Association of intraprocedural blood pressure and end tidal carbon dioxide with outcome after acute stroke intervention.

BACKGROUND: General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association. METHODS: Consecutive patients treated at our institution between August 2007 and December 2010 were identified from a prospective database. Clinical data were then extracted by retrospective chart review. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established prespecified predictors of functional outcome. RESULTS: Of the 106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased significantly after induction of GA, but there was no association between BP and outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were significantly associated with outcomes in both univariate and multivariate analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale (mRS) 0-3) was higher than in those with unfavorable outcomes (mRS 4-6): 35.2 mmHg versus 32.2 (p = 0.03) at 60 min and 34.9 versus 31.9 (p = 0.04) at 90 min. The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were the same: 0.76 (95 % CI 0.65-0.92; p = 0.004) at 60 min and 0.76 (95 % CI 0.61-0.93; p = 0.01) at 90 min. CONCLUSIONS: While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.

Elevated BNP is associated with vasospasm-independent cerebral infarction following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH. METHODS: Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm. RESULTS: BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37-275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥ 276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006). CONCLUSIONS: Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

Prophylaxis for venous thrombo-embolism in neurocritical care: a critical appraisal.

Venous thrombo-embolism (VTE) is frequently encountered in critically ill neurological and neurosurgical patients admitted to intensive care units. This patient population includes those with brain neoplasm, intracranial hemorrhage, ischemic stroke, subarachnoid hemorrhage, pre- and post-operative patients undergoing neurosurgical procedures and those with traumatic brain injury, and acute spinal cord injury (SCI). There is a wide variability in clinical practice for thromboprophylaxis in these patients, in part due to paucity of data based on randomized clinical trials. Here, we review the current literature on the incidence of VTE in the critically ill neurological and neurosurgical patients as well as appraise available data to support particular practice paradigms for specific subsets of these patients. Data synthesis was conducted via search of Medline, Cochrane databases, and manual review of article bibliographies. Critically ill neurological and neurosurgical patients have higher susceptibility to VTE. Intermittent compression devices with or without anti-thrombotics is generally the method of choice for thromboprophylaxis. Low molecular weight heparin is the method of choice in certain patient subgroups such as those with SCI and ischemic stroke. Inferior vena cava filters may play a role in thromboprophylaxis in selected cases. Without clear guidelines that can be universally applied to this diverse group of patients, prophylaxis for VTE should be tailored to the individual patient with cautious assessment of benefits versus risks. There is a need for higher level evidence to guide VTE prophylaxis in certain subgroups of this patient population.

Levodopa-responsive parkinsonism after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Levodopa-responsive Parkinsonism is a rare complication of subarachnoid hemorrhage and no cases have been reported to occur in the absence of hydrocephalus. METHODS: Case report. RESULTS: We describe a 42-year-old woman who developed progressive severe Parkinsonism in the second week after aneurysmal subarachnoid hemorrhage. No hydrocephalus was present. Neuroimaging revealed striking abnormalities of the midbrain in the region of the substantia nigra. She was ultimately treated with high dose levodopa/carbidopa with a dramatic response. CONCLUSIONS: This case suggests that Parkinsonism may occur as a delayed complication of subarachnoid hemorrhage, and that in these patients, a trial of levodopa-carbidopa may be warranted.

Immunomodulatory therapies in neurologic critical care.

INTRODUCTION: Neurologic disorders with autoimmune dysregulation are commonly encountered in the critical care setting. Frequently encountered diseases include Guillain-Barré syndrome (GBS), myasthenia gravis, multiple sclerosis, acute demyelinating encephalomyelitis, and encephalitides. Immunomodulatory therapies, including high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins, are the cornerstone of the treatment of these diseases. Here we review the efficacy and side effects of immunomodulatory therapies commonly utilized in critically ill neurologic patients in the intensive care setting. METHODS: Search of Medline, Cochrane databases, and manual review of article bibliographies. RESULTS: The efficacy of high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins have been studied extensively in GBS, myasthenia gravis, and demyelinating disorders such as multiple sclerosis and acute demyelinating encephalomyelitis. For these diseases, however, the duration of treatment, dosing regimens, and choices among different therapeutic modalities remain controversial. For many of the other diseases (e.g., encephalitis and status epilepticus of autoimmune etiology) discussed in this review, evidence is limited to small case series. CONCLUSIONS: There is good evidence for the efficacy and tolerability of immunomodulatory therapies in GBS, myasthenia gravis, and acute central nervous system demyelination, though data to establish superiority of one therapeutic regimen over another remains lacking. For most other conditions, the data for immunomodulatory therapies are limited, and further research is required.

Clinical presentation and long-term outcome of cerebral venous thrombosis.

BACKGROUND: Despite recent advances, the clinical features of cerebral venous thrombosis (CVT) remain incompletely characterized. To our knowledge, no case series have been reported from North American centers with detailed long-term outcome data, and few studies have evaluated recanalization rates. METHODS: All cases of CVT at a single tertiary care hospital between 1995 and 2004 were retrospectively reviewed. Follow-up information was obtained from direct patient interviews. RESULTS: Follow-up data were available for 58 of 61 CVT patients (median 50 months). Average age was 40, and 66% were women. Headache and focal neurological deficits were noted in 82% and 72%, respectively. Intracranial hemorrhage was seen in 44%. Hypercoagulable risk factors were identified in 84%. Anticoagulation was initiated acutely in 84%, including in all patients with intraparenchymal hemorrhage (IPH). The percentage of patients with a modified Rankin Score (mRS) of 0 to 2 at admission, hospital discharge and last follow-up were 41%, 67%, 90%, respectively; the rate of favorable long-term outcome did not differ significantly between patients with and without IPH. In the subset of 21 patients with follow-up imaging available for direct review, 90% had partial or complete recanalization. CONCLUSIONS: The demographics, clinical presentation, imaging findings, and risk factors in this large North American cohort of CVT patients strongly support the observations of previous European case series. In addition, the favorable long-term outcome and recanalization rates observed lend further support to the safety and efficacy of acute heparin therapy for the treatment of symptomatic CVT (irrespective of the presence of ICH).

The formation mechanism for printed silver-contacts for silicon solar cells.

Screen-printing provides an economically attractive means for making Ag electrical contacts to Si solar cells, but the use of Ag substantiates a significant manufacturing cost, and the glass frit used in the paste to enable contact formation contains Pb. To achieve optimal electrical performance and to develop pastes with alternative, abundant and non-toxic materials, a better understanding the contact formation process during firing is required. Here, we use in situ X-ray diffraction during firing to reveal the reaction sequence. The findings suggest that between 500 and 650 °C PbO in the frit etches the SiNx antireflective-coating on the solar cell, exposing the Si surface. Then, above 650 °C, Ag(+) dissolves into the molten glass frit - key for enabling deposition of metallic Ag on the emitter surface and precipitation of Ag nanocrystals within the glass. Ultimately, this work clarifies contact formation mechanisms and suggests approaches for development of inexpensive, nontoxic solar cell contacting pastes.

Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke.

BACKGROUND: The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment. OBJECTIVES: To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study. DESIGN AND SETTING: Case studies at a university hospital. INTERVENTIONS: Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment. MAIN OUTCOME MEASURES: National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up. CONCLUSION: Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

Rapid thermal processing chamber for in-situ x-ray diffraction.

Rapid thermal processing (RTP) is widely used for processing a variety of materials, including electronics and photovoltaics. Presently, optimization of RTP is done primarily based on ex-situ studies. As a consequence, the precise reaction pathways and phase progression during the RTP remain unclear. More awareness of the reaction pathways would better enable process optimization and foster increased adoption of RTP, which offers numerous advantages for synthesis of a broad range of materials systems. To achieve this, we have designed and developed a RTP instrument that enables real-time collection of X-ray diffraction data with intervals as short as 100 ms, while heating with ramp rates up to 100 °Cs(-1), and with a maximum operating temperature of 1200 °C. The system is portable and can be installed on a synchrotron beamline. The unique capabilities of this instrument are demonstrated with in-situ characterization of a Bi2O3-SiO2 glass frit obtained during heating with ramp rates 5 °C s(-1) and 100 °C s(-1), revealing numerous phase changes.

Children with classic congenital adrenal hyperplasia have decreased amygdala volume: potential prenatal and postnatal hormonal effects.

Children with classic congenital adrenal hyperplasia (CAH) have multiple endocrine imbalances, including prenatal glucocorticoid and adrenomedullary deficiency and androgen excess, with possible postnatal iatrogenic glucocorticoid excess, hyperandrogenism, and adrenomedullary hypofunction. Prenatal masculinization of the brain has been suggested in girls with classic CAH. Hormones of the hypothalamic-pituitary-adrenal axis and sex hormones interact with extrahypothalamic regulatory centers of the brain, including the amygdala and hippocampus. The amygdala is important in the processing of emotion and generation of fear, whereas the hippocampus plays an important role in memory. Chronic hypercortisolemia has been shown to be associated with hippocampal damage, while glucocorticoids and corticotropin-releasing factor play a major role in the regulation of amygdala function. We performed magnetic resonance imaging of the brain on 27 children with classic CAH and 47 sex- and age-matched controls. Volumes of the cerebrum, ventricles, temporal lobe, amygdala, and hippocampus were quantified. Females with CAH did not have brains with male-specific characteristics. In contrast, a significant decrease in amygdala volume was observed in both males and females with CAH (males, P = 0.01; females, P = 0.002). Iatrogenic effects on the hippocampus due to glucocorticoid therapy were not observed in children with CAH. These results suggest that prenatal glucocorticoid deficiency with resulting alterations in hypothalamic-pituitary-adrenal axis regulation, sex steroid excess, or some combination of these preferentially affect the growth and development of the amygdala, a structure with major functional implications that warrant further exploration.

Effects of hormones and sex chromosomes on stress-influenced regions of the developing pediatric brain.

Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological factors may account for many of the sex differences in stress reactivity. In this study, we have relied on studies of naturally occurring anomalous processes, such as congenital adrenal hyperplasia (CAH) and Klinefelter's syndrome (XXY), to observe the effects of hormones and sex chromosomes on brain structures thought to influence an individual's vulnerability to stress. Brain magnetic resonance imaging (MRI) scans were obtained both from 16 boys with classic CAH and 34 age- and sex-matched controls and from 20 XXY children and 40 age-matched controls. Smaller amygdala volumes were observed in boys with CAH than in matched controls, and in XXY patients than in matched controls. XXY patients were also found to have smaller hippocampus volumes when compared with matched controls. Acknowledging that hormone and sex chromosome effects upon the developing human brain are widespread and complex, it is difficult to conclude, with any certainty, the etiology of the differences found in this study. Future studies that examine longitudinal data and/or other diagnostic groups, however, may help to better elucidate specific hormone and sex chromosome effects upon stress-related structures in the brain.

Dural venous sinus angioplasty and stenting for the treatment of idiopathic intracranial hypertension.

BACKGROUND: Lumboperitoneal shunt (LPS), ventriculoperitoneal shunt (VPS) and optic nerve sheath fenestration (ONSF) are accepted surgical therapies for medically refractory idiopathic intracranial hypertension (IIH). In the subset of patients with IIH and venous sinus stenosis, dural venous sinus stenting has emerged as an alternative surgical approach. METHODS: All cases of dural stents for IIH at our institution were retrospectively reviewed. Eligibility criteria included medically refractory IIH with documented papilledema and dural venous sinus stenosis of the dominant venous outflow system (gradient ≥10 mm Hg). RESULTS: Fifteen cases (all women) of mean age 34 years were identified. All had failed medical therapy and six had failed surgical intervention. Technical success was achieved in all patients without major periprocedural complications. The mean preprocedural gradient across the venous stenosis was reduced from 24 mm Hg before the procedure to 4 mm Hg after the procedure. Headache resolved or improved in 10 patients. Papilledema resolved in all patients and visual acuity stabilized or improved in 14 patients. There were no instances of restenosis among the 14 patients with follow-up imaging. CONCLUSION: In this small case series, dural sinus stenting for IIH was performed safely with a high degree of technical success and with excellent clinical outcomes. These results suggest that angioplasty and stenting for the treatment of medically refractory IIH in patients with dural sinus stenosis warrants further investigation as an alternative to LPS, VPS and ONSF.

Stent assisted coil embolization of unruptured middle cerebral artery aneurysms.

BACKGROUND: Due to anatomic features, including wide necks and incorporation of important branches, endovascular coiling of middle cerebral artery (MCA) aneurysms has proved challenging. Stent assisted embolization may increase the likelihood of successful treatment. METHODS: Consecutive patients undergoing stent assisted coil embolization utilizing the Neuroform stent from 2004 to 2009 were identified by hospital billing records. Procedural and clinical information-including procedure related mortality and morbidity and long term outcomes-were then obtained by retrospective chart review. RESULTS: Treatment was successful in 22/23 (96%) patients. Median age was 61 years and 16/22 (73%) were women. Aneurysm size was: <5 mm in 5/22 (23%); 5-9 mm in 14/22 (64%); and ≥10 mm in 3/22 (14%) patients. There were four periprocedural complications (including one stroke and one intraprocedural rupture), none associated with neurological dysfunction. Angiographic follow-up was available in 18/22 (82%) and clinical follow-up in 19/22 (86%) patients, both at a median of 1 year (mean 1.2 years) after coiling. Aneurysm occlusion was complete in 12/18 (67%), a neck remnant was present in 3/18 (17%) and persistent aneurysmal filling was present in 3/18 (17%) patients, requiring retreatment in 1/18 (6%) patient. In-stent stenosis of 50%, which was asymptomatic, occurred in 1/18 (6%) patient. No subarachnoid hemorrhages and no ischemic events related to the procedure were observed during follow-up. CONCLUSION: In this small series, the technical success rate was 96%, there were no transient or permanent neurological complications and complete aneurysmal occlusion was achieved in two-thirds of treated aneurysms on follow-up angiography. These results suggest that in appropriately selected patients, stent assisted coil embolization of MCA aneurysms can be performed with a high degree of safety and acceptable durability.

Meta-analysis of randomized intra-arterial thrombolytic trials for the treatment of acute stroke due to middle cerebral artery occlusion.

BACKGROUND: Randomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints. METHODS: All randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h. RESULTS: Three trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤ 1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤ 2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02). CONCLUSIONS: Our meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

Mechanical thrombectomy for the treatment of acute ischemic stroke.

Acute ischemic stroke is the leading cause of severe disability and the third leading cause of death in the USA. Intravenous tissue plasminogen activator (IV tPA) remains the most widely advocated treatment, but this therapy is limited by a narrow time window (<4.5 h after stroke onset), exclusion of patients with coagulopathy and recanalization rates of less than 50%. As a result, only 5% of acute stroke patients are treated with IV tPA. Endovascular mechanical thrombectomy may be employed, either as a standalone therapy or as an adjunct to IV tPA, and has several potential advantages, including a wider time window (up to 8 h), the capacity for use in coagulopathic patients and higher recanalization rates (up to 82%). Nonetheless, mechanical thrombectomy has engendered controversy because no randomized trials have yet been performed to support its use. In this article, we review the clinical applications of mechanical thrombectomy for the treatment of acute ischemic stroke. Ultimately, the results of ongoing trials are necessary to delineate the patient populations most likely to benefit from this therapy.