Neuronal protection from cerebral ischemia by synthetic fibronectin peptides to leukocyte adhesion molecules.

Leukocytes play an important role in the development of ischemia/reperfusion injury. Recent work in our laboratory has demonstrated that a mixture of synthetic fibronectin peptides to leukocyte adhesion molecules reduces ischemic brain damage after transient focal cerebral ischemia. The purpose of this study was to evaluate the efficacy of the individual peptides on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transient ischemia without treatment (Group I), treatment with arginyl-glycyl-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 peptide (Group III), fibronectin (FN)-C/H-V peptide (Group IV), and scrambled FN-C/H-V peptide (Group V). Groups III and IV showed a significant decrease in the degree of leukocyte infiltration in the lesion and in the infarct size (p < 0.05) when compared to Groups I, II, and V. The neurological grade of Groups III and IV was significantly better than in Groups I, II, and V at 48 h after reperfusion (p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic peptides as therapeutic agents for ischemia-reperfusion, these results also offer new insights into the mechanisms of leukocyte arrest and recruitment in ischemia/reperfusion injury.

Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma.

We describe the unusual association of two ocular motor abnormalities: upbeat nystagmus and internuclear ophthalmoplegia in a young woman originally believed to have demyelinating disease. Quantitative eye movement recordings documented a unidirectional defect in upward visual pursuit with preservation of the vertical vestibulo-ocular reflexes. The ocular oscillation was characterized as a type of "pursuit defect" nystagmus. An enhancing lesion of the upper brainstem seen on computerized tomography was primarily localized to the midbrain on pneumoencephalography. Biosy of the lesion disclosed a malignant glial tumor. The patient's course initally progressed but became stable following radiotherapy and chemotherapy during the next eight months. We believe the association of upbeat nystagmus and internuclear ophthalmoglegia should prompt a detailed search for a structural lesion.

Is surgical therapy needed for unruptured arteriovenous malformations?

A conservative attitude toward unruptured arteriovenous malformations (AVMs) has been based on the belief that surgical resection is too risky and that their natural history is benign. We have operated on 103 patients with a cerebral AVM. In the 49 patients with unruptured AVMs, there was no mortality, and the morbidity was 14.2%. Similarly, low surgical morbidity has been reported from several centers during the last few years. The chance of hemorrhage for both ruptured and unruptured AVMs is about 3% per year, and the combined morbidity and mortality of each hemorrhage is at least 40%. All patients with an AVM should be individually considered for possible surgical resection, whether or not they have bled.

Occluded but nonthrombosed internal carotid artery: an indication for endarterectomy.

The indications for carotid endarterectomy are sometimes imprecise. Total occlusion of the internal carotid artery has often implied irreversibility. Carotid thromboendarterectomy was performed on eight patients who on angiography had a complete occlusion of proximal internal carotid artery but showed antegrade opacification of the infraophthalmic carotid siphon. Direct magnification, delayed radiography, and subtraction were used on all patients. In five of eight patients, normal antegrade cervical internal carotid blood flow was restored. The possible restoration of the occluded internal carotid artery lumen offers a viable alternative to bypass surgery in selected cases.

A neuroradiologic approach to the patient with a diagnosis of subarachnoid hemorrhage.

If early CT confirms the presence of subarachnoid hemorrhage, no intratemporal clot is present, and the patient is neurologically normal, surgery is planned in approximately eight to ten days. The first angiogram is performed just before surgery. If that angiogram shows severe vasospasm, surgery is deferred for approximately five to seven days. If the initial angiogram clearly shows the anatomy of the aneurysm and completely visualizes the intracranial circulation, it does not need to be repeated. If the initial angiogram is incomplete, then all vessels are studied prior to surgery. In cases of middle cerebral artery aneurysm with temporal clot, an angiogram is obtained early. In the future, early complete angiography followed by surgery may be possible in those patients with little blood on the initial CT scan. Those patients are not considered to be in jeopardy of developing severe vasospasm.

Common carotid occlusion for unclippable carotid aneurysms: an old but still effective operation.

We present a selected series of nine patients with unclippable internal carotid artery aneurysms to illustrate our current approach to this problem. Eight of the nine underwent common carotid ligation after preoperative angiographic evaluation. Tolerance to carotid occlusion was determined intraoperatively by awake examination, electroencephalogram (EEG) monitoring, and carotid stump pressure measurements. No patient developed a permanent deficit; seven of eight treated aneurysms have thrombosed. Our experience and review of the literature indicate that most ischemic complications after carotid ligation seem to be thromboembolic, rather than due to "low flow" from poor collateral circulation. For this reason, we have gradually come to favor common carotid (CCA) over internal carotid (ICA) occlusion in many of these patients. After CCA occlusion, the ICA frequently remains open and embolic complications are therefore less likely. An extracranial-intracranial bypass procedure is performed only in those patients with poor collateral circulation demonstrated by cross compression angiographic studies, by the development of new deficits during test occlusion, or by the appearance of EEG changes during test occlusion. We suggest that CCA ligation remains a useful alternative in the management of unclippable internal carotid aneurysms.

The combined pterional/anterior temporal approach for aneurysms of the upper basilar complex: technical report.

A technique for achieving a combined pterional (subfrontal) and anterior temporal exposure for aneurysms of the upper basilar complex is described. The technique is not new, but it does involve several modifications not previously described. A standard pterional skin incision that extends below the zygoma just anterior to the tragus is used. The skin flap is separated from the temporal fascia down to the fat pad over the zygoma; at this point, the superficial layer of the temporalis fascia is incorporated and retracted with the skin flap to expose the zygomaticofrontal process and the zygomatic arch. The muscle is cut anteriorly and inferiorly and is retracted posteriorly over the ear. The bone flap includes the anterior temporal squama down to the temporal floor anteriorly. The pterion and the sphenoidal wings are drilled so as to expose completely the dura over the anterior temporal pole. After opening the dura on a flap centered on the sylvian fissure, the medial cisterns are opened widely and the fissure is opened all the way to the middle cerebral bifurcation. Posterolateral temporal retraction and, when necessary, subpial resection of the anteromedial portion of the uncus enhance the exposure posterolateral to the oculomotor nerve. The advantages of this combined approach are as follows: it combines the more anterior angle of vision offered by the pterional approach with the lateral line of vision offered by the subtemporal approach; it eliminates the need for temporal lobe elevation and it allows simultaneous clipping of other aneurysms of the ipsilateral anterior circle of Willis; and it also reduces the frequency and severity of oculomotor palsy, when compared with the subtemporal approach.

Multiple peripheral aneurysms of the posterior inferior cerebellar artery.

Peripheral aneurysms of the posterior inferior cerebellar artery (PICA) are rare. The authors describe a case in which five distinct peripheral aneurysms of the PICA were diagnosed and microsurgically clipped while preserving the parent vessel. One of the aneurysmal sacs was excised and examined pathologically, and no evidence of an infectious etiology was found. The surgical approach to peripheral PICA aneurysms is discussed and the literature concerning these unusual aneurysms is reviewed.

"Subclinoid" carotid aneurysm with erosion of the anterior clinoid process and fatal intraoperative rupture.

We present the case of a patient with an aneurysm of the right internal carotid artery with subarachnoid hemorrhage. The aneurysm had resulted in erosion of the anterior clinoid process, but this was not recognized preoperatively. Intraoperative rupture during drilling of the clinoid necessitated vigorous packing that led to unintended carotid occlusion with subsequent fatal cerebral infarction. Preoperative recognition of the clinoid erosion may have prevented this catastrophe. To call attention to the potential for intraoperative rupture during exposure, we suggest the term subclinoid aneurysm to refer to aneurysms of the internal carotid artery that grow superolaterally and remain confined under the anterior clinoid process.

Origin, growth, and rupture of saccular aneurysms: a review.

Pathological and hemodynamic concepts regarding the origin, growth, and rupture of intracranial saccular aneurysms are reviewed. Aneurysms form as a result of an interplay between hemodynamic factors, such as axial stream impingement and the water hammer effect, and structural weaknesses at apices of arterial bifurcations, such as congenital and acquired medial defects, funnel-shaped dilatations, and areas of thinning. Hypertension and time aid the formation of aneurysms. Unknown factors in women and in some families also play a role. Enlargement of aneurysms results from an interplay between mechanical factors, such as self-excitation and resonance, that produce structural fatigue and pathological processes of repair of the aneurysmal wall. Rupture of aneurysms is caused by the same hemodynamic factors that effect growth and is also influenced by extramural pressure. Pathologically, a major rupture may be preceded by fibrinous and leukocytic infiltration of the wall, bleb formation, and a minor hemorrhage. Such minor leaks can be followed by healing and growth. Aneurysms that escape major hemorrhage or heal successfully after a hemorrhage can grow to giant proportions, but remain susceptible to rupture despite their size, unless they become completely thrombosed. Intramural thrombosis may be stimulated by minor leaks and is dependent upon the physical characteristics of aneurysms. Experimental, angiographic, and clinical studies that pertain to the origin, growth, and rupture of aneurysms are also reviewed.

Giant intracranial aneurysms presenting with massive cerebral edema.

Two cases of giant left middle cerebral artery aneurysm presenting with rapidly progressing hemiparesis and aphasia are presented. In both, the computed tomographic scan showed recent intraaneurysmal thrombosis and massive edema and swelling of the cerebral hemisphere. There was no evidence of recent hemorrhage in either case. In both patients, surgical resection of the aneurysm was accomplished, but the outcome was disastrous. The literature is reviewed and the possible mechanisms responsible for brain swelling in these cases are discussed.

The use of somatosensory evoked potential monitoring to produce a canine model of uniform, moderately severe stroke with permanent arterial occlusion.

To develop a reliable canine model of cerebral infarction of moderate size, we compared infarctions caused by permanent occlusion of the following vessels in 42 dogs: 1) the middle cerebral artery (MCA), 2) the MCA and azygous anterior cerebral artery (ACA), 3) the MCA, azygous ACA, and posterior cerebral artery (PCA), and 4) sham-operated controls. The infarction volume was determined at 6 hours in half the animals and at 6 days in the others. Studies of somatosensory evoked potentials (SSEPs) and regional cerebral blood flow (rCBF) were performed before and after arterial occlusion, and good correlation was observed between the decrease in amplitude of the SSEPs and the decrease in rCBF observed after arterial occlusion. Only the groups in which the MCA and azygous ACA were occluded showed moderate infarctions of relatively consistent size. Analysis involving all groups revealed that the animals with SSEP amplitude preserved after vessel occlusion had only small infarctions; thus, preservation of SSEP amplitude after occlusion of the MCA and azygous ACA could in the future be used prospectively as a rejection criterion to improve the uniformity of infarction size. Conversely, animals with loss of SSEP amplitude after vessel occlusion had infarctions of moderate to large size; thus, loss of SSEP amplitude after MCA occlusion alone could in the future be used prospectively as a rejection criterion. When these rejection criteria were retrospectively applied to the groups in which both the MCA and azygous ACA were occluded, the resulting mean infarction volumes +/- 1 SEM) for the acute and chronic subgroups were 20.3 +/- 2.8% and 38.2 +/- 4.5% of the hemisphere, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical excision of cerebral arteriovenous malformations: late results.

A follow-up study of 153 consecutive patients who underwent complete excision of an angiographically visualized intracerebral arteriovenous malformation was conducted. The follow-up period ranged from 0.5 to 10.6 years, with a mean of 3.8 years. The presenting clinical event was hemorrhage in about one-half of the patients and seizure in about one-third. There was a marked tendency for postoperative neurological deficits to improve with time, so that whereas the immediate postoperative rate of serious morbidity was 24.2%, only 7.8% of the patients were found to have serious morbidity at follow-up. An additional 3 patients had died, one of an unrelated carcinoma, making the mortality related to arteriovenous malformation 1.3%. The classification of Spetzler and Martin (43) was used retrospectively; the percentages of Grade I (easiest) through Grade V (most difficult) lesions were 7.8%, 22.9%, 28.8%, 26.8%, and 13.8%, respectively. The early result was well correlated to grade, with good or excellent results in 100%, 94.3%, 88.6%, 61%, and 28.6% of the patients in Grades I through V, respectively. At follow-up, 98.7% of the patients with arteriovenous malformations of Grades I, II, and III were in good or excellent condition. The late morbidity and mortality rates for the patients in Grades IV and V were 12.2% and 38.4%, respectively. Of the patients who did not have seizures before surgery, 8.2% had only one or two seizures during the immediate postoperative period, and 7.1% had late seizures that were well controlled with medication in all. Of the patients who had seizures before surgery, over half were either cured or greatly improved with respect to the seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Leptomeningeal cyst resulting from adulthood trauma: case report.

The authors report a rare sequelae of a skull fracture in an adult, a leptomeningeal cyst. A unique method for repairing this defect is described as well.

"Brain attack": the rationale for treating stroke as a medical emergency.

Stroke is the third leading cause of death in the United States, behind only heart disease and cancer. With an estimated three million survivors of stroke in the United States, the cost to society, both directly in health care and indirectly in lost income, is staggering. Despite recent advances in basic and clinical neurosciences, which have the potential to improve the treatment of acute stroke, the general approach to the acute stroke patient remains one of therapeutic nihilism. Most basic science studies show that to be effective, acute intervention to reperfuse ischemic tissue must take place within the first several hours, as is the case with ischemic myocardium. In addition, most neuroprotective agents must also be administered within a short time frame to be effective at salvaging at-risk tissue. Recent studies have suggested that the outcome after intracerebral and subarachnoid hemorrhage is improved with early intervention. However, most stroke patients fail to present to medical attention within this short "window of opportunity." The public's knowledge about stroke is woefully inadequate. However, clinicians who deal with stroke can use the dramatic changes in the treatment of acute myocardial infarction over the last 2 decades as a guide for shaping changes in the management of acute stroke. Comprehensive educational efforts aimed at clinicians and the public at large have dramatically reduced the time from symptom onset to presentation and treatment for acute myocardial infarction, enabling treatment methods such as thrombolysis to be effective. The Decade of the Brain offers a unique opportunity to all concerned with the treatment of the patient with acute stroke to engage in a concerted effort to bring patients with a "brain attack" to specialized neurological attention within the same timeframe that the "heart attack" patient is handled. Such an effort is justified because, although at the present time there are few therapeutic interventions of "proven" value in the treatment of acute stroke, there is more than sufficient suggestive evidence that a number of approaches may be beneficial within the first few hours after the onset of the stroke.

Cost-effectiveness of carotid endarterectomy.

Carotid endarterectomy (CEA) reduces the risk of stroke in symptomatic patients with high-grade carotid stenosis. In this study, we evaluated the long-term, societal cost-benefit ratio of endarterectomy using a decision analysis model. We reviewed the results of 150 CEAs performed at an academic center and established a Markov model comparing cohorts of patients who experienced transient ischemic attacks and then underwent observation, aspirin therapy, or CEA. The cost-effectiveness of CEA was estimated using perioperative complication rates from our review and from the North American Symptomatic Carotid Endarterectomy Trial. Stroke and mortality rates were estimated from the literature. Cost estimates were based on medicare reimbursement data. Among the 150 CEAs reviewed, complications included major stroke (0.67%), minor stroke (1.33%), myocardial infarction (1.33%), pulmonary edema (0.67%), and wound hematoma (3.33%). There were no deaths or intracerebral hemorrhages. Using complication rates from our review, CEA produced cost savings of $5730.62 over the cost of observation and $3264.66 over the cost of aspirin treatment. CEA extended the average quality-adjusted life expectancy 15.8 months over that of observation and 13.2 months over that of aspirin. Substituting the North American Symptomatic Carotid Endarterectomy Trial results, CEA yielded savings of $2997.50 over the cost of observation and $531.54 over the cost of aspirin. Quality-adjusted life expectancy was extended 13.8 months compared with observation and 11.2 months compared with aspirin therapy. This analysis demonstrates that when performed with low perioperative morbidity and mortality rates, CEA is a highly cost-effective therapy for symptomatic carotid stenosis and results in substantial societal cost and life savings.

Therapeutic time window for the 21-aminosteroid, U-74389G, in global cerebral ischemia.

A novel 21-aminosteroid (U-74389G), a new potent antioxidant, was evaluated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intraperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third injection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration was initiated. Group I (n = 8) began vehicle administration 30 minutes before occlusion. Group II (n = 9) started 21-aminosteroid administration 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes after reperfusion, and in Group V (n = 6), 60 minutes after reperfusion. Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counted in the hippocampal CA1 subfield. The results were as follows: the number of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 44.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 +/- 3.3. Groups II, III, and IV demonstrated significantly higher numbers of living neurons compared with Group I (P < 0.05). The present study revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the ischemic episode.

Monitoring of cortical somatosensory evoked potentials to determine the safety of sacrificing the anterior cerebral artery.

Cortical somatosensory evoked potentials (SSEPs) reflect the functional integrity of somatosensory pathways from the site of stimulation to the primary somatosensory cortex. We used intraoperative monitoring of cortical SSEPs to determine whether the right anterior cerebral artery (RACA), the major feeding vessel of a large arteriovenous malformation (AVM), could be sacrificed without compromising sensorimotor function in the left lower extremity. The SSEPs recorded after test occlusion of the RACA showed preservation of the initial cortical positivity, and the RACA was divided. The AVM was excised completely, and the patient suffered no neurological deficit.

Superior temporal gyrus approach to middle cerebral artery aneurysms: technique and results.

Aneurysms of the bifurcation of the middle cerebral artery (MCA) can be approached through a small incision in the anterior portion of the superior temporal gyrus. The pterion and the lateral aspect of the lesser wing of the sphenoid bone are removed. The aneurysm is approached, using microsurgical techniques, by following the main divisions of the MCA to the parent trunk and the base of the aneurysm. Once the parent vessel and the origin of the major divisions are clearly identified, it is usually preferable to dissect and mobilize the entire aneurysmal complex to elucidate the anatomy and prepare the neck for clipping. This approach offers the advantages of minimal brain retraction and minimal manipulation of the main trunk and perforators of the MCA. In addition, it allows a more complete exposure of the aneurysmal complex and facilitates dissection behind the aneurysm, which is more difficult when the aneurysm is approached from the front by opening the sylvian fissure medially to laterally. A potential disadvantage of this method is that proximal control is not obtained until the base of the aneurysm is reached, but this has not been a problem in our experience. Other disadvantages are the need for a slightly larger bone flap and the potentially increased risk of epilepsy. This approach is not suitable when the main trunk of the MCA is short and the aneurysm is in front of the insula. It is also not recommended for the rare cases in which the aneurysm points back over the insula. During a 6-year period, this approach was used in 49 of 58 cases of MCA aneurysm. The only deaths in this group occurred in patients who were in deep coma before operation. Two patients were made worse by operative complications, and 2 more worsened as a result of postoperative vasospasm. There was a significant incidence of thrombophlebitis and pulmonary embolism in this series.

Evaluation of monoaminergic neurotransmitters in the rat striatum during varied global cerebral ischemia.

Neurotransmitter release during cerebral ischemia has been extensively studied and is thought to play a key role in excitotoxic neuronal death. The changes in neurotransmitter release and its metabolism may reflect changes in cellular metabolism during ischemia. The purpose of this study is to assess alterations in extracellular dopamine and serotonin and their metabolites under varied degrees of ischemia in rat striatum to elucidate the pathophysiology of cerebral ischemia. Twenty rats were used to induce varied forebrain ischemia by means of bilateral common carotid artery occlusion along with hemorrhagic hypotension. Cerebral blood flow (CBF) in the striatum was measured every 40 minutes by methods of hydrogen clearance and maintained within certain ranges for 6 hours. Dopamine, serotonin, and their metabolites were measured every 20 minutes by in vivo microdialysis. Varying degrees of ischemia were obtained, ranging from 9.4 to 81.3% of control CBF. The animals were divided into three groups according to CBF levels measured 20 minutes after the induction of ischemia. In the mild ischemia group (n = 5), CBF ranged from 65 to 88% of baseline levels and resulted in only a slight increase of dopamine. In the moderate ischemia group (n = 10), CBF ranged from 21 to 48% of baseline levels and resulted in transient increases of dopamine (24-fold) and serotonin (5-fold). In the severe ischemia group (n = 5), CBF was below 14% of baseline levels and resulted in marked increases in dopamine (462-fold) and serotonin (225-fold). These alterations remained elevated for 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)