Lowering blood pressure in acute intracerebral hemorrhage: safe, but will it help?
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Acute Disease↗
Biomedical subjects
H Yonas
Publications and source records attributed to H Yonas.
Molecular anatomy of an intracranial aneurysm: coordinated expression of genes involved in wound healing and tissue remodeling.
BACKGROUND AND PURPOSE: Approximately 6% of human beings harbor an unruptured intracranial aneurysm. Each year in the United States, >30 000 people suffer a ruptured intracranial aneurysm, resulting in subarachnoid hemorrhage. Despite the high incidence and catastrophic consequences of a ruptured intracranial aneurysm and the fact that there is considerable evidence that predisposition to intracranial aneurysm has a strong genetic component, very little is understood with regard to the pathology and pathogenesis of this disease. METHODS: To begin characterizing the molecular pathology of intracranial aneurysm, we used a global gene expression analysis approach (SAGE-Lite) in combination with a novel data-mining approach to perform a high-resolution transcript analysis of a single intracranial aneurysm, obtained from a 3-year-old girl. RESULTS: SAGE-Lite provides a detailed molecular snapshot of a single intracranial aneurysm. These data suggest that, at least in this specific case, aneurysmal dilation results in a highly dynamic cellular environment in which extensive wound healing and tissue/extracellular matrix remodeling are taking place. Specifically, we observed significant overexpression of genes encoding extracellular matrix components (eg, COL3A1, COL1A1, COL1A2, COL6A1, COL6A2, elastin) and genes involved in extracellular matrix turnover (TIMP-3, OSF-2), cell adhesion and antiadhesion (SPARC, hevin), cytokinesis (PNUTL2), and cell migration (tetraspanin-5). CONCLUSIONS: Although these are preliminary data, representing analysis of only one individual, we present a unique first insight into the molecular basis of aneurysmal disease and define numerous candidate markers for future biochemical, physiological, and genetic studies of intracranial aneurysm. Products of these genes will be the focus of future studies in wider sample sets.
Calcium-Binding Proteins↗
Revisiting the question, "is the acetazolamide test valid for quantitative assessment of maximal cerebral autoregulatory vasodilation?".
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Acetazolamide↗
Cerebrovascular reserve in patients with carotid occlusive disease assessed by stable xenon-enhanced ct cerebral blood flow and transcranial Doppler.
BACKGROUND AND PURPOSE: Cerebrovascular reserve (CVR) by both transcranial Doppler ultrasonography (TCD) and quantitative cerebral blood flow (CBF) can identify subgroups of patients at increased risk for stroke. A direct comparison of CVR measurements obtained with both technologies in patients with cerebrovascular occlusive disease is lacking. METHODS: CVRs before and after acetazolamide administration (1 g IV) were measured by TCD insonation of the middle cerebral artery (MCA) and CBF obtained with stable xenon CT (Xe/CT) in 38 patients with carotid occlusive disease. Sensitivity/specificity calculations were based on 2 Xe/CT MCA values: an average over 4 levels and the level with the lowest percent change in CBF. Compromised CVR was defined as no reactivity or a decrease in reactivity. RESULTS: Using the analysis of the systolic TCD, we found that velocity changes compared with the average Xe/CT MCA CVR showed a sensitivity of 33%, specificity of 90.6%, positive predictive value of 54.5%, and negative predictive value of 80%. The sensitivity of TCD compared with the lowest Xe/CT CBF CVR was 35.5%, specificity and positive predictive values were 100%, and negative predictive value was 66.7%. The index of validity was between 72% and 76%. CONCLUSIONS: TCD is much less sensitive than Xe/CT CBF in identifying patients with compromised CVR. This may be a result of the inability of TCD to identify patients with compromised reserves when their MCA blood flow comes from collateral sources. The lack of correlation between TCD and Xe/CT CBF for identifying patients with compromised CVR should be considered when stroke risk assessments are made by TCD.
Acetazolamide↗
CT-based assessment of acute stroke: CT, CT angiography, and xenon-enhanced CT cerebral blood flow.
BACKGROUND AND PURPOSE: Only a small percentage of acute-stroke patients receive thrombolytic therapy because of time constraints and the risks associated with thrombolytic therapy. We sought to determine whether xenon-enhanced CT (XeCT) cerebral blood flow (CBF) and/or CT angiography (CTA) in conjunction with CT can distinguish subgroups of acute ischemic stroke victims and thereby better predict the subgroups most likely to benefit and not to benefit from thrombolytic therapy. METHODS: An analysis of 51 patients who had a CT, CTA, and stable XeCT CBF examination within 24 hours of stroke symptom onset was conducted. These initial radiographic studies and National Institutes of Health Stroke Scale score on admission were assessed to determine whether they could predict new infarction on follow-up CT or discharge disposition by use of the Fisher exact test to determine statistical significance. RESULTS: Patients with no infarction on initial CT and normal XeCT CBF had significantly fewer new infarctions and were discharged home more often than those with compromised CBF. The same held true for patients with an open internal carotid artery and middle cerebral artery by CTA and normal CT compared with those with an occluded internal carotid artery and/or middle cerebral artery by CTA. Either was superior to CT and the National Institutes of Health Stroke Scale in prediction of outcome. Both enable the selection of a group of patients not identifiable by CT alone that would do well without being exposed to the risks of thrombolytic therapy. This study included too few patients to statistically assess the role of combining CTA and XeCT CBF information. CONCLUSIONS: The combination of CT, CTA, and Xe/CT CBF does define potentially significant subgroups of patients. The utility of this classification is supported by the observation that CTA and XeCT CBF are superior to CT alone in predicting infarction on follow-up CT and clinical outcome. This information may be useful in selecting patients for acute-stroke treatment.
Acute Disease↗
Absence of selective deep white matter ischemia in chronic carotid disease.
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Brain Ischemia↗
Cerebral revascularization for cerebral ischemia and stroke prevention in patients with atherosclerotic occlusive disease: defining the population that benefits.
The decision to perform a revascularization procedure on a patient who may or may not benefit from it must be based on an understanding of the impact of spontaneous or therapeutic vascular occlusion on the physiologic, by which the cerebral circulation compensates for vascular occlusions. This impact is patient specific and requires examination of a number of possible physiologic parameters.
Arterial Occlusive Diseases↗
Clinical experience with cerebral oximetry in stroke and cardiac arrest.
OBJECTIVE: To address the ability and reliability of the INVOS 3100A (Somanetics, Troy, MI) cerebral oximeter to detect cerebral desaturation in patients and the interpretation of cerebral oximetry measurements using the INVOS 3100A in stroke and cardiac arrest. DESIGN: Case reports of two patients. SETTING: Neurologic Intensive Care Unit of a University Hospital. PATIENTS: Two patients suffering occlusive strokes of the middle cerebral artery. One later suffered a cardiac arrest. RESULTS: The first case, a patient who suffered cardiac arrest while undergoing continuous cerebral oximetry, clearly demonstrated the ability of the INVOS 3100A to detect rapid tissue vascular oxyhemoglobin desaturation in the brain during circulatory arrest. In the second case, oximetry readings were obtained in a patient with a right internal carotid artery occlusion and an infarct in the middle cerebral artery territory. The circulation of the anterior cerebral artery (ACA) territory was intact. Stable xenon-computed tomography of local cerebral blood flow showed no perfusion in the infarct, and oximetry readings were between 60 and 65. In the border zone between the middle cerebral artery and the ACA, readings of 35 to 40 were obtained, and over the ACA territory, the readings were in the 60s. CONCLUSIONS: Oximetry by near infrared spectroscopy reflects the balance between regional oxygen supply and demand. In dead or infarcted nonmetabolizing brain, saturation may be near normal because of sequestered cerebral venous blood in capillaries and venous capacitance vessels and contribution from overlying tissue. In regionally or globally ischemic, but metabolizing brain, saturation decreases because oxygen supply is insufficient to meet metabolic demand. These observations are supported by previously reported "normal" readings in unperfused or dead brains.
Aged↗
Hyperthermia in the neurosurgical intensive care unit.
OBJECTIVE: In patients with traumatic or ischemic brain injury, hyperthermia is thought to worsen the neurological injury. We studied fever in the neurosurgical intensive care unit (ICU) population using a definition common to surgical practice (rectal temperature >38.5 degrees C). We sought to determine fever incidence, fever duration, and peak temperature and to quantify the use of antipyretic therapy. We also attempted to determine the patient subgroups that are at highest risk for development of fever. METHODS: In a retrospective chart review of a 6-month period, all febrile episodes that occurred in a consecutive series of neurosurgical ICU patients in a university hospital setting were studied. A febrile episode was defined as a rectal temperature of at least 38.5 degrees C; an episode lasted until the temperature fell below this threshold. RESULTS: The 428 patients studied had 946 febrile episodes. Fever occurred in 47% of patients, with a mean of 4.7 febrile episodes in each febrile patient. Fevers occurred in more than 50% of patients who were admitted to the ICU for subarachnoid hemorrhage, a central nervous system infection, seizure control, or hemorrhagic stroke, but they occurred in only 27% of patients admitted for spinal disorders. Fevers occurred in 15% of the patients who stayed in the ICU less than 24 hours, but in 93% of those who remained longer than 14 days. Despite the use of antipyretic therapy for 86% of the febrile episodes, 57% lasted longer than 4 hours and 5% lasted longer than 12 hours. CONCLUSION: Fever is common in critically ill neurosurgical patients, especially those with a prolonged length of stay in the ICU or a cranial disease. If hyperthermia worsens the functional outcome after a primary ischemic or traumatic injury, as has been suggested by several studies of stroke patients, treatment of fever is a clinical issue that requires better management.
Analgesics, Non-Narcotic↗
Comparison of two commercially available near-infrared spectroscopy instruments for cerebral oximetry. Technical note.
Two near-infrared spectroscopy (NIRS) devices were compared with regard to their responses to changes in cerebral hemoglobin oxygenation induced by hypoxia and hypercapnia in five healthy volunteers. Sensors belonging to each NIRS device were placed on opposite sides of the volunteer's forehead. The INVOS-3100A device, approved by the United States Food and Drug Administration, records the percentage of oxyhemoglobin (HbO2) saturation and the investigational NIRO500 device records absolute changes in HbO2, deoxyhemoglobin, and total hemoglobin in micromolar concentrations referenced to an arbitrary baseline. The volunteers breathed separate mixtures of 7% CO2 in O2 and 10% O2 for 5 minutes in random order. Arterial blood pressure, end-tidal CO2 (ETCO2), arterial O2 saturation, and electrocardiographic data were continuously monitored. Hypercapnia increased (p < 0.01) ETCO2 from 42+/-2 to 56+/-3 mm Hg (mean +/- standard deviation), resulting in a 7.3+/-0.2% increase (p < 0.005) in cerebral HbO2 saturation detected by the INVOS3100A device and an 11.6+/-3 microM increase (p < 0.0008) in HbO2 detected by the NIRO500. Hypoxia decreased (p < 0.01) arterial HbO2 saturation from 98+/-1 to 87+/-3%, causing a 5.1+/-1.2% decrease (p < 0.01) in the percentage of HbO2 saturation detected by the INVOS3100A device and a 9.7+/-6.3 microM decrease in HbO2 detected by the NIRO500. The responses of the NIRO500 and the INVOS3100A instruments to changes in cerebral oxygenation resulting from hypercapnia and hypoxia were generally similar; however, responses tended to be greater when recorded by the NIRO500 device, perhaps because, unlike the INVOS3100A device, the NIRO500 does not correct for skin and bone contamination.
Blood Gas Monitoring, Transcutaneous↗
Clinical application of cerebrovascular reserve assessment as a strategy for stroke prevention.
Patients diagnosed as having symptomatic carotid occlusion, who are at increased risk for stroke, can be readily identified by methods designed to measure cerebrovascular reserves. This paper reviews the use of xenon-enhanced computed tomography (Xe/CT) cerebral blood flow (CBF) methods for quantitatively assessing cerebrovascular reserves.
Acidosis↗
The utility of XeCT cerebral blood flow in the management of acute stroke.
The fundamental pathophysiologic event underlying acute ischemic stroke is a reduction in cerebral blood flow (CBF). Over 100 patients with acute stroke have been studied with xenon-enhanced computed tomography (XeCT) during the past three years. A retrospective analysis of these patients has revealed several important observations. XeCT is very sensitive in detecting acute ischemia. The pattern and depth of ischemia can be correlated with the physical examination, CT findings, and angiographic results. Patients with large volumes of severely ischemic tissue are more likely to suffer herniation, hemorrhagic conversion, and death than patients with small volumes of less ischemic tissue. Patients with normal CBF studies are more likely to have their deficits resolved within 24 hours that patients with abnormal CBF maps. It is likely that future prospective studies will better define the precise utility of XeCT in the acute management of cerebral ischemia.
Brain Ischemia↗
Xenon-enhanced computed tomography in the management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
At the University of Pittsburgh, xenon-enhanced computed tomography (XeCT) serves numerous critical roles in the management of patients following aneurysmal subarachnoid hemorrhage (SAH). Routine baseline XeCT studies are obtained within 24 hours of surgery and are used for comparison to later studies. In the setting of a delayed neurological deficit, XeCT is used emergently to distinguish vasospasm from other possible causes and to triage patients to appropriate non-invasive or invasive therapies. In cases of a delayed neurologic deficit without CBF changes, regardless of transcranial doppler results which can be unreliable, XeCT can prevent unnecessary angiography and potentially harmful invasive treatments. For patients demonstrating territorial ischemia diagnostic of symptomatic vasospasm, XeCT is used to monitor the efficacy of both invasive and non-invasive interventions. This paper summarizes the results and significance of clinical studies of XeCT in the management of patients after SAH at our institution.
Humans↗
Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite.
Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that SAGE does not require prior knowledge of the genes of interest and provides quantitative and qualitative data of potentially every transcribed sequence in a particular tissue or cell type. Furthermore, SAGE can quantify low-abundance transcripts and reliably detect relatively small differences in transcript abundance between cell populations. However, SAGE demands high input levels of mRNA which are often unavailable, particularly when studying human disease. To overcome this limitation, we have developed a modification of SAGE that allows detailed global analysis of gene expression in extremely small quantities of tissue or cultured cells. We have called this approach 'SAGE-Lite'. This technique was used for the global analysis of transcription in samples of normal and pathological human cerebrovasculature to study the molecular pathology of intracranial aneurysms. These samples, which are obtained during operative surgical repair, are typically no bigger than 1 or 2 mm and yield <100 ng of total RNA. In addition, we show that SAGE-Lite allows simple and rapid isolation of long cDNAs from short (15 bp) SAGE sequence tags.
Cell Line↗
Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
BACKGROUND: Intra-arterial papaverine (IAP) has been described as a treatment for cerebral vasospasm refractory to standard therapy. METHODS: We report a series of 15 consecutive patients with aneurysmal subarachnoid hemorrhage in which IAP was employed for the treatment of symptomatic vasospasm. All patients exhibited delayed ischemic neurologic deficits, focal cerebral hypoperfusion on stable xenon-enhanced computerized tomography cerebral blood flow studies, and angiographically defined arterial narrowing. Papaverine was infused into 32 arteries on 23 occasions. Six patients required multiple treatments between 1 and 8 days apart. In five instances, IAP was combined with angioplasty. RESULTS: Angiographically defined vasospasm was at least partially reversed immediately following treatment on 18 of 23 occasions. The associated clinical improvement was major on 6 occasions, and either minor or none on 17. Post-treatment cerebral blood flow was assessed on 13 occasions and showed improvement in previously ischemic areas on six occasions and no improvement on seven. Complications were encountered on four occasions. Systemic hypotension and transient brain-stem depression were seen with vertebral artery infusions; a generalized seizure and paradoxical aggravation of vasospasm resulting in hemispheric infarction occurred with internal carotid artery infusions. CONCLUSIONS: Intra-arterial papaverine resulted in reversal of arterial narrowing in the majority of cases (78%). However, this angiographic improvement was associated with cerebral blood flow augmentation in only 46% of cases analyzed, and major clinical improvement in 26%.
Adult↗
Development of obstructive hydrocephalus with lumboperitoneal shunting following subarachnoid hemorrhage.
Hydrocephalus is a frequent complication of subarachnoid hemorrhage (SAH). The optimum method of treating hydrocephalus in this setting has not been determined. We review our experience with patients developing communicating hydrocephalus secondary to SAH and subsequently treated with lumboperitoneal (LP) shunts. Following hospitalization for the treatment of SAH, patients who developed clinical symptoms and radiologic signs of hydrocephalus were treated with (ventriculoperitoneal) VP or LP shunting. Eighteen patients received an LP shunt, of which seven (28%) developed a non-communicating or obstructive hydrocephalus. These seven patients underwent replacement with a VP shunt and have not had further complications. In the setting of post-SAH communicating hydrocephalus, obstructive hydrocephalus may develop after LP shunt placement. Patients who develop this complication and have their LP shunts converted to VP shunts have a favorable prognosis.
Adult↗
Subarachnoid hemorrhage, systemic immune response syndrome, and MODS: is there cross-talk between the injured brain and the extra-cerebral organ systems? Multiple organ dysfunction syndrome.
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Brain↗
Factors affecting survival rates for acute vertebrobasilar artery occlusions treated with intra-arterial thrombolytic therapy: a meta-analytical approach.
OBJECTIVE: To determine whether recanalization, coma at presentation, or clot location in the basilar artery influences the relative mortality risk after intra-arterial thrombolytic therapy for acute vertebrobasilar artery occlusions. METHODS: Studies were identified using the MEDLINE database for January 1987 to November 1997. Series were included if they involved 10 or more patients with basilar or vertebrobasilar artery occlusions, used urokinase and/or recombinant tissue plasminogen activator, and were written in English. A fixed-effect meta-analysis approach was used to estimate the risk of death with the aforementioned risk factors. Each study was weighted according to sample size. Relative risks were calculated with 95% confidence intervals. RESULTS: As calculated from peer-reviewed published data, the relative mortality risk for patients for whom recanalization was attempted but not achieved was 2.34 (95% confidence interval, 1.48-3.71; n = 126). Coma at presentation was associated with a relative mortality risk of 1.95 (95% confidence interval, 1.26-2.99; n = 145). Clot locations in the distal one-third of the basilar artery were shown to favor survival, compared with clots located in the proximal and/or middle portions of the basilar artery (relative risk, 0.52; 95% confidence interval, 0.31-0.86; n = 126). CONCLUSION: The combined data suggest that coma at presentation has an independent and adverse effect on survival rates. Complete recanalization, distal clot location, and responsiveness at the time of presentation are statistically significant factors for increased patient survival rates.
Adolescent↗