Neuropsychological function after endovascular and neurosurgical treatment of subarachnoid hemorrhage: a systematic review and meta-analysis.

OBJECTIVE Subarachnoid hemorrhage (SAH) is treated with either surgical clipping or endovascular coiling, though the latter is the preferred treatment method given its more favorable functional outcomes. However, neuropsychological functioning after treatment is rarely taken into account. In this meta-analysis, the authors synthesized relevant data from the literature and compared neuropsychological functioning in patients after coiling and clipping of SAH. They hypothesized that the coiled patients would outperform the clipped patients; that group differences would be greater with higher posterior circulation rupture rates, in older patients, and in more recent publications; that group differences would be smaller with greater rates of middle cerebral artery (MCA) rupture; and that anterior communicating artery (ACoA) rupture rates would not influence effect sizes. METHODS The MEDLINE, Embase, and PsycINFO databases were searched for clinical studies that compared neuropsychological functioning after either endovascular coiling or surgical clipping for SAH. Hedge's g and 95% confidence intervals were calculated using random effects models. Patients who had undergone coiling or clipping were compared on test performance in 8 neuropsychological domains: executive functions, language, attention/processing speed, verbal memory, visual memory, spatial memory, visuospatial functions, and intelligence. Patients were also compared with healthy controls, and meta-regressions were used to explore the relation between effect sizes and publication year, delay between treatment and neuropsychological testing, mean patient age, and rates of posterior circulation, ACoA, and MCA ruptures. RESULTS Thirteen studies with 396 clipped cases, 314 coiled cases, and 169 healthy controls were included in the study. The coil-treated patients outperformed the clip-treated patients on executive function (g = 0.17, 95% CI 0.08-0.25) and language tests (g = 0.23, 95% CI 0.07-0.39), and all patients were impaired relative to healthy controls (g ranged from -0.93 to -0.29). Coiled patients outperformed clipped patients to a greater degree in more recent publications, over longer posttreatment testing delays, and among older patients. Higher rates of posterior circulation and MCA aneurysms were associated with smaller group differences, while ACoA rupture rates did not influence effect sizes. CONCLUSIONS Coiling of SAH may promote superior neuropsychological functioning under certain circumstances and could have applications for the specialized care of SAH patients.

Vasospasm: my first 25 years-what worked? what didn't? what next?

Angiographic vasospasm as a complication of aneurysmal and other types of subarachnoid hemorrhage (SAH) was identified about 62 years ago. It is now hypothesized that angiographic vasospasm contributes to delayed cerebral ischemia (DCI) by multiple pathways, including reduced blood flow from angiographic vasospasm as well as microcirculatory constriction, microthrombosis, cortical spreading ischemia, and delayed effects of early brain injury. It is likely that other factors, such as systemic complications, effects of the subarachnoid blood, brain collateral and anastomotic blood flow, and the genetic and epigenetic makeup of the patient, contribute to the individual's response to SAH. Treatment of aneurysmal SAH and DCI includes neurocritical care management, early aneurysm repair, prophylactic administration of nimodipine, and rescue therapies (induced hypertension and balloon or pharmacologic angioplasty) if the patient develops DCI. Well-designed clinical trials of tirilazad, clasozentan, antiplatelet drugs, and magnesium have been conducted using more than a 1,000 patients each. Some of these drugs have almost purely vascular effects; other drugs are theoretically neuroprotective as well, but they share in common the ability to reduce angiographic vasospasm and, in many cases, DCI, but have no effect on clinical outcome. Experimental research in SAH continues to identify new targets for therapy. Challenges for the future will be to identify the most promising drugs to advance from preclinical studies and to understand why clinical trials have so frequently failed to show drug benefit on clinical outcome. Similar issues with treatment of ischemic stroke are being addressed by suggestions for improving the quality of experimental studies, collaborative preclinical trials, and multinational, multicenter clinical studies that can rapidly include many patients and be large enough to account for numerous factors that conspire to disrupt clinical trials.

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

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

Valproic Acid treatment after experimental subarachnoid hemorrhage.

INTRODUCTION: Subarachnoid hemorrhage (SAH) can result in significant brain injury. Valproic acid (VPA), a widely-used anti-epileptic drug, was investigated as a possible neuroprotective drug in a prechiasmatic injection model of SAH in mice. METHODS: Mice were randomized to the following experimental groups: SAH, SAH + VPA, Sham, and Sham + VPA. VPA (400 mg/kg) or saline was administered within 30 min of SAH induction and every 12 h thereafter for 48 h. Neurobehavioral assessments using the modified Garcia Score were conducted at 24 and 48 h. Brain injury was assessed at 48 h with fluoro-jade b and caspase-3/NeuN histo- and immunohistochemistry. Vasospasm was assessed in the MCA branches using hematoxylin & eosin histology. RESULTS: SAH mice treated with VPA appeared to have improved neurobehavioral assessments at both 24 and 48 h compared to untreated SAH mice. VPA treatment in SAH mice also significantly decreased the number of degenerating neurons on fluoro-jade b staining. In VPA-treated SAH mice, there was a trend toward a decrease in the number of apoptotic neurons on caspase-3/NeuN immunohistochemistry. VPA did not significantly affect vasospasm. CONCLUSION: This study demonstrated that VPA improves neurological outcome and decreases brain injury in a mouse model of SAH.

Nitric oxide synthases: three pieces to the puzzle?

Subarachnoid hemorrhage remains to be a devastating diagnosis in this day and age, with very few effective interventions. Rising evidence is now pointing towards the marked importance of secondary complications after the hemorrhage, and its active role in morbidity and mortality of this stroke. This review will focus on the role of Nitric Oxide Synthases (NOSes) the role they play in the pathogenesis of SAH.

Anterior circulation model of subarachnoid hemorrhage in mice.

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.

Experimental models of chronic subdural hematoma.

OBJECTIVES: Chronic subdural hematoma (CSDH) is a common neurosurgical problem. Most studies of pathogenesis and treatment involve humans. Advances in understanding of human diseases may be made using animal models. We reviewed all animal models of CSDH and report here their results, conclusions and limitations in order to set a baseline upon which further advanced experimental work related to this disease can be made. METHODS: PubMed, Medline, Embase and ISI Web of Knowledge were searched with no time limits using the keyword 'chronic subdural hematoma' and MeSH term 'hematoma, subdural, chronic'. The authors reviewed all papers written related to this disease and selected all publications involving animals. There were no other restrictions. The findings and conclusions of the papers are summarized here. No formal analysis was done because of the variation in species used, methods for induction of CSDH, times of assessment and reporting of results. RESULTS: Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description. DISCUSSION: We did not find a report of a reproducible, well-described animal model of human CSDH.

Systematic review of primary intracranial glioblastoma multiforme with symptomatic spinal metastases, with two illustrative patients.

Glioblastoma multiforme is a malignant tumour with a universally fatal diagnosis. We report two patients with glioblastoma with symptomatic metastasis to the spinal cord and perform a systematic review all 35 reports of symptomatic glioblastoma dissemination to the spinal leptomeninges and/or intramedullary spinal axis. Our analysis of the data shows a median time to spinal metastasis of 10 months and a median time of three months from spinal metastasis to death. Treatments described include palliative laminectomies, radiotherapy and chemotherapy. No treatment strategy offered a therapeutic advantage as patients deteriorated rapidly regardless of intervention. Patients who underwent only a biopsy for intracranial glioblastoma had a shorter time to development of spinal metastasis. In addition, there may be an association between intramedullary metastasis and shorter survival. This paper highlights the importance of considering symptomatic spinal dissemination in glioblastoma multiforme. We also review the incidence and postulate mechanisms of tumour dissemination in the central nervous system. Clearly, further research into radiotherapeutic and chemotherapeutic options in this clinical setting is required.

Circulatory and vascular changes after aneurysmal subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) is a major complication that afflicts approximately 30% of patients who suffer an aneursymal subarachnoid hemorrhage (SAH). DCI is often associated with neurological infarction, poor outcome and mortality. Though the pathogenesis of DCI is not yet clear, it is traditionally been attributed to angiographic vasospasm. Unfortunately, clinical trials based on this premise have mostly been disappointing, predominantly unable to prevent ischemic damage and improve patient outcome despite reducing angiographic vasospasm. More recently, increasing concern that vasospasm could not fully account for DCI development has incited novel proposals as to the pathogenesis of DCI. A general theme exists among these theories (microcirculatory constriction, cortical spreading depression, blood brain barrier breakdown, microthrombosis) in that a majority seems to revolve around dysfunction and changes to the microvasculature. This purpose of this review was then to juxtapose macrovascular and microvascular changes after SAH, and provide an overview of current and prospective treatments.

Malignant ganglioglioma: case report and review of literature.

We report a case of de novo malignant ganglioglioma. A 61-year-old male presented with a 12-day history of headaches and general malaise. Pre-operative magnetic resonance imaging revealed an irregular enhancing mass in the left temporal lobe with associated dural enhancement and subacute subdural hematoma. The findings at surgery were of a vascular tumor intimately involving the surrounding white matter, with central necrosis. Histological and immunohistochemical studies showed an anaplastic ganglioglioma with World Health Organization grade IV characteristics. Gangliogliomas of the central nervous system are rare and are typified by a pediatric predilection and indolent behavior. A review of the de novo anaplastic and malignant gangliogliomas is presented.

Locked-in syndrome from rostro-caudal herniation.

Locked-in syndrome (LIS) is often caused by ventral pontine injury involving the perforating pontine vessels of the basilar artery and recovery is rarely reported. We report a patient who developed LIS acutely after aneurysmal subarachnoid haemorrhage and rostro-caudal herniation from hydrocephalus. The patient's clinical course and diagnostic studies suggest that the likely mechanism of this patient's LIS is mechanical compression of the ventral pons anteriorly against the clivus. The patient's slow but full recovery allowed us to further differentiate this clinical entity from the more common LIS due to ischaemic mechanisms.

Management of cerebral vasospasm.

Cerebral vasospasm is delayed narrowing of the large arteries of the circle of Willis occurring 4 to 14 days after aneurysmal subarachnoid hemorrhage (SAH). It is but one cause of delayed deterioration after SAH but, in general, is the most important potentially treatable cause of morbidity and mortality after SAH. Development of vasospasm is best predicted by the volume, location, persistence and density of subarachnoid clot early after SAH. Diagnosis is made by catheter angiography or, with less accuracy, by computed tomographic angiography, transcranial Doppler ultrasound or other methods. Treatment remains problematic because it is expensive, time-consuming, associated with substantial risk and largely ineffective. Treatment includes optimization of factors that affect cerebral blood flow and metabolism, systemic administration of nimodipine, hemodynamic therapy and pharmacologic and mechanical angioplasty.

Treatment of deep cerebral venous thrombosis by local infusion of tissue plasminogen activator.

BACKGROUND: Treatment of extensive intracranial venous sinus thrombosis with thrombolytic drugs is described, although the indications for and most efficacious technique for achieving thrombolysis remain uncertain. We report the successful lysis of superficial and deep venous system thrombosis by infusion of recombinant human tissue-type plasminogen activator (rt-PA) into the anterior superior sagittal sinus. CASE DESCRIPTION: A 34-year-old man presented with headaches followed by decreased level of consciousness and left hemiplegia. Angiography showed thrombosis of the superior sagittal and both transverse and straight sinuses with extension into the internal cerebral veins. The superior sagittal sinus was catheterized via a transfemoral route and rt-PA, 25 mg, was infused. There was no significant change in the thrombosis. The catheter was left in place and rt-PA was infused at 1 mg/minute for 19 hours. Repeat angiography showed resolution of the thrombosis. The patient was placed on heparin and then coumadin. He recovered completely. CONCLUSIONS: This report suggests that superselective infusion of thrombolytics into thrombosed intracranial venous sinuses can lyse intracranial venous sinus thrombosis. The thrombolytic agent must be infused for hours. The apparent successful lysis of clot in the deep venous system when infusion was into the superior sagittal sinus might be related to diffusion of rt-PA throughout the intracranial venous system or to improved venous outflow caused by lysis of clot in superficial dural sinuses.

Angiographic vasospasm in a contemporary series of patients with aneurysmal subarachnoid haemorrhage.

Over the last decade there have been significant changes in the management of patients with aneurysmal subarachnoid haemorrhage (SAH). Many of these changes, such as haemodilutional, hypervolaemic, hypertensive therapy and the use of calcium channel blockers, have been directed at the prevention and treatment of vasospasm. The angiograms of a contemporary series of 56 consecutive surgically treated patients with aneurysmal SAH were examined to compare angiographic vasospasm with that seen in historical studies. The time course of angiographic vasospasm was found to be broadly similar to that reported in previous studies, with onset after day 3 following SAH, maximal narrowing during the second week, and resolution after day 16. The times of peak narrowing and resolution were slightly earlier in previous studies. 30% of patients had clinical vasospasm (delayed neurological deficit for which other causes had been excluded), and these patients had a trend to more severe angiographic narrowing than those without clinical vasospasm, particularly in the second week following SAH. 44 angiograms were performed between days 1-3 post SAH and repeated between days 4-16. 95% of these showed arterial narrowing at the second angiogram. Patients not achieving an independent outcome tended to have had both more clinical vasospasm and more severe angiographic spasm than those achieving independence. It is concluded that angiographic vasospasm remains a common occurrence in the modern era, and continues to be associated with clinical events and a poor outcome.