Alexander, Mathew; Patil, Anil Kumar B.; Mathew, Vivek; Sivadasan, Ajith; Chacko, Geeta; Mani, Sunithi E.
Cerebral amyloid angiopathy (CAA) usually manifests as cerebral hemorrhage, especially as nontraumatic hemorrhages in normotensive elderly patients. Other manifestations are subarachnoid (SAH), subdural, intraventricular hemorrhage (IVH) and superficial hemosiderosis. A 52-year-old hypertensive woman presented with recurrent neurological deficits over a period of 2 years. Her serial brain magnetic resonance imaging and computed tomography scans showed recurrent SAH hemorrhage, and also intracerebral, IVH and spinal hemorrhage, with superficial siderosis. Cerebral angiograms were normal. Right frontal lobe biopsy showed features of CAA. CAA can present with unexplained recurrent SAH hemorrhage, and may be the initial and prominent finding in the course of disease in addition to superficial cortical siderosis and intracerebal and spinal hemorrhages. PMID:23661974
Alexander, Mathew; Patil, Anil Kumar B; Mathew, Vivek; Sivadasan, Ajith; Chacko, Geeta; Mani, Sunithi E
Cerebral amyloid angiopathy (CAA) usually manifests as cerebral hemorrhage, especially as nontraumatic hemorrhages in normotensive elderly patients. Other manifestations are subarachnoid (SAH), subdural, intraventricular hemorrhage (IVH) and superficial hemosiderosis. A 52-year-old hypertensive woman presented with recurrent neurological deficits over a period of 2 years. Her serial brain magnetic resonance imaging and computed tomography scans showed recurrent SAH hemorrhage, and also intracerebral, IVH and spinal hemorrhage, with superficial siderosis. Cerebral angiograms were normal. Right frontal lobe biopsy showed features of CAA. CAA can present with unexplained recurrent SAH hemorrhage, and may be the initial and prominent finding in the course of disease in addition to superficial cortical siderosis and intracerebal and spinal hemorrhages.
... 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 ...
... into the compartment surrounding the brain, the subarachnoid space and is therefore also known as a subarachnoid ... leak into the CSF (cerebrospinal fluid) in the space around the brain (subarachnoid space). The pool of ...
Covey, Judith; Noble, Adam J; Schenk, Thomas
Patients with subarachnoid hemorrhage (SAH) and their close friends and family may be excessively fearful that the patient will have a recurrence, and such fears could play a critical role in the poor recovery shown by many patients The authors examined whether these fears could account for significant variance in psychosocial outcomes. The authors prospectively studied a sample of 69 patients with SAH alongside their spouse, other family member, and/or close friend identified as their significant other (SO). The patient/SO pairs were assessed at 13 months postictus for their fears of recurrence and for health-related quality of life on the 8 domains of the 36-Item Short Form Health Survey. The SOs were found to be significantly more fearful of SAH recurrence than the patients. The SO's fears also explained unique variance in the patient's recovery on 4 of the 36-Item Short Form Health Survey domains over and above the patient's own fears, demographic and/or neurological variables, and the patient's history of psychiatric or neurological problems. The domains affected reflected activity-based and functional aspects of the patient's quality of life as opposed to more general characteristics of their emotional well-being or physical health state. The patient's recovery may be compromised if their spouse, close family, and/or friends are excessively fearful about their suffering a recurrence. Perhaps the SO's fears cause them to be overprotective of the patient and to restrict their day-to-day activities. Attention must therefore be given to the experience of having a loved one suffer from an SAH, and alleviating the caregiver's fears could help to promote a better outcome for the patient.
Chiriac, A; Poeată, I; Baldauf, J; Schroeder, H W
Nontraumatic subarachnoid hemorrhage is a neurosurgical emergency characterized by the extravasation of blood into the spaces covering the central nervous system that are filled with cerebrospinal fluid. The leading cause of nontraumatic subarachnoid hemorrhage is rupture of an intracranial aneurysm, which accounts for about 80 percent of cases and has a high rate of death and complications. The management of aneurysmal SAH has changed significantly over the past few years. This change is mostly due to the demonstration of the superiority of early diagnosis, surgical clipping or endovascular embolization of ruptured aneurysms. This superiority derives from the relative safety of early aneurysm occlusion and the major threat of early rebleeding (approximately 25% in three weeks after SAH).
Marder, Carrie P; Narla, Vinod; Fink, James R; Tozer Fink, Kathleen R
Spontaneous subarachnoid hemorrhage (SAH) typically prompts a search for an underlying ruptured saccular aneurysm, which is the most common nontraumatic cause. Depending on the clinical presentation and pattern of SAH, the differential diagnosis may include a diverse group of causes other than aneurysm rupture. For the purposes of this review, we classify SAH into three main patterns, defined by the distribution of blood on unenhanced CT: diffuse, perimesencephalic, and convexal. The epicenter of the hemorrhage further refines the differential diagnosis and guides subsequent imaging. Additionally, we review multiple clinical conditions that can simulate the appearance of SAH on CT or MRI, an imaging artifact known as pseudo-SAH.
Raya, Amanda K; Diringer, Michael N
Nontraumatic subarachnoid hemorrhage from intracranial aneurysm rupture presents with sudden severe headache. Initial treatment focuses on airway management, blood pressure control, and extraventricular drain for hydrocephalus. After identifying the aneurysm, they may be clipped surgically or endovascularly coiled. Nimodipine is administered to maintain a euvolemic state and prevent delayed cerebral ischemia (DCI). Patients may receive anticonvulsants. Monitoring includes serial neurologic assessments, transcranial Doppler ultrasonography, computed tomography perfusion, and angiographic studies. Treatment includes augmentation of blood pressure and cardiac output, cerebral angioplasty, and intra-arterial infusions of vasodilators. Although early mortality is high, about one half of survivors recover with little disability. Copyright © 2014 Elsevier Inc. All rights reserved.
Kellner, P; Stoevesandt, D; Soukup, J; Bucher, M; Raspé, C
Acute subarachnoid hemorrhage (SAH) is a severe and acute life-threatening cerebrovascular disease. Approximately 80% of all acute non-traumatic SAHs are the result of a ruptured cerebrovascular aneurysm. Despite advances in diagnosis and treatment a high morbidity and mortality still exists. Apart from the primary cerebral damage there are also secondary complications, such as vasospasm, rebleeding, hydrocephalus, cerebral edema or hydrocephalus. For an appropriate therapy an understanding of the extensive pathophysiology, the options in diagnostics and therapy and the complications of the disease are essential. Anesthesiologists are decisively involved in the therapy of the primary and secondary damages and subsequently in the outcome as well. This article provides an overview of the perioperative and intensive care management of patients with SAH.
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. PMID:25272066
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.
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
Introduction Non-aneurysmal spontaneous subarachnoid hemorrhage is characterized by an accumulation of a limited amount of subarachnoid hemorrhage, predominantly around the midbrain, and a lack of blood in the brain parenchyma or ventricular system. It represents 5% of all spontaneous subarachnoid hemorrhage cases. In spite of extensive investigation, understanding of the mechanisms leading to perimesencephalic non-aneurysmal subarachnoid hemorrhage remains incompletely defined. A growing body of evidence has supported a familial predisposition for non-aneurysmal spontaneous subarachnoid hemorrhage. Case presentation A 39-year-old Caucasian man presented with sudden onset headache associated with diplopia. His computed tomography scan revealed perimesencephalic subarachnoid hemorrhage. A cerebral angiogram showed no apparent source of bleeding. He was treated conservatively and discharged after 1 week without any neurological deficits. The older brother of the first case, a 44-year-old Caucasian man, presented 1.5 years later with acute onset of headache and his computed tomography scan also showed perimesencephalic non-aneurysmal subarachnoid hemorrhage. He was discharged home with normal neurological examination 1 week later. Follow-up angiograms did not reveal any source of bleeding in either patient. Conclusions We report the cases of two siblings with perimesencephalic non-aneurysmal subarachnoid hemorrhage, which may further suggest a familial predisposition of non-aneurysmal spontaneous subarachnoid hemorrhage and may also point out the possible higher risk of perimesencephalic non-aneurysmal subarachnoid hemorrhage in the first-degree relatives of patients with perimesencephalic non-aneurysmal subarachnoid hemorrhage. PMID:25416614
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
El Otmani, H; Moutaouakil, F; Fadel, H; Slassi, I
Nontraumatic subarachnoid hemorrhage is a relatively rare disease, typically secondary to a ruptured aneurysm. We report the case of a 23-year-old patient who developed a subarachnoid hemorrhage caused by extensive cerebral venous thrombosis due to a factor V Leiden mutation. Cerebral venous thrombosis is an uncommon etiology of subarachnoid hemorrhage. This raises diagnostic difficulties and a therapeutic dilemma regarding the use of anticoagulants. Copyright © 2012. Published by Elsevier Masson SAS.
Diringer, Michael N.
Objective Acute aneurysmal subarachnoid hemorrhage (SAH) is a complex multifaceted disorder that plays out over days to weeks. Many SAH patients are seriously ill and require a prolonged ICU stay. Cardiopulmonary complications are common. The management of SAH patients focuses on the anticipation, prevention and management of these secondary complications. Data Sources Source data were obtained from a PubMed search of the medical literature. Data Synthesis and Conclusion The rupture of an intracranial aneurysm is a sudden devastating event with immediate neurologic and cardiac consequences that require stabilization to allow for early diagnostic angiography. Early complications include rebleeding, hydrocephalus, and seizures. Early repair of the aneurysm (within 1-3 days) should take place by surgical or endovascular means. Over the first 1-2 weeks after hemorrhage, patients are at risk for delayed ischemic deficits due to vasospasm, autoregulatory failure and intravascular volume contraction. Delayed ischemia is treated with combinations of volume expansion, induced hypertension, augmentation of cardiac output, angioplasty and intra-arterial vasodilators. Subarachnoid hemorrhage is a complex disease with a prolonged course that can be particularly challenging and rewarding to the intensivist. PMID:19114880
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.
Sommargren, Claire E
Subarachnoid hemorrhage is a serious neurological disorder that is often complicated by the occurrence of electrocardiographic abnormalities unexplained by preexisting cardiac conditions. These morphological waveform changes and arrhythmias often are unrecognized or misinterpreted, potentially placing patients at risk for inappropriate management. Many previous investigations were retrospective and relied on data collected in an unsystematic manner. More recent studies that included use of serial electrocardiograms and Holter recordings have provided new insight into the high prevalence of electrocardiographic changes in subarachnoid hemorrhage. Research on the prevalence, duration, and clinical significance of these electrocardiographic abnormalities and on associated factors and etiological theories is reviewed.
Choi, Kyu-Sun; Yi, Hyeong-Joong
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset headache with focal neurologic deficit and prolonged but reversible multifocal narrowing of the distal cerebral arteries. Stroke, either hemorrhagic or ischemic, is a relatively frequent presentation in RCVS, but progressive manifestations of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction in a patient is seldom described. We report a rare case of a 56-year-old woman with reversible cerebral vasoconstriction syndrome consecutively presenting as cortical subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction. When she complained of severe headache with subtle cortical subarachnoid hemorrhage, her angiography was non-specific. But, computed tomographic angiography showed typical angiographic features of this syndrome after four days. Day 12, she suffered mental deterioration and hemiplegia due to contralateral intracerebral hematoma, and she was surgically treated. For recurrent attacks of headache, medical management with calcium channel blockers has been instituted. Normalized angiographic features were documented after 8 weeks. Reversible cerebral vasoconstriction syndrome should be considered as differential diagnosis of non-aneurysmal subarachnoid hemorrhage, and repeated angiography is recommended for the diagnosis of this under-recognized syndrome.
Kumar, S; Goddeau, R P; Selim, M H; Thomas, A; Schlaug, G; Alhazzani, A; Searls, D E; Caplan, L R
To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases-9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients < or =60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.
Albertine, Paul; Borofsky, Samuel; Brown, Derek; Patel, Smita; Lee, Woojin; Caputy, Anthony; Taheri, M Reza
With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests
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.
Wei, Helen S; Reitz, Katherine M; Kang, Hongyi; Takano, Takahiro; Vates, G Edward; Nedergaard, Maiken
Aneurysmal subarachnoid hemorrhage remains one of the more devastating forms of stroke due in large part to delayed cerebral ischemia that appears days to weeks following the initial hemorrhage. Therapies exclusively targeting large caliber arterial vasospasm have fallen short, and thus we asked whether capillary dysfunction contributes to delayed cerebral ischemia after subarachnoid hemorrhage. Using a mouse model of subarachnoid hemorrhage and two-photon microscopy we showed capillary dysfunction unrelated to upstream arterial constriction. Subarachnoid hemorrhage decreased RBC velocity by 30%, decreased capillary pulsatility by 50%, and increased length of non-perfusing capillaries by 15%. This was accompanied by severe brain hypoxia and neuronal loss. Hyaluronidase, an enzyme that alters capillary blood flow by removing the luminal glycocalyx, returned RBC velocity and pulsatility to normal. Hyaluronidase also reversed brain hypoxia and prevented neuron loss typically seen after subarachnoid hemorrhage. Thus, subarachnoid hemorrhage causes specific changes in capillary RBC flow independent of arterial spasm, and hyaluronidase treatment that normalizes capillary blood flow can prevent brain hypoxia and injury after subarachnoid hemorrhage. Prevention or treatment of capillary dysfunction after subarachnoid hemorrhage may reduce the incidence or severity of subarachnoid hemorrhage-induced delayed cerebral ischemia. PMID:26661183
Pereira, Julio Leonardo Barbosa; de Albuquerque, Lucas Alverne Freitas; Dellaretti, Marcos; de Carvalho, Gervásio Teles Cardoso; Jr, Gerival Vieira; Brochado, Vitor Michelstaedter; Drummond, Austen Venâncio; de Morais, Joyce Espeschit; Ferreira, Leticia Maia; Miranda, Paulo Augusto Carvalho; de Sousa, Atos Alves
OBJECTIVE: Aneurysmal subarachnoid hemorrhage puts patients at high risk for the development of pituitary insufficiency. We evaluated the incidence of pituitary dysfunction in these patients and its correlation with clinical outcome. METHODS: Pituitary function was tested in 66 consecutive patients in the first 15 days after aneurysmal subarachnoid hemorrhage. The following were measured in all patients: thyroid-stimulating hormone, free thyroxine, triiodothyronine, luteinizing hormone, follicle-stimulating hormone, total testosterone (in males), estradiol (in females), prolactin, serum cortisol, plasma adrenocorticotropic hormone, growth hormone and insulin growth factor. RESULTS: The endocrine assessment was made at a mean of 7.4 days (standard deviation ±6.6) after subarachnoid hemorrhage. Forty-four (66.7%) female and 22 (33.3%) male patients were evaluated. Thirty-nine patients (59.1%) had some type of pituitary dysfunction. Follicle-stimulating hormone/luteinizing hormone deficiency was the most frequent disorder (34.8%), followed by growth hormone/insulin growth factor (28.7%), adrenocorticotropic hormone (18.1%) and thyroid-stimulating hormone (9%). Seventeen (25.7%) patients showed deficiencies in more than one axis. A greater incidence of hormone deficiency was observed in patients with a Glasgow Coma Scale score ≤13 (t test, p = 0.008), Hunt-Hess grade ≥4 (t test, p<0.001), or Fisher grade 4 (t test, p = 0.039). Hormone deficiency was not significantly associated (p>0.05) with increased hospitalization or clinical outcome. CONCLUSION: Pituitary dysfunction was identified in a substantial portion of patients with previous aneurysmal subarachnoid hemorrhage, but no association was found between this dysfunction and poor clinical outcome. PMID:23778478
THE WORST HEADACHE OF LIFE: EVALUATION OF NONTRAUMATIC SUBARACHNOID HEMORRHAGE . 6. AUTHOR(S) MAJ SHERMAN PAUL M 7. PERFORMING ORGANIZATION NAME(S) AND...one primary cause (2). There are approximately 30,000 cases of nontraumatic subarachnoid hemorrhage in the United States each year (2, 3). The classic...presentation of nontraumatic subarachnoid hemorrhage is an acute onset, severe headache which reaches its maximum intensity within minutes, often
Bray, David P; Ellis, Jason A; Lavine, Sean D; Meyers, Philip M; Connolly, E Sander
Antiplatelet medication use is associated with worsened outcome after angiogram-negative subarachnoid hemorrhage (SAH). It has been hypothesized that these worsened outcomes may be the result of an association between antiplatelet medication use and increased hemorrhage volumes after angiogram-negative SAH. To test this hypothesis, we performed volumetric analysis of computed tomography (CT)-defined hemorrhage after angiogram-negative SAH. This was a retrospective analysis of patients presenting with nontraumatic, angiogram-negative SAH in the Columbia University Subarachnoid Hemorrhage Outcomes database between 2000 and 2013. SAH volumes on admission head CT scans were measured using the MIPAV software package, version 7.20 in a semiautomated fashion. A total of 108 presenting CT scans from patients with angiogram-negative SAH were analyzed. The mean hemorrhage volume was 14.3 mL in the patients with a history of antiplatelet medication use, compared with 6.8 mL in those with no history of antiplatelet use. This difference was found to be significant (P = 0.0029). Antiplatelet medication use is associated with increased SAH volumes in patients with angiogram-negative SAH. Increased hemorrhage volumes may contribute to poor outcomes in this patient population. Prospective studies are warranted to confirm this association. Copyright © 2016 Elsevier Inc. All rights reserved.
Eden, S V.; Meurer, W J.; Sánchez, B N.; Lisabeth, L D.; Smith, M A.; Brown, D L.; Morgenstern, L B.
Background: Mexican Americans (MAs) comprise the largest component of the largest minority group within the United States. The purpose of this study was to examine ethnic and gender differences in the epidemiology, presentation, and outcomes after subarachnoid hemorrhage (SAH) in a representative United States community. Targeted public health interventions are dependent on accurate assessments of groups at highest disease risk. Methods: All patients with nontraumatic SAH older than 44 years were prospectively identified from January 1, 2000, to December 31, 2006, as part of the Brain Attack Surveillance In Corpus Christi project, an urban population-based study in southeast Texas. Risk ratios for cumulative SAH incidence comparing MAs with non Hispanic whites (NHWs) and women with men were calculated. Descriptive statistics for other clinical and demographic variables were computed overall, by gender, and by ethnicity. Results: A total of 107 patients had a SAH during the time period (7-year cumulative incidence: 11/10,000); of these, 43 were NHW (40% of cases vs 53% of the population) and 64 were MA (60% of cases vs 48% of the population). The overall age-adjusted risk ratio for SAH in MAs compared with NHWs was 1.67 (95% CI: 1.13, 2.47), and in women compared to men was 1.74 (95% CI 1.16, 2.62). Overall in-hospital mortality was 32.2%. No ethnic difference was observed for discharge disability or in-hospital mortality. Conclusions: Subarachnoid hemorrhage disproportionately affects Mexican Americans and women. Public health interventions should target these groups to reduce the impact of this severe disease. GLOSSARY BASIC = Brain Attack Surveillance in Corpus Christi; GCS = Glasgow Coma Scale; ICD = International Classification of Diseases; ICH = intracerebral hemorrhage; MA = Mexican American; mRS = modified Rankin Scale; NHW = non-Hispanic white; SAH = subarachnoid hemorrhage. PMID:18550859
Packer, Rebecca A; Bergman, Robert L; Coates, Joan R; Essman, Stephanie C; Weis, Kevin; O'Brien, Dennis P; Johnson, Gayle C
Intracranial subarachnoid hemorrhage is a rare but serious complication of lumbar puncture in humans. Possible sequelae include increased intracranial pressure, cerebral vasospasm, or mass effect, which can result in dysfunction or brain herniation. We describe two dogs that developed intracranial subarachnoid hemorrhage following lumbar myelography. In both dogs, myelography was performed by lumbar injection of iohexol (Omnipaque). Both the dogs underwent uneventful ventral decompressive surgery for disk herniation; however, the dogs failed to recover consciousness or spontaneous respiration following anesthesia. Neurologic assessment in both dogs postoperatively suggested loss of brain stem function, and the dogs were euthanized. There was diffuse subarachnoid hemorrhage and leptomeningeal hemorrhage throughout the entire length of the spinal cord, brain stem, and ventrum of brain. No evidence of infectious or inflammatory etiology was identified. The diagnosis for cause of brain death was acute subarachnoid hemorrhage. Our findings suggest that fatal subarachnoid hemorrhage is a potential complication of lumbar myelography in dogs. The cause of subarachnoid hemorrhage is not known, but may be due to traumatic lumbar tap or idiosyncratic response to contrast medium. Subsequent brain death may be a result of mass effect and increased intracranial pressure, cerebral vasospasm, or interaction between subarachnoid hemorrhage and contrast medium.
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.
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.
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
Liu, Yan; Jolly, Suneil; Pokala, Krishna
Paroxysmal sympathetic storming (PSS) is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH), there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.
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
Morris, Paul Graham; Wilson, J T Lindsay; Dunn, Laurence
Relatively little attention has been paid to emotional outcome after subarachnoid hemorrhage (SAH). This study assessed levels of anxiety and depression among SAH survivors and related these to clinical indices. Seventy SAH patients from a consecutive series of neurosurgical admissions participated in semistructured assessments of functional outcome; 52 of the patients also returned standardized measures of emotional outcome. These data were compared with clinical indices collected during the initial hospital admission. Moderate to severe levels of anxiety were present in approximately 40% of patients 16 months after hemorrhage, with approximately 20% experiencing moderate to severe levels of depression. Although anxiety was more likely to be reported at interview by those with an SAH of Fisher Grade 4, the standardized measures of anxiety and depression were not associated with severity of hemorrhage or any other clinical variables. Both anxiety and depression were significantly associated with outcome indices such as return to work and engagement in social activities. Anxiety is a significant and lasting problem for approximately 40% of survivors of SAH. It is suggested that measures taken to prevent or treat such anxiety among survivors of SAH may serve to significantly improve functional outcome.
Coelho, Luís Guilherme Bastos Silva Aguiar; Costa, José Manuel Dias; Silva, Elsa Irene Peixoto Azevedo
Objective To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Methods The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Results Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 ± 10.3 months). Conclusion Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources. PMID:27410409
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.
Schmidt, J Michael; Rincon, Fred; Fernandez, Andres; Resor, Charles; Kowalski, Robert G; Claassen, Jan; Connolly, E Sander; Fitzsimmons, Brian-Fred M; Mayer, Stephan A
Cerebral infarction is a common complication of aneurysmal subarachnoid hemorrhage (SAH), but usually occurs several days after onset as a complication of vasospasm or aneurysm repair. The frequency, causes, and clinical impact of acute infarction associated with the primary hemorrhage are poorly understood. We evaluated the presence of cerebral infarction on admission CT in 487 patients admitted within 3 days of SAH onset to our center between July 1996 and September 2002. Infarctions due to angiography or treatment complications were rigorously excluded. Outcome at 3 months was assessed with the modified Rankin Scale. A total of 17 patients (3%) had acute infarction on admission CT; eight had solitary and nine had multiple infarcts. Solitary infarcts usually appeared in the vascular territory distal to the ruptured aneurysm, whereas multiple infarcts tended to be territorial and symmetric. Global cerebral edema (P < 0.001), coma on presentation (P = 0.001), intraventricular hemorrhage (P = 0.002), elevated APACHE-II physiological subscores (P = 0.026) and loss of consciousness at onset (P = 0.029) were associated with early cerebral infarction. Mortality (P = 0.003) and death or moderate-to-severe disability (mRS 4-6, P = 0.01) occurred more frequently in the early cerebral infarction group. Early cerebral infarction on CT is a rare but devastating complication of acute SAH. The observed associations with coma, global cerebral edema, intraventricular hemorrhage, and loss of consciousness at onset suggest that intracranial circulatory arrest may play a role in the pathogenesis of this disorder.
Mark, Dustin G; Pines, Jesse M
Nontraumatic subarachnoid hemorrhage is one of the most elusive diagnoses in emergency medicine; it is a potentially lethal disease that is often considered and rarely found. The current practice as determined by the American College of Emergency Physicians 1996 Clinical Policy on Headache is a noncontrast head computed tomography (CT) followed by diagnostic lumbar puncture (LP) to exclude subarachnoid hemorrhage. Whereas the guideline does not consider pretest probability of subarachnoid hemorrhage in determining which patients require LP after negative head CT, patients' acceptance of LP, technical aspects of performing a LP in patients with nonideal anatomy, and risks associated with LP must all be considered when choosing to proceed with invasive testing. This article outlines the use of current testing modalities including CT, magnetic resonance imaging, angiography and LP to provide an up-to-date understanding of diagnostic testing for subarachnoid hemorrhage.
Cruz, Juan Pablo; Sarma, Dipanka; Noel de Tilly, Lyne
To evaluate the yield of digital subtraction angiography (DSA) and repeated follow-up imaging in patients with initial pattern of perimesencephalic subarachnoid hemorrhage (PSAH) and negative computed tomography angiography (CTA) in excluding an underlying aneurysm. We conducted a retrospective analysis of all nontraumatic SAH who underwent a DSA between January 2006 and January 2010 and selected those with a PSAH pattern on CT done within 72 h from ictus. All CTAs were performed with a 64-section multidetector row CT scanner, and findings were compared with DSA and to follow-up imaging. Forty-nine patients with initial PSAH pattern and negative CTA who underwent subsequent DSA were identified. Six patients were excluded because CTA was not available in hospitals or 72 h after ictus. Only one patient (2.4%) had a false negative CTA with a 1-mm left ICA aneurysm seen on DSA, considered not to be the source of hemorrhage. An average of 2.0 ± 1.2 follow-up exams per patient (range 0-5) revealed no source of bleeding. One patient had a procedure-related transient complication, but evolved with no sequels. In patients with PSAH, CTA is reliable for ruling out an underlying aneurysm. DSA and, especially, further follow-up imaging have no increased diagnostic yield compared to initial negative CTA.
Gilmore, Emily; Choi, H Alex; Hirsch, Lawrence J; Claassen, Jan
Convulsive and nonconvulsive seizures frequently complicate acute brain injury particularly central nervous system hemorrhages and both have been associated with poor outcome. No randomized controlled trials have been conducted to guide decisions on seizure prophylaxis or treatment. The magnitude of additional injury from nonconvulsive seizures remains controversial and some argue that these epileptiform patterns primarily represent surrogate markers of severely injured brain. The deleterious effects of seizures on brain recovering from a recent injury have to be weighed against the deleterious effects of antiepileptic medications when making decisions on prophylaxis and treatment. Currently seizure prophylaxis is not generally recommended for patients with spontaneous intracerebral hemorrhage (ICH) or aneurysmal subarachnoid hemorrhage (aSAH). However, short-term prophylaxis (during the acute critical illness) is commonly instituted for patients in whom seizures would likely lead to additional injury such as herniation or rebleeding. ICH or aSAH patients with seizures at the onset of their hemorrhage, patients with ICH in close proximity to the cortical surface, and aSAH patients with a poor clinical grade (poor neurologic examination and/or thick cisternal blood) are at high risk of seizures, especially nonconvulsive, and are frequently kept on short-term prophylaxis. Convulsive seizures occur in 7% to 17% of patients with spontaneous ICH and in between 6% and 26% of those with aneurysmal aSAH. These should be treated as soon as possible regardless of the underlying causative factors. Nonconvulsive seizures are seen in about 20% of patients with ICH and in 8% to 18% of those with aSAH. It is controversial how aggressively to treat nonconvulsive seizures. Convulsive and nonconvulsive seizures are frequent after central nervous system hemorrhage and treatment is controversial, particularly for nonconvulsive seizures. Randomized controlled trials need to be
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…
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…
Lantigua, Hector; Ortega-Gutierrez, Santiago; Schmidt, J Michael; Lee, Kiwon; Badjatia, Neeraj; Agarwal, Sachin; Claassen, Jan; Connolly, E Sander; Mayer, Stephan A
Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Causes and mechanisms of in-hospital death after SAH in the modern era of neurocritical care remain incompletely understood. We studied 1200 consecutive SAH patients prospectively enrolled in the Columbia University SAH Outcomes Project between July 1996 and January 2009. Analysis was performed to identify predictors of in-hospital mortality. In-hospital mortality was 18% (216/1200): 3% for Hunt-Hess grade 1 or 2, 9% for grade 3, 24% for grade 4, and 71% for grade 5. The most common adjudicated primary causes of death or neurological devastation leading to withdrawal of support were direct effects of the primary hemorrhage (55%), aneurysm rebleeding (17%), and medical complications (15%). Among those who died, brain death was declared in 42%, 50% were do-not-resuscitate at the time of cardiac death (86% of whom had life support actively withdrawn), and 8% died despite full support. Admission predictors of mortality were age, loss of consciousness at ictus, admission Glasgow Coma Scale score, large aneurysm size, Acute Physiology and Chronic Health Evaluation II (APACHE II) physiologic subscore, and Modified Fisher Scale score. Hospital complications that further increased the risk of dying in multivariable analysis included rebleeding, global cerebral edema, hypernatremia, clinical signs of brain stem herniation, hypotension of less than 90 mm Hg treated with pressors, pulmonary edema, myocardial ischemia, and hepatic failure. Delayed cerebral ischemia, defined as deterioration or infarction from vasospasm, did not predict mortality. Strategies directed toward minimizing early brain injury and aneurysm rebleeding, along with prevention and treatment of medical complication, hold the best promise for further reducing mortality after SAH.
Anderson, Brian; Sabat, Shyamsunder; Agarwal, Amit; Thamburaj, Krishnamoorthy
Aneurysmal rupture accounts for the majority of nontraumatic subarachnoid hemorrhage (SAH). Increasingly recognized is the occurrence of nontraumatic convexity SAH unaccounted for by aneurysmal rupture. These presentations require consideration of rare but clinically significant sources of SAH. We report a patient presenting with prolonged mild headaches and acute onset of seizure like activity found to have diffuse subarachnoid hemorrhage and extensive dural venous sinus thrombosis involving the superior sagittal sinus and right transverse-sigmoid sinuses. There are few reported cases of SAH secondary to dural sinus thrombosis; however most of these are convexity hemorrhage. Sinus thrombosis presenting as diffuse SAH is extremely rare, as is showcased in this report.
Roth, C; Ferbert, A
Worldwide there are differences in the procedure of determining brain death. An irreversible loss of all brain functions, including cerebrum, cerebellum and brainstem is mandatory for the diagnosis of brain death in Germany. On the basis of a case report some important aspects of the new recommendations of the German guidelines are discussed. We present the case of a 41-year old patient who was admitted to our clinic due to acute subarachnoid hemorrhage (SAH). Angiography revealed an aneurysm of the posterior inferior cerebellar artery. The patient was comatose without any brainstem reflexes and showed apnoea. However, on day 3, EEG showed alpha activity as a sign of residual cortical function. We diagnosed an isolated brainstem death. The next day EEG was isoelectric and brain death was confirmed. The diagnosis of isolated brainstem death does not allow a confirmation of death in Germany. Our case presents a primary infratentorial brain damage mandating additional confirmatory tests. © Georg Thieme Verlag KG Stuttgart · New York.
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.
Long, Brit; Koyfman, Alex
Headache is a common chief complaint in emergency departments, accounting for 2% of visits, and subarachnoid hemorrhage (SAH) is a life-threating cause of headache. This deadly disease is most commonly due to aneurysmal rupture. Various approaches exist for diagnosis, with recent studies evaluating these approaches. A great deal of controversy exists about the optimal diagnosis strategy for SAH. This article in the Best Clinical Practice Series seeks to educate emergency physicians on the recent literature in the diagnosis of SAH and provide an evidence-based approach. Various diagnostic strategies exist, including use of noncontrast head computed tomography (CT) alone, CT/lumbar puncture (LP) in combination, CT/CT angiography, and magnetic resonance imaging/magnetic resonance angiography. The use of clinical decision rules has also been espoused, and several contemporary studies have evaluated cerebrospinal fluid results of red blood cell count and xanthochromia in the diagnosis of SAH. Recent literature supports that a negative head CT done within 6 h of headache onset places the patient at a < 1% risk for SAH. With the complex literature, a shared decision-making model should be followed with options, risks, and benefits discussed with the patient. Literature support exists for all of the diagnostic strategies. The American College of Emergency Physicians Clinical Policy supports CT and LP for definitive diagnosis. Risk stratification and a shared decision-making model with the patient should be followed, and a negative head CT within 6 h of headache onset places patient at a risk of < 1% for having SAH. Published by Elsevier Inc.
Tujjar, Omar; Belloni, Ilaria; Hougardy, Jean-Michel; Scolletta, Sabino; Vincent, Jean-Louis; Creteur, Jacques; Taccone, Fabio S
Acute kidney injury (AKI) is common in critically ill patients and may contribute to poor outcome. Few data are available on the incidence and impact of AKI in patients suffering from nontraumatic subarachnoid hemorrhage (SAH). We reviewed all patients admitted to our Department of Intensive Care with SAH over a 3-year period. Exclusion criteria were time from SAH symptoms to intensive care unit (ICU) admission >96 hours and ICU stay <48 hours. AKI was defined as sustained oligoanuria (urine output <0.5 mL/kg/h for 24 h) or an increase in plasma creatinine (≥0.3 mg/dL or a 1.5-fold increase from baseline level within 48 h). Neurological status was assessed at day 28 using the Glasgow Outcome Scale (GOS) (from 1=death to 5=good recovery; favorable outcome=GOS 4 to 5). Of 243 patients admitted for SAH during the study period, 202 met the inclusion/exclusion criteria (median age 56 y, 78 male). Twenty-five patients (12%) developed AKI, a median of 8 (4 to 10) days after admission. Independent predictors of AKI were development of clinical vasospasm, and treatment with vancomycin. AKI was more frequent in ICU nonsurvivors than in survivors (11/50 vs. 14/152, P=0.03), and in patients with an unfavorable neurological outcome than in other patients (17/93 vs. 8/109, P=0.03). Nevertheless, in multivariable regression analysis, AKI was not an independent predictor of outcome. AKI occurred in >10% of patients after SAH. These patients had more severe neurological impairment and needed more aggressive ICU therapy; AKI did not significantly influence outcome.
Carvi y Nievas, Mario Nazareno; Archavlis, Eleftherios
To analyze the management and outcome of patients presenting with atypical causes of intracranial subarachnoid hemorrhage (SAH). We performed a review of our last 820 nontraumatic-SAH patients and analyzed the management and outcome of patients where the SAH origin was not a ruptured aneurysm. The Glasgow Outcome Scale (GOS) was used to assess outcome 3 months after event. Thirty-two patients had atypical causes of SAH. In 15 patients with Hunt and Hess (H&H) scores from 1 to 3 without focal neurological deficit (FND), 8 perimesencephalic non-aneurysmal SAH, 4 blood coagulation disorders, 1 sinus thrombosis, 1 vasculitis, and 1 unknown-origin-SAH (UOS) were diagnosed. Fourteen (93%) of these 15 patients were conservatively treated. In 17 patients with H&H scores from 3 to 5 and FND, 8 tumors, 1 cavernoma, 1 sinus thrombosis, 1 arteriovenous malformation, 1 blood coagulation disorders, 2 UOS, and 3 dural fistulas were diagnosed. Fifteen (88%) of these 17 patients were interventionally treated. The neurological condition 3 months later was good (GOS 4 and 5) in 12 of the 15 cases (80%) admitted with low-H&H scores, as well as in 13 of the 17 cases (76%) admitted with high-H&H scores. Three patients died and four developed a severe disability. Patients presenting with atypical causes of SAH and high-H&H scores at admission are likely to harbor an intracranial organic process producing the bleeding. Despite this poor initial condition, their 3-month outcome can be similar to those of patients with low-H&H scores if the origin of the bleeding is properly treated.
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.
Lindbohm, Joni Valdemar; Kaprio, Jaakko; Jousilahti, Pekka; Salomaa, Veikko; Korja, Miikka
Women are at higher risk for subarachnoid hemorrhage (SAH) than men for unknown reasons. Also cumulative effects of smoking have been neglected among prospective studies. We studied associations between smoking habits and SAH and interactions between known SAH risk factors in a prospective population-based study. The population-based FINRISK study cohort of 65 521 individuals was followed up for 1.38 million person-years. We used the Cox proportional hazards model to calculate hazard ratios and evaluated additive and multiplicative interactions between study variables, with all analyses adjusted for known SAH risk factors. During follow-up, we identified 492 SAHs (266 women). Smoking had a linear dose-dependent and cumulative association with risk for SAH in both sexes. Women smoking >20 cigarettes per day had a hazard ratio of 8.35 (95% confidence interval, 3.86-18.06) compared with a hazard ratio of 2.76 (95% confidence interval, 1.68-4.52) in men in the same cigarettes per day group. Hazard ratios differed by sex in all cigarettes per day and pack-year categories; this association was stronger in women in all categories (P=0.01). When an adjusted model included interaction terms between sex and cigarettes per day or pack-years, female sex was no longer an independent SAH risk factor. Former smokers had a markedly decreased risk for SAH in both sexes when compared with current smokers. Smoking has a dose-dependent and cumulative association with SAH risk, and this risk is highest in female heavy smokers. Vulnerability to smoking seems to explain in part the increased SAH risk in women. © 2016 American Heart Association, Inc.
Kaloostian, Paul; Westhout, Franklin; Taylor, Chris L
The authors report the first retrospective analysis of all reported cases of death from aneurysmal subarachnoid hemorrhage in the state of New Mexico from 1 January 2001 to 31 December 2007. Data were obtained from the New Mexico Vital Records and Health Statistics Department in Santa Fe, New Mexico. The incidence of death from aneurysmal subarachnoid hemorrhage in the state of New Mexico is 2.96/100,000 people per year. Each cultural subgroup and various risk factors in these patients were further analyzed. This report represents the first documented review of death from aneurysmal subarachnoid hemorrhage in the state of New Mexico. There was a lower incidence in New Mexico compared with the national average. Cultural breakdowns and associated epidemiological factors are discussed.
Izenberg, Aaron; Aviv, Richard I; Demaerschalk, Bart M; Dodick, David W; Hopyan, Julia; Black, Sandra E; Gladstone, David J
Diagnosis of transient ischemic attack can be difficult because many mimics exist. We report the clinical and neuroimaging features of a distinct hemorrhagic transient ischemic attack mimic. Case series. We describe 4 elderly patients presenting with a cluster of stereotyped somatosensory migraine auras, initially referred for "crescendo transient ischemic attacks". Neuroimaging in each patient revealed an unexpected finding of spontaneous focal subarachnoid hemorrhage conforming to a cortical sulcus in the contralateral hemisphere. We postulate that the episodic aura symptoms corresponded to recurrent cortical spreading depression triggered by the presence of subarachnoid blood, and speculate that such episodes could be a presenting feature of cerebral amyloid angiopathy in the absence of typical cerebral microbleeds or history of cognitive impairment. Focal subarachnoid hemorrhage can present clinically with transient repetitive migraine auras. Awareness of this entity is important because misdiagnosis as cerebral ischemic events could lead to incorrect treatment. We recommend that elderly patients presenting with a cluster of new unexplained migraine auras should be investigated ideally with MRI to detect focal subarachnoid hemorrhage.
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…
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…
Lucke-Wold, Brandon P.; Logsdon, Aric F.; Manoranjan, Branavan; Turner, Ryan C.; McConnell, Evan; Vates, George Edward; Huber, Jason D.; Rosen, Charles L.; Simard, J. Marc
Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials. PMID:27049383
Guo, Jia; Shi, Zhenghong; Yang, Kehu; Tian, Jin Hui; Jiang, Lei
A subarachnoid hemorrhage (SAH) is a serious and potentially life-threatening condition where blood leaks out of blood vessels over the surface of the brain. Delayed ischemic neurological deficit (DIND) and the related feature of vasospasm, where patients experience a delayed deterioration, have long been recognized as the leading potentially treatable cause of death and disability in patients with SAH. Endothelin is a potent, long-lasting endogenous vasoconstrictor that has been implicated in the pathogenesis of DIND. Therefore, endothelin receptor antagonists (ETAs) have emerged as a promising therapeutic option for SAH-induced cerebral vasospasm. To assess the efficacy and tolerability of ETAs for SAH. We searched the Cochrane Stroke Group Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 11), MEDLINE (1950 to December 2011), EMBASE (1946 to December 2011) and the Chinese Biomedical Database (1978 to December 2011). In an effort to identify further published, unpublished and ongoing trials we searched additional Chinese databases, ongoing trials registers, Google Scholar and Medical Matrix, handsearched journals, scanned reference lists, and contacted researchers and pharmaceutical companies. We only included randomized controlled trials (RCTs) that compared an ETA with placebo for SAH in adult (18 years of age or older) patients who met the diagnostic criteria for SAH based on clinical symptoms, with confirmation on computerized tomography scan results or angiography. Two review authors independently selected RCTs according to the inclusion criteria. We resolved disagreements by discussion with a third review author. Two review authors independently selected relevant articles and assessed their eligibility according to the inclusion and exclusion criteria. We resolved disagreements by discussion with a third review author. We used the random-effects model and expressed the results as
Anderson, Brian; Sabat, Shyamsunder; Agarwal, Amit; Thamburaj, Krishnamoorthy
Summary Background Aneurysmal rupture accounts for the majority of nontraumatic subarachnoid hemorrhage (SAH). Increasingly recognized is the occurrence of nontraumatic convexity SAH unaccounted for by aneurysmal rupture. Case Report These presentations require consideration of rare but clinically significant sources of SAH. We report a patient presenting with prolonged mild headaches and acute onset of seizure like activity found to have diffuse subarachnoid hemorrhage and extensive dural venous sinus thrombosis involving the superior sagittal sinus and right transverse-sigmoid sinuses. Conclusions There are few reported cases of SAH secondary to dural sinus thrombosis; however most of these are convexity hemorrhage. Sinus thrombosis presenting as diffuse SAH is extremely rare, as is showcased in this report. PMID:26097524
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.
Beitzke, Markus; Gattringer, Thomas; Enzinger, Christian; Wagner, Gerit; Niederkorn, Kurt; Fazekas, Franz
Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. The 24 patients with cSAH had a mean age of 70 years (range, 37-88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3-6), including 5 deaths. We did not observe recurrent cSAH. Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis.
Jaja, Blessing N R; Attalla, Daniel; Macdonald, R Loch; Schweizer, Tom A; Cusimano, Michael D; Etminan, Nima; Hanggi, Daniel; Hasan, David; Johnston, S Claiborne; Le Roux, Peter; Lo, Benjamin; Louffat-Olivares, Ada; Mayer, Stephan; Molyneux, Andrew; Noble, Adam; Quinn, Audrey; Schenk, Thomas; Spears, Julian; Singh, Jeffrey; Todd, Michael; Torner, James; Tseng, Ming; van den Bergh, William; Vergouwen, Mervyn D I; Wong, George K C
Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15 years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuroimaging, and laboratory results and various outcome measures. We have compiled the largest known dataset of patients with SAH. The SAHIT repository may be an important resource for advancing clinical research in SAH and will benefit from contributions of additional datasets.
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.
Larsen, Carl C; Hansen-Schwartz, Jacob; Nielsen, Jørn D; Astrup, Jens
Aneurysmal rebleeding poses a serious risk in patients with subarachnoid hemorrhage (SAH). Studies have shown that antifibrinolytic therapy with tranexamic acid has a dramatic effect on the rate of rebleeding. Therefore, changes in the fibrinolytic system could be hypothesized. We have used an experimental SAH rat model to demonstrate serial changes in the haemostatic system as evaluated by Thromboelastography (TEG). In the SAH group, a shorter reaction time (R-time) and higher maximum amplitude (MA) were observed. In the saline group, only a shorter R-time was observed. The study has shown that a hypercoagulable state is present immediately after experimental SAH is induced as determined by TEG. The reduction in R-time and rise in MA observed in the SAH group indicate that blood in the subarachnoid space is necessary to accomplish a full systemic coagulation response. This abnormality in coagulation profile seems to be a response to the acute traumatic event caused by induction of SAH.
Cuvinciuc, V; Viguier, A; Calviere, L; Raposo, N; Larrue, V; Cognard, C; Bonneville, F
Our aim was to review the etiologic background of isolated acute nontraumatic cSAH. While SAH located in the basal cisterns originates from a ruptured aneurysm in approximately 85% of cases, a broad spectrum of vascular and even nonvascular pathologies can cause acute nontraumatic SAH along the convexity. Arteriovenous malformations or fistulas, cortical venous and/or dural sinus thrombosis, and distal and proximal arteriopathies (RCVS, vasculitides, mycotic aneurysms, Moyamoya, or severe atherosclerotic carotid disease) should be sought by noninvasive imaging methods or/and conventional angiography. Additionally, PRES may also be a source of acute cSAH. In elderly patients, cSAH might be attributed to CAA if numerous hemorrhages are demonstrated by GRE T2 images. Finally, cSAH is rarely observed in nonvascular disorders, such as abscess and primitive or secondary brain tumors.
Wu, Z; Li, Shaowu; Lei, J; An, D; Haacke, E M
SWI is an MR imaging technique that is very sensitive to hemorrhage. Our goal was to compare SWI and CT to determine if SWI can show traumatic SAH in different parts of the subarachnoid space. Twenty acute TBI patients identified by CT with SAH underwent MR imaging scans. Two neuroradiologists analyzed the CT and SWI data to decide whether there were SAHs in 8 anatomical parts of the subarachnoid space. Fifty-five areas with SAH were identified by both CT and SWI. Ten areas were identified by CT only and 13 by SWI only. SAH was recognized on SWI by its very dark signal intensity surrounded by CSF signal intensity in the sulci or cisterns. Compared with the smooth-looking veins, SAH tended to have a rough boundary and inhomogeneous signal intensity. In many instances, blood in the sulcus left an area of signal intensity loss that had a "triangle" shape. SWI showed 5 more cases of intraventricular hemorrhage than did CT. SAH can be recognized by SWI through its signal intensity and unique morphology. SWI can provide complementary information to CT in terms of small amounts of SAH and hemorrhage inside the ventricles.
de Lima Oliveira, Marcelo; de Azevedo, Daniel Silva; de Azevedo, Milena Krajnyk; de Carvalho Nogueira, Ricardo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson
Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses. PMID:26109948
Badjatia, Neeraj; Seres, David; Carpenter, Amanda; Schmidt, J Michael; Lee, Kiwon; Mayer, Stephan A; Claassen, Jan; Connolly, E Sander; Elkind, Mitchell S
The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI. There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt-Hess score of 3. Adjusting for Hunt-Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (P=0.01), mean n-6:n-3 FFA ratio (P=0.02), and mean oxygen consumption level (P=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (P<0.001), younger age (P=0.05), and modified Fisher scale (P=0.004) were associated with time to DCI. Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.
Mao, David Qiyuan; Addess, Daniel; Valsamis, Helen
Report a case of cortical subarachnoid hemorrhage (cSAH) and discuss its management. A 66-year-old woman presents with acute onset left arm numbness and weakness. Initial head CT shows small hyperdensity in sulci typical for cSAH. Extensive workup with MRI, lumbar puncture and blood tests is performed. No signs of infection, vascular malformations, thrombosis or cancer are found. At outpatient follow-up, she is diagnosed with cSAH secondary to amyloid angiopathy. She is treated with gabapentin. Diagnosis of cSAH is challenging given its subtle findings, and management is empiric as there are only a few case series in literature.
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).
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
Dhar, Rajat; Zazulia, Allyson R; Derdeyn, Colin P; Diringer, Michael N
Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5 mL/100 g/min. PET facility located within the Neurology/Neurosurgery ICU. Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13 g/dL. Transfusion of one unit of RBCs over 1 hour. Baseline hemoglobin was 9.7 g/dL (range, 6.9-12.9), and cerebral blood flow was 43 ± 11 mL/100 g/min. After transfusion, hemoglobin rose from 9.6 ± 1.4 to 10.8 ± 1.4 g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5 mL/100 g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that
Abdul Rashid, Anna Misyail; Md Noh, Mohamad Syafeeq Faeez
Non-traumatic, spontaneous subarachnoid hemorrhage occurs in approximately 85% of cases where there is a ruptured saccular aneurysm. An additional 10% of cases arise from non-aneurysmal peri-mesencephalic hemorrhages. We report a rare case of a young female, with underlying Evans syndrome, who was initially thought to have non-hemorrhagic stroke, eventually diagnosed having isolated non-traumatic, non-aneurysmal convexal subarachnoid haemorrhage. Spontaneous non-traumatic, non-aneurysmal convexal subarachnoid hemorrhage is a rare entity - of which there are multiple possible etiologies.
Nakau, Reiko; Nomura, Motohiro; Kida, Shinya; Yamashita, Junkoh; Kinoshita, Akira; Nitta, Hisashi; Muramatsu, Naoki
A 59-year-old woman with type IIA von Willebrand's disease (VWD) presented with subarachnoid hemorrhage (SAH). Computed tomography showed SAH in the right sylvian fissure and intracranial hemorrhage in the right temporal lobe. Angiography demonstrated an aneurysm at the bifurcation of the right middle cerebral artery. Neck clipping was performed on the 3rd day after the onset with intra- and postoperative administration of factor VIII/von Willebrand factor concentrate. No excessive bleeding occurred. Patients with prolonged bleeding time should be screened for VWD before surgery. This is a rare case of VWD presenting with SAH secondary to ruptured intracranial aneurysm. The clinical characteristics and the management of SAH in a patient with VWD are discussed.
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.
Perry, Jeffrey J; Alyahya, Bader; Sivilotti, Marco L A; Bullard, Michael J; Émond, Marcel; Sutherland, Jane; Worster, Andrew; Hohl, Corinne; Lee, Jacques S; Eisenhauer, Mary A; Pauls, Merril; Lesiuk, Howard; Wells, George A; Stiell, Ian G
To describe the findings in cerebrospinal fluid from patients with acute headache that could distinguish subarachnoid hemorrhage from the effects of a traumatic lumbar puncture. A substudy of a prospective multicenter cohort study. 12 Canadian academic emergency departments, from November 2000 to December 2009. Alert patients aged over 15 with an acute non-traumatic headache who underwent lumbar puncture to rule out subarachnoid hemorrhage. Aneurysmal subarachnoid hemorrhage requiring intervention or resulting in death. Of the 1739 patients enrolled, 641 (36.9%) had abnormal results on cerebrospinal fluid analysis with >1 × 10(6)/L red blood cells in the final tube of cerebrospinal fluid and/or xanthochromia in one or more tubes. There were 15 (0.9%) patients with aneurysmal subarachnoid hemorrhage based on abnormal results of a lumbar puncture. The presence of fewer than 2000 × 10(6)/L red blood cells in addition to no xanthochromia excluded the diagnosis of aneurysmal subarachnoid hemorrhage, with a sensitivity of 100% (95% confidence interval 74.7% to 100%) and specificity of 91.2% (88.6% to 93.3%). No xanthochromia and red blood cell count <2000 × 10(6)/L reasonably excludes the diagnosis of aneurysmal subarachnoid hemorrhage. Most patients with acute headache who meet this cut off will need no further investigations and aneurysmal subarachnoid hemorrhage can be excluded as a cause of their headache. © Perry et al 2015.
Alyahya, Bader; Sivilotti, Marco L A; Bullard, Michael J; Émond, Marcel; Sutherland, Jane; Worster, Andrew; Hohl, Corinne; Lee, Jacques S; Eisenhauer, Mary A; Pauls, Merril; Lesiuk, Howard; Wells, George A; Stiell, Ian G
Objectives To describe the findings in cerebrospinal fluid from patients with acute headache that could distinguish subarachnoid hemorrhage from the effects of a traumatic lumbar puncture. Design A substudy of a prospective multicenter cohort study. Setting 12 Canadian academic emergency departments, from November 2000 to December 2009. Participants Alert patients aged over 15 with an acute non-traumatic headache who underwent lumbar puncture to rule out subarachnoid hemorrhage. Main outcome measure Aneurysmal subarachnoid hemorrhage requiring intervention or resulting in death. Results Of the 1739 patients enrolled, 641 (36.9%) had abnormal results on cerebrospinal fluid analysis with >1×106/L red blood cells in the final tube of cerebrospinal fluid and/or xanthochromia in one or more tubes. There were 15 (0.9%) patients with aneurysmal subarachnoid hemorrhage based on abnormal results of a lumbar puncture. The presence of fewer than 2000×106/L red blood cells in addition to no xanthochromia excluded the diagnosis of aneurysmal subarachnoid hemorrhage, with a sensitivity of 100% (95% confidence interval 74.7% to 100%) and specificity of 91.2% (88.6% to 93.3%). Conclusion No xanthochromia and red blood cell count <2000×106/L reasonably excludes the diagnosis of aneurysmal subarachnoid hemorrhage. Most patients with acute headache who meet this cut off will need no further investigations and aneurysmal subarachnoid hemorrhage can be excluded as a cause of their headache. PMID:25694274
Stiebel-Kalish, Hadas; Turtel, Lawrence S; Kupersmith, Mark J
To describe the natural history of intraocular hemorrhages related to subarachnoid hemorrhage (SAH) as a result of ruptured intracranial aneurysms. Retrospective review of patients with cerebral aneurysms examined by a referral neuro-ophthalmology service between 1980 and 1998. Patients with intraocular hemorrhages associated with SAH as a result of ruptured aneurysms were followed up without vitrectomy, unless bilateral vitreous hemorrhage occurred. Seventy of 450 patients with cerebral aneurysms had an SAH. Of these, 30 eyes of 19 patients had intraocular hemorrhages. Fourteen eyes had a vitreous hemorrhage; 12 had subhyaloid blood without a vitreous hemorrhage; and four had retinal hemorrhages alone. Two patients died shortly after presentation. Twenty-eight eyes were followed up for a mean of 4.8 years. Initial visual acuity was 20/100 to light perception in eyes with a vitreous hemorrhage, 20/20 to 20/400 in eyes with subhyaloid blood, and 20/20 to 20/40 in eyes with retinal hemorrhages. Three of the 12 eyes with a vitreous hemorrhage underwent vitrectomy. Of the nonoperated eyes, final visual acuity was at least 20/30 in 19 (76%) eyes, 20/40 to 20/60 in four (16%) eyes, and 20/100 in both eyes of one patient with premacular subhyaloid blood. None of the nonoperated eyes developed cataract formation or progression, retinal tears, or retinal detachment. Epiretinal membrane developed in one eye and pigmentary maculopathy developed in five. Except for patients with bilateral vitreous hemorrhages, early vitrectomy may not be necessary in most cases of intraocular hemorrhages associated with nontraumatic SAH.
Fu, Fang-Wang; Rao, Jie; Zheng, Yuan-Yuan; Song, Liang; Chen, Wei; Zhou, Qi-Hui; Yang, Jian-Guang; Ke, Jiang-Qiong; Zheng, Guo-Qing
Abstract Rationale: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is characterized by a pattern of extravasated blood restricted to the perimesencephalic cisterns, normal angiographic findings, and an excellent prognosis with an uneventful course and low risks of complication. The precise etiology of bleeding in patients with PNSAH has not yet been established. The most common hypothesis is that PNSAH is venous in origin. Intracranial venous hypertension has been considered as the pivotal factor in the pathogenesis of PNSAH. The underlying venous pathology such as straight sinus stenosis, jugular vein occlusion may contribute to PNSAH. We describe a patient in whom transverse sinus thrombosis preceded intracranial venous hypertension and PNSAH. These findings supported that the source of the subarachnoid hemorrhage is venous in origin. Patient concerns and diagnoses: A 45-year-old right-handed man was admitted to the hospital with a sudden onset of severe headache associated with nausea, vomiting, and mild photophobia for 6 hours. The patient was fully conscious and totally alert. An emergency brain computed tomography (CT) revealed an acute subarachnoid hemorrhage restricted to the perimesencephalic cisterns. CT angiography revealed no evidence of an intracranial aneurysm or underlying vascular malformation. Digital subtraction angiography of arterial and capillary phases confirmed the CT angiographic findings. Assessment of the venous phase demonstrated right transverse sinus thrombosis. Magnetic resonance imaging confirmed the diagnosis of cerebral venous sinus thrombosis (CVST). Lumbar puncture revealed an opening pressure of 360 mmH2O, suggestive of intracranial venous hypertension. Grave disease was diagnosed by endocrinological investigation. Interventions: Low-molecular-weight heparin, followed by oral warfarin, was initiated immediately as the treatment for cerebral venous sinus thrombosis and PNSAH. Outcomes: The patient discharged
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.
Friedrich, Victor; Flores, Rowena; Muller, Artur; Sehba, Fatima A.
Platelet aggregates are present in parenchymal vessels as early as 10 minutes after experimental subarachnoid hemorrhage (SAH). Structural injury to parenchymal vessel walls and depletion of collagen-IV (the major protein of basal lamina) occur in a similar time frame. Since platelets upon activation release enzymes which can digest collagen-IV, we investigated the topographical relationship between platelet aggregates, endothelium, and basal lamina after SAH produced by endovascular perforation, using triple immunofluorescence and confocal microscopy with deconvolution. The location of platelet aggregates in relation to zymography-detected active collagenase was also examined. As reported previously, most cerebral vessels profiles contained platelets aggregates at 10 minutes after SAH. High-resolution three-dimensional image analysis placed many platelets at the ab-luminal (basal) side of endothelium at 10 minutes, and others either within the vascular basal lamina or in nearby parenchyma. By 24 hours post-hemorrhage, large numbers of platelets had entered the brain parenchyma. The vascular sites of platelet movement were devoid of endothelium and collagen IV. Collagenase activity colocalized with vascular platelet aggregates. Our data demonstrate that parenchymal entry of platelets into brain parenchyma begins within minutes after hemorrhage. Three-dimensional analysis suggests that platelet aggregates initiate or stimulate local disruption of endothelium and destruction of adjacent basal lamina after SAH. PMID:19861151
Calviere, Lionel; Cuvinciuc, Victor; Raposo, Nicolas; Faury, Alexandre; Cognard, Christophe; Larrue, Vincent; Viguier, Alain; Bonneville, Fabrice
The specificities of acute convexity subarachnoid hemorrhage (cSAH) related to cerebral amyloid angiopathy (CAA) and its evolution are not well known. We aimed to describe the clinicoradiological pattern, the magnetic resonance imaging (MRI) evolution, and the risk of recurrent bleeding in such patients. Among consecutive patients with an acute nontraumatic cSAH, subjects with available MRI who meet the modified Boston criteria for probable CAA were included. Review of medical records, MRI findings, and follow-up data was performed. Twenty-three patients (14 women; mean age ± standard deviation: 75.9 ± 7.3 years) were included. cSAH was revealed by transient focal neurological episodes (TFNEs) in 18 of 23 (78.3%) patients. In all patients, acute cSAH appeared as a sulcal fluid-attenuated inversion recovery hyperintensity and GRE T2 hypointensity. Cortical superficial siderosis and cortical microbleeds, respectively, were observed in 21 (91.3%) and 20 (86.9%) patients. Twenty patients (87%) had available follow-up data with a mean duration of 29.8 ± 20.2 months. Recurrent TFNEs occurred in 40% of patients. Acute cSAH evolved into cortical superficial siderosis in all patients. New subarachnoid bleedings defined by recurrent acute cSAH (n = 8) or extension of siderosis (n = 14) were detected in 83.3% of the patients. Lobar intracerebral hemorrhage (ICH) occurred in 7 patients (35%). CAA-related cSAH has a specific pattern defined by a high prevalence of TFNEs and cortical superficial siderosis, with a high risk of recurrent bleeding, either cSAH or lobar ICH. The systematic evolution from cSAH to focal cortical superficial siderosis reveals data on siderosis physiopathology. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Cárdenas, Graciela; Guevara-Silva, Erik; Fleury, Agnes; Sciutto, Edda; Luis Soto-Hernández, José
The cerebrovascular complications in neurocysticercosis (NC) are uncommon. However, their pathophysiology remains unknown, but may be likely related to chronic inflammatory processes in the subarachnoid space (basal meningitis). Alterations of inflammatory cytokines in cerebrospinal fluid and sera correlate with vasospasm in SAH; these inflammatory mediators in NC may induce aneurysm formation. A 7-year retrospective study in a neurological referral center (Instituto Nacional de Neurología y Neurocirugía), showed 3 cases of subarachnoid hemorrhage (SAH) among the 267 NC patients admitted during the study period. The clinical status, cerebrospinal fluid parameters, and clinical outcome were retrieved to compare them with previous NC-related SAH reported patients. Six of 15 patients showed aneurysm. These aneurysms were found within foci of inflammation and fibrosis surrounding the parasites. We found that, in contrast with the ominous prognosis of SAH for ruptured congenital aneurysm, cases associated with NC may have a more benign course. However with limited clinical information provided by previous reports, we only propose a possible direct relationship between chronic inflammation and NC as an inference because of the limited evidence available.
Han, Sang Myung; Wan, Hoyee; Kudo, Gen; Foltz, Warren D; Vines, Douglass C; Green, David E; Zoerle, Tommaso; Tariq, Asma; Brathwaite, Shakira; D'Abbondanza, Josephine; Ai, Jinglu; Macdonald, R Loch
Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation. PMID:24064494
Rodríguez-Rodríguez, Ana; Egea-Guerrero, Juan José; Ruiz de Azúa-López, Zaida; Murillo-Cabezas, Francisco
Aneurysmal subarachnoid hemorrhage (SAH) is a neurologic emergency caused by a brain aneurysm burst, resulting in a bleeding into the subarachnoid space. Its incidence is estimated between 4 and 28/10,000 inhabitants and it is the main cause of sudden death from stroke. The prognosis of patients with SAH is directly related to neurological status on admission, to the magnitude of the initial bleeding, as well as to the development of cerebral vasospasm (CVS). Numerous researchers have studied the role of different biomarkers in CVS development. These biomarkers form part of the metabolic cascade that is triggered as a result of the SAH. Hence, among these metabolites we found biomarkers of oxidative stress, inflammation biomarkers, indicators of brain damage, and markers of vascular pathology. However, to the author knowledge, none of these biomarkers has been demonstrated as a useful tool for predicting neither CVS development nor outcome after SAH. In order to reach success on future researches, firstly it should be stated which pathophysiological process is mainly responsible for CVS development. Once this process has been determined, the temporal course of this pathophysiologic cascade should be characterized, and then, perform further studies on biomarkers already analyzed, as well as on new biomarkers not yet studied in the SAH pathology, focusing attention on the temporal course of the diverse metabolites and the sampling time for its quantification.
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
Chen, Sheng; Li, Qian; Wu, Haijian; Krafft, Paul R.; Wang, Zhen; Zhang, John H.
Subarachnoid hemorrhage (SAH) is a devastating neurological disorder. Patients with aneurysmal SAH develop secondary complications that are important causes of morbidity and mortality. Aside from secondary neurological injuries, SAH has been associated with nonneurologic medical complications, such as neurocardiogenic injury, neurogenic pulmonary edema, hyperglycemia, and electrolyte imbalance, of which cardiac and pulmonary complications are most common. The related mechanisms include activation of the sympathetic nervous system, release of catecholamines and other hormones, and inflammatory responses. Extracerebral complications are directly related to the severity of SAH-induced brain injury and indicate the clinical outcome in patients. This review provides an overview of the extracerebral complications after SAH. We also aim to describe the manifestations, underlying mechanisms, and the effects of those extracerebral complications on outcome following SAH. PMID:25110700
Mao, David Qiyuan; Addess, Daniel; Valsamis, Helen
Aim: Report a case of cortical subarachnoid hemorrhage (cSAH) and discuss its management. Patient & methods: A 66-year-old woman presents with acute onset left arm numbness and weakness. Initial head CT shows small hyperdensity in sulci typical for cSAH. Extensive workup with MRI, lumbar puncture and blood tests is performed. No signs of infection, vascular malformations, thrombosis or cancer are found. At outpatient follow-up, she is diagnosed with cSAH secondary to amyloid angiopathy. She is treated with gabapentin. Results & conclusion: Diagnosis of cSAH is challenging given its subtle findings, and management is empiric as there are only a few case series in literature. PMID:28757807
Oh, Min Seok; Kwon, Jee Eun; Kim, Kyung Jun; Jo, Joon Hwan; Min, Yun Ju; Byun, Jun Soo; Kim, Kyung Tae; Kim, Sang Wook; Kim, Tae Ho
We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days.
Pahl, Felix Hendrik; Oliveira, Matheus Fernandes de; Rotta, José Marcus
Aging is a major risk factor for poor outcome in patients with ruptured or unruptured intracranial aneurysms (IA) submitted to treatment. It impairs several physiologic patterns related to cerebrovascular hemodynamics and homeostasis. Evaluate clinical, radiological patterns and prognostic factors of subarachnoid hemorrhage (SAH) patients according to age. Three hundred and eighty nine patients with aneurismal SAH from a Brazilian tertiary institution (Hospital do Servidor Público Estadual de São Paulo) were consecutively evaluated from 2002 to 2012 according to Fisher and Hunt Hess classifications and Glasgow Outcome Scale. There was statistically significant association of age with impaired clinical, radiological presentation and outcomes in cases of SAH. Natural course of SAH is worse in elderly patients and thus, proper recognition of the profile of such patients and their outcome is necessary to propose standard treatment.
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
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
Takahashi, Masataka; Zhang, Zhen-Du; Macdonald, R Loch
Sphenopalatine ganglion stimulation activates perivascular vasodilatory nerves in the ipsilateral anterior circle of Willis. This experiment tested whether stimulation of the ganglion could reverse vasospasm and improve cerebral perfusion after subarachnoid hemorrhage (SAH) in monkeys. Thirteen cynomolgus monkeys underwent baseline angiography followed by creation of SAH by placement of autologous blood against the right intradural internal carotid artery, the middle cerebral artery (MCA), and the anterior cerebral artery. Seven days later, angiography was repeated, and the right sphenopalatine ganglion was exposed microsurgically. Angiography was repeated 15 minutes after exposure of the ganglion. The ganglion was stimulated electrically 3 times, and angiography was repeated during and 15 and 30 minutes after stimulation. Cerebral blood flow (CBF) was monitored using laser Doppler flowmetry, and intracranial pressure (ICP) was measured throughout. The protocol was repeated again. Evans blue was injected and the animals were killed. The brains were removed for analysis of water and Evans blue content and histology. Subarachnoid hemorrhage was associated with significant vasospasm of the ipsilateral major cerebral arteries (23% ± 10% to 39% ± 4%; p < 0.05, paired t-tests). Exposure of the ganglion and sham stimulation had no significant effects on arterial diameters, ICP, or CBF (4 monkeys, ANOVA and paired t-tests). Sphenopalatine ganglion stimulation dilated the ipsilateral extracranial and intracranial internal carotid artery, MCA, and anterior cerebral artery compared with the contralateral arteries (9 monkeys, 7% ± 9% to 15% ± 19%; p < 0.05, ANOVA). There was a significant increase in ipsilateral CBF. Stimulation had no effect on ICP or brain histology. Brain water content did not increase but Evans blue content was significantly elevated in the MCA territory of the stimulated hemisphere. Sphenopalatine ganglion stimulation decreased vasospasm and increased
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
Temes, Richard E; Bleck, Thomas; Dugar, Siddharth; Ouyang, Bichun; Mohammad, Yousef; John, Sayona; Patel, Pratik; Lee, Vivien; Prabhakaran, Shyam; Quigg, Mark
Temporal patterns in aneurysmal subarachnoid hemorrhage (aSAH) may provide insight into modulation, and therefore, prevention of hemorrhage. We investigated the time of hemorrhage and its relationship to traditional risk factors among patients admitted with aSAH. Admitted patients with aSAH were prospectively followed through outcomes and baseline demographics were abstracted through chart review. The group temporal distribution by hour of onset was summarized with cosinor nonlinear least squares. aSAH onset was gathered into night (2300-0500), morning (0500-1100), afternoon (1100-1700), and evening (0500-2300) daily phases. The odds ratio (OR) with 95% CI was calculated for having an aSAH during the morning, afternoon, and evening hours using night as a reference. Multinomial logit models were fitted using aSAH cases across time blocks to determine their associations with different risk factors. 202 patients had the hour of hemorrhage available, and 49 had phase identifiable [total 251: 38 (15%) night, 98 (39%) morning, 58 (23%) afternoon, 57 (23%) evening]. The peak hours of aSAH were between 0700 and 0800 representing 13% of the sample, with a significant cosinor-fitted phase of 7.33(95% CI 5.30, 9.36). For all aSAH cases, morning onset was significantly more common than night onset (OR = 2.58, 95% CI = 1.77-3.75). Nonsmokers were more likely to have aSAH in the morning than smokers (P = 0.043, OR = 3.10, 95% CI = 1.33-7.23). aSAH occur in a diurnal, morning prevalent pattern regardless of traditional aSAH risk factors. The association of these risk factors with existing onset patterns should be investigated in future studies.
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
Nakajima, Makoto; Inatomi, Yuichiro; Yonehara, Toshiro; Hirano, Teruyuki; Ando, Yukio
Nontraumatic convexal subarachnoid hemorrhage (cSAH) rarely occurs subsequent to acute ischemic stroke. The incidence, clinical background characteristics, and outcomes in acute ischemic stroke patients with cSAH were investigated. Our stroke center database was reviewed to identify patients with acute ischemic stroke/transient ischemic attack (TIA) who demonstrated acute cSAH within 14 days of admission between 2005 and 2011. Background characteristics, clinical course, and outcomes at discharge and 3 months after onset were investigated in these patients. Of 4953 acute stroke/TIA patients, cSAH was observed in 8 (.14%) patients (7 men, mean age 71 years): 7 were detected incidentally, and the other was found immediately after a convulsion. Two patients died during their hospital stay, 1 died after discharge, and 3 were dependent at 3 months. Major artery occlusion or severe stenosis was observed in 5 patients. Two patients subsequently developed subcortical hemorrhage. On gradient echo imaging, lobar cerebral microbleeds were observed in 2 patients, and chronic superficial siderosis was observed in 2 patients. In this retrospective review of cases with ischemic stroke and cSAH, over half of patients had occlusion of major arteries. Cerebral amyloid angiopathy was suggested by magnetic resonance imaging findings and subsequent events in 3 patients. The overall outcome was unfavorable although the causal relationship with cSAH was unclear. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
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. Copyright © 2016 Elsevier Inc. All rights reserved.
Cerejo, Russell; John, Seby; Grabowski, Matthew; Bauer, Andrew; Chaudhry, Burhan; Toth, Gabor; Hui, Ferdinand; Bain, Mark
Cryptogenic intracranial subarachnoid hemorrhage accounts for approximately 15% of all subarachnoid hemorrhage cases. Diagnostic workup after negative cerebral digital subtraction angiogram typically includes magnetic resonance imaging of the brain and cervical spine for arteriovenous malformations, tumors, and fistulae. Only a few cases of thoracolumbar spinal vascular malformations have been associated with intracranial subarachnoid hemorrhage. Case series and review of the literature. We found 3 patients at our institution who had nontraumatic, nonaneurysmal intracranial subarachnoid hemorrhage with isolated spinal vascular malformation in the thoracolumbar region. Including our 3 cases, we found a total of 15 similar cases in the literature. Most of the patients were younger, most having concurrent spinal cord symptoms of radiculopathy (27%), myelopathy (20%), or bladder bowel involvement (20%). Most of the spinal vascular malformations were intramedullary or conus medullaris type. Locations of intracranial subarachnoid hemorrhage were mostly isolated to the perimesencephalic area and posterior fossa. In younger populations presenting with nonaneurysmal intracranial subarachnoid hemorrhage and symptoms related to the spinal cord, evaluation for thoracolumbar spinal vascular malformations must be included in the initial workup. Copyright © 2016 Elsevier Inc. All rights reserved.
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.
Kolár, M; Nohejlová, K
Subarachnoid hemorrhage (SAH) of CNS is acute life-threating condition. In addition to its well understood sequential increase in intracranial pressure and decreased cerebral perfusion pressure, there is also early and late vasoconstriction. Mechanism of vasoconstriction is complex and one of important roles play changes in the amount of nitric oxide (NO). Present work overviews known pathogenesis of non-traumatic SAH, with stress on NO regulation of cerebral blood flow and its changes during SAH. It also describes mechanisms of early and late brain damage following subarachnoid hemorrhage. We discuss possible pharmacological prevention of the damage and laboratory models of nontraumatic SAH.
Schebesch, Karl-M; Bründl, Elisabeth; Schödel, Petra; Hochreiter, Andreas; Scheitzach, Judith; Bele, Sylvia; Brawanski, Alexander; Störr, Eva-M; Lohmeier, Anette; Proescholdt, Martin
Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Seventy-nine patients were prospectively included: SAH patients (n=66) (historic population) and intracerebral hemorrhage patients (n=13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P<0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.
Chen, Gang; Hu, Tong; Li, Qi; Li, Jianke; Jia, Yang; Wang, Zhong
Synaptosomal-associated protein-25 is an important factor for synaptic functions and cognition. In this study, subarachnoid hemorrhage models with spatial learning disorder were established through a blood injection into the chiasmatic cistern. Immunohistochemical staining and western blot analysis results showed that synaptosomal-associated protein-25 expression in the temporal lobe, hippocampus, and cerebellum significantly lower at days 1 and 3 following subarachnoid morrhage. Our findings indicate that synaptosomal-associated protein-25 expression was down-regulated in the rat brain after subarachnoid hemorrhage. PMID:25206580
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.
Oda, Shinri; Shimoda, Masami; Hoshikawa, Kaori; Osada, Takahiro; Yoshiyama, Michitsura; Matsumae, Mitsunori
Patients with non-traumatic, non-aneurysmal, and non-perimesencephalic subarachnoid hemorrhage (SAH) tend to have clots circumscribed along the cortical convexity, a condition referred to as acute cortical SAH. Cerebral venous thrombosis (CVT) is a potential cause of cortical SAH. The study tried to establish the diagnosis and management of cortical SAH caused by CVT. Retrospective review of 145 patients with non-traumatic SAH identified 15 patients with no ruptured aneurysm. Clinical features were investigated with a specific focus on patients with SAH caused by CVT. Eight of the 15 patients had perimesencephalic SAH, and 7 had cortical SAH. SAH caused by CVT was diagnosed in 4 of the 7 patients with cortical SAH. The cortical SAH involved the unilateral convexity or sylvian cistern and spared the basal cistern on computed tomography in all 4 patients. CVT occurred in the transverse sinus and cortical vein (1 patient), insular vein (1 patient), and cortical vein (2 patients). Identification of thrombosed veins or sinuses was established directly by T(2)*-weighted and diffusion-weighted magnetic resonance (MR) imaging in the acute stage and diffusion-weighted and T(1)-weighted MR imaging in the subacute stage. All patients had cortical swelling without findings of venous hemorrhagic infarction on T(2)*-weighted MR imaging. None of the 4 patients received active treatment, and all had favorable outcomes. CVT in patients with non-traumatic cortical SAH should be first excluded as a potential hemorrhagic cause by MR imaging for thrombosed veins or sinuses before initiating antifibrinolytic therapy.
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
Mehdaoui, Hossein; Hamlat, Abderrahmane; Piotin, Michel; Banydeen, Rishika; Mejdoubi, Mehdi
Background Incidence of spontaneous subarachnoid hemorrhages (SAH) varies wildly across the world and seems to be low in Central and South America (4.2 per 100 000 person-years; CI 95%; 3.1–5.7). The objective of our study was to describe the characteristics of SAH and to estimate its incidence and severity in Martinique, a small French island located in the Caribbean Sea. Methods Due to its insular nature and small captive population, Martinique is ideal for the setting up of population-based epidemiological studies with good exhaustiveness. Our study, spanning a 7 year period (2007–2013), consisted of retrospective case ascertainment with multiple overlapping methods. Crude incidence and 30 day case-fatality rates for SAH among the Martinican population were computed for the study period. Incidence and disease severity was also analyzed according to age, gender and aneurysm presence. World age-standardized incidence rates were also calculated. Results A total of 121 patients had a SAH during the study period, with a higher frequency of female cases (71.1% versus 28.9%, p<0.001). Patient mean age was 57.1 years (median = 55 [46–66]). An aneurysmal origin was found in 96 SAH cases (79.3%). Crude annual incidence was 4.36 per 100 000 person-years (CI 95% 2.30–6.42). World age-standardized incidence was 3.29 per 100 000 person-years (CI 95% 1.74–4.84). During the 30 days following SAH diagnosis, 29 patients died (case fatality rate: 24% (CI 95% 16.4–31.6)). Conclusions The incidence of spontaneous subarachnoid hemorrhage in Martinique is much lower than in other parts of the world and similar to countries in Central and South America. These results are possibly related to environmental factors and most particularly to a low rate of smoking in the Martinican population. Thirty-day case-fatality rate is similar to what is observed in developed countries. PMID:27213614
Lum, Cheemun; Hogan, Matthew J; Sinclair, John; English, Shane; Lesiuk, Howard; Shankar, Jai; Ayoub, Hala
Computed tomography perfusion (CTP) has been performed to predict which patients with aneurysmal subarachnoid hemorrhage are at risk of developing delayed cerebral ischemia (DCI). Patients with severe arterial narrowing may have significant reduction in perfusion. However, many patients have less severe arterial narrowing. There is a paucity of literature evaluating perfusion changes which occur with mild to moderate narrowing. The purpose of our study was to investigate serial whole-brain CTP/computed tomography angiography in aneurysm-related subarachnoid hemorrhage (aSAH) patients with mild to moderate angiographic narrowing. We retrospectively studied 18 aSAH patients who had baseline and follow-up whole-brain CTP/computed tomography angiography. Thirty-one regions of interest/hemisphere at six levels were grouped by vascular territory. Arterial diameters were measured at the circle of Willis. The correlation between arterial diameter and change in CTP values, change in CTP in with and without DCI, and response to intra-arterial vasodilator therapy in DCI patients was evaluated. There was correlation among the overall average cerebral blood flow (CBF; R=0.49, p<0.04), mean transit time (R=-0.48, p=0.04), and angiographic narrowing. In individual arterial territories, there was correlation between changes in CBF and arterial diameter in the middle cerebral artery (R=0.53, p=0.03), posterior cerebral artery (R=0.5, p=0.03), and anterior cerebral artery (R=0.54, p=0.02) territories. Prolonged mean transit time was correlated with arterial diameter narrowing in the middle cerebral artery territory (R=0.52, p=0.03). Patients with DCI tended to have serial worsening of CBF compared with those without DCI (p=0.055). Our preliminary study demonstrates there is a correlation between mild to moderate angiographic narrowing and serial changes in perfusion in patients with aSAH. Patients developing DCI tended to have progressively worsening CBF compared with those not
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
Okten, Ali Ihsan; Gezercan, Yurdal; Ergün, Rüçhan
We evaluated the prognostic factors in traumatic subarachnoid hemorrhage (tSAH). This study was conducted with 58 patients (44 males, 14 females; mean age 39.2; range 17 to 79 years) with tSAH, between 2001 and 2003. The patients who were admitted to the hospital within in the first 6 hours of head injury were included, whereas patients with gun shot wounds, multiple injured patients and postoperative patients were excluded. Fifty-eight patients with tSAH were prospectively followed. The neurological status of the patients and the outcomes were evaluated using Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS), respectively and computed tomography (CT) examinations were done according to the grading criteria by Hijdra and Fisher. The etiology of tSAH included traffic accidents (73%), falls (20%) and others (7%). The GCS scores of patients at admission were mild (9%), moderate (39%) and severe (52%). In the CT scans, the amount and distribution of bleeding was grade 1 (small SAH) in 21 patients, grade 2 (moderate SAH) in 17 patients, and grade 3 (extensive SAH) in 20 patients according to Hijdra grading system and according to Fisher's criteria. The thickness of blood layer was grade 1 (no blood) in 6 patients, grade 2 (bleeding layer less than 1 mm) in 21 patients, grade 3 (bleeding layer more than 1 mm) in 15 patients and grade 4 (ventricular bleeding) in 16 patients. Neurological outcomes of patients were favorable (good recovery or moderate disability) in 59%, and unfavorable (severe disability, persistent vegetative state or death) in 41% according to GOS. We have found in our series that the prognosis was poor in patients with poor admission scores of GCS, cysternal or fissural hemorrhage, tSAH with cerebral contusion or acute subdural hematoma, higher than 13 points according to Hidjra's classification and patients of grade 3 or 4 in Fisher's criteria.
Aisiku, Imo P; Chen, Peng Roc; Truong, Hanh; Monsivais, Daniel R; Edlow, Jonathan
Aneurysmal subarachnoid hemorrhage (SAH) is the most devastating form of hemorrhagic stroke. Primary predictors of mortality are based on initial clinical presentation. Initial serum lactic acid levels have been shown to predict mortality and disease severity. Initial serum lactate may be an objective predictor or mortality. Retrospective review of aneurysmal SAH in a large academic center over a 42-month period. Data collected included demographics, clinical data, serum, and clinical outcomes data. Epidemiologic data were collected at baseline, and patients were followed up through their inpatient stay. We compared data in the group of patients who were deceased (group A) vs survivors (group B). There were a total of 249 patients. Mortality was 21.5%. Mean age was the same for both groups: 57 years (group A) and 55 years (group B). Mean admission serum lactate level was 3.5 ± 2.5 (group A) and 2.2 ± 1.6 (group B; P <. 0001). The range was 0.01 to 14.7. Multivariable analysis controlling for Hunt and Hess grades showed lactic acid levels to be an independent predictor of mortality with a P value of .0018. In aneurysmal SAH, elevated serum lactate levels on admission may have a predictive role for mortality and represent a marker of disease severity. Currently, lactic acid levels are not ordered on all patients with SAH but perhaps should be part of the routine initial blood work and may serve as an additional prognostic marker. Copyright © 2016 Elsevier Inc. All rights reserved.
Jaja, Blessing N R; Cusimano, Michael D; Etminan, Nima; Hanggi, Daniel; Hasan, David; Ilodigwe, Don; 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; Singh, Jeff; Macdonald, R Loch
Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. We searched the EMBASE, MEDLINE, and Web of Science databases from January 1995 to June 2012 to identify studies that reported clinical prediction models for mortality and functional outcome in aSAH. Validated methods were used to minimize bias. Eleven studies were identified; 3 developed models from datasets of phase 3 clinical trials, the others from single hospital records. The median patient sample size was 340 (interquartile range 149-733). The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess grade (n = 3). Age was consistently dichotomized. Potential predictors were prescreened by univariate analysis in 36 % of studies. Only one study was penalized for model optimism. Details about model development were often insufficiently described and no published studies provided external validation. While clinical prediction models for aSAH use a few simple predictors, there are substantial methodological problems with the models and none have had external validation. This precludes the use of existing models for clinical or research purposes. We recommend further studies to develop and validate reliable clinical prediction models for aSAH.
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
Fujii, Mutsumi; Takasato, Yoshio; Masaoka, Hiroyuki; Ohta, Yoshihisa; Hayakawa, Takanori; Honma, Masato
Seven hundred and fifty five cases of acute non-traumatic subarachnoid hemorrhage were admitted to the department of neurosurgery of our hospital from July, 1995 to March, 2004. In 555 patients cerebral angiography was conducted but initial angiography was negative in 30 patients. Except 10 general condition poor patients, in 20 initial angiogram-negative patients were undergone repeated angiography. The cause of SAH could not be demonstrated in 13 cases. The SAH in perimesencephalic and non-perimesencephalic cisturns was seen in 7 and 6 cases, respectively. Occipital and/or neck pain on admission was statistically more common among patients with perimesencephalic SAH than those with non-perimesencephalic SAH (p = 0.029), and the prognosis of perimesencephalic SAH was good. We conclude that repeat angiography should not be recommended in patients with perimesencephalic SAH. Patients with non-perimesencephalic SAH had a higher rate of complication. In the non-perimesencephalic group, 3 patients developed hydrocephalus and 3 patients had vasospasm, which were found by repeated angiography. Therefore, repeated angiography is recommended for better clinical outcome by early detection and management of serious complications in this group of patients.
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
Khurram, Ashan; Kleinig, Timothy; Leyden, James
It has been previously found noted that ≈15% to 20% of subarachnoid hemorrhage (SAH) is nonaneurysmal. Nontraumatic convexity SAH (cSAH) is increasingly recognized. Data concerning incidence and associations are scant. We identified all SAH-coded cases from South Australian public hospitals between January 2005 and July 2011. Electronic discharge summaries were reviewed, and cases of cSAH were ascertained. Clinical and radiological features were recorded, and pathogenesis was assigned. Of 742 cases with SAH, 41 (6%) cases were cSAH, giving a minimum population annual incidence of 5.1 per million (95% confidence interval, 3.7-7.0). Median age was 70 years (interquartile range, 48-79). Commonest causes were cerebral amyloid angiopathy (39%), reversible cerebral vasoconstriction syndrome (17%), cerebral venous sinus thrombosis (10%), large-vessel stenotic atherosclerosis (10%), and posterior reversible encephalopathy syndrome (5%). No cause was identified in 20% (mostly elderly patients with incomplete evaluation). Most (63%) presented with transient neurological symptoms. Many (49%) were misdiagnosed as transient ischemic attacks and treated inappropriately with antithrombotics. cSAH comprises a significant proportion of SAH. Commonest causes are cerebral amyloid angiopathy in the elderly and reversible cerebral vasoconstriction syndrome in the young, but differential diagnosis is broad. Misdiagnosis is common and leads to potentially harmful treatments.
Santos, Gabriela A; Petersen, Nils; Zamani, Amir A; Du, Rose; LaRose, Sarah; Monk, Andrew; Sorond, Farzaneh A; Tan, Can Ozan
To understand the physiologic basis of impaired cerebral autoregulation in subarachnoid hemorrhage (SAH) and its relationship to neurologic outcomes. The cohort included 121 patients with nontraumatic SAH admitted to a neurointensive critical care unit from March 2010 to May 2015. Vasospasm was ascertained from digital subtraction angiography and delayed cerebral ischemia (DCI) was defined as new cerebral infarction on high-resolution CT. Cerebral blood flow and beat-by-beat pressure were recorded daily on days 2-4 after admission. Autoregulatory capacity was quantified from pressure flow relation via projection pursuit regression. The main outcome was early alterations in autoregulatory mechanisms as they relate to vasospasm and DCI. Forty-three patients developed only vasospasm, 9 only DCI, and 14 both. Autoregulatory capacity correctly predicted DCI in 86% of training cohort patients, generalizing to 80% of the patients who were not included in the original model. Patients who developed DCI had a distinct autoregulatory profile compared to patients who did not develop secondary complications or those who developed only vasospasm. The rate of decrease in flow was significantly steeper in response to transient reductions in pressure. The rate of increase in flow was markedly lower, suggesting a diminished ability to increase flow despite transient increases in pressure. The extent and nature of impairment in autoregulation accurately predicts neurologic complications on an individual patient level, and suggests potentially differential impairments in underlying physiologic mechanisms. A better understanding of these can lead to targeted interventions to mitigate neurologic morbidity. © 2016 American Academy of Neurology.
Santos, Gabriela A.; Petersen, Nils; Zamani, Amir A.; Du, Rose; LaRose, Sarah; Monk, Andrew; Sorond, Farzaneh A.
Objective: To understand the physiologic basis of impaired cerebral autoregulation in subarachnoid hemorrhage (SAH) and its relationship to neurologic outcomes. Methods: The cohort included 121 patients with nontraumatic SAH admitted to a neurointensive critical care unit from March 2010 to May 2015. Vasospasm was ascertained from digital subtraction angiography and delayed cerebral ischemia (DCI) was defined as new cerebral infarction on high-resolution CT. Cerebral blood flow and beat-by-beat pressure were recorded daily on days 2–4 after admission. Autoregulatory capacity was quantified from pressure flow relation via projection pursuit regression. The main outcome was early alterations in autoregulatory mechanisms as they relate to vasospasm and DCI. Results: Forty-three patients developed only vasospasm, 9 only DCI, and 14 both. Autoregulatory capacity correctly predicted DCI in 86% of training cohort patients, generalizing to 80% of the patients who were not included in the original model. Patients who developed DCI had a distinct autoregulatory profile compared to patients who did not develop secondary complications or those who developed only vasospasm. The rate of decrease in flow was significantly steeper in response to transient reductions in pressure. The rate of increase in flow was markedly lower, suggesting a diminished ability to increase flow despite transient increases in pressure. Conclusions: The extent and nature of impairment in autoregulation accurately predicts neurologic complications on an individual patient level, and suggests potentially differential impairments in underlying physiologic mechanisms. A better understanding of these can lead to targeted interventions to mitigate neurologic morbidity. PMID:27164675
Dupont, Stefan A; Wijdicks, Eelco F M; Lanzino, Giuseppe; Rabinstein, Alejandro A
Subarachnoid hemorrhage (SAH) accounts for ~5% of strokes, but causes high rates of morbidity and mortality and occurs at a relatively young age. The rupture of an intracranial aneurysm is the leading cause of nontraumatic SAH and will be the subject of this review. Rebleeding remains the most imminent danger until the aneurysm is secured (i.e., excluded from the cerebral circulation). Therefore, prompt aneurysm treatment is crucial to minimize this risk. Endovascular occlusion of the aneurysm with coils has been shown to be associated with better short- and long-term outcomes than surgical clipping in select patients. Yet, angiographic surveillance is necessary after endovascular treatment and retreatment with additional coiling may be required. Delayed cerebral vasospasm is the leading cause of brain damage once the aneurysm has been treated. Hemodynamic augmentation therapy remains the mainstay of medical treatment, but various agents are being tested as means to prevent or ameliorate vasospasm, including magnesium sulfate, statins, and an endothelin antagonist. Medically refractory vasospasm demands angioplasty of the affected vessel or intraarterial infusion of vasodilators. In this review, the authors provide an overview of the diagnosis and management of aneurysmal SAH with an emphasis on these main topics. © Thieme Medical Publishers.
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).
Bache, Søren; Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten
Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. In a prospective case-control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients (P<0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without (P<0.05) in both the screening and validation. SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. © 2017 The Authors.
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
Chen, Sheng; Wu, Haijian; Tang, Jiping; Zhang, Jianmin; Zhang, John H.
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Early brain injury (EBI) and cerebral vasospasm (CVS) are the two most important pathophysiological mechanisms for brain injury and poor outcomes for patients with SAH. CVS has traditionally been considered the sole cause of delayed ischemic neurological deficits after SAH. However, the failure of antivasospastic therapy in patients with SAH supported changing the research target from CVS to other mechanisms. Currently, more attention has been focused on global brain injury within 3 days after ictus, designated as EBI. The dysfunction of subcellular organelles, such as endoplasmic reticulum stress, mitochondrial failure, and autophagy–lysosomal system activation, has developed during EBI and delayed brain injury after SAH. To our knowledge, there is a lack of review articles addressing the direction of organelle dysfunction after SAH. In this review, we discuss the roles of organelle dysfunction in the pathogenesis of SAH and present the opportunity to develop novel therapeutic strategies of SAH via modulating the functions of organelles. PMID:25366597
Chen, Sheng; Wu, Haijian; Tang, Jiping; Zhang, Jianmin; Zhang, John H
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Early brain injury (EBI) and cerebral vasospasm (CVS) are the two most important pathophysiological mechanisms for brain injury and poor outcomes for patients with SAH. CVS has traditionally been considered the sole cause of delayed ischemic neurological deficits after SAH. However, the failure of antivasospastic therapy in patients with SAH supported changing the research target from CVS to other mechanisms. Currently, more attention has been focused on global brain injury within 3 days after ictus, designated as EBI. The dysfunction of subcellular organelles, such as endoplasmic reticulum stress, mitochondrial failure, and autophagy-lysosomal system activation, has developed during EBI and delayed brain injury after SAH. To our knowledge, there is a lack of review articles addressing the direction of organelle dysfunction after SAH. In this review, we discuss the roles of organelle dysfunction in the pathogenesis of SAH and present the opportunity to develop novel therapeutic strategies of SAH via modulating the functions of organelles.
McIntyre, Lauralyn; Fergusson, Dean; Turgeon, Alexis; dos Santos, Marlise P.; Lum, Cheemun; Chassé, Michaël; Sinclair, John; Forster, Alan; van Walraven, Carl
Objective: To create an accurate prediction model using variables collected in widely available health administrative data records to identify hospitalizations for primary subarachnoid hemorrhage (SAH). Methods: A previously established complete cohort of consecutive primary SAH patients was combined with a random sample of control hospitalizations. Chi-square recursive partitioning was used to derive and internally validate a model to predict the probability that a patient had primary SAH (due to aneurysm or arteriovenous malformation) using health administrative data. Results: A total of 10,322 hospitalizations with 631 having primary SAH (6.1%) were included in the study (5,122 derivation, 5,200 validation). In the validation patients, our recursive partitioning algorithm had a sensitivity of 96.5% (95% confidence interval [CI] 93.9–98.0), a specificity of 99.8% (95% CI 99.6–99.9), and a positive likelihood ratio of 483 (95% CI 254–879). In this population, patients meeting criteria for the algorithm had a probability of 45% of truly having primary SAH. Conclusions: Routinely collected health administrative data can be used to accurately identify hospitalized patients with a high probability of having a primary SAH. This algorithm may allow, upon validation, an easy and accurate method to create validated cohorts of primary SAH from either ruptured aneurysm or arteriovenous malformation. PMID:27629096
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.
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
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
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
Mas, J; Bouly, S; Mourand, I; Renard, D; de Champfleur, N; Labauge, P
Clinical presentation and etiology of localized nontraumatic convexal subarachnoid hemorrhage (cSAH) have been described in a few patients. They differ from those of aneurysmal subarachnoid bleeding which is diffuse. The purpose of this study was to describe the clinical presentation, the radiologic findings and causes of cSAH. We selected patients admitted to the neurology department of CHU of Nîmes or Montpellier, from May 2008 to May 2011, who presented with cSAH, observed in a single cortical sulcus unrelated to trauma and identified on brain MRI T2* weighted images as a hyposignal in one sulcus of the convexity. Data collection was retrospective. Twenty-three patients (14 men and nine women) were included. Mean age was 69.5years (range 29-86). Patients had mostly sensory or sensorimotor deficits which was regressive in less than 30minutes, recurrent, and seldom accompanied by headache. Brain MRI allowed the identification of patients with old brain hematomas (n=2), lobar microbleeds (n=7) and superficial cortical hemosiderosis (n=6). The etiologic diagnosis was determined in 43% (n=10/23): cerebral amyloid angiopathy (n=3), reversible cerebral vasoconstriction syndrome (n=2), primary cerebral angiitis (n=1), posterior reversible encephalopathy syndrome (n=1), cortical vein thrombosis (n=3, two of them associated with dural sinus thrombosis). Cerebral angiography was performed in 11 patients and gave the etiologic diagnosis (angiitis, cortical vein thrombosis) in two. Follow-up was available for 16 patients (mean 12months, range 3months to 5years). Etiology was established during follow-up in two patients, both had cerebral amyloid angiopathy diagnosed after recurrent lobar hematomas. cSAH has various causes, but clinical presentations appear to be relatively stereotyped with recurrent and brief episodes of sensorimotor deficits. A comprehensive assessment and monitoring would lead to an etiologic diagnosis in some patients. Copyright © 2012 Elsevier
Sangra, Meharpal S; Teasdale, Evelyn; Siddiqui, Mohammed A; Lindsay, Kenneth W
The cause of perimesencephalic nonaneurysmal subarachnoid hemorrhage remains unknown. We describe a patient in whom jugular venous occlusion preceded the occurrence of perimesencephalic nonaneurysmal subarachnoid hemorrhage. This finding supports the theory that the source of the hemorrhage is venous in origin. A 25-year-old man presented with sudden onset of headache after his head was held in a headlock during a playful fight 48 hours before the ictus. His computed tomographic (CT) scan on admission demonstrated a perimesencephalic pattern of subarachnoid hemorrhage. CT angiography excluded the presence of an underlying aneurysm or vascular malformation but showed bilateral jugular venous obstruction with hematoma surrounding the right internal jugular vein. Magnetic resonance imaging and a 4-vessel cerebral angiogram confirmed the CT angiographic findings. The patient was observed as an inpatient and had no complication of his hemorrhage. Follow-up at 5 months with CT angiography showed resolution of his neck hematoma and reopening of his internal jugular veins. The presence of acute jugular venous occlusion as a cause of perimesencephalic nonaneurysmal subarachnoid hemorrhage supports a venous origin of hemorrhage.
Mutoh, Tatsushi; Kobayashi, Shinya; Ishikawa, Tatsuya; Moroi, Junta; Miyata, Hajime; Suzuki, Akifumi; Yasui, Nobuyuki
We report a rare case of pathologically confirmed cryptic vascular malformation as a cause of primary convexity subarachnoid hemorrhage (SAH) of unknown etiology. A 48-year-old woman presented with sudden severe headache. Localized right convexity SAH was observed on computed tomography (CT) scan, but the origin could not be detected despite extensive workup covering the entire head by using 3.0-Tesla magnetic resonance (MR) imaging with MR angiography and CT angiography combined with venous-phase imaging with a 320-detector row CT scanner. Subsequent digital subtraction angiography (DSA) performed 2.5 hours after admission failed to reveal any cause of SAH; however, a right frontoparietal avascular region was suspected to be due to a newly developed intracerebral hematoma. The lesion was simultaneously confirmed by angiographic cone-beam CT imaging. Because she remained neurologically intact, we decided to perform a follow-up study later with medical management. However, she developed left hemiparesis 3 hours after DSA. CT scan demonstrated progression of the hematoma, and her symptoms gradually worsened. Emergent surgical exploration along the SAH superficial to the postcentral sulcus and hematoma evacuation were performed, with favorable functional outcome. Pathological examination confirmed cryptic vascular malformation with several abnormally dilated arterioles within the subarachnoid space surrounded by a thick SAH clot. It is important to consider the possibility of ruptured cryptic vascular malformation as a cause of nontraumatic nonaneurysmal convexity SAH when recurrent hemorrhage occurs despite thorough diagnostic workup, because surgical resection may be the only curative treatment option to eliminate the risk of rebleeding and disabling symptoms.
Cremers, Charlotte H P; van der Schaaf, Irene C; Dankbaar, Jan Willem; Velthuis, Birgitta K; Rinkel, Gabriel J E
The cause of perimesencephalic hemorrhage is unknown, but a venous source is suggested. If perimesencephalic hemorrhage is of venous origin, less elevation of the intracranial pressure and less perfusion deficits are expected than after aneurysmal subarachnoid hemorrhage. We compared perfusion in the acute stage after perimesencephalic hemorrhage and aneurysmal subarachnoid hemorrhage. We included 45 perimesencephalic hemorrhage patients and 45 aneurysmal subarachnoid hemorrhage patients, who were matched on clinical condition at admission and underwent computerized tomographic scanning <72 h after subarachnoid hemorrhage. Cerebral blood flow was assessed in 12 predefined regions of interest. Differences in cerebral blood flow values with corresponding 95% confidence intervals were calculated. Sub-group analyses were performed stratified on comparable amounts of blood and location of blood (posterior circulation aneurysms and additionally in infratentorial and supratentorial aneurysms). Cerebral blood flow was higher in perimesencephalic hemorrhage patients (mean: 63·8) than in aneurysmal sub-arachnoid hemorrhage patients (mean: 55·9; difference of means: -7·9 [95% confidence interval: -10·7 to -5·2]) and also in the sub-group with comparable amounts of blood (mean cerebral blood flow: 56·4; difference of means: -7·4 [95% confidence interval: -10·4 to -4·3]). Cerebral blood flow was comparable with perimesencephalic hemorrhage patients for the sub-group with posterior circulation aneurysms (difference of means: -0·7 [95% confidence interval: -5·2 to 3·8]); however, differences diverged after stratifying posterior circulation aneurysms into supratentorial (difference of means -3·9 [95% confidence interval: -9·3 to 1·4]) and infratentorial aneurysms (difference of means 3·0 [95% confidence interval: -2·8 to 8·8]). Perimesencephalic hemorrhage patients have a higher cerebral blood flow than aneurysmal subarachnoid hemorrhage patients. The findings
Ogiichi, T; Endo, S; Onizuka, K; Takaba, M; Takaku, A; Yasuda, M
A 60-year-old male presented with subarachnoid hemorrhage (SAH) of unknown origin and died of peritonitis 2 months after the ictus. Computed tomography on admission revealed localized hemorrhage at the interpedunclar cistern and sedimentation in both posterior horns. Repeat angiography could not detect any aneurysm. Postmortem histological examination revealed disruption of the wall associated with intramural hemorrhage at the top of the basilar artery, and subintimal hemorrhages of the lower basilar artery and the left vertebral artery. Arterial dissection of the vertebrobasilar system may be a cause of SAH of unknown origin including perimesencephalic hemorrhage.
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.
Korbakis, Georgia; Prabhakaran, Shyam; John, Sayona; Garg, Rajeev; Conners, James J; Bleck, Thomas P; Lee, Vivien H
To investigate magnetic resonance imaging (MRI) detection of cerebral infarction (CI) in patients presenting with subarachnoid hemorrhage (SAH). CI is a well-known complication of SAH that is typically detected on computed tomography (CT). MRI has improved sensitivity for acute CI over CT, particularly with multiple, small, or asymptomatic lesions. With IRB approval, 400 consecutive SAH patients admitted to our institution from August 2006 to March 2011 were retrospectively reviewed. Traumatic SAH and secondary SAH were excluded. Data were collected on demographics, cause of SAH, Hunt Hess and World Federation of Neurosurgical Societies grades, and neuroimaging results. MRIs were categorized by CI pattern as single cortical (SC), single deep (SD), multiple cortical (MC), multiple deep (MD), and multiple cortical and deep (MCD). Among 123 (30.8 %) SAH patients who underwent MRIs during their hospitalization, 64 (52 %) demonstrated acute CI. The mean time from hospital admission to MRI was 5.7 days (range 0-29 days). Among the 64 patients with MRI infarcts, MRI CI pattern was as follows: MC in 20 (31 %), MCD in 18 (28 %), SC in 16 (25 %), SD in 3 (5 %), MD in 2 (3 %), and 5 (8 %) did not have images available for review. Most infarcts detected on MRI (39/64 or 61 %) were not visible on CT. The use of MRI increases the detection of CI in SAH. Unlike CT studies, MRI-detected CI in SAH tends to involve multiple vascular territories. Studies that rely on CT may underestimate the burden of CI after SAH.
Sehba, Fatima A.; Hou, Jack; Pluta, Ryszard M.; Zhang, John H.
Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH. PMID:22414893
Helbok, Raimund; Schmidt, J Michael; Kurtz, Pedro; Hanafy, Khalid A; Fernandez, Luis; Stuart, R Morgan; Presciutti, Mary; Ostapkovich, Noeleen D; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A; Claassen, Jan
Brain energy metabolic crisis (MC) and lactate-pyruvate ratio (LPR) elevations have been linked to poor outcome in comatose patients. We sought to determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are associated with acute reductions in serum glucose. Twenty-eight consecutive comatose SAH patients that underwent multimodality monitoring with intracranial pressure and microdialysis were studied. MC was defined as lactate/pyruvate ratio (LPR) > or = 40 and brain glucose < 0.7 mmol/l. Time-series data were analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. Multimodality monitoring included 3,178 h of observation (mean 114 +/- 65 h per patient). In exploratory analysis, serum glucose significantly decreased from 8.2 +/- 1.8 mmol/l (148 mg/dl) 2 h before to 6.9 +/- 1.9 mmol/l (124 mg/dl) at the onset of MC (P < 0.001). Reductions in serum glucose of 25% or more were significantly associated with new onset MC (adjusted odds ratio [OR] 3.6, 95% confidence interval [CI] 2.2-6.0). Acute reductions in serum glucose of 25% or more were also significantly associated with an LPR rise of 25% or more (adjusted OR 1.6, 95% CI 1.1-2.4). All analyses were adjusted for significant covariates including Glasgow Coma Scale and cerebral perfusion pressure. Acute reductions in serum glucose, even to levels within the normal range, may be associated with brain energy metabolic crisis and LPR elevation in poor-grade SAH patients.
Geraldes, Ruth; Sousa, Paulo R; Fonseca, Ana C; Falcão, Filipa; Canhão, Patrícia; Pinho e Melo, Teresa
Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with multiple etiologies. We report the clinical presentation, imaging findings, etiologies, and long-term outcomes of a case series of cSAH. We retrospectively analyzed consecutive cases of cSAH, admitted at a Stroke Unit of a tertiary hospital (January 2006 to March 2012). Recorded variables were demographics, clinical presentation, complementary investigation, etiology, and outcome. We included 15 patients (9 men, median age of 65 years), 7% of the 210 nontraumatic SAH patients in this period. The most common clinical manifestation was a focal neurologic deficit. Predominant location of the cSAH was frontal. In 5 cases, there was a clinical significant internal carotid artery (ICA) atheromatous stenosis, ipsilateral to cSAH. Two patients had a possible cerebral amyloid angiopathy (CAA) at presentation. There were 2 cases of reversible cerebral vasoconstriction syndrome, 1 cerebral venous thrombosis, 2 dural fistulae, and 3 undetermined. Short-term outcomes were good in most patients. At follow-up (24.3 months), 2 of the patients with undetermined etiology had a lobar hematoma conferring a severe disability, and the diagnosis of CAA was made. There were no other relevant events or added disability in the other patients. Significant ICA atherosclerotic stenosis was the most frequent cause of cSAH in our series, reinforcing that cSAH should prompt vascular imagiological evaluation including cervical vessels. Outcomes in cSAH seem to be related to etiology. Patients with undetermined etiology should be followed up because cSAH may be the first manifestation of CAA. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Chiu, Te-Fa; Huang, Chien-Cheng; Chen, Jiann-Hwa; Chen, Wei-Lung
The objective of this study is to investigate the role of sympathovagal balance in predicting inhospital mortality by assessing power spectral analysis of heart rate variability (HRV) among patients with nontraumatic subarachnoid hemorrhage (SAH) in an emergency department (ED). A cohort of 132 adult patients with spontaneous SAH in an ED was prospectively enrolled. A continuous 10-minute electrocardiography for off-line power spectral analysis of the HRV was recorded. Using the inhospital mortality, the patients were classified into 2 groups: nonsurvivors (n=38) and survivors (n=94). The HRV measures were compared between these 2 groups of patients. Having compared the various measurements, the very low-frequency component, low-frequency component, normalized low-frequency component (LF%), and low-/high-frequency component ratio (LF/HF) were significantly lower, whereas the normalized high-frequency component was significantly higher among the nonsurvivors than among the survivors. A multiple logistic regression model identified LF/HF (odds ratio, 2.16; 95% confidence interval [CI], 1.18-3.97; P=.013) and LF% (odds ratio, 0.78; 95% CI, 0.69-0.88; P<.001) as independent variables that were able to predict inhospital mortality for patients with SAH in an ED. The receiver operating characteristic area for LF/HF in predicting inhospital mortality was 0.957 (95% CI, 0.914-1.000; P<.001), and the best cutoff points was 0.8 (sensitivity, 92.1%; specificity, 90.4%). Power spectral analysis of the HRV is able to predict inhospital mortality for patients after SAH in an ED. A tilt in the sympathovagal balance toward depressed sympathovagal balance, as indicated by HRV analysis, might contribute to the poor outcome among these patients. Copyright © 2012 Elsevier Inc. All rights reserved.
Sakhuja, Ankit; Schold, Jesse D; Kumar, Gagan; Katzan, Irene; Navaneethan, Sankar D
Subarachnoid hemorrhage (SAH) is associated with high mortality, and patients on maintenance dialysis have been shown to be at higher risk for stroke including SAH. However, the outcomes of patients on maintenance dialysis with SAH are not well known. This study was designed to look at incidence and outcomes of SAH in those on maintenance dialysis. Using the Nationwide Inpatient Sample Database, hospitalizations with nontraumatic SAH were identified. Age-adjusted incidence rates were calculated by direct standardization to the 2000 US standard population. Logistic regression was used to assess the risk factors for mortality. Of an estimated 149,091 hospitalizations with SAH, 1631 patients (10.9%) were on maintenance dialysis. Unadjusted incidence of SAH hospitalizations was higher in maintenance dialysis than in the general population (73.5 versus 11.2 per 100,000 population), and similar results were seen on age-adjusted analysis. The unadjusted all-cause inpatient mortality rate for SAH admissions was higher in maintenance dialysis versus the general population (38.4% versus 21.9%; P<0.001). Maintenance dialysis was an independent predictor of mortality (odds ratio, 2.48; 95% confidence interval, 1.85-3.34), although other significant predictors of mortality were similar in both subgroups. Incidence of SAH hospitalizations has been relatively stable during the study period, but mortality seems to be decreasing. SAH hospitalizations are more common and associated with higher mortality in patients on maintenance dialysis than in the general population. Although being on maintenance dialysis is an independent predictor for mortality in patients with SAH, other predictors of mortality evaluated in this study are not necessarily different between the 2 groups.
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
Latorre, Julius Gene S.; Lodi, Yahia; El-Zammar, Ziad; Devasenapathy, Ashok
Background: Vasospasm occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH), but only half becomes symptomatic. It is unclear whether asymptomatic vasospasm (AV) detected by noninvasive testing affects outcome. Prophylactic hemodilutional, hypertensive, and hypervolemic (HHH) therapy is widely used but the benefit remains unproven. We aim to determine whether AV increases the risk of poor outcome and whether HHH is safe. Methods: A total of 175 consecutive patients with aSAH without clinical vasospasm were included. Patients with sonographic (transcranial doppler) or radiologic (computed tomography [CT] Angiography) vasospasm were assigned to AV group, while those without were assigned to no vasospasm (NV) group. Logistic regression was used to determine the association between AV and HHH on poor outcome, defined as modified Rankin scale (mRS) >3 at discharge or 3 to 6 months' follow-up. Results: In all, 106 patients had NV and 25 received HHH. A total of 69 patients had AV and 54 received HHH. Asymptomatic vasospasm compared to NV was not associated with poor outcome (odds ratio [OR] 2.6, 95% confidence interval [CI]: 0.75-8.9; P = .1). Hemodilutional, hypertensive, and hypervolemic use in patients with AV did not improve the outcome (OR 0.16, 95%CI: 0.009-2.84; P = .2). In patients with NV, HHH use showed trend toward poor outcome after multivariable adjustment (OR 12.6, 95%CI: 1.08-146.5 P = .04). Conclusion: Asymptomatic vasospasm does not appear to be associated with poor outcome in aSAH. Hemodilutional, hypertensive, and hypervolemic therapy in AV was not associated with improved outcome and may be harmful to patients who do not have vasospasm. Further research is needed to validate this finding. PMID:23983851
Moscovici, Samuel; Fraifeld, Shifra; Ramirez-de-Noriega, Fernando; Rosenthal, Guy; Leker, Ronen R; Itshayek, Eyal; Cohen, José E
We aimed to compare the presentation, management, and clinical course in patients with perimesencephalic and nonperimesencephalic (aneurysmal) bleeding patterns on noncontrast CT, but negative initial 4-vessel digital subtraction angiography (DSA). We retrospectively reviewed clinical and imaging data for 280 patients presenting with spontaneous SAH admitted between 2005 and 2011. We identified 56 patients (20%) with SAH diagnosed on high resolution head CT performed within 48 hours of admission, and negative initial DSA, and divided them into perimesencephalic and non-perimesencephalic groups based on hemorrhage patterns. Patients with traumatic subarachnoid bleeding and those with initial positive DSA were excluded from this analysis. Perimesencephalic SAH was seen in 25 patients (45%); non-perimesencephalic bleeding patterns were seen in 31 (55%). All patients with perimesencephalic SAH presented with Hunt and Hess (HH) I, versus 45% HH I and 55% HH II-IV in those with non-perimecenphalic SAH. All patients with perimesencephalic SAH achieved modified Rankin score (mRS) 0 at discharge and 6-month follow-up, compared with 45% mRS 0 at discharge and 68% at 6-month follow-up in non-perimesencephalic SAH. Patients with perimesencephalic SAH presented a uniformly uncomplicated clinical course. Among non-perimesencephalic SAH patients there were 19 neurological/neurosurgical and 10 medical complications, two small aneurysms diagnosed at follow-up DSA, and one death. In this series, perimesencephalic SAH was associated with good clinical grades, consistently negative initial and follow-up angiograms, and an excellent prognosis. In contrast, non-perimesencephalic SAH was associated with a worse clinical presentation, higher complication rates, higher rates of true aneurysm detection on follow-up angiogram, and a poorer outcome.
Dasenbrock, Hormuzdiyar H; Angriman, Frederico; Smith, Timothy R; Gormley, William B; Frerichs, Kai U; Aziz-Sultan, M Ali; Du, Rose
The goal of this nationwide study is to evaluate the suitability of readmission as a quality indicator in the aneurysmal subarachnoid hemorrhage (SAH) population. Patients with aneurysmal SAH were extracted from the Nationwide Readmission Database (2013). Multivariable Cox proportional hazard regression was used to evaluate predictors of a 30-day readmission, and multivariable linear regression was used to analyze the association of hospital readmission rates with hospital mortality rates. Predictors screened included patient demographics, comorbidities, severity of SAH, complications from the SAH hospitalization, and hospital characteristics. The 30-day readmission rate was 10.2% (n=346) among the 3387 patients evaluated, and the most common reasons for readmission were neurological, hydrocephalus, infectious, and venous thromboembolic complications. Greater number of comorbidities, increased severity of SAH, and discharge disposition other than to home were independent predictors of readmission (P≤0.03). Although hydrocephalus during the SAH hospitalization was associated with readmission for the same diagnosis, other readmissions were not associated with having sustained the same complication during the SAH hospitalization. Hospital mortality rate was inversely associated with hospital SAH volume (P=0.03) but not significantly associated with hospital readmission rate; hospital SAH volume was also not associated with SAH readmissions. In this national analysis, readmission was primarily attributable to new medical complications in patients with greater comorbidities and severity of SAH rather than exacerbation of complications from the SAH hospitalization. Additionally, hospital readmission rates did not correlate with other established quality metrics. Therefore, readmission may be a suboptimal quality indicator in the SAH population. © 2017 American Heart Association, Inc.
Kreiter, Kurt T; Rosengart, Axel J; Claassen, Jan; Fitzsimmons, Brian F; Peery, Shelley; Du, Y Evelyn; Connolly, E Sander; Mayer, Stephan A
Cognitive impairment is widely considered the main cause of disability and handicap after subarachnoid hemorrhage (SAH). The impact of depression on recovery after SAH remains poorly defined. We sought to determine the frequency of post-SAH depression, identify risk factors for its development, and evaluate the impact of depression on quality of life (QOL) during the first year of recovery. We prospectively studied 216 of 534 SAH patients treated between July 1996 and December 2001 with complete one-year follow-up data. Depression was evaluated with the Center for Epidemiological Studies Depression (CES-D) scale, cognitive status with the Telephone Interview for Cognitive Status (TICS), and QOL with the Sickness Impact Profile (SIP) 3 and 12 months after SAH. Depressed mood occurred in 47% of patients during the first year of recovery; 26% were depressed at both 3 and 12 months. Non-white ethnicity predicted early (3 month) and late (12 month) depressions; early depression was also predicted by previously-diagnosed depression, cigarette smoking, and cerebral infarction, whereas late depression was predicted by prior social isolation and lack of medical insurance. Depression was associated with inferior QOL in all domains of the SIP, and changes in depression status were associated with striking parallel changes in QOL, disability, and cognitive function during the first year of recovery. CES-D scores accounted for over 60% of the explained variance in SIP total scores, whereas TICS performance accounted for no more than 6%. Depression affects nearly half of SAH patients during the first year of recovery, and is associated with poor QOL. Systematic screening and early treatment for depression are promising strategies for improving outcome after SAH. © 2013.
Naidech, Andrew M; Shaibani, Ali; Garg, Rajeev K; Duran, Isis M; Liebling, Storm M; Bassin, Sarice L; Bendok, Bernard R; Bernstein, Richard A; Batjer, H Hunt; Alberts, Mark J
In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH. Forty-four patients with SAH and high risk for vasospasm were randomized to goal HGB concentration of at least 10 or 11.5 g/dl. We obtained blinded clinical outcomes at 14 days (NIH Stroke Scale and modified Rankin Scale, mRS), 28 days (mRS), and 3 months (mRS), and blinded interpretation of brain MRI for cerebral infarction at 14 days. This trial is registered at www.stroketrials.org. Forty-four patients were randomized. Patients with goal HGB 11.5 g/dl received more PRBC units per transfusion [1 (1-2) vs. 1 (1-1), P < 0.001] and more total PRBC units [3 (2-4) vs. 2 (1-3), P = 0.045]. Prospectively defined safety endpoints were not different between groups. HGB concentration was different between study groups from day 4 onwards. The number of cerebral infarctions on MRI (6 of 20 vs. 9 of 22), NIH Stroke Scale scores at 14 days [1 (0-9.75) vs. 2 (0-16)], and rates of independence on the mRS at 14 days (65% vs. 44%) and 28 days (80% vs. 67%) were similar, but favored higher goal HGB (P > 0.1 for all). Higher goal hemoglobin in patients with SAH seems to be safe and feasible. A phase III trial of goal HGB after SAH is warranted.
Behrouz, Réza; Birnbaum, Lee; Grandhi, Ramesh; Johnson, Jeremiah; Misra, Vivek; Palacio, Santiago; Seifi, Ali; Topel, Christopher; Garvin, Rachel; Caron, Jean-Louis
The incidence of cannabis use in patients with aneurysmal subarachnoid hemorrhage (aSAH) and its impact on morbidity, mortality, and outcomes are unknown. Our objective was to evaluate the relationship between cannabis use and outcomes in patients with aSAH. Records of consecutive patients admitted with aSAH between 2010 and 2015 were reviewed. Clinical features and outcomes of aSAH patients with negative urine drug screen and cannabinoids-positive (CB+) were compared. Regression analyses were used to assess for associations. The study group consisted of 108 patients; 25.9% with CB+. Delayed cerebral ischemia was diagnosed in 50% of CB+ and 23.8% of urine drug screen negative patients (P=0.01). CB+ was independently associated with development of delayed cerebral ischemia (odds ratio, 2.68; 95% confidence interval, 1.03-6.99; P=0.01). A significantly higher number of CB+ than urine drug screen negative patients had poor outcome (35.7% versus 13.8%; P=0.01). In univariate analysis, CB+ was associated with the composite end point of hospital mortality/severe disability (odds ratio, 2.93; 95% confidence interval, 1.07-8.01; P=0.04). However, after adjusting for other predictors, this effect was no longer significant. We offer preliminary data that CB+ is independently associated with delayed cerebral ischemia and possibly poor outcome in patients with aSAH. Our findings add to the growing evidence on the association of cannabis with cerebrovascular risk. © 2016 American Heart Association, Inc.
Lindbohm, Joni Valdemar; Kaprio, Jaakko; Jousilahti, Pekka; Salomaa, Veikko; Korja, Miikka
One in every 4 subarachnoid hemorrhage (SAH) patients dies suddenly outside hospital, but most SAH risk factor studies focus on hospitalized patients. We studied the differences in risk factors between hospitalized SAH and sudden-death SAH patients. The population-based FINRISK study cohort of 65 521 individuals was followed up for 1.52 million person-years. The Cox proportional hazards model calculated hazard ratios (HRs), with all analyses adjusted for known SAH risk factors, marital status, and socioeconomic status. A competing risks model analyzed differences in risk factors between hospitalized SAHs and sudden-death SAHs. We identified 98 sudden-death SAHs and 445 hospitalized SAHs confirmed by autopsy or by standard SAH diagnostics. Increase by 5 cigarettes smoked per day elevated sudden-death SAH risk (HR, 1.28; 95% confidence interval [CI], 1.17-1.39) more than hospitalized SAH risk (HR, 1.19; 95% CI, 1.13-1.24; P=0.05 for difference). Per SD (21.4 mm Hg) increase, systolic blood pressure elevated risk of sudden-death SAH (HR, 1.34; 95% CI, 1.09-1.65) more than risk for hospitalized SAH (HR, 1.25; (95% CI, 1.12-1.38; P=0.05 for difference). Participants living without a partner were at elevated risk of sudden-death SAH (HR, 2.09; 95% CI, 1.33-3.28) but not of hospitalized SAH. No sudden-death SAHs occurred in normotensive never smokers aged <50 years. Sudden-death SAH risk seems to be highest among those individuals with the most adverse risk factor profiles and among those who live without a partner, whereas it is rare among normotensive never smokers aged <50 years. © 2017 American Heart Association, Inc.
Budohoski, Karol P; Czosnyka, Marek; Smielewski, Peter; Varsos, Georgios V; Kasprowicz, Magdalena; Brady, Ken M; Pickard, John D; Kirkpatrick, Peter J
In patients after subarachnoid hemorrhage (SAH) failure of cerebral autoregulation is associated with delayed cerebral ischemia (DCI). Various methods of assessing autoregulation are available, but their predictive values remain unknown. We characterize the relationship between different indices of autoregulation. Patients with SAH within 5 days were included in a prospective study. The relationship between three indices of autoregulation was analyzed: two indices calculated using spontaneous blood pressure fluctuations, Sxa (based on transcranial Doppler) and TOxa (based on near-infrared spectroscopy); and transient hyperemic response test (THRT) where a brief compression of the common carotid artery is used. The predictive value of indices was assessed using data from the first 5 days. Overall there was only moderate correlation between indices. However, both Sxa and TOxa showed good accuracy in predicting impaired autoregulation evidenced by a negative THRT (area under the curve (AUC): 0.788, 95% CI: 0.723 to 0.854 and AUC: 0.827, 95% CI: 0.769 to 0.885, respectively). All indices proved accurate in predicting DCI when 0- to 5-day data were used (AUC: 0.801, 95% CI: 0.660 to 0.942; AUC: 0.857, 95% CI: 0.731 to 0.984, AUC: 0.796, 95% CI: 0.658 to 0.934 for THRT, Sxa, and TOxa, respectively). Combining all three indices had 100% specificity for predicting DCI. While multiple colinearities exist between the assessed methods, multimodal monitoring of cerebral autoregulation can aid in predicting DCI. PMID:23232948
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
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
Jeon, Sang-Beom; Parikh, Gunjan; Choi, H Alex; Badjatia, Neeraj; Lee, Kiwon; Schmidt, J Michael; Lantigua, Hector; Connolly, E Sander; Mayer, Stephan A; Claassen, Jan
Cerebral microbleeds (CMBs) are commonly found after stroke but have not previously been studied in patients with subarachnoid hemorrhage (SAH). To study the prevalence, radiographic patterns, predictors, and impact on outcome of CMBs in patients with SAH. We analyzed retrospectively 39 consecutive patients who underwent T2*-weighted gradient-echo imaging within 7 days after onset of spontaneous SAH. We report the frequency and location of CMBs and show their association with demographics, vascular risk factors, the Hunt-Hess grade, the modified Fisher Scale, the Acute Physiological and Chronic Health Evaluation II, magnetic resonance imaging findings including diffusion-weighted imaging lesions, and laboratory data, as well as data on rebleeding, global cerebral edema, delayed cerebral ischemia, seizures, the Telephone Interview for Cognitive Status, and the modified Rankin Scale. Eighteen patients (46%) had CMBs. Of these patients, 9 had multiple CMBs, and overall a total of 50 CMBs were identified. The most common locations of CMBs were lobar (n = 23), followed by deep (n = 15) and infratentorial (n = 12). After adjustment for age and history of hypertension, CMBs were related to the presence of diffusion-weighted imaging lesions (odds ratio, 5.24; 95% confidence interval, 1.14-24.00; P = .03). Three months after SAH, patients with CMBs had nonsignificantly higher modified Rankin Scale scores (odds ratio, 2.50; 95% confidence interval, 0.67-9.39; P = .18). This study suggests that CMBs are commonly observed and associated with diffusion-weighted imaging lesions in patients with SAH. Our findings may represent a new mechanism of tissue injury in SAH. Further studies are needed to investigate the clinical implications of CMBs.
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
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. We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury. 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). 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 rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside. © 2013 American Neurological Association.
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 S V; Connolly, E Sander; Dukic, Vanja; Hripcsak, George; Badjatia, Neeraj
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. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures. 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 (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), 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 (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz. © 2014 American Neurological Association.
Lin, Chih-Lung; Dumont, Aaron S; Lieu, Ann-Shung; Yen, Chen-Po; Hwang, Shith-Lin; Kwan, Aij-Lie; Kassell, Neal F; Howng, Shen-Long
The reported incidence, timing, and predictive factors of perioperative seizures and epilepsy after subarachnoid hemorrhage (SAH) have differed considerably because of a lack of uniform definitions and variable follow-up periods. In this study the authors evaluate the incidence, temporal course, and predictive factors of perioperative seizures and epilepsy during long-term follow up of patients with SAH who underwent surgical treatment. Two hundred seventeen patients who survived more than 2 years after surgery for ruptured intracranial aneurysms were enrolled and retrospectively studied. Episodes were categorized into onset seizures (< or = 12 hours of initial hemorrhage), preoperative seizures, postoperative seizures, and late epilepsy, according to their timing. The mean follow-up time was 78.7 months (range 24-157 months). Forty-six patients (21.2%) had at least one seizure post-SAH. Seventeen patients (7.8%) had onset seizures, five (2.3%) had preoperative seizures, four (1.8%) had postoperative seizures, 21 (9.7%) had at least one seizure episode after the 1st week postoperatively, and late epilepsy developed in 15 (6.9%). One (3.8%) of 26 patients with perioperative seizures (onset, preoperative, or postoperative seizure) had late epilepsy at follow up. The mean latency between the operation and the onset of late epilepsy was 8.3 months (range 0.3-19 months). Younger age (< 40 years old), loss of consciousness of more than 1 hour at ictus, and Fisher Grade 3 or greater on computerized tomography scans proved to be significantly related to onset seizures. Onset seizure was also a significant predictor of persistent neurological deficits (Glasgow Outcome Scale Scores 2-4) at follow up. Factors associated with the development of late epilepsy were loss of consciousness of more than 1 hour at ictus and persistent postoperative neurological deficit. Although up to one fifth of patients experienced seizure(s) after SAH, more than half had seizure(s) during the
Chalif, D J; Black, K; Rosenstein, D
Negative findings on four-vessel angiography after a subarachnoid hemorrhage are seen in 5 to 30% of patients. A previously silent lesion in the spinal canal may be responsible for the ictus in a small percentage of this group. The etiological factors include tumors and arteriovenous malformations; however, investigations of such lesions have been limited to patients with signs and symptoms of spinal cord or nerve root pathological processes. This report describes the management of a 56-year-old woman with clinical findings typical of an aneurysmal subarachnoid hemorrhage and negative findings on cerebral angiography, in whom magnetic resonance imaging with gadolinium enhancement revealed an intradural extramedullary cervical schwannoma. For this reason, cervicothoracic magnetic resonance imaging with gadolinium enhancement should be considered as an adjunctive scanning examination in all patients with a subarachnoid hemorrhage and negative findings on angiography.
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.
Lin, Tzu-Kang; Tsai, Hong-Chieh; Hsieh, Tsung-Che
To clarify the clinical role of traumatic subarachnoid hemorrhage (tSAH), stratified analysis with grouping of tSAH was performed. Their blood flow changes and correlations with outcome were assayed. One hundred seventeen tSAH patients were classified into several groups according to their initial computerized tomography scans. Group I included patients with tSAH only in the posterior interhemispheric fissure, whereas Group II contained patients with tSAH located elsewhere. Group II was further subdivided into IIa, little SAH; IIb, extensive SAH; IIc, little SAH with intraventricular hemorrhage (IVH); and IId, extensive SAH with IVH. The cerebral blood flow velocity was monitored using transcranial Doppler sonography (TCD). Both age and initial coma scale were independent predictors of poor outcome. The poor outcome rates in various subgroups of tSAH increased stepwise from group I to group IId (I, 7.4%; IIa, 18.4%; IIb, 33.3%; IIc, 62.5%; and IId, 90.9%) (p = 0.0010). Stratified analyses revealed that patients with extensive tSAH (group IIb + IId) were more likely to have unfavorable outcomes (47.7%) than patients with little tSAH (group IIa + IIc) (26.1%) (p = 0.0185); patients with IVH (group IIc + IId) also displayed a higher incidence (78.9%) of poor outcomes than patients without IVH (group IIa + IIb) (25.4%) (p = 0.0030). TCD study demonstrated that patients with extensive tSAH (group IIb + IId) were more likely to have the vasospasm based on TCD criteria than did patients in group I and group IIa + IIc (37.5% vs. 5.9% and 7.7%, p = 0.0105). Notably, there was a tendency of worse outcome in patients with vasospasm on the basis of TCD-derived criteria than those without, with the unfavorable outcome rates being 47.4% and 24.7% (p = 0.0799). Age, initial coma scale, extensive tSAH, and IVH are independent predictors of poor outcome in the cohort of tSAH patients. Statistically, patients with extensive tSAH are significantly more likely to have vasospasm.
Cohen-Gadol, Aaron A; Bohnstedt, Bradley N
Swift diagnosis and treatment are critical for good outcomes in patients with nontraumatic subarachnoid hemorrhage, which is usually caused by a ruptured aneurysm. This type of stroke often results in death or disability. Rates of misdiagnosis and treatment delays for subarachnoid hemorrhage have improved over the years, but these are still common occurrences. Subarachnoid hemorrhage can be more easily diagnosed in patients who present with severe symptoms, unconsciousness, or with thunderclap headache, which is often accompanied by vomiting. The diagnosis is more elusive in patients who present in good condition, yet these patients have the best chance for good outcome if they are correctly diagnosed at the time of presentation. Physicians should be alert for warning headaches, which are often severe, and headaches that feel different to the patient. Other symptoms may include nausea, vomiting, impaired consciousness, nuchal rigidity, orbital pain, focal neurologic deficits, dysphasia, lightheadedness, and dizziness. The most important risk factors for subarachnoid hemorrhage include cigarette smoking, hypertension, heavy alcohol use, and personal or family history of aneurysm or hemorrhagic stroke. The first step in the diagnostic workup is noncontrast computed tomography of the head. If computed tomography is negative or equivocal, a lumbar puncture should be performed. Subsequent imaging may include computed tomographic angiography, catheter angiography, and magnetic resonance angiography.
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.
Perry, Jeffrey J; Stiell, Ian G; Sivilotti, Marco L A; Bullard, Michael J; Hohl, Corinne M; Sutherland, Jane; Émond, Marcel; Worster, Andrew; Lee, Jacques S; Mackey, Duncan; Pauls, Merril; Lesiuk, Howard; Symington, Cheryl; Wells, George A
Three clinical decision rules were previously derived to identify patients with headache requiring investigations to rule out subarachnoid hemorrhage. To assess the accuracy, reliability, acceptability, and potential refinement (ie, to improve sensitivity or specificity) of these rules in a new cohort of patients with headache. Multicenter cohort study conducted at 10 university-affiliated Canadian tertiary care emergency departments from April 2006 to July 2010. Enrolled patients were 2131 adults with a headache peaking within 1 hour and no neurologic deficits. Physicians completed data forms after assessing eligible patients prior to investigations. Subarachnoid hemorrhage, defined as (1) subarachnoid blood on computed tomography scan; (2) xanthochromia in cerebrospinal fluid; or (3) red blood cells in the final tube of cerebrospinal fluid, with positive angiography findings. Of the 2131 enrolled patients, 132 (6.2%) had subarachnoid hemorrhage. The decision rule including any of age 40 years or older, neck pain or stiffness, witnessed loss of consciousness, or onset during exertion had 98.5% (95% CI, 94.6%-99.6%) sensitivity and 27.5% (95% CI, 25.6%-29.5%) specificity for subarachnoid hemorrhage. Adding "thunderclap headache" (ie, instantly peaking pain) and "limited neck flexion on examination" resulted in the Ottawa SAH Rule, with 100% (95% CI, 97.2%-100.0%) sensitivity and 15.3% (95% CI, 13.8%-16.9%) specificity. Among patients presenting to the emergency department with acute nontraumatic headache that reached maximal intensity within 1 hour and who had normal neurologic examination findings, the Ottawa SAH Rule was highly sensitive for identifying subarachnoid hemorrhage. These findings apply only to patients with these specific clinical characteristics and require additional evaluation in implementation studies before the rule is applied in routine clinical care.
Fukuda, T; Hasue, M; Ito, H
To examine whether traumatic subarachnoid hemorrhage (TSAH) caused by severe diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome, as does aneurysmal subarachnoid hemorrhage (ASAH). We examined 99 patients with diffuse brain injury with TSAH and 114 patients with ASAH. Computed tomographic (CT) findings, cerebral blood flow, and neurological outcomes were assessed during the acute and subacute phases and were compared between the two groups. The distribution of subarachnoid hemorrhage on the CT scans differed between the two groups. Unlike ASAH, TSAH was not limited to cisterns surrounding the circle of Willis but extended to supratentorial regions and interhemispheric fissures. Computed tomography-detected subarachnoid hemorrhage disappeared very early with TSAH and gradually with ASAH. In the ASAH group, mean cerebral blood flow decreased to 75% of normal during the acute phase and decreased a further 10% during the subacute phase. In the TSAH group, mean cerebral blood flow decreased to 85% of normal during the acute phase and increased slightly during the subacute phase. Neurological deterioration and in-hospital death peaked on Day 0 in association with TSAH and showed twin peaks in association with ASAH. The incidence of low-density areas on the CT scans was significantly higher with ASAH than with TSAH. All low-density areas on the CT scans of patients with ASAH corresponded to vascular territories, but low-density areas on the CT scans of patients with TSAH were rarely associated with vascular territories and contained deep-seated or gliding contusion types. The findings suggest that the incidence of vasospasm is low in association with TSAH and that the cause is different compared with ASAH. There is no evidence that the presence of TSAH in cases of diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome.
Monahan, Aimee; Carpenter, Amanda; Zimmerman, Jacqueline; Schmidt, J. Michael; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.; Karmally, Wahida; Seres, David
Objective: To analyze the impact of inflammation and negative nitrogen balance (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH). Methods: This was a prospective observational study of SAH patients admitted between May 2008 and June 2012. Measurements of C-reactive protein (CRP), transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were performed over 4 preset time periods during the first 14 postbleed days (PBD) in addition to daily caloric intake. Factors associated with REE and NBAL were analyzed with multivariable linear regression. Hospital-acquired infections (HAI) were tracked daily for time-to-event analyses. Poor outcome at 3 months was defined as a modified Rankin Scale score ≥4 and assessed by multivariable logistic regression. Results: There were 229 patients with an average age of 55 ± 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001), higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 ± 3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p = 0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at 3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p < 0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p = 0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p = 0.04). Conclusions: Negative NBAL after SAH is influenced by inflammation and associated with an increased risk of HAI and poor outcome. Underfeeding and systemic inflammation are potential modifiable risk factors for negative NBAL and poor outcome after SAH. PMID:25596503
Quigley, Matthew R; Chew, Brandon G; Swartz, Christopher E; Wilberger, Jack E
Mild traumatic brain injury is a clinical diagnosis predicated on a patient's neurologic status and encompasses a variety of pathologies on computed tomography. We wondered whether isolated traumatic subarachnoid hemorrhage (iSAH) without other intracranial pathologic diagnosis is a more benign form of minor head injury that does not warrant extensive (and expensive) observation and follow-up. This is a retrospective review of patients identified prospectively via a trauma registry during a period of 7 years, who had the computed tomographic finding of iSAH on admission scan and a Glasgow Coma Scale (GCS) score of 13 or greater. There were 478 patients identified, with a mean age 61 years, and 223 were male. Median Injury Severity Score (ISS) was 10 (range, 9-48), and the distribution was 415, 54, and 12 for those with GCS score of 15, 14, and 13, respectively. In-hospital follow-up imaging in nine patients demonstrated increased pathologic findings, but subsequent imaging showed stable or decreasing blood, and none experienced a neurologic decline or underwent a neurosurgical procedure.Among those with no other injuries (ISS = 9, n = 118) patients spent a mean of 2.0 (95% confidence interval, 1.1-2.9) days in intensive care unit and 4.9 (95% confidence interval, 3.9-6.0) days in hospital. The likelihood of discharge home was significantly related to age (p < 0.0001), ISS (p < 0.01), and admission GCS (p < 0.01) (stepwise logistic regression), but not progression of SAH.At 6-week follow-up, one patient (0.2%) developed bilateral chronic subdurals requiring drainage, without neurologic sequela. In this largest reported series to date of iSAH in the setting of mild traumatic brain injury, the finding seems to be benign and can likely be managed without routine follow-up imaging or intensive care unit admission in the absence of other significant trauma. Epidemiologic/prognostic study, level III; therapeutic study, level IV.
Kaech, D L; Despland, P A; de Tribolet, N
Flow velocities (F.V.) in 65 patients admitted for subarachnoid hemorrhage (S.A.H.) were measured 4-7 times a week by Transcranial Doppler (T.C.D.). Patients were classified into 4 T.C.D. groups according to the highest mean flow velocity recorded in the M.C.A. during hospitalization: Group 1 (18 patients) with F.V. below 100 cm/s (normal), group 2 (19 patients) with F.V. between 100-150 cm/s (starting spasm), group 3 (23 patients) with F.V. between 150-200 cm/s (major spasm) and group 4 (5 patients) with F.V. over 200 cm/s (critical spasm). Based on clinical, radiological and ultrasound data as well as patient outcome (good results with no specific problems or with transient deficit, permanent deficit and pre- or postoperative death), the authors analyse the value of T.C.D. in the evaluation of vasospasms following S.A.H. The review involves 49 patients with surgically treated aneurysms (including two associated A.V.M.s), 9 patients who had suffered a S.A.H. of unknown origin and 7 patients who had died prior to surgery. T.C.D. is a non-invasive method of following post-S.A.H. spasms and the close correlation between the angiography and the T.C.D. makes pre-operative control angiographies unnecessary. A correlation between clinical status and T.C.D. was only observed in extreme cases where F.V. exceeded 200 cm/s or increased by 100 cm/s or more within 3 days (6 patients out of 65). M.C.A. spasm can, however, be underestimated by the T.C.D. approach in cases where there is an associated spasm of the infraclinoidal carotid artery. In these cases, classical Doppler evaluation of the cervical portion of the I.C.A. is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)
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
Rudas, G; Varga, E; Méder, U; Pataki, M; Taylor, G A
The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH. Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12-24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations. The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6-7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not. Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.
Agostoni, E; Zagaria, M; Longoni, M
Headache is a critical problem in the emergency setting. In this paper we briefly review the epidemiological data regarding headache in Subarachnoid Hemorrhage (SAH), considering the role of headache as a warning symptom and the other clinical manifestation of SAH. We have also introduced a recent clinical entity, represented by headache associated to intracranial endovascular procedures (IEPs).
Pickup, Michael J; Pollanen, Michael S
We describe two previously unreported associations in four cases. The first two cases demonstrate an association between segmental mediolytic arteriopathy and vascular Ehlers-Danlos syndrome. The second two cases illustrate an association between vascular Ehlers-Danlos syndrome and traumatic subarachnoid hemorrhage. In case 1, there was acute subarachnoid hemorrhage and mesenteric artery dissection. In case 2, there was an acute mesenteric artery dissection with intestinal infarction. In both cases 1 and 2, segmental mediolytic arteriopathy was found in the vertebral arteries. Cases 3 and 4 were sudden deaths from traumatic subarachnoid hemorrhage with intracranial vertebral artery rupture. Genetic testing in all four cases revealed point mutations in the type 3 procollagen gene (COL3A1), as observed in vascular Ehlers-Danlos syndrome. Based on the first two cases, we propose that segmental mediolytic arteriopathy may be a marker for this disease. We further suggest that vascular Ehlers-Danlos syndrome may be related to the pathogenesis of traumatic vertebral artery injury, in some cases. We recommend that cases of segmental mediolytic arteriopathy and traumatic subarachnoid hemorrhage undergo genetic testing for COL3A1 mutations.
Lima, Sandro Júnior Henrique; Azevedo Filho, Hildo Rocha Cirne de; Silva, Hilton Justino da
To systematically review the methods for evaluation of smell in aneurysmal subarachnoid hemorrhage victims and to identify the changes found with the use of these methods. The literature search was performed in PubMed search platform and in the databases Web of Science, Scopus, PsycINFO, CINAHL, and ScienceDirect in August and September 2014. Original articles published in any language, which addressed smell changes in aneurysmal subarachnoid hemorrhage and addressed to evaluate this function through specific methods were included. Review studies, case studies, book chapters, editorial, and studies that address the nonaneurysmal subarachnoid hemorrhage were excluded. The following variables were considered in data analysis: author/year, country, sample/age, treatment, method, the moment of smell evaluation, and results. The search for articles resulted in 1,763 articles, of which, 9 original articles were selected for this review. It was observed that all articles were from European and Asian countries. Standardized and nonstandardized tests and questionnaires were used in olfactory assessment, and the goals ranged from assessing the smell before and/or after surgery in this population. Heterogeneity was observed in the methods used to evaluate the smell in aneurysmal subarachnoid hemorrhage and in the methods selected for application of evaluations. In addition, studies have demonstrated the existence of olfactory deficits in patients and the relationship between surgery and olfactory dysfunction.
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.
Rico, María; Benavente, Lorena; Para, Marta; Santamarta, Elena; Pascual, Julio; Calleja, Sergio
Convexal subarachnoid hemorrhage has been associated with different diseases, reversible cerebral vasoconstriction syndrome and cerebral amyloid angiopathy being the 2 main causes. To investigate whether headache at onset is determinant in identifying the underlying etiology for convexal subarachnoid hemorrhage. After searching in the database of our hospital, 24 patients were found with convexal subarachnoid hemorrhage in the last 10 years. The mean age of the sample was 69.5 years. We recorded data referring to demographics, symptoms and neuroimaging. Cerebral amyloid angiopathy patients accounted for 46% of the sample, 13% were diagnosed with reversible cerebral vasoconstriction syndrome, 16% with several other etiologies, and in 25%, the cause remained unknown. Mild headache was present only in 1 (9%) of the 11 cerebral amyloid angiopathy patients, while severe headache was the dominant feature in 86% of cases of the remaining etiologies. Headache is a key symptom allowing a presumptive etiological diagnosis of convexal subarachnoid hemorrhage. While the absence of headache suggests cerebral amyloid angiopathy as the more probable cause, severe headache obliges us to rule out other etiologies, such as reversible cerebral vasoconstriction syndrome. © 2013 American Headache Society.
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
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
Budohoski, Karol; Smith, Christopher; Hutchinson, Peter J.; Kirkpatrick, Peter J.
BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome. ABBREVIATIONS: ALP, alkaline phosphatase ALT, alanine aminotransferase CK, creatine kinase CRP, C-reactive protein EVD, external ventricular drainage ICH GCP, International Conference on Harmonisation guidelines for good clinical practice mRS, modified Rankin Scale SAH, subarachnoid hemorrhage STASH, Simvastatin in
Liu, Hongju; Xu, Xiaoli
Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of simvastatin for aneurysmal subarachnoid hemorrhage. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of simvastatin versus placebo on aneurysmal subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were delayed ischaemic deficit and delayed cerebral infarction. Meta-analysis was performed using the random-effect model. Six RCTs involving 1053 patients were included in the meta-analysis. Overall, compared with control intervention, simvastatin intervention had no influence on delayed ischaemic deficit (RR=0.99; 95% CI=0.78 to 1.27; P=0.96), delayed cerebral infarction (RR=1.17; 95% CI=0.60 to 2.29; P=0.65), mRS≤2 (RR=0.97; 95% CI=0.87 to 1.09; P=0.61), vasospasm (RR=0.79; 95% CI=0.49 to 1.29; P=0.35), ICU stay (Std. mean difference=0.04; 95% CI=-0.54 to 0.63; P=0.88), hospital stay (Std. mean difference=0.01; 95% CI=-0.13 to 0.14; P=0.90) and mortality (RR=0.71; 95% CI=0.25 to 2.05; P=0.53) after aneurysmal subarachnoid hemorrhage. Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
Perry, Jeffrey J; Spacek, Alena; Forbes, Melissa; Wells, George A; Mortensen, Melodie; Symington, Cheryl; Fortin, Nicole; Stiell, Ian G
Current clinical practice assumes a negative computed tomography (CT) head scan result and a negative lumbar puncture result together are adequate to rule out subarachnoid hemorrhage in patients with acute headache. Our objective is to determine the sensitivity of a negative CT result combined with a negative lumbar puncture result to exclude subarachnoid hemorrhage. This prospective cohort study was conducted at 2 tertiary care emergency departments (EDs) during 3 years. We enrolled all patients who were older than 15 years, had a nontraumatic acute headache and normal neurologic examination result, and who had a CT head scan and a lumbar puncture if the CT result was negative (ie, no blood in the subarachnoid space). Patients were followed up with a structured telephone questionnaire 6 to 36 months after their ED visit and electronic hospital records review to ensure no missed subarachnoid hemorrhage. We calculated sensitivity, specificity, and likelihood ratios of the strategy of CT and then lumbar puncture for subarachnoid hemorrhage. Five hundred ninety-two patients were enrolled, including 61 with subarachnoid hemorrhage. The mean patient age was 43.6 years, with 59.1% female patients. All cases of subarachnoid hemorrhage were identified on initial CT or lumbar puncture. One patient without subarachnoid hemorrhage was subsequently diagnosed with cerebral aneurysm, requiring surgery. The strategy classified patients with subarachnoid hemorrhage with sensitivity, specificity, and positive and negative likelihood ratios (with 95% confidence intervals [CIs]) of 100% (95% CI 94% to 100%), 67% (95% CI 63% to 71%), 3.03 (95% CI 2.69 to 3.53), and 0. For diagnosis of subarachnoid hemorrhage or aneurysm, these were 98% (95% CI 91% to 100%), 67% (95% CI 63% to 71%), 2.98 (95% CI 2.63 to 3.38), and 0.02 (95% CI 0.00 to 0.17), respectively. To our knowledge, this is the largest prospective study evaluating the accuracy of a strategy of CT and lumbar puncture to rule out
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.
Lo, Benjamin W Y; Macdonald, R Loch; Baker, Andrew; Levine, Mitchell A H
The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH). The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients). Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters. This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication.
Yuan, Falei; Chen, Lujia; He, Chuan; Bao, Yuhai; Chen, Zuoquan; Lou, Meiqing; Xia, Weiliang; Yang, Guo-Yuan; Ling, Feng
Precise in vivo evaluation of cerebral vasospasm caused by subarachnoid hemorrhage has remained a critical but unsolved issue in experimental small animal models. In this study, we used synchrotron radiation angiography to study the vasospasm of anterior circulation arteries in two subarachnoid hemorrhage models in rats. Synchrotron radiation angiography, laser Doppler flowmetry-cerebral blood flow measurement, [125I]N-isopropyl-p-iodoamphetamine cerebral blood flow measurement and terminal examinations were applied to evaluate the changes of anterior circulation arteries in two subarachnoid hemorrhage models made by blood injection into cisterna magna and prechiasmatic cistern. Using synchrotron radiation angiography technique, we detected cerebral vasospasm in subarachnoid hemorrhage rats compared to the controls (p<0.05). We also identified two interesting findings: 1) both middle cerebral artery and anterior cerebral artery shrunk the most at day 3 after subarachnoid hemorrhage; 2) the diameter of anterior cerebral artery in the prechiasmatic cistern injection group was smaller than that in the cisterna magna injection group (p<0.05), but not for middle cerebral artery. We concluded that synchrotron radiation angiography provided a novel technique, which could directly evaluate cerebral vasospasm in small animal experimental subarachnoid hemorrhage models. The courses of vasospasm in these two injection models are similar; however, the model produced by prechiasmatic cistern injection is more suitable for study of anterior circulation vasospasm. PMID:22428033
Kneyber, M C J; Rinkel, G J E; Ramos, L M P; Tulleken, C A F; Braun, K P J
Subarachnoid hemorrhage (SAH) due to a ruptured saccular aneurysm is uncommon in children. Pediatric traumatic aneurysms have been reported relatively frequently, tending to bleed after an interval of weeks after head injury. The authors describe three children with acute SAH after head injury caused by intracranial dissecting aneurysms. When head trauma in children is complicated by SAH in basal cisterns, dissecting aneurysms should be considered and treated, because rebleeding may occur.
Jaja, Blessing N R; Saposnik, Gustavo; Nisenbaum, Rosane; Schweizer, Tom A; Reddy, Deven; Thorpe, Kelvin E; Macdonald, R Loch
Studies in the United States and Canada have demonstrated socioeconomic gradients in outcomes of acute life-threatening cardiovascular and cerebrovascular diseases. The extent to which these findings are applicable to subarachnoid hemorrhage is uncertain. This study investigated socioeconomic status-related differences in risk of inpatient mortality and use of institutional postacute care after subarachnoid hemorrhage in the United States and Canada. Subarachnoid hemorrhage patient records in the US Nationwide Inpatient Sample database (2005-2010) and the Canadian Discharge Abstract Database (2004-2010) were analyzed separately, and summative results were compared. Both databases are nationally representative and contain relevant sociodemographic, diagnostic, procedural, and administrative information. We determined socioeconomic status on the basis of estimated median household income of residents for patient's ZIP or postal code. Multinomial logistic regression models were fitted with adjustment for relevant confounding covariates. The cohort consisted of 31,631 US patients and 16,531 Canadian patients. Mean age (58 years) and crude inpatient mortality rates (22%) were similar in both countries. A significant income-mortality association was observed among US patients (odds ratio, 0.77; 95% CI, 0.65-0.93), which was absent among Canadian patients (odds ratio, 0.97; 95% CI, 0.85-1.12). Neighborhood income status was not significantly associated with use of postacute care in the 2 countries. Socioeconomic status is associated with subarachnoid hemorrhage inpatient mortality risk in the United States, but not in Canada, although it does not influence the pattern of use of institutional care among survivors in both countries.
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
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.
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
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.
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.
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
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
Ono, Hideaki; Inoue, Tomohiro; Suematsu, Shinya; Tanishima, Takeo; Tamura, Akira; Saito, Isamu; Saito, Nobuhito
Spontaneous intracranial arterial dissection (IAD) is an increasingly important cause of stroke, such as subarachnoid hemorrhage (SAH) and hemodynamic or thromboembolic cerebral ischemia. IAD usually occurs in the posterior circulation, and is relatively rare in the anterior circulation including the middle cerebral artery (MCA). Various surgical and endovascular methods to reduce blood flow in the dissected lesion have been proposed, but no optimum treatment has been established. An 80-year-old woman with dissection in the M1 portion of the MCA manifesting as SAH presented with repeated hemorrhage and cerebral infarction in the area of the inferior trunk of the MCA. High-flow bypass to the MCA was performed and the dissecting lesion was trapped. Prevention of repeated hemorrhage was achieved, and blood flow was preserved to the lenticulostriate artery as well as the MCA area distal to the lesion. Treatment strategy for IAD of the MCA should be planned for each patient and condition, and surgery should be performed promptly to prevent critical rebleeding given the high recurrence rate. In addition, preventing re-rupture of the IAD, and preserving important perforators around the lesion and blood flow distal to the dissection should be targeted by the treatment strategy.
Stovell, Matthew George; Pillay, Robin
Case report. To present a previously unreported complication of subarachnoid hemorrhage and hydrocephalus after C1 lateral mass screw insertion. To inform spine specialists of this potential postoperative complication. Damage to the carotid artery, vertebral artery, hypoglossal nerve and dural tears are all recognized complications. Acute hydrocephalus as a result of subarachnoid hemorrhage is not previously reported. A 63-year-old female with a traumatic C1 ring and C2 peg fracture underwent C1-C2 fixation. During insertion of the C1 lateral mass screws there was significant hemorrhage from the C1-C2 venous plexus. Three days postoperatively, she developed headache, confusion, and became drowsy. Computed tomographic scan of the brain revealed hydrocephalus and intraventricular blood that was managed with an external ventricular drain. The case of acute hydrocephalus due to intraventricular hemorrhage from C1 lateral mass screw placement has not previously been reported. Surgeons performing the procedure should consider the diagnosis if patients display signs of raised intracranial pressure postoperatively. N/A.
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.
Höllig, Anke; Weinandy, Agnieszka; Liu, Jingjin; Clusmann, Hans; Rossaint, Rolf; Coburn, Mark
Until now, treatment ameliorating early brain injury following subarachnoid hemorrhage has been nonexistent. Here, we evaluate the neuroprotective properties of argon after experimental subarachnoid hemorrhage with mortality as the primary endpoint and functional outcome, as well as hippocampal cellular and molecular stress response as secondary endpoints. Randomized controlled animal study. University research laboratory. Ninety-eight male Sprague-Dawley rats. One hour after subarachnoid hemorrhage induction via endovascular perforation technique or sham surgery, a breathing gas mixture containing 50 vol% argon/50 vol% oxygen (argon group) or 50 vol% nitrogen/50 vol% oxygen (control group) was applied for 1 hour. The primary objective was mortality after subarachnoid hemorrhage. Additionally, outcome was assessed via 1) neurologic testing and 2) an open-field test 24 hours after subarachnoid hemorrhage, 3) protein analysis of hippocampal samples for hypoxia-inducible factor 1α and heme oxygenase 1, and 4) immunohistochemistry of hippocampal slices to quantify vital neurons. Animals were euthanized 6, 24, or 72 hours after subarachnoid hemorrhage or sham surgery. Occurrence of premature death (death prior to scheduled euthanasia) was assessed. Postconditioning with argon resulted in a reduction of risk with respect to premature death to 20.6% compared with the control group (95% CI, 4.39-96.7). Body weight was higher in the argon group over the entire observation period (p < 0.05). There was no difference in the neuroscore (p = 0.550). Expression of hypoxia-inducible factor 1α and heme oxygenase 1 in the hippocampus was increased in the argon group. Higher quantity of vital neurons in the hippocampal samples of the argon group was discovered 24 hours after subarachnoid hemorrhage. Argon application after experimental subarachnoid hemorrhage met the primary endpoint of reducing the risk of mortality. In addition, higher body weight indicating good overall
Boers, A M; Zijlstra, I A; Gathier, C S; van den Berg, R; Slump, C H; Marquering, H A; Majoie, C B
Quantification of blood after SAH on initial NCCT is an important radiologic measure to predict patient outcome and guide treatment decisions. In current scales, hemorrhage volume and density are not accounted for. The purpose of this study was to develop and validate a fully automatic method for SAH volume and density quantification. The automatic method is based on a relative density increase due to the presence of blood from different brain structures in NCCT. The method incorporates density variation due to partial volume effect, beam-hardening, and patient-specific characteristics. For validation, automatic volume and density measurements were compared with manual delineation on NCCT images of 30 patients by 2 radiologists. The agreement with the manual reference was compared with interobserver agreement by using the intraclass correlation coefficient and Bland-Altman analysis for volume and density. The automatic measurement successfully segmented the hemorrhage of all 30 patients and showed high correlation with the manual reference standard for hemorrhage volume (intraclass correlation coefficient = 0.98 [95% CI, 0.96-0.99]) and hemorrhage density (intraclass correlation coefficient = 0.80 [95% CI, 0.62-0.90]) compared with intraclass correlation coefficient = 0.97 (95% CI, 0.77-0.99) and 0.98 (95% CI, 0.89-0.99) for manual interobserver agreement. Mean SAH volume and density were, respectively, 39.3 ± 31.5 mL and 62.2 ± 5.9 Hounsfield units for automatic measurement versus 39.7 ± 32.8 mL and 61.4 ± 7.3 Hounsfield units for manual measurement. The accuracy of the automatic method was excellent, with limits of agreement of -12.9-12.1 mL and -7.6-9.2 Hounsfield units. The automatic volume and density quantification is very accurate compared with manual assessment. As such, it has the potential to provide important determinants in clinical practice and research. © 2014 by American Journal of Neuroradiology.
Balinger, Kathryn J; Elmously, Adham; Hoey, Brian A; Stehly, Christy D; Stawicki, Stanislaw Peter; Portner, Marc E
Computed tomographic angiography (CTA) tends to be overused in patients with traumatic subarachnoid hemorrhage (tSAH) to rule out intracranial aneurysmal disease. We hypothesized that there are two exclusive subsets of patients with tSAH that maybe at increased risk for aneurysm and thus should undergo CTA, those "found down" with an unknown mechanism of injury and those with "central subarachnoid hemorrhage" (CSH, in the subarachnoid cisterns and Sylvian fissures). This pilot study was performed to provide more information on the validity of our hypothesis. A retrospective analysis was performed on trauma patients with tSAH who underwent CTA of the brain. Patients presented to a level I trauma center from January 2008-December 2012. Our principal outcome was the diagnosis of an intracranial aneurysm. Student t-test, chi-squared test, Mann-Whitney U test, and binary logistic regression were used for statistical analysis, with significance set at alpha = 0.05. Of 617 total patients with tSAH, 186 patients underwent CTA. Majority of patients were male (64%), with median age of 56 y. Median Glasgow coma scale on presentation was 15, and the median injury severity score was 16. Thirteen patients (6.99%) had an aneurysm on the follow-up CTA. Of those, 8 of 13 (61.5%) were felt to have presented with a ruptured aneurysm. Among those, 5 of 8 (62.5%) sustained a fall and 3 of 8 (37.5%) resulted from a motor vehicle crash. Among the 14 patients (7.5%) "found down", none had an aneurysm. All eight patients with a ruptured aneurysm (100%) had CSH, whereas none of the five patients with unruptured aneurysm had CSH. On multivariate analysis, suprasellar cistern hemorrhage was the most predictive noncontrast computed tomographic finding with regard to aneurysm presence (odds ratio, 4.78; 95% confidence interval, 1.33-17.1). Patients with an aneurysmal disease had a significantly higher mean arterial pressure on presentation (median, 115 mm Hg) than those without an aneurysm
Brouwers, H Bart; Backes, Daan; Kimberly, W Taylor; Schwab, Kristin; Romero, Javier M; Velthuis, Birgitta K; Klijn, Catharina J M; Ogilvy, Christopher S; Regli, Luca; Greenberg, Steven M; Rosand, Jonathan; Rinkel, Gabriel J E; Goldstein, Joshua N
Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.
Choi, H Alex; Fernandez, Andres; Jeon, Sang-Beom; Schmidt, J Michael; Connolly, E Sander; Mayer, Stephan A; Claassen, Jan; Badjatia, Neeraj; Prager, Kenneth M; Lee, Kiwon
It is common for patients who die from subarachnoid hemorrhage to have a focus on comfort measures at the end of life. The potential role of ethnicity in end-of-life decisions after brain injury has not been extensively studied. Patients with subarachnoid hemorrhage were prospectively followed in an observational database. Demographic information including ethnicity was collected from medical records and self-reported by patients or their family. Significant in-hospital events including do-not-resuscitate orders, comfort measures only orders (CMO; care withheld or withdrawn), and mortality were recorded prospectively. 1255 patients were included in our analysis: 650 (52 %) were White, 387 (31 %) Hispanic, and 218 (17 %) Black. Mortality was similar between the groups. CMO was more commonly observed in Whites (14 %) compared to either Blacks (10 %) or Hispanics (9 %) (p = 0.04). In a multivariate analysis controlling for age and Hunt-Hess grade, Hispanics were less likely to have CMO than Whites (OR, 0.6; 95 %CI, 0.4-0.9; p = 0.02). Of the 229 patients who died, 77 % of Whites had CMO compared to 54 % of Blacks and 49 % of Hispanics (p < 0.01). In a multivariate analysis, Blacks (OR, 0.3; 95 %CI, 0.2-0.7; p < 0.01) and Hispanics (OR, 0.3; 95 %CI, 0.2-0.6; p < 0.01) were less likely to die with CMO orders than Whites. After subarachnoid hemorrhage, Blacks and Hispanics are less likely to die with CMO orders than Whites. Further research to confirm and investigate the causes of these ethnic differences should be performed.
Claassen, Jan; Velasquez, Angela; Meyers, Emma; Witsch, Jens; Falo, Christina Maria; Park, Soojin; Agarwal, Sachin; Schmidt, J. Michael; Schiff, Nicholas D.; Sitt, Jacobo D.; Naccache, Lionel; Connolly, E. Sander; Frey, Hans-Peter
Objective Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain-injured patients. We evaluated whether EEG and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage. Methods A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into three groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending towards a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression. Results We identified 389 artifact-free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta-delta oscillations differentiated patients that were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (e.g., pupillary light reflex) contributed heavily to a linear model predicting behavioral state while brain physiology measures (e.g., brain oxygenation), structural injury, and clinical course added less. Interpretation EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness. PMID:27472071
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
Chu, Kevin; Hann, Angus; Greenslade, Jaimi; Williams, Julian; Brown, Anthony
We assess the sensitivity and specificity of xanthochromia as adjudicated by visual inspection and spectrophotometry at predicting the presence of cerebral aneurysm in patients with suspected subarachnoid hemorrhage who have a normal computed tomography (CT) head scan result. A systematic review was performed. MEDLINE and EMBASE databases were searched. Relevant studies with clinical data on the diagnostic accuracy of visual inspection or spectrophotometry were considered. Patients who had a normal CT head scan result followed by a lumbar puncture were included in this review. Sensitivities, specificities, and heterogeneity (I(2)) were calculated. Subgroup analyses were performed to explore reasons for the heterogeneity. There were major methodological limitations in the studies found. Twenty-two relevant articles were heterogeneous in regard to time to lumbar puncture, spectrophotometry methods, and follow-up of patients not undergoing cerebral angiography. Twelve of the 22 studies selected patients on the basis of a cerebral aneurysm or subarachnoid hemorrhage on imaging, or a positive lumbar puncture result. These studies were excluded from our initial analysis, which included only patients with clinically suspected subarachnoid hemorrhage. In this initial analysis, pooled estimates of sensitivity and specificity for spectrophotometry were 87% (95% confidence interval [CI] 71% to 96%; I(2)=26%) and 86% (95% CI 84% to 88%; I(2)=96%), respectively. For visual inspection, pooled sensitivity and specificity were 83% (95% CI 59% to 96%; I(2)=52%) and 96% (95% CI 93% to 97%; I(2)=76%), respectively. Sensitivity estimates are difficult to interpret without knowing time to lumbar puncture. The heterogeneity in the underlying studies, combined with significant overlap in pooled confidence limits, makes it impossible to provide a definite conclusion about the diagnostic accuracy of spectrophotometry versus visual inspection. Copyright © 2014 American College of Emergency
de Oliveira Manoel, Airton Leonardo; Jaja, Blessing N; Germans, Menno R; Yan, Han; Qian, Winnie; Kouzmina, Ekaterina; Marotta, Tom R; Turkel-Parrella, David; Schweizer, Tom A; Macdonald, R Loch
Patients are classically at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading scale-the VASOGRADE-for prediction of DCI. We used data of 3 phase II randomized clinical trials and a single hospital series to assess the relationship between the VASOGRADE and DCI. The VASOGRADE derived from previously published risk charts and consists of 3 categories: VASOGRADE-Green (modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [WFNS] 1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1-3); and VASOGRADE-Red (WFNS 4 or 5, irrespective of modified Fisher grade). The relation between the VASOGRADE and DCI was assessed by logistic regression models. The predictive accuracy of the VASOGRADE was assessed by receiver operating characteristics curve and calibration plots. In a cohort of 746 patients, the VASOGRADE significantly predicted DCI (P<0.001). The VASOGRADE-Yellow had a tendency for increased risk for DCI (odds ratio [OR], 1.31; 95% CI, 0.77-2.23) when compared with VASOGRADE-Green; those with VASOGRADE-Red had a 3-fold higher risk of DCI (OR, 3.19; 95% CI, 2.07-4.50). Studies were not a significant confounding factor between the VASOGRADE and DCI. The VASOGRADE had an adequate discrimination for prediction of DCI (area under the receiver operating characteristics curve=0.63) and good calibration. The VASOGRADE results validated previously published risk charts in a large and diverse sample of subarachnoid hemorrhage patients, which allows DCI risk stratification on presentation after subarachnoid hemorrhage. It could help to select patients at high risk of DCI, as well as standardize treatment protocols and research studies. © 2015 American Heart Association, Inc.
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.
Hong, Caron M.; Tosun, Cigdem; Kurland, David B.; Gerzanich, Volodymyr; Schreibman, David; Simard, J. Marc
Context Subarachnoid hemorrhage (SAH) has a high fatality rate and many suffer from delayed neurological deficits. Biomarkers may aid in the identification of high-risk patients, guide treatment/management and improve outcome. Objective The aim of this review was to summarize biomarkers of SAH associated with outcome. Methods An electronic database query was completed, including an additional review of reference lists to include all potential human studies. Results A total of 298 articles were identified; 112 were reviewed; 55 studies were included. Conclusion This review details biomarkers of SAH that correlate with outcome. It provides the basis for research investigating their possible translation into the management of SAH patients. PMID:24499240
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.
Lazaridis, Christos; Bodle, Jeffrey; Chaudry, Imran; Hays, Angela; Chalela, Julio
Family history is a recognized risk factor in aneurysmal subarachnoid hemorrhage (SAH). The genetic and environmental contributions are actively researched. The authors of this report present a case series of 3 first-degree siblings affected by nontraumatic, angiographically negative SAH. Data in this study suggest that familial predisposition may also apply to spontaneous, nonaneurysmal SAH and that family history should be actively investigated in all such patients. The identification of families with multiple affected members could lead to an improved understanding of the genetic and environmental factors associated with this condition.
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
Noda, Kazuyuki; Fukae, Jiro; Fujishima, Kenji; Mori, Kentaro; Urabe, Takao; Hattori, Nobutaka; Okuma, Yasuyuki
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute severe headache with or without additional neurological symptoms and reversible cerebral vasoconstriction. Unruptured aneurysm has been reported in some cases with RCVS. We report a severe case of a 53-year-old woman with RCVS having an unruptured cerebral aneurysm and presenting as cortical subarachnoid hemorrhage, reversible posterior leukoencephalopathy syndrome, and cerebral infarction. She was successfully treated with corticosteroids and a calcium channel blocker and the aneurysm was clipped. Her various complications are due to the responsible vasoconstriction that started distally and progressed towards proximal arteries. This case demonstrates the spectrum of presentations of RCVS, a clinically complicated condition.
Dang, Baoqi; Li, Haiying; Xu, Xiang; Shen, Haitao; Wang, Yang; Gao, Anju; He, Weichun; Wang, Zhong; Chen, Gang
Cyclophilin A has been found to be involved in many inflammatory diseases via its receptor, cluster of differentiation 147 (CD147). This study was designed to estimate the potential role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. Controlled in vivo laboratory study. Animal research laboratory. Two hundred ninety adult male Sprague-Dawley rats weighing 300-350 g. A prechiasmatic cistern single-injection model was used to produce experimental subarachnoid hemorrhage in Sprague-Dawley rats. The expressions of cyclophilin A and CD147, the interaction between cyclophilin A and CD147, and the secretion of cyclophilin A were assessed using immunofluorescence staining, Western blot analysis, and coimmunoprecipitation analysis. Down-regulation of cyclophilin A expression by small interfering RNA was performed, and recombinant human cyclophilin A and monoclonal antibody of CD147 were exploited to study the role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. The expressions of cyclophilin A and CD147 in neurons were higher than that of the sham group and peaked at 24 hours after subarachnoid hemorrhage. Compared with sham group, subarachnoid hemorrhage was found to increase the secretion of cyclophilin A and the interaction between cyclophilin A and CD147. Cyclophilin A small interfering RNA and anti-CD147 treatments were found to ameliorate subarachnoid hemorrhage-induced early brain injury, including cortical apoptosis and necrosis, brain edema, blood-brain barrier damage, and neurobehavioral deficits. Cyclophilin A small interfering RNA and anti-CD147 treatments also decreased the phosphorylation of extracellular signal-regulated protein kinase 1/2, the protein levels of p53 and caspase-3, and the level of active nuclear factor-κB. Finally, recombinant human cyclophilin A treatment resulted in an opposite effect, which was inhibited by anti-CD147 treatment. Cyclophilin A/CD147 interactions may participate
Mee, E; Dorrance, D; Lowe, D; Neil-Dwyer, G
We enrolled 75 consecutive patients admitted with subarachnoid hemorrhages in a randomized, double-blind, placebo-controlled trial to determine the effect of early intervention with nimodipine on outcome and cerebral blood flow. The cardioprotective effect of nimodipine was assessed by measuring the electrocardiographic changes over the first 3 days of drug treatment. There was a mild lowering of the mean cerebral blood flow in the nimodipine-treated group over the 21-day period. Analysis of the continuous electrocardiographic traces showed no difference between the nimodipine and placebo groups in the frequency or type of abnormality detected. At 3 months, 4 of the 38 patients receiving nimodipine had died, compared with 10 of the 37 placebo-receiving patients. Of the 50 eligible patients who had a proven cerebral aneurysm, 1 patient (4%) on nimodipine died compared with 6 (24%) receiving placebo (0.01 less than P less than 0.05, chi 2 test; approximate 95% confidence interval for mortality difference, 0.4% to 39.6%). We conclude that nimodipine does not increase the cerebral blood flow or protect the heart after a subarachnoid hemorrhage. There were no side effects from nimodipine. The trend toward improved outcome should be verified in a larger series of patients.
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.
Suehiro, Eiichi; Sadahiro, Hirokazu; Goto, Hisaharu; Oku, Takayuki; Oka, Fumiaki; Fujiyama, Yuichi; Shirao, Satoshi; Yoneda, Hiroshi; Koizumi, Hiroyasu; Ishihara, Hideyuki; Suzuki, Michiyasu
The importance of acute-phase brain temperature management is widely accepted for prevention of exacerbation of brain damage by a high body temperature. In this study, we investigated the influence of body temperature in the early postoperative period on the outcomes of 62 patients with subarachnoid hemorrhage who were admitted to our department. Body temperature was measured from day 4 to day 14 after onset. The patients were divided into those treated with surgical clipping (clip group) and coil embolization (coil group), those graded I-III (mild) and IV-V (severe) based on the Hunt & Hess classification on admission, those with and without development of delayed cerebral ischemia (DCI), and those with favorable and poor outcomes. Body temperatures throughout the hospital stay were compared in each group. There was no significant difference in body temperature between the clip and coil groups or between the mild and severe groups, but body temperature was significantly higher in patients with DCI compared to those without DCI, and in patients with a poor outcome compared to those with a favorable outcome. Fever in the early postoperative period of subarachnoid hemorrhage is associated with development of DCI and a poor outcome. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Mapa, Ben; Taylor, Blake E S; Appelboom, Geoffrey; Bruce, Eliza M; Claassen, Jan; Connolly, E Sander
Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH. We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization. A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion. Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality. Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence. Copyright © 2016 Elsevier Inc. All rights reserved.
Thomé, Claudius; Schubert, Gerrit A; Schilling, Lothar
Aneurysmal subarachnoid hemorrhage (SAH) remains a very prevalent challenge in neurosurgery associated with a high morbidity and mortality due to the lack of specific treatment modalities. The prognosis of SAH patients depends primarily on three factors: (i) the severity of the initial bleed, (ii) the endovascular or neurosurgical procedure to occlude the aneurysm and (iii) the occurrence of late sequelae, namely delayed ischemic neurological deficits due to cerebral vasospasm. While neurosurgeons and interventionalists have put significant efforts in minimizing periprocedural complications and a multitude of investigators have been devoted to the research on chronic vasospasm, the acute phase of SAH has not been studied in comparable detail. In various experimental studies during the past decade, hypothermia has been shown to reduce neuronal damage after ischemia, traumatic brain injury and other cerebrovascular diseases. Clinically, only some of these encouraging results could be reproduced. This review analyses results of studies on the effects of hypothermia on SAH with special respect to the acute phase in an experimental setting. Based on the available data, some considerations for the application of mild to moderate hypothermia in patients with subarachnoid hemorrhage are given.
Leal-Noval, Santiago R; Múñoz-Gómez, Manuel; Murillo-Cabezas, Francisco
The review outlines recent clinical and experimental studies regarding the effects of red blood-cell transfusion on clinical outcome in neurocritical patients, including patients with subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury. Optimal hemoglobin transfusion trigger and the role of other transfusion indicators for neurocritical patients are discussed. Acute anemia (hemoglobin levels near 7 g/dl) is well tolerated by healthy subjects, but extreme anemia might negatively affect clinical outcome of neurocritical patients. Conversely, high hemoglobin levels, attained by means other than red blood-cell transfusion, improve clinical outcome, whereas red blood-cell transfusion is associated with poorer clinical outcome (mortality, length of stay and disability) in patients presenting subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury. Studies defining the optimal hemoglobin concentration in neurocritical patients are lacking, but a restrictive transfusion policy seems to be safe and is often recommended. In the near future, signals coming from the brain, such as brain tissue oxygen tension and regional cerebral oxygen saturation, might potentially be developed into transfusion triggers. Both severe anemia and red blood-cell transfusion may negatively influence clinical outcome in neurocritical patients. Acceptance of low hemoglobin concentrations may be justified by avoiding negative transfusion effects. No evidence-based transfusion trigger in neurocritical patients can be recommended.
Sprenker, Collin; Patel, Jaymin; Camporesi, Enrico; Vasan, Rosit; Van Loveren, Harry; Chen, Henian; Agazzi, Siviero
Common management of angionegative subarachnoid hemorrhage includes mandatory intensive care unit stay for up to 14 days with strict bedrest, constant neurologic serial examination, invasive arterial and central line monitoring, and aneurysm rupture precautions. We evaluated the frequency of neurologic and nonneurologic complications in this patient population. This was a retrospective chart review from July 2008 to 2011. Adult patients with International Classification of Diseases, Ninth Revision code for nontraumatic subarachnoid hemorrhage who had angiograms and cranial cat scans (CTs) were evaluated as the first screening measure. Negative screening angiograms constituted our study population and were divided into 2 groups (aneurysmal or perimesencephalic) based on the CT blood pattern. Fifty-one patients met the study criteria (aneurysmal CT, n = 26; perimesencephalic CT pattern, n = 25). There were no incidences of rebleeding or mortality, and patients were discharged after a mean of 15.24 hospital days and a mean of 11 bedrest days. Seventeen patients (65%) in the aneurysmal group developed at least 1 nonneurologic complication compared with 2 patients (8%) in the perimesencephalic group (P = .001). Eleven patients in the aneurysmal group (42.3%) developed at least 1 neurologic complication compared with 1 patient (4%) in the perimesecephalic group (P = .001). Based on our results, we propose admission to the medical floor for patients with World Federation of Neurosurgical Societies score 1 to 3, perimesencephalic CT pattern, and no hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.
Alfieri, Alex; Gazzeri, Roberto; Pircher, Martina; Unterhuber, Vera; Schwarz, Andreas
Patients generally have a good prognosis and develop only occasional neurological complications after nontraumatic, nonaneurysmal subarachnoid hemorrhage (SAH). This prospective long-term study investigated the normal return to work of patients who had experienced nontraumatic nonaneurysmal SAH. From June 2001 to June 2004, all patients presenting with nonaneurysmal nontraumatic SAH were asked to participate in this study. The population was divided in two groups: perimesencephalic (pSAH) and nonperimesencephalic pattern (npSAH). All patients underwent a battery of neuropsychological tests and completed psychological questionnaires assessing their general cognitive and language functions, memory and construction ability, attention, anxiety and depression, and quality of life. The patients were interviewed at the hospital, and neuropsychological assessments were conducted regularly for 7 years. The cognitive assessment after 7 years revealed a statistically significant difference between the pSAH and npSAH groups with respect to the activation and elaboration speed of attention as well as long-term non-verbal memory. Nine patients could not return to their former jobs after nonaneurysmal SAH. Although nontraumatic nonaneurysmal subarachnoid hemorrhage is typically a pathology with an excellent prognosis, there is evidence that this event may influence working life for a long time. Copyright © 2011 Elsevier Ltd. All rights reserved.
Wallmark, Svante; Lundström, Erik; Wikström, Johan; Ronne-Engström, Elisabeth
The aim of this pilot study was to assess attention deficits in patients with aneurysmal subarachnoid hemorrhage using the test of variables of attention (TOVA). This is a computer-based continuous performance test providing objective measures of attention. We also compared the TOVA results with the attention and concentration domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment, 2 examiner-administrated neuropsychological instruments. Nineteen patients with moderate to good recovery (Glasgow outcome scale, 4-5) were assessed using the TOVA, Montgomery Åsberg Depression Rating Scale, and Montreal cognitive assessment. The measurements were done when the patients visited the hospital for a routine magnetic resonance imaging control of the aneurysm. TOVA performance was pathological in 58%. The dominating pattern was a worsening of performance in the second half of the test, commonly a failing to react to correct stimuli. We found no correlation between TOVA and the performance in concentration and attention domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment. Attention deficits, measured by the TOVA, were common after subarachnoid hemorrhage. This should be further studied to improve outcome. © 2015 American Heart Association, Inc.
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.
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.
Choi, H Alex; Ko, Sang-Bae; Chen, Huahiou; Gilmore, Emily; Carpenter, Amanda M; Lee, Danielle; Claassen, Jan; Mayer, Stephan A; Schmidt, J Michael; Lee, Kiwon; Connelly, E Sander; Paik, Myunghee; Badjatia, Neeraj
Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH. This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined. Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P < 0.001) and a 1.22 mmHg decrease in CPP (P < 0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P < 0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased. Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.
Hertle, Daniel N; Beynon, Christopher; Neumann, Jan O; Santos, Edgar; Sánchez-Porras, Renan; Unterberg, Andreas W; Sakowitz, Oliver W
Recent experimental evidence identified GABAergic sedation as a possible cause for deprived neuroregeneration and poor outcome after acute brain injury. Patients with aneurysmal subarachnoid hemorrhage are often sedated, and GABAergic sedation, such as midazolam and propofol, is commonly used. Retrospective cohort study based on a prospectively established database. Single-center neurointensive care unit. Twenty-nine patients after subarachnoid hemorrhage. Noninterventional study. The relationship between mean GABAergic sedative dose during the acute phase and outcome after 6 months according to the Glasgow Outcome Scale, and initial Glasgow Coma Scale was investigated. Use of GABAergic sedatives was negatively correlated with Glasgow Outcome Scale (r(2)=0.267; P=.008). Administration of sedatives was independent of the initial Glasgow Coma Scale. GABAergic sedatives flunitrazepam, midazolam, and propofol were used differently during the first 10 days after ictus. Administration of GABAergic sedation was associated with an unfavorable outcome after 6 months. To avoid bias (mainly through the indication to use sedation), additional experimental and comparative clinical investigation of, for example, non-GABAergic sedation, and clinical protocols of no sedation is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.
Burns, Joseph D; Jacob, Jeffrey T; Luetmer, Patrick H; Wijdicks, Eelco F M
Cardiac arrest and aneurysmal subarachnoid hemorrhage both cause sudden, severe cerebral hypoperfusion at ictus. Animal studies indicate that the resultant microvascular dysfunction and cerebral perfusion abnormalities are important determinants of the associated cerebral injury in both conditions. Although this suggests that perfusion imaging might be a useful tool for prognostication in patients with these conditions, this hypothesis has not been thoroughly investigated in humans. Case report. A 49-year-old man developed cardiac arrest upon rupture of an intracranial aneurysm. When he arrived at our institution 10 h later, he was comatose, had neurogenic hyperventilation, absent corneal reflexes, and continuous multifocal myoclonus. Despite normal intracranial pressure, normal cerebral perfusion pressure, normal flow in the proximal cerebral arteries on CT angiography, and a lack of diffuse cerebral edema, CT perfusion imaging performed 12 h after ictus showed severe, diffuse hypoperfusion. After the development of refractory intracranial hypertension, physiologic support was withdrawn and the patient died. Early global cerebral hypoperfusion can be demonstrated by CT perfusion imaging after cardiac arrest associated with high-grade aneurysmal subarachnoid hemorrhage and may be indicative of poor neurologic outcome. CT perfusion should be investigated as a prognostic tool in these conditions.
Kreiter, Kurt T; Mayer, Stephan A; Howard, George; Knappertz, Volker; Ilodigwe, Don; Sloan, Michael A; Macdonald, R Loch
Clinical trials for prevention of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) seldom have improved overall outcome; one reason may be inadequate sample size. We used data from the tirilizad trials and the Columbia University subarachnoid hemorrhage outcomes project to estimate sample sizes for clinical trials for reduction of vasospasm after SAH, assuming trials must show effect on 90-day patient-centered outcome. Sample size calculations were based on different definitions of vasospasm, enrichment strategies, sensitivity of short- and long-term outcome instruments for reflecting vasospasm-related morbidity, different event rates of vasospasm, calculation of effect size of vasospasm on outcome instruments, and different treatment effect sizes. Sensitivity analysis was performed for variable event rates of vasospasm for a given treatment effect size. Sample size tables were constructed for different rates of vasospasm and outcome instruments for a given treatment effect size. Vasospasm occurred in 12% to 30% of patients. Symptomatic deterioration and infarction from vasospasm exhibited the strongest relationship to mortality and morbidity after SAH. Enriching for vasospasm by selection of patients with thick SAH slightly decreased sample sizes. Assuming beta=0.80, alpha=0.05 (2-tailed) and treatment effect size of 50%, total sample size exceeds 5000 patients to demonstrate efficacy on 3-month patient-centered outcome (modified Rankin Scale). Clinical trials targeting vasospasm and using traditional patient-centered outcome require very high sample sizes and will therefore be costly, time-consuming, and impractical. This will hinder development of new treatment strategies.
Winkler, Maren Kl; Dengler, Nora; Hecht, Nils; Hartings, Jed A; Kang, Eun J; Major, Sebastian; Martus, Peter; Vajkoczy, Peter; Woitzik, Johannes; Dreier, Jens P
Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.
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.
Takeda, Shigeki; Yamazaki, Kazunori; Miyakawa, Teruo; Onda, Kiyoshi; Hinokuma, Kaoru; Ikuta, Fusahiro; Arai, Hiroyuki
Six autopsy cases of subcortical hematoma caused by CAA were examined to elucidate the primary site of hemorrhage. Immunohistochemistry for amyloid beta-protein (A beta) revealed extensive CAA in the intrasulcal meningeal vessels rather than in the cerebral cortical vessels. All of the examined cases had multiple hematomas in the subarachnoid space, mainly in the cerebral sulci, as well as intracerebral hematomas. Each intracerebral hematoma was connected to the subarachnoid hematomas at the depth of cerebral sulci or through the lateral side of the cortex. There was no debris of the cerebral cortical tissue in the subarachnoid hematomas. In case 2, another solitary subarachnoid hematoma, which was not connected to any intracerebral hematoma, was seen. In all of these subarachnoid hematomas, many ruptured A beta-immunopositive arteries were observed. These ruptured arteries did not accompany any debris of the brain tissue, some of them were large in diameter (250-300 microm), and several of them were far from the cerebral cortex. Therefore, it was considered that they were not cortical arteries but meningeal arteries. Within the cerebral cortex, there were only a few ruptured arteries associated with small hemorrhages. There were no ruptured vessels within the intracerebral hematomas. There was a strong suggestion that all of the subarachnoid hematomas, including the solitary one in case 2, originated from the rupture of the meningeal arteries. The present study indicates that in some cases of subcortical hematoma caused by CAA, the primary hemorrhage occurs in the subarachnoid space, in particular the cerebral sulci, because of rupture of multiple meningeal arteries. Infarction occurs subsequently in the cortex around the hematoma, the hematoma penetrates into the brain parenchyma, and finally, a subcortical hematoma is formed.
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.
Shi, Xianqing; Fu, Yongjian; Zhang, SongSong; Ding, Hao; Chen, Jin
In subarachnoid hemorrhagic brain injury, the early crucial events are edema formation due to inflammatory responses and blood-brain barrier disruption. Baicalin, a flavone glycoside, has antineuroinflammatory and antioxidant properties. We examined the effect of baicalin in subarachnoid hemorrhagic brain injury. Subarachnoid hemorrhage was induced through filament perforation and either baicalin or vehicle was administered 30 min prior to surgery. Brain tissues were collected 24 hours after surgery after evaluation of neurological scores. Brain tissues were processed for water content, real-time PCR, and immunoblot analyses. Baicalin improved neurological score and brain water content. Decreased levels of tight junction proteins (occludin, claudin-5, ZO-1, and collagen IV) required for blood-brain barrier function were restored to normal level by baicalin. Real-time PCR data demonstrated that baicalin attenuated increased proinflammatory cytokine (IL-1β, IL-6, and CXCL-3) production in subarachnoid hemorrhage mice. In addition to that, baicalin attenuated microglial cell secretion of IL-1β and IL-6 induced by lipopolysaccharide (100 ng/ml) dose dependently. Finally, baicalin attenuated induction of NOS-2 and NOX-2 in SAH mice at the mRNA and protein level. Thus, we demonstrated that baicalin inhibited microglial cell activation and reduced inflammation, oxidative damage, and brain edema.
Borczuk, Pierre; Penn, Joshua; Peak, David; Chang, Yuchiao
Current standard of care for patients with traumatic intracranial hemorrhage (TIH) includes neurosurgical consultation and/or transfer to a trauma center with neurosurgical backup. We hypothesize that a set of low-risk criteria can be applied to such patients to identify those who may not require neurosurgical evaluation. This is a cross-sectional study of consecutive emergency department patients in 2009 and 2010 with TIH on computerized tomographic scan owing to blunt head trauma. Patients presented to an urban academic Level I trauma center (volume, 92,000) were older than 15 years and had a Glasgow Coma Scale (GCS) score of 13 or greater. Charts were abstracted using a standardized data form by two emergency physicians. Our principal outcome was deterioration represented by a composite of neurosurgical intervention, clinical deterioration, or worsening computerized tomographic scan result. During the study period, 404 patients were seen with TIH and met our inclusion criteria, and 48 of those patients (11.8%) deteriorated. Patients with isolated subarachnoid hemorrhage, were less likely to deteriorate (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.011-0.58). Characteristics associated with deterioration were subdural hematomas (OR, 2.63; 95% CI, 1.198-5.81) or presenting GCS of less than 15 (OR, 2.12; 95% CI, 1.01-4.43).The use of anticoagulant medications or antiplatelet agents were not associated with deterioration for warfarin, aspirin, or clopidogrel; however bleeding diatheses were corrected with vitamin K, fresh frozen plasma, and platelets as necessary. Patients with isolated traumatic subarachnoid hemorrhage are at low risk for deterioration. These individuals may not need neurosurgical consultation or transfer to a trauma center where neurosurgical backup is available. Those patients with subdural hematoma or a GCS of less than 15 have a higher risk of deterioration and require neurosurgical evaluation. Therapeutic/care management, level IV.
Tjahjadi, Martin; König, Ralph; Wirtz, Christian Rainer; Woischneck, Dieter; Kapapa, Thomas
To examine the influence of cerebral vasospasm on health-related quality of life after subarachnoid hemorrhage. An additional objective was to determine how the timing of nimodipine therapy can influence health-related quality of life. Patients treated between 1998 and 2008 for nontraumatic subarachnoid hemorrhages were sent a standardized questionnaire for the purposes of documenting their health-related quality of life. Initially the patients were divided into two groups: those with and those without cerebral vasospasm after hemorrhage (radiologically confirmed). They were then differentiated according to four types of treatment options for vasospasm: 1) nimodipine since admission (N = 179); 2) nimodipine since diagnosis of vasospasm (N = 14); 3) no nimodipine/no vasospasm (N = 34); and 4) no nimodipine despite vasospasm (N = 5). Significance was established as P ≤ 0.05. Evaluable questionnaires were returned by 236 patients (68% women, mean age 56.35 ± 12.68 years; 32% men, mean age 54.57 ± 12.20 years). Health-related quality of life generally appeared to be impaired. Yet with the exception of the subscale (1 of 8) of physical role (P = 0.019), there were no differences between patients with and without vasospasm. Variations in the different treatment options revealed significant effects in terms of the component summaries and subscales: physical role and pain, general health, vitality, social functioning, emotional role, mental health, and mental component summary (P ≤ 0.04). Cerebral vasospasm had little influence on health-related quality of life in our patient population. Health-related quality of life cannot be used as the only argument in favor of treating cerebral vasospasm with nimodipine. Copyright © 2013 Elsevier Inc. All rights reserved.
Hong, Jennifer; Rubino, Sebastian; Lollis, Stuart Scott
Helicopter transport may shorten transport time to neurosurgical intervention; however, there are few data regarding its utility for nontraumatic emergencies. Prehospital and hospital records of all patients transferred via helicopter to Dartmouth-Hitchcock Medical Center for spontaneous subarachnoid hemorrhage between January 2007 and December 2011 were reviewed. Primary outcome measure was emergent tertiary-level care intervention, defined as ventriculostomy, conventional angiography, endovascular treatment, or craniotomy within 3 hours of arrival. Fifty-one patients met inclusion criteria. Median helicopter transport time, defined as time from telephone referral to arrival, was 97 minutes (range, 61-214 minutes). Fifteen patients underwent intervention within 3 hours of arrival (29%), 19 patients underwent intervention between 3 and 6 hours (37%), 9 patients underwent intervention between 6 to 12 hours (18%), and 11 patients underwent intervention greater than 12 hours after arrival (16%). Univariate analysis of pretransfer clinical and radiographic findings showed significant correlations between Glasgow Coma Scale (GCS) score less than 15 (odds ratio [OR], 22.8; 95% confidence interval [CI], 4.2-122.5), World Federation of Neurologic Surgeons (WFNS) scale greater than 2 (OR, 46.75; 95% CI, 7.511-290.99), presence of intraparenchymal hemorrhage (OR, 4.7; 95% CI, 1.3-17.5), and intubation (OR, 12.4; 95% CI, 2.9-51.8) with emergent intervention. On logistic multivariate regression analysis, GCS score less than 15 and WFNS scale score greater than 2 independently predicted emergent intervention. A majority of patients with spontaneous subarachnoid hemorrhage who were transferred by interfacility helicopter ambulance did not require emergent intervention. GCS score less than 15 at an outside hospital was independently associated with emergent intervention on multivariate analysis. Copyright © 2016 Elsevier Inc. All rights reserved.
Elgendy, Akram Y; Elgendy, Islam Y; Mansoor, Hend; Mahmoud, Ahmed N
Evidence remains inconsistent regarding the incidence and prognosis of Takotsubo syndrome in the setting of subarachnoid hemorrhage. Thus, we aimed to evaluate the clinical presentation and in-hospital mortality of these patients. A systematic review of the electronic databases was conducted for studies involving patients with spontaneous subarachnoid hemorrhage and concomitant findings of classical Takotsubo syndrome on transthoracic echocardiogram. A meta-analysis was conducted for the primary outcome of in-hospital mortality using the Mantel-Haenszel method for fixed effects and the DerSimonian and Laird method for random effects, with 95% confidence interval and a p-value <0.05 for statistical significance. Ten studies were retrieved with a total of 157 patients presenting with classical Takotsubo syndrome, representing 4.4% of the subarachnoid hemorrhage total population. The overall incidence of in-hospital mortality was 30% in the patients who developed Takotsubo syndrome. Meta-analysis illustrated a significant increase in the odds of in-hospital mortality for the Takotsubo syndrome patients by fixed effects model (odds ratio 2.6, 95% confidence interval 1.16-5.85, p=0.02, I(2)=39%), with a trend towards increased risk of in-hospital mortality by random effects model (odds ratio 3.00, 95% confidence interval 0.90-9.77, p = 0.07). The incidence of Takotsubo syndrome in patients with spontaneous subarachnoid hemorrhage seems to be high with a trend towards higher risk of in-hospital mortality in those patients. Thus, patients presenting with subarachnoid hemorrhage might benefit from a comprehensive cardiac evaluation upon presentation for early detection and proper triage of this high-risk population. © The European Society of Cardiology 2016.
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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
Shinoda, Narihide; Hirai, Osamu; Mikami, Kazuyuki; Bando, Toshiaki; Shimo, Daisuke; Kuroyama, Takahiro; Matsumoto, Masato; Itoh, Tomoo; Kuramoto, Yoji; Ueno, Yasushi
Segmental arterial mediolysis (SAM) is not yet well known in the neurosurgical field, even though it has become an increasingly recognized pathology in arterial dissection. A case of SAM presented as subarachnoid hemorrhage (SAH) due to a dissecting aneurysm of the left intracranial vertebral artery (VA), which extended from the proximal VA union to the distal portion of the left posterior inferior cerebellar artery. The lesion was successfully embolized by an endovascular technique. However, subsequent intraperitoneal hemorrhage due to rupture of a fusiform aneurysm of the middle colic artery prompted surgical treatments. The features of the extirpated visceral vascular lesion were compatible with the diagnosis of SAM based on histopathologic examinations. It is very important that SAM is recognized as a systemic disease that affects the central nervous system, visceral arteries, and coronary arteries. The possibility of SAM should always be considered, particularly in patients with ruptured VA dissection-which is nowadays treated by endovascular techniques-since concomitantly involved visceral arteries may cause unexpected hemorrhagic complications other than SAH. Copyright © 2016 Elsevier Inc. All rights reserved.
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. Copyright © 2016 Elsevier Ltd. All rights reserved.
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.
Chung, David Y.; Oka, Fumiaki; Ayata, Cenk
Delayed cerebral ischemia (DCI) is the most feared mechanism of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggest a more complex picture with multiple concurrent and synergistic mechanisms underlying DCI, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SD) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970’s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. Today we know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. Here, we review the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression. PMID:27258442
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.
Chou, Sherry H-Y; Lan, Jing; Esposito, Elga; Ning, MingMing; Balaj, Leonora; Ji, Xunming; Lo, Eng H; Hayakawa, Kazuhide
Recent studies suggest that extracellular mitochondria may be involved in the pathophysiology of stroke. In this study, we assessed the functional relevance of endogenous extracellular mitochondria in cerebrospinal fluid (CSF) in rats and humans after subarachnoid hemorrhage (SAH). A standard rat model of SAH was used, where an intraluminal suture was used to perforate a cerebral artery, thus leading to blood extravasation into subarachnoid space. At 24 and 72 hours after SAH, neurological outcomes were measured, and the standard JC1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanineiodide) assay was used to quantify mitochondrial membrane potentials in the CSF. To further support the rat model experiments, CSF samples were obtained from 41 patients with SAH and 27 control subjects. Mitochondrial membrane potentials were measured with the JC1 assay, and correlations with clinical outcomes were assessed at 3 months. In the standard rat model of SAH, extracellular mitochondria was detected in CSF at 24 and 72 hours after injury. JC1 assays demonstrated that mitochondrial membrane potentials in CSF were decreased after SAH compared with sham-operated controls. In human CSF samples, extracellular mitochondria were also detected, and JC1 levels were also reduced after SAH. Furthermore, higher mitochondrial membrane potentials in the CSF were correlated with good clinical recovery at 3 months after SAH onset. This proof-of-concept study suggests that extracellular mitochondria may provide a biomarker-like glimpse into brain integrity and recovery after injury. © 2017 American Heart Association, Inc.
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.
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
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.
Yamada, Shoko M; Aoki, Makoto; Nakane, Makoto; Nakayama, Hitoshi
Steroid therapy is considered to improve clinical symptoms in hypertrophic pachymeningitis. We present a 70-year-old man with idiopathic hypertrophic pachymeningitis, whose clinical signs progressively worsened despite steroid therapy. He died of subarachnoid hemorrhage (SAH) with pituitary apoplexy 2 months after the admission regardless of improvement of laboratory data and magnetic resonance imaging appearance by one-and-half-month steroid therapy. Autopsy revealed thickened dura mater supporting the diagnosis of hypertrophic pachymeningitis. Brain parenchyma is generally not affected by the disease; however, histological investigation suggested that inflammation of the dura caused damage to superior hypophyseal artery resulting in SAH and apoplexy in the anterior lobe of the pituitary gland. The higher dose and the longer duration of steroid therapy should have achieved in our case although most laboratory data recovered within the normal range. The aggressiveness of hypertrophic pachymeningitis must be evaluated by clinical signs rather than by laboratory data or imaging examinations.
Wu, An; Liu, Rongcai; Dai, Weimin; Jie, Yuanqing; Yu, Guofeng; Fan, Xiaofeng; Huang, Qiang
Early brain injury (EBI), following subarachnoid hemorrhage (SAH), includes blood-brain barrier (BBB) disruption and consequent edema formation. This study aims to evaluate the effect of lycopene on early brain injury and inflammation in SAH. Neurological deficits, brain water content and Evans blue dye extravasation were evaluated after the treatment with lycopene. Besides neuronal apoptosis,some inflammatory cytokines were also detected. The results suggested that administration of lycopene following SAH significantly ameliorated EBI, including brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In addition, it also ameliorated inflammation triggered by SAH. In conclusion, post-SAH lycopene administration may attenuate EBI in SAH, possibly through ameliorating neuronal apoptosis, maintaining BBB integrity and attenuating inflammation. PMID:26550416
Lee, Min Hyung; Kim, Sang Uk; Lee, Dong Hoon; Kim, Young Il; Cho, Chul Bum; Yang, Seung Ho; Kim, Il Sup; Hong, Jae Taek; Sung, Jae Hoon; Lee, Sang Won
Non-traumatic convexal subarachnoid hemorrhage (CSAH) is a comparatively infrequent with various vascular and nonvascular causes, it rarely occurs concomitant to acute ischemic stroke. We report a case of a 59-year-old woman, visited emergency room with right side subjective weakness spontaneously. Magnetic resonance diffusion-weighted images revealed an acute infarction of anterior cerebral arterial territory. Computed tomographic angiography showed a left frontal CSAH without any vascular lesions. And other laboratory studies were non-specific. We treated with dual antiplatelet drugs (cilostazole [Otsuka Pharmaceutical Co., Ltd. tokyo, Japan] and Aspirin [Bayer Pharma AG., Leverkusen, Germany]). She has done well for a follow-up period. (5 months) This case demonstrates the CSAH with acute infarction is rare but need to work up to identify the etiology and antiplatelet dugs are taken into account for treatments.
Milner, Eric; Holtzman, Jacob C; Friess, Stuart; Hartman, Richard E; Brody, David L; Han, Byung H; Zipfel, Gregory J
Cognitive dysfunction is the primary driver of poor long-term outcome in aneurysmal subarachnoid hemorrhage (SAH) survivors; modeling such deficits preclinically is thus key for mechanistic and translational investigation. Although rat SAH causes long-term deficits in learning and memory, it remains unknown whether similar deficits are seen in the mouse, a species particularly amenable to powerful, targeted genetic manipulation. We thus subjected mice to endovascular perforation SAH and assessed long-term cognitive outcome via the Morris water maze (MWM), the most commonly used metric for rodent neurocognition. No significant differences in MWM performance (by either of two protocols) were seen in SAH versus sham mice. Moreover, SAH caused negligible hippocampal CA1 injury. These results undercut the potential of commonly used methods (of SAH induction and assessment of long-term neurocognitive outcome) for use in targeted molecular studies of SAH-induced cognitive deficits in the mouse. PMID:24938403
Kruyt, Nyika D; Biessels, Geert Jan; DeVries, J Hans; Luitse, Merel J A; Vermeulen, Marinus; Rinkel, Gabriel J E; Vandertop, W Peter; Roos, Yvo B
Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) occurs frequently and is associated with delayed cerebral ischemia (DCI) and poor clinical outcome. In this review, we highlight the mechanisms that cause hyperglycemia after aSAH, and we discuss how hyperglycemia may contribute to poor clinical outcome in these patients. As hyperglycemia is potentially modifiable with intensive insulin therapy (IIT), we systematically reviewed the literature on IIT in aSAH patients. In these patients, IIT seems to be difficult to achieve in terms of lowering blood glucose levels substantially without an increased risk of (serious) hypoglycemia. Therefore, before initiating a large-scale randomized trial to investigate the clinical benefit of IIT, phase II studies, possibly with the help of cerebral blood glucose monitoring by microdialysis, will first have to improve this therapy in terms of both safety and adequacy. PMID:20628402
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
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.
Mondel, Prabath Kumar; Saraf, Rashmi; Limaye, Uday S
A 43-year-old man presented with acute subarachnoid hemorrhage. He was investigated and found to have a rare posterior condylar canal dural arteriovenous fistula (DAVF). DAVFs of the posterior condylar canal are rare. Venous drainage of the DAVF was through a long, tortuous, and aneurysmal bridging vein. We describe the clinical presentation, cross sectional imaging, angiographic features, and endovascular management of this patient. The patient was treated by transarterial embolization of the fistula through the ascending pharyngeal artery. This is the first report of an acutely bled posterior condylar canal DAVF treated by transarterial Onyx embolization with balloon protection in the vertebral artery. The patient recovered without any neurological deficit and had an excellent outcome. On 6 month follow-up angiogram, there was stable occlusion of the dural fistula. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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.
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.
Ibrahim, George M; Morgan, Benjamin R; Macdonald, R Loch
Predictors of outcome after aneurysmal subarachnoid hemorrhage have been determined previously through hypothesis-driven methods that often exclude putative covariates and require a priori knowledge of potential confounders. Here, we apply a data-driven approach, principal component analysis, to identify baseline patient phenotypes that may predict neurological outcomes. Principal component analysis was performed on 120 subjects enrolled in a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. Correlation matrices were created using a combination of Pearson, polyserial, and polychoric regressions among 46 variables. Scores of significant components (with eigenvalues>1) were included in multivariate logistic regression models with incidence of severe angiographic vasospasm, delayed ischemic neurological deficit, and long-term outcome as outcomes of interest. Sixteen significant principal components accounting for 74.6% of the variance were identified. A single component dominated by the patients' initial hemodynamic status, World Federation of Neurosurgical Societies score, neurological injury, and initial neutrophil/leukocyte counts was significantly associated with poor outcome. Two additional components were associated with angiographic vasospasm, of which one was also associated with delayed ischemic neurological deficit. The first was dominated by the aneurysm-securing procedure, subarachnoid clot clearance, and intracerebral hemorrhage, whereas the second had high contributions from markers of anemia and albumin levels. Principal component analysis, a data-driven approach, identified patient phenotypes that are associated with worse neurological outcomes. Such data reduction methods may provide a better approximation of unique patient phenotypes and may inform clinical care as well as patient recruitment into clinical trials. http://www.clinicaltrials.gov. Unique identifier: NCT00111085.
Bellolio, M Fernanda; Hess, Erik P; Gilani, Waqas I; VanDyck, Tyler J; Ostby, Stuart A; Schwarz, Jessica A; Lohse, Christine M; Rabinstein, Alejandro A
We aim to externally validate the Ottawa subarachnoid hemorrhage (OSAH) clinical decision rule. This rule identifies patients with acute nontraumatic headache who require further investigation. We conducted a medical record review of all patients presenting to the emergency department (ED) with headache from January 2011 to November 2013. Per the OSAH rule, patients with any of the following predictors require further investigation: age 40 years or older, neck pain, stiffness or limited flexion, loss of consciousness, onset during exertion, or thunderclap. The rule was applied following the OSAH rule criteria. Patients were followed up for repeat visits within 7 days of initial presentation. Data were electronically harvested from the electronic medical record and manually abstracted from individual patient charts using a standardized data abstraction form. Calibration between trained reviewers was performed periodically. A total of 5034 ED visits with acute headache were reviewed for eligibility. There were 1521 visits that met exclusion criteria, and 3059 had headache of gradual onset or time to maximal intensity greater than or equal to 1 hour. The rule was applied to 454 patients (9.0%). There were 9 cases of subarachnoid hemorrhage (SAH), yielding an incidence of 2.0% (95% confidence interval [CI], 1.0%-3.9%) in the eligible cohort. The sensitivity for SAH was 100% (95% CI, 62.9%-100%); specificity, 7.6% (95% CI, 5.4%-10.6%); positive predictive value, 2.1% (95% CI 1.0%-4.2%); and negative predictive value, 100% (95% CI, 87.4%-100%). The OSAH rule was 100% sensitive for SAH in the eligible cohort. However, its low specificity and applicability to only a minority of ED patients with headache (9%) reduce its potential impact on practice. Copyright © 2014 Elsevier Inc. All rights reserved.
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
Laidlaw, John D; Siu, Kevin H
We sought to determine whether the rebleeding rate in poor-grade patients justified a period of supportive observation before selective treatment and whether unselected ultraearly surgery would lead to acceptable results. A prospectively audited, nonselected series of 177 consecutive poor-grade (i.e., World Federation of Neurological Surgeons Grades IV and V) patients with aneurysmal subarachnoid hemorrhage managed during a 9-year period was analyzed. A management policy of aggressive ultraearly surgery (not selected by age or by grade) was followed. Coiling was not available. Outcomes were assessed at 3 months. Despite the aggressive management policy, surgery could be performed in only 132 poor-grade patients (75%). Twenty percent of all patients were 70 years of age or older (15% of the surgical cases). All surgery was performed within 12 hours of subarachnoid hemorrhage (majority <6 h). Preoperative rebleeding occurred within the first 12 hours (>85% within 6 h) in 20% of the patients, which is four times the rate found in good-grade patients managed according to the same policy. Outcome assessment performed at 3 months in the 132 poor-grade surgical patients revealed that 40% were independent, 15% were dependent, and 45% had died. There was no significant difference in outcomes for young and old (70+ yr) poor-grade surgical patients (P > 0.05). The high ultraearly rebleeding rate indicates a need to urgently secure the ruptured aneurysm by performing surgery or coiling, and this indication is more pronounced for poor-grade patients than for good-grade patients. The outcome results of ultraearly surgery indicate that a nonselective policy does not lead to a large number of dependent survivors, even among elderly poor-grade patients.
Bhambri, Pallavi; Sarvi, Ali; Wong, John H; Sundararaj, Uttandaraman; Mitha, Alim P
The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm. Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days. Electrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase. Development of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Tam, Alan K H; Kapadia, Anish; Ilodigwe, Don; Li, Zeyu; Schweizer, Tom A; Macdonald, R Loch
Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH. This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis. Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group-5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit. Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.
Witsch, Jens; Frey, Hans-Peter; Patel, Sweta; Park, Soojin; Lahiri, Shouri; Schmidt, J Michael; Agarwal, Sachin; Falo, Maria Cristina; Velazquez, Angela; Jaja, Blessing; Macdonald, R Loch; Connolly, E Sander; Claassen, Jan
To create a multidimensional tool to prognosticate long-term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours after admission. Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data. Twelve-month functional, cognitive, and quality of life outcomes were measured using the modified Rankin scale (mRS), Telephone Interview for Cognitive Status, and Sickness Impact Profile. Based on the LM residuals, we constructed the FRESH score (Functional Recovery Expected after Subarachnoid Hemorrhage). Score performance, discrimination, and internal validity were tested using the area under the receiver operating characteristic curve (AUC), Nagelkerke and Cox/Snell R(2) , and bootstrapping. For external validation, we used a control population of SAH patients from the CONSCIOUS-1 study (n = 413). The FRESH score was composed of Hunt & Hess and APACHE-II physiologic scores on admission, age, and aneurysmal rebleed within 48 hours. Separate scores to prognosticate 1-year cognition (FRESH-cog) and quality of life (FRESH-quol) were developed controlling for education and premorbid disability. Poor functional outcome (mRS = 4-6) for score levels 1 through 9 respectively was present in 3, 6, 12, 38, 61, 83, 92, 98, and 100% at 1-year follow-up. Performance of FRESH (AUC = 0.90), FRESH-cog (AUC = 0.80), and FRESH-quol (AUC = 0.78) was high. External validation of our cohort using mRS as endpoint showed satisfactory results (AUC = 0.77). To allow for convenient score calculation, we built a smartphone app available for free download. FRESH is the first clinical tool to prognosticate long-term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46-58. © 2016 American Neurological Association.
Lovelock, C E; Rinkel, G J E; Rothwell, P M
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. 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. 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. 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.
JI, Yong; MENG, Qin-Hu; WANG, Zhi-Gang
The aim of this study was to investigate the dynamic changes in the coagulation and fibrinolytic system with subarachnoid hemorrhage. The blood coagulation enzyme-AT complex (TAT), anticoagulant enzyme (AT), tissue plasminogen activator (tPA), plasminogen activin inhibitor (PAI-1), and mean blood flow velocity were measured. The TAT level was significantly higher 6 h after subarachnoid hemorrhage (SAH), whereas AT was significantly lower. These changes were maintained at 12 h to 1 d after SAH, returned to normal at 3 d, significantly changed again at 7 d to 14 d. The tPA level gradually increased after SAH and peaked at 14 d, and then returned to normal at 21 d. The PAI-1 levels were significantly lower than those in the control group 1 d after SAH gradually increased, and returned to normal at 21 d. In the cerebral vasospasm (CVS) groups, the levels of TAT, and AT significantly changed compared to the non-CVS groups after SAH. The PAI-1 levels were higher at 7 d and 14 d, but the changes were not significant. In groups Fisher III and IV as well as Hunt III to V, the TAT, AT, tPA, and PAI-1 levels were significantly higher than those in both Fisher and Hunt I and II 6 h, 12 h, 1 d, 7 d, and 14 d after SAH. The changes in the coagulation and fibrinolytic system of patients with SAH are correlated with the progress and symptoms of SAH as well as the blood content and CVS. PMID:24305025
Kadooka, Keisuke; Hadeishi, Hiromu; Kadooka, Kosuke
Takotsubo cardiomyopathy (TCM) is caused by excessive physical and mental stress, and sometimes causes potentially fatal arrhythmias such as torsades de pointes. This study characterized the features of TCM due to aneurysmal subarachnoid hemorrhage, particularly the delayed normalization of electrocardiograms compared with that of transthoracic echocardiograms. Ten patients with TCM were selected from the 450 patients with subarachnoid hemorrhage treated in our hospital between January 2007 and November 2015. We retrospectively examined these 10 patients with regard to various factors, including durations of abnormal electrocardiographic and echocardiographic findings. All 10 patients were women. Mean age at diagnosis was 69.3 years (range, 40-90 years). Electrocardiographic findings were as follows: inverted or flattened T waves (100%); QTc prolongation >0.45 seconds (90.0%); ST segment elevation (60.0%); and ST segment depression (20.0%). Echocardiograms showed typical findings of TCM in 9 cases and inverted TCM in 1 case. In 1 case, ventral fibrillation was observed. Normalization of electrocardiograms was consistently delayed compared with that of echocardiograms, by more than 3 weeks in at least 5 cases (50%). If follow-up of electrocardiographic parameters is discontinued at the point of normalization of wall motion and the end of the vasospasm period, fatal arrhythmia may occur in the aftermath. This study showed a notable delay in recovery of abnormal electrocardiographic findings compared with the recovery of echocardiographic findings. Sufficient attention to persistent abnormalities on electrocardiography is warranted, even after improvements in cardiac wall motion and the vasospasm period. Copyright © 2017 Elsevier Inc. All rights reserved.
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
Arauz, A; López, M; Cantú, C; Barinagarrementeria, F
Nonaneurysmal subarachnoid hemorrhage (SAH) accounts for 15% to 20% of all the cases of SAH. Its prognosis may vary from complete recovery to different and serious complications. We describe a series of cases with nonaneurysmal SAHs, their clinical and tomographic characteristics and causes as well as long term prognosis. 50 patients diagnosed of SAH and two negative brain angiographies for aneurysm were followed-up for an average period of 62 months. The demographic data of importance, vascular risk factors, were recorded. They were evaluated during the acute phase with the Hunt and Hess clinical scale and Fisher topographic scale. The distribution of the hemorrhage was listed as absent, perimesencephalic, focal, ventricular or diffuse. Presence of rebleeding, death and the functional course, measured by the Rankin modified scale, were recorded during the follow-up. According to this scale, Rankin of 0 to 2 was considered as a favorable prognosis. This series represents 8.6 of all the SAH cases in our hospital. In 6 cases (12%), there was a causal relationship between the use of sympathicomimetic drugs and the development of SAH. In 80% of them, it was not possible to document the cause of the hemorrhage, while difference causes )cerebral venous thrombosis in 4 [8%], spontaneous dissection of the vertebral artery in 2 [4%], vasculitis secondary to neurocystecerosis in 2 [4%], cavernous angioma in 1 [2%] and spinal arteriovenous malformation in 1) were found. Rebleeding did not occur in any of the cases and only one patient died. In 45 patients (90%), the final functional prognosis was good (Rankin 0-2). We found no significant differences between the tomographic pattern of the hemorrhage, initial clinical condition and long term prognosis. Our findings show a low frequency of nonaneurysmal SAH in our population and a diversity of causes greater than those reported by other series. The good functional prognosis in these cases was confirmed.
Background Hydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital. Methods One hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score. Results Hydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without. Conclusions The presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization. PMID:22765765
Chalouhi, Nohra; Whiting, Alex; Anderson, Eliza C; Witte, Samantha; Zanaty, Mario; Tjoumakaris, Stavropoula; Gonzalez, L Fernando; Hasan, David; Starke, Robert M; Hann, Shannon; Ghobrial, George M; Rosenwasser, Robert; Jabbour, Pascal
It is common practice to use a new contralateral bur hole for ventriculoperitoneal shunt (VPS) placement in subarachnoid hemorrhage (SAH) patients with an existing ventriculostomy. At Thomas Jefferson University and Jefferson Hospital for Neuroscience, the authors have primarily used the ventriculostomy site for the VPS. The purpose of this study was to compare the safety of the 2 techniques in patients with SAH. The rates of VPS-related hemorrhage, infection, and proximal revision were compared between the 2 techniques in 523 patients undergoing VPS placement (same site in 464 and contralateral site in 59 patients). The rate of new VPS-related hemorrhage was significantly higher in the contralateral-site group (1.7%) than in the same-site group (0%; p = 0.006). The rate of VPS infection did not differ between the 2 groups (6.4% for same site vs 5.1% for contralateral site; p = 0.7). In multivariate analysis, higher Hunt and Hess grades (p = 0.05) and open versus endovascular treatment (p = 0.04) predicted shunt infection, but the VPS technique was not a predictive factor (p = 0.9). The rate of proximal shunt revision was 6% in the same-site group versus 8.5% in the contralateralsite group (p = 0.4). In multivariate analysis, open surgery was the only factor predicting proximal VPS revision (p = 0.05). The results of this study suggest that the use of the ventriculostomy site for VPS placement may be feasible and safe and may not add morbidity (infection or need for revision) compared with the use of a fresh contralateral site. This rapid and simple technique also was associated with a lower risk of shunt-related hemorrhage. While both techniques appear to be feasible and safe, a definitive answer to the question of which technique is superior awaits a higher level of medical evidence.
Tagami, Takashi; Kuwamoto, Kentaro; Watanabe, Akihiro; Unemoto, Kyoko; Yokobori, Shoji; Matsumoto, Gaku; Yokota, Hiroyuki
Limited evidence supports the use of hemodynamic variables that correlate with delayed cerebral ischemia or pulmonary edema after aneurysmal subarachnoid hemorrhage. The aim of this study was to identify those hemodynamic variables that are associated with delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. A multicenter prospective cohort study. Nine university hospitals in Japan. A total of 180 patients with aneurysmal subarachnoid hemorrhage. None. Patients were prospectively monitored using a transpulmonary thermodilution system in the 14 days following subarachnoid hemorrhage. Delayed cerebral ischemia was developed in 35 patients (19.4%) and severe pulmonary edema was developed in 47 patients (26.1%). Using the Cox proportional hazards model, the mean global end-diastolic volume index (normal range, 680-800 mL/m) was the independent factor associated with the occurrence of delayed cerebral ischemia (hazard ratio, 0.74; 95% CI, 0.60-0.93; p = 0.008). Significant differences in global end-diastolic volume index were detected between the delayed cerebral ischemia and non-delayed cerebral ischemia groups (783 ± 25 mL/m vs 870 ± 14 mL/m; p = 0.007). The global end-diastolic volume index threshold that best correlated with delayed cerebral ischemia was less than 822 mL/m, as determined by receiver operating characteristic curves. Analysis of the Cox proportional hazards model indicated that the mean global end-diastolic volume index was the independent factor that associated with the occurrence of pulmonary edema (hazard ratio, 1.31; 95% CI, 1.02-1.71; p = 0.03). Furthermore, a significant positive correlation was identified between global end-diastolic volume index and extravascular lung water (r = 0.46; p < 0.001). The global end-diastolic volume index threshold that best correlated with severe pulmonary edema was greater than 921 mL/m. Our findings suggest that global end-diastolic volume index impacts both delayed cerebral ischemia
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
Salvatori, Marcus; Kodikara, Sarathchandra; Pollanen, Michael
Traumatic subarachnoid hemorrhage (TSAH) is a life-threatening intracranial bleed often associated with violent assault or motor vehicle accidents. The vast majority of TSAH is associated with rupture of the vertebral artery, although rare cases of traumatic aneurysm of the internal carotid artery (ICA) have been reported. A 27-year-old man was found bleeding and unresponsive following a violent altercation in which he received repeated blows to the head and neck. CT scan showed acute SAH, and death ensued within 24 h. Autopsy revealed generalized bruising of the face, a complete midline mandibular fracture, and massive basal SAH resulting from traumatic rupture of the right terminal internal carotid artery at the origin of the middle cerebral artery. Anterior and posterior neck dissection revealed focal hemorrhage associated with the right neural arch of the first cervical vertebra (C1). Autopsy findings were consistent with TSAH resulting from rupture of the ICA following blunt force trauma to the head. The rupture site in TSAH can be difficult to locate, and injury to the ICA may be overlooked if not routinely examined. Dissection of the neck and skull base is required to ensure accurate identification of the site of vascular injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Xu, Hao-Liang; Garcia, Maggie; Testai, Fernando; Vetri, Francesco; Barabanova, Alexandra; Pelligrino, Dale A; Paisansathan, Chanannait
Aneurysmal subarachnoid hemorrhage (SAH) is a potentially devastating clinical problem. Despite advances in the diagnosis and treatment of SAH, outcome remains unfavorable. An increased inflammatory state, one that is characterized by enhanced leukocyte trafficking has been reported to contribute to neuronal injury in association with multiple brain insults, including hemorrhagic and ischemic stroke. This study was designed to investigate, in rats, the neuropathologic consequences of heightened leukocyte trafficking following SAH, induced via endovascular perforation of the anterior cerebral artery. Experiments focused on the initial 48 h post-SAH and sought to establish whether blockade of vascular adhesion protein-1 (VAP-1), with LJP-1586, was able to provide dose-dependent neuroprotection. Treatment with LJP-1586 was initiated at 6h post-SAH. An intravital microscopy and closed cranial window system, that permitted examination of temporal patterns of rhodamine-6G-labeled leukocyte adhesion/extravasation, was used. Effects of LJP-1586 on neurologic outcomes and leukocyte trafficking at 24 h and 48 h post-SAH were examined. In VAP-1-inhibited vs control rats, results revealed a significant attenuation in leukocyte trafficking at both 24 h and 48 h after SAH, along with an improvement in neurologic outcome. In conclusion, our findings support the involvement of an amplified inflammatory state, characterized by enhanced leukocyte trafficking, during the first 48 h after SAH. VAP-1 blockade yielded neuroprotection that was associated with an attenuation of leukocyte trafficking and improved neurologic outcome. Published by Elsevier B.V.
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.
Aneurysmal subarachnoid hemorrhage (aSAH) is a kind of hemorrhagic stroke with high mortality and morbidity. Although the preoperative diagnosis, surgical clipping, endovascular treatment, and intensive care have progressed in recent years, the overall prognosis of aSAH patients remains poor. In 2011, the Neurocritical Care Society organized an international, multidisciplinary consensus conference addressed the critical care management of SAH. In 2012, the American Stroke Association (AHA) updated the guidelines of diagnosis and treatment of aSAH published in 2009. In 2013, European Stroke Organization established the guideline for management of intracranial aneurysms and SAH. In 2014, the Korean Society of Interventional Neuroradiology (KSIN) published clinical practice guideline for the management of ruptured and unruptured aneurysms. The guideline for diagnosis and management of aSAH for Chinese patients has been drafted in this year. Thus, the diagnosis and management of aSAH is a hot topic in neurosurgery. This editorial summarizes the above mentioned guidelines and focuses on the progress and update of these guidelines. In this article we discuss the advantage and disadvantage of those imaging techniques, the pros and cons of surgical clipping and endovascular treatment.
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
Burkhardt, Jan-Karl; Neidert, Marian Christoph; Stienen, Martin Nikolaus; Schöni, Daniel; Fung, Christian; Roethlisberger, Michel; Corniola, Marco Vincenzo; Bervini, David; Maduri, Rodolfo; Valsecchi, Daniele; Tok, Sina; Schatlo, Bawarjan; Bijlenga, Philippe; Schaller, Karl; Bozinov, Oliver; Regli, Luca
To analyze whether the computed tomography angiography (CTA) spot sign predicts the intraprocedural rupture rate and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). From a prospective nationwide multicenter registry database, 1023 patients with aneurysmal subarachnoid hemorrhage (aSAH) were analyzed retrospectively. Descriptive statistics and logistic regression analysis were used to compare spot sign-positive and -negative patients with aneurysmal intracerebral hemorrhage (aICH) for baseline characteristics, aneurysmal and ICH imaging characteristics, treatment and admission status as well as outcome at discharge and 1-year follow-up (1YFU) using the modified Rankin Scale (mRS). A total of 218 out of 1023 aSAH patients (21%) presented with aICH including 23/218 (11%) patients with spot sign. Baseline characteristics were comparable between spot sign-positive and -negative patients. There was a higher clip-to-coil ratio in patients with than without aICH (both spot sign positive and negative). Median aICH volume was significantly higher in the spot sign-positive group (50 ml, 13-223 ml) than in the spot sign-negative group (18 ml, 1-416; p < 0.0001). Patients with a spot sign-positive aICH thus were three times as likely as those with spot sign-negative aICH to show an intraoperative aneurysm rupture [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.04-8.92, p = 0.046]. Spot sign-positive aICH patients showed a significantly worse mRS at discharge (p = 0.039) than patients with spot sign-negative aICH (median mRS 5 vs. 4). Logistic regression analysis showed that the spot sign was an aICH volume-dependent predictor for outcome. Both spot sign-positive and -negative aICH patients showed comparable rates of hospital death, death at 1YFU and mRS at 1YFU. In this multicenter data analysis, patients with spot sign-positive aICH showed higher aICH volumes and a higher rate of intraprocedural aneurysm rupture, but comparable long
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
Moon, Karam; Albuquerque, Felipe C; Mitkov, Mario; Ducruet, Andrew F; Wilson, David A; Crowley, R Webster; Nakaji, Peter; McDougall, Cameron G
Clinical outcomes of methamphetamine users with aneurysmal subarachnoid hemorrhage (aSAH) are unknown. To analyze differences in presentation, in-hospital morbidity, and outcomes between methamphetamine users and non-users. All 472 patients included in the Barrow Ruptured Aneurysm Trial from 2003 to 2007 were reviewed. Patients with 1- and 3-year follow-up were included in this analysis (n=398). Methamphetamine users were identified as patients who provided a history of methamphetamine use on admission or tested positive on urine toxicology testing. Methamphetamine users were compared with non-users using univariate analysis. Outcomes were then analyzed using multivariate logistic regression models for demographic characteristics, medical comorbidities, radiographic and clinical presentation, and vasospasm. Thirty-one patients (7.8%) were identified as methamphetamine users in this cohort. Methamphetamine users were younger than non-users (mean age 42.8 vs 55 years, p<0.001). In multivariate logistic regression models, methamphetamine use was an independent predictor of poor Glasgow Outcome Scale score at both 1 year (OR=5.02; 95% CI 1.03 to 24.48; p<0.05) and 3 years (OR=7.18; 95% CI 1.73 to 29.87; p=0.007). Other independent predictors in this model included older age, clinical vasospasm, diabetes, and aneurysm size. Cocaine and tobacco use were not significantly associated with poor outcome in our cohort. Methamphetamine use was not significantly associated with vasospasm, higher Fisher or Hunt and Hess grade, or intraparenchymal hemorrhage/intraventricular hemorrhage. Methamphetamine users have significantly worse outcomes at 1 and 3 years following aSAH. Further analysis is necessary to understand the pathological response associated with methamphetamine use in this setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Wang, Haipeng; Yu, Xiaojun; Xu, Guohui; Xu, Guangtao; Gao, Guishan; Xu, Xiaohu
Traumatic subarachnoid hemorrhage (TSAH) related to alcohol abuse is a notable risk factor. Here, we investigated the vascular morphology and biomechanics of TSAH in rat models of acute alcoholic intoxication and chronic alcoholism rats to explore the possible mechanisms of TSAH. Sixty male Sprague-Dawley rats were divided into acute alcoholic intoxication and chronic alcoholism groups. Edible spirituous liquor (56% vol/vol) was intragastrically given (15 mL/kg) once to the rats in the acute group, and given twice daily (8 mL/kg for 2 weeks and 12 mL/kg for another 2 weeks) to rats in the chronic group. A self-made instrument was used to inflict head injury. Whole brain, arterial blood, and thoracic aorta of rats were sampled for morphologic and biomechanical examination. Compared with the acute alcoholic rats, the chronic alcoholic rats showed significant morphologic and biomechanical changes: (1) decreased body weight (p<0.05), (2) higher morbidity and mortality from TSAH (p<0.01), (3) greater mean thickness of vascular wall of subarachnoid small arteries and each layer thickness of thoracic aorta (p<0.05), (4) decreased failure load and corresponding extensibility (60 kPa and limit load) of thoracic aorta, and (5) increased elastic modulus (30 kPa, range in physiologic stress) (p<0.05). Chronic alcoholism can induce the morphologic and biomechanical changes in cerebral vessels and thoracic aorta. The synergistic effect of alcohol abuse and minor blow may be one of the mechanisms of TSAH. High blood pressure from long-term alcohol abuse is also a notable factor.
Wan, Anthony; Jaja, Blessing N R; Schweizer, Tom A; Macdonald, R Loch
OBJECTIVE Intracerebral hematoma (ICH) with subarachnoid hemorrhage (SAH) indicates a unique feature of intracranial aneurysm rupture since the aneurysm is in the subarachnoid space and separated from the brain by pia mater. Broad consensus is lacking regarding the concept that ultra-early treatment improves outcome. The aim of this study is to determine the associative factors for ICH, ascertain the prognostic value of ICH, and investigate how the timing of treatment relates to the outcome of SAH with concurrent ICH. METHODS The study data were pooled from the SAH International Trialists repository. Logistic regression was applied to study the associations of clinical and aneurysm characteristics with ICH. Proportional odds models and dominance analysis were applied to study the effect of ICH on 3-month outcome (Glasgow Outcome Scale) and investigate the effect of time from ictus to treatment on outcome. RESULTS Of the 5362 SAH patients analyzed, 1120 (21%) had concurrent ICH. In order of importance, neurological status, aneurysm location, aneurysm size, and patient ethnicity were significantly associated with ICH. Patients with ICH experienced poorer outcome than those without ICH (OR 1.58; 95% CI 1.37-1.82). Treatment within 6 hours of SAH was associated with poorer outcome than treatment thereafter (adjusted OR 1.67; 95% CI 1.04-2.69). Subgroup analysis with adjustment for ICH volume, location, and midline shift resulted in no association between time from ictus to treatment and outcome (OR 0.99; 95% CI 0.94-1.07). CONCLUSIONS The most important associative factor for ICH is neurological status on admission. The finding regarding the value of ultra-early treatment suggests the need to more robustly reevaluate the concept that hematoma evacuation of an ICH and repair of a ruptured aneurysm within 6 hours of ictus is the most optimal treatment path.
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.
Noble, Adam J; Baisch, Stefanie; Mendelow, A David; Allen, Lizanne; Kane, Philip; Schenk, Thomas
A subarachnoid hemorrhage reduces patients' quality of life (QoL) in both the short and long term. Neurological problems alone cannot explain this reduction. We examined whether posttraumatic stress disorder (PTSD) and fatigue provide an explanation. We prospectively studied a representative sample of 105 subarachnoid hemorrhage patients. Patients were examined at approximately 3 and 13 months postictus. Examinations included assessments of PTSD, fatigue, sleep, cognitive and physical outcomes, and QoL. Patients' coping skills were also assessed. Regression analyses identified predictors for QoL and PTSD. Thirty-seven percent met the diagnostic criteria for PTSD at both assessment points. This is a fourfold increase compared with the rate of PTSD in the general population. Fatigue in patients was also consistently elevated, higher, in fact, than the notoriously high fatigue level reported for cancer patients undergoing chemotherapy. PTSD was the best predictor for mental QoL, the domain most persistently impaired. It also helped predict physical QoL. Moreover, PTSD was linked to increased sleep problems and may, therefore, have led to fatigue in both the acute and later stages of recovery. To establish the cause of PTSD, a logistic regression was performed. This showed that maladaptive coping was the best predictor of PTSD. PTSD explains why some subarachnoid hemorrhage patients, despite relatively good clinical outcomes, continue to experience a reduced QoL. Given that maladaptive coping skills seem the main cause of PTSD, teaching patients better coping skills early on might prevent PTSD and QoL reduction.
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.
July, Julius; As'ad, Suryani; Suhadi, Budhianto; Islam, Andi Asadul
One of aneurysmal subarachnoid hemorrhage complication is delayed ischemic neurological deficits (DIND). It is postulated that cortisol dynamics might be associated with the severity of this complication. The goal of the study is to investigate whether the peak of morning serum cortisol levels are associated with the severity of its complication during the course of the disease. This is a prospective cohort study conducted from January 2009 to June 2011, at our institution. The study follows a consecutive cohort of patients for 14 days after the aneurysmal subarachnoid hemorrhage. Serum cortisols, cortisol binding globulin, adenocorticotrophic hormone (ACTH) were measured pre operatively and then on post operative days (POD) 2, 4, 7, and 10. Blood was drawn to coincide with peak cortisol levels between 08.00-09.00 hours. Neurological examinations were conducted at least twice daily and patient outcome were graded according to modified Ranklin Scale. DIND was defined by a decrease in the Glasgow Coma Scale of two or more points compared to the status on POD 1. All the results were analyzed using statistical software, Statistical Package for Social Sciences (SPSS v61; SPSS, Inc., Chicago, IL). Logistic regression analysis was used to compare the relationship between the variables. Thirty six consecutive patients are collected, but only 28 patients (12 M and 16 F) were eligible for the cohort analysis. Average patient age is 50.75 years old (50.75±12.27), and more than 50% (15/28) arrived with World Federation of Neurologic Surgeons grade 3 or better. Elevated total cortisol levels of more than 24 mg/dl on day 2, 4, and 10 were associated with DIND, and the most significant being on day 4 (P=0.011). These patients also had a higher grade on the modified Ranklin scale of disability. This study shows that the elevated levels of morning total cortisol in the serum are associated with the onset of DIND during the disease course, and it's also associated with bad outcomes.
July, Julius; As’ad, Suryani; Suhadi, Budhianto; Islam, Andi Asadul
Context: One of aneurysmal subarachnoid hemorrhage complication is delayed ischemic neurological deficits (DIND). It is postulated that cortisol dynamics might be associated with the severity of this complication. Aims: The goal of the study is to investigate whether the peak of morning serum cortisol levels are associated with the severity of its complication during the course of the disease. Settings and Design: This is a prospective cohort study conducted from January 2009 to June 2011, at our institution. Materials and Methods: The study follows a consecutive cohort of patients for 14 days after the aneurysmal subarachnoid hemorrhage. Serum cortisols, cortisol binding globulin, adenocorticotrophic hormone (ACTH) were measured pre operatively and then on post operative days (POD) 2, 4, 7, and 10. Blood was drawn to coincide with peak cortisol levels between 08.00-09.00 hours. Neurological examinations were conducted at least twice daily and patient outcome were graded according to modified Ranklin Scale. DIND was defined by a decrease in the Glasgow Coma Scale of two or more points compared to the status on POD 1. Statistical Analysis: All the results were analyzed using statistical software, Statistical Package for Social Sciences (SPSS v61; SPSS, Inc., Chicago, IL). Logistic regression analysis was used to compare the relationship between the variables. Results: Thirty six consecutive patients are collected, but only 28 patients (12 M and 16 F) were eligible for the cohort analysis. Average patient age is 50.75 years old (50.75±12.27), and more than 50% (15/28) arrived with World Federation of Neurologic Surgeons grade 3 or better. Elevated total cortisol levels of more than 24 mg/dl on day 2, 4, and 10 were associated with DIND, and the most significant being on day 4 (P=0.011). These patients also had a higher grade on the modified Ranklin scale of disability. Conclusions: This study shows that the elevated levels of morning total cortisol in the serum are
Todd, Michael M; Hindman, Bradley J; Clarke, William R; Torner, James C; Weeks, Julie B; Bayman, Emine O; Shi, Qian; Spofford, Christina M
We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination
Oishi, Tomoya; Sakai, Naoto; Sameshima, Tetsuro; Kawaji, Hiroshi; Namba, Hiroki
Intradural extramedullary cavernous angiomas of the central nervous system are a rare type of cavernous angioma, but they can cause fatal subarachnoid hemorrhage. The efficacy of resection for this type of cavernous malformations remains uncertain. This is the first report to recommend surgical resection of these types of lesions regardless of the fatal condition. Our patient was a 70-year-old Japanese man who experienced a sudden onset of an occipital headache, followed by bilateral abducens nerve palsy. Magnetic resonance imaging revealed a small amount of hemorrhage in both of the lateral ventricles and an intradural extramedullary mass lesion in the left side of his foramen magnum. Two weeks after the appearance of initial symptoms, he became comatose. A computed tomography scan showed an increase in the subarachnoid intraventricular hemorrhaging and of the acute hydrocephalus. Following ventricular drainage, total tumor resection was performed using the lateral suboccipital transcondylar approach in conjunction with a first cervical hemilaminectomy. We observed a grape-like vascular-rich tumor with calcification that was adhering tightly to the wall of his left vertebral artery. A histopathological examination of the surgery specimen identified it as a cavernous angioma. After placement of a ventriculoperitoneal shunt and 2 months of rehabilitation, he recovered completely. An intradural extramedullary foramen magnum cavernous malformation is quite rare. The fragile surface of our patient's lesion was causing repeated subarachnoid hemorrhage and consequently progressive fatal neurological deterioration. Surgical resection of the lesion to prevent repeated hemorrhage was performed and he recovered fully. Therefore, we recommend surgical resection of the lesion regardless of the potentially fatal condition.
Mark, Dustin G; Hung, Yun-Yi; Offerman, Steven R; Rauchwerger, Adina S; Reed, Mary E; Chettipally, Uli; Vinson, David R; Ballard, Dustin W
Clinical variables can reliably exclude a diagnosis of nontraumatic subarachnoid hemorrhage in patients with negative cranial computed tomography (CT) results. We externally validated 2 decision rules with 100% reported sensitivity for a diagnosis of subarachnoid hemorrhage, among patients undergoing lumbar puncture after a negative cranial CT result: (1) clinical rule: presence of any combination of age 40 years and older, neck pain or stiffness, loss of consciousness, or headache onset during exertion; and (2) imaging rule: cranial CT performed within 6 hours of headache onset. This was a matched case-control study of patients presenting to 21 emergency departments between 2000 and 2011. Patients with a diagnosis of subarachnoid hemorrhage as determined by lumbar puncture after a negative cranial CT result were screened for inclusion. A matched control cohort was selected among patients with a diagnosis of headache after negative cranial CT and lumbar puncture results. Fifty-five cases of subarachnoid hemorrhage meeting inclusion criteria were identified, 34 (62%) of which were attributed to cerebral aneurysms. External validation of the clinical rule demonstrated a sensitivity of 97.1% (95% confidence interval [CI] 88.6% to 99.7%), a specificity of 22.7% (95% CI 16.6% to 29.8%), and a negative likelihood ratio of 0.13 (95% CI 0.03 to 0.61) for a diagnosis of subarachnoid hemorrhage. External validation of the imaging rule revealed that 11 of 55 subarachnoid hemorrhage cases (20%) had negative cranial CT results for tests performed within 6 hours of headache onset. The clinical rule demonstrated useful Bayesian test characteristics when retrospectively validated against this patient cohort. The imaging rule, however, failed to identify 20% of subarachnoid hemorrhage patients with a negative cranial CT result. Copyright © 2012 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.
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.
Dhar, Rajat; Diringer, Michael N
Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome (SIRS). This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia, contributing to worse outcome. We ascertained the frequency and predictors of SIRS after spontaneous SAH, and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome. Retrospective analysis of prospectively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute, non-traumatic SAH between 2002 and 2005. A daily SIRS score was derived by summing the number of variables meeting standard criteria (HR >90, RR >20, Temperature >38 degrees C, or <36 degrees C, WBC count <4,000 or >12,000). SIRS was considered present if two or more criteria were met, while SIRS burden over the first four days was calculated by averaging daily scores. Regression modeling was used to determine the relationship among SIRS burden (after controlling for confounders including infection, surgery, and corticosteroid use), symptomatic vasospasm, and outcome, determined by hospital disposition. SIRS was present in over half the patients on admission and developed in 85% within the first four days. Factors associated with SIRS included poor clinical grade, thick cisternal blood, larger aneurysm size, higher admission blood pressure, and surgery for aneurysm clipping. Higher SIRS burden was independently associated with death or discharge to nursing home (OR 2.20/point, 95% CI 1.27-3.81). All of those developing clinical vasospasm had evidence of SIRS, with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits (OR 1.77/point, 95% CI 1.12-2.80). Systemic inflammatory activation is common after SAH even in the absence of infection; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping. Higher burden of
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.
Deibert, Ellen; Barzilai, Benico; Braverman, Alan C; Edwards, Dorothy Farrar; Aiyagari, Venkatesh; Dacey, Ralph; Diringer, Michael
Aneurysmal subarachnoid hemorrhage (SAH) is associated with electrocardiographic abnormalities, regional or focal wall-motion abnormalities on echocardiograms, and/or increased creatine kinase MB isoenzyme (CK-MB) or cardiac troponin I (cTnI). The goal of this prospective study was to compare the sensitivity and specificity of cTnI with those of CK-MB in the prediction of left ventricular dysfunction on echocardiograms in patients with nontraumatic SAH. In addition, those patients with abnormal findings on their echocardiograms and elevated cTnI levels were further evaluated for the presence of coronary artery disease (CAD) by a cardiologist and to determine whether any left ventricular dysfunction that had been detected was reversible. The authors obtained electrocardiograms and echocardiograms, and measured serial levels of cardiac enzymes (CK-MB and cTnI) in 43 patients with nontraumatic SAH. Patients with known CAD were excluded. Those patients found to have elevated enzyme levels and abnormal findings on their echocardiograms underwent additional evaluation for CAD. The sensitivity and specificity of both cTnI and CK-MB for detecting left ventricular function were determined. Twenty-eight percent of patients with SAH in the study had elevated cTnI levels within the first 24 hours after hemorrhage. Seven of the 12 patients had evidence of left ventricular dysfunction on echocardiograms. In all these patients a return to baseline function was found during follow-up examinations. The authors found that cTnI is much more sensitive than CK-MB (100% compared with 29%) in the detection of left ventricular dysfunction in patients with SAH. An elevated level of cTnI is a good indicator of left ventricular dysfunction in patients with SAH. In this study cardiac dysfunction was reversible and should not necessarily preclude these patients from undergoing operative interventions or becoming heart donors. Clinical management may require more aggressive hemodynamic
Kang, Peter; Raya, Amanda; Zipfel, Gregory J; Dhar, Rajat
Hydrocephalus requiring external ventricular drain (EVD) or shunt placement commonly complicates aneurysmal subarachnoid hemorrhage (SAH), but its frequency is not as well known for nonaneurysmal SAH (NA-SAH). Those with diffuse bleeding may have greater risk of hydrocephalus compared to those with a perimesencephalic pattern. We evaluated the frequency of hydrocephalus in NA-SAH and whether imaging factors could predict the need for EVD and shunting. We collected admission clinical and imaging variables for 105 NA-SAH patients, including bicaudate index (BI), Hijdra sum score (HSS), intraventricular hemorrhage (IVH) score, modified Fisher scale (mFS), and bleeding pattern. Hydrocephalus was categorized as acute (need for EVD) or chronic (shunt). We applied logistic regression to determine whether hydrocephalus risk was independently related to bleeding pattern or mediated through blood volume or ventriculomegaly. Acute hydrocephalus was seen in 26 (25%) patients but was more common with diffuse (15/28, 54%) versus perimesencephalic (10/59, 17%, p < 0.001) bleeding. Patients developing acute hydrocephalus had worse clinical grade and higher BI, HSS, and IVH scores. Adjusting the relationship between hydrocephalus and diffuse bleeding for HSS (but not BI) nullified this association. Nine (35%) patients requiring EVD eventually required shunting for chronic hydrocephalus, which was associated with greater blood burden but not poor clinical grade. Acute hydrocephalus occurs in one-quarter of NA-SAH patients. The greater risk in diffuse bleeding appears to be mediated by greater cisternal blood volume but not by greater ventriculomegaly. Imaging characteristics may aid in anticipatory management of hydrocephalus in NA-SAH.
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
Zhao, Bing; Fan, Yilin; Xiong, Ye; Yin, Rong; Zheng, Kuang; Li, Zequn; Tan, Xianxi; Yang, Hua; Zhong, Ming
Aneurysm rebleeding is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH) and more often occurs in patients with poor-grade aSAH. Limited data on predictors of rebleeding in these patients are available. To investigate predictors of aneurysm rebleeding after poor-grade aSAH and the association of rebleeding with clinical outcomes. A multicenter poor-grade aneurysm study was a prospective and observational registry of consecutive patients who presented with poor-grade aSAH defined as a World Federation of Neurosurgical Societies (WFNS) grade of IV or V. Rebleeding was defined as a new hemorrhage on computed tomography scan. Clinical outcomes were assessed with modified Rankin score. Multivariate logistic regression analyses were used to determine independent predictors of rebleeding and association between the rebleeding and clinical outcomes at 12months. Of the 297 patients included in this study, 30 (10.1%) patients experienced rebleeding. Most rebleeding occurred within 24h after ictus. 22 (73.3%) patients died at discharge. Aneurysm rebleeding was independently associated with poor outcome (odds ratio [OR] 36.37, p<0.001) and associated with mortality (OR 25.03, p<0.001) at 12months. The multivariate analysis showed that a lower Fisher grade (OR 0.49, 95% CI 0.31-0.77; p=0.002), ruptured anterior cerebral artery aneurysms (OR 4.26, 95% CI 1.07-16.90; p=0.039), external ventricular drainage (OR 4.62, 95% CI 1.46-14.59; p=0.009) were independently associated with aneurysm rebleeding. The outcome of aneurysm rebleeding remains very poor. A lower Fisher grade, ruptured anterior cerebral artery aneurysms, external ventricular drainage were associated with increased risk of rebleeding. Copyright © 2016 Elsevier B.V. All rights reserved.
Simard, J. Marc; Aldrich, E. Francois; Schreibman, David; James, Robert F.; Polifka, Adam; Beaty, Narlin
Object Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. Methods The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. Results Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). Conclusions In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial. PMID:24032706
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.
Čomić, Hata; Rinkel, Gabriel J E; Vergouwen, Mervyn D I
If acute severe headache disappears early after its onset, the question arises whether subarachnoid hemorrhage (SAH) should still be ruled out. We studied the initial time-course and minimal duration of headache in a consecutive series of neurologically intact patients with spontaneous SAH. We included patients admitted between 2012 and 2015 within 48h after spontaneous SAH with a normal level of consciousness and no focal deficits. We retrieved data on headache severity, measured with a Numeric Rating Scale (NRS), <48h after ictus. We analyzed the proportion of patients with a first NRS 0 and NRS <3 within 48h after ictus and minimal headache duration. Patients were censored in case of a decrease in level of consciousness, aneurysm treatment, or early discharge. We included 106 patients (62 aneurysmal SAH, 33 perimesencephalic hemorrhage, 11 other spontaneous SAH). All patients were treated with analgesics. Within 48h after ictus, a first NRS 0 was reported by 9 patients (8%;95%CI:3%-14%) and a first NRS <3 by 22 patients (21%;95%CI:13%-28%). Shortest time lapse until NRS 0 was 10h in a patient with aneurysmal SAH who had been on acetaminophen and tramadol since 2:35h after ictus. In a cohort of SAH patients with a normal level of consciousness and no focal deficits who all used analgetics, headache disappeared in around 10% within 48h after ictus. Our data indicate that a diagnostic work-up for SAH is also needed in patients using analgesics in whom headache has disappeared after 10h. Copyright © 2017 Elsevier B.V. All rights reserved.
Lannes, Marcelo; Teitelbaum, Jeanne; del Pilar Cortés, Maria; Cardoso, Mauro; Angle, Mark
For the treatment of cerebral vasospasm, current therapies have focused on increasing blood flow through blood pressure augmentation, hypervolemia, the use of intra-arterial vasodilators, and angioplasty of proximal cerebral vessels. Through a large case series, we present our experience of treating cerebral vasospasm with a protocol based on maintenance of homeostasis (correction of electrolyte and glucose disturbances, prevention and treatment of hyperthermia, replacement of fluid losses), and the use of intravenous milrinone to improve microcirculation (the Montreal Neurological Hospital protocol). Our objective is to describe the use milrinone in our practice and the neurological outcomes associated with this approach. Large case series based on the review of all patients diagnosed with delayed ischemic neurologic deficits after aneurysmal subarachnoid hemorrhage between April 1999 and April 2006. 88 patients were followed for a mean time of 44.6 months. An intravenous milrinone infusion was used for a mean of 9.8 days without any significant side effects. No medical complications associated with this protocol were observed. There were five deaths; of the surviving patients, 48.9 % were able to go back to their previous baseline and 75 % had a good functional outcome (modified Rankin scale ≤ 2). A protocol using intravenous milrinone, and the maintenance of homeostasis is simple to use and requires less intensive monitoring and resources than the standard triple H therapy. Despite the obvious limitations of this study's design, we believe that it would be now appropriate to proceed with formal prospective studies of this protocol.
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.
Lo, Benjamin W Y; Fukuda, Hitoshi; Nishimura, Yusuke; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H
Clinical prediction tools assist in clinical outcome prediction. They quantify the relative contributions of certain variables and condense information that identifies important indicators or predictors to a targeted condition. This systematic review synthesizes and critically appraises the methodologic quality of studies that derive both clinical predictors and clinical predictor tools used to determine outcome prognosis in patients suffering from aneurysmal subarachnoid hemorrhage (SAH). This systematic review included prospective and retrospective cohort studies, and randomized controlled trials (RCTs) investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adult patients with aneurysmal SAH. Twenty-two studies were included in this systemic review. Independent, confounding, and outcome variables were studied. Methodologic quality of individual studies was also analyzed. Included were 3 studies analyzing databases from RCTs, 8 prospective cohort studies, and 11 retrospective cohort studies. The most frequently retained significant clinical prognostic factors for long-term neurologic outcome prediction include age, neurological grade, blood clot thickness, and aneurysm size. Systematic reviews for clinical prognostic factors and clinical prediction tools in aneurysmal SAH face a number of methodological challenges. These include within and between study patient heterogeneity, regional variations in treatment protocols, patient referral biases, and differences in treatment, and prognosis viewpoints across different cultures.
Acuña, Mónica Y; A Cifuentes, Lucía
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. 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. 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. 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.
Zheng, Bingjie; Liu, Huailei; Wang, Ruke; Xu, Shancai; Liu, Yaohua; Wang, Kaikai; Hou, Xu; Shen, Chen; Wu, Jianing; Chen, Xin; Wu, Pei; Zhang, Guang; Ji, Zhiyong; Wang, Hongyu; Xiao, Yao; Han, Jianyi; Shi, Huaizhang; Zhao, Shiguang
Subarachnoid hemorrhage (SAH) is an important cause of mortality in stroke patients. Long non-coding RNAs (LncRNAs) have important functions in brain disease, however their expression profiles in SAH remain to be elucidated. The present study aimed to investigate the expression signatures of LncRNAs and mRNAs in early brain injury (EBI) following SAH in a rat model. Male Wistar rats were randomly divided into an SAH group and a sham operation group. The expression signatures of the LncRNAs and mRNAs in the temporal lobe cortex were investigated using a rat LncRNAs array following experimental SAH. The results revealed that there were 144 downregulated and 64 upregulated LncRNAs and 181 downregulated and 221 upregulated mRNAs following SAH. Additionally, two upregulated (BC092207, MRuc008hvl) and three downregulated (XR_006756, MRAK038897, MRAK017168) LncRNAs were confirmed using reverse transcription quantitative polymerase chain reaction. The differentially expressed mRNAs were further analyzed using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The pathway analysis results provided by the KEGG database indicated that eight pathways associated with inflammation were involved in EBI following SAH. In conclusion, these results demonstrated that the expression profiles of the LncRNAs and mRNAs were significantly different between the SAH-induced EBI group and the sham operation group. These differently expressed LncRNAs may be important in EBI following SAH.
Otawara, Yasunari; Ogasawara, Kuniaki; Kubo, Yoshitaka; Sasoh, Masayuki; Ogawa, Akira
External cerebrospinal fluid (CSF) drainage is an effective method to remove massive subarachnoid hemorrhage (SAH), but carries the risk of meningitis and shunt-dependent hydrocephalus. This study investigated whether postoperative cisternal CSF drainage affects the incidence of cerebral vasospasm and clinical outcome in patients with thin SAH. Seventy-eight patients with thin SAH, 22 men and 56 women aged from 17 to 73 years (mean 51.2 years), underwent surgical repair for ruptured anterior circulation aneurysm. Patients were divided into groups with (38 patients) and without (40 patients) postoperative cisternal CSF drainage, and the incidences of angiographical and symptomatic vasospasm, shunt-dependent hydrocephalus, meningitis, and the clinical outcome were compared. The incidences of angiographical vasospasm (31.6% vs 50.0%), symptomatic vasospasm (7.9% vs 12.5%), shunt-dependent hydrocephalus (5.3% vs 0%), and meningitis (2.6% vs 0%) did not differ between patients with and without cisternal CSF drainage. All patients in both groups resulted in good recovery. Postoperative cisternal CSF drainage does not affect the incidence of cerebral vasospasm or the clinical outcome in patients with thin SAH. PMID:17969369
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.
Da Silva, Ivan R; Gomes, Joao A; Wachsman, Ari; Rodriguez de Freitas, Gabriel; Provencio, Jose Javier
It is not well understood whether age impacts transcranial Doppler (TCD) mean flow velocities (MFVs) in patients with aneurysmal subarachnoid hemorrhage (SAH) with or without delayed cerebral ischemia (DCI). The aim of our study was to analyze the behavior of TCD MFV during the first 7 days after SAH in patients of different ages and correlate them with the occurrence of DCI. This study is a databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. We analyzed mean MFV of bilateral middle cerebral arteries (MCAs) in all patients enrolled in the study on days 1, 3 and 7. The correlation between age and TCD MFV was analyzed using a univariate linear regression model. Fifty-five patients were studied. Starting on the third day after the bleeding, increasing age was associated with slower MFVs. This trend was not affected by the interrogation of the right or left MCA. After correction to include only patients who developed DCI, the same findings persisted on days 3 and 7. Older age was correlated with a significant decrease on TCD velocities in patients with SAH, even after correction for patients who developed DCI. © 2016 S. Karger AG, Basel.
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
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
Burrell, Christian; Avalon, Nicole E.; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M. Cristine; Freeman, William D.
Introduction Precision medicine is an emerging paradigm aimed at providing individualized prevention and treatment of diseases through understanding and leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage (aSAH) carries tremendous morbidity and mortality with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) proving devastating and unpredictable. The paucity of effective treatment or prevention measures for these conditions could potentially be improved through implementation of precision medicine. Areas covered This review presents the basic pathophysiology of CV and DCI, current treatment guidelines, and evidence for the use of precision medicine in the prediction and prevention of poor outcomes following aSAH. An extensive PubMed literature search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were reviewed. The studies presented focus on biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert Commentary The array of novel biomarkers reviewed here, ranging from genotypes to metabolites, has been found to correlate with CV, DCI, and neurologic outcomes after aSAH. Though their practical use in the clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine in the treatment of aSAH. PMID:27314601
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. PMID:27774520
Uysal, Ender; Yanbuloğlu, Bariş; Ertürk, Mehmet; Kilinç, Bekir M; Başak, Muzaffer
To investigate the diagnostic accuracy of spiral CT angiography (CTA) in detection of cerebral aneurysms in cases with acute subarachnoid hemorrhage (SAH). Spiral CT angiography and DSA examinations were performed in 32 cases due to non-traumatic SAH. CTA data were obtained by maximum intensity projection (MIP) method. CTA and DSA findings were evaluated and compared in terms of existence of aneurysm, size and location. In 32 patients, DSA detected 34 aneurysms with diameters ranging from 3 to 13 mm while four cases were free of aneurysms. With CTA, an aneurysm at anterior communicating artery location could not be demonstrated. In all other cases CTA correlated well with DSA in detecting the site, size and orientation of the aneurysms. It was found that CTA sensitivity was 97% and specificity was 100% in diagnosis of intracranial aneurysms. Spiral CTA is a highly accurate, cheap and non-invasive imaging method in diagnosis of intracranial aneurysms in cases with SAH and can be used as a safe alternative method to DSA when emergency surgery is needed.
Limbrick, David D; Behdad, Amir; Derdeyn, Colin P; Custer, Phillip L; Zipfel, Gregory J; Santiago, Paul
Traumatic, nonaneurysmal subarachnoid hemorrhage (SAH) is common after closed head injury and most often results from ruptured cortical microvessels. Here, the authors present the case of a 60-year-old woman who fell and struck her head, causing traumatic enucleation and avulsion of both the optic nerve and ophthalmic artery. The arterial avulsion caused a Fisher Grade 3 SAH. During her stay in the intensive care unit, hydrocephalus and vasospasm developed, clinical conditions commonly observed after aneurysmal SAH. Epileptiform activity also developed, although this may have been related to concurrent Pantoea agglomerans ventriculitis. It is reasonable to suggest that intracerebral arterial avulsion with profuse arterial bleeding may be more likely than traditional traumatic SAH to result in clinical events similar to that of aneurysmal SAH. Special consideration should be given to the acute care of patients with intracranial arterial avulsions (conservative management vs surgical exploration or endovascular treatment), as well as long-term follow-up for vascular or other neurosurgical complications.
Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed. SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH. Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult. PMID:24386932
Ishikawa, Kouhei; Omori, Kazuhiko; Takeuchi, Ikuto; Jitsuiki, Kei; Yoshizawa, Toshihiko; Ohsaka, Hiromichi; Nakao, Yasuaki; Yamamoto, Takuji; Yanagawa, Youichi
We investigated the changes in the vital signs and the final outcomes subarachnoid hemorrhage (SAH) patients who were evacuated from the scene using the doctor-helicopter (Dr. Heli) service and those who only underwent interhospital transportation using the doctor-helicopter Dr. Heli service to investigate safety of this system. We retrospectively investigated all of the patients with non-traumatic SAH who were transported by a Dr. Heli between January 2010 and March 2016. The subjects were divided into two groups: the Scene group included subjects who were evacuated from the scene by a Dr. Heli, while the Interhospital group included subjects who were transported by a ground ambulance to a nearby medical facility and then transported by a Dr. Heli to a single tertiary center. The systolic blood pressure, ratio of cardiac arrest, and Fisher classification values of the patients in the Scene group were significantly greater than those in the Interhospital group. The Glasgow Coma Scale in the Scene group was significantly lower than that in the Interhospital group. After excluding the patients with cardiac arrest, the Glasgow Coma Scale scores of the patients in the two groups did not differ to a statistically significant extent during, before or after transportation. There were no significant differences in Glasgow Outcome Scores or the survival ratio of the two groups, even when cardiac arrest patients were included. The present study indirectly suggests the safety of using a Dr. Heli to evacuate SAH patients from the scene. Copyright © 2016 Elsevier Inc. All rights reserved.
Ramgren, B; Cronqvist, M; Romner, B; Brandt, L; Holtås, S; Larsson, E-M
We have reviewed initial diagnostic features, treatment, and outcome in 29 patients with acute subarachnoid hemorrhage due to non-traumatic vertebrobasilar artery dissection diagnosed in our hospital between 1993 and 2003. The dissections occurred in the vertebral artery in 19 patients, the posterior inferior cerebellar artery (PICA) in two patients, the basilar artery in four patients, and in the vertebral artery extending into the PICA in four patients. A pseudoaneurysm was found in 20 patients. Clinical manifestations typically included sudden onset of moderate to severe headache, nuchal rigidity, and drowsiness. Fourteen patients were treated conservatively. Fifteen patients underwent endovascular treatment with either parent artery occlusion (13 patients) or aneurysmal coil occlusion with preservation of the parent artery (2 patients). Re-bleeding occurred within 12 days and before treatment in nine patients. Eight of these had a pseudoaneurysm. No patient bled after endovascular treatment. Poor grade and early re-bleeding were associated with less favorable outcome. Outcome at 6 months did not differ significantly between endovascular and conservative treatment. Altogether, good recovery was achieved for 16 patients, moderate disability was seen in one, severe disability in four, and eight patients (27%) died. The absence of bleeding subsequent to endovascular treatment in this study suggests that endovascular treatment may be a rational approach in these patients at high risk of re-bleeding, especially those with a pseudoaneurysm.
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.
Chen, Wei-Lung; Huang, Chi-Hung; Chen, Jiann-Hwa; Tai, Henry Chih-Hung; Chang, Su-Hen; Wang, Yung-Cheng
The study aims to assess if electrocardiographic (ECG) abnormalities could predict the development of neurogenic pulmonary edema (NPE) within 24 hours in cases of spontaneous subarachnoid hemorrhage (SAH). We studied prospectively a cohort of 269 adult patients with nontraumatic SAH in an emergency department of a university-affiliated medical center. A 12-lead ECG was taken for these patients. The patients were stratified into NPE and non-NPE based on serially clinical and radiologic findings. The ECG abnormalities were compared between these 2 groups of patients. Compared with the non-NPE (n = 229), the NPE (n = 40) had significantly higher World Federation of Neurological Surgeons class (P < .001), higher Hunt-Hess scale (P < .001), and higher prevalence of diabetes mellitus (P = .033). In addition, the percentage of ECG morphological abnormality was significantly higher in NPE, in which nonspecific ST- or T-wave changes (NSSTTCs) are significantly higher. Multiple logistic regression model identified World Federation of Neurological Surgeons class (95% confidence interval [CI], 2.6-13.3; P < .001), abnormal Q or QS wave (95% CI, 1.1-9.1; P = .038), and NSSTTCs (95% CI, 1.2-7.5; P = .016) as the significant variables associated with NPE. Electrocardiographic abnormalities, especially abnormal Q or QS wave and NSSTTCs, may predict the development of NPE within 24 hours in adult patients with spontaneous SAH. Copyright © 2015 Elsevier Inc. All rights reserved.
Boluijt, Jacoline; Meijers, Joost CM; Rinkel, Gabriel JE; Vergouwen, Mervyn DI
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. PMID:25690473
Wu, Te-Chang; Tsui, Yu-Kun; Chen, Tai-Yuan; Lin, Chien-Jen; Wu, Tai-Ching; Tzeng, Wen-Sheng
For patients with subarachnoid hemorrhage (SAH), computed tomography angiography (CTA) has been the first imaging modality for aneurysm detection. We evaluate the rate, time distribution, risk factors, and clinical outcome of aneurysmal rebleeding by CTA findings. Consecutive patients with SAH presenting to our hospital, a tertiary care hospital, were retrospectively included. We reviewed images for all patients receiving an initial noncontrast computed tomography scan and further CTA for nontraumatic SAH surveillance with focus on rebleeding evidence. A total of 12 patients with early aneurysmal rebleeding (12/110 patients [10.9%]) within 6 hours after emergency room arrival were found with dismal outcome (50% mortality) and 3 rebleeding patterns: pattern 1 of rapid active bleeding with contrast extravasation, pattern 2 of slow active bleeding with contrast leakage in the delayed venous phase, and pattern 3 of hematoma enlargement. The risk factor and poor prognostic sign include larger aneurysm diameter (≧7 mm) and contrast extravasation during CTA. Rebleeding rate of aneurysmal SAH in the hyperacute stage at less than 6 hours is 10.9% with poor prognosis in this study, especially in patients with active bleeding demonstrated in CTA.
Whiting, Jobyna; Reavey-Cantwell, John; Velat, Gregory; Fautheree, Gregory; Firment, Christopher; Lewis, Stephen; Hoh, Brian
Angiogram-negative subarachnoid hemorrhage (SAH) accounts for 15% of nontraumatic SAH and has been reported with low morbidity and mortality rates. We report on a large series of patients with angiogram-negative SAH who experienced an atypical nonbenign clinical course. Between December 2001 and November 2006, 95 patients with spontaneous nonaneurysmal SAH and negative initial angiographic evaluation were treated at the University of Florida. The authors retrospectively reviewed the patients' medical records and radiological images to determine associated morbidity and mortality. Aneurysms were found in 6 of the 95 patients on follow-up imaging after an initial negative angiogram (6.3% false negative rate); these patients were excluded leaving 89 patients as the study group. Hydrocephalus necessitating temporary CSF diversion developed in 22 of these patients (25%); 12 (13%) ultimately required permanent CSF diversion. Clinically significant vasospasm developed in 4 patients (4%), and 2 (2%) had cerebral infarctions. Three patients (3%) died. The authors' experience with a large series of angiogram-negative SAH patients who had an atypical nonbenign clinical course associated with hydrocephalus, vasospasm, stroke, and mortality differs significantly from previously published case series of angiogram-negative SAH.
Guterman, Elan L; Kamel, Hooman; Azran, Carmil; Shah, Maulik P; Claude Hemphill, J; Smith, Wade S; Navi, Babak B
The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population. We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients' baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS). Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86%, 95% CI 78-95%). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95% CI 0.987-1.001). In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.
Ringelstein, A; Mueller, O; Goericke, S L; Moenninghoff, C; Sure, U; Wanke, I; Forsting, M; Schlamann, M
This study aimed to determine the yield of repetitive catheter angiography (digital subtraction angiography (DSA)) for the detection of causative vascular lesions in patients with nontraumatic subarachnoidal hemorrhage (SAH) and negative initial DSA. We hypothesize that a second DSA might be helpful to detect an initially occult bleeding source. We retrospectively evaluated 649 patients with acute SAH and invasive catheter angiographies between 2004 and 2012. In 90 SAH patients initial imaging was negative concerning a causative bleeding source. A total of 113 repetitive DSA were performed. Two neuroradiologists reanalyzed the initial imaging and the result of the reangiography independently. In 4/90 patients (4.5 %) bleeding source was first detected in the second or third DSA. In all other patients, no causative vascular lesion was found. Reasons for the initially false negative diagnostics were one dissecting aneurysm and thrombosis of three aneurysms within the acute phase of SAH. Repetitive DSA revealed the cause of SAH in 4.5 % of the cases. These findings have a therapeutic and prognostic impact. We think that at least a second DSA should be part of diagnostic work-up in patients with SAH and missing bleeding source, even considering the risk of an additional invasive angiography itself.
Yang, Lijun; Wang, Feng; Han, Haie; Yang, Liang; Zhang, Gengshen; Fan, Zhenzeng
Subarachnoid hemorrhage (SAH) is a life-threatening disease that causes high morbidity and mortality. Pirfenidone is a SAH drug that prevents secondary bleeding and cerebral infarction. To improve its therapeutic efficacy, this study aimed to employ a functionalized graphene oxide nanosheet (FGO) as a drug carrier loading pirfenidone to treat SAH. The graphene oxide nanosheet was introduced with transcription activator peptide (Tat), followed by functionalization with methoxy polyethylene glycol (mPEG) and loading with pirfenidone. The pirfenidone-loaded FGO (pirfenidone-FGO) exhibits better treatment efficacy than the single pirfenidone due to more effective loading and controlled release of the drug in tissue. The introduction of Tat and mPEG onto GO nanosheet contributes to the ability to cross the blood-brain barrier and the stability in blood circulation of the drug. At lower pH values, the highly efficient release of the drug from the pirfenidone-FGO exerts effective treatment to acidic inflammatory lesion after severe SAH. Besides its treatment function, FGO is also shown as a strong near infrared absorbing material which can be applied in photoacoustic imaging, allowing rapid real-time monitoring with deep resolution of brain tissues after SAH. The treatment efficacy of pirfenidone-FGO for central nervous system injuries is further demonstrated by hematoxylin and eosin staining of coronal brain slices, as well as measurements of brain water content and blood-brain barrier permeability. Our study supports the potential of FGO in clinical application in treatment of SAH.
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
Petzold, Axel; Keir, Geoffrey; Kerr, Mary; Kay, Andrew; Kitchen, Neil; Smith, Martin; Thompson, Edward J
Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus. Cerebrospinal fluid (CSF) was collected daily for up to 14 days. CSF GFAP was quantified using a standard ELISA. In the patients, we found that the CSF GFAP values were pathologically elevated in 83/89 (93%) of the CSF samples. The levels were highest on day 1 (median = 47.64 ng/mL) and decreased to 11.19 ng/mL on day 3, leveling out at approximately 1 ng/mL after 10 days. In non-survivors, a secondary rise of GFAP levels became significant during the high-risk period for vasospasm, with median levels of 21.76 ng/mL compared to 2.62 ng/mL in the survivors (p = 0.037) on day 6. This study suggests that CSF GFAP levels are of prognostic value in SAH. Additionally, the difference in the slope of GFAP levels between survivors (rapid wash-out) and non-survivors (secondary peaks) may allow difierentiation between primary brain injury from secondary brain damage due to delayed cerebral ischaemia.
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
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.
Cowperthwaite, Matthew C; Burnett, Mark G
A seasonal and meteorological influence on the incidence of spontaneous subarachnoid hemorrhage (SAH) has been suggested, but a consensus in the literature has yet to emerge. This study examines the impact of weather patterns on the incidence of SAH using a geographically broad analysis of hospital admissions and represents the largest study of the topic to date. We retrospectively analyzed SAH admissions to 155 US hospitals during the calendar years 2004 to 2008 (N = 7758). Daily weather readings for temperature, pressure, and humidity were obtained for the same period from National Oceanic and Atmospheric Administration weather stations located near each hospital. The daily values of each weather variable were associated with the daily volume of SAH admissions using a combination of correlation and time-series analyses. No seasonal trends were observed in the monthly volume of SAH admissions during the study period. No significant correlation was detected between the daily SAH admission volume and the day's weather, the previous day's weather, or the 24-hour weather change. This study represents the most comprehensive investigation of the association between weather and spontaneous SAH to date. The results suggest that neither season nor weather significantly influences the incidence of SAH.
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.
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. Copyright © 2011 Elsevier B.V. All rights reserved.
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
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
Burrell, Christian; Avalon, Nicole E; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M Cristine; Freeman, William D
Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.
Cosar, Murat; Eser, Olcay; Fidan, Huseyin; Sahin, Onder; Buyukbas, Sadik; Ela, Yuksel; Yagmurca, Murat; Ozen, Oguz A
Subarachnoid hemorrhage is a serious condition, often accompanied by cerebral vasospasm, which may lead to brain ischemia and neurologic deterioration. We evaluated if dexmedetomidine has neuroprotective effects in the hippocampus of vasospastic SAH rabbits or not. Eighteen New Zealand rabbits were taken. An experimental SAH model was formed by injecting 0.9 mL of autologous arterial blood per 1 kg of body weight to the cisterna magna of 12 rabbits. Craniotomy was performed in the control group (n = 6) except performing experimental SAH. Rabbits in the SAH-alone (n = 6) group were infused with 5 mL.kg(-1).h(-1) 0.9% sodium chloride, and rabbits (n = 6) in the SAH-dexmedetomidine group were infused with 5 microg.kg(-1).h(-1) dexmedetomidine for 2 hours, 48 hours after SAH was established. Rabbits of all groups were sacrificed via penthotal 24 hours after dexmedetomidine administration. Brains were removed immediately, and hippocampal tissues were blocked from the right hemisphere for histopathologic study. In addition to this, hippocampal tissues of left hemispheres were dissected for biochemical analyses to evaluate MDA levels, activity of XO, and SOD. The histopathologic study showed that dexmedetomidine may have a neuroprotective effect in SAH-induced hippocampal injuries. The biochemical parameters support the neuroprotective effect of dexmedetomidine (P < .05). Our study showed that dexmedetomidine may have a neuroprotective effect in the hippocampus of vasospastic SAH rabbits.
Lewis, Ariane; Irvine, Hannah; Ogilvy, Christopher; Kimberly, W Taylor
Hydrocephalus after subarachnoid hemorrhage (SAH) requires temporary cerebrospinal fluid (CSF) drainage using an external ventricular drain (EVD). This drain is removed if patients pass a clamp trial, or a ventriculoperitoneal shunt (VPS) is placed. Little is known about the risk factors for delayed VPS placement in patients who pass a clamp trial and have their EVD removed. In order to explore the risk factors associated with delayed VPS placement, we studied a retrospective cohort of SAH patients at our institution. We performed a retrospective analysis of SAH patients who had an EVD placed between January 2008 and June 2012 at our institution. We extracted demographic, imaging, and CSF data from the medical record and analyzed risk factors associated with delayed VPS placement. Of 91 patients who passed a clamp trial and had their EVD removed, 12 (13%) required delayed VPS placement at a median of 54 (interquartile range: 15-75) days after EVD removal. After multivariate analysis, risk factors for delayed VPS placement included increased CSF protein concentration within the first 7 days of EVD placement (OR: 1.02, CI: 1-1.04, p=0.023) and increased third ventricular diameter prior to EVD removal (OR: 1.59, CI: 1.11-2.6, p=0.026). Patients with increased CSF protein concentration at time of EVD placement and those with increased third ventricular diameter at time of EVD removal should be carefully monitored for development of delayed hydrocephalus.
Hendrix, Philipp; Foreman, Paul M; Harrigan, Mark R; Fisher, Winfield S; Vyas, Nilesh A; Lipsky, Robert H; Lin, Minkuan; Walters, Beverly C; Tubbs, R Shane; Shoja, Mohammadali M; Pittet, Jean-Francois; Mathru, Mali; Griessenauer, Christoph J
The pathophysiologic mechanisms underlying cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understand. Ryanodine receptors (RYR) are intracellular calcium channels involved in the regulation of vascular smooth muscle cells and cerebrovascular tone and diameter. Previous work reported an association between an RYR polymorphism and cerebral vasospasm. Here, we sought to assess the impact of that RYR polymorphism on aSAH and its clinical sequelae. Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The RYR1 single nucleotide polymorphism (SNP) rs35364374 was detected using 5'exonuclease (Taqman) genotyping assays. Associations between the RYR1 polymorphism and aSAH and its clinical sequelae were analyzed. Samples from 149 patients with aSAH and 50 controls were available for analysis. Multivariable regression analysis did not show an association of RYR1 SNP rs35364374 with aSAH. Moreover, there was no association of RYR1 SNP rs35364374 with clinical vasospasm, delayed cerebral ischemia, functional outcome at discharge, or functional outcome at last follow-up. Contrary to a previous report, the RYR1 SNP rs35364374 was not associated with aSAH or its clinical sequelae. Copyright © 2017 Elsevier Inc. All rights reserved.
Miao, Chun-ming; Luo, Qi; Wang, Wei-wei; Kang, Jin-song; Shi, Guo-ying; Li, Hong-yan; Zhang, Yong
To study the significance and expression of FKHR and AKT after subarachnoid hemorrhage (SAH) in rat brain cortex. Twenty-four rats were randomly divided into three groups: sham, SAH and SAH plus nimodipine (n=8 each). A reliable SAH model was established by double injections of blood into cistern magna in Wistar rats. The neurological scores were measured by Loeffler and the expressions of FKHR, P-FKHR, AKT and P-FKHR detected by Western blot. Compared with sham group, the neurological score of SAH group obviously decreased (P < 0.05), the expression of FKHR became elevated in rat cortex (P < 0.01), the expression of AKT had no change and the expressions of P-AKT and P-FKHR obviously decreased (all P < 0.01). But the neurological score markedly increased (P < 0.01) and the expressions of P-AKT and P-FKHR became elevated (all P < 0.01) after administration of nimodipine. Both P-AKT and P-FKHR are involved in the process of brain cortex damage induced by SAH. The protective effects of nimodipine on brain injury induced by SAH may be related to the elevated expressions of P-AKT and P-FKHR in brain cortex.
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
Millon, Domitille; Derelle, Anne Laure; Omoumi, Patrick; Tisserand, Marie; Schmitt, Emmanuelle; Foscolo, Sylvain; Anxionnat, René; Bracard, Serge
To evaluate the technical quality and the diagnostic performance of a protocol with use of low volumes of contrast medium (25 mL) at 64-detector spiral computed tomography (CT) in the diagnosis and management of adult, nontraumatic subarachnoid hemorrhage (SAH). This study was performed outside the United States and was approved by the institutional review board. Intracranial CT angiography was performed in 73 consecutive patients with nontraumatic SAH diagnosed at nonenhanced CT. Image quality was evaluated by two observers using two criteria: degree of arterial enhancement and venous contamination. The two independent readers evaluated diagnostic performance (lesion detection and correct therapeutic decision-making process) by using rotational angiographic findings as the standard of reference. Sensitivity, specificity, and positive and negative predictive values were calculated for patients who underwent CT angiography and three-dimensional rotational angiography. The intraclass correlation coefficient was calculated to assess interobserver concordance concerning aneurysm measurements and therapeutic management. All aneurysms were detected, either ruptured or unruptured. Arterial opacification was excellent in 62 cases (85%), and venous contamination was absent or minor in 61 cases (84%). In 95% of cases, CT angiographic findings allowed optimal therapeutic management. The intraclass correlation coefficient ranged between 0.93 and 0.95, indicating excellent interobserver agreement. With only 25 mL of iodinated contrast medium focused on the arterial phase, 64-detector CT angiography allowed satisfactory diagnostic and therapeutic management of nontraumatic SAH. © RSNA, 2012.
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.
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
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
Panczykowski, David; Pease, Matthew; Zhao, Yin; Weiner, Gregory; Ares, William; Crago, Elizabeth; Jankowitz, Brian; Ducruet, Andrew F.
Background and Purpose The utility of prophylactic antiepileptic drug (AED) administration following spontaneous subarachnoid hemorrhage (SAH) remains controversial. AEDs have not clearly been associated with a reduction in seizure incidence and have been associated with both neurologic worsening and delayed functional recovery in this setting. Methods We retrospectively analyzed a prospectively collected database of SAH patients admitted to our institution between 2005 and 2010. Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007 no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score-matched analysis was then performed to compare the development of clinical and/or electrographic seizures in these two populations. Results 353 patients with spontaneous SAH were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patients suffered clinical and/or electrographic seizures, most frequently occurring within 24-hrs of ictus (47%). The incidence of seizures did not vary significantly based on the use of prophylactic AEDs (11 vs. 8%, p=0.33). Propensity score-matched analyses suggest that patients receiving prophylactic AEDs had a similar likelihood of suffering seizures as those who did not (p=0.49). Conclusions Propensity score-matched analysis suggests that prophylactic AEDs do not significantly reduce the risk of seizure occurrence in patients with spontaneous SAH. PMID:27301932
Sehba, Fatima A; Chereshnev, Igor; Maayani, Saul; Friedrich, Victor; Bederson, Joshua B
Subarachnoid hemorrhage (SAH) is associated with acute decreases and subsequent recovery of cerebral nitric oxide (NO) levels, but the mechanisms of these alterations are not known. In this study, we measured NO synthase (NOS) protein and kinetics to determine its involvement in the alterations of cerebral NO levels after SAH. The endovascular rat model of SAH was used. The number of NOS-1 (neuronal) and NOS-2 (inducible)-positive cells (0-96 h) was determined by counting immunoreactive cells in 8-microm cryostat sections. The tissue content of active NOS and its kinetic parameters were studied with an enzymatic l-citrulline assay. The number of NOS-1-positive cells increased between 1 and 3 hours after SAH, decreased to and below control values at 6 and 72 hours after SAH, and increased to control values 96 hours after SAH. The number of NOS-2-positive cells increased 1 hour after SAH, decreased to control values at 24 hours, and increased above control values 96 hours after SAH. The Michaelis-Menten kinetic parameters (V(max), K(m), slope) of NOS remained unchanged at 10 and 90 minutes after SAH. NOS-1 and -2 proteins undergo a triphasic alteration after SAH, whereas the amount of active NOS and its kinetic parameters remain unchanged during the first 90 minutes after SAH. Depletion of NOS is not involved in the acute alterations of cerebral NO levels after SAH.
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.
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
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.
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.
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.
Mrak, Goran; Duric, Kresimir Sasa; Nemir, Jakob
Background: Ischemic stroke is a well-described but less frequent consequence of ruptured or unruptured intracranial aneurysms. To date, the optimal form of treatment for patients with a thrombosed cerebral aneurysm has not yet been well-defined. Case Description: Here, we report a case of a 68-year-old female patient presenting with cerebral stroke. Five days poststroke multislice computed tomography (MSCT) and MSCT angiography were performed for the evaluation of clinical deterioration, showing a left M2 middle cerebral artery (MCA) bifurcation aneurysm and subarachnoid hemorrhage. Having in mind the high mortality and morbidity rates after a re-rupture, as well as the digital subtraction angiography features of the aneurysm, urgent surgery was performed consisting of aneurysm trapping and superficial temporal artery (STA) to M3 MCA segment end-to-side anastomosis. The surgery and early postoperative period proceeded uneventfully and the patient gradually recovered from the previously diagnosed expressive dysphasia and cranial and extremity motor deficit. Conclusion: Our case describes a complex aneurysm treatment that consisted of aneurysm trapping, thrombus removal and an STA-M3 MCA branch bypass creation for the protection of the patent M3 insular MCA branch and prevention of further ischemia. This procedure rewarded us with an excellent clinical result. PMID:27127709
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.
Yoshioka, Seiichiro; Takano, Tomoyuki; Ryujin, Fukiko; Takeuchi, Yoshihiro
Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disorder characterized by acute onset, severe headache, with reversible vasoconstriction of cerebral arteries often accompanied by additional neurological symptoms. This syndrome is seen mainly in middle-aged adults, predominantly women. Herein, we report on a pediatric case of RCVS with cortical subarachnoid hemorrhage (SAH). A 12-year-old boy developed acute, severe headache with paralysis of lower extremities causing gait disturbance after administration of eletriptan. Brain magnetic resonance angiography (MRA) revealed multifocal narrowing of the cerebral arteries, whereas magnetic resonance imaging (MRI) demonstrated sulcal hyperintensity on fluid-attenuated inversion recovery, consistent with cortical SAH. The patient's clinical symptoms resolved spontaneously after a few days and the MRI and MRA findings disappeared 3 months later, suggesting a diagnosis of RCVS. Eletriptan might cause vasoconstriction of cerebral arteries. Although most patients with RCVS are adults and pediatric cases are rare, RCVS should be considered in a child complaining of severe headache. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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.
Ku, Jerry C; Alotaibi, Naif M; Wang, Justin; Ibrahim, George M; Schweizer, Tom A; Macdonald, R Loch
Results of previous studies examining seasonal variation in the incidence of aneurysmal subarachnoid hemorrhage (SAH) are conflicting. The aim of this brief report is to investigate whether there is a seasonal effect in online search queries for SAH that may reflect an association between meteorological factors and aneurysm rupture. We used the Google Trends data service to analyze the volume of internet queries for SAH on Google's search engine from January 1, 2004 to November 2016. We used comprehensive search terms and collected data from: USA, Canada, and countries known for their high prevalence of SAH (Finland, and Japan), as well as worldwide search volume. Potential seasonal variations in the data were assessed by comparative non-parametric tests and curve-fit regression model. Our analyses revealed that USA had the highest median value in cumulative search scores (115 vs. 86, 46, 46 for Finland, Canada and Japan, respectively). The term "brain aneurysm" was the commonly used search term among countries, followed by "cerebral aneurysm". There was no evidence of seasonality in any of the countries studied on both univariate tests and regression time-adjusted analysis. There are no seasonal variations in internet search query volume for SAH. Further studies are needed to explore whether online search volumes correlate with the actual incidence of SAH. Copyright © 2017 Elsevier B.V. All rights reserved.
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
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
Nyquist, Paul A; Wang, Honghui; Suffredini, Anthony F
Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease. It has many sequelae, including vasospasm and delayed ischemic neurological deficits (DINDs). We explored the blood proteome in patients with aSAH using transcranial Doppler (TCD) velocity as a guide to patients who are at risk for symptomatic vasospasm and DIND. Blood was drawn on all days that patients were observed in the neurocritical care unit (NCCU) after aSAH. A team of neurologists and neurosurgeons identified patients with clinical evidence of vasospasm and DIND. Serum was fractionated using protein chips and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS). We detected a pattern of protein expression associated with those at risk for elevated TCD velocities by day 8, compared with blood collected in the presymptomatic stage (days 1-3). We further analyzed serum using pooled samples from study entry to the time of elevated TCD velocities using a protein microarray that analyzed 500 human proteins thematically oriented toward inflammation. After identifying several candidates with elevated concentrations in the pooled samples, we then used reverse protein arrays to quantitate the concentration of potential candidate proteins in the individual samples. Proteins with significantly elevated concentrations included apolipoprotein-E, apolipoprotein-A, serum amyloid protein-4, and serum amyloid protein-P. Future studies in larger sample populations are needed to evaluate these biomarkers further as representative of biosystems involved in vasospasm and DIND or as potential biomarkers predictive of risk associated with disease.
Pan, De-Sheng; Yan, Min; Hassan, Muhammad; Fang, Ze-Bin; Chen, Man-Tao
8-iso-Prostaglandin F2α (8-iso-PGF2α) is a potential biomarker of oxidative stress. This study clarified whether plasma 8-iso-PGF2α concentrations were affected and its underlying relevance to prognosis in aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational study, a total of 170 controls and 170 aSAH patients were enrolled. Plasma 8-iso-PGF2α concentrations were detected using an ELISA. Severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale. Clinical outcomes included 6-month mortality and poor outcome referred to as Glasgow outcome scale score of 1-3. As compared to controls, admission plasma 8-iso-PGF2α concentrations were significantly enhanced. Increased concentrations of plasma 8-iso-PGF2α correlated with WFNS scores and modified Fisher scores. 8-iso-PGF2α in plasma was an independent predictor for clinical outcomes. Under ROC curve, the predictive values of 8-iso-PGF2α concentrations resembled those of WFNS scores and modified Fisher scores for clinical outcomes. An elevation in plasma 8-iso-PGF2α concentrations is associated with the severity and poor outcome after aSAH, substantializing 8-iso-PGF2α as a potential prognostic biomarker of aSAH. Copyright © 2017. Published by Elsevier B.V.
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.
Hsieh, Peiyuan F; Lee, Yi-Chung; Chang, Ming-Hong
Postpartum arterial dissection combined with subarachnoid hemorrhage (SAH) is rare and its mechanism is uncertain. A 32 year-old woman had a delivery by cesarean section 12 days prior to admission to our hospital. From the first day of delivery, she breast-fed her baby, sitting with her head always turned to the right. Each feeding lasted around 2 hours. A bilateral throbbing headache began two days after childbirth, and intermittent numbness of the right face, chest and hand as well as weakness of the right hand developed nine days after giving birth. A physical examination revealed transient mild hypertension and right hemiparesis. Her cholesterol ranged from 204 to 263 mg/dl. Computed tomography, magnetic resonance angiography and duplex ultrasound disclosed left fronto-parietal junction SAH and dissections of the right internal carotid (ICA) and vertebral arteries. Our patient demonstrated (1) that postpartum arterial dissection was not limited to natural delivery, (2) postpartum SAH could occur with dissections of the contralateral extracranial carotid and vertebral arteries, and (3) that turning one's head always to the same side during breast-feeding might be a risk factor for this unusual stroke pattern.
Fukui, Shinji; Katoh, Hiroshi; Tsuzuki, Nobusuke; Ishihara, Shoichiro; Otani, Naoki; Ooigawa, Hidetoshi; Toyooka, Terushige; Ohnuki, Akira; Miyazawa, Takahito; Nawashiro, Hiroshi; Shima, Katsuji
Background Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis. Method We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose. Results The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients. Conclusion These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH. PMID:12793884
Maslehaty, Homajoun; Petridis, Athanassios K; Barth, Harald; Mehdorn, Hubertus Maximilian
The aim of this study was to evaluate the diagnostic value of MR imaging in perimesencephalic (PM) and nonperimesencephalic (non-PM) subarachnoid hemorrhage (SAH) of unknown origin. The authors conducted a retrospective review of all patients with SAH (1226 patients) in their department between January 1991 and December 2008. Included in the study were cases of spontaneous SAH diagnosed using CT scans obtained within 24 hours of the initial symptoms and initially negative digital subtraction (DS) angiograms. Patients with traumatic SAH and an unknown history were excluded from the study. Patients with initially negative DS angiograms were divided into 2 groups: Group 1, a typically PM bleeding pattern (PM SAH); and Group 2, a non-PM bleeding pattern (non-PM SAH) such as hemorrhage in the sylvian or interhemispheric fissure. Cranial MR imaging including the craniocervical region was performed within 72 hours after SAH was diagnosed in all patients in Groups 1 and 2. One thousand sixty-eight patients underwent DS angiography, and among them were 179 (16.7%) with negative angiograms--47 patients (26.3%) from Group 1 and 132 patients (73.7%) from Group 2. Magnetic resonance imaging demonstrated no bleeding sources in any case (100% negative). Thirty-four patients in Group 1 and 120 patients in Group 2 underwent a second DS angiography study. Digital subtraction angiography revealed an aneurysm as the bleeding source in 1 case in Group 1 and in 13 cases in Group 2. Magnetic resonance imaging of the brain and craniocervical region did not produce additional benefit for the detection of a bleeding source and the therapy administered for PM SAH and non-PM SAH (100% negative). The costs of this examination exceeded the clinical value. Despite the results of this study, MR imaging should be discussed on a case-by-case basis because rare bleeding sources are periodically diagnosed in cases of non-PM SAH. A second-look DS angiogram is necessary because aneurysmal hemorrhage
Suwatcharangkoon, Sureerat; Meyers, Emma; Falo, Cristina; Schmidt, J Michael; Agarwal, Sachin; Claassen, Jan; Mayer, Stephan A
Loss of consciousness (LOC) is a common presenting symptom of subarachnoid hemorrhage (SAH) that is presumed to result from transient intracranial circulatory arrest. To clarify the association between LOC at onset of SAH, complications while in the hospital, and long-term outcome after SAH. A retrospective analysis was conducted of 1460 consecutively treated patients with spontaneous SAH who were part of a prospective observational cohort study at a large urban academic medical center (the Columbia University SAH Outcomes Project or SHOP). Patients were enrolled between August 6, 1996, and July 23, 2012. Analysis was conducted from December 1, 2013, to February 28, 2015. Loss of consciousness at onset was identified by structured interview of the patient and first responders. Patients (80.5%) were observed for up to 1 year to assess functional recovery. Modified Rankin scale scores were assigned based on telephone or in-person interviews of the patient, family members, or caregivers. Complications while in the hospital were predefined and adjudicated by the study team. Five hundred ninety patients (40.4%) reported LOC at onset of SAH. Loss of consciousness was associated with poor clinical grade, more subarachnoid and intraventricular blood seen on admission computed tomographic scan, and a higher frequency of global cerebral edema (P < .001). Loss of consciousness was also associated with more prehospital tonic-clonic activity (22.7% vs 4.2%; P < .001) and cardiopulmonary arrest (9.7% vs 0.5%, P < .001) vs patients who did not experience LOC. In multivariable analysis, death or severe disability at 12 months was independently associated with LOC after adjusting for established risk factors for poor outcome, including poor admission clinical grade (adjusted odds ratio, 1.94; 95% CI, 1.38-2.72; P < .001). There was no association between LOC at onset and delayed cerebral ischemia or aneurysm rebleeding. Loss of consciousness at symptom onset is an
Macdonald, R Loch; Jaja, Blessing; Cusimano, Michael D; Etminan, Nima; Hanggi, Daniel; Hasan, David; Ilodigwe, Don; 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; Singh, Jeff
Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last decades. Yet, case fatality remains nearly 40% and survivors often have permanent neurological, cognitive and/or behavioural sequelae. Other than nimodipine drug or clinical trials have not consistently improved outcome. We formed a collaboration of SAH investigators to create a resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase 3 trials in aneurysmal SAH. We identified investigators with data from randomized, clinical trials of patients with aneurysmal SAH or prospectively collected single- or multicentre databases of aneurysmal SAH patients. Data are being collected and proposals to use the data and to design future phase 3 clinical trials are being discussed. This paper reviews some issues discussed at the first meeting of the SAH international trialists (SAHIT) repository meeting. Investigators contributed or have agreed to contribute data from several phase 3 trials including the tirilazad trials, intraoperative hypothermia for aneurysmal SAH trial, nicardipine clinical trials, international subarachnoid aneurysm trial, intravenous magnesium sulphate for aneurysmal SAH, magnesium for aneurysmal SAH and from prospectively-collected data from four institutions. The number of patients should reach 15,000. Some industry investigators refused to provide data and others reported that their institutional research ethics boards would not permit even deidentified or anonymized data to be included. Others reported conflict of interest that prevented them from submitting data. The problems with merging data were related to lack of common definitions and coding of variables, differences in outcome scales used, and times of assessment. Some questions for investigation that arose are discussed. SAHIT demonstrates the possibility of SAH investigators to contribute data for collaborative research. The problems are similar to those
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.
Ro, Ayako; Kageyama, Norimasa; Abe, Nobuyuki; Takatsu, Akihiro; Fukunaga, Tatsushige
Subarachnoid hemorrhage (SAH) due to a ruptured intracranial vertebral artery (VA) dissection sometimes results in a sudden fatal outcome. The authors analyzed the relationship between clinical features and histopathological characteristics among fatal cases to establish valuable information for clinical diagnostics and prophylaxis. This study included 58 medicolegal autopsy cases of ruptured intracranial VA dissection among 553 fatal nontraumatic cases of SAH that occurred between January 2000 and December 2007. Their clinical features were obtained from autopsy records. Histopathological investigations were performed on cross-sections obtained from all 4-mm segments of whole bilateral intracranial VAs and prepared with H & E and elastica van Gieson staining. The autopsy cases included 47 males and 11 females, showing a marked predilection for males. The mean age was 46.8 +/- 7.7 years, with 78% of the patients in their 40s or 50s. Hypertension was the most frequently encountered history; it was found in 36% of cases from clinical history and in 55% of cases based on autopsy findings. Prodromal symptoms related to intracranial VA dissections were detected in 43% of patients. Headache or neck pain lasting hours to weeks was a frequent complaint. Of patients with prodromal symptoms, 44% had consulted doctors; however, in none of these was SAH or intracranial VA dissection diagnosed at a preventable stage. Autopsy revealed fusiform aneurysms with medial dissecting hematomas. Apart from ruptured intracranial VA dissection, previous intracranial VA dissection was detected in 25 cases (43%); among them, 10 showed previous dissection of the bilateral intracranial VAs. The incidence of prodromal symptoms (60%) among the patients with previous intracranial VA dissection was significantly higher than that (30%) among cases without previous dissection (chi-square test; p = 0.023). Most previous intracranial VA dissections formed a single lumen resembling nonspecific
Ohshima, Tomotaka; Tamari, Yosuke; Yamamoto, Taiki; Goto, Shunsaku; Ishikawa, Kojiro
The mechanisms and prognosis of underlying subarachnoid hemorrhage of unknown origin remain unclear. Previous investigators have suggested a relationship between nonaneurysmal perimesencephalic subarachnoid hemorrhage and venous abnormalities like a primitive venous drainage of the basal vein of Rosenthal. We report the outcome of a midterm follow-up of 20 consecutive patients with nonaneurysmal subarachnoid hemorrhage of unknown origin, and 2 patients in whom the development of new dural arteriovenous fistulas after subarachnoid hemorrhage of unknown origin were detected during follow-up. All patients who were admitted to our hospital for nontraumatic subarachnoid hemorrhage between April 2008 and March 2016 were retrospectively analyzed. Of 705 patients included in the study, 20 (2.8%) were diagnosed with nontraumatic subarachnoid hemorrhage of unknown origin. During the follow-up periods, there was no rebleeding. Although 18 patients did not show any vascular abnormalities, the other 2 patients were diagnosed with dural arteriovenous fistula. Both fistulas were successfully treated with endovascular embolization. Subarachnoid hemorrhage of unknown origin had a low incidence rate, and its clinical course was excellent without rebleeding. Although no vascular abnormalities were observed during the patients' initial admission, venous lesions might have been involved in both subarachnoid hemorrhages and delayed dural arteriovenous fistulas. Here, the possible pathogenesis is discussed with a review of the literature. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
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.
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
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
Gilard, V; Ferracci, F-X; Langlois, O; Derrey, S; Proust, F; Curey, S
Survivors of aneurysmal subarachnoid hemorrhage (aSAH) commonly experience sleep disorders resulting in asthenia. The objective of this prospective study was to determine, in a cohort of patients with treated ruptured intracranial aneurysm (IA), the proportion of asthenia at 2months, in a cohort of patients treated with melatonin and in a control cohort. Twenty consecutive patients admitted for the treatment of ruptured IA and able to answer a standardized questionnaire were included in the study. After evaluation for fatigue at discharge, we divided our population into 2 cohorts of 10 patients: the first cohort was treated with melatonin for a period of 2months; the second cohort had no specific treatment for fatigue. The primary endpoint was the proportion of asthenia at 2months in both groups. Confounding factors, such as depression, autonomy and apathy were evaluated at the same time. At discharge, there was no significant difference observed between both groups in terms of mean age and initial clinical status (WFNS, Rankin Scale and Fatigue Severity Scale). At 2months, the mean FSS score in the control group was of 4.7±1.0 versus 3.8±0.9 in the melatonin group (P=0.03). The mean MADRS score in the control group was of 1.1±1.45 versus 2.7±2.5 in the melatonin group (P=0.10). The mean LARS score in the control group was of -32.5±1.7 versus -31.7±1.9 in the melatonin group (P=0.24). In a prospective evaluation of post-aSAH fatigue, we suggest that melatonin could decrease fatigue. There is no significant impact on depression and apathy. Further studies would be necessary to improve our comprehension of fatigue physiopathology in a context of aSAH. Copyright Â© 2016 Elsevier Masson SAS. All rights reserved.
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.
Taufique, Zahrah; May, Teresa; Meyers, Emma; Falo, Cristina; Mayer, Stephan A; Agarwal, Sachin; Park, Soojin; Connolly, E Sander; Claassen, Jan; Schmidt, J Michael
Risk factors for poor quality of life (QOL) after subarachnoid hemorrhage (SAH) remain poorly described. To identify the frequency and predictors of poor QOL 1 year after SAH. We studied 1-year QOL in a prospectively collected cohort of 1181 consecutively admitted SAH survivors between July 1996 and May 2013. Patient clinical, radiographic, surgical, and acute clinical course information was recorded. Reduced QOL (overall, physical, and psychosocial) at 1 year was assessed with the Sickness Impact Profile and defined as 2 SD below population-based normative Sickness Impact Profile values. Logistic regression leveraging multiple imputation to handle missing data was used to evaluate reduced QOL. Poor overall QOL was observed in 35% of patients. Multivariable analysis revealed that nonwhite ethnicity, high school education or less, history of depression, poor clinical grade (Hunt-Hess Grade ≥3), and delayed infarction were predictors of poor overall and psychosocial QOL. Poor physical QOL was additionally associated with older age, hydrocephalus, pneumonia, and sepsis. At 1 year, patients with poor QOL had increased difficulty concentrating, cognitive dysfunction, depression, and reduced activities of daily living. More than 91% of patients with poor QOL failed to fully return to work. These patients frequently received physical rehabilitation, but few received cognitive rehabilitation or emotional-behavioral support. Reduced QOL affects as many as one-third of SAH survivors 1 year after SAH. Delayed infarction is the most important in-hospital modifiable factor that affects QOL. Increased attention to cognitive and emotional difficulties after hospital discharge may help patients achieve greater QOL.
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.
Fan, Ruiming; Enkhjargal, Budbazar; Camara, Richard; Yan, Feng; Gong, Lei; ShengtaoYao; Tang, Jiping; Chen, Yangmei; Zhang, John H
Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH. Small interfering RNA (siRNA) for EphA4, recombinant Ephexin-1 (rEphx-1), and Fasudil, a potent ROCK2 inhibitor, were used for intervention to study a role of EphA4 on EBI after SAH. The expression of EphA4, Ephexin-1, RhoA, and ROCK2 significantly increased after SAH. Knockdown of EphA4 using EphA4 siRNA injection intracerebroventricularly (i.c.v) reduced Evans blue extravasation, decreased brain water content, and alleviated neurobehavioral dysfunction after SAH. Additionally, the expression of Ephexin-1, RhoA, ROCK2 and cleaved caspase-3 were decreased. Tight junction proteins increased, and apoptotic neuron death decreased. The effects of EphA4 siRNA were abolished by rEphx-1. In contrast, Fasudil abolished the effects of rEphx-1. These results suggest that EphA4, a novel and promising target for treatment, exacerbates EBI through an Ephexin-1/ROCK2 pathway after SAH. Copyright © 2017. Published by Elsevier Inc.
Cremers, Charlotte H P; Dankbaar, Jan Willem; Vergouwen, Mervyn D I; Vos, Pieter C; Bennink, Edwin; Rinkel, Gabriel J E; Velthuis, Birgitta K; van der Schaaf, Irene C
Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.
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.
Morris, Nicholas A; Cool, Joséphine; Merkler, Alexander E; Kamel, Hooman
Recent studies suggest that traumatic brain injury (TBI) is a risk factor for subsequent ischemic stroke, even years after the initial insult. The mechanisms of the association remain unclear. The presence of traumatic subarachnoid hemorrhage (tSAH) may mediate the effect of TBI on long-term stroke risk, as it has previously been linked to short-term vasospasm and delayed cerebral ischemia. Using administrative claims data, we conducted a retrospective cohort study of acute care hospitalizations. Patients discharged with a first-recorded diagnosis of tSAH were followed for a primary diagnosis of stroke. They were matched to patients with TBI but not tSAH. Cox proportional hazards modeling was used to assess the association between tSAH and stroke while adjusting for covariates. We identified 40 908 patients with TBI (20 454 patients with tSAH) who were followed for a mean of 4.3 + 1.8 years. A total of 531 had an ischemic stroke after discharge. There was no significant difference in stroke risk between those with tSAH (1.79%; 95% confidence interval [CI] 1.54%-2.08%) versus without tSAH (2.12%; 95% CI 1.83%-2.44%). The same pattern was found in adjusted analyses even when the group was stratified by age-group or by proxies of TBI severity. Our findings do not support a role of tSAH in mediating the association between TBI and protracted stroke risk. Further study is required to elucidate the mechanisms of long-term increased stroke risk after TBI.
Pierot, Laurent; Portefaix, Christophe; Rodriguez-Régent, Christine; Gallas, Sophie; Meder, Jean-François; Oppenheim, Catherine
Magnetic resonance angiography (MRA) has been evaluated for the detection of unruptured intracranial aneurysms with favorable results at 3 Tesla (3T) and with similar diagnostic accuracy as both 3D time-of-flight (3D-TOF) and contrast-enhanced (CE-MRA) MRA. However, the diagnostic value and place of MRA in the detection of ruptured aneurysms has been little evaluated. Thus, the goal of this prospective single-center series was to assess the feasibility and diagnostic value of 3T 3D-TOF MRA and CE-MRA for aneurysm detection in acute non-traumatic subarachnoid hemorrhage (SAH). From March 2006 to December 2007, all consecutive patients admitted to our hospital with acute non-traumatic SAH (≤10 days) were prospectively included in this study evaluating MRA in the diagnostic workup of SAH. Feasibility of MRA and sensitivity/specificity of 3D-TOF and CE-MRA were assessed compared with gold standard DSA. In all, 84 consecutive patients (45 women, 39 men; age 23-86 years) were included. The feasibility of MRA was low (43/84, 51.2%). The reasons given for patients not undergoing magnetic resonance imaging (MRI) examination were clinical status (27 patients), potential delay in aneurysm treatment (11 patients) and contraindications to MRI (three patients). In patients explored by MRA, the sensitivity of CE-MRA (95%) was higher compared with 3D-TOF (86%) with similar specificity (80%). Also, 3D-TOF missed five aneurysms while CE-MRA missed two. The value of MRA in the diagnostic workup of ruptured aneurysms is limited due to its low feasibility during the acute phase of bleeding. Sensitivity for aneurysm detection was good for both MRA techniques, but tended to be better with CE-MRA. Copyright © 2013. Published by Elsevier Masson SAS.
Chaichana, Kaisorn L; Pradilla, Gustavo; Huang, Judy; Tamargo, Rafael J
Delayed vasospasm is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). This phenomenon was first described more than 50 years ago, but only recently has the role of inflammation in this condition become better understood. The literature was reviewed for studies on delayed vasospasm and inflammation. There is increasing evidence that inflammation and, more specifically, leukocyte-endothelial cell interactions play a critical role in the pathogenesis of vasospasm after aSAH, as well as in other conditions including meningitis and traumatic brain injury. Although earlier clinical observations and indirect experimental evidence suggested an association between inflammation and chronic vasospasm, recently direct molecular evidence demonstrates the central role of leukocyte-endothelial cell interactions in the development of chronic vasospasm. This evidence shows in both clinical and experimental studies that cell adhesion molecules (CAMs) are up-regulated in the perivasospasm period. Moreover, the use of monoclonal antibodies against these CAMs, as well as drugs that decrease the expression of CAMs, decreases vasospasm in experimental studies. It also appears that certain individuals are genetically predisposed to a severe inflammatory response after aSAH based on their haptoglobin genotype, which in turn predisposes them to develop clinically symptomatic vasospasm. Based on this evidence, leukocyte-endothelial cell interactions appear to be the root cause of chronic vasospasm. This hypothesis predicts many surprising features of vasospasm and explains apparently unrelated phenomena observed in aSAH patients. Therapies aimed at preventing inflammation may prevent and/or reverse arterial narrowing in patients with aSAH and result in improved outcomes. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Zaroff, Jonathan G; Leong, Jonathan; Kim, Helen; Young, William L; Cullen, Sean P; Rao, Vivek A; Sorel, Michael; Quesenberry, Charles P; Sidney, Steve
Cardiac injury is common after subarachnoid hemorrhage (SAH) and is associated with adverse early outcomes, but long-term effects are unknown. The first aim of this study was to compare the long-term rates of death, stroke, and cardiac events in SAH survivors versus a matched population without SAH. The second aim was to quantify the effects of cardiac injury on the outcome rates. This was a retrospective cohort study of patients with and without non-traumatic SAH. For aim #1, the predictor variable was SAH and the outcome variables were all-cause and cerebrovascular mortality, stroke, cardiac mortality, acute coronary syndrome (ACS), and heart failure (HF) admission. A multivariable Cox proportional hazards analysis was performed. For aim #2, the predictor variables were cardiac injury (elevated serum cardiac enzymes or a diagnosis code for ACS) and dysfunction (pulmonary edema on X-Ray or a diagnosis code for HF). Compared with 4,695 members without SAH, the 910 SAH patients had higher rates of all-cause mortality (hazard ratio [HR 2.6], 95% confidence intervals [CI] 2.0-3.4), cerebrovascular mortality (HR 30.6, CI 13.5-69.4), and stroke (HR 10.2, CI 7.5-13.8). Compared with the non-SAH group, the SAH patients with cardiac injury had increased rates of all-cause mortality (HR 5.3, CI 3.0-9.3), cardiac mortality (HR 7.3, CI 1.7-31.6), and heart failure (HR 4.3, CI 1.53-11.88). SAH survivors have increased long-term mortality and stroke rates compared with a matched non-SAH population. SAH-induced cardiac injury is associated with an increased risk of death and heart failure hospitalization.
Otite, Fadar; Mink, Susanne; Tan, Can Ozan; Puri, Ajit; Zamani, Amir A; Mehregan, Aujan; Chou, Sherry; Orzell, Susannah; Purkayastha, Sushmita; Du, Rose; Sorond, Farzaneh A
Cerebral autoregulation may be impaired in the early days after subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationship between cerebral autoregulation and angiographic vasospasm (aVSP) and radiographic delayed cerebral ischemia (DCI) in patients with SAH. Sixty-eight patients (54±13 years) with a diagnosis of nontraumatic SAH were studied. Dynamic cerebral autoregulation was assessed using transfer function analysis (phase and gain) of the spontaneous blood pressure and blood flow velocity oscillations on days 2 to 4 post-SAH. aVSP was diagnosed using a 4-vessel conventional angiogram. DCI was diagnosed from CT. Decision tree models were used to identify optimal cut-off points for clinical and physiological predictors of aVSP and DCI. Multivariate logistic regression models were used to develop and validate a risk scoring tool for each outcome. Sixty-two percent of patients developed aVSP, and 19% developed DCI. Patients with aVSP had higher transfer function gain (1.06±0.33 versus 0.89±0.30; P=0.04) and patients with DCI had lower transfer function phase (17.5±39.6 versus 38.3±18.2; P=0.03) compared with those who did not develop either. Multivariable scoring tools using transfer function gain>0.98 and phase<12.5 were strongly predictive of aVSP (92% positive predictive value; 77% negative predictive value; area under the receiver operating characteristic curve, 0.92) and DCI (80% positive predictive value; 91% negative predictive value; area under the curve, 0.94), respectively. Dynamic cerebral autoregulation is impaired in the early days after SAH. Including autoregulation as part of the initial clinical and radiographic assessment may enhance our ability to identify patients at a high risk for developing secondary complications after SAH.
Song, Jian-Ping; Ni, Wei; Gu, Yu-Xiang; Zhu, Wei; Chen, Liang; Xu, Bin; Leng, Bin; Tian, Yan-Long; Mao, Ying
Nontraumatic spontaneous subarachnoid hemorrhage (SAH) is associated with a high mortality. This study was conducted to investigate the epidemiological features of nontraumatic spontaneous SAH in China. From January 2006 to December 2008, the clinical data of patients with nontraumatic SAH from 32 major neurosurgical centers of China were evaluated. Emergent digital subtraction angiography (DSA) was performed for the diagnosis of SAH sources in the acute stage of SAH (≤3 days). The results and complications of emergent DSA were analyzed. Repeated DSA or computed tomography angiography (CTA) was suggested 2 weeks later if initial angiographic result was negative. A total of 2562 patients were enrolled, including 81.4% of aneurysmal SAH and 18.6% of nonaneurysmal SAH. The total complication rate of emergent DSA was 3.9% without any mortality. Among the patients with aneurysmal SAH, 321 cases (15.4%) had multiple aneurysms, and a total of 2435 aneurysms were detected. The aneurysms mostly originated from the anterior communicating artery (30.1%), posterior communicating artery (28.7%), and middle cerebral artery (15.9%). Among the nonaneurysmal SAH cases, 76.5% (n = 365) had negative initial DSA, including 62 cases with peri-mesencephalic nonaneurysmal SAH (PNSAH). Repeated DSA or CTA was performed in 252 patients with negative initial DSA, including 45 PNSAH cases. Among them, the repeated angiographic results remained negative in 45 PNSAH cases, but 28 (13.5%) intracranial aneurysms were detected in the remaining 207 cases. In addition, brain arteriovenous malformation (AVM, 7.5%), Moyamoya disease (7.3%), stenosis or sclerosis of the cerebral artery (2.7%), and dural arteriovenous fistula or carotid cavernous fistula (2.3%) were the major causes of nonaneurysmal SAH. DSA can be performed safely for pathological diagnosis in the acute stage of SAH. Ruptured intracranial aneurysms, AVM, and Moyamoya disease are the major causes of SAH detected by emergent DSA in
Zhang, Limin; Qi, Sihua
We conducted a retrospective cohort study of a large sample to assess whether electrocardiographic (ECG) abnormalities are independently associated with the occurrence of neurogenic pulmonary edema (NPE), delayed cerebral ischemia (DCI), and in-hospital death after nontraumatic subarachnoid hemorrhage (SAH). In this retrospective observational study, patients who were admitted within 72 hours of SAH symptom onset between 2013 and 2015 were enrolled. Twelve-lead ECG findings obtained within 72 hours after SAH and the presence of NPE, DCI, and in-hospital death were collected based on the results reported in the medical records. We included 834 patients. NPE occurred in 192 patients (23%). The median delay from SAH onset to NPE was 3 days (interquartile range [IQR]: 5 days). DCI occurred in 223 patients (27%; median delay to DCI, 4 days; IQR: 5 days). In total, 141 patients (17%) died in the hospital (median time to death, 12 days; IQR: 18 days). The frequency of ECG abnormalities for all enrolled patients was 65%. Corrected QT prolongation had an adjusted risk ratio (RR) of 1.5 (1.1-2.2) for NPE and 1.8 (1.3-2.4) for DCI. ST depression had an adjusted RR of 3.0 (1.2-7.5) for in-hospital death. NSSTTCs (nonspecific ST- or T-wave changes) had an adjusted RR of 2.7 (1.8-4.2) for NPE, 2.8 (1.9-4.3) for DCI, and 2.2 (1.3-3.5) for in-hospital death. All RRs were adjusted for age and Hunt-Hess scores. ECG abnormalities assessed within 72 hours after SAH using a standard 12-lead ECG are independently associated with an increased risk of adverse clinical outcomes in patients with nontraumatic SAH. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Ellis, Jason A; McDowell, Michael M; Mayer, Stephan A; Lavine, Sean D; Meyers, Philip M; Connolly, E Sander
The use of antiplatelet medications has greatly expanded and this has been associated with an increased rate of complications after aneurysmal subarachnoid hemorrhage (SAH). The influence of antiplatelet medications on outcomes after non-aneurysmal SAH is unknown. To analyze the frequency and impact on outcome of antiplatelet medication use among patients with angiogram-negative SAH. An analysis of patients within the Columbia University SAH Outcomes Project database was performed. All patients who underwent catheter cerebral angiography after presenting with nontraumatic SAH between 1996 and 2013 were included. Outcomes were assessed by using the modified Rankin Scale. A total of 1351 patients underwent catheter angiography for evaluation of SAH. Of these, 173 (13%) were designated angiogram-negative. The fraction of patients presenting with angiogram-negative SAH as well as the frequency of antiplatelet use among these patients significantly increased during the study period. Antiplatelet use was more commonly associated with angiogram-negative SAH than with angiogram-positive SAH (27% vs 14%, P = .001). At 14 days after presentation, poor outcome was significantly more frequent among patients who took antiplatelet agents than among those who did not (38% vs 20%, P = .017). This effect was also seen after multivariate analysis (odds ratio, 2.58; P = .034), although no difference was observed by 12 months (P > .05). Antiplatelet medication use is associated with poor early, but not late, outcomes after angiogram-negative SAH. Corresponding increased rates of antiplatelet medication use and angiogram-negative SAH may be related. Additional studies are needed to confirm this association.
Shea, Alisa M; Reed, Shelby D; Curtis, Lesley H; Alexander, Michael J; Villani, John J; Schulman, Kevin A
Substantial progress has been made in the diagnosis and treatment of subarachnoid hemorrhage (SAH). However, studies of SAH in the United States do not include information more recent than 2001, precluding analysis of shifts in treatment methods. We examined the epidemiology and in-hospital outcomes of nontraumatic SAH in the United States. We analyzed nationally representative data from the 2003 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to determine demographic and hospital characteristics, treatments, and in-hospital outcomes of patients with nontraumatic SAH. In 2003, there were an estimated 31,476 discharges for nontraumatic SAH among patients aged 17 years or older, or 14.5 discharges per 100,000 adults. The in-hospital mortality rate was 25.3%. Microvascular clipping was performed in 7513 discharges, or 23.9% of inpatients with nontraumatic SAH; endovascular coiling was performed in 2849 discharges (9.1%). Adjusted odds of treatment with either procedure were significantly higher in urban teaching hospitals compared with urban nonteaching hospitals (odds ratio, 1.62; 95% confidence interval, 1.00-2.62) or rural hospitals (odds ratio, 3.08; 95% confidence interval, 1.93-4.91). The in-hospital mortality rate associated with nontraumatic SAH continues to exceed 25%. Although it is unclear how many patients with nontraumatic SAH were actually diagnosed with a cerebral aneurysm, this study suggests that less than one-third of patients hospitalized for SAH receive surgical or endovascular treatment. Prospective studies are needed to elucidate either what systematic coding error is occurring in the national database or why patients may not receive treatment to secure a ruptured aneurysm.
Claassen, Jan; Bateman, Brian T; Willey, Joshua Z; Inati, Sarah; Hirsch, Lawrence J; Mayer, Stephan A; Sacco, Ralph L; Schumacher, H Christian
To identify the frequency of and impact on outcome of generalized convulsive status epilepticus (GCSE) among patients with nontraumatic subarachnoid hemorrhage (SAH). We used the Nationwide Inpatient Sample, a database of admissions to nonfederal United States hospitals between 1994 and 2002, for this study. From this database, we identified all adult patients with nontraumatic SAH who were admitted through the emergency department. Independent predictors of GCSE and mortality were identified using multivariate logistic regression. Multivariate linear regression analysis was used to determine whether GCSE was independently associated with increased cost and/or duration of hospitalization. Among the 29,998 patients hospitalized with nontraumatic SAH, GCSE was reported to occur in 0.2% of patients (N = 73 patients). GCSE occurred more frequently among those in the youngest tertiale (49 years old or younger; odds ratio, 3.2; 95% confidence interval, 2.0-5.1), those with renal disease (odds ratio, 4.8; 95% confidence interval, 2.6-8.8), and those who did not undergo a neurosurgical procedure involving a craniotomy (odds ratio, 2.2; 95% confidence interval, 1.3-3.8). GCSE was independently associated with higher in-hospital mortality (48% versus 33% of patients; odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P = 0.002) and longer (9 versus 7 days; P = 0.016) and more expensive (US $39,677 versus US $26,686; P = 0.007) hospitalizations. GCSE rarely complicates SAH; however, it is associated with increased patient mortality, length of hospital stay, and cost. GCSE occurs more frequently in young patients, those with a history of renal disease, and patients who do not undergo a craniotomy.
Song, Jian-Ping; Ni, Wei; Gu, Yu-Xiang; Zhu, Wei; Chen, Liang; Xu, Bin; Leng, Bin; Tian, Yan-Long; Mao, Ying
Background: Nontraumatic spontaneous subarachnoid hemorrhage (SAH) is associated with a high mortality. This study was conducted to investigate the epidemiological features of nontraumatic spontaneous SAH in China. Methods: From January 2006 to December 2008, the clinical data of patients with nontraumatic SAH from 32 major neurosurgical centers of China were evaluated. Emergent digital subtraction angiography (DSA) was performed for the diagnosis of SAH sources in the acute stage of SAH (≤3 days). The results and complications of emergent DSA were analyzed. Repeated DSA or computed tomography angiography (CTA) was suggested 2 weeks later if initial angiographic result was negative. Results: A total of 2562 patients were enrolled, including 81.4% of aneurysmal SAH and 18.6% of nonaneurysmal SAH. The total complication rate of emergent DSA was 3.9% without any mortality. Among the patients with aneurysmal SAH, 321 cases (15.4%) had multiple aneurysms, and a total of 2435 aneurysms were detected. The aneurysms mostly originated from the anterior communicating artery (30.1%), posterior communicating artery (28.7%), and middle cerebral artery (15.9%). Among the nonaneurysmal SAH cases, 76.5% (n = 365) had negative initial DSA, including 62 cases with peri-mesencephalic nonaneurysmal SAH (PNSAH). Repeated DSA or CTA was performed in 252 patients with negative initial DSA, including 45 PNSAH cases. Among them, the repeated angiographic results remained negative in 45 PNSAH cases, but 28 (13.5%) intracranial aneurysms were detected in the remaining 207 cases. In addition, brain arteriovenous malformation (AVM, 7.5%), Moyamoya disease (7.3%), stenosis or sclerosis of the cerebral artery (2.7%), and dural arteriovenous fistula or carotid cavernous fistula (2.3%) were the major causes of nonaneurysmal SAH. Conclusions: DSA can be performed safely for pathological diagnosis in the acute stage of SAH. Ruptured intracranial aneurysms, AVM, and Moyamoya disease are the major
Rincon, Fred; Rossenwasser, Robert H; Dumont, Aaron
Subarachnoid hemorrhage (SAH) is the cause of 5% to 10% of strokes annually in the United States. To study the incidence and mortality trends of admissions of SAH from 1979 to 2008 using a nationally representative sample of all nonfederal acute-care hospitals in the United States: The National Hospital Discharge Survey. The sample was obtained from the hospital discharge records according to the International Classification of Disease, 9th Revision, Clinical Modification code 430. We reviewed data on approximately 1 billion hospitalizations in the United States over a 30-year study period and identified 612,500 cases of SAH, which was more common in women (relative risk 1.71, 95% confidence interval 1.7-1.72) and nonwhite persons than white persons (relative risk 1.46, 95% confidence interval 1.4-1.5). The estimated incidence rate of admission after SAH was 7.2 to 9.0 per 100,000/year and did not significantly change over the study period. Overall, in-hospital mortality after SAH fell from 30% during the period from 1979 to 1983 to 20% during the subperiod from 2004 to 2008 (P = .03) and was lower in larger treating hospitals. The average days of care for SAH hospitalizations decreased, but the rate of discharge to long-term care facilities increased. The incidence rate of admission after SAH has remained stable over the past 30 years. Total deaths and in-hospital mortality after SAH have decreased significantly. In-hospital mortality after SAH is lower in larger treating hospitals.
Tiebosch, Ivo A C W; Dijkhuizen, Rick M; Cobelens, Pieter M; Bouts, Mark J R J; Zwartbol, René; van der Meide, Peter H; van den Bergh, Walter M
Aneurysmal subarachnoid hemorrhage (SAH) has a poor outcome, particularly attributed to progressive injury after the initial incident. Several studies suggest a critical role for inflammation in lesion progression after SAH. Our goal was to test whether treatment with anti-inflammatory interferon-β, which has shown promise as a therapeutic agent in experimental ischaemic stroke, can protect the brain after SAH. SAH was induced in adult male Wistar rats by puncturing the intracranial bifurcation of the right internal carotid artery. Treatment effects of daily interferon-β (n = 16) or vehicle (n = 14) injections were serially evaluated with multiparametric MRI and behavioral tests from day 0 to 7, in compliance with recent recommendations for pre-clinical drug testing. Outcome measures included neurological status, brain lesion volume, blood-brain barrier (BBB) leakage, and levels of inflammatory markers. In animals that survived up to 7 days post-SAH, we found no significant differences between vehicle- and interferon-β-treated animals with respect to final neurological score (14.3 ± 1.0 vs. 13.0 ± 2.2), brain lesion size on T(2)-weighted MR images (59 ± 83 vs. 124 ± 99 mm(3)), BBB leakage (0.26 ± 0.05 vs. 0.22 ± 0.08 contrast-induced relative MR signal change), upregulation of brain RNA for cytokines, chemokines and cell adhesion molecules, and increased neutrophil activation. In contrast to previously published findings in experimental ischemic stroke models, interferon-β has no clear efficacy to protect the brain after SAH. In line with recent highlighting of the significance of negative findings, our data currently do not recommend clinical testing of interferon-β to prevent neurological damage in SAH patients.
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
Agid, R; Lee, S K; Willinsky, R A; Farb, R I; terBrugge, K G
To evaluate the clinical role of CT angiography (CTA) in patients with acute subarachnoid hemorrhage (SAH) for treatment decision-making. Consecutive patients with acute SAH had CTA using a 64-slice scanner for initial clinical decision-making. Image processing included multiplanar volume reformatted (MPVR) maximum intensity projections (MIP) and 3D volume-rendered reconstructions. CTAs were used for (1) evaluating the cause of SAH, and (2) triaging aneurysm-bearing patients to the more appropriate management, either surgical clipping or endovascular coiling. CTA findings were confirmed by neurosurgical exploration or catheter angiography (digital subtraction angiography, DSA). Successful coiling provided evidence that triaging to endovascular treatment was correct. Included in the study were 73 patients. CTA findings were confirmed by DSA or neurosurgical operation in 65 patients, and of these 65, 47 had aneurysmal SAH, 3 had vasculitis, 1 had arterial dissection and 14 had no underlying arterial abnormality. The cause of SAH was detected with CTA in 62 out of the 65 patients (95.4%, sensitivity 94%, specificity 100%). CTA revealed the aneurysm in 46 of 47 patients (98%, sensitivity 98%, specificity 100%, positive predictive value 100%, negative predictive value 82.3%), 1 of 3 vasculitides and 1 of 1 dissection. Of the 46 patients with aneurysm, 44 (95.7%) were referred for treatment based on CTA. In 2 patients (2 of 46, 4.4%) CTA was not informative enough to choose treatment requiring DSA. Of the 44 patients, 27 (61.4%) were referred to endovascular treatment and successful coiling was achieved in 25 (25 of 27, 92.6%). CTA using a 64-slice scanner is an accurate tool for detecting and characterizing aneurysms in acute SAH. CTA is useful in the decision process whether to coil or clip an aneurysm.
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
Venkatraman, Anand; Khawaja, Ayaz M; Gupta, Sahil; Hardas, Shalaka; Deveikis, John P; Harrigan, Mark R; Kumar, Gyanendra
The efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs. We searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model. Inclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management). IAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly
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
Beseoglu, Kerim; Etminan, Nima; Steiger, Hans-Jakob; Hänggi, Daniel
Sodium dysregulation in the course after aneurysmal subarachnoid hemorrhage (aSAH) has been identified as one contributor to adverse clinical outcome. However, the correlation of acute dysnatremia and early brain injury (EBI) remains unclear. We investigated the early course and prognostic relevance of changes in serum sodium concentrations and its relation to EBI after aSAH. Retrospectively, the serum sodium concentration (SSC) of 264 patients with aSAH was analyzed. The first SSC was obtained within 8h after initial ictus and then repeatedly analyzed every 8h over the first five days. Incidence of hypernatremia (defined as SSC>145mmol/l) was correlated with initial neurological condition according to World Federation of Neurological Surgeons grade (WFNS), incidence of delayed cerebral ischemia (DCI) and clinical outcome at 12 month according to modified Rankin Scale (mRS). Within 56h, 82 patients (31.1%) developed hypernatremia which correlated significantly with initial neurological condition (p<0.001). Initial SSC within 8h after SAH did not correlate with patient outcome at 12 month (r=-0.026, p=0.694), however SSC obtained 56h after ictus did significantly (r=0.365, p<0.001; OR 4.14 95% CI (1.84-9.31)). A correlation with the incidence of DCI was not found (r=0.079, p=0.217). The occurrence of hypernatremia within 56h after aSAH was shown to be an independent predictor for poor neurological outcome. Early serum sodium levels after aSAH can be considered as surrogate markers to predict outcome after aSAH irrespective to the occurrence of DCI. However, prospective studies are necessary to validate this concept. Copyright © 2014 Elsevier B.V. All rights reserved.
Cheng, Chongjie; Jiang, Li; Yang, Yanhong; Wu, Haitao; Huang, Zhijian; Sun, Xiaochuan
High mortality following aneurysmal subarachnoid hemorrhage (aSAH) occurs in the early phase, but the underlying mechanism of early brain injury (EBI) in aSAH was less elucidated. In this study, we aimed to investigate the association of apolipoprotein E (APOE) genotypes and early cerebral perfusion after aSAH. We collected venous blood of aSAH patients on admission for APOE genotype identification, applying computed tomography perfusion (CTP) scanning within 24 h after onset. The CTP parameters between patients with different APOE genotypes were compared. Then, a positive item was chosen for separate uni- and multivariate logistic regression analyses to seek its risk factors. Our results showed mean transit time (MTT) rather than other parameters was significantly longer in patients with the APOEε4 allele, compared to those without APOEε4 (6.45 ± 1.17 versus 5.83 ± 0.84 s, P = 0.019). APOEε4 acted as an independent risk factor for MTT prolongation (>5.9 s) in uni- (P = 0.031, OR = 3.960, 95 % CI = 1.131-13.863) and multivariate (P = 0.019, OR = 9.822, 95 % CI = 1.458-66.193) logistic regression analyses, respectively. APOEε4 may induce cerebral perfusion impairment in the early phase, contributing to EBI following aSAH, and assessment of APOE genotypes could serve as a useful tool in the prognostic evaluation and therapeutic management of aSAH.
Lilla, Nadine; Rinne, Christoph; Weiland, Judith; Linsenmann, Thomas; Ernestus, Ralf-Ingo; Westermaier, Thomas
Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. 20 male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34° C) or served as controls by continuous maintenance of normothermia (37.0° C). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (CBF) over both hemispheres were continuously measured. Neurological assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin and eosin and Caspase-3 staining. By a slight increase of MABP in the cooling phase and a significant reduction of ICP, hypothermia improved cerebral perfusion pressure (CPP) in the first 60 minutes after SAH. Accordingly, a trend to increased CBF was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared to normothermic controls. The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH. Copyright © 2017 Elsevier Inc. All rights reserved.
Wallmark, Svante; Ronne-Engström, Elisabeth; Lundström, Erik
Returning to work is a major issue for patients having had an aneurysmal subarachnoid hemorrhage (SAH). It is important, at an early stage, to identify the patients that are unlikely to return to work. The objective of this study was to assess the predictive value of the Montreal Cognitive Assessment (MoCA) at 6 months after ictus on return to work at 12 months. In this prospective study were 96 patients with SAH included in the acute phase. Cognitive functions were assessed at 6 months using the MoCA and return to work at 12 months. The predictive value of MoCA on return to work was analyzed using the area under the receiver operating characteristic curve as well as logistic regression. Of those that had work before the SAH, 52 % were working at 12 months after the ictus. These patients had scored significantly better on MoCA at 6 months (p = 0.01). The area under the receiver operating characteristic curve was 0.75. By using a cut-off on MoCA of <27, 68 % of the patients could be correctly classified as returned/not returned to work. Adding data from the acute phase to the MoCA in a logistic regression model increased the percentage of patients correctly classified as returned/not returned to work by 2 %. Returning to work is a major issue for SAH patients. It is important to identify factors that may interfere with a patient's ability to return to work, and address these issues appropriately. In our study, estimating cognitive functions at 6 months after SAH using the MoCA alone allowed us to predict return to work correctly in 68 % of the cases. We feel that this provides useful information in planning rehabilitation, but that other post-SAH symptoms have to be considered as well.
Spatenkova, Vera; Bradac, Ondrej; de Lacy, Patricia; Skrabalek, Pavel; Suchomel, Petr
Dysnatremias are common and carry a risk of poor prognosis in acute subarachnoid hemorrhage (SAH) patients. The aim of this study was to determine the frequency and outcome of dysnatremias in 344 SAH patients treated by a targeted sodium management regimen. We performed a 10-year observational dysnatremia study. Hyponatremia was defined as serum sodium (SNa) below 135 mmol/L, hypernatremia SNa above 150 mmol/L. Dysnatremia occurred in 35.8% patients; this was more frequently hyponatremia (19.8%) with a mean SNa 132.23±2.09 mmol/L, (16.0% mild, 3.2% moderate, 0.6% severe). Hypernatremia occurred less commonly in 11.9%, P<0.001 with a mean SNa 154.21±3.72 mmol/L, (6.1% mild, 2.9% moderate, 2.9% severe). In 4.8% of patients there were episodes of both dysnatremias. The incidence of hypo-osmolar hyponatremia was 6.4%, Cerebral salt wasting (CSW) 3.5%, syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 0.3% and Central diabetes insipidus 1.7%. The hypernatremic patients had a higher inpatient mortality rate (P=0.001) and a worse overall outcome (P<0.001) than those hyponatremic or normotremic patients. Multivariate logistic regression showed that hypernatremia was an independent risk factor for increased inpatient mortality and poor outcome in patients with SAH. Our 10-year targeted sodium management regimen in acute SAH patients showed that dysnatremias were frequent, predominantly hyponatremia of which the more usual causes were CSW and not SIADH. Hypernatremia was shown to be an independent risk factor for inpatient mortality and poor outcome.
Aries, Marcel J H; de Jong, Sytse F; van Dijk, J Marc C; Regtien, Joost; Depreitere, Bart; Czosnyka, Marek; Smielewski, Peter; Elting, Jan Willem J
Cerebral autoregulation is increasingly recognized as a factor that requires evaluation when managing poor grade aneurysmal subarachnoidal hemorrhage (aSAH) patients. In this single center pilot study, we investigated whether intraventricular intracranial pressure (ICP) derived when extraventricular drain (EVD) is open can be used to calculate dynamic autoregulation estimates in ICU aSAH patients. Ten patients with the diagnosis of aSAH as confirmed by computed tomography (CT) and CT-angiography were enrolled. ICP was monitored via a transducer connected to the most proximal side exit of the EVD catheter. From at least 30 min periods of brain monitoring before, during, and after temporarily EVD closure, commonly used indexes of dynamic cerebral autoregulation were calculated. Preserved pulsatile ICP signals were seen with open EVD. There were no significant changes in parameters describing cerebral autoregulation between EVD open and closed conditions. Power spectra of ABP and ICP showed no significant changes for the selected frequency ranges. There was a small significant increase in absolute ICP [2.4 (3.8) mmHg, p < 0.001] upon short-term EVD closure. Cerebral spinal reserve capacity (RAP index) worsened significantly by short-term EVD closure. Due to preserved slow fluctuations in the ICP signal, an open EVD system can be used to calculate dynamic autoregulation indices in aSAH patients requiring intensive care monitoring with the pressure measurement from the most proximal part of drain. If these results are confirmed in larger study, this technique can open the way for investigating the role of autoregulation disturbance in aSAH patients.
Hendrix, Philipp; Foreman, Paul M; Harrigan, Mark R; Fisher, Winfield S; Vyas, Nilesh A; Lipsky, Robert H; Lin, Minkuan; Walters, Beverly C; Tubbs, R Shane; Shoja, Mohammadali M; Pittet, Jean-Francois; Mathru, Mali; Griessenauer, Christoph J
Nitric oxide is critical in the regulation of cerebral blood flow and smooth muscle proliferation. It is synthesized by 3 nitric oxide synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (eNOS). Aneurysmal subarachnoid hemorrhage (aSAH) causes endothelial dysfunction that, in turn, contributes to pathophysiologic processes surrounding aSAH. Previous studies reported an association of an eNOS single nucleotide polymorphism (SNP) with the clinical sequelae of aSAH. Here, we further elucidate the impact of this eNOS SNP on the clinical course after aSAH. The Cerebral Aneurysm Renin Angiotensin System study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012-2015. Blood samples from all patients enrolled in the study were used for genetic evaluation using 5'exonuclease (Taqman) genotyping assays. Associations between the eNOS SNP rs2070744 (786 T->C) and clinical course after aSAH were analyzed. Samples from 149 aSAH patients were available for analysis. The C allele of the eNOS SNP independently predicted an increased risk for delayed cerebral ischemia (OR = 2.936, 95% CI 1.048-8.226, P = 0.040). The eNOS SNP rs2070744 was not associated with functional outcome or size of aneurysm at the time of rupture. The present study is the first to demonstrate that the C allele of the eNOS SNP 786 T->C rs2070744 is independently associated with an increased risk for delayed cerebral ischemia following aSAH. Copyright © 2017 Elsevier Inc. All rights reserved.
Sakamaki, Tsuyako; Hara, Motohiko; Kayaba, Kazunori; Kotani, Kazuhiko; Ishikawa, Shizukiyo
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. 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). 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). 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.
Kirkness, Catherine J.; Burr, Robert L.; Mitchell, Pamela H.
Background Care of individuals in the intensive care unit (ICU) with brain injury traditionally focuses on maintaining ABP and ICP within prescribed ranges. However research suggests that the dynamic variability of these pressure signals provides additional information about physiologic functioning and may reflect adaptive capacity. Objectives The purpose of this study was to examine the ability to predict long-term outcome from arterial blood pressure (ABP) and intracranial pressure (ICP) variability in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods ABP and ICP were monitored continuously for four days in 90 patients (74% female; mean age 53 years) in an ICU following SAH. Variability of ABP and ICP signals was calculated at four time scales (24-hour, hourly, 5-minute, and difference of sequential 5second averages). Long-term functional outcome was assessed 6 months post-SAH using the Extended Glasgow Outcome Scale. Results Pressure (ABP, ICP) variability indices were better predictors of 6-month functional outcome than mean pressure levels. Indices reflecting faster variability (particularly 5-second) were positively associated with better long-term outcome (typical p<0.001), while greater 24-hour variability was related to poorer outcomes (typical p <0.001), controlling for initial neurologic condition. Conclusions Beyond the measurement of ABP and ICP levels in acutely ill patients with SAH, simple measures of variability of these signals provide prognostic information regarding long-term functional outcome. The relationship between outcome and ICP and ABP variability in SAH 2 variability was dependent on the time scale at which the variability was measured. Given its positive association with better outcome, greater faster variability may reflect better physiologic adaptive capacity. PMID:19411584
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.
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
Bihorac, Azra; Ozrazgat-Baslanti, Tezcan; Mahanna, Elizabeth; Malik, Seemab; White, Peggy; Sorensen, Matthew; Fahy, Brenda G; Petersen, John W
Stress-induced cardiomyopathy (SCM) after subarachnoid hemorrhage (SAH) includes predominant apical or basal regional left ventricular dysfunction (RLVD) with concomitant changes in electrocardiogram or increase in cardiac enzymes. We hypothesized that difference in outcome is associated with the type of RLVD after SAH. We studied a single-center retrospective cohort of SAH patients hospitalized between 2000 and 2010 with follow-up until 2013. We classified patients who had an echocardiogram for clinically indicated reasons according to the predominate location of RLVD as classic SCM-apical form and variant SCM-basal form. A Cox proportional hazard model and logistic regression were used to estimate the risk for death and hospital complications associated with different RLVD after adjustment for propensity to undergo echocardiography given clinical characteristics on admission. Among 715 SAH patients, 28% (200/715) had an echocardiogram for clinical evidence of cardiac dysfunction during hospitalization, the most common being acute left ventricular dysfunction, suspected acute ischemic event, changes in electrocardiogram and cardiac enzymes, and arrhythmia. SCM was present in 59 patients (8% of all cohort and 30% of patients with echocardiogram, respectively) with similar distribution of SCM-basal (25/59) and SCM-apical forms (34/59). SAH patients who had an echocardiogram for clinically indicated reasons had a significantly decreased risk-adjusted long-term survival compared with those without an echocardiogram, regardless of the presence of RLVD. SCM-basal form was associated with cardiac complications (odds ratio, 6.1; 99% confidence interval, 1.8-20.2) and severe sepsis (odds ratio, 5.3; 99% confidence interval, 1.6-17.2). SAH patients with echocardiogram for a clinically indicated reason have a decreased long-term survival, regardless of the presence of RLVD. The association between severe sepsis and SCM-basal warrants future studies to determine their
Reznik, Michael E; Schmidt, J Michael; Mahta, Ali; Agarwal, Sachin; Roh, David J; Park, Soojin; Frey, Hans Peter; Claassen, Jan
Agitated delirium is frequent following acute brain injury, but data are limited in patients with subarachnoid hemorrhage (SAH). We examined incidence, risk factors, and consequences of agitation in these patients in a single-center retrospective study. We identified all patients treated with antipsychotics or dexmedetomidine from a prospective observational cohort of patients with spontaneous SAH. Agitation was confirmed by chart review. Outcomes were assessed at 12 months using the modified Rankin Scale (mRS), Telephone Interview for Cognitive Status (TICS), and Lawton IADL (Instrumental Activities of Daily Living) scores. Independent predictors were identified using logistic regression. From 309 SAH patients admitted between January 2011 and December 2015, 52 (17 %) developed agitation, frequently in the first 72 h (50 %) and in patients with Hunt-Hess grades 3-4 (12 % of grades 1-2, 28 % of grades 3-4, 8 % of grade 5). There was also a significant association between agitation and a history of cocaine use or prior psychiatric diagnosis. Agitated patients were more likely to develop multiple hospital complications; and in half of these patients, complications were diagnosed within 24 h of agitation onset. Agitation was associated with IADL impairment at 12 months (Lawton >8; p = 0.03, OR 2.7, 95 % CI, 1.1-6.8) in non-comatose patients (Hunt-Hess 1-4), but not with functional outcome (mRS >3), cognitive impairment (TICS ≤30), or ICU/hospital length of stay after controlling for other predictors. Agitation occurs frequently after SAH, especially in non-comatose patients with higher clinical grades. It is associated with the development of multiple hospital complications and may have an independent impact on long-term outcomes.
Dhar, Rajat; Washington, Chad; Diringer, Michael; Zazulia, Allyson; Jafri, Hussain; Derdeyn, Colin; Zipfel, Gregory
Background The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI. Methods Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9 ± 2 days after aneurysmal SAH). Each underwent 15O-PET imaging to measure global and regional CBF at baseline and post-sildenafil. Results Mean arterial pressure declined by 10 mm Hg on average post-sildenafil (8 %, p = 0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5 ± 7 ml/100g/min at baseline vs. 33.9 ± 8.0 ml/100g/min post-sildenafil, p = 0.84). The proportion of brain regions with low CBF (<25 ml/100g/min) was also unchanged after sildenafil infusion. Conclusions Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH. PMID:26940913
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.
Lindbohm, Joni Valdemar; Kaprio, Jaakko; Korja, Miikka
Background The role played by total cholesterol (TC) in risk for subarachnoid hemorrhage (SAH) is unclear because studies report both high and low TC each as a risk factor. We performed a systematic review to clarify associations between lipid profile and SAH. Methods Our literature search comprised Pubmed, Scopus, and Cochrane Library databases with no language, publication year, or study type limitations. The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) checklist guided our reporting. Data forms adapted from the Critical Appraisal Skills Program (CASP), and Cochrane Collaboration guidelines provided a platform for risk-of-bias evaluation. We used a random effects model to calculate pooled estimates and assessed heterogeneity with I2-statistics. Results Of the final 21 studies reviewed, 12 were prospective and 9 retrospective. All studies assessed TC, four assessed HDL, and none LDL in risk for SAH. Heterogeneity among all, retrospective, and Asian studies was high (I2 = 79.5%, I2 = 89.0%, and I2 = 84.3%) and considerable in prospective (I2 = 46.0%). We therefore focused on qualitative analysis and found that only two studies had a low risk of bias. According to these studies high TC increases risk for SAH in men, whereas the role of HDL remained unclear. Conclusion The low-risk-of-bias studies suggest that elevated TC levels elevate risk for SAH in men. Due to the high prevalence of hypercholesterolemia, population attributable risk (PAR) of hypercholesterolemia may exceed the PARs of smoking and hypertension in men. Apart from diabetes and obesity, the risk-factor profile of SAH seems to resemble that of other cerebrovascular diseases, at least in men. PMID:27077917
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.