Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance angiography.

We reviewed 1440 MRA studies to identify patients with middle cerebral artery stenosis (MCAS). We identified 99 cases, and after reviewing the clinical records, classified 28 as asymptomatic MCAS (AMCAS), a prevalence of 2%. Suspected stroke was the most frequent indication for MRA. Follow-up was available for 21, mean 46.7 months (range 2.4-75.6 months). One stroke occurred in the AMCAS territory (5%), other strokes in five patients (24%). There were five deaths in patients with MCAS; age > 69 (P = 0.045) was the only associated risk factor. This study suggests that patients in whom MRA is performed and shows AMCAS may be at increased risk of strokes in any vascular distribution or of death.

Benefits of perfusion MR imaging relative to diffusion MR imaging in the diagnosis and treatment of hyperacute stroke.

BACKGROUND AND PURPOSE: The development of thrombolytic agents for use with compromised cerebral blood flow has made it critical to quickly identify those patients to best treat. We hypothesized that combined diffusion and perfusion MR imaging adds vital diagnostic value for patients for whom the greatest potential benefits exist and far exceeds the diagnostic value of diffusion MR imaging alone. METHODS: The cases of patients with neurologic symptoms of acute ischemic stroke who underwent ultra-fast emergent MR imaging within 6 hours were reviewed. In all cases, automatic processing yielded isotropic diffusion images and perfusion time-to-peak maps. Images with large vessel distribution ischemia and with mismatched perfusion abnormalities were correlated with patient records. All follow-up images were reviewed and compared with outcomes resulting from hyperacute therapies. RESULTS: For 16 (26%) of 62 patients, hypoperfusion was the best MR imaging evidence of disease distribution, and for 15 of the 16, hypoperfusion (not abnormal diffusion) comprised the only imaging evidence for disease involving large vessels. For seven patients, diffusion imaging findings were entirely normal, and for nine, diffusion imaging delineated abnormal signal in either small vessel distributions or in a notably smaller cortical branch in one case. In all cases, perfusion maps were predictive of eventual lesions, as confirmed by angiography, CT, or subsequent MR imaging. CONCLUSION: If only diffusion MR imaging is used in assessing patients with hyperacute stroke, nearly one quarter of the cases may be incorrectly categorized with respect to the distribution of ischemic at-risk tissue. Addition of perfusion information further enables better categorizing of vascular distribution to allow the best selection among therapeutic options and to improve patient outcomes.

Functional evaluation of arteriovenous malformations.

Detailed knowledge of the angioarchitecture of arteriovenous malformations (AVMs) is necessary in determining the optimal timing and method of treatment of these challenging lesions. Many techniques are available for studying the functionality of surrounding cortical structures of AVMs. These include the use of positron emission tomography, functional magnetic resonance imaging, magnetoencephalography, and direct provocative testing of cortical function. The use of these methods to determine flow dynamics and tissue perfusion is also reviewed. These techniques are discussed in the present study, and their judicious utilization will enhance the safety of AVM therapy.

Intraoperative magnetic resonance image guidance in neurosurgery.

Recently, there has been a burgeoning interest in the use of image-guided navigation to improve the safety and effectiveness of neurosurgical procedures. The intraoperative use of magnetic resonance imaging (MRI) provides the most accurate guidance available. This report discusses the hardware and software improvements that have made intraoperative MRI a reality and describes the use of this technology for neurosurgical intraoperative guidance.

The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas.

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.

Emergency management of ischemic stroke.

The accurate diagnosis of acute ischemic stroke is possible using clinical skills and diagnostic tools that are familiar to all neurosurgeons. Avoidance of immediate complications relies on the fundamentals of critical care. Effective treatment for ischemic stroke is available in the form of intravenous thrombolysis, but many stroke patients are denied this therapy because of the narrow window of opportunity for safe administration. Intra-arterial delivery may extend this benefit to a greater number of patients and may eventually prove more effective than intravenous treatment. Surgical treatment in a small number of ischemic stroke patients can be lifesaving and may afford reasonable functional recovery. This article discusses typical clinical presentations and differential diagnosis, diagnostic imaging for ischemic stroke, and possible treatments.

Predictors of clinical improvement, angiographic recanalization, and intracranial hemorrhage after intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to evaluate predictors of clinical outcome, angiographic success, and adverse effects after intra-arterial administration of urokinase for acute ischemic stroke. METHODS: We designed a Brain Attack program at University Hospitals of Cleveland for diagnosis and treatment of patients presenting within 6 hours of onset of neurological deficit. Patients with ischemia referable to the carotid circulation were treated with intra-arterial urokinase. Angiographic recanalization was assessed at the end of medication infusion. Intracerebral hemorrhage was investigated immediately after and 24 hours after treatment. Stroke severity was determined, followed by long-term outcome. RESULTS: Fifty-four patients were treated. There was improvement of >/=4 points on the National Institutes of Health Stroke Scale from presentation to 24 hours after onset in 43% of the treated patients, and this was related to the severity of the initial deficit. Forty-eight percent of patients had a Barthel Index score of 95 to 100 at 90 days, and total mortality was 24%. Cranial CT scans revealed intracerebral hemorrhage in 17% of patients in the first 24 hours, and these patients had more severe deficits at presentation. Eighty-seven percent of patients received intravenous heparin after thrombolysis, and 9% of them developed a hemorrhage into infarction. Angiographic recanalization was the rule in complete occlusions of the horizontal portion of the middle cerebral artery, but distal carotid occlusions responded less well to thrombolysis. CONCLUSIONS: The intra-arterial route for thrombolysis allows for greater diagnostic precision and achievement of a higher concentration of the thrombolytic agent in the vicinity of the clot. Disadvantages of this therapy lie in the cost and delay. Severity of stroke and site of angiographic occlusion may be important predictors of successful treatment.

Hyperacute stroke: ultrafast MR imaging to triage patients prior to therapy.

PURPOSE: To test diffusion- and perfusion-weighted MR imaging techniques within the extreme time constraints of stroke evaluation before therapy, and then, with MR imaging, stratify patients into those without ischemia, those with noncortical ischemia, and those with cortical ischemia. MATERIALS AND METHODS: T2-weighted turbo gradient- and spin-echo images and echo-planar diffusion- and perfusion-weighted images were obtained. Trace diffusion-weighted images and time-to-peak perfusion maps were automatically postprocessed and immediately available for interpretation. RESULTS: Forty-one patients with acute stroke symptoms underwent imaging within 6 hours of symptom onset; 35 were eligible for the therapy protocol. The mean time from entering the emergency department to beginning MR imaging was 45 minutes; the mean total MR imaging time was less than 15 minutes. Immediate image analysis directly affected individual clinical management. Four patients showed evidence of no infarct; seven, of lacunar infarct; and 24, of acute cortical infarct. Sixteen patients underwent angiography, thirteen had large-vessel occlusion, eleven were treated intraarterially, and in seven, recanalization was achieved. CONCLUSION: Echo-planar diffusion- and perfusion-weighted MR imaging for acute stroke is feasible and applicable before therapy decisions. Ultrafast MR imaging permitted immediate triage of 35 patients with symptoms of hyperacute stroke and thus helped avoid the risks from angiography and thrombolytic agents in some or spurred the judicious use of more aggressive intervention in others.

Temporary vascular occlusion during cerebral aneurysm surgery.

Temporary artery occlusion is an effective way to reduce the detrimental effects of intraoperative aneurysm rupture and to facilitate aneurysm dissection. The major risk incurred is of cerebral infarction. Dilemmas in the use of this technique include the amount of time that arterial flow may be interrupted safely and whether or not there is benefit to intermittent reperfusion. Protocol for the use of temporary occlusion is described.

Brain attack: emergency treatment of ischemic stroke.

Thrombolysis has been demonstrated to be an effective treatment for ischemic stroke. The major obstacles to more widespread use of this therapy are lack of awareness that the treatment is possible and the short (less than three hours) therapeutic window. Indiscriminant use of this therapy can lead to an unacceptably high rate of intracerebral hemorrhage. Early recognition of the onset of stroke. Immediate transfer to a suitably equipped treatment facility and careful screening of a computed tomographic scan of the head for signs of early infarction are necessary for the safe administration of intravenous thrombolysis.

Mortality rates, hospital length of stay, and the cost of treating subarachnoid hemorrhage in older patients: institutional and geographical differences.

The risk of disability and death and the cost of medical care are particularly high for patients with aneurysmal subarachnoid hemorrhage (SAH) who are 65 years of age or older. A retrospective analysis of 47,408 Medicare patients treated over an 8-year period was performed to determine whether a relationship exists between the mortality rate and surgical volume for older patients with SAH. The mortality rate, length of stay in the hospital, and cost of treatment for patients with SAH in California and New York state were also compared. The mortality rate was 14.3% for patients with SAH who were 65 years old or older and who were treated surgically in hospitals in which an average of five or more craniotomies were performed per year; in hospitals averaging between one and five craniotomies annually the mortality rate was 18.4%; and in those averaging less than one such operation per year the rate was 20.5% (trend p = 0.01). There was no difference in the mortality rate for patients in California versus the rate for those in New York. Surgically and medically treated patients, respectively, left the hospital an average of 6.7 and 5.1 days sooner in California than in New York. The unadjusted average reimbursement from Medicare to hospitals for surgically treated patients averaged $1468 more in New York than in California (p < 0.0001), but was equivalent for medically treated patients in the two states. The mortality rate in older patients who are treated surgically for SAH may be inversely correlated with the annual number of craniotomies performed for SAH in patients 65 years of age or older at a given institution. Hospital stays for patients with SAH are significantly shorter in California than in New York.

Thrombolysis for acute ischemic stroke.

The use of thrombolytic agents to restore cerebral blood flow is one of the most notable advances in the treatment of ischemic stroke. This article reviews thrombolytic therapy, its limitations, and the techniques by which thrombolytic agents can be delivered.

Brain attack. The emergent management of hypertensive hemorrhage.

Intracerebral hemorrhage (ICH) accounts for one half of stroke-related deaths, with hypertensive hemorrhage being the primary etiology. The evolution of minimally invasive devices for removal of ICHs, and the earlier delivery of patients for medical attention may have a great impact on the management of hypertensive hemorrhage.

Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition.

N-Methyl-D-aspartate causes a rapid increase in intracellular Ca2+ leading to collapse of the mitochondrial membrane potential and eventually cell death in cortical neurons. The aim of this study was to investigate the mechanism responsible for mitochondrial depolarization using laser scanning confocal microscopy of single cultured rate cortical neurons. To monitor mitochondrial membrane potential, neuronal mitochondria were labeled with tetramethylrhodamine methyl ester, a cationic fluorophore that accumulates in polarized mitochondria. In neurons cultured on poly-D-lysine-coated coverslips, N-methyl-D-aspartate caused mitochondrial depolarization in 88% of cells in 30 min. Cyclosporin A, an inhibitor of the mitochondrial permeability transition, delayed depolarization in a dose-dependent manner (0.2-1 microM). In neurons cultured on an astrocyte feeder layer, N-methyl-D-aspartate also caused mitochondrial depolarization. Cyclosporin A again delayed mitochondrial depolarization, although higher concentrations were needed. These data show for the first time that mitochondrial depolarization induced by N-methyl-D-aspartate may be due to the induction of the mitochondrial permeability transition.

Temporary vessel occlusion during intracranial aneurysm repair.

Any method that decreases the risk of intraoperative rupture should improve outcome if complications associated with its use do not negate positive effect. If application time is limited and a form of cerebral protection and appropriate monitoring of cerebral function are used, temporary clip application may meet these requirements. The efficacy of temporary occlusion as an adjunct to aneurysm clipping may be limited by technical considerations with respect to regional anatomy, aneurysm size, and aneurysm consistency. In areas of limited access, positioning proximal clips may not be feasible. The use of endovascular techniques of balloon occlusion may provide proximal control in these situations (9, 106). The decision to use total circulatory arrest and profound hypothermia, as opposed to temporary clip application, remains largely a matter of the surgeon's judgment. The role of proximal parent vessel ligation must also be considered in the decision-making process regarding the treatment of giant or technically difficult aneurysms (114). Further refinements in cerebral monitoring that can accurately reflect intracellular processes in all territories affected by the application of temporary clips or balloon occlusion and development of more effective forms of cerebral protection may permit safer use of this technique. An adequately controlled clinical trial of temporary occlusion with or without putative "cerebral protection" is needed to confirm the efficacy of this technique.

Good clinical outcome in a patient with a large CT scan hypodensity treated with intra-arterial urokinase after an embolic stroke.

Hypodense regions demonstrated by CT within 6 hours of the onset of stroke may reflect irreversibly damaged tissue, and some have suggested that patients with such findings should be spared the risks of thrombolytic therapy since they are unable to benefit from it. We report here a patient with a low-density area demonstrated by CT less than 6 hours after onset of symptoms who improved dramatically after successful intra-arterial thrombolysis.

Dynamics of prolactin secretion in patients with hypopituitarism and pituitary macroadenomas.

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. We postulated that hypopituitarism in this setting, is primarily caused by compression of the portal vessels and/or pituitary stalk. If this were the case, the dynamics of PRL secretion in this instance would be similar to those in patients with stalk section, dopamine deficiency, or hypothalamic disease. Furthermore, as hypopituitarism in this setting is largely reversible, we postulate that PRL dynamics should also normalize after adenomectomy as a result of the resumption of hypothalamic regulation of pituitary hormone secretion. To test these hypotheses, we examined PRL responsiveness to TRH and the dopamine antagonist, perphenazine (PZ), in patients with pituitary macroadenomas who had hypopituitarism and others with intact pituitary function (controls). Dynamic studies were performed before and 2-3 months after total or subtotal adenomectomy, and the results were correlated with alterations in other pituitary function. In addition, plasma ACTH, cortisol, and PRL levels were measured hours to days after surgery to investigate immediate alterations in pituitary function following surgical decompression. Before surgery, hypopituitary patients had higher serum PRL level than controls (25.5 +/- 12 vs. 11 +/- 3 micrograms/L; P < 0.001). Preoperative dynamic testing of PRL secretion in hypopituitary patients demonstrated an increase in PRL levels after TRH, but not after PZ, administration. In contrast, PRL levels increased appropriately when either stimulus was given to controls. Hours after adenomectomy, PRL levels decreased by 50% in hypopituitary patients (P < 0.0001) and remained so until discharge. In contrast, controls had a transient increase in serum PRL levels after adenomectomy. After surgery, 25 of 43 previously hypopituitary patients recovered part or all pituitary function. Serum PRL levels in the latter subgroup became normal and increased appropriately after stimulation with either TRH or PZ. In contrast, patients who did not recover pituitary function had lower PRL levels that increased minimally after TRH or PZ. The mild increase in serum PRL levels in hypopituitary patients and the discordant responses to stimulation with TRH and PZ suggest dopamine deficiency as a cause of hyperprolactinemia. The drop in serum PRL levels immediately after surgery, at a time when other pituitary hormones (e.g. ACTH), were documented to rise suggests restoration of hypothalamic control over pituitary hormone secretion. The pattern of PRL responses to stimulation in patients recovering function postoperatively was similar to that in controls, although the incremental rise was subnormal.(ABSTRACT TRUNCATED AT 400 WORDS)

Cost-effectiveness of emergency intraarterial intracerebral thrombolysis: a pilot study.

PURPOSE: To assess the clinical efficacy and cost-effectiveness of emergency thrombolysis as a treatment strategy for thromboembolic intracerebral events. METHODS: Thirty-four patients with symptoms suggestive of middle cerebral artery occlusion were included. Eight of these patients were treated with intraarterial urokinase. Effectiveness was determined by comparing the admission National Institutes of Health stroke score to the 24-hour National Institutes of Health stroke score. The cost and length of stay of both populations were derived and used as measures of direct cost. The likelihood of admission to extended care facilities and estimated length cost of admission was used as a measure of indirect cost. RESULTS: The control population became slightly worse, with a change in National Institutes of Health score of -0.5, whereas the treated population improved slightly, with a change in National Institutes of Health score of +5.12. Analysis of the direct costs data between the two populations revealed a slight increased mean for the treated population ($15,202) as compared with the control population ($13,478). The unpaired t test, however, revealed no significant cost difference between the two groups. By reducing the number of completed strokes by one third or by decreasing the severity by the same factor (as shown in our study), the likelihood of admission to an extended nursing facility also is decreased. The cost saving per patient from extended care facilities is approximately $3435. CONCLUSION: The emergency application of intraarterial thrombolysis with urokinase results in a statistically significant positive change in National Institutes of Health score by at least five points. A statistically significant benefit is realized through the use of intraarterial urokinase. A statistically insignificant additional cost is shown by this study. This insignificant cost is more than offset by the saved nursing home costs.

Cerebral arterial aneurysm formation and rupture in 20,767 elderly patients: hypertension and other risk factors.

Cerebral arterial aneurysms are common in the general population and their rupture is a catastrophic event. Considerable uncertainty remains concerning the conditions that predispose individuals to aneurysm formation or rupture. The role of systemic hypertension in aneurysm formation and rupture has been especially controversial. Demographic variables have rarely been addressed because of the small sample sizes in previous studies. The authors describe the demographics and prevalence of hypertension in 20,767 Medicare patients with an unruptured aneurysm and compared these to a random sample of the hospitalized Medicare population. The prevalence of hypertension in patients with unruptured aneurysms was 43.2% compared with 34.4% in the random sample. Patients who survived their initial hospitalization were separated into two groups: those with an unruptured cerebral aneurysm as the primary diagnosis and those with an unruptured cerebral aneurysm as a secondary diagnosis. Follow-up data for 18,119 patients were examined to determine the risk of subarachnoid hemorrhage (SAH) associated with age, gender, race, hypertension, insulin-dependent diabetes mellitus, and surgical treatment. For patients with an unruptured cerebral aneurysm as the primary diagnosis, hypertension was found to be a significant risk factor for future SAH (risk ratio: 1.46, 95% confidence interval (CI): 1.01-2.11), whereas surgical treatment (risk ratio: 0.29, 95% CI: 0.09-0.97) had a significant protective effect. Advancing age had a small but significant protective effect in both groups. Elderly patients identified with unruptured aneurysms are more likely to have coexisting hypertension than the general hospitalized population. In elderly patients hospitalized with an unruptured cerebral aneurysm as their primary diagnosis, hypertension is a risk factor for subsequent SAH, whereas surgical treatment is a protective factor against SAH.