 (0.66%) who were diagnosed with SAH based on LP (number-needed-to diagnose: 151); both of these patients had a known intracranial aneurysm. Eighteen (5.96%) patients experienced a LP-related complication (p<0.01 compared to number with SAH diagnosed; number-needed-to-harm: 17). Complications included 12 patients with low-pressure headaches, 4 with pain at the LP site, and 2 with contaminated CSF cultures. Conclusion The yield of LP for diagnosing SAH in adults with nontraumatic headache after a normal head CT was very low. The severity of LP-related complications was low, but complications were more common than SAH diagnoses. LP may not be advisable after a normal head CT to evaluate for SAH, particularly in patients with low-risk clinical features for SAH. PMID:26189054
Kitami, K; Suzuki, A; Hadeishi, H; Nishimura, H; Yasui, N
Twenty-four adult cases of suspected normal pressure hydrocephalus (NPH) after subarachnoid hemorrhage (SAH) were investigated clinically from the aspect of predicting the efficacy of the shunting procedure. They consisted of 13 men and 11 women, with the mean age of 55-y-o. In addition to checking neurological signs, pre- and postoperative CT scans, RI (or CT) cisternography and bolus infusion test were performed in each of them. Shunt surgery was done, all of which ventriculoperitoneal shunt, in 17 patients. They were divided into three groups, namely, shunt effective group (A), neurologically unchanged group after surgery (B) and worsened group (C). The A group had 8 cases, B had 8 also and C contained only one. Effectiveness of shunt procedure was measured by an improvement in the activity of daily life (ADL). Compared with group B, group A tended to have more cases of delayed onset of NPH (mean days of 112 from SAH attack in group A while 55 days in group B), cases with "trias" (3 against 0) and moderate ventricular dilatation with periventricular lucency (8 against 2). The finding of delayed clearance in cisternogram did not make an accurate judgement in the efficacy of shunt surgery. By using the bolus method of infusion test, the true cause of shunt non-effective ventricular dilatation was suggested to the disturbance of cerebral blood circulation due to elevation of intracranial venous outflow resistance. This suggestion was elicited by the analysis of pressure response curve gained from the bolus injection, in which group A cases mainly reached the baseline pressure within 22 minutes, but on the contrary group B showed more than 22 minutes as a rule.(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider, Harald J; Schneider, Manfred; Kreitschmann-Andermahr, Ilonka; Tuschy, Ulrich; Wallaschofski, Henri; Fleck, Steffen; Faust, Michael; Renner, Caroline I E; Kopczak, Anna; Saller, Bernhard; Buchfelder, Michael; Jordan, Martina; Stalla, Günter K
Clinical studies have demonstrated that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. This study aimed to assess the prevalence and associated factors of post-traumatic hypopituitarism in a large national registry of patients with TBI and SAH. Data were collected from 14 centers in Germany and Austria treating patients for TBI or SAH and performing endocrine assessments. Data were collected using a structured, internet-based study sheet, obtaining information on clinical, radiological, and hormonal parameters. A total of 1242 patients (825 TBI, age 43.5±19.7 years; 417 SAH, age 49.7±11.8 years) were included. We studied the prevalence of hypopituitarism reported based on different definitions of laboratory values and stimulation tests. Stimulation tests for the corticotropic and somatotropic axes were performed in 26% and 22% of the patients, respectively. The prevalence of hypopituitarism in the chronic phase (at least 5 months after the event) by laboratory values, physician diagnoses, and stimulation tests, was 35%, 36%, and 70%, respectively. Hypopituitarism was less common in the acute phase. According to the frequency of endocrine dysfunction, pituitary hormone secretion was impaired in the following sequence: ACTH, LH/FSH, GH, and TSH. TBI patients with abnormal stimulation tests had suffered from more severe TBI than patients with normal stimulation tests. In conclusion, our data confirm that hypopituitarism is a common complication of TBI and SAH. It is possible that patients with a higher likelihood of hypopituitarism were selected for endocrine stimulation tests.
Bai, Shutang; Wang, Zhiheng; Zhang, Liang; Fu, Hongdu; Zhuang, Huanwei; Cao, Xianjun; Liang, Liming; Yang, Yanqi
Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit.
Koskimäki, Janne; Tarkia, Miikka; Ahtola-Sätilä, Tuula; Saloranta, Lasse; Laakso, Aki; Frantzén, Janek
Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. PMID:25685803
Jun, P.; Ko, N.U.; English, J.D.; Dowd, C.F.; Halbach, V.V.; Higashida, R.T.; Lawton, M.T.; Hetts, S.W.
BACKGROUND AND PURPOSE CV following aneurysmal SAH is a significant cause of morbidity and mortality. We review our experiences using PTA and IA verapamil infusion for treating medically refractory cases. MATERIALS AND METHODS We performed a retrospective review of patients with SAH admitted from July 2003 to January 2008. RESULTS Of 546 patients admitted within 72 hours of symptom onset, 231 patients (42%) developed symptomatic CV and 189 patients (35%) required endovascular therapy. A total of 346 endovascular sessions were performed consisting of 1 single angioplasty, 286 IA verapamil infusions, and 59 combined treatments. PTA was performed on 151 vessel segments, and IA verapamil was infused in 720 vessel segments. IA verapamil doses ranged from 2.0 to 30.0 mg per vessel segment and from 3.0 to 55.0 mg per treatment session. Repeat treatments were necessary in 102 patients (54%) for persistent, recurrent, or worsening CV. There were 6 treatment-related complications, of which 2 resulted in clinical worsening. No deaths were attributable to endovascular therapy. At follow-up, 115 patients (61%) had a good outcome and 55 patients (29%) had a poor outcome. Sixteen patients died from causes related to SAH, while 3 died from other medical complications. CONCLUSIONS Endovascular treatments are an integral part of managing patients with medically refractory CV. In our experience, PTA and IA verapamil are safe, with a low complication rate, but further studies are required to determine appropriate patient selection and treatment efficacy. PMID:20616179
de Oliveira, Jean G; Beck, Jürgen; Ulrich, Christian; Rathert, Julian; Raabe, Andreas; Seifert, Volker
Cerebral vasospasm is one of the most important complications of aneurysmal subarachnoid hemorrhage. The effect of aneurysm occlusion technique on incidence of vasospasm is not exactly known. The objective was to analyze surgical clipping versus endovascular coiling on the incidence of cerebral vasospasm and its consequences. Using the MEDLINE PubMed (1966-present) database, all English-language manuscripts comparing patients treated by surgical clipping with patients treated by endovascular coiling, regarding vasospasm incidence after aneurysmal subarachnoid hemorrhage, were analyzed. Data extracted from eligible studies included the following outcome measures: incidence of total vasospasm, symptomatic vasospasm, ischemic infarct vasospasm-induced and delayed ischemic neurological deficit (DIND). A pooled estimate of the effect size was computed and the test of heterogeneity between studies was carried out using The Cochrane Collaboration's Review Manager software, RevMan 4.2. Nine manuscripts that fulfilled the eligibility criteria were included and analyzed. The studies differed substantially with respect to design and methodological quality. The overall results showed no significant difference between clipping and coiling regarding to outcome measures. According to the available data, there is no significant difference between the types of technique used for aneurysm occlusion (clipping or coiling) on the risk of cerebral vasospasm development and its consequences.
Tanabe, Masaki; Crago, Elizabeth A.; Suffoletto, Matthew S.; Hravnak, Marilyn; Frangiskakis, J. Michael; Kassam, Amin B.; Horowitz, Michael B.; Gorcsan, John
An increase in cardiac troponin I (cTnI) occurs often after aneurysmal subarachnoid hemorrhage (SAH), but its significance is not well understood. One hundred three patients with SAH were prospectively evaluated in the SAHMII Study to determine the relations of cTnI to clinical severity, systolic and diastolic cardiac function, pulmonary congestion, and length of intensive care unit stay. Echocardiographic ejection fraction, wall motion score, mitral inflow early diastolic (E) and mitral annular early (E′) velocities were assessed. Thirty patients (29%) had mildly positive cTnI (0.1 to 1.0 ng/ml), 24 (23%) had highly positive cTnI (>1.0 ng/ml), and 49 (48%) had negative cTnI (<0.1 ng/ml). Highly positive cTnI was associated with worse neurologic disease, longer intensive care unit stay, and slight depression of ejection fraction (51 ± 11% [p <0.05] vs 59 ± 8% and 63 ± 6% in mildly positive or negative cTnI groups, respectively). Highly positive cTnI was also associated with abnormal wall motion acutely (>1.31 ng/ml; 76% sensitivity, 91% specificity), which typically resolved within 5 to 10 days. Both mildly or highly positive cTnI were associated with acute diastolic dysfunction, with E/E′ of 17 ± 6 and 16 ± 6 (both p <0.05) vs 13 ± 4 in patients with negative cTnI. Prevalences of pulmonary congestion were 79% (p <0.05) in patients with highly positive cTnI, 53% (p <0.05) in patients with mildly positive cTnI, and 29% in cTnI-negative patients. In conclusion, highly positive cTnI with SAH was associated with clinical neurologic severity, systolic and diastolic cardiac dysfunction, pulmonary congestion, and longer intensive care unit stay. Even mild increases in cTnI were associated with diastolic dysfunction and pulmonary congestion. PMID:19026312
Eide, Per K.; Rapoport, Benjamin I.; Gormley, William B.; Madsen, Joseph R.
Object In the search for optimal monitoring and predictive tools in neurocritical care, the relationship of the pulsatile component of intracranial pressure (ICP) and the pressure itself has long been of great interest. Higher pressure often correlates with a higher pulsatile response to the heartbeat, interpreted as a type of compliance curve. Various mathematical approaches have been used, but regardless of the formula used, it is implicitly assumed that a reproducible curve exists. The authors investigated the stability of the correlation between static and pulsatile ICPs in patients with subarachnoid hemorrhage (SAH) who were observed for several hours by using data sets large enough to allow such calculations to be made. Methods The ICP recordings were obtained in 39 patients with SAH and were parsed into 6-second time windows (1,998,944 windows in 197 recordings). The ICP parameters were computed for each window as follows: static ICP was defined as the mean ICP, and pulsatile ICP was characterized by mean ICP wave amplitude, rise time, and rise time coefficient. Results The mean ICP and ICP wave amplitudes were simultaneously high or low (the expected correlation) in only ~ 60% of observations. Furthermore, static and pulsatile ICP correlated well only over short intervals; the degree of correlation weakened over periods of hours and was inconsistent across patients and within individual patients over time. Decorrelation originated with abrupt shifting and gradual drifting of mean ICP and ICP wave amplitude over several hours. Conclusions The relationship between the static and pulsatile components of ICPs changes over time. It evolves, even in individual patients, over a number of hours. This can be one reason the observation of high pulsatile ICP (indicative of reduced intracranial compliance) despite normal mean ICP that is seen in some patients with SAH. The meaning and potential clinical usefulness of such changes in the curves is uncertain, but it
Axier, Aximujiang; Amuti, Maiwulanjiang; Guohua, Zhu; Xiaojiang, Cheng; Kadeer, Kaheerman; Xixian, Wang; Geng, Dangmurenjiafu; Maimaitili, Aisha
Introduction Cerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH. Methods We retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction. Results 343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3–4) and poor Hunt-Hess grade (4–5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ≥53 years, leukocyte count ≥11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ≥11× 109/L on admission and aneurysm size ≥ 10 mm were independent risk factors of SV. Serum glucose level ≥7.0 mmol/L on admission was an independent risk factor of AV. Conclusion Risk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend
Egeto, Peter; Loch Macdonald, R; Ornstein, Tisha J; Schweizer, Tom A
OBJECTIVE Subarachnoid hemorrhage (SAH) is treated with either surgical clipping or endovascular coiling, though the latter is the preferred treatment method given its more favorable functional outcomes. However, neuropsychological functioning after treatment is rarely taken into account. In this meta-analysis, the authors synthesized relevant data from the literature and compared neuropsychological functioning in patients after coiling and clipping of SAH. They hypothesized that the coiled patients would outperform the clipped patients; that group differences would be greater with higher posterior circulation rupture rates, in older patients, and in more recent publications; that group differences would be smaller with greater rates of middle cerebral artery (MCA) rupture; and that anterior communicating artery (ACoA) rupture rates would not influence effect sizes. METHODS The MEDLINE, Embase, and PsycINFO databases were searched for clinical studies that compared neuropsychological functioning after either endovascular coiling or surgical clipping for SAH. Hedge's g and 95% confidence intervals were calculated using random effects models. Patients who had undergone coiling or clipping were compared on test performance in 8 neuropsychological domains: executive functions, language, attention/processing speed, verbal memory, visual memory, spatial memory, visuospatial functions, and intelligence. Patients were also compared with healthy controls, and meta-regressions were used to explore the relation between effect sizes and publication year, delay between treatment and neuropsychological testing, mean patient age, and rates of posterior circulation, ACoA, and MCA ruptures. RESULTS Thirteen studies with 396 clipped cases, 314 coiled cases, and 169 healthy controls were included in the study. The coil-treated patients outperformed the clip-treated patients on executive function (g = 0.17, 95% CI 0.08-0.25) and language tests (g = 0.23, 95% CI 0.07-0.39), and all
Joo, Hye Myung; Lee, Sung Jae; Chung, Yong Gu
Objective In this study, the Mindfulness Based Stress Reduction (MBSR) program was applied to patients presenting with depression and anxiety after surgery from spontaneous subarachnoid hemorrhage (SAH) and the effects were assessed. Methods The subjects were patients admitted for cerebral aneurysm rupture and treated by means of surgery from March to December, 2007. More than 6 months had passed after surgery, without any special lesions showing up on computed tomography (CT), and the Glasgow outcome scale (GOS) was 5 points. Among patients with anxiety and depression symptoms, 11 patients completed the program. The MBSR program was conducted once a week, 2.5 hours each, for 8 weeks. The evaluation criteria were : 1) the Beck Depression Inventory (BDI): it measures the type and level of depression, 2) the State-Trait Anxiety Inventory : the anxiety state of normal adults without mental disorder, and 3) Heart Rate Variability (HRV) : the influence of the autonomous nervous system on the sinoarterial node varies continuously in response to the change of the internal/external environment. Results The BDI value was decreased from 18.5 ± 10.9 to 9.5 ± 7.1 (p = 0.013) : it was statistically significant, and the depression level of patients was lowered. The state anxiety was decreased from 51.3 ± 13.9 to 42.3 ± 15.2; the trait anxiety was reduced from 50.9 ± 12.3 to 41.3 ± 12.8, and a borderline significant difference was shown (p = 0.091, p = 0.056). In other words, after the treatment, although it was not statistically significant, a decreased tendency in anxiety was shown. In the HRV measurement, standard deviation normal to normal (SDNN), square root of the square root of the mean sum of squared differences between adjacent normal to normal intervals (RMSSD), and total power (TP) showed significant increase, Physical Stress Index (PSI) showed a significant reduction, and thus an improvement in the homeostatic control mechanism of the autonomic nervous system
Daftari Besheli, Laleh; Tan, Can Ozan; Bell, Donnie L.; Hirsch, Joshua A.; Gupta, Rajiv
Intra-arterial (IA) vasodilator therapy is one of the recommended treatments to minimize the impact of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm refractory to standard management. However, its usefulness and efficacy is not well established. We evaluated the effect IA vasodilator therapy on middle cerebral artery blood flow and on discharge outcome. We reviewed records for 115 adults admitted to Neurointensive Care Unit to test whether there was a difference in clinical outcome (discharge mRS) in those who received IA infusions. In a subset of 19 patients (33 vessels) treated using IA therapy, we tested whether therapy was effective in reversing the trends in blood flow. All measures of MCA blood flow increased from day -2 to -1 before infusion (maximum Peak Systolic Velocity (PSV) 232.2±9.4 to 262.4±12.5 cm/s [p = 0.02]; average PSV 202.1±8.5 to 229.9±10.9 [p = 0.02]; highest Mean Flow Velocity (MFV) 154.3±8.3 to 172.9±10.5 [p = 0.10]; average MFV 125.5±6.3 to 147.8±9.5 cm/s, [p = 0.02]) but not post-infusion (maximum PSV 261.2±14.6 cm/s [p = .89]; average PSV 223.4±11.4 [p = 0.56]; highest MFV 182.9±12.4 cm/s [p = 0.38]; average MFV 153.0±10.2 cm/s [p = 0.54]). After IA therapy, flow velocities were consistently reduced (day X infusion interaction p<0.01 for all measures). However, discharge mRS was higher in IA infusion group, even after adjusting for sex, age, and admission grades. Thus, while IA vasodilator therapy was effective in reversing the vasospasm-mediated deterioration in blood flow, clinical outcomes in the treated group were worse than the untreated group. There is need for a prospective randomized controlled trial to avoid potential confounding effect of selection bias. PMID:28339483
Desai, Nirmit; Patel, Sagar; Nwosu, Chinyere; Sung, Lok; Buscaglia, Jonathan M.; Nord, Edward P.; Wadhwa, Nand K.
We present a case of a patient with a failed pancreaticoduodenal allograft with exocrine enteric-drainage who developed catastrophic gastrointestinal (GI) hemorrhage. Over the course of a week, she presented with recurrent GI bleeds of obscure etiology. Multiple esophago-gastro-duodenoscopic (EGD) and colonoscopic evaluations failed to reveal the source of the hemorrhage. A capsule endoscopy and a technetium-labeled red blood cells (RBC) imaging study were similarly unrevealing for source of bleeding. She subsequently developed hemorrhagic shock requiring emergent superior mesenteric arteriography. Run off images revealed an external iliac artery aneurysm with fistulization into the jejunum. Coiled embolization was attempted but abandoned because of hemodynamic instability. Deployment of a covered endovascular stent into the right external iliac artery over the fistula site resulted in immediate hemodynamic stabilization. A high index of suspicion for arterioenteric fistulae is needed for diagnosis of this uncommon but eminently treatable form of GI hemorrhage in this patient population. PMID:24455393
Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H; Chen, Yujie; Feng, Hua
Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia.
Longatti, Pierluigi; Giombelli, Ermanno; Pavesi, Giacomo; Carteri, Alessandro; Feletti, Alberto
For a curious and extraordinary coincidence, 5 of the 7 most relevant leaders of the Italian Communist Party (Partito Comunista Italiano, which was established in 1921, has been the biggest Communist Party in Western Countries) suffered a cerebral stroke. Cerebrovascular diseases afflicted also Stalin and Lenin, and a number of Presidents of the United States. We present the stories of 2 important Italian political leaders who shared both the leadership role of the major left Italian Party and the dramatic experience of a subarachnoid hemorrhage. Retracing their medical incidents, separated by 50 years of history, we show how a fatal medical disease has become neurosurgical and successfully cured thanks to the advances of neurosurgery, neuroradiology, and hospital organization. A neurologic disease that was disgraceful 50 years ago has lost any disquieting and embarrassing significance in the present time to the light of evolution of vascular neurosurgery.
Delgado, T.J.; Diemer, N.H.; Svendgaard, N.A.
A double-isotope autoradiographic technique was used to evaluate CBF and glucose metabolism 2 days after a subarachnoid hemorrhage (SAH) in rats with lesions in the lower brainstem. Lesioning in the mesencephalon of the ascending catecholamine pathways from locus ceruleus and from the A1 and A2 nuclei, or lesioning in the medulla oblongata of the ascending fibers from A1 and A2, prevents the development of the global changes in flow and metabolism seen in normal animals post SAH. Also the focal low-flow areas with markedly elevated deoxyglucose uptake, which can develop in normal animals 2 days post SAH, were not seen in the lesioned animals after the SAH. The findings indicate that the A1 and A2 nuclei, which project to the hypothalamus-pituitary, are essential for the flow and metabolic changes after an SAH. The lesions per se did not change baseline flow and metabolism as compared with sham-lesioned animals.
Kumar, Gyanendra; Shahripour, Reza Bavarsad; Harrigan, Mark R
OBJECT The impact of transcranial Doppler (TCD) ultrasonography evidence of vasospasm on patient-centered clinical outcomes following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Vasospasm is known to lead to delayed cerebral ischemia (DCI) and poor outcomes. This systematic review and meta-analysis evaluates the predictive value of vasospasm on DCI, as diagnosed on TCD. METHODS MEDLINE, Scopus, the Cochrane trial register, and clinicaltrials.gov were searched through September 2014 using key words and the terms "subarachnoid hemorrhage," "aneurysm," "aneurysmal," "cerebral vasospasm," "vasospasm," "transcranial Doppler," and "TCD." Sensitivities, specificities, and positive and negative predictive values were pooled by a DerSimonian and Laird random-effects model. RESULTS Seventeen studies (n = 2870 patients) met inclusion criteria. The amount of variance attributable to heterogeneity was significant (I(2) > 50%) for all syntheses. No studies reported the impact of TCD evidence of vasospasm on functional outcome or mortality. TCD evidence of vasospasm was found to be highly predictive of DCI. Pooled estimates for TCD diagnosis of vasospasm (for DCI) were sensitivity 90% (95% confidence interval [CI] 77%-96%), specificity 71% (95% CI 51%-84%), positive predictive value 57% (95% CI 38%-71%), and negative predictive value 92% (95% CI 83%-96%). CONCLUSIONS TCD evidence of vasospasm is predictive of DCI with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aSAH due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed.
Ma, Chunxiao; Zhou, Wei; Yan, Zhaoyue; Qu, Mingqi; Bu, Xingyao
Toll-like receptor 4 (TLR4) is one of key players in regulation of inflammation. Animal experiments have suggested an important role of TLR4 in the pathophysiology of subarachnoid hemorrhage (SAH). In present study, TLR4 is investigated in clinical SAH patients to explore its clinical significance. 30 patients with aneurysmal subarachnoid hemorrhage (aSAH) and 20 healthy control patients (HC) were enrolled in this prospective study. Blood samples were collected on days 1, 3 and 7 after admission. TLR4 expression level on cell surface of peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and presented as mean fluorescence intensity (MFI). Patients were clinically assessed every day after admission to monitor the occurrence of delayed cerebral ischemia (DCI). Participants were followed up until completion of 3 months after SAH. Functional outcome was defined by modified Rankin score (mRs). Results show that SAH patients presented a significantly higher TLR4 levels on days 1 and 3 post SAH compared to HC; TLR4 levels in SAH patients on day 1 was highest compared with that on days 3 and 7 and in HC. TLR4 of SAH patients on day 7 declined to the level showing no significant difference with that of HC. In patients with Hunt-Hess grades I-III lower TLR4 levels were observed. Patients with DCI showed significantly higher TLR4 levels than those without DCI. High TLR4 levels were statistically significantly associated with poor functional outcome after 3 months. Logistic regression analysis showed that TLR4 level on day 1 was independent predictor for DCI and 3-month poor neurological outcome of aneurysmal SAH patients. In summary, admission TLR4 level on PBMCs (day 1) is an independent risk factor to predict the occurrence of DCI and 3-month poor neurological outcome in aneurysmal SAH patients.
Jo, Kyung-Il; Kim, Min Soo; Yeon, Je Young; Kim, Jong-Soo
Objective Hemorrhagic moyamoya disease (hMMD) is associated with a poor clinical course. Furthermore, poorer clinical outcomes occur in cases of recurrent bleeding. However, the effect of hemodynamic insufficiency on rebleeding risk has not been investigated yet. This study evaluated the prognostic implications of the perfusion status during the clinical course of adult hMMD. Methods This retrospective study enrolled 52 adult hMMD patients between April 1995 and October 2010 from a single institute. Demographic data, clinical and radiologic characteristics, including hemodynamic status using single photon emission computed tomography (SPECT), and follow up data were obtained via a retrospective review of medical charts and imaging. Statistical analyses were performed to explore potential prognostic factors. Results Hemodynamic abnormality was identified in 44 (84.6%) patients. Subsequent revascularization surgery was performed in 22 (42.3%) patients. During a 58-month (median, range 3–160) follow-up assessment period, 17 showed subsequent stroke (hemorrhagic n=12, ischemic n=5, Actuarial stroke rate 5.8±1.4%/year). Recurrent hemorrhage was associated with decreased basal perfusion (HR 19.872; 95% CI=1.196–294.117) and omission of revascularization (10.218; 95%; CI=1.532–68.136). Conclusion Decreased basal perfusion seems to be associated with recurrent bleeding. Revascularization might prevent recurrent stroke in hMMD by rectifying the perfusion abnormality. A larger-sized, controlled study is required to address this issue. PMID:26962416
Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie
Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression.
Tao, Chuanyuan; Fan, Chaofeng; Hu, Xin; Ma, Junpeng; Ma, Lu; Li, Hao; Liu, Yi; Sun, Hong; He, Min; You, Chao
Abstract Background: Shunt-dependent hydrocephalus (SDH) is a well-known sequela following aneurysmal hemorrhage, adversely affecting the outcome after securing ruptured aneurysm. Fenestration of lamina terminalis (FLT) creates an anterior ventriculostomy, facilitates cerebrospinal fluid circulation and clot clearance in the basal cistern. However, controversy exists over whether microsurgical FLT during aneurysm repair can decrease the incidence of SDH. Aims: The study is designed to determine the efficacy of lamina terminalis fenestration on the reduction of SDH after aneurysm clipping. Methods/Design: A total of 288 patients who meet the inclusion criteria will be randomized into single aneurysm clipping or aneurysm clipping plus FLT in the Department of Neurosurgery, West China Hospital. Follow-up was performed 1, 3, 6, and 12 months after aneurysm clipping. The primary outcome is the incidence of SDH and the secondary outcomes include cerebral vasospasm, functional outcome evaluated by the modified Rankin Scale and Extended Glasgow Outcome Scale, and mortality. Discussion: The FISH trial is a large randomized, parallel controlled clinical trial to define the therapeutic value of FLT, the results of which will help to guide the surgical procedure and resolve the long-puzzled debate in the neurosurgical community. Conclusions: This protocol will determine the efficacy of FLT in the setting of aneurysmal subarachnoid hemorrhage. Trial registration identifier: http://www.chictr.org.cn/edit.aspx?pid=15691&htm=4 Chinese Clinical Trial Registry: ChiCTR-INR-16009249. PMID:28033279
Nambu, Iku; Uchiyama, Naoyuki; Misaki, Kouichi; Mohri, Masanao; Nakada, Mitsutoshi
Background: We report the concurrence of a spinal dural arteriovenous fistula (DAVF) and multiple perimedullary arteriovenous fistulas (PAVFs) presenting with subarachnoid hemorrhage (SAH). Moreover, the bleeding site was detected 1 month after onset. Case Description: A 56-year-old man was admitted to our hospital with an SAH. A DAVF and two PAVFs were detected at the C2 level by two rounds of digital subtraction angiography. The source of bleeding, an aneurysm on the feeding artery of PAVF, was detected at the second angiogram, which was performed 1 month after the onset of SAH. The aneurysm was not demonstrated at initial angiogram because of thrombosis in the aneurysm. The DAVF was interrupted by transarterial embolization, and the two PAVFs were subsequently treated with surgery. Conclusion: A part of the whole AVFs or the source of bleeding may be invisible in the acute stage just after hemorrhage. Repeated angiography is necessary to diagnose such complex AVFs especially in case of an SAH and treatment should be performed during the subacute stage. PMID:28217381
Akdag, Arzu; Arici, Sule; Kaya, Mete; Turgut, Ahmet
Pulmonary sequestration is acystic or solid congenital lung malformation comprised of non functional lung tissue that does not communicate with the normal tracheobronchial tree and has a systemic arterial blood supply. There are two forms of sequestration: intralobar and extralobar. Its treatment is surgical resection. Here we presented a case of premature neonate with extralobar pulmonary sequestration who had respiratory failure and recurrent pulmonary hemorrhage. Following surgery, the patient showed significant clinical improvement.
Nataraju, Kamalesh Tagadur; Mukherjee, Tirthankar; Doddaiah, Ramachandra Prabhu Hosahalli; Nanjappa, Nagesh Gabbadi; Narasegowda, Lakshmikanth
Arteriovenous malformation (AVM) is a rare vascular anomaly of the lung, which manifests predominantly as dyspnea (due to right to left shunting) and paradoxical embolism. Hereditary Hemorrhagic Telangiectasia (HHT) being a rare genetic disorder is one of the most common causes of pulmonary arteriovenous malformation (PAVM). Here we report an interesting case of recurrent anemia in an elderly female, who was subsequently found to have multiple cutaneous and mucosal telangiectasias and a large pulmonary AVM. PMID:26180392
Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H.; Chen, Yujie; Feng, Hua
Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia. PMID:27698742
Schmidt, Linnea Boegeskov; Goertz, Sanne; Wohlfahrt, Jan; Melbye, Mads; Munch, Tina Noergaard
Background Intracerebral hemorrhage (ICH) is a disease with high mortality and a substantial risk of recurrence. However, the recurrence risk is poorly documented and the knowledge of potential predictors for recurrence among co-morbidities and medicine with antithrombotic effect is limited. Objectives 1) To estimate the short- and long-term cumulative risks of recurrent intracerebral hemorrhage (ICH). 2) To investigate associations between typical comorbid diseases, surgical treatment, use of medicine with antithrombotic effects, including antithrombotic treatment (ATT), selective serotonin reuptake inhibitors (SSRI’s), and nonsteroidal anti-inflammatory drugs (NSAID’s) with recurrent ICH. Methods The cohort consisted of all individuals diagnosed with a primary ICH in Denmark 1996–2011. Information on comorbidities, surgical treatment for the primary ICH, and the use of ATT, SSRI’s and NSAID’s was retrieved from the Danish national health registers. The cumulative recurrence risk of ICH was estimated using the Aalen-Johansen estimator, thus taking into account the competing risk of death. Associations with potential predictors of recurrent ICH were estimated as rate ratios (RR’s) using Poisson regression. Propensity score matching was used for the analyses of medicine with antithrombotic effects. Results Among 15,270 individuals diagnosed with a primary ICH, 2,053 recurrences were recorded, resulting in cumulative recurrence risk of 8.9% after one year and 13.7% after five years. Surgical treatment and renal insufficiency were associated with increased recurrence risks (RR 1.64, 95% CI 1.39–1.93 and RR 1.72, 95% CI 1.34–2.17, respectively), whereas anti-hypertensive treatment was associated with a reduced risk (RR 0.82, 95% CI 0.74–0.91). We observed non-significant associations between the use of any of the investigated medicines with antithrombotic effect (ATT, SSRI’s, NSAID’s) and recurrent ICH. Conclusions The substantial short-and long
Tang, Qi-Feng; Lu, Shi-Qi; Zhao, Yi-Ming; Qian, Jin-Xian
The aim of this study was to investigate the role of Von Willebrand Factor/thrombospondin type I repeats-13 (VWF/ADAMTS13) balance in aSAH. Fifty eight patients with aSAH at the First Affiliated hospital of Soochow University, Suzhou, China, between January 2012 and January 2014 were eligible for the study. They were divided into delayed cerebral ischemia group (DCI group) and non-delayed cerebral ischemia group (no DCI group), or cerebral vasospasm group (CVS group) and no spasm group (no CVS group), or good outcome group and poor outcome group. The control group consisted of twenty healthy people. All patients underwent CT, DSA, or (and) CTA diagnosed with intracranial subarachnoid hemorrhage which is caused by aneurysm rupture. Venous blood was drawn in tubes at 3 time points: 1 day after SAH (T1), (4±1) days after SAH (T2), and (9±1) days after SAH (T3) to determine plasma concentrations of ADAMTS13, VWF, P-selectin and IL-6 via enzyme-linked immunosorbent assay (ELISA). Transcranial doppler sonography (TCD) was used to measure mean blood flow velocity of the middle cerebral artery (VMCA). Glasgow Outcome Scale (GOS) was measured before discharge. Among 58 patients, 12 (20.7%) had DCI, 40 (68.9%) had TCD evidence of CVS, and 20 (34.5%) had poor outcome. The concentrations of VWF, P-selectin and IL-6 on T1, T2 and T3 after SAH were significantly higher in DCI, CVS and poor outcome groups compared with those of the control group (P < 0.05). The concentrations of VWF, P-selectin and IL-6 were significantly higher in DCI, CVS and poor outcome groups compared with those of the no DCI, no CVS and good outcome groups. The activity of ADAMTS13 was lower in DCI and poor outcome groups compared with those of the no DCI and good outcome groups (P < 0.05). The activity of ADAMTS13 showed no difference in CVS group and no CVS group (P > 0.05). The results of our study suggest that the increased VWF and decreased ADAMTS13 activity were associated with DCI and poor outcome
Zhang, Tingting; Su, Jingyuan; Guo, Bingyu; Wang, Kaiwen; Li, Xiaoming; Liang, Guobiao
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption.
Zhang, Hongrong; Jiang, Li; Guo, Zongduo; Zhong, Jianjun; Wu, Jingchuan; He, Junchi; Liu, Han; He, Zhaohui; Wu, Haitao; Cheng, Chongjie; Sun, Xiaochuan
Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARβ/δ on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPARβ/δ-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that Ad-PPARβ/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARβ/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia.
Wang, Zhong; Wang, Yibin; Tian, Xiaodi; Shen, Haitao; Dou, Yang; Li, Haiying; Chen, Gang
Transient receptor potential channel 1/4 (TRPC1/4) are considered to be related to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. In this study, a SAH rat model was employed to study the roles of TRPC1/4 in the early brain injury (EBI) after SAH. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. The protein levels of TRPC1/4 increased and peaked at 5 days after SAH in rats. Inhibition of TRPC1/4 by SKF96365 aggravated SAH-induced EBI, such as cortical cell death (by TUNEL staining) and degenerating (by FJB staining). In addition, TRPC1/4 overexpression could increase calcineurin activity, while increased calcineurin activity could promote the dephosphorylation of N-methyl-D-aspartate receptor (NMDAR). Calcineurin antagonist FK506 could weaken the neuroprotection and the dephosphorylation of NMDAR induced by TRPC1/4 overexpression. Contrarily, calcineurin agonist chlorogenic acid inhibited SAH-induced EBI, even when siRNA intervention of TRPC1/4 was performed. Moreover, calcineurin also could lead to the nuclear transfer of nuclear factor of activated T cells (NFAT), which is a transcription factor promoting the expressions of TRPC1/4. TRPC1/4 could inhibit SAH-induced EBI by supressing the phosphorylation of NMDAR via calcineurin. TRPC1/4-induced calcineurin activation also could promote the nuclear transfer of NFAT, suggesting a positive feedback regulation of TRPC1/4 expressions.
Huang, Wei; Huang, Yong; Huang, Ren-qiang; Gu, Jin-mao; Dong, Yan
Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH. PMID:28053989
Wu, Pei; Li, Yuchen; Zhu, Shiyi; Wang, Chunlei; Dai, Jiaxing; Zhang, Guang; Zheng, Bingjie; Xu, Shancai; Wang, Ligang; Zhang, Tongyu; Zhou, PeiQuan; Zhang, John H; Shi, Huaizhang
Mdivi-1 is a selective inhibitor of mitochondrial fission protein, Drp1, and can penetrate the blood-brain barrier. Previous studies have shown that Mdivi-1 improves neurological outcomes after ischemia, seizures and trauma but it remains unclear whether Mdivi-1 can attenuate early brain injury after subarachnoid hemorrhage (SAH). We thus investigated the therapeutic effect of Mdivi-1 on early brain injury following SAH. Rats were randomly divided into four groups: sham; SAH; SAH + vehicle; and SAH + Mdivi-1. The SAH model was induced by standard intravascular perforation and all of the rats were subsequently sacrificed 24 h after SAH. Mdivi-1 (1.2 mg/kg) was administered to rats 30 min after SAH. We found that Mdivi-1 markedly improved neurologic deficits, alleviated brain edema and BBB permeability, and attenuated apoptotic cell death. Mdivi-1 also significantly reduced the expression of cleaved caspase-3, Drp1 and p-Drp1((Ser616)), attenuated the release of Cytochrome C from mitochondria, inhibited excessive mitochondrial fission, and restored the ultra-structure of mitochondria. Furthermore, Mdivi-1 reduced levels of MDA, 3-NT, and 8-OHdG, and improved SOD activity. Taken together, our data suggest that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress.
Hao, Guangzhi; Dong, Yushu; Huo, Rentao; Wen, Kai; Zhang, Yinsong; Liang, Guobiao
As is known to all, neuroinflammation plays a vital role in early brain injury pathogenesis following subarachnoid hemorrhage (SAH). It has been shown that rutin have a property of inhibiting inflammation in many kinds of animal models. However, the effect of rutin on neuroinflammation after SAH remains uninvestigated. In this study, we investigated the potential effects of rutin on neuroinflammation and the underlying mechanism in an experimental rat model of SAH performed by endovascular perforation. Adult male SD rats were randomly divided into three groups, including sham group, SAH + vehicle group and SAH + rutin group (50 mg/kg) intraperitoneally (i.p.) administered at 30 min after SAH. After sacrificed at 24 h after SAH, all rats were examined by following tests, including neurologic scores, blood-brain barrier permeability, brain water content and neuronal cell death in cerebral cortex. The level of inflammation in brain was estimated by means of multiple molecules, including RAGE, NF-κB, and inflammation cytokines. Our results indicated that rutin could significantly downregulate the increased level of REGE, NF-κB and inflammatory cytokines in protein level. In addition, rutin could also ameliorate a series of secondary brain injuries such as brain edema, destruction of blood-brain barrier, neurological deficits and neuronal death. This study indicated that rutin administration had a neuroprotective effect in an experimental rat model of SAH, possibly through inhibiting RAGE-NF-κB mediated inflammation signaling pathway.
Li, Hua; Yu, Jia-Sheng; Zhang, Ding-Ding; Yang, Yi-Qing; Huang, Li-Tian; Yu, Zhuang; Chen, Ru-Dong; Yang, Hong-Kuan; Hang, Chun-Hua
Subarachnoid hemorrhage (SAH) is a threatening and devastating neurological insult with high mortality and morbidity rates. Despite considerable efforts, the underlying pathophysiological mechanisms are still poorly understood. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been implicated in various pathological conditions. We previously showed that RAGE was upregulated and may be involved in pathophysiology of SAH. In the current study, we investigated its potential role in SAH. We found that the upregulation of RAGE after SAH was NF-κB-dependent positive feedback regulation. Further, pharmacological inhibition of RAGE attenuated neuroinflammation, indicating a possible contributive role of RAGE in inflammation-associated brain injury after SAH. Conversely, however, inhibition of RAGE sensitized neurons, exacerbating cell death, which correlated with augmented apoptosis and diminished autophagy, suggesting that activation of RAGE may protect against SAH-induced neuronal injury. Furthermore, we demonstrate that inhibition of RAGE significantly reduced brain edema and improved neurological function at day 1 but not at day 3 post-SAH. Taken together, these results suggest that RAGE exerts dual role after SAH. Our findings also suggest caution should be exercised in setting RAGE-targeted treatment for SAH.
Solodov, A A; Petrikov, S S; Klychnikova, E V; Tazina, E V; Krylov, V V; Godkov, M A; Khamidova, L T
The development of cerebral vasospasm in subarachnoid hemorrhage (SAH) due to cerebral aneurysms rupture results in cerebral circulation disturbances. Application of normobaric hyperoxia can be an effective way for improving of oxygen delivery to injured brain tissues. The purpose of this study was to assess of normobaric hyperoxia influence on intracranial pressure (ICP), cerebral oxygenation and metabolism, oxidative stress and endogenous factors of vascular regulation in II critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture. Increase of FiO2 from 0.3 to 0.5 and 1.0 was accompanied with brain oxygen tension (PbrO2) increase and cerebral extraction ratio for oxygen (O2ER) decrease. Application of normobaric hyperoxia had no effect on ICP, cerebral perfusion pressure, arterial blood pressure and cerebral metabolism. The results obtained from patients with nontraumatic SAH showed an evident increase of oxidative stress which had a significant effect on vascular endothelial function, causing an imbalance in the endogenous regulation of vascular tone. Application of normobaric hyperoxia was not accompanied by an increase of free-radical processes in critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture.
Zhang, Hongrong; Jiang, Li; Guo, Zongduo; Zhong, Jianjun; Wu, Jingchuan; He, Junchi; Liu, Han; He, Zhaohui; Wu, Haitao; Cheng, Chongjie; Sun, Xiaochuan
Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARβ/δ on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPARβ/δ-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that Ad-PPARβ/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARβ/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. PMID:28327554
Chen, Yujie; Luo, Chunxia; Zhao, Mingyue; Li, Qiang; Hu, Rong; Zhang, John H; Liu, Zhi; Feng, Hua
The aim of this study was to investigate whether the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor dipotassium bisperoxo(pyridine-2-carboxyl) oxovanadate (BPV(pic)) attenuates early brain injury by modulating α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor subunits after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. BPV(pic) treatment (0.2mg/kg) was evaluated for effects on neurological score, brain water content, Evans blue extravasation, hippocampal neuronal death and AMPA receptor subunits alterations after SAH. We found that BPV(pic) is effective in attenuating BBB disruption, lowering edema, reducing hippocampal neural death and improving neurological outcomes. In addition, the AMPA receptor subunit GluR1 protein expression at cytomembrane was downregulated, whereas the expression of GluR2 and GluR3 was upregulated after BPV(pic) treatment. Our results suggest that PTEN inhibited by BPV(pic) plays a neuroprotective role in SAH pathophysiology, possibly by alterations in glutamate AMPA receptor subunits.
Zhao, Lei; Liu, Haixiao; Yue, Liang; Zhang, Jingbo; Li, Xia; Wang, Bodong; Lin, Yan; Qu, Yan
Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.
FU, PENG; HU, QUAN
3,4-Dihydroxyphenylethanol (DOPET) is a naturally occurring polyphenolic compound, present in olive oil and in the wastewater generated during olive oil processing. DOPET has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammatory effects. This study was designed to determine whether DOPET alleviates early brain injury (EBI) associated with subarachnoid hemorrhage (SAH) through suppression of oxidative stress and Akt and nuclear factor (NF)-κB pathways. Rats were randomly divided into the following groups: Sham group, SAH group, SAH + vehicle group and SAH + DOPET group. Mortality, blood-brain barrier (BBB) permeability and brain water content were assessed. Oxidative stress, Akt, NF-κB p65 and caspase-3 assays were also performed. DOPET induced a reduction in brain water content, and decreased the BBB permeability of SAH model rats. Furthermore, DOPET effectively controlled oxidative stress, NF-κB p65 and caspase-3 levels, in addition to significantly increasing Akt levels in the cortex following SAH. These results provide evidence that DOPET attenuates apoptosis in a rat SAH model through modulating oxidative stress and Akt and NF-κB signaling pathways. PMID:27168841
Nyberg, Christoffer; Karlsson, Torbjörn; Hillered, Lars; Engström, Elisabeth Ronne
Background Aneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed. Objective To study early cerebral energy changes in an animal model. Methods Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate. Results In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia. Conclusion The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans. PMID:24940881
Su, C C; Saito, K; Nakagawa, A; Endo, T; Suzuki, Y; Shirane, R
Of 250 patients admitted with aneurysmal subarachnoid hemorrhage (SAH) from 1994 to 2000, 16 had massive intra-sylvian hematomas. To predict the useful determinants of the clinical outcome for such patients we analyzed our last 16 cases. The study was performed in 2 parts. Part 1 covered the period from 1994 to 1996 and included 5 patients who underwent early surgery. Immediately before operation, Hunt & Kosnik grade (H&K) III was observed in 1, IV in 3 and V in 1 patient. Part 2, from 1997 to 2000, included 11 patients who underwent ultra-early surgery (within 3 hours after admission) with ventriculostomy and with 2 weeks' postoperative management in the ICU. Preoperatively, there were 2 patients with H&K III, 7 with IV, and 2 with V. The results in part 1 showed that 3 out of the 5 patients had poor outcome with symptomatic vasospasm. While in Part 2, seven returned to work, 2 had minimal and 1 had severe neurological deficits with symptomatic vasospasm, and 1 died. We therefore suggest that ultra-early surgery with ventriculostomy and postoperative management in the ICU is the most useful determinant to improve the clinical outcome in the treatment of SAH patients with massive intra-sylvian hematoma.
Haruma, Jun; Teshigawara, Kiyoshi; Hishikawa, Tomohito; Wang, Dengli; Liu, Keyue; Wake, Hidenori; Mori, Shuji; Takahashi, Hideo Kohka; Sugiu, Kenji; Date, Isao; Nishibori, Masahiro
Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH) is closely related to the progression of brain damage, little is known about the molecular mechanism underlying its development. High mobility group box-1 (HMGB1) plays an important role as an initial inflammatory mediator in SAH. In this study, an SAH rat model was employed to evaluate the effects of anti-HMGB1 monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb administration significantly suppressed these effects. Up-regulations of inflammation-related molecules and vasoconstriction-mediating receptors in the BA of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated the enhanced vasocontractile response to thrombin of the isolated BA from SAH rats and prevented activation of cerebrocortical microglia. Moreover, locomotor activity and weight loss recovery were also enhanced by anti-HMGB1 mAb administration. The vasocontractile response of the BA under SAH may be induced by events that are downstream of responses to HMGB1-induced inflammation and inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel therapeutic strategy for DCV and early brain injury after SAH. PMID:27883038
Wang, Zhong; Wang, Yibin; Tian, Xiaodi; Shen, Haitao; Dou, Yang; Li, Haiying; Chen, Gang
Transient receptor potential channel 1/4 (TRPC1/4) are considered to be related to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. In this study, a SAH rat model was employed to study the roles of TRPC1/4 in the early brain injury (EBI) after SAH. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. The protein levels of TRPC1/4 increased and peaked at 5 days after SAH in rats. Inhibition of TRPC1/4 by SKF96365 aggravated SAH-induced EBI, such as cortical cell death (by TUNEL staining) and degenerating (by FJB staining). In addition, TRPC1/4 overexpression could increase calcineurin activity, while increased calcineurin activity could promote the dephosphorylation of N-methyl-D-aspartate receptor (NMDAR). Calcineurin antagonist FK506 could weaken the neuroprotection and the dephosphorylation of NMDAR induced by TRPC1/4 overexpression. Contrarily, calcineurin agonist chlorogenic acid inhibited SAH-induced EBI, even when siRNA intervention of TRPC1/4 was performed. Moreover, calcineurin also could lead to the nuclear transfer of nuclear factor of activated T cells (NFAT), which is a transcription factor promoting the expressions of TRPC1/4. TRPC1/4 could inhibit SAH-induced EBI by supressing the phosphorylation of NMDAR via calcineurin. TRPC1/4-induced calcineurin activation also could promote the nuclear transfer of NFAT, suggesting a positive feedback regulation of TRPC1/4 expressions. PMID:27641617
Egea-Guerrero, Juan José; Murillo-Cabezas, Francisco; Muñoz-Sánchez, María Ángeles; Vilches-Arenas, Angel; Porras-González, Cristina; Castellano, Antonio; Ureña, Juan; González-Montelongo, María del Carmen
We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery. A significant increase of basal tone, measured 4 and 60min after normalization, was observed on day 5 after SAH and at 60min on days 2 and 3 after SAH. This phenomenon was suppressed with LTCCs and ROCK inhibitors. We have also studied arterial rings vasoreactivity in response to high K(+) solutions. Interestingly, there were no significant differences in the phasic component of the high K(+)-induced contraction between sham and SAH groups, whereas a significant increase in the sustained contraction was observed on day 5 after SAH. This latter component was sensitive to fasudil, and selectively reduced by low nifedipine concentration, and phospholipase C and SR-ATPase inhibitors. Therefore, our data suggest that the metabotropic function of LTCCs is potentiated in SAH. Our results could provide a new strategy to optimize the pharmacological treatment of this pathological process.
Sinha, Santosh Kumar; Goel, Amit; Sachan, Mohit; Saraf, Sameer; Verma, Chandra Mohan
Filariasis presenting with pericardial effusion with tamponade is rare. We report a case of a 30-year-old female who was admitted with severe dyspnea and chest pain since 2 days. Echocardiogram showed massive pericardial effusion with tamponade. Pericardial fluid aspiration drained 1.2 L of hemorrhagic fluid. Cytology examination revealed microfilaria of Wuchereria bancrofti. She was treated with diethyl carbamazine and discharged. Six weeks later, she presented again with massive pericardial effusion with cardiac tamponade. Pericardiocentesis was done. Cytology examination revealed microfilaria of W. bancrofti. This time she was treated with ivermectin and albendazole and cured. Hemorrhagic effusion resolved completely. Though relatively uncommon, tropical diseases must always be considered in the etiological diagnosis of recurrent pericardial effusion.
Di Pasquale, Piero; Zanatta, Paolo; Morghen, Ilaria; Bosco, Enrico; Forini, Elena
Background: Normal subjects present interhemispheric symmetry of middle cerebral artery (MCA) mean flow velocity and N20 cortical somatosensory evoked potential (SSEP). Subarachnoid haemorrhage (SAH) can modify this pattern, since high regional brain vascular resistances increase blood flow velocity, and impaired regional brain perfusion reduces N20 amplitude. The aim of the study is to investigate the variability of MCA resistances and N20 amplitude between hemispheres in SAH. Methods: Measurements of MCA blood flow velocity (vMCA) by transcranial color-Doppler and median nerve SSEP were bilaterally performed in sixteen patients. MCA vascular changes on the compromised hemisphere were calculated as a ratio of the reciprocal of mean flow velocity (1/vMCA) to contralateral value and correlated to the simultaneous variations of interhemispheric ratio of N20 amplitude, within each subject. Data were analysed with respect to neuroimaging of MCA supplied areas. Results: Both interhemispheric ratios of 1/vMCA and N20 amplitude were detected >0.65 (p <0,01) in patients without neuroimages of injury. Both ratios became <0.65 (p <0.01) when patients showed unilateral images of ischemic penumbra and returned >0.65 if penumbra disappeared. The two ratios no longer correlated after structural lesion developed, as N20 detected in the damaged side remained pathological (ratio <0.65), whereas 1/vMCA reverted to symmetric interhemispheric state (ratio >0.65), suggesting a luxury perfusion. Conclusion: Variations of interhemispheric ratios of MCA resistance and cortical N20 amplitude correlate closely in SAH and allow identification of the reversible ischemic penumbra threshold, when both ratios become <0.65. The correlation is lost when structural damage develops. PMID:21660110
ALtamimi, Zaid Abu Rajab; Sheikh, Rashid; Omar, Hassen; Taweel, Hayam Al; Ganesan, Shanmugam
Case series Patients: Male, 20 • Male, 4 • Male, 27 • Male, 25 • Female, 5 • Female, 26 Final Diagnosis: Post tonsillectomy secondary hemorrhage Symptoms: Bleeding • bleeding per oral Medication: — Clinical Procedure: Control of post tonsillectomy secondary hemorrhage Specialty: Otolaryngology Objective: Rare disease Background: Post-tonsillectomy hemorrhage (PTH) has been reported in the literature as a serious complication after tonsillectomy that has high morbidity and can be life threatening. In cases of recurrent secondary PTH, one should consider coagulopathies as the hidden pathology. Factor XIII deficiency is very rare, suggested to be present 1 in 2 million people. Patients with undiagnosed factor XIII deficiency with secondary PTH are extremely rare. Case Report: We report on the cases of six patients (four adults and two children) who presented with recurrent attacks of secondary PTH. Conclusion: Recurrent, severe PTH could be related to undiagnosed hematological disorders. PMID:27843132
Shen, Jian; Huang, Kai-Yuan; Zhu, Yu; Pan, Jian-Wei; Jiang, Hao; Weng, Yu-Xiang; Zhan, Ren-Ya
OBJECTIVE The efficacy of statin therapy in treating aneurysmal subarachnoid hemorrhage (SAH) remains controversial. In this meta-analysis, the authors investigated whether statin treatment significantly reduced the incidence of cerebral vasospasm and delayed neurological deficits, promoting a better outcome after aneurysmal SAH. METHODS A literature search of the PubMed, Ovid, and Cochrane Library databases was performed for randomized controlled trials (RCTs) and prospective cohort studies investigating the effect of statin treatment. The end points of cerebral vasospasm, delayed ischemic neurological deficit (DIND), delayed cerebral infarction, mortality, and favorable outcome were statistically analyzed. RESULTS Six RCTs and 2 prospective cohort studies met the eligibility criteria, and a total of 1461 patients were included. The meta-analysis demonstrated a significant decrease in the incidence of cerebral vasospasm (relative risk [RR] 0.76, 95% confidence interval [CI] 0.61-0.96) in patients treated with statins after aneurysmal SAH. However, no significant benefit was observed for DIND (RR 0.88, 95% CI 0.70-1.12), delayed cerebral infarction (RR 0.66, 95% CI 0.33-1.31), mortality (RR 0.69, 95% CI 0.39-1.24) or favorable outcome, according to assessment by the modified Rankin Scale or Glasgow Outcome Scale (RR 0.99, 95% CI 0.92-1.17). CONCLUSIONS Treatment with statins significantly decreased the occurrence of vasospasm after aneurysmal SAH. The incidence of DIND, delayed cerebral infarction, and mortality were not affected by statin treatment. Future research should focus on DIND and how statins influence DIND.
Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin
Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway.
Li, Jian; Lu, Jianfei; Mi, Yongjie; Shi, Zhao; Chen, Chunhua; Riley, John; Zhou, Changman
The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48h after SAH injury in rats. Specifically evaluating whether mitophagy, through voltage dependant anion channels (VDACs) interacting with microtubule-associated protein 1 light chain 3, could orchestrate the induction of apoptotic and necrotic cell death in neurons, a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH, SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain edema, BBB disruption, and neurobehavioral testing. We also used western blotting techniques to analyze the expressions of key mitophagic/autophagic proteins and pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin treatment significantly improved the mortality rate, cerebral edema, and neurobehavioral deficits; apoptotic and necrotic cell death in neurons were reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain injury following SAH. Immunohistochemical staining and western blot analysis demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced by VDAC1 following SAH injury may in fact play a significant role in neuroprotection, the mechanism which may be through the attenuation of the apoptosic and necrosic molecular pathways. This translates a preservation of functional integrity and an improvement in mortality.
Karamchandani, Rahul Ramesh; Fletcher, Jeffrey James; Pandey, Aditya Swarup; Rajajee, Venkatakrishna
Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated.
Chen, G; Li, Q; Feng, D; Hu, T; Fang, Q; Wang, Z
Approximately 50% of patients who survived after aneurysmal subarachnoid hemorrhage (SAH) have cognitive or neurobehavioral dysfunction. The mechanisms are not known. NR2B, one of the subunits of N-methyl-d-aspartate (NMDA) receptors, has been proved to be an important factor for synapse function and behavior cognition. Experiment 1 aimed to investigate the timecourse of the NR2B expression in the cortex, hippocampus, and cerebellum after SAH in rats. In experiment 2, we assessed the effect of Ro 25-6981 (a specific NR2B antagonist) on regulation of learning deficits and behavioral activity following SAH. All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once on day 0. NR2B was assessed by Western blot analysis and immunohistochemistry. Cognitive and memory changes were investigated in the Morris water maze. As a result, the expression of NR2B was decreased remarkably in SAH groups compared with the control group and the low ebb was on days 1-3. The immunohistochemical staining demonstrated expression of NR2B was present mainly in the neurons in all of the three different regions, such as the cortex, hippocampus, and cerebellum. After Ro 25-6981 intraperitoneal administration, learning deficits induced by SAH was markedly aggravated and clinical behavior scale was also significantly decreased. Our results suggest that NR2B expression is down-regulated in the brain after experimental SAH and NR2B antagonism resulted in augmentation of the development of cognitive dysfunction after SAH.
Ma, Junwei; Wang, Zhong; Liu, Chenglin; Shen, Haitao; Chen, Zhouqing; Yin, Jia; Zuo, Gang; Duan, Xiaochun; Li, Haiying; Chen, Gang
Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway. PMID:27026509
[Spontaneous dissection of the anterior cerebral artery that simultaneously presented with cerebral infarction and subarachnoid hemorrhage, successfully treated with conservative management: a case report].
Nanbara, Sho; Tsutsumi, Keisuke; Takahata, Hideaki; Fujimoto, Takashi; Kawahara, Ichiro; Ono, Tomonori; Toda, Keisuke; Baba, Hiroshi; Yonekura, Masahiro
We recently encountered a rare case of anterior cerebral artery dissection (ACAD) that accompanied fresh cerebral infarction (CI) and subarachnoid hemorrhage (SAH). An initial head CT showed a thin SAH in the interhemispheric cistern and cortical sulcus of the left frontal surface. Subsequent MRI performed 10 min after head CT scan revealed a fresh infarction in the left ACA region. MR-and digital subtraction angiograms demonstrated a dissection in the A2 portion of the left ACA with a leak of contrast media around the left A3 portion, suggesting that the bleeding occurred in a distal portion of the main dilation. Without anti-thrombotic therapy, the patient recovered without complications by blood pressure control and administration of brain-function protection therapies. We found 11 cases similar to the present case in the literature. All cases presented with lower-extremity dominant hemiparesis; however, sudden onset headache was rare. Blood pressure was not well-controlled in 4 out of the 6 known hypertensive cases. Main sites of dissection were located at the A2 portion in all cases except one A3 lesion, and extended to A3 in 2 cases. Conservative therapy led to favorable outcome in 8 cases, while 4 cases underwent surgical interventions for increasing risk of aneurysm rupture after initial observational therapies. Re-bleeding did not occur in any of the 12 cases reviewed. These data suggest that conservative treatment can be considered for an initial management of ACAD with simultaneous CI and SAH. More evidence needs to be accumulated to establish the optimal therapeutic approach for ACAD associated with CI and SAH.
Tang, Junjia; Hu, Qin; Chen, Yujie; Liu, Fei; Zheng, Yun; Tang, Jiping; Zhang, Jianmin; Zhang, John H
N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), an N-acetyl serotonin derivative, selectively activates tropomyosin-related kinase receptor B (TrkB). This study is to investigate a potential role of HIOC on ameliorating early brain injury after experimental subarachnoid hemorrhage (SAH). One hundred and fifty-six adult male Sprague-Dawley rats were used. SAH model was induced by endovascular perforation. TrkB small interfering RNA (siRNA) or scramble siRNA was injected intracerebroventricularly 24h before SAH. HIOC was administrated intracerebroventricularly 3h after SAH and compared with brain-derived neurotrophic factor (BDNF). SAH grade and neurologic scores were evaluated for the outcome study. For the mechanism study, the expression of TrkB, phosphorylated TrkB (p-TrkB), phosphorylated extracellular signal regulated kinase (p-ERK), B-cell lymphoma 2 (Bcl-2) and cleaved caspase 3 (CC3) was detected by Western blots, and neuronal injury was determined by double immunofluorescence staining of neuronal nuclei and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling. Knocking down of TrkB decreased the expression of Bcl-2 and aggravated neurologic deficits 24h after SAH. HIOC activated TrkB/ERK pathway, decreased neuronal cell death, and improved neurobehavioral outcome, and these effects were abolished by TrkB siRNA. HIOC was more potent than BDNF in reduction of apoptosis 24h post-SAH. Thus, we conclude that administration of HIOC activated TrkB/ERK signaling cascade and attenuated early brain injury after SAH. HIOC may be a promising agent for further treatment for SAH and other stroke events.
Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul
Context: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. Aims: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. Settings and Design: This was an experimental study conducted on rabbits. Materials and Methods: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6–C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. Results: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. Conclusion: We noticed interestingly that C6–C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms. PMID:28250634
Zuo, Shilun; Ge, Hongfei; Li, Qiang; Zhang, Xuan; Hu, Rong; Hu, Shengli; Liu, Xin; Zhang, John H; Chen, Yujie; Feng, Hua
Blood-brain barrier preservation plays an important role in attenuating vasogenic brain edema after subarachnoid hemorrhage (SAH). This study was designed to investigate the protective effect and mechanism of artesunate, a traditional anti-malaria drug, on blood-brain barrier after SAH. Three hundred and seventy-seven (377) male Sprague-Dawley rats were subjected to endovascular perforation model for SAH. The rats received artesunate alone or in combination with Sphingosine-1-phosphate receptor-1 (S1P1) small interfering RNA (siRNA), antagonist VPC23019, or phosphatidylinositol 3-kinase inhibitor wortmannin after SAH. Modified Garcia score, SAH grades, brain water content, Evans blue leakage, transmission electron microscope, immunohistochemistry staining, Western blot, and cultured endothelial cells were used to investigate the optimum concentration and the therapeutic mechanism of artesunate. We found that artesunate (200 mg/kg) could do better in raising modified Garcia score, reducing brain water content and Evans blue leakage than other groups after SAH. Moreover, artesunate elevated S1P1 expression, enhanced phosphatidylinositol 3-kinase activation, lowered GSK-3β activation, stabilized β-catenin, and improved the expression of Claudin-3 and Claudin-5 after SAH in rats. These effects were eliminated by S1P1 siRNA, VPC23019, and wortmannin. This study revealed that artesunate could preserve blood-brain barrier integrity and improve neurological outcome after SAH, possibly through activating S1P1, enhancing phosphatidylinositol 3-kinase activation, stabilizing β-catenin via GSK-3β inhibition, and then effectively raising the expression of Claudin-3 and Claudin-5. Therefore, artesunate may be favorable for the blood-brain barrier (BBB) protection after SAH and become a potential candidate for the treatment of SAH patients.
Mutoh, Tomoko; Mutoh, Tatsushi; Sasaki, Kazumasu; Nakamura, Kazuhiro; Taki, Yasuyuki; Ishikawa, Tatsuya
BACKGROUND Subarachnoid hemorrhage (SAH) is one of the most devastating cerebrovascular disorders. We report on the diagnostic value of three-dimensional (3-D) maximum intensity projection (MIP) reconstruction of T2*-weighted magnetic resonance images (MRI), processed using graphical user interface-based software, to aid in the accurate grading of endovascular-perforation-induced SAH in a mouse model. MATERIAL AND METHODS A total of 30 mice were subjected to SAH by endovascular perforation; three (10%) were scored as grade 0, six (20%) as grade 1, six (20%) as grade 2, eight (27%) as grade 3, and seven (23%) as grade 4 according to T2*-weighted coronal slices. In comparison, none of mice were scored as grade 0, eight (27%) as grade 1, five (17%) as grade 2, nine (30%) as grade 3, and eight (27%) as grade 4 based on subsequent evaluation using reconstructed 3-D MIP images. RESULTS Mice scored as grade 0 (10%; no visible SAH) on T2*-coronal images were categorized as grades 1 (thin/localized SAH) and 3 (thick/diffuse SAH) according to 3-D MIP images. Grades based on T2* 3-D MIP images were more closely correlated with conventional SAH score (r2=0.59; P<0.0001) and neurological score (r2=0.25; P=0.005) than those based on T2*-coronal slices (r2=0.46; P<0.0001 for conventional score and r2=0.15; P=0.035 for neurological score). CONCLUSIONS These results suggest that 3-D MIP images generated from T2*-weighted MRI data may be useful for the simple and precise grading of SAH severity in mice to overcome the weakness of the current MRI-based SAH grading system.
Malinova, Vesna; Psychogios, Marios N.; Tsogkas, Ioannis; Koennecke, Birte; Bleuel, Kim; Iliev, Bogdan; Rohde, Veit; Mielke, Dorothee
Objective Magnetic resonance (MR) imaging has been used for the detection of cerebral vasospasm (VSP) related infarction in experimental subarachnoid hemorrhage (eSAH) in rats. Conventional angiography is generally used to visualize VSP, which is an invasive technique with a possible increase in morbidity and mortality. In this study we evaluated the validity of MR-angiography (MRA) in detecting VSP and its feasibility to define VSP severity grades after eSAH in rats. Methods SAH was induced using the double-hemorrhage model in 12 rats. In two rats, saline solution was injected instead of blood (sham group). MR was performed on day 1, 2 and on day 5. T1-, T2-, T2*-weighted and time-of-flight MR sequences were applied, which were analyzed by two blinded neuroradiologists. Vessel narrowing of 25–50% was defined as mild, 50–75% as moderate and >75% as severe VSP. Results We performed a total of 34 MRAs in 14 rats. In 14 rats, MRA was performed on day 2 and day 5. In six rats MRA was additionally performed on day1 before the blood injection. A good visualization of cerebral vessels was possible in all cases. No VSP was seen in the sham group neither on day 2 nor on day 5. We found vasospasm on day 2 in 7 of the 14 rats (50%) whereas all 7 rats had mild and one rat had additionally moderate and severe vasospasm in one vessel, respectively. On day 5 we found vasospasm in 8 of the 14 rats (60%) whereas 4 rats had severe vasospasm, 1 rat had moderate vasospasm and 3 rats demonstrated mild vasospasm. In 4 of the 14 rats (30%) an ischemic lesion was detected on day 5. Three of these rats had severe vasospasm and one rat had mild vasospasm. Severe vasospasm on day 5 was statistically significant correlated with the occurrence of ischemic lesions (Fisher’s Exact test, OR 19.5, p = 0.03). Conclusions MRA is a noninvasive diagnostic tool, which allows a good visualization of the cerebral vasculature and provides reproducible results concerning the detection of VSP and the
Tse, J R; Schwab, K E; McMahon, M; Simon, W
Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.
Chambliss, Jeffrey M.
Purpura, particularly when accompanied by fever, is a worrisome finding in children. Acute hemorrhagic edema of infancy (AHEI) is a benign type of small-vessel leukocytoclastic vasculitis that presents with progressive purpura and has an excellent prognosis. Patients with AHEI present with large, target-like purpuric plaques affecting the face, ear lobes, and extremities. While the rapid onset of these skin findings can be dramatic, the child with AHEI is usually well appearing with reassuring laboratory testing. We describe a case of a previously healthy 8-month-old female who presented with progressive purpura in a nondependent distribution, low-grade fevers, and extremity swelling. An extensive workup was performed prior to making the diagnosis of AHEI. Coronavirus was implicated as the likely triggering pathogen, and the patient suffered a recurrence of purpuric rash and swelling several weeks after her initial presentation. PMID:28243478
Kim, Dae Sung; Lee, Minhyeok; Kwon, Oh Jung; Jeong, Inbeom; Son, Ji Woong; Na, Moon Jun
A 45-year-old man presented with dyspnea and hemoptysis during exercise. A chest computed tomography (CT) revealed multifocal diffuse patchy ground glass opacity and interlobular septal thickening in both the lungs. Permeability pulmonary edema or pulmonary hemorrhage was suspected. Serologic studies for autoimmune disorders and vasculitis were negative. There was no laboratory evidence of coagulopathy, other hematopoietic disease or infectious disease. Considering correlation with exercise, we diagnosed exercise-induced pulmonary hemorrhage (EIPH) or exercise-induced pulmonary edema (EIPE). The patient was managed with antifibrinolytics, antibiotics, and antitussive agent. After a week, follow-up chest CT revealed completely resolved pulmonary hemorrhage. About 2 months after the first event, he visited again with dyspnea and hemoptysis during running. In the present study, we report a case of recurrent pulmonary hemorrhage after exercise. PMID:26508928
Lv, Tao; Miao, Yi-Feng; Jin, Yi-Chao; Yang, Shao-Feng; Wu, Hui; Dai, Jiong; Zhang, Xiao-Hua
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.
Rostami, Elham; Engquist, Henrik; Johnson, Ulf; Howells, Timothy; Ronne-Engström, Elisabeth; Nilsson, Pelle; Hillered, Lars; Lewén, Anders; Enblad, Per
Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed cerebral ischemia (DCI). Early detection and management of reversible ischemia is of critical importance in patients with SAH. Using a bedside Xenon enhanced computerized tomography (Xenon-CT) scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive care setting and intracerebral microdialysis (MD) is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here, we present results from nine SAH patients with both MD monitoring and bedside Xenon-CT measurements. CBF measurements were performed within the first 72 h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100 g/min whereas one had 53 ml/100 g/min. The three patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate (L/P) ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had L/P ratio ≥25 and four of these patients had CBF ≤ 22 ml/100 g/min. These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied with metabolic disturbances determined by the MD. Most importantly, pathological findings on the Xenon-CT and MD could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to be useful and feasible. Further studies are needed to evaluate if DCI can be detected before any other signs of DCI to prevent progress to infarction. PMID:24917850
Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Describing the Diagnostic Accuracy of History, Physical Exam, Imaging, and Lumbar Puncture with an Exploration of Test Thresholds
Carpenter, Christopher R.; Hussain, Adnan M.; Ward, Michael J.; Zipfel, Gregory J.; Fowler, Susan; Pines, Jesse M.; Sivilotti, Marco L.A.
Background Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. Objectives To perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). Methods PUBMED, EMBASE, SCOPUS, and research meeting abstracts were searched up to June 2015 for studies of emergency department (ED) patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, positive (LR+) and negative (LR−) likelihood ratios. To identify test- and treatment-thresholds, we employed the Pauker-Kassirer method with Bernstein test-indication curves using the summary estimates of diagnostic accuracy. Results A total of 5,022 publications were identified, of which 122 underwent full text-review; 22 studies were included (average SAH prevalence 7.5%). Diagnostic studies differed in assessment of history and physical exam findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low-risk of biases. A history of neck pain (LR+ 4.1 [95% CI 2.2-7.6]) and neck stiffness on physical exam (LR+ 6.6 [4.0-11.0]) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Non-contrast cranial CT within 6 hours of headache onset accurately ruled-in (LR+ 230 [6-8700]) and ruled-out SAH (LR− 0
Serial angiographic appearance of segmental arterial mediolysis manifesting as vertebral, internal mammary and intra-abdominal visceral artery aneurysms in a patient presenting with subarachnoid hemorrhage and review of the literature.
Cooke, Daniel L; Meisel, Karl M; Kim, Warren T; Stout, Charles E; Halbach, Van V; Dowd, Christopher F; Higashida, Randall T
Segmental arterial mediolysis (SAM) is a rare, non-inflammatory, non-atherosclerotic vasculopathy typically affecting the abdominal arteries although it may also affect the great vessels and cerebral vasculature. Diseased vessels manifest with aneurysms and/or dissections, often presenting clinically with catastrophic thromboembolic injury and less frequently with subarachnoid hemorrhage (SAH). The etiology of SAM remains indeterminate although there is evidence it may be an endogenous pathological response to vasospasm. The SAM literature is reviewed and a case of SAH related to a ruptured dissecting-type vertebral artery aneurysm is described. In addition to furthering awareness of SAM, this unique case offers insight into the acute phase of the disease and the potential role of vasospastic induction.
Fischbein, Nancy J; Wijman, Christine A C
Nontraumatic (or spontaneous) intracranial hemorrhage most commonly involves the brain parenchyma and subarachnoid space. This entity accounts for at least 10% of strokes and is a leading cause of death and disability in adults. Important causes of spontaneous intracranial hemorrhage include hypertension, cerebral amyloid angiopathy, aneurysms, vascular malformations, and hemorrhagic infarcts (both venous and arterial). Imaging findings in common and less common causes of spontaneous intracranial hemorrhage are reviewed.
Bender, Matthew T; Colby, Geoffrey P; Huang, Judy
Hydrocephalus has varied presentations in patients with a history of spinal dysraphism. This is a unique case of post-subarachnoid hemorrhage hydrocephalus presenting as cauda equina syndrome. We report on a 32-year-old woman with remotely repaired spinal defect who experienced subarachnoid hemorrhage and underwent anterior communicating artery aneurysm clipping. Post-operatively, she developed urinary and fecal incontinence as the sole presenting symptom of communicating post-hemorrhagic hydrocephalus. New neurological deficits in this population can also be attributed to recurrent cord tethering or syrinx, both of which were demonstrated on her lumbar spine MRI, but her incontinence resolved with external ventricular drain placement and cerebrospinal fluid diversion. There are few case reports of patients with closed neural tube defects and hydrocephalus and none in the adult population to our knowledge. Neurological change in patients with any history of spinal dysraphism may reflect altered cerebrospinal fluid dynamics affecting either end of the neuraxis.
Nakamura, Yuri; Takase, Kei-Ichiro; Matsushita, Takuya; Yoshimura, Satoshi; Yamasaki, Ryo; Murai, Hiroyuki; Kikuchi, Kazufumi; Kira, Jun-Ichi
A 34-year-old man presented with an acute onset of upbeat nystagmus, slurred speech, and limb and truncal ataxias. The patient had a history of limb ataxia and gait disturbance previously treated as brainstem encephalitis with corticosteroids 3 years previously. Brain magnetic resonance imaging showed pontine developmental venous anomaly (DVA) and hemorrhagic infarction within the drainage territory of the DVA. Three months later, the patient exhibited recurrent limb ataxia, double vision, and numbness of the left side of the body. The brain magnetic resonance imaging revealed recurrent hemorrhagic venous infarction within the same territory of the pontine DVA. Laboratory tests disclosed a hypercoagulable state owing to a decrease of protein S activity despite the normal antigen level. Genetic testing indicated that the patient was a homozygous carrier of protein S Tokushima. The patient's severe disability remained unchanged in spite of treatment with anticoagulation therapy using warfarin. We propose that further research on hereditary coagulopathy be carried out in patients with recurrent episodes of DVA-related infarction.
Bros, Sebastien Chabrot, Pascal Kastler, Adrian; Ouchchane, Lemlih; Cassagnes, Lucie; Gallot, Denis; Boyer, Louis
Purpose: To retrospectively identify predictive factors of recurrent bleeding within 24 h after uterine artery embolization (UAE) for postpartum hemorrhage (PPH). Materials and Methods: A total of 194 patients underwent UAE for PPH between August 1999 and April 2009 at our institution. Twelve patients experienced recurrent bleeding within the next 24 h; a second attempt at UAE was thus necessary, which was successful in 10 cases. In two cases, hemostatic hysterectomy was performed. Epidemiological, gynecological-obstetrical, anatomic, and biological data were analyzed. Results: Complete data were available for 148 of the 194 (76%) included patients. Sixty-four (43%) were primiparous, 18 (12.2%) had a placenta accreta, 21 (14%) had a coagulopathy, and 28 (18.9%) had an anatomic variant of the uterine arterial vasculature. Mean age and pregnancy term were similar in both recurring and nonrecurrent bleeding groups. After multivariate analysis, three criteria emerged as risk factors of recurrent bleeding: primiparity (10 patients, 83%; odds ratio [OR] = 18.84; P = 0.014), coagulation disorders (6 patients, 50%; OR = 12.08; P = 0.006), and anatomic variant of the uterine arterial vasculature (28 patients; OR = 9.83; P = 0.003). Conclusions: earch for uterine collaterals must be performed before UAE for PPH. Primiparity and coagulation disorders increase the risk of recurrent bleeding after UAE for PPH.
Sheng, Huaxin; Spasojevic, Ivan; Tse, Hubert M.; Jung, Jin Yong; Hong, Jun; Zhang, Zhiquan; Piganelli, Jon D.; Batinic-Haberle, Ines
Intracerebroventricular treatment with redox-regulating Mn(III) N-hexylpyridylporphyrin (MnPorphyrin) is remarkably efficacious in experimental central nervous system (CNS) injury. Clinical development has been arrested because of poor blood-brain barrier penetration. Mn(III) meso-tetrakis (N-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP) was synthesized to include four six-carbon (hexyl) side chains on the core MnPorphyrin structure. This has been shown to increase in vitro lipophilicity 13,500-fold relative to the hydrophilic ethyl analog Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP). In normal mice, we found brain MnTnHex-2-PyP accumulation to be ∼9-fold greater than MnTE-2-PyP 24 h after a single intraperitoneal dose. We then evaluated MnTnHex-2-PyP efficacy in outcome-oriented models of focal cerebral ischemia and subarachnoid hemorrhage. For focal ischemia, rats underwent 90-min middle cerebral artery occlusion. Parenteral MnTnHex-2-PyP treatment began 5 min or 6 h after reperfusion onset and continued for 7 days. Neurologic function was improved with both early (P = 0.002) and delayed (P = 0.002) treatment onset. Total infarct size was decreased with both early (P = 0.03) and delayed (P = 0.01) treatment. MnTnHex-2-PyP attenuated nuclear factor κB nuclear DNA binding activity and suppressed tumor necrosis factor-α and interleukin-6 expression. For subarachnoid hemorrhage, mice underwent perforation of the anterior cerebral artery and were treated with intraperitoneal MnTnHex-2-PyP or vehicle for 3 days. Neurologic function was improved (P = 0.02), and vasoconstriction of the anterior cerebral (P = 0.0005), middle cerebral (P = 0.003), and internal carotid (P = 0.015) arteries was decreased by MnTnHex-2-PyP. Side-chain elongation preserved MnPorphyrin redox activity, but improved CNS bioavailability sufficient to cause improved outcome from acute CNS injury, despite delay in parenteral treatment onset of up to 6 h. This advance now
Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Lin, Chih-Lung; Kwan, Aij-Lie
Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH. PMID:26539501
Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Lin, Chih-Lung; Kwan, Aij-Lie
Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH.
Bhattad, Venugopal Brijmohan; Bowman, Jennifer N.; Panchal, Hemang B.; Paul, Timir K.
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare genetic blood disorder that leads to abnormal bleeding due to absent capillaries and multiple abnormal blood vessels known as arteriovenous malformations. A feature of HHT is high-output heart failure due to multiple arteriovenous malformations. High-output heart failure can lead to recurrent epistaxis Kiesselbach area syndrome (REKAS), further exacerbating heart failure through increased blood loss and resultant anemia. We report a patient with HHT who presented with high-output heart failure contributing to REKAS. In patients with REKAS, we propose if anemia is present, REKAS can be avoided by correcting the anemia by increasing the hemoglobin level to greater than 9 to 10 g/dL. This decreases hyperdynamic circulation and reduces pressure in the blood vessels of the nose. PMID:28210642
Peng, Jianhua; Yang, Ping; Kuai, Li; Qin, Xinghu; Cao, Fang; Sun, Xiaochuan; Chen, Ligang; Vitek, Michael P.; Jiang, Yong
Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential role of APOE in EBI post-SAH. Multiple techniques were used to determine the early BBB disruption in EBI post-SAH in a murine model using wild-type (WT) and Apoe−/− (KO) mice. Progressive BBB disruption (Evans blue extravasation and T2 hyperintensity in magnetic resonance imaging) was observed before the peak of endogenous APOE expression elevation at 48h after SAH. Moreover, Apoe−/− mice exhibited more severe BBB disruption charcteristics after SAH than WT mice, including higher levels of Evans blue and IgG extravasation, T2 hyperintensity in magnetic resonance imaging, tight junction proteins degradation and endothelial cells death. Mechanistically, we found that APOE restores the BBB integrity in the acute stage after SAH via the cyclophilin A (CypA)-NF-κB-proinflammatory cytokines-MMP-9 signalling pathway. Consequently, although early BBB disruption causes neurological dysfunctions after SAH, we capture a different aspect of the effects of APOE on EBI after SAH that previous studies had overlooked and open up the idea of BBB disruption as a target of APOE-based therapy for EBI amelioration research in the future. PMID:27463015
Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.
Ehlert, Angelika; Schmidt, Christoph; Wölfer, Johannes; Manthei, Gerd; Jacobs, Andreas H; Brüning, Roland; Heindel, Walter; Ringelstein, E Bernd; Stummer, Walter; Pluta, Ryszard M; Hesselmann, Volker
OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.
Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.
Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang
Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH.
Anokwute, Miracle C; Braca, John A; Bohnstedt, Bradley; DeNardo, Andrew; Scott, John; Cohen-Gadol, Aaron; Sahlein, Daniel H
Successful endovascular coiling of ruptured tiny saccular intracranial aneurysms (⩽3mm) is technically challenging and traditionally has been associated with technical failures, as well as morbidity related to thromboembolic events and high intraoperative rupture rates. This study analyzes the feasibility, technical efficacy, and clinical outcomes of coil embolization of ruptured tiny intracranial aneurysms using current coil and microcatheter technology and techniques. We performed a retrospective review of 20 patients with 20 ruptured tiny aneurysms treated with endovascular coil embolization from 2013 to 2016 at a single high-volume academic tertiary care practice. The mean aneurysm size was 2.4mm (median 2.5mm, 1-3). Complete occlusion was achieved in 12 of 20 patients (60%), the remaining 7 of 20 patients (35%) had a small neck remnant, and there was 1 failure (5%) converted to microsurgical clipping. Two patients had a failed attempted surgical clip reconstruction and were subsequently coiled. There was 1 intraprocedural rupture (5%) and 1 severe parent artery vasospasm (5%) during coiling. At discharge, 60% of patients were living independently. At follow-up three patients were deceased. Mean angiographic follow-up was 139days (SD 120). There were no aneurysm recurrences among occluded patients and there were no retreatments among those with neck remnants. Coiling of ruptured aneurysms ⩽3mm is feasible with high occlusion rates and low complication rates. The availability of softer coils with flexible detachment zones has led to safe and effective endovascular treatment of tiny ruptured aneurysms.
Tongsong, Theera; Puntachai, Pongsun; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee
The purpose of this series was to describe sonographic features of an isolated widened fetal subarachnoid space with a thin cerebral mantle and possible associations. Between January 2004 and December 2013, fetuses with a prenatal diagnosis of a widened subarachnoid space were prospectively recruited and followed. Histories of medical and familial diseases, as well as other demographic data such as drug exposure and lifestyles, were assessed and prospectively recorded. The women were investigated for possible associated factors. Ten pregnant women were recruited. Their fetuses showed various degrees of a widened subarachnoid space, ranging from 5 to 20 mm. Nearly all were diagnosed in the second half of pregnancy. Four cases had normal brain structures documented at midpregnancy anomaly screening. Only 1 case had a prenatal diagnosis of a widened subarachnoid space at 20 weeks' gestation. Two fetuses had exposure to alcohol in utero; 2 were proven to have cytomegalovirus infection; 1 had subarachnoid hemorrhage secondary to maternal use of warfarin; and 1 had a diagnosis of lissencephaly. Only 1 case in this series had normal postnatal development. A prenatal series of fetal widened subarachnoid spaces with possible associated factors is described. Although such relationships were not fully proven, they should be index cases for future studies.
Loffroy, Romaric Rao, Pramod; Ota, Shinichi; Lin Mingde; Kwak, Byung-Kook; Geschwind, Jean-Francois
Acute nonvariceal upper gastrointestinal (UGI) hemorrhage is a frequent complication associated with significant morbidity and mortality. The most common cause of UGI bleeding is peptic ulcer disease, but the differential diagnosis is diverse and includes tumors; ischemia; gastritis; arteriovenous malformations, such as Dieulafoy lesions; Mallory-Weiss tears; trauma; and iatrogenic causes. Aggressive treatment with early endoscopic hemostasis is essential for a favorable outcome. However, severe bleeding despite conservative medical treatment or endoscopic intervention occurs in 5-10% of patients, requiring surgery or transcatheter arterial embolization. Surgical intervention is usually an expeditious and gratifying endeavor, but it can be associated with high operative mortality rates. Endovascular management using superselective catheterization of the culprit vessel, < sandwich> occlusion, or blind embolization has emerged as an alternative to emergent operative intervention for high-risk patients and is now considered the first-line therapy for massive UGI bleeding refractory to endoscopic treatment. Indeed, many published studies have confirmed the feasibility of this approach and its high technical and clinical success rates, which range from 69 to 100% and from 63 to 97%, respectively, even if the choice of the best embolic agent among coils, cyanaocrylate glue, gelatin sponge, or calibrated particles remains a matter of debate. However, factors influencing clinical outcome, especially predictors of early rebleeding, are poorly understood, and few studies have addressed this issue. This review of the literature will attempt to define the role of embolotherapy for acute nonvariceal UGI hemorrhage that fails to respond to endoscopic hemostasis and to summarize data on factors predicting angiographic and embolization failure.
Wu, Hai-Jian; Wu, Cheng; Niu, Huan-Jiang; Wang, Kun; Mo, Lian-Jie; Shao, An-Wen; Dixon, Brandon J; Zhang, Jian-Min; Yang, Shu-Xu; Wang, Yi-Rong
Hemorrhagic stroke which consists of subarachnoid hemorrhage and intracerebral hemorrhage is a dominant cause of death and disability worldwide. Although great efforts have been made, the physiological mechanisms of these diseases are not fully understood and effective pharmacological interventions are still lacking. Melatonin (N-acetyl-5-methoxytryptamine), a neurohormone produced by the pineal gland, is a broad-spectrum antioxidant and potent free radical scavenger. More importantly, there is extensive evidence demonstrating that melatonin confers neuroprotective effects in experimental models of hemorrhagic stroke. Multiple molecular mechanisms such as antioxidant, anti-apoptosis, and anti-inflammation, contribute to melatonin-mediated neuroprotection against brain injury after hemorrhagic stroke. This review article aims to summarize current knowledge regarding the beneficial effects of melatonin in experimental models of hemorrhagic stroke and explores the underlying mechanisms. We propose that melatonin is a promising neuroprotective candidate that is worthy of further evaluation for its potential therapeutic applications in hemorrhagic stroke.
Invernizzi, Rosangela; Quaglia, Federica; Klersy, Caherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L
Summary Background Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anemia. Multiple therapeutic approaches have been tried, but they are largely palliative with variable results.We aimed to assess the efficacy of thalidomide in reducing epistaxis in patients with HHT refractory to standard therapy. Methods HHT patients with severe recurrent epistaxis refractory to mini-invasive surgical procedures were included in an open label, phase II, prospective, non-randomized, single-centre study. Thalidomide was administered at a starting dose of 50 mg/day orally. In the event of no response, thalidomide dosage was increased by 50 mg/day every four weeks until response to a maximum dose of 200 mg/day. After response achievement, patients were treated for eight to16 additional weeks. Monthly follow-up was based on the epistaxis severity score and transfusion need, with adverse events being reported (ClinicalTrials.gov Identifier: NCT01485224). Findings Thirty-one patients, mean age 62∙6 (SD 11∙1) years, were enrolled (median follow-up 15∙9 months, 25th-75th 10∙1-22∙3). Treatment induced cessation of bleeding in three cases (9∙7%) and a significant decrease in all epistaxis parameters in 28 cases (90∙3%). Twenty-five patients (80∙7%) obtained remission with 50 mg/day of thalidomide, five (16∙1%) with 100 mg/day and one (3∙2%) with 150 mg/day. Treatment significantly increased hemoglobin levels (p<0∙001), and abolished or greatly decreased the transfusion need (p<0∙001).Only nonserious, grade I, adverse effects were observed, including constipation and drowsiness. Median time to relapse after the end of therapy was 6∙4 months. No correlation was found between genetic or clinical features and response to thalidomide or toxicity. Interpretation Low-dose thalidomide is safe and very effective in reducing
Kobayashi, S.; Satoh, A.; Koguchi, Y.; Wada, M.; Tokunaga, H.; Miyata, A.; Nakamura, H.; Watanabe, Y.; Yagishita, T.
Summary It is apparent that subarachnoid clots play an important role in the development of delayed vasospasm that is one of the major causes of mortality and morbidity in patients with acutely ruptured cerebral aneurysm. The purpose of this study is to compare the clearance of subarachnoid clots in the acute stage after the treatment with Guglielmi detachable coils (GDC) and after treatment with direct surgery. Forty-nine patients were treated by GDC embolization within four days of the ictus. After GDC embolization, adjunctive therapies, such as ventricular and/or spinal drainage (67%), intrathecal administration of urokinase (41%), continuous cisternal irrigation (16%), and external decompression (16%), were performed. Seventy-four surgically treated patients were subsequently treated by continuous cisternal irrigation with mock-CSF containing ascorbic acid for ten days. The clearance of subarachnoid clots was assessed by the Hounsfield number serial changes on the CT scans taken on days 0, 4, 7,10 after subarachnoid hemorrhage. The incidence of symptomatic vasospasm was lower in the GDC group (6%) than in the surgery group (12%). The clearance of subarachnoid clots from both the basal cistern and the Sylvian fissure was more rapid in the GDC cases than in the surgery cases in the first four days. Intrathecal administration of urokinase accelerated the clearance significantly. GDC embolization followed by intrathecal administration of thrombolytic agents accelerates the reduction of subarachnoid clots and favorably acts to prevent delayed vasospasm. PMID:20663379
Tachibana, Toshiya; Moriyama, Tokuhide; Maruo, Keishi; Inoue, Shinichi; Arizumi, Fumihiro; Yoshiya, Shinichi
The authors report a case of adhesive arachnoiditis (AA) and arachnoid cyst successfully treated by subarachnoid to subarachnoid bypass (S-S bypass). Arachnoid cysts or syringes sometimes compress the spinal cord and cause compressive myelopathy that requires surgical treatment. However, surgical treatment for AA is challenging. A 57-year-old woman developed leg pain and gait disturbance. A dorsal arachnoid cyst compressed the spinal cord at T7-9, the spinal cord was swollen, and a small syrinx was present at T9-10. An S-S bypass was performed from T6-7 to T11-12. The patient's gait disturbance resolved immediately after surgery. Two years later, a small arachnoid cyst developed. However, there was no neurological deterioration. The myelopathy associated with thoracic spinal AA, subarachnoid cyst, and syrinx improved after S-S bypass.
Iwatsuki, Koichi; Yoshimine, Toshiki; Ohnishi, Yu-Ichiro; Ninomiya, Koshi; Moriwaki, Takashi; Ohkawa, Toshika
The authors describe a new modified surgical approach to minimize the postoperative recurrence of a syrinx after surgery to treat syringomyelia associated with spinal adhesive arachnoiditis in two cases. Both patients presented with progressive gait disturbance without any remarkable history, and spinal magnetic resonance imaging revealed a syrinx and broad irregular disappearance of the subarachnoid space and/or deformity of the cord. We successfully performed a partial arachnoid dissection and syrinx-far distal subarachnoid shunt for both cases.
Iwatsuki, Koichi; Yoshimine, Toshiki; Ohnishi, Yu-Ichiro; Ninomiya, Koshi; Moriwaki, Takashi; Ohkawa, Toshika
The authors describe a new modified surgical approach to minimize the postoperative recurrence of a syrinx after surgery to treat syringomyelia associated with spinal adhesive arachnoiditis in two cases. Both patients presented with progressive gait disturbance without any remarkable history, and spinal magnetic resonance imaging revealed a syrinx and broad irregular disappearance of the subarachnoid space and/or deformity of the cord. We successfully performed a partial arachnoid dissection and syrinx-far distal subarachnoid shunt for both cases. PMID:25232285
Martinez, Bridget; Peplow, Philip V.
Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke, which in current practice is performed by computerized tomography (CT) or magnetic resonance imaging (MRI) scans. A panel of microRNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke. This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models. It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke. The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke. Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke. Administration in vivo of miR-130a inhibitor or miRNA mimic (miR-367, miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes. PMID:28250731
A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...
Maekawa, Hidetsugu; Hadeishi, Hiromu
A 67-year-old woman was admitted with aneurysmal subarachnoid haemorrhage and a 12-lead ECG showed ST segment elevation. Transthoracic echocardiography confirmed akinesis of the left ventricular mid-apical segment, with an ejection fraction of 26%, features characteristic of takotsubo cardiomyopathy. Five days later, we identified thrombus in the apex of the left ventricle. Sixteen days after onset, the thrombus had disappeared and wall motion improved (ejection fraction 58%) without evidence of cardioembolism. Takotsubo cardiomyopathy is a cause of cardiac dysfunction after stroke, including SAH. It is characterised by transiently depressed contractile function of the left mid and apical ventricle, without obstructive coronary artery disease. Clinicians should suspect takotsubo cardiomyopathy in patients with subarachnoid haemorrhage who have an ECG abnormality. Echocardiography is needed to detect the distinctive regional wall motion abnormality. Despite its severity in the acute phase, takotsubo cardiomyopathy is self-limiting and its management is conservative.
Iwamuro, Y; Miyake, H; Ito, T; Kumai, J; Kuroda, T; Sugino, T
The patient was a 71-year-old female. On December 20, 1995, she suddenly developed a severe headache with vomiting and was transferred to our hospital. On admission, her conciousness level was 1-2 on the Japan Coma Scale, but there was no neurological deficit except for right oculomotor palsy. Computed tomography showed subarachnoid hemorrhage which had permeated the right lateral ventricle. On cerebral angiography, a giant fusiform aneurysm in the right internal carotid artery was recognized. During the emergency operation, neither neck clipping nor carotid reconstruction was possible because of the tight adhesion of the aneurysm to the peripheral tissue. On account of this, proximal clipping of the carotid artery with external carotid-middle cerebral artery anastomosis with saphenous vein graft was selected. This patient had had an episode of subarachnoid hemorrhage owing to rupture of the right internal carotid-posterior communicating artery aneurysm ten years earlier. At that time, the aneurysmal neck was clipped with a slight residual neck and she left the hospital on foot. Five days later, when the aneurysm was found to be completely thrombosed on CT scan, antiplatelet therapy was started. Although low density areas which corresponded to the regions fed by the right anterior choroidal artery were presented, re-rupture did not occur. Follow-up angiography showed that the aneurysm was completely thrombosed and that the right middle cerebral and the anterior cerebral artery blood was circulated via the vein graft. Among recurrent cases of aneurysm after neck clipping, it is unusual for a giant fusiform aneurysm to be recognized. The growth may have been caused by sclerotic change of the arterial wall. Oculomotor palsy may have delayed the detection of the recurrence of the aneurysm. When residual neck is presented on follow-up angiography, the next angiography should be carried out within at least three years. In this case, antiplatelet therapy was effective to
Francoeur, Charles L; Mayer, Stephan A
For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.
Background Subarachnoid cysts are rare conditions in veterinary medicine, associated with spinal cord dysfunction. Most of the 100 cases of subarachnoid cysts described since the first report in 1968 were apparently not true cysts. Reported cysts are usually situated in the cervical area and occur in predisposed breeds such as the Rottweiler. The purpose of this retrospective study, from May 2003 to April 2012, was to describe the distinctive features of thoracolumbar spinal subarachnoid cysts, together with their surgical treatment and outcome in 6 chondrodystrophic dogs. Results Five Pugs and 1 French Bulldog were examined. Images suggestive of a subarachnoid cyst were obtained by myelography (2/6) and computed tomography myelography (4/6), and associated disc herniation was observed in 3/6 dogs. A hemilaminectomy was performed. The protruding disc eventually found in 5/6 dogs was treated by lateral corpectomy. The ventral leptomeningeal adhesions observed in all dogs after durotomy were dissected. No or only mild post-operative neurological degradation was observed. Follow-up studies (7 months to 4 years) indicated good outcome and no recurrence. Conclusions All the thoracolumbar subarachnoid cysts described in these 6 chondrodystrophic dogs were associated with leptomeningeal adhesions. Good results seemed to be obtained by dissecting and removing these adhesions. A protruding disc, found here in 5/6 dogs, needs to be ruled out and can be treated by lateral corpectomy. PMID:24884635
Wöpking, Sigrid; Kastrup, Andreas; Lentschig, Markus; Brunner, Freimuth
Vasospasms of the intracranial arteries are a well-known complication of subarachnoid hemorrhage and are also frequently encountered in other disorders such as migraine, cerebral vasculitis or reversible cerebral vasoconstriction syndrome. In contrast, recurrent spontaneous vasospasms of the extracranial circulation appear to be extremely rare and have most often been associated with migraine. We present a patient with recurrent strokes due to spontaneous transient vasospastic occlusions of the internal carotid artery (ICA) without migraine over a time period of at least 13 years. Initially, the patient had presented with a bilateral ICA occlusion and a cerebral infarct on the right side. While the right ICA remained occluded, a reopening of the left ICA could be detected 3 days after this initial event. In subsequent years, both duplex sonography and magnetic resonance angiography revealed recurrent occlusions of the left ICA, which resolved spontaneously within days. This case and other rare previous reports indicate that recurrent non-migrainous vasospasms of the extracranial carotid artery likely reflect a distinct entity which can cause ischemic strokes. PMID:24052791
Brown, W.H.; Stothert, J.C. Jr.
Traumatic subarachnoid-pleural fistulas are rare. The authors found nine cases reported since 1959. Seven have been secondary to trauma and two following thoracotomy. One patient's death is thought to be directly related to the fistula. The diagnosis should be suspected in patients with a pleural effusion and associated vertebral trauma. The diagnosis can usually be confirmed with contrast or radioisotopic myelography. Successful closure of the fistula will usually occur spontaneously with closed tube drainage and antibiotics; occasionally, thoracotomy is necessary to close the rent in the dura.
Durnford, A; Dunbar, J; Galea, J; Bulters, D; Nicoll, J A R; Boche, D; Galea, I
Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.
Post-clipping intraparenchymal hemorrhage of the contralateral hemisphere is a very unusual phenomenon in a patient with aneurysmal subarachnoid hemorrhage, unless there is an underlying condition. We report a complicated case of 47-year-old man, who underwent uneventful clipping of ruptured aneurysm and experienced vasospasm two weeks later. Vasospasm was treated by intra-arterial nimodipine and systemic hyperdynamic therapy. One week thereafter, he became unconscious due to intraparenchymal hemorrhage on the anterior border-zone of contalateral hemisphere, but intraoperative and pathologic findings failed to disclose any vascular anomaly. We suggest that the anti-spastic regimens cause local hemodynamic redistribution through the vasodilatory effect and in turn, resulted in such an unexpected bleeding. PMID:19096626
Alexander, James M; Wortman, Alison C
Intrapartum hemorrhage is a serious and sometimes life-threatening event. Several etiologies are known and include placental abruption, uterine atony, placenta accreta, and genital tract lacerations. Prompt recognition of blood loss, identification of the source of the hemorrhage, volume resuscitation, including red blood cells and blood products when required, will result in excellent maternal outcomes.
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
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
Tomii, M; Nakajima, M; Ikeuchi, S; Ogawa, T; Abe, T
Hemorrhage in regions remote from the site of initial intracranial operations is rare, but does occur. We report three cases of cerebellar hemorrhage that developed after supratentorial surgery, all of which had similar clinical findings and CT images. The first case was a 37-year-old man with a craniopharyngioma in the suprasellar lesion. Partial removal of the tumor was performed through frontal craniotomy and the translaminaterminals approach. A large quantity of cerebospinal fluid (CSF) was suctioned from the third ventricle during the operation, resulting in marked brain shrinkage. The second and third cases were 34- and 51-year-old women with unruptured right middle cerebral aneurysms. Clipping of the aneurysms through the pterional approach was performed in both cases. In the second case, CSF was suctioned in large quantity from the carotid and prechiasmal cistern at the operation, resulting in marked brain shrinkage. In the third case, however, only a small volume of CSF was suctioned from the carotid and prechiasmal cistern during the operation, and no marked brain shrinkage was observed. CT scan showed that the hematomas were located mainly in the subdural or the subarachnoid spaces over the cerebellar hemisphere and partially extending into the cerebellar cortex. The mechanism of cerebellar hemorrhage in these series of patients was thought to be multifactorial. The possible etiology for cerebellar hemorrhage in the three cases presented was examined, including the role of CSF suction during surgery and disturbance of venous circulation in the posterior fossa. Suction of the CSF may cause intracranial hypotension. Further reduction of intracranial pressure leads to an increased transluminal venous pressure. There was no episode of hypertension or disturbed blood coagulation during or after the operation. The preoperative angiogram also revealed no abnormality at the region of the posterior fossa. Neuroimaging of infratentorial hemorrhage after
Parrot, A; Fartoukh, M; Cadranel, J
Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority.
Chaudhary, Neeraj; Pandey, Aditya S; Gemmete, Joseph J; Hua, Ya; Huang, Yining; Gu, Yuxiang; Xi, Guohua
Diffusion Tensor Imaging (DTI) has evolved considerably over the last decade to now be knocking on the doors of wider clinical applications. There have been several efforts over the last decade to seek valuable and reliable application of DTI in different neurological disorders. The role of DTI in predicting outcomes in patients with brain tumors has been extensively studied and has become a fairly established clinical tool in this scenario. More recently DTI has been applied in mild traumatic brain injury to predict clinical outcomes based on DTI of the white matter tracts. The resolution of white matter fiber tractography based on DTI has improved over the years with increased magnet strength and better tractography post processing. The role of DTI in hemorrhagic stroke has been studied preliminarily in the scientific literature. There is some evidence that DTI may be efficacious in predicting outcomes of motor function in animal models of intracranial hemorrhage. Only a handful of studies of DTI have been performed in subarachnoid hemorrhage or intraventricular hemorrhage scenarios. In this manuscript we will review the evolution of DTI, the existing evidence for its role in hemorrhagic stroke and discuss possible application of this non-invasive evaluation technique of human cerebral white matter tracts in the future. PMID:26015333
Seki, Toshitaka; Hida, Kazutoshi; Yano, Syunsuke; Iwasaki, Yoshinobu
Effective surgical treatment of adhesive spinal arachnoiditis has not been established because of its complex clinical manifestation. The authors present a new surgical technique to minimize the postoperative recurrence of adhesion after microlysis of adhesion to treat spinal adhesive arachnoiditis. After complete release and reconstruction of the spinal cord, a 0.1 mm Gore-Tex surgical membrane was placed over the cord and fixed to the lateral dural surface with stay sutures. Furthermore, maximal expansion of a subarachnoid space was performed by expansive dural plasty with a 0.3 mm Gore-Tex surgical membrane. We performed this surgical method in tree cases of spinal adhesive arachnoiditis. During a postoperative follow-up period ranging from 2 to 3 years, postoperative neurological deterioration did not occur in all cases, and postoperative MR imaging studied showed no adhesion spinal cord and reconstructed subarachnoid space. The authors believe that this procedure is an effective surgical treatment for spinal adhesive arachnoiditis.
Vinas, F C; Dujovny, M; Fandino, R; Chavez, V
The understanding of the anatomy of the subarachnoid cisterns and trabecular membranes is of paramount importance in the surgical treatment of pathology of the posterior fossa. Aneurysms, arteriovenous malformations, and some tumors should be approached through the subarachnoid space. The subarachnoid cisterns provide natural pathways to approach neurovascular and cranial nerve structures. The microsurgical anatomy of the infratentorial subarachnoid cisterns was studied in twenty adult brains, using the 'immersion technique'. Air was injected into the subarachnoid cisterns and brains were dissected under the operative microscope. Six main compartmental trabecular membranes were identified in the infratentorial level. They divide the subarachnoid space into six cisterns. Cisternal divisions and the disposition of the trabecular membranes were closely related to the vascular divisional patterns of the principal arteries. Thorough knowledge of the microsurgical anatomy of the subarachnoid space will aid neurosurgeons during the surgical approach of many vascular and tumoral lesions located in the posterior fossa.
Vangosa, Alessandra Briatico; Tortora, Domenico; Modestino, Francesco; Cotroneo, Antonio R
The presence of sulcal hyperdensity in patients after endovascular procedures is not necessarily attributable to hemorrhage. It may frequently indicate the absolute or concomitant extravasation of contrast material into the subarachnoid spaces. This case report describes the clinical case of an 84-year-old patient with 90% stenosis of the right internal carotid who presented with a diffuse gyral and sulcal hyperdensity in the right temporal-occipital and frontal lobes at routine post-carotid stenting (CAS) brain CT scan. The patient was asymptomatic and CT findings were interpreted as contrast enhancement hyperattenuation and no therapeutic decisions were made. A 24-hour follow-up brain CT demonstrated the complete resolution of the hyperdensity, confirming the diagnosis. In this patient we considered the concomitant presence of gyral and sulcal hyperdensity as the consequence of reversible damage to the blood-brain barrier (BBB) determining a transitory extravasation of contrast material. Asymptomatic gyral and subarachnoid contrast enhancement following CAS is generally indicative of benign and transitory damage to the BBB and is not to be misinterpreted as hemorrhage. PMID:25923674
Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A
Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism.
Johnston, S. D.; Robinson, T. J.
Aneurysmal subarachnoid haemorrhage is associated with a uniquely severe headache of acute onset. Classical cases are readily identified as such, although this is not always the case. Four cases who were admitted to a district general hospital within a 3-month period are presented, because they demonstrate a variety of presentations, management options, and outcomes. PMID:10320890
Messerer, Mahmoud; Oddo, Mauro; Daniel, Roy Thomas
Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-called early brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed. PMID:24967389
Brinjikji, Waleed; Shahi, Varun; Cloft, Harry J.; Lanzino, Giuseppe; Kallmes, David F; Kadirvel, Ramanathan
Background and Purpose A number of studies have examined the role of matrix metalloproteinases (MMPs) in aneurysm healing following endovascular coiling. Because ruptured aneurysms are known to express higher levels of MMPs, we hypothesized that subarachnoid hemorrhage patients who were on a statin at the time of coil embolization would have lower aneurysm recanalization and retreatment rates than non-statin patients. Materials and Methods We performed a retrospective chart review of patients who received intrasaccular coil embolization of ruptured intracranial aneurysms≤10mm with at least 6-months of imaging follow-up. Patients were separated into two groups: 1) patients who were on an oral statin medication at the time of coiling and 2) patients who were not on a statin. Outcomes studied were aneurysm recurrence and aneurysm retreatment after endovascular coiling. Student’s t-test and chi-squared tests were used to test statistical significance of differences between groups. Results 132 ruptured aneurysm patients with 132 ruptured aneurysms were included in our study. 16 were on statin (12.1%) and 116 were not (87.9%). Recurrence rate was 6.3% in the statin group (1/16) and 36.2% in the non-statin group (42/107) (P=0.017). Unplanned retreatment rates were 6.3% (1/16) for the statin group and 25.9% (30/116) for the non-statin group (P=0.08). Conclusions Statins were associated with a lower rate of aneurysm recurrence following endovascular coiling of small and medium sized ruptured aneurysms in this small retrospective study. Further studies are needed to confirm this finding to determine if statins can be used to reduce recurrence rates in these aneurysms. PMID:26272974
Webb, S T; Farling, P A
The management of patients with subarachnoid haemorrhage following rupture of an intracranial aneurysm is changing. The recent introduction of endovascular occlusion of the aneurysm using detachable coils offers an alternative to craniotomy and clipping of the aneurysm for the prevention of recurrent aneurysmal haemorrhage. The aim of this survey was to evaluate the current provision of peri-operative care for patients with an aneurysmal subarachnoid haemorrhage in the United Kingdom and Republic of Ireland. A survey was conducted of the 34 neuroscience centres which provide an adult neurosurgery service in the United Kingdom and Republic of Ireland. Most centres reported an increasing role for coiling, and a decreasing role for clipping in the management of aneurysmal subarachnoid haemorrhage. The provision of peri-operative care for patients undergoing interventional neuroradiology procedures varied greatly between centres. Neurovascular services in the UK are being reorganised and adequate staff and facilities should be available for the peri-operative care of patients undergoing interventional neuroradiology procedures.
Su, Cindy W
Postpartum hemorrhage (PPH) is a very common obstetric emergency with high morbidity and mortality rates worldwide. Understanding its etiology is fundamental to effectively managing PPH in an acute setting. Active management of the third stage of labor is also a key component in its prevention. Management strategies include conservative measures (medications, uterine tamponade, and arterial embolization) as well as surgical interventions (arterial ligations, compression sutures, and hysterectomy). Creating a standardized PPH protocol and running simulation-based drills with a multidisciplinary team may also help decrease maternal morbidity and improve perinatal outcomes, although further studies are needed.
Hussain, Z; Ahmed, M S; Alexander, D J; Miller, G V; Chintapatla, S
We describe the second reported case of three consecutive episodes of gallstone ileus and ask the question whether recurrent gallstone ileus justifies definitive surgery to the fistula itself or can be safely managed by repeated enterotomies.
Alexander, Matthew D; Hetts, Steven W; Young, William L; Halbach, Van V; Dowd, Christopher F; Higashida, Randall T; English, Joey D
Hemorrhage represents the most feared complication of cerebral arteriovenous malformations (AVMs) in both untreated patients and those treated with gamma knife radiosurgery. Radiosurgery does not immediately lead to obliteration of the malformation, which often does not occur until years following treatment. Post-obliteration hemorrhage is rare, occurring months to years after radiosurgery, and has been associated with residual or recurrent AVM despite prior apparent nidus elimination. Three cases are reported of delayed intracranial hemorrhage in patients with cerebral AVMs treated with radiosurgery in which no residual AVM was found on catheter angiography at the time of delayed post-treatment hemorrhage. That the pathophysiology of these hemorrhages involves progressive venous outflow occlusion is speculated and the possible mechanistic link to subsequent vascular rupture is discussed.
Sato, Kota; Kato, Shunsuke; Nagano, Hiroto; Ohtsukasa, Shunro; Kawachi, Yasuyuki
A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities. PMID:27807449
Takamatsu, Susumu; Sato, Kota; Kato, Shunsuke; Nagano, Hiroto; Ohtsukasa, Shunro; Kawachi, Yasuyuki
A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.
Dohi, K; Jimbo, H; Ikeda, Y; Fujita, S; Ohtaki, H; Shioda, S; Abe, T; Aruga, T
We evaluated the effects of a novel pharmacological brain cooling (PBC) method with indomethacin (IND), a nonselective cyclooxygenase inhibitor, without the use of cooling blankets in patients with hemorrhagic stroke. Forty-six patients with hemorrhagic stroke (subarachnoid hemorrhage; n = 35, intracerebral hemorrhage; n = 11) were enrolled in this study. Brain temperature was measured directly with a temperature sensor. Patients were cooled by administering transrectal IND (100 mg) and a modified nasopharyngeal cooling method (positive selective brain cooling) initially. Brain temperature was controlled with IND 6 mg/kg/day for 14 days. Cerebrospinal fluid concentrations of interleukin-1beta (CSF IL-1beta) and serum bilirubin levels were measured at 1, 2, 4, and 7 days. The incidence of complicating symptomatic vasospasm after subarachnoid hemorrhage was lower than in non-PBC patients. CSF IL-1beta and serum bilirubin levels were suppressed in treated patients. IND has several beneficial effects on damaged brain tissues (anticytokine, free radical scavenger, antiprostaglandin effects, etc.) and prevents initial and secondary brain damage. PBC treatment for hemorrhagic stroke in patients appears to yield favorable results by acting as an antiinflammatory cytokine and reducing oxidative stress.
Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C
Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.
Ussia, Anastasia; Betsas, George; Corona, Roberta; De Cicco, Carlo; Koninckx, Philippe R
Massive hemorrhagic ascites (4470 mL, range 1-10 L) in women with endometriosis is a rare condition occurring predominantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascites is predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomy cures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%; during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment. Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recurrence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigs syndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted given the cure rate of some 20%. It is unknown what the effect of ovulation induction would be.
Kranthi, Sannepaneni; Sahu, Barada P.; Aniruddh, Purohit
Context: Poor grade subarachnoid hemorrhage (SAH) is usually associated with unfavorable outcomes and optimal management is deemed complicated. Most centres follow an expectant management strategy or a less aggressive approach till patients improve to good clinical grades. This approach has been associated with higher mortality and morbidity. However, not all patients with poor clinical condition fare badly. Identification and early aggressive management of this select group of patients may lead to favorable outcomes. Settings and Design: Prospective non-randomized study. Materials and Methods: We prospectively analyzed 19 cases presented in WFNS grade 4 and 5 and factors affecting their outcome at a tertiary care centre in south India. This study was aimed at identifying those few poor grade patients who are probable candidates for a good outcome. Statistical Analysis Used: All the variables were analyzed for possible correlations with the SPSS version 13 software. The Chi-square test with a P < 0.05 was taken as statistically significant. Results: Of 19 cases, 13 were operated and good outcome was seen in 53.8% of the patients who underwent surgery and aggressive management. All 7 patients who were managed conservatively died. 15.8% of the patients had low density changes (P = 0.625). Absence of such changes was associated with a good long term outcome (P = 0.004). 9 patients had intraventricular hemorrhage at presentation and 5 patients having hydrocephalus underwent extra-ventricular drainage. Statistically significant factors precluding good outcome were the presence of infarcts and thick SAH in the cisterns. Conclusions: Poor grade (WFNS 4 and 5) SAH patients with or without ICH, IVH, if operated within 3 days can give rise to favorable outcome in around 50%. However, presence of patchy infarcts associated with thick subarachnoid blood (Fisher grade 3) precludes long term survival or meaningful recovery. Hence, aggressive management is unlikely to alter the
Heit, Jeremy J.; Iv, Michael; Wintermark, Max
Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage. PMID:28030895
Pandey, Nityanand; Mahapatra, Ashok; Singh, Pankaj Kumar
Traumatic bilateral basal ganglia bleed is extremely rare. It is defined as a hemorrhagic lesion located in the basal ganglia or neighboring structures such as the internal capsule and the thalamus. This report describes a 37-year-old man who had large bilateral basal ganglia hemorrhage (BGH) with subdural hematoma and traumatic subarachnoid hemorrhage. With regards to an etiology of bilateral hemorrhage of the basal ganglia, we could not disclose any possible cause except head injury in spite of full diagnostic work-up. Our final diagnosis was bilateral traumatic BGH (TBGH). The pathomechanism of such injuries is still not clear and it is proposed to be due to shear injury to the lenticulostriate and choroidal arteries. Rather than any features of the TBGH itself, duration of coma and/or associated temporal herniation predicted slower recovery and worse outcome. Bilateral TBGH is an extremely rare entity, compatible with a favorable recovery, if not associated with damage to other cortical and subcortical structures and occurring in isolation. TBGH can be considered as a marker of poor outcome rather than its cause. The BGHs seem to be hemorrhagic contusions resulting from a shearing injury, due to high velocity impact. PMID:25685230
Singla, Navneet; Aggarwal, Ashish; Vyas, Sameer; Sanghvi, Ankur; Salunke, Pravin; Garg, Ravi
Background A sudden onset of neurological symptoms in patients is conventionally thought to be due to vascular phenomenon, with one common differential diagnosis being subarachnoid hemorrhage. Another important differential diagnosis is ischemic stroke. An uncommon cause of such acute symptoms can be hemorrhage in a pre-existing tumor, that is, intratumoral hemorrhage (ITH). Purpose ITH is an important, though uncommon differential diagnosis in cases of sudden onset of neurological deterioration. Methods and Result A 60-year-old male presented with seizures and loss of consciousness 12 h prior to admission. The episode was sudden in onset. After detailed clinical and radiological investigations, the patient was diagnosed with glioma with bleed and was successfully operated upon. Conclusion The combination of hemorrhage and ischemic stroke pointed more towards an aneurysm rather than a tumor bleed. There were pointers both in favor of and against both the diagnosis. Therefore, a complex hemorrhagic cerebral tumor with acute presentation and discordant finding on CT or CT angiography should be characterized preoperatively. A large thrombosed aneurysm remains an important differential diagnosis. PMID:27780994
Finsterer, Josef; Sehnal, Ernst
Recent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT), low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis), insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability. PMID:26167029
Yoshida, H; Moriyama, Y; Tatekawa, T; Tominaga, N; Teshima, H; Hiraoka, A; Masaoka, T; Yoshinaga, T
This manuscript reports Bacillus cereus sepsis in two cases with acute myelogenous leukemia (AML) who suffered complications of fatal intracranial hemorrhage during remission induction therapy. The first case was 43-year-old male with AML (M0) receiving first consolidation chemotherapy who developed sudden diarrhea, abdominal pain and spiking fever. Two days later, he died of intracranial hemorrhage. The second case was 15-year-old male with AML (M5b) who was receiving first induction chemotherapy. He developed headache and vomiting following spiking fever and diarrhea. He died of subarachnoid hemorrhage the next day. In both cases, Bacillus cereus was isolated from blood culture. Fatal intracranial hemorrhage due to severe bleeding tendency caused rapid to death in both cases. These bleeding tendencies might have been induced by B. cereus sepsis. In addition, we should not overlook B. cereus as contamination, but rather consider it as a potential pathogen, when isolated from blood culture.
Graeb, D.A.; Robertson, W.D.; Lapointe, J.S.; Nugent, R.A.; Harrison, P.B.
Sixty-eight patients with intraventricular hemorrhage (IVH) diagnosed by computed tomography (CT) were reviewed retrospectively to determine the etiology and prognosis, relationship to delayed hydrocephalus, and effect on neurological outcome. The most common causes were a ruptured aneurysm, trauma, and hypertensive hemorrhage. Ruptured aneurysms of the anterior communicating artery can often be predicted from the nonenhanced CT scan. The total mortality rate was 50%; however, 21% of patients returned to normal or had only mild disability. Patients in whom no cause was identified had a better prognosis. Delayed hydrocephalus was related to the effects of subarachnoid hemorrahage rather than obstruction of the ventricular system by blood. IVH per se is seldon a major factor in the neurological outcome.
Jakobs, Martin; Orakcioglu, Berk
Ectopic recurrence of craniopharyngioma is a rare phenomenon after transcranial resection of the primary tumor. The authors present a case of ectopic recurrent adamantinomatous craniopharyngioma of the frontal bone resected 16 years after initial transcranial resection of the primary tumor. The lesion was first radiographically described 12 years after surgery and was adjacent to the osteosynthesis plate that had been implanted at the craniotomy site. The recurrent craniopharyngioma was totally resected via a lateral eyebrow approach. No infiltration of the meninges or the brain was detected. Only 50 cases of ectopic recurrent craniopharyngioma have been described to date, with the present case being the first one with recurrence located at the skull bone. So far 2 mechanisms have been described: contamination with tumor cells alongside the surgical tract and spreading via CSF and the subarachnoid space. The authors reviewed the literature, provided the largest collection of cases so far, and performed basic statistical analysis regarding ectopic recurrence. Pediatric and adult patients as well as male and female ones are affected equally by this phenomenon. The mean time of ectopic recurrence after initial surgery was 7.1 years. Ectopic recurrence, although rare, should always be considered in a patient with a newly diagnosed intracranial lesion who has undergone transcranial craniopharyngioma resection before.
Liebenberg, W; Worth, R; Firth, G; Olney, J; Norris, J
Background: The natural history of untreated aneurysmal subarachnoid haemorrhage carries a dismal prognosis. Case fatalities range between 32% and 67%. Treatment with either surgical clipping or endovascular coiling is highly successful at preventing re-bleeding and yet the diagnosis is still missed. Methods: Based on the national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage and a review of other available literature this study has compiled guidance in making the diagnosis. Conclusion: In patients presenting with a suspected non-traumatic subarachnoid haemorrhage, computed tomography within 12 hours will reliably show 98% of subarachnoid haemorrhage. In patients who present after 12 hours with a negative computed tomogram, formal cerebrospinal fluid spectophotometry will detect subarachnoid haemorrhage for the next two weeks with a reliability of 96%. Between the early diagnosis with the aid of computed tomography and the later diagnosis with the added benefit of spectophotometry in the period where computed tomograms become less reliable, it should be possible to diagnose most cases of subarachnoid haemorrhage correctly. PMID:15998826
Ameen, A A; Illingworth, R
One hundred consecutive patients treated with epsilon aminocaproic acid 24 grams daily prior to surgery for ruptured intracranial aneurysms have been compared with the previous 100 patients managed similarly but without anti-fibrinolytic drugs. No other alterations in management were made and the two series are closely comparable in all other respects. Fewer episodes of recurrent haemorrhage and deaths from this cause occurred in the treated patients, but more cases of cerebral ischaemia occurred. Neither difference is statistically significant and overall more deaths occurred in the patients treated with antifibrinolytic drugs. The value of this method of treatment in the management of aneurysmal subarachnoid haemorrhage is questioned. PMID:7229645
Guttmacher, A E; Callahan, J R
Chronic illness played a major role in the life and literary success of Robert Louis Stevenson. However, the exact nature of his chronic illness remains unclear. It is possible that Stevenson had hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber Syndrome). This would explain his chronic respiratory complaints, recurrent episodes of pulmonary hemorrhage, and his death, at age 44 years, of probable cerebral hemorrhage. It would also explain his mother's hitherto unreported but apparent stroke, at age 38 years. Further support for this hypothesis might come from new details about the health of Stevenson and his relatives or from molecular analysis of tissue specimens remaining from him.
Mitsuyama, Tetsuryu; Asamoto, Shunji; Kawamata, Takakazu
Spinal cord tethering and cerebrospinal fluid (CSF) flow disturbance are two major features in the pathophysiology of spinal adhesive arachnoiditis. We hypothesized that insufficient CSF supply to the surgically untethered spinal cord may be one of the causes of the typical post-operative recurrent extensive lesion. We report a patient with extensive spinal adhesive arachnoiditis, who was successfully treated using a novel surgical technique consisting of two procedures. First, microdissection of the thickened adherent arachnoid was performed to resolve spinal cord tethering. Next, a ventriculo-subarachnoid shunt was placed to provide sufficient flow of CSF. Clinical improvement was sustained for at least 22 months after surgery. The present surgical procedure may improve clinical outcome in patients with longitudinally extensive spinal adhesive arachnoiditis.
Pease, Anthony; Sullivan, Stacey; Olby, Natasha; Galano, Heather; Cerda-Gonzalez, Sophia; Robertson, Ian D; Gavin, Patrick; Thrall, Donald
Three case history reports are presented to illustrate the value of the single-shot turbo spin-echo pulse sequence for assessment of the subarachnoid space. The use of the single-shot turbo spin-echo pulse sequence, which is a heavily T2-weighted sequence, allows for a rapid, noninvasive evaluation of the subarachnoid space by using the high signal from cerebrospinal fluid. This sequence can be completed in seconds rather than the several minutes required for a T2-fast spin-echo sequence. Unlike the standard T2-fast spin-echo sequence, a single-shot turbo spin-echo pulse sequence also provides qualitative information about the protein and the cellular content of the cerebrospinal fluid, such as in patients with inflammatory debris or hemorrhage in the cerebrospinal fluid. Although the resolution of the single-shot turbo spin-echo pulse sequence images is relatively poor compared with more conventional sequences, the qualitative information about the subarachnoid space and cerebrospinal fluid and the rapid acquisition time, make it a useful sequence to include in standard protocols of spinal magnetic resonance imaging.
Dohi, K; Mochizuki, Y; Satoh, K; Jimbo, H; Hayashi, M; Toyoda, I; Ikeda, Y; Abe, T; Aruga, T
Bilirubin (Bil) is the end product of heme catabolism. The production of Bil reflects heme oxygenase-1 expression in response to oxidative stress in various diseases. To assess the role of Bil as a marker of oxidative stress in cases of brain damage, we measured serum Bil concentrations in patients with hemorrhagic stroke. Serum levels of total Bil were measured in 20 subarachnoid hemorrhage patients with symptomatic vasospasms and in 23 patients with intracerebral hemorrhage; concentrations were measured every day for 14 consecutive days. Serum Bil levels were significantly elevated in the early phases in both groups. Moreover, transient elevation was observed on the day prior to the observation of clinical manifestations of symptomatic vasospasm after SAH. Bil, known to be a powerful antioxidant, was induced after hemorrhagic stroke, reflecting the intensity of oxidative stress. Plasma Bil concentrations might serve as a useful marker of oxidative stress in hemorrhagic stroke patients.
Marcì, Marcello; Savatteri, Paolino; Pizzuto, Antonino; Giammona, Giuseppe; Renda, Baldassare; Lojacono, Francesca; Sanfilippo, Nicola
It is well known that cardiopulmonary complications are often associated to subarachnoid haemorrhage. For appropriate therapeutic managing it is very important to distinguish acute coronary syndrome from neurogenic myocardial injury, which is a reversible condition. Furthermore, because the hearts of brain dead patients may be utilized for therapeutic purpose, it has became of importance to rule out erroneous diagnosis of cardiac ischemia in order to avoid rejection of hearts potential suitable for transplantation.We present a report of two female patients affected by cardiac complications caused by aneurismal subarachnoid haemorrhage admitted to our neurosurgical intensive care department.
Fletcher, Jeffrey J.; Rajajee, Venkatakrishna; Wilson, Thomas J.; Zahuranec, Darin B.
Background Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression following stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal SAH (aSAH). Methods Data were obtained from a single center cohort study of aSAH patients admitted January 1, 2007 through April 1, 2012. AS was defined as at least one early (<72 hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates. Results A total 167 patients were included in the analysis (mean age 56, 27% male). AS was seen in 66/167 (40%; 95% CI, 32%–47%), and infection was seen in 80/167 (48%; 95% CI, 40%–55%). AS was associated with subsequent infection on unadjusted analysis (OR=2.11; 95% CI, 1.12–3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, 0.67–2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection following aSAH. Conclusions We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding. PMID:24189451
Ikeda, Daniel S; Villelli, Nicolas; Shaw, Andrew; Powers, Ciarán
Bow hunter's syndrome (BHS), or positional vertebrobasilar insufficiency, is a rare disorder characterized by positional stenosis or occlusion of the dominant vertebral artery (VA) with concordant signs and symptoms of brainstem ischemia. Many etiologies have been described, with the most common level of obstruction occurring at the craniocervical junction. The authors report acquired BHS after the patient's contralateral VA was sacrificed for ruptured aneurysm. A 44-year-old man was referred to our institution for years of continued positional tinnitus, vertigo, and nausea. This symptomatology began 5 years prior, immediately after the patient's right VA was endovascularly sacrificed to treat a ruptured VA aneurysm. From the time of treatment, right head turning caused instantaneous symptoms consistent with brainstem ischemia. Evaluations performed during the 5 year interim before referral included computed tomography angiography, MRI, and diagnostic cerebral angiography (DCA). All failed to identify a causal etiology. A diagnosis of BHS was made with dynamic DCA. With the patient's head turned to the right, angiography of the left VA demonstrated a positional block. The patient underwent left VA decompression. Intraoperative dynamic DCA was utilized to demonstrate adequacy of decompression. The patient tolerated the procedure without complication. Symptomatology immediately completely subsided and remained absent at his 3 month follow-up. An acquired BHS should be recognized as a possible complication if VA sacrifice is considered for an unclippable or uncoilable aneurysm.
Gao, Cheng; Liu, Xiangzhen; Liu, Wei; Shi, Huaizhang; Zhao, Zhenhuan; Chen, Huirong; Zhao, Shiguang
This study was designed to explore the effects of Tetramethylpyrazine on cerebral vasospasm and early brain injury and its underlying mechanisms after experimental SAH in rats. Male Sprague-Dawley rats (n=164) were allocated randomly to SAH+TMP, SAH+vehicle (sodium chloride), or sham-operated group. The SAH model was induced through perforating internal carotid artery. TMP (30 mg/kg) or the vehicle was injected via vena caudalis 60 min before the perforation. Mortality, neurological scores, water content of brain and cerebral vasospasm were recorded at 24 h after SAH. Apoptosis of cerebral cortex was determined by TUNEL staining; caspase-3, bax and bcl-2 by Western blotting; P53 expression by immunohistochemical staining. TMP administrated in advance improved neurological scores, ameliorated cerebral edema and cerebral vasospasm. TUNEL-positive cells were reduced significantly in TMP-treated group. P53 was not found significantly different between TMP-treated and vehicle-treated group, while P53 positive cells were markedly higher in SAH group than that in sham-operated group. Cleaved caspase-3 protein was decreased significantly in TMP-treated group, while bax, bcl-2 protein expression did not differ statistically among the three groups. In conclusion, TMP ameliorated cerebral vasospasm and early brain injury after experimental SAH in rats. The underlying mechanisms may be partly related to inhibition of caspase-3 dependent proapoptosis pathway.
Lo, Benjamin W. Y.; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R. Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A. H.
Background: Brain–body associations are essential in influencing outcome in patients with ruptured brain aneurysms. Thus far, there is scarce literature on such important relationships. Methods: The multicenter Tirilazad database (3551 patients) was used to create this clinical outcome prediction model in order to elucidate significant brain–body associations. Traditional binary logistic regression models were used. Results: Binary logistic regression main effects model included four statistically significant single prognostic variables, namely, neurological grade, age, stroke, and time to surgery. Logistic regression models demonstrated the significance of hypertension and liver disease in development of brain swelling, as well as the negative consequences of seizures in patients with a history of myocardial infarction and post-admission fever worsening neurological outcome. Conclusions: Using the aforementioned results generated from binary logistic regression models, we can identify potential patients who are in the high risk group of neurological deterioration. Specific therapies can be tailored to prevent these detriments, including treatment of hypertension, seizures, early detection and treatment of myocardial infarction, and prevention of hepatic encephalopathy. PMID:27583179
Adult mongrel dogs were used. The posterior communicating artery was punctured with a fine needle and subarachnoid hemorrhage was produced, which simulated aneurysmal rupture in human. The cerebral basal arteries were constricted remarkably after the puncture. However this vasospasm disappeared in about 60-120 minutes. After this restoration, the vessels began to be constricted again and reduced their diameter in greater degree with lapse of time. Effect of various drugs and sympathectomy on the experimental spasm induced by this method were studied utilizing the magnified vertebral angiography. The drugs used were papverine, isoxuprine, methysergide, phentolamine and propranolol. One of these drugs was given to each dog into the vertebral artery 15 minutes after the puncture of the artery for study of the early spasm, and the same procedure was carried out 24 hours after the late spasm. Vertebral arteriograms were taken immediately after and at 5, 10 and 30 minutes after injection of the drug. Diameter changes of the cerebral basal arteries were measured on the film. Smooth muscle relaxtants, papaverine and isoxsuprine, were effective on relieving the early and the late spasm. An antiserotonin agent, methysergide, relieved slightly the early spasm, but it had no effect on the late spasm. Phentolamine, that is an adrenergic blocking agent, relieved the early spam remarkably, but it was less effective on the late spam. A beta adrenergic blocking agent, propranolol, was effective on relieving neither the early nor the late spasm. Two weeks after the removal of the bilateral upper cervical ganglia, subarachnoid hemorrhage was produced by the smae method as mentioned above in four dogs. Arteriograms taken 24 hours after puncture of the posterior communicating artery in these dogs showed vasoconstriction as same as in the non-sympathectomized dogs. From these experimental results, it was suggested that an etiological difference in the early and the late spasm may exist
Powell, Anna M; Nyirjesy, Paul
Vulvovaginitis (VV) is one of the most commonly encountered problems by a gynecologist. Many women frequently self-treat with over-the-counter medications, and may present to their health-care provider after a treatment failure. Vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis may occur as discreet or recurrent episodes, and have been associated with significant treatment cost and morbidity. We present an update on diagnostic capabilities and treatment modalities that address recurrent and refractory episodes of VV.
Yılmaz, Baran; Işık, Semra; Ekşi, Murat Şakir; Ekşi, Emel Ece Özcan; Akakın, Akın; Toktaş, Zafer Orkun; Konya, Deniz
Remote cerebellar hemorrhage after cranial and spinal surgeries is a well-documented entity, so far concomitant supra- and infra-tentorial hemorrhage after spine surgery has rarely been reported in the literature. A 57-year-old woman presented with intractable low back pain and severely impaired mobility. One year ago, she underwent lumbar laminectomy and fusion with posterior spinal instrumentation between L2 and S1. She developed adjacent segment disease at the upper level of the instrumented vertebra. She had a revision surgery and underwent posterior laminectomy and fusion with bilateral transpedicular instrumentation between T10 and S1. She had severe headache, somnolence, and left hemiparesia 48 h after the surgery. Her emergent head computed tomography depicted intra-parenchymal hemorrhage in the right parietal lobe accompanying with subarachnoid hemorrhage, bilateral symmetrical cerebellar hemorrhages and pneumocephalus. She was treated nonsurgically and she got better despite some residual deficits. Symptoms including constant headache, nausea, vomiting, impaired consciousness, new onset seizure, and focal neurological deficit after spine surgeries should raise suspicion for intracranial intra-parenchymal hemorrhage. PMID:26692705
Yılmaz, Baran; Işık, Semra; Ekşi, Murat Şakir; Ekşi, Emel Ece Özcan; Akakın, Akın; Toktaş, Zafer Orkun; Konya, Deniz
Remote cerebellar hemorrhage after cranial and spinal surgeries is a well-documented entity, so far concomitant supra- and infra-tentorial hemorrhage after spine surgery has rarely been reported in the literature. A 57-year-old woman presented with intractable low back pain and severely impaired mobility. One year ago, she underwent lumbar laminectomy and fusion with posterior spinal instrumentation between L2 and S1. She developed adjacent segment disease at the upper level of the instrumented vertebra. She had a revision surgery and underwent posterior laminectomy and fusion with bilateral transpedicular instrumentation between T10 and S1. She had severe headache, somnolence, and left hemiparesia 48 h after the surgery. Her emergent head computed tomography depicted intra-parenchymal hemorrhage in the right parietal lobe accompanying with subarachnoid hemorrhage, bilateral symmetrical cerebellar hemorrhages and pneumocephalus. She was treated nonsurgically and she got better despite some residual deficits. Symptoms including constant headache, nausea, vomiting, impaired consciousness, new onset seizure, and focal neurological deficit after spine surgeries should raise suspicion for intracranial intra-parenchymal hemorrhage.
Kahlke, Volker; Brossmann, Joachim; Klomp, Hans-Juergen
A 55-year-old women developed an aortointestinal fistula between the bifurcation of the aorta and the distal ileum following implantation of multiple endovascular stents into both common iliac arteries for treatment of aortoiliac occlusive disease. Ten months before the acute onset of the gastrointestinal hemorrhage two balloon-expandable steel stents had been implanted into both common iliac arteries. Due to restenosis and recurrent intermittent claudication, three balloon-expandable covered stents were implanted 4 months later on reintervention. The patient presented with abdominal pain and melena, and fell into hemorrhagic shock with signs of upper gastrointestinal bleeding. After transfer to our hospital, she again developed hemorrhagic shock with massive upper and lower gastrointestinal bleeding and died during emergency laparotomy. The development of aortoenteric fistulas following endovascular surgery/stent implantation is very rare and has to be considered in cases of acute gastrointestinal hemorrhage.
Bencze, János; Varkoly, Gréta; Kouhsari, Mahan C; Klekner, Álmos
Abstract Meningioma accounts for more than 30% of all intracranial tumours. It affects mainly the elderly above the age of 60, at a female:male ratio of 3:2. The prognosis is variable: it is usually favourable with no progression in tumour grade and no recurrence in WHO grade 1 tumours. However, a minority of tumours represent atypical (grade 2) or anaplastic (grade 3) meningiomas; this heterogeneity is also reflected in histopathological appearances. Irrespective of the grade, the size of the tumour and the localisation may have severe, sometimes lethal consequences. Following neurosurgical interventions to remove the tumour, recurrence and progression in WHO grade may occur. Our knowledge on predisposing histomorphological and molecular factors of recurrence is rather limited. These can be classified as I) demographic II) environmental, III) genetic and epigenetic IV) imaging, V) neuropathological, and VI) neurosurgical. In view of the complex background of tumour recurrence, the recognition of often subtle signs of increased risk of recurrence requires close collaboration of experts from several medical specialties. This multidisciplinary approach results in better therapy and fewer complications related to tumour recurrence. PMID:28352788
Pigott, David C
This article reviews the epidemiology, pathophysiology, and clinical management of patients with suspected or confirmed viral hemorrhagic fever infection. The focus is on clinical management based on case series from naturally occuring outbreaks of viral hemorrhagic fever infection as well as imported cases of viral hemorrhagic fever encountered in industrialized nations. The potential risk of bioterrorism involving these agents is discussed as well as emergency department and critical care management of isolated cases or larger outbreaks. Important aspects of management, including recognition of infected patients, isolation and decontamination procedures, as well as available vaccines and therapies are emphasized.
Haynes, H R; Visca, A; Renowden, S; Malcolm, G
A case of thrombus formation occurring within a dilation of the dural venous sinuses following aneurysmal sub-arachnoid haemorrhage is presented. Acute neurological deterioration accompanied propagation of the thrombus. The patient was anticoagulated on day 5 post-SAH with no haemorrhagic complications and made a full recovery. The optimum time to commence anticoagulation is not clear and is discussed.
Haddad, Waleed S.; Trebes, James E.
The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stroke in human or animal patients as well as for the detection of hemorrhage within a patient's body.
Haddad, Waleed S.; Trebes, James E.
The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stoke in human or animal patients as well as for the detection of hemorrhage within a patient's body.
This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...
Burnett, Mark W
Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers.
Liu, Hua; Luo, Zhengxiang; Liu, Zhongkun; Yang, Jian; Kan, Shifeng
Objective: Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage with a substantial recurrence rate. Atorvastatin may reduce CSDH via its anti-inflammatory and pro-angiogenesis effects, but its effectiveness for preventing recurrent CSDH has never been explored. We hypothesized that atorvastatin is effective in reducing recurrence of CSDH after surgery and identified determining factors predictive of hematoma recurrence. Methods: A prospective study was conducted in 168 surgical cases of CSDH.All patients were randomly assigned to the group treated with atorvastatin or control group. Clinically relevant data were compared between two groups, and subsequently between the recurrence and non-recurrence patients. Multiple logistic regression analysis of the relationship between atorvastatin treatment and the recurrence using brain atrophy, septated and bilateral hematoma was performed. Results: Atorvastatin group conferred an advantage by significantly decreasing the recurrence rate (P = 0.023), and patients managed with atorvastatin also had a longer time-to-recurrence (P = 0.038). Admission brain atrophy and bilateral hematoma differed significantly between the recurrence and non-recurrence patients (P = 0.047 and P = 0.045). The results of logistic regression analysis showed that atorvastatin significantly reduced the probability of recurrence; severe brain atrophy and bilateral hematoma were independent risk factors for recurrent CSDH. Conclusions: Atorvastatin administration may decrease the risks of recurrence.Patients with severe brain atrophy and bilateral CSDH are prone to the recurrence. PMID:27445673
Hack, Margherita; Selvelli, Pierluigi
Recurrent novae seem to be a rather inhomogeneous group: T CrB is a binary with a M III companion; U Sco probably has a late dwarf as companion. Three are fast novae; two are slow novae. Some of them appear to have normal chemical composition; others may present He and CNO excess. Some present a mass-loss that is lower by two orders of magnitude than classical novae. However, our sample is too small for saying whether there are several classes of recurrent novae, which may be related to the various classes of classical novae, or whether the low mass-loss is a general property of the class or just a peculiarity of one member of the larger class of classical novae and recurrent novae.
Kazimi, Mircelal; Ulas, Murat; Ibis, Cem; Unver, Mutlu; Ozsan, Nazan; Yilmaz, Funda; Ersoz, Galip; Zeytunlu, Murat; Kilic, Murat; Coker, Ahmet
Lower gastrointestinal hemorrhage accounts for approximately 20% of gastrointestinal hemorrhage. The most common causes of lower gastrointestinal hemorrhage in adults are diverticular disease, inflammatory bowel disease, benign anorectal diseases, intestinal neoplasias, coagulopathies and arterio-venous malformations. Hemangiomas of gastrointestinal tract are rare. Mesenteric hemangiomas are also extremely rare. We present a 25-year-old female who was admitted to the emergency room with recurrent lower gastrointestinal bleeding. An intraluminal bleeding mass inside the small intestinal segment was detected during explorative laparotomy as the cause of the recurrent lower gastrointestinal bleeding. After partial resection of small bowel segment, the histopathologic examination revealed a cavernous hemagioma of mesenteric origin. Although rare, gastrointestinal hemangioma should be thought in differential diagnosis as a cause of recurrent lower gastrointestinal bleeding. PMID:19178725
Samosudova, N V; Reutov, V P; Krushinsky, A L; Kuzenkov, V S; Sorokina, E G
We studied the effect of locomotor activity on the ultrastructure of cerebellar neurons, neurological disturbances, and survival rate in Krushinsky-Molodkina rats during the development of hemorrhagic induced by acoustic stress. In animals with high spontaneous locomotor activity, severe edema of cerebellar neurons (resulting in the destruction of surrounding structures) and swelling of the synapses (terminals of mossy fibers on granule cell dendrites) were observed. By contrast, the areas of intracerebral, subdural, and subarachnoid hemorrhages were lower in rats under conditions of forced rest.
Sabageh, Donatus; Odujoko, Oluwole Olaniyi; Komolafe, Akinwumi Oluwole
Right atrial myxomas are rare primary tumors of the heart. They may remain asymptomatic or eventually cause constitutional signs and symptoms. Less frequently, obstruction of the tricuspid valve occurs, resulting in exertional dyspnea, syncope, or sudden death. Neurological manifestation as initial presentation of atrial myxomas is rarely, if ever, associated with right atrial myxomas and may be secondary to cerebral infarction, cerebral hemorrhage and, more rarely subarachnoid hemorrhage. We review the case of a previously unknown, middle-aged Nigerian man who presented to hospital with severe headache and sudden loss of consciousness. A clinical diagnosis of hypertensive hemorrhagic cerebrovascular accident was made. The patient died suddenly a few hours after presentation. Post-mortem examination revealed a small intracerebral hemorrhage in the left superior temporal lobe as well as a large right atrial myxoma, a ventricular septal defect in the muscular septum, and right ventricular hypertrophy. The liver showed fatty change while the kidneys showed evidence of benign nephrosclerosis. Right atrial myxomas may, therefore, be remotely considered as a cause of intracranial hemorrhage, especially in the presence of predisposing cardiac anomalies such as a ventricular septal defect. Similarly, being a known cause of right heart failure, sudden death, and other constitutional derangements, it may contribute significantly to disease outcome. Hence, it should be given due consideration in the differential diagnosis of cerebrovascular accidents.
de Carvalho, Felipe Gonçalves; de Freitas, Gabriel Rodriguez
Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field. PMID:27698671
Giansante Abud, Daniel; Mounayer, Charbel; Saint-Maurice, Jean Pierre; Salles Rezende, Marco Tulio; Houdart, Emmanuel; Moret, Jacques
We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved to be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.
Batts, William N.; Winton, James R.
Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae
... VHFs) are caused by several families of enveloped RNA viruses: filoviruses (Ebola and Marburg hemorrhagic fever), arenaviruses ( ... in hemorrhagic fever with high death rates. Old World (Eastern Hemisphere) and New World (Western Hemisphere) viruses ...
Chaudhary, Sujata; Salhotra, Rashmi
Pregnancy-induced hypertension constitutes a major cause of morbidity and mortality in developing nations and it complicates about 6-8% of pregnancies. Severe preeclampsia poses a dilemma for the anesthesiologist especially in emergency situations where caesarean deliveries are planned for uninvestigated or partially investigated parturients. This article is aimed to review the literature with regards to the type of anesthesia for such situations. A thorough search of literature was conducted on PubMed, EMBASE, and Google to retrieve the articles. Studies on parturients with severe preeclampsia, undergoing caesarean section, were included in this article. There is growing evidence to support the use of subarachnoid block in such situations when the platelet counts are >80,000 mm(-3). Better hemodynamic stability with the use of low-dose local anesthetic along with additives and better neonatal outcomes has been found with the use of subarachnoid block when compared to general anesthesia.
AD-A<m 761 KOREA UNIV SEOUL COLL OF MEDICINE KOREAN HEM0RRHA6IC FEVER.(U) MAR 80 H W LEE UNCLASSIFIED ICFI F/6 6/5 DAM017-79-6-9<*55 NL...I» > I,,iu. •Uli ••-. SUMMARY There were 364 hospitalized cases of Korean hemorrhagic fever (KHF) in 1979 in Korea . Lee et al...STANDARDS-1963-A ?H "LEVEtf® AD <o KOREAN HEMORRHAGIC F EVER A D A 09 47 Final Report HO WANG LEE, M. D. March 1980 i MIL. IIB«I . Mm k iw
Steinberg, Jacob; Cohen, José E; Gomori, John M; Fraifeld, Shifra; Moscovici, Samuel; Rosenthal, Guy; Shoshan, Yigal; Itshayek, Eyal
Superficial siderosis of the central nervous system (CNS) is a rare disorder caused by deposition of hemosiderin in neuronal tissue in the subpial layer of the CNS due to slow subarachnoid or intraventricular hemorrhage. The most common neurologic manifestations include progressive gait ataxia, sensorineural hearing loss, and corticospinal tract signs. We present a case of superficial siderosis in a 43-year-old man who presented to the Emergency Department with sudden onset bilateral visual deterioration and a loss of consciousness. A hemorrhagic giant prolactinoma was diagnosed based on brain CT scan, T1-weighted MRI, and an endocrine blood examination. Susceptibility-weighted non-contrast MRI showed pathognomonic signs of superficial siderosis in the form of a hypointensity rim surrounding the brainstem, cerebellar fissures, and cranial nerves VII and VIII. This report demonstrates that superficial siderosis can be caused by pituitary apoplexy.
Yan, Tao; Chopp, Michael; Chen, Jieli
Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans. PMID:26625873
Wu, Chris Y; Riangwiwat, Tanawan; Nakamoto, Beau K
Longitudinally extensive transverse myelitis (LETM) may be associated with viral triggers, including both infections and vaccinations. We present a case of a healthy immunocompetent 33-year-old woman who developed a hemorrhagic LETM 2 weeks after seasonal influenza vaccination. Hemorrhagic LETM has not to our knowledge been reported after influenza vaccination. It may represent a forme fruste variant of acute hemorrhagic leukoencephalitis.
RD-RI55 255 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL 11 SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H U LEE RUG 83 DRMDi...the first time in Korea (4,13). WHO has recently adapted to call Korean hemorrhagic fever and clinically similar diseases with a different name, HFRS...AD_______ I •. KOREAN HEMORRHAGIC FEVER • (HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)) I Final Report 0 In HO WANG LEE, M.D. August 1983 Supported by U.S
Gutierrez, Guillermo; Reines, H David; Wulf-Gutierrez, Marian E
This review addresses the pathophysiology and treatment of hemorrhagic shock – a condition produced by rapid and significant loss of intravascular volume, which may lead sequentially to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage, and death. Hemorrhagic shock can be rapidly fatal. The primary goals are to stop the bleeding and to restore circulating blood volume. Resuscitation may well depend on the estimated severity of hemorrhage. It now appears that patients with moderate hypotension from bleeding may benefit by delaying massive fluid resuscitation until they reach a definitive care facility. On the other hand, the use of intravenous fluids, crystalloids or colloids, and blood products can be life saving in those patients who are in severe hemorrhagic shock. The optimal method of resuscitation has not been clearly established. A hemoglobin level of 7–8 g/dl appears to be an appropriate threshold for transfusion in critically ill patients with no evidence of tissue hypoxia. However, maintaining a higher hemoglobin level of 10 g/dl is a reasonable goal in actively bleeding patients, the elderly, or individuals who are at risk for myocardial infarction. Moreover, hemoglobin concentration should not be the only therapeutic guide in actively bleeding patients. Instead, therapy should be aimed at restoring intravascular volume and adequate hemodynamic parameters. PMID:15469601
Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 400 cases have been being reportee every year
Iaroshenko, K O
There were examined 113 patients, suffering pyloroduodenal zone ulcers, complicated by an acute hemorrhage. H. pylori was revealed in 108 (96%) patients. To escape a false-negative results a serological method was applied, which was used to determine a content of IgG antibodies to H. pylori with the help of diagnostic panel GastroPanel (Biohit PLc firm, Finland). The H. pylori presence in patients must be considered as a risk factor for the early recurrent hemorrhage occurrence. A timely conducted examination, determination of H. pylori and timely prescription of antihelicobacter therapy promote the improvement of the treatment results in patients, suffering gastroduodenal ulcers, complicated by an acute hemorrhage due to reduction of the occurrence rate of early recurrence of hemorrhage.
Xu, Shao-Yan; Sun, Ke; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen; Wang, Wei-Lin
Abstract Background: Schwannomas are mesenchymal tumors arising from the neural sheaths of peripheral nerves. They can almost develop in any part of the body, while head, neck and extremities are the most common sites. Occurrence in the retroperitoneum is rare. Schwannomas can show secondary degenerative changes including cyst formation, hyalinization, hemorrhage, and calcification, whereas the ossified retroperitoneal schwannoma was only reported in a malignant one. Case summary: We first present a benign ossified retroperitoneal schwannoma in a 61-year-old female. The mass was found by a routine health examination. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a well-defined mass in the area among duodenum, right liver, and kidney. Definitive preoperative diagnosis of the mass was difficult. By laparotomy, the mass was found in the retroperitoneum. We completely removed the tumor and gross specimen showed a mass with a capsule and 6 × 6 × 4.8 cm in size. Microscopic examination showed the tumor is composed of spindle-shaped cells with degenerative changes of hemorrhage, calcification, and ossification. Immunohistochemically, S-100 protein was strongly positive. Finally, the mass was diagnosed as a hemorrhagic, calcified, and ossified benign schwannoma in the retroperitoneum. The patient was followed up for a period of 21 months, during which she was well with no evidence of recurrence. Conclusion: We report the first case of a benign retroperitoneal schwannoma with secondary degenerative changes including hemorrhage, calcification, and ossification. Precise preoperative diagnosis of the tumor is challenging even with multiple preoperative imaging modalities. After complete resection, patients with benign retroperitoneal schwanommas generally have good prognosis. PMID:27472709
Dorhout Mees, Sanne M; Kerr, Richard S; Rinkel, Gabriel J E; Algra, Ale; Molyneux, Andrew J
Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial. We calculated odds ratios (OR) for DCI for clipping versus coiling with logistic regression analysis. With coiled patients without DCI as the reference group, we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without, and with DCI. With these ORs, we calculated relative excess risk due to Interaction (RERI). Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24, 95% confidence interval (95% CI 1.01-1.51). Coiled patients with DCI, clipped patients without DCI, and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI. Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12 (95% CI -1.16 to 1.40) or 1 year: RERI -0.48 (95% CI -1.69 to 0.74). Only for patients treated within 4 days, coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI (RERI -2.02, 95% CI -3.97 to -0.08). DCI was more common after clipping than after coiling in SAH patients in ISAT. Impact of DCI on poor outcome did not differ between clipped and coiled patients, except for patients treated within 4 days, in whom DCI resulted more often in poor outcome after coiling than after clipping.
Lee, Myung-Ki; Kim, Woo-Jae; Kim, Ho-Sang; Kim, Jeong-Ho; Kim, Yun-Suk
Development of a communication between the spinal subarachnoid space and the pleural space after thoracic spine surgery is uncommon. Subarachnoid pleural fistula (SAPF), a distressing condition, involves cerebrospinal fluid leakage. Here we report an unusual case of SAPF, occurring after thoracic spine surgery, that was further complicated by pneumocephalus and pneumorrhachis postthoracentesis, which was performed for unilateral pleural effusion. PMID:27799999
Radian, A B; Corşatea, L; Alupei, L
The paper presents the evolution at ten eyes (nine patients) that presented expulsive hemorrhage during surgical act of extracapsular extraction with implant of crystalline lens. There are several cases of extracapsular extraction than intracapsular extraction which were more short like duration. The frequency of female was 90% from cases. The good results show the efficiency of associated treatment: closing of the eyeball with scleral punctura and internal tamponing. Only one eye was lost functionally.
Hilsden, R. J.; Shaffer, E. A.
Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time. Images Figure 1 Figure 2 PMID:8563510
Medicine Seoul, Korea * S 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SUM ARY Urban rats captured in Seoul and four nearby Korean cities were found to have...rattus, urban Korean cities, 1980. . . . 15 Table 2. Isolation of Hantaan virus from antigen-positive wild house rats, Korea , 1980 .... ........... .. 16...Figures Figure 1. Map of Seoul City, South Korea and metropolitan area showing locations of urban Korean hemorrhagic fever cases, andRattu s positive
53 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea devel6ped a rare hemorrhagic fever which attracted...patients in the Republic of Korea . Year Korean Korean US Total civilian soldiers soldiers 1951 ...... 627 827 1952 .... 833 833 1953 ... ... 455 455...0 RI m HEMORRHAGIC FEVER WITH RENAL SYNDROME ( KOREAN HEMORRHAGIC FEVER) ANNUAL SUMMARY REPORT HO WANG LEE, M.D. June 30, 1988 Door., Supported by U.S
Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Kudliński, Bartosz; Skrzywanek, Paweł; Smól, Sławomir; Rzymski, Stanisław
In typical takotsubo cardiomyopathy (TC) apical transient left ventricular dysfunction with concomitant ECG changes mimicking acute anterior myocardial infarction can be observed. Reverse TC (RTC) characterized by contractile disturbances in all basal and often simultaneous mid-ventricular segments is definitely less frequent. ECG pattern of RTC is less known. The authors present ECG findings in 5 cases of RTC in course of intracranial hemorrhage (ICH); 3 patients were diagnosed with subarachnoid hemorrhage (SAH) and the other two with intracerebral hemorrhage or subdural posttraumatic hematoma. In all patients, initial ECG appearance was dominated by ST segment depression in inferior leads (II, III, avF) and/or lateral leads (V4-6). In 4 patients, concurrent ST segment elevation in avR and avL leads was seen, additionally 4 patients had low QRS voltage in high lateral leads (I, avL). Potential normalization of these changes did not influence the patient`s survival. In one woman, immediately before death, early repolarization was recorded. In subjects with an increased risk of TC, for example in intracranial hemorrhage, particularly in SAH, the ECG abnormalities presented may indicate a need for further search of its atypical echocardiographic variants.
Ulrich, C T; Beck, J; Seifert, V; Marquardt, G
Subarachnoid haemorrhage (SAH) due to spinal ependymoma is very rare. We report a 37 year old man who presented with typical clinical signs of SAH. Lumbar puncture confirmed SAH but cerebral angiography was negative, and further diagnostic work-up revealed an ependymoma of the conus medullaris as the source of the haemorrhage. A comprehensive review of the literature was conducted. Only 17 patients with spontaneous SAH due to a spinal ependymoma have been reported since 1958. However, in cases of SAH and negative diagnostic findings for cerebral aneurysms or malformations, this aetiology should be considered and work-up of the spinal axis completed.
Lai, C-H; Juan, Y-H; Chang, S-L; Lee, W-L; How, C-K; Hsu, T-F
Patients often present to the emergency department with loss of consciousness. The differential diagnosis of such condition may be difficult because of limited clinical information. The authors present a case of subarachnoid haemorrhage (SAH) with initial electrocardiographic (ECG) finding mimicking ST-segment elevation myocardial infarction (STEMI), which was confirmed to resolve in a follow-up study. Accurate and timely diagnosis of SAH-related ST-segment elevation was important, as the therapeutic strategy for SAH is completely different from that for STEMI. If the clinicians do not have other tools for diagnosis, the follow-up ECG may help us make a most possible diagnosis.
Wu, Chris Y.; Riangwiwat, Tanawan
Longitudinally extensive transverse myelitis (LETM) may be associated with viral triggers, including both infections and vaccinations. We present a case of a healthy immunocompetent 33-year-old woman who developed a hemorrhagic LETM 2 weeks after seasonal influenza vaccination. Hemorrhagic LETM has not to our knowledge been reported after influenza vaccination. It may represent a forme fruste variant of acute hemorrhagic leukoencephalitis. PMID:27847660
Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 300 cases have been reported every year. The aims...but in 1971 affected the middle districts and in 1972 invaded the southern parts of South Korea . The number of patients and the areas of KHF in 1972
Fogelholm, R; Murros, K
Smoking habits were analysed in 114 patients with subarachnoid haemorrhage, less than 70 years old, obtained from an epidemiological study. One control, matched for age, sex, and domicile, was selected for each patient. Current cigarette smokers were significantly more prevalent among cases than controls, and the relative risk of subarachnoid haemorrhage compared with non-smokers was 2.7 in men and 3.0 in women. The so called metastatic emphysema theory with increased elastolytic activity in the serum of smokers is proposed as biochemical basis for the increased risk of subarachnoid haemorrhage. PMID:3819759
Ambrosio, Ana; Saavedra, Maria; Mariani, Mauricio; Gamboa, Graciela; Maiza, Andrea
Argentine hemorrhagic fever (AHF), an acute disease caused by Junin virus (JUNV, Arenaviridae), has been an important issue to public health in Argentina since the early 1950s. The field rodent Calomys musculinus is JUNV natural reservoir and human disease is a consequence of contact with infected rodents. A steady extention of AHF endemic area is being observed since the first reports of the disease. Important achievements have been made in: (a) improvement of methods for the etiological diagnosis; (b) implementation and validation of therapeutical measures; (c) development of vaccines to protect against AHF. Reference is made to different research strategies used to obtain anti-AHF vaccines in the past and anti-arenaviral diseases in the present. Information is updated on features and field performance of Candid #1 vaccine, a live attenuted vaccine currently used to prevent AHF. This vaccine was developed through a joint international effort that envisioned it as an orphan drug. With transferred technology, Argentine government was committed to be Candid #1 manufacturer and to register this vaccine as a novel medical product under the Argentine regulatory authority. Candid #1 vaccine is the first one used to control an arenaviral hemorrhagic fever, the first live viral vaccine to be manufactured and registered in Argentina, reaching its target population through governmental effort.
AD-Ai55 228 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL in. SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H W LEE JUL 84...INTRODUCTION During the Korean War, more than 2,400 United Nations troops stationed in the 38th Parallel in Korea developed a rare disease which had not... Korean hemorrhagic fever patients in urban areas of Seoul. Korean J. Virol. 10: 1-6, 1980. 8. Lee, H. W. New epidemiological findings of HFRS in Korea . J
Sanchez-Larsen, Alvaro; Monteagudo, Maria; Lozano-Setien, Elena; Garcia-Garcia, Jorge
Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.
Marsot-Dupuch, K; Djouhri, H; Meyer, B; Pharaboz, C; Tran Ba Huy, P
The purpose of this article is to describe, with 5 clinical cases, the physiological communications between the inner ear and the subarachnoid spaces (SAS) and present the imaging features with regard to. Therefore we briefly illustrate abnormal communications between SAS and perilymphatic fluids in certain cochlear and internal acoustic meatus (IAM) malformations and their consequences. Imaging features may depict diffusion pathway of bacterial meningitis to membranous labyrinth via the cochlear aqueduct or via the IAM. Rarely, in some patients referred for cochleovestibular symptoms, imaging features may display skull base tumors involving the area of cochlear or vestibular aqueduct aperture. Therefore, in patients referred for cochleovestibular symptoms, MR and CT study should carefully scrutinise not only the IAM but also the aperture of the cochlear and the vestibular aqueducts and the cerebellopontine meninges.
Beyazit, Yavuz; Kekilli, Murat; Haznedaroglu, Ibrahim C; Kayacetin, Ertugrul; Basaranoglu, Metin
Gastrointestinal (GI) bleeding refers to any hemorrhage ascribed to the pathologies of the gastrointestinal tract, extending from the mouth to the anal canal. Despite the recent improvements in the endoscopic, hemostatic and adjuvant pharmacologic techniques, the reported mortality is still around 5%-10% for peptic ulcer bleeding and about 15%-20% for variceal hemorrhages. Although endoscopic management reduces the rates of re-bleeding, surgery, and mortality in active bleeding; early recurrence ratios still occur in around 20% of the cases even with effective initial hemostatic measures. In this quest for an alternative pro-hemostatic agent for the management of GI bleedings, Ankaferd blood stopper (ABS) offers a successful candidate, specifically for “difficult-to-manage” situations as evidenced by data presented in several studies. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. It is effective in both bleeding individuals with normal hemostatic parameters and in patients with deficient primary and/or secondary hemostasis. ABS also modulates the cellular apoptotic responses to hemorrhagic stress, as well as hemostatic hemodynamic activity. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and wound healing, ABS is now becoming an effective alternative hemostatic medicine for gastrointestinal bleedings that are resistant to conventional anti-hemorrhagic measurements. The aim of this review is to outline current literature experience suggesting the place of ABS in the management of GI bleeding, and potential future controlled trials in this complicated field. PMID:22046083
Racsa, Lori D.; Kraft, Colleen S.; Olinger, Gene G.; Hensley, Lisa E.
There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968
Mracsko, Eva; Veltkamp, Roland
Spontaneous intracerebral hemorrhage (ICH) is a particularly severe type of stroke for which no specific treatment has been established yet. Although preclinical models of ICH have substantial methodological limitations, important insight into the pathophysiology has been gained. Mounting evidence suggests an important contribution of inflammatory mechanisms to brain damage and potential repair. Neuroinflammation evoked by intracerebral blood involves the activation of resident microglia, the infiltration of systemic immune cells and the production of cytokines, chemokines, extracellular proteases and reactive oxygen species (ROS). Previous studies focused on innate immunity including microglia, monocytes and granulocytes. More recently, the role of adaptive immune cells has received increasing attention. Little is currently known about the interactions among different immune cell populations in the setting of ICH. Nevertheless, immunomodulatory strategies are already being explored in ICH. To improve the chances of translation from preclinical models to patients, a better characterization of the neuroinflammation in patients is desirable. PMID:25477782
Gulati, Deepak; Dua, Dharti; Torbey, Michel T.
Spontaneous non-traumatic intracerebral hemorrhage (ICH) is associated with high morbidity and mortality throughout the world with no proven effective treatment. Majority of hematoma expansion occur within 4 h after symptom onset and is associated with early deterioration and poor clinical outcome. There is a vital role of ultra-early hemostatic therapy in ICH to limit hematoma expansion. Patients at risk for hematoma expansion are with underlying hemostatic abnormalities. Treatment strategy should include appropriate intervention based on the history of use of antithrombotic use or an underlying coagulopathy in patients with ICH. For antiplatelet-associated ICH, recommendation is to discontinue antiplatelet agent and transfuse platelets to those who will undergo neurosurgical procedure with moderate quality of evidence. For vitamin K antagonist-associated ICH, administration of 3-factor or 4-factor prothrombin complex concentrates (PCCs) rather than fresh frozen plasma to patients with INR >1.4 is strongly recommended. For patients with novel oral anticoagulant-associated ICH, administering activated charcoal to those who present within 2 h of ingestion is recommended. Idarucizumab, a humanized monoclonal antibody fragment against dabigatran (direct thrombin inhibitor) is approved by FDA for emergency situations. Administer activated PCC (50 U/kg) or 4-factor PCC (50 U/kg) to patients with ICH associated with direct thrombin inhibitors (DTI) if idarucizumab is not available or if the hemorrhage is associated with a DTI other than dabigatran. For factor Xa inhibitor-associated ICH, administration of 4-factor PCC or aPCC is preferred over recombinant FVIIa because of the lower risk of adverse thrombotic events. PMID:28360881
36 DISTRIBUTION LIST. .................... 40 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a rare...hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea . This...Kyunggido and Kangwondo, northern parts of South Korea . All of the 97 HFRS patients among Korean soldiers occurred in Kyunggido, Kangwondo and Seoul
DISTRIBUTION LIST .............. .................... 47 5 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a...rare hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea ...Chungchoongnsmdo, and Kangwendo, norLhern parts of South Korea . Almost all HFRS patients among Korean soldiers occurred in Kyunggido aind Ksngwmndo where
13 Table 5. Monthly incidence of HFRS among Korean in the Republic of Korea , 1966-1985 . . . . . . . 14 A Table 6. Incidence of HFRS by...GRANT SUPPORT .. ........ 57.... 5 INTRODUCTION During the Korean War more than 3,000 United Nations .00 troops in Korea developed a rare hemorrhagic...8217;.-.* * S.’ . " 10 ... Table 1. Hospitalized cases of Hemorrhagic fever with renal syndrome patients in the Republic of Korea Year US Korean Korean
Iida, Yuko; Takano, Yuki; Ishiwatari, Yusaku; Yoshida, Akiko; Shimizu, Tetsuo; Ito, Reiko; Hattori, Tomohiro; Takahashi, Noriaki; Hashimoto, Shu
We herein describe the first known case of diffuse alveolar hemorrhage (DAH) associated with the administration of Makyo-kanseki-to, a Chinese herbal drug. A 64-year-old man with bronchial asthma presented with persistent cough. Makyo-kanseki-to was prescribed as an adjunctive treatment for bronchial asthma. Immediately after drug ingestion, the patient expectorated bloody sputum. DAH was diagnosed based on the presence of bilateral ground-glass opacity which was identified on chest computed tomography and bloody bronchoalveolar lavage fluid. We diagnosed that the administration of Makyo-kanseki-to was the responsible medication because the hemorrhage developed immediately after drug ingestion and resolved after the cessation of such medication with no subsequent recurrence. PMID:27853076
Kim, Jae Soo; Lee, Hyun Jong; Lee, Sang Hoon; Lee, Bong Hyo
Acupuncture and pharmacopuncture have been shown to be effective in tumor treatment. However, their effectiveness for treating oligodendroglioma has not been reported yet. The purpose of this study was to provide an initial report on the effectiveness of acupuncture and pharmacopuncture for the treatment of an oligodendroglioma by presenting a case that was treated successfully. A 54-year-old man, who had experienced intracranial hemorrhage, was diagnosed with recurrent oligodendroglioma. His expected survival period was 3-6 months. The patient received daily acupuncture and weekly pharmacopuncture of mountain ginseng and bee venom. After treatment for 18 months, the tumor size was decreased markedly on brain magnetic resonance imaging, and severe seizures had disappeared. In this case, a combination of acupuncture and pharmacopuncture was shown to be effective for the treatment of recurrent oligodendroglioma.
Cox, P. J.; Leach, R. D.; Ellis, Harold
One hundred consecutive recurrences following repair of inguinal hernias have been studied; 62 were direct, 30 indirect, 7 pantaloon and one a femoral hernia. Half the indirect recurrences occurred within a year of repair and probably represented failure to detect a small indirect sac. Later indirect recurrences probably represented failure to repair the internal ring. Nine of the direct hernias were medial funicular recurrences and represented failure to anchor the darn medially. The rest of the direct recurrences were attributable to tissue insufficiency and could probably have been averted by larger tissue bites. Recurrences following inguinal herniorrhaphy remain an all too common problem but can be reduced by meticulous surgical technique. PMID:7339602
Moraz, Marie-Laurence; Kunz, Stefan
Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.
Postpartum hemorrhage remains a major cause of maternal morbidity and mortality. The incidence of postpartum hemorrhage appears to be increasing in developed countries due to an increased number of placenta accreta or percreta after previous Cesarean deliveries. The initial therapy of postpartum hemorrhage consists of uterotonic drugs and inspection of the uterine cavum. At the same time, optimization of the clotting potential should be initiated early. Tranexamic acid may be considered as a first line choice, followed by fibrinogen if necessary. If bleeding continues, fresh frozen plasma and packed red cells should be ordered in a ratio of 1:1, as this ratio has been shown to improve survival in trauma victims. All labor and delivery suites should have standard operating procedures for the management of postpartum hemorrhage in place with regular drills.
Endozain Sosa, J C; Muñoz Núñez, F; Rodríguez Blanes, J A; González Murillo, M; González García, D; Berges Magaña, M; Castillo Grau, P; Presa Valle, M; Crespo Sánchez, M
Upper gastrointestinal hemorrhage secondary to gastric varices still has a high death rate. Fourteen patients were admitted to our unit with bleeding gastric varices from November 1989 to August 1991. Endoscopic injection sclerotherapy obtained control of the bleeding in 92.3%; however, recurrences occurred in 33% of these cases in the first 24-48 hours, with a death rate of 50% during the second stage of the upper gastrointestinal hemorrhage. Total mortality rate was 21.4%. Of the fourteen patients, nine exhibited junctional varices, while five hand fundic varices. In ten of the fourteen patients, gastric varices developed during esophageal sclerotherapy. While hospitalized, it was observed that patients with gastric varices in the fundus had more recurrences and mortality, than those located next to the cardio-esophageal junction. Sclerosis of the varices only obtained temporary control of the bleeding with greater frequency of recurrences and mortality.
Bunick, Christopher G.; Aasi, Sumaira Z.
The ability to recognize, manage, and, most importantly, prevent hemorrhagic complications is critical to performing dermatologic procedures that have safe and high quality outcomes. This article reviews the preoperative, intraoperative, and postoperative factors and patient dynamics that are central to preventing such an adverse outcome. Specifically, the role that anticoagulants and antiplatelet agents, hypertension, and other medical conditions play in the development of postoperative hemorrhage are discussed. In addition, this article provides practical guidelines on managing bleeding during and after surgery. PMID:22515669
Meng, Hui; Li, Fei; Hu, Rong; Yuan, Yikai; Gong, Guoqi; Hu, Shengli; Feng, Hua
Post-hemorrhagic chronic hydrocephalus (PHCH) is a common complication after intraventricular hemorrhage (IVH). The mechanism of PHCH is not fully understood, and its treatment is relatively difficult. In the present study, a rat model of PHCH was used to elucidate the role of iron in the pathogenesis of PHCH. The action of deferoxamine (DFX) in IVH-induced PHCH, the expression of brain ferritin, the concentration of iron in cerebrospinal fluid (CSF), and changes in Wnt1/Wnt3a gene expression were determined. Results indicate that iron plays an important role in the occurrence of hydrocephalus after IVH. The iron chelator, DFX, can decrease the concentrations of iron and ferritin after cerebral hemorrhage and can thereby decrease the incidence of hydrocephalus. In addition, after IVH, the gene expression of Wnt1 and Wnt3a was enhanced, with protein expression also upregulated; DFX was able to suppress both gene and protein expression of Wnt1 and Wnt3a in brain tissue. This indicates that iron may be the key stimulus that activates the Wnt signaling pathway and regulates subarachnoid fibrosis after cerebral hemorrhage, and that DFX may be a candidate for preventing PHCH in patients with IVH.
Chattopadhyay, Amit; Shetty, Kishore V
Recurrent aphthous stomatitis is a common oral ulcerative disease, affecting 10% to 15% of the general US population. This article reviews the epidemiology and clinical presentations of recurrent aphthous stomatitis, including diagnosis and management.
Marrero Calvo, M; Merino Arribas, J; Rodrigo Palacios, J; Bartolomé Albistegui, M; Camino Fernández, A; Grande Sáez, C
Chronic recurrent multifocal osteomyelitis is a rare disorder of unknown etiology, characterized by multiple bone lesions and a variable clinical course. We present a 10 year old boy with chronic recurrent multifocal osteomyelitis who improved after treatment with naproxen.
Kim, Jun Yup; Bae, Hee-Joon
Spontaneous non-traumatic intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. To improve the devastating course of ICH, various clinical trials for medical and surgical interventions have been conducted in the last 10 years. Recent large-scale clinical trials have reported that early intensive blood pressure reduction can be a safe and feasible strategy for ICH, and have suggested a safe target range for systolic blood pressure. While new medical therapies associated with warfarin and non-vitamin K antagonist oral anticoagulants have been developed to treat ICH, recent trials have not been able to demonstrate the overall beneficial effects of surgical intervention on mortality and functional outcomes. However, some patients with ICH may benefit from surgical management in specific clinical contexts and/or at specific times. Furthermore, clinical trials for minimally invasive surgical evacuation methods are ongoing and may provide positive evidence. Upon understanding the current guidelines for the management of ICH, clinicians can administer appropriate treatment and attempt to improve the clinical outcome of ICH. The purpose of this review is to help in the decision-making of the medical and surgical management of ICH. PMID:28178413
Gupta, Kirti; Radotra, Bishan Dass; Suri, Deepti; Sharma, Kusum; Saxena, Akshay Kumar; Singhi, Pratibha
We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell-rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.
Kamali Aghdam, Mojtaba; Davari, Kambiz; Eftekhari, Kambiz
Severe thrombocytopenia with bleeding is rarely reported in children with brucellosis, and recurrent epistaxis is extremely rare. Brucellosis with hemorrhage should be differentiated from viral hemorrhagic fever, malignancy, and other blood disorders. Bone marrow aspiration (BMA) is mandatory to differentiate from other blood diseases. An 8-year-old boy was admitted with recurrent epistaxis, petechiae and purpura on face and extremities and bleeding from the gums. During the hospitalization, he was febrile and complained of muscle pain. Leukopenias associated with thrombocytopenia were observed. BMA showed to be normal. Among the multiple tests requested, only serum agglutination test (SAT) and 2-MercaptoEthanol test (2-ME) were positive. He was treated with Intravenous immunoglobulin (IVIG) associated with co-trimoxazole and rifampin. Finally, fever subsided, and he was discharged with good condition and normal platelet count. Brucellosis should be a differential diagnosis in patients with fever and bleeding disorders and a history of consumption of unpasteurized dairy, in endemic areas.
Jackson, R T; Tigges, J; Arnold, W
We have briefly reviewed the literature pertaining to the movement of tracer molecules and infectious organisms within the olfactory nerve. There is a body of evidence indicating that tracers placed in the CSF will quickly move via the olfactory nerve to the nasal mucosa and then to the cervical lymph nodes. Organic and inorganic tracer materials and organisms as diverse as viruses, a bacillus, and an amoeba, when placed in the nasal cavity, have been shown to move from the nasal mucosa via the olfactory nerve to the olfactory bulb and the CSF. We think that a portion of the data on tracer movement is due to incorporation of tracer materials and organisms into the axoplasm of the olfactory neurons with subsequent anterograde or retrograde axoplasmic transport. However, some of the movement of tracers may occur within the olfactory perineural space. This space may be continuous with a subarachnoid extension that surrounds the olfactory nerve as it penetrates the cribriform plate. To our knowledge, no one has yet followed the perineural space to determine if it is continuous from olfactory receptor to olfactory bulb. The consideration of this space and its role is the main reason for this review.
Henry, Gerard D.; Saccà, Antonino; Eisenhart, Elizabeth; Cleves, Mario A.; Kramer, Andrew C.
The leading patient complaint during the perioperative period for penile prosthesis implantation is postoperative pain, while emesis and urticaria also affect the procedure's perceived success. In analyzing surgical outcomes, assessment of the anesthetic for postoperative pain and side effects should be included. This paper retrospectively reviews 90 consecutive, primary inflatable penile prosthetic operations performed by a single surgeon at one private medical center. Fifty-seven patients were included in final analysis. Patients who had more than one procedure that day or who used chronic pain medication were excluded. The type and amount of each drug used for each respective side effect (within the first 24 hours after procedure) were compared to determine relative benefit. Twenty patients received general anesthesia (denoted herein as “GA”) and 37 received spinal (or also known as subarachnoid) anesthesia (denoted herein as “SA”). Patients receiving GA had significantly greater (P < 0.0001) occurrence and amount of intravenous pain treatment than those receiving SA. Patients with SA required less intravenous pain medication and less treatment for nausea/emesis. PMID:22927841
Sonobe, M; Suzuki, J
Fresh blood and supernatants of blood-CSF mixtures incubated for 1 to 15 days were applied to the basilar artery of adult cats, and the degree of constriction was measured with a surgical microscope. The constriction due to fresh blood was weak and transient. It seems possible to assume that serotonin isolated from platelets participates greatly in the transient vasoconstriction induced by fresh blood. Supernatants of blood-CSF mixtures incubated for three days had weak activity in comparison with the powerful and long-lasting activity of those incubated for seven days. Furthermore, mixtures incubated for 15 days had little or no activity. This change in the vasoconstrictive activity was similar to, and coincides chronologically with clinical late spasm following subarachnoid haemorrhage 34. We investigated the vasospasmogenic substance in the seventh day mixture. Heat coagulation, ultrafiltration, sephadex G-100 gel-chromatography, disc-electrophoresis, and Spectrophotography show that extracellular oxyHb has a strong spasmogenic activity. In the 15th day mixture, oxyHb is spontaneously converted to metHb. Experimentally, oxyHb has a strong vasoconstrictive activity, and metHb has no vasoconstrictive activity. We have had success in oxidizing oxyHb into metHb with sodium nitrite, thus preventing experimental vasospasm.
The technical problems of surgery for anterior circle aneurysm have in large measure been solved. The problem of reduced perfusion to the brain which characterises the patient with aneurysmal subarachnoid haemorrhage in a poor clinical condition demands more subtle physiological handling. It appears likely that maintenance of an intact cell membrane and blood brain barrier may be aided by the exhibition of pre and post-operative steriods, and that concentration on regional perfusion should be the main aim in post-operative management of such cases. This demands maintenance of adequate blood volume, avoidance of platelet stickiness, and utilisation of the pathological paralysis of autoregulation to improve flow to ischaemic zones by hypertensive agents if necessary. The possibility that early operation with evacuation of blood from the basal cisterns may in the end prevent the vascular damage and disordered vaso-reactivity which encourages the development of transient ischaemic deficits, is a concept which has to be actively pursued. The problem is a continuing one which has bedevilled aneurysm surgery for 25 years, but the omens suggest that a solution is appreciably nearer at hand.
Goffman, Dena; Nathan, Lisa; Chazotte, Cynthia
Postpartum hemorrhage remains the number one cause of maternal death globally despite the fact that it is largely a preventable and most often a treatable condition. While the global problem is appreciated, some may not realize that in the United States postpartum hemorrhage is a leading cause of mortality and unfortunately, the incidence is on the rise. In New York, obstetric hemorrhage is the second leading cause of maternal mortality in the state. National data suggests that hemorrhage is disproportionally overrepresented as a contributor to severe maternal morbidity and we suspect as we explore further this will be true in New York State as well. Given the persistent and significant contribution to maternal mortality, it may be useful to analyze the persistence of this largely preventable cause of death within the framework of the historic "Three Delays" model of maternal mortality. The ongoing national and statewide problem with postpartum hemorrhage will be reviewed in this context of delays in an effort to inform potential solutions.
Kim, Seon-Hwan; Youm, Jin-Young; Kwon, Hyon-Jo
Various surgical procedures for the treatment of post-traumatic syringomyelia have been introduced recently, but most surgical strategies have been unreliable. We introduce the concept and technique of a new shunting procedure, syringo-subarachnoid-peritoneal shunt. A 54-year-old patient presented to our hospital with a progressive impairment of motion and position sense on the right side. Sixteen years before this admission, he had been treated by decompressive laminectomy for a burst fracture of L1. On his recent admission, magnetic resonance (MR) imaging studies of the whole spine revealed the presence of a huge syrinx extending from the medulla to the L1 vertebral level. We performed a syringo-subarachnoid-peritoneal shunt, including insertion of a T-tube into the syrinx, subarachnoid space and peritoneal cavity. Clinical manifestations and radiological findings improved after the operation. The syringo-subarachnoid-peritoneal shunt has several advantages. First, fluid can communicate freely between the syrinx, the subarachnoid space, and the peritoneal cavity. Secondly, we can prevent shunt catheter from migrating because dural anchoring of the T-tube is easy. Finally, we can perform shunt revision easily, because only one arm of the T-tube is inserted into the intraspinal syringx cavity. We think that this procedure is the most beneficial method among the various shunting procedures. PMID:22993681
... Congo Hemorrhagic Fever (CCHF) [PDF - 2 pages] Virus Ecology Viral Hemorrhagic Fever (VHF) Information for Specific Groups ... Diagnosis Treatment Prevention Outbreak Distribution Map Resources Virus Ecology File Formats Help: How do I view different ...
Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit
Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426
Hartman, Amy L; Towner, Jonathan S; Nichol, Stuart T
Ebola and Marburg viruses cause a severe viral hemorrhagic fever disease mainly in Sub-Saharan Africa. Although outbreaks are sporadic, there is the potential for filoviruses to spread to other continents unintentionally because of air travel or intentionally because of bioterrorism. This article discusses the natural history, epidemiology, and clinical presentation of patients infected with Ebola and Marburg viruses. Clinicians in the United States should be aware of the symptoms of these viral infections in humans and know the appropriate procedures for contacting local, state, and national reference laboratories in the event of a suspected case of filoviral hemorrhagic fever.
Ramos-López, L; Pons-Canosa, V; Juncal-Díaz, J L; Núñez-Centeno, M B
Sheehan's syndrome is described as panhypopituitarism secondary to a pituitary hypoperfusion during or just after obstetric hemorrhage. Advances in obstetric care make this syndrome quite unusual, but some cases are reported in underdeveloped countries. Clinical presentation may change depending on the severity of the hormone deficiencies. The diagnosis is clinical, but abnormalities are observed in the magnetic resonance in up to 70% of patients. We present a case of a woman with hypotension, hypothermia and edemas in relation to a previous massive postpartum hemorrhage. Failure in lactation was the clue to the diagnosis. A review of its main features, its diagnosis and treatment in the current literature is also presented.
trauma victims occur within 1 hourvOf injury and are due to rapid hemorrhage or CNS trauma . We developed a rapid hemorrhage model in unanesthetized swine...UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGErmUen Data Enteed) q g ABSTRACT One-half of deaths among trauma victims occur within 1 hour of injury and...are due to rapid hemorrhage or CNS trauma . We developed a rapid hemorrhage model in unanesthetized swine to simulate human exsanguination. We compared
Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.
Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.
Akiguchi, Ichiro; Shirakashi, Yoshitomo; Budka, Herbert; Watanabe, Yuko; Watanabe, Toshiyuki; Shiino, Akihiko; Ogita, Mihoko; Kawamoto, Yasuhiro; Jungwirth, Susanne; Krampla, Wolfgang; Fischer, Peter
Objective We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH-iNPH) and to describe the clinico-radiological features and outcomes of a community-based investigation (The Vienna Trans-Danube Aging study). Methods Of the 697 inhabitants (all 75 years old), 503 completed extensive neurological examinations at baseline and were followed up every 30 months thereafter with MRIs, mini-mental state examination (MMSE), and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). The DESH-iNPH participant data were compared with the data from participants with Evans index ratios >0.3 (ex vacuo hydrocephalus), cerebral small-vessel diseases, and normal MRIs. The widening of perivascular space was also evaluated by MRI in these groups. Results Eight participants with DESH-iNPH (1.6%) and 76 with ex vacuo hydrocephalus (16.1%) at baseline were identified. The mean MMSE in DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs was 26.4, 27.9, and 28.3, respectively, and the mean UPDRSM was 9.75, 2.96, and 1.87, respectively. After a 90-month follow-up, the mortality rates for DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs were 25.0%, 21.3%, and 10.9%, respectively. The perivascular-space widening scores were significantly smaller in the DESH-iNPH cases, particularly at the centrum semiovale, compared to cerebral small-vessel disease and ex vacuo hydrocephalus cases. Interpretation The prevalence of DESH-iNPH was 1.6% for participants aged 75 years and revealed significantly lower MMSE and higher UPDRSM scores compared to the ex vacuo hydrocephalus and controls. Moreover, it is suggested that perivascular-space narrowing is a morphological and pathophysiological marker of DESH-iNPH. PMID:25356428
Osuka, K; Suzuki, Y; Tanazawa, T; Hattori, K; Yamamoto, N; Takayasu, M; Shibuya, M; Yoshida, J
The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.
Garg, Neetika; Khunger, Monica; Gupta, Arjun; Kumar, Nilay
Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler–Weber–Rendu syndrome, is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as brain, lungs, and liver. Its prevalence is currently estimated at one in 5,000 to 8,000. Most cases are due to mutations in the endoglin (HHT1) or ACVRLK1 (HHT2) genes. Telangiectasias in nasal and gastrointestinal mucosa generally present with recurrent/chronic bleeding and iron deficiency anemia. Larger AVMs occur in lungs (~40%–60% of affected individuals), liver (~40%–70%), brain (~10%), and spine (~1%). Due to the devastating and potentially fatal complications of some of these lesions (for example, strokes and brain abscesses with pulmonary AVMs), presymptomatic screening and treatment are of utmost importance. However, due to the rarity of this condition, many providers lack an appreciation for the whole gamut of its manifestations and complications, age-dependent penetrance, and marked intrafamilial variation. As a result, HHT remains frequently underdiagnosed and many families do not receive the appropriate screening and treatments. This article provides an overview of the clinical features of HHT, discusses the clinical and genetic diagnostic strategies, and presents an up-to-date review of literature and detailed considerations regarding screening for visceral AVMs, preventive modalities, and treatment options. PMID:25342923
A retrospective study was made of 50 consecutive patients with spontaneous subarachnoid haemorrhage for which no cause was found, looking for evidence of delayed cerebral ischaemia particularly during the first 2 weeks after the bleed. Twenty-three patients had blood visible on the CT scan but only 4-6% developed delayed ischaemia, all of whom made a good recovery. The low incidence of this complication in this group of patients suggests that subarachnoid blood is not a sufficient cause for delayed ischaemia. PMID:3981169
Ha, Minsu; Kim, Yoon Jae; Kwon, Kwang An; Hahm, Ki Baik; Kim, Mi-Jung; Kim, Dong Kyu; Lee, Young Jae; Oh, S Paul
Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people. Clinical diagnosis of HHT is made when a person presents three of the following four criteria: family history, recurrent nosebleeds, mucocutaneous telangiectasis, and arteriovenous malformations (AVM) in the brain, lung, liver and gastrointestinal (GI) tract. Although epistaxis is the most common presenting symptom, AVMs affecting the lungs, brain and GI tract provoke a more serious outcome. Heterozygous mutations in endoglin, activin receptor-like kinase 1 (ACVRL1; ALK1), and SMAD4, the genes involved in the transforming growth factor-β family signaling cascade, cause HHT. We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes, proven to be caused by bleeding from multiple gastric angiodysplasia. Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach. Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia. The patient has been admitted several times with episodes of hemoptysis and hematochezia. One year ago, the patient was hospitalized due to right-sided weakness, which was caused by left basal ganglia hemorrhage as the part of HHT presentation. In family history, the patient's mother and elder sister had died, due to intracranial hemorrhage, and his eldest son has been suffered from recurrent epistaxis for 20 years. A genetic study revealed a mutation in exon 3 of ALK1 (c.199C > T; p.Arg67Trp) in the proband and his eldest son presenting epistaxis.
Sheward, S E; Davis, M; Amparo, E G; Gogel, H K
We report a case of benign gastric ulcer with secondary extensive intramural hemorrhage causing a radiographic appearance consistent with a large ulcerated gastric neoplasm. This is the second such case reported and the first studied with sonography and computed tomographic scan. A brief review of the literature on intramural gastric hematoma is presented.
Ziegelmann, Matthew J.; Boorjian, Stephen A.; Joyce, Daniel D.; Montgomery, Brian D.; Linder, Brian J.
Introduction Hemorrhagic cystitis presents a difficult clinical challenge, yet data regarding treatment options is sparse. Here, we sought to evaluate outcomes of a contemporary cohort of patients treated with intravesical formalin for hemorrhagic cystitis. Methods We identified a retrospective cohort of eight patients managed with formalin for hemorrhagic cystitis from 2000–2014. All patients failed prior measures, including bladder irrigation, clot evacuation, and other intravesical agents. Treatment success was defined as hematuria resolution during the given hospitalization without use of additional invasive therapies. We also evaluated treatment complications and additional treatments following hospital dismissal. Results Etiology of cystitis was radiation for malignancy in all cases. The formalin concentration ranged from 1–4%, with escalation used in treatment failures. Five patients (62.5%) received a single dose of 1% formalin, two patients received two doses, and one patient received three doses. Notably, intraoperative cystography identified vesicoureteral reflux (VUR) in 50.0% of patients. Six patients (75.0%) achieved treatment success, with a median time to resolution of four days (range 1–17 days). Of those refractory to formalin, one was managed with indwelling nephrostomy tubes and one underwent cystectomy. Median followup was eight months. Of the responders, two eventually required cystectomy, one for recurrent hematuria and one for recalcitrant bladder neck contracture and bladder dysfunction. The remaining four patients (50%) required no additional therapy. Conclusions Formalin remains an important tool for treating refractory hemorrhagic cystitis, with roughly 75.0% of patients requiring no additional therapy prior to hospital discharge. Notably, there is a risk of bladder dysfunction following formalin. PMID:28360951
Tam, Emily W.Y.; Miller, Steven P.; Studholme, Colin; Chau, Vann; Glidden, David; Poskitt, Kenneth J.; Ferriero, Donna M.; Barkovich, A. James
Objective To hypothesize that detailed examination of early cerebellar volumes over time would distinguish differences in cerebellar growth associated with intraventricular hemorrhage (IVH) and white matter injury (WMI) in preterm infants. Study design Preterm newborns at the University of California San Francisco (n=57) and the University of British Columbia (n=115) were studied using serial MRI scans near birth and again at near term-equivalent age. Interactive semi-automated tools were used to determine volumes of the cerebellar hemispheres. Results Adjusting for supratentorial brain injury, cerebellar hemorrhage, and study site, cerebellar volume increased 1.7cm3/week postmenstrual age (95% CI 1.6–1.7, P<0.001). More severe supratentorial IVH was associated with slower growth of cerebellar volumes (P<0.001). Volumes by 40 weeks were 1.4 cm3 lower in premature infants with grade 1–2 IVH and 5.4 cm3 lower with grade 3–4 IVH. The same magnitude of decrease was found between ipsilateral and contralateral IVH. No association was found with severity of WMI (P=0.3). Conclusions Early effects of decreased cerebellar volume associated with supratentorial IVH in either hemisphere may be a result of concurrent cerebellar injury or direct effects of subarachnoid blood on cerebellar development. PMID:20961562
Traudt, Christopher M; McPherson, Ron J; Studholme, Colin; Millen, Kathleen J; Juul, Sandra E
Background Cerebellar hypoplasia is common problem for preterm infants, and infants that suffer intraventricular hemorrhage (IVH). To evaluate the effects of IVH on cerebellar growth and development, we used a neonatal rabbit model of systemic glycerol to produce IVH. Methods New Zealand White rabbit kits were surgically delivered 2 d preterm, and treated with i.p. glycerol (3.25 to 6.5 g/kg). Controls were born at term. IVH was documented by ultrasound. Brain MRI volumes, cerebellar foliation, proliferation (Ki-67) and Purkinje cell density were done at two weeks of life. Tissue glycerol and glutathione concentrations were measured. Results Glycerol increased IVH, subarachnoid hemorrhages and mortality in a dose-dependent manner. Total cerebellar volumes, cerebellar foliation and cerebellar proliferation were decreased in a dose-dependent manner. Glycerol accumulated rapidly in blood, brain and liver and was associated with increased glutathione concentration. All of these results were independent of IVH status. Conclusions Cerebellar hypoplasia was induced after glycerol administration in a dose-dependent manner. Given rapid tissue accumulation of glycerol, dose dependent decreased brain growth and lack of IVH effect on measured outcomes we question the validity of this model as glycerol toxicity cannot be ruled out. A more physiologic model of IVH is needed. PMID:24346111
Wei, Ning; Wei, Yinghai; Li, Binru; Pang, Linlin
Intracerebral hemorrhage (ICH) is an important public health problem in neurology, which is not only associated with high mortality but also leading to disability. Yet no satisfactory treatment has been developed. The secondary injury that resulted from a number of self-destructive processes such as neuroinflammation, apoptosis and oxidative stress, is the key factor contributing to ICH-induced brain damage. Baicalein has been proved to improve neuronal functional recovery in rat model of subarachnoid hemorrhage and ischemic brain damage. To investigate the effect of baicalein on ICH and its underlying mechanism, a collagenase-induced ICH rat model was performed. Baicalein treatment significantly decreased neurological severity score at day 1 and 3 after ICH injury. Our results showed that the lesion volume, the brain water content, the expression levels of four pro-inflammatory cytokines (IL-1β, IL-4 and IL-6 and TNF-α) and the numbers of apoptotic cells were reduced significantly in ICH rats receiving baicalein treatment, especially in 50 mg/kg baicalein-treated group. Moreover, baicalein increased SOD and GSH-Px activities and down-regulated MDA level of brain tissues in rats. These results suggested that the therapeutic efficacy of baicalein on repairing brain damage is probably caused by suppressing apoptosis, oxidative stress and neuroinflammation. Baicalein could be developed into a novel drug for clinical treatment of ICH and ICH-related brain injuries.
Havakeshian, Sina; Bozinov, Oliver; Burkhardt, Jan-Karl
Simultaneous rupture of more than one intracranial aneurysm is a rare event and difficult to diagnose. In this case report, we present the case of a patient with a simultaneous rupture of two middle cerebral artery (MCA) aneurysms with two separately localized aneurysm-associated intracerebral hemorrhages (ICH). Initially, the patient presented with headache and neck stiffness as well as progressive decrease of consciousness. Computed tomography (CT) revealed a subarachnoid hemorrhage with a frontal and temporal space-occupying ICH. CT angiography demonstrated two MCA aneurysms located in adjacency to the ICHs, one located at the M1 segment and the other in the bifurcation of the left MCA. Rupture of both aneurysms was confirmed during surgery, and both aneurysms were clipped microsurgically without complications. Although rupture of one aneurysm in patients with multiple aneurysms is the most common event, this case indicates that simultaneous rupture should be kept in mind in patients with multiple aneurysms. In patients with multiple aneurysms, the identification of the ruptured aneurysm(s) is necessary to avoid leaving a ruptured aneurysm untreated.
Frölich, Andreas M.; Buhk, Jan-Hendrik; Fiehler, Jens; Kemmling, Andre
Objectives Flat-panel CT (FPCT) allows cross-sectional parenchymal, vascular and perfusion imaging within the angiography suite, which could greatly facilitate acute stroke management. We hypothesized that FPCT offers equal diagnostic accuracy compared to multi-detector CT (MDCT) as a primary tool to exclude intracranial hemorrhage. Methods 22 patients with intracranial hematomas who had both MDCT and FPCT performed within 24 hours were retrospectively identified. Patients with visible change in hematoma size or configuration were excluded. Two raters independently segmented hemorrhagic lesions. Data sets and corresponding binary lesion maps were co-registered to compare hematoma volume. Diagnostic accuracy of FPCT to detect hemorrhage was calculated from voxel-wise analysis of lesion overlap compared to reference MDCT. Results Mean hematoma size was similar between MDCT (16.2±8.9 ml) and FPCT (16.1±8.6 ml), with near perfect correlation of hematoma sizes between modalities (ρ = 0.95, p<0.001). Sensitivity and specificity of FPCT to detect hemorrhagic voxels was 61.6% and 99.8% for intraventricular hematomas and 67.7% and 99.5% for all other intracranial hematomas. Conclusions In this small sample containing predominantly cases with subarachnoid hemorrhage, FPCT based assessment of hemorrhagic volume in brain yields acceptable accuracy compared to reference MDCT, albeit with a limited sensitivity on a voxel level. Further assessment and improvement of FPCT is necessary before it can be applied as a primary imaging modality to exclude intracranial hemorrhage in acute stroke patients. PMID:27806106
Bulwa, Zachary B.; Ward, G. Carter; Kramer, Owen N.; Rao, Birju; Wichter, Melvin
Patient: Female, 63 Final Diagnosis: Cerebral amyloid angiopathy Symptoms: Altered mental state • aphasia • hemiplegia Medication: — Clinical Procedure: — Specialty: Neurology Objective: Unusual clinical course Background: Cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of lobar intracerebral hemorrhage (ICH) and cognitive impairment in the aging population. Magnetic resonance imaging (MRI) of cerebral microbleeds is the most reliable option for clinical diagnosis of suspected CAA. The pathophysiology of microbleeds and ICH in CAA is not well understood, but it is thought to be the result of vessel weakening and rupture secondary to amyloid deposition. Little evidence has been established pertaining to the time course of recurrent CAA-related microbleeds or larger hemorrhages. Although several risk factors have been associated with an increased risk of ICH in CAA, there are no current treatment guidelines for recurrent hemorrhaging in CAA. Case Report: We present a rare case of rapidly sequential and fatal lobar hemorrhaging in the setting of suspected CAA, diagnosed by numerous microbleeds on MRI, compounded by the use of subcutaneous heparin in a 63-year-old female patient. Conclusions: This case broadens our understanding of a rarely identified progression of CAA and illustrates the need for further investigation of the use of subcutaneous heparin in the setting of probable CAA. PMID:27853131
Postlethwait, R W
An analysis of 584 operations for recurrent inguinal hernia was made in an attempt to determine the cause of the recurrence based on the anatomic findings. The recurrence was indirect in 300, direct in 241, and various other in 43 operations. The causes of the indirect recurrences appeared to be an unrecognized hernia, incomplete dissection or improper ligation of the sac, failure to narrow the cord, or inadequate reconstruction of the internal ring. No cause for the diffuse direct recurrences was apparent. Of the 241 hernias in Hesselbach's triangle, 144 were small localized defects, usually (112) just lateral to the symphysis. These were considered to be caused by the cutting action of a suture placed under tension. On the basis of these findings, suggestions are made for primary inguinal hernia operations. PMID:4073990
Hillman N, Peoples JB (1982): The effects of dehydration on the dynamics of transcapillary refill. Am Surg 48:412-416. Becker H, Hottenrott C ...hemorrhagic shock: improved outcome with hypertonic saline/6% Dextran 70. Am J Emerg Med 7:357-363. Coli G, Frascaroli C , Guibilei G, Grillone G, Nanni...Di Nino GF, Melcni C ’, Rossi R (1982a): Considerazioni sulle modificaziomi della viscosita del sangue nel circolo polmonare ed in quello sistemico
Ghosh, D; Dubey, T; Prabhakar, S
The coexistence of brain parenchymal cysts at various stages of evolution, both intraventricular and subarachnoid racemose, is reported in a patient with neurocysticercosis. The condition has a variety of presentations, depending on the location of the cyst. This case is of particular interest because of the rarity of this condition in India. Keywords: brain parenchymal cyst; cysticercosis; albendazole PMID:10448497
Zhang, Zi-Huan; Han, Yan-Ling; Wang, Chun-Xi; Zhou, Chen-Hui; Wu, Ling-Yun; Zhang, Hua-Sheng; Chen, Qiang; Fan, Jie-Mei; Zhou, Meng-Liang; Hang, Chun-Hua
Abundant erythrocytes remain and lyse partially in the subarachnoid space after severe subarachnoid haemorrhage (SAH). But the effect of subarachnoid erythrocyte lysate on brain injury is still not completely clear. In this study, autologous erythrocytes (the non-lysate group) and their lysate (the lysate group) were injected separately into the cistern magna of rabbits to induce a model of experimental SAH, although the control group received isotonic sodium chloride solution instead of erythrocyte solution. Results showed that vasospasm of the basilar artery was observed at 72 h after experimental SAH, but there was no significant difference between the non-lysate group and the lysate group. Brain injury was more severe in the lysate group than in the non-lysate group. Meanwhile, the levels of peroxiredoxin 2 (Prx2), IL-6 and TNF-α in brain cortex and in CSF were significantly higher in the lysate group than those in the non-lysate group. These results demonstrated that brain injury was more likely to be caused by erythrocyte lysate than by intact erythrocytes in subarachnoid space, and inflammation response positively correlated with Prx2 expression might be involved in mechanism of brain injury after SAH. PMID:27279653
OBJECTIVES—The purpose was to define the incidence and case fatality rates of subarachnoid haemorrhage in the population of Devon and Cornwall. METHODS—A retrospective population based design was employed with multiple overlapping methods of case ascertainment. A strict definition of subarachnoid haemorrhage was used. Age and sex specific incidence rates and relative risks for death at different time intervals are calculated. RESULTS—Eight hundred cases of first ever subarachnoid haemorrhage were identified; 77% of cases were verified by CT, 22% by necropsy, and 1% by lumbar puncture. The incidence rates are higher than those previously reported in the United Kingdom. The age standardised incidence rate (/100 000 person-years) for females was 11.9 (95% confidence interval (95% CI) 9.5-15.0), for males 7.4 (5.4-10.0), and the total rate was 9.7 (7.5-12.6). The case fatality rates at 24 hours, 1 week, and 30 days were 21 (18-24)%, 37 (33-41)%, and 44 (40-49)% respectively. The relative risk for death at 30days for those over 60 years:under 60 years was 2.95 (2.18-3.97). CONCLUSION—The incidence of subarachnoid haemorrhage in the United Kingdom is higher than previously reported. Three quarters of the mortality occurs within 3days. PMID:11181855
Mathur, Arun; Nagappa, C. Venkatesh
Subarachnoid block (SAB) is an extensively used regional anesthesia technique for many surgeries. Neurological complications are rare following spinal anesthesia. We are reporting neurological complication in a patient the following appendectomy under SAB with unsuspected coagulopathy. The complication was noticed early and managed conservatively with a high dose of intravenous steroid and improved drastically in a short period. PMID:28298799
... With Fear of Recurrence Request Permissions Coping With Fear of Recurrence Approved by the Cancer.Net Editorial ... affects your life. Tips for coping with the fear of recurrence Living with uncertainty is never easy. ...
Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H
Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology.
Godard, Clémence; Berhoune, Malik; Bertrand, Eric; Schlatter, Joël; Chiadmi, Fouad; Toledano, Audrey; Cisternino, Salvatore; Fontan, Jean-Eudes
Postpartum hemorrhage is defined by bleeding > 500 mL through the vagina. It is one of the obstetrical complications that obstetricians fear most. It is the leading cause of maternal mortality in the world, especially in developing countries. The reference treatments in France are parenteral oxytocin and sulprostone. Sulprostone involves sometimes fatal side effects, and must be administered only in appropriate health care facilities. It also has the major disadvantage of requiring refrigeration. Misoprostol has uterotonic properties that have led to its occasional off-label use in the treatment of postpartum hemorrhage, by rectal or sublingual administration, as an alternative to sulprostone. A careful review of the literature on this particular use of misoprostol is essential.
Shayan, Sara; Bokaean, Mohammad; Shahrivar, Mona Ranjvar; Chinikar, Sadegh
Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.
Welch, Claude E.
In the past few years gastric resection has become the therapy of choice for patients with massive hemorrhage from duodenal ulcer. When this is done as an emergency procedure the ability of the surgeon is often taxed to the limit. Although sometimes easy, control is often extraordinarily difficult. Many important technical details must be considered in order to attain a successful outcome. This method of therapy has proved to be very satisfactory with patients who are in good condition for operation, and even in the poorer risks seen on ward service has resulted in a surgical mortality of only 7 per cent in all patients less than 60 years of age treated for this extremely severe type of hemorrhage. In the older age groups mortality rates still remain high. PMID:13284635
Burnett, Mark W
In mid-September 2009, a 22-year-old critically ill Soldier was medically evacuated from a treatment facility in southern Afghanistan to Landstuhl Regional Medical Center in Germany. Despite the efforts of the team at Landstuhl, this patient died and became the US military's first known victim of Crimean-Congo hemorrhagic fever (CCHF). CCHF is caused by a virus, which bears the same name. Because a