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This article describes the efforts of the US Food and Drug Administration (FDA) Office of Neurological and Physical Medicine Devices to facilitate early clinical testing of potentially beneficial neurological devices in the US. Over the past 5 years, the FDA has made significant advances to this aim by developing early feasibility study best practices and encouraging developers and innovators to initiate their clinical studies in the US. The FDA uses several regulatory approaches to help start neurological device clinical studies, such as early engagement with sponsors and developers, in-depth interaction during the FDA review phase of a regulatory submission, and provision of an FDA toolkit that reviewers can apply to the most challenging submissions.

Management of anticoagulation and antiplatelet medications after neurosurgery can be complex, especially given that these patients have multiple medical comorbidities. In turn, neurosurgical patients are at high risk for the development of venous thromboembolism after surgery, so neurosurgeons must consider the use of pharmacologic prophylaxis. Developments in endovascular neurosurgery have produced therapies that require close management of antiplatelet medications to prevent postoperative complications. Any of these patient populations may need intrathecal access. This article highlights current strategies for managing these issues in the neurosurgical patient population.

The United States Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) is charged with ensuring patients in the US have timely access to high-quality, safe, and effective medical devices of public health importance. Within CDRH, the Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the central and peripheral nervous system (neurotechnologies), including neurointerventional medical devices that are used in the treatment of stroke. Endovascular treatments have demonstrated recent advances in reaching the marketplace and providing more options for patients with acute ischemic stroke and intracranial aneurysms specifically. Depending upon the pathway chosen for regulatory approval, and the evidentiary standard for different regulatory pathways, neurotechnologies can have well-established safety and effectiveness profiles, varying degrees of scientific and clinical uncertainty regarding safety and effectiveness, or when a humanitarian use exists, need only demonstrate a probable benefit and safety to the patient so potentially life-saving treatments can reach the marketplace. Reperfusion therapies have had specific advances in the treatment of stroke patients that originally had limited or no treatment options and for preventative treatments in providing care to patients with intracranial aneurysms to avoid potentially more catastrophic outcomes. Collaboration in multiple forums and environments will be important to continue to foster the neurointerventional technology sector and positively impact clinical medicine, from diagnosing and treating a neurological disorder, to potentially altering the progression of disease, and in many ways, contemporary approved devices have brought a new sense of hope and optimism that serious and otherwise disabling neurological diseases can be treated and in many cases cured with modern therapy. We present here the scope of FDA’s regulatory landscape for neurological devices and neurointerventional endovascular approaches for acute ischemic stroke; this is essential information for those seeking to successfully translate medical device neurotechnologies for patient and consumer use.

ost of us were taught, in simpler times, the technical mastery of complex surgery, and we learned the indicaM tions for these procedures from our mentors, who showed us, primarily by direct example, that performing these surgeries was “the right thing to do.” We focused more on the techniques themselves, and consummate mastery of same, than we do now, when the focus is on the evidence and data-driven rationale for surgical interventions. The article by Mukerji et al., a masterpiece of carotid surgery technique and results by a masterful senior cerebrovascular surgeon, reminds us of our student days, whensingle-surgeon series’were the standard, and surgical training was more of a guild and mentorship than perhaps it is today.

Our chapter concerns the safety of placing cerebrospinal fluid diversionary techniques, either temporary or permanent, while patients are taking antiplatelet and/or anticoagulation medications. We review the current literature, as well as provide the experience from our institution.

Cerebral vasospasm is a devastating medical consequence of aneurysmal subarachnoid hemorrhage (aSAH), which is associated with a high level of morbidity and mortality and for which current therapies are inadequate. Ion channels in the smooth muscle cells of the cerebral vasculature have been considered as important molecular targets for anti-vasospastic therapies, but, other than the calcium channel blocker nimodipine, no therapies directed toward these targets have been demonstrated to improve patient outcomes. Recent research has revealed that a family of previously identified neuronal voltage-activated potassium channels, Kv7 (KCNQ) channels, is expressed in arterial smooth muscle cells, including cerebral arterial myocytes. This finding, along with the availability of clinically used drugs that were developed to target the neuronal Kv7 channels, provides an opportunity to develop novel therapeutic strategies to relieve or prevent cerebral vasospasm. Recent studies using both in vitro and in vivo approaches provide evidence to support the utility of Kv7 channel activators as anti-vasospastic agents, while revealing a number of additional potentially beneficial effects that could attenuate other neurological or inflammatory co-morbidities associated with aSAH.

An aging population and improved management of chronic conditions are at the crux of an issue confronting all surgeons—the increasing use of anticoagulation in older patients more likely to harbor surgical pathology and more susceptible to even trivial trauma when compared to younger cohorts. Cardiac, vascular, and prothrombotic conditions are the primary indications for antiplatelet or anticoagulant therapy, with the specific indications continually expanding. Furthermore, inconveniences and failures in past experience with these agents drives discovery and utilization of new agents, often before a reliable inhibitor or reversal agent exists [1–3]. The inherent risk in this situation is magnified further in neurosurgery due to the complex, unforgiving system involved.

Object Spinal cord injury (SCI) continues to be a problem without a definitive cure. Research based on improved understanding of the immunological aspects of SCI has revealed targets for treating and ameliorating the extent of secondary injury. Hypertonic saline (HTS), a substance both easy to create and to transport, has been investigated as an immunologically active material that can be used in a clinically relevant interval after injury. In this pilot study, HTS was investigated in a murine model for its abilities to ameliorate secondary injury after a severe spinal cord contusion. Methods Female C57Bl/6 mice with severe T8–10 contusion injuries were used as the model subjects. A group of 41 mice were studied in a blinded fashion. Mice received treatments with HTS (HTS, 7.5%) or normal saline solution (NSS, 0.9%) at 2 discreet time points (3 and 24 hours after injury.) A separate group of 9 untreated animals were also used as controls. Animals were assessed for autonomic outcome (bladder function). In a group of 33 mice, histological assessment (cellular infiltration) was also measured. Results Bladder function was found to be improved significantly in those treated with HTS compared with those who received NSS and also at later treatment times (24 hours) than at earlier treatment times (3 hours). Decreased cellular infiltration in each group correlated with bladder recovery. Conclusions The increased effectiveness of later administration time of the more osmotically active and immunomodulatory substance (HTS) suggests that interaction with events occurring around 24 hours after injury is critical. These events may be related to the invasion of leukocytes peaking at 8–24 hours postinjury and/or the peak benefit time of subject rehydration.

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

Objective Spinal dural arteriovenous fistulas (DAVFs) are insidious pathologies that, if left untreated, harbor potentially devastating consequences to the central nervous system. Spinal DAVFs are rare in the adult population and exceedingly uncommon in the pediatric population. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is subarachnoid hemorrhage (SAH). Balloon-test occlusion and balloon–catheter-assisted embolization of DAVF have not been previously described, and their advantages over alternative embolic and surgical techniques are discussed. Methods We performed a literature search on MEDLINE/PubMed to review current reports describing the epidemiology, clinical presentation, and treatment of spinal DAVFs. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is SAH. Results A spinal DAVF was diagnosed after deciding to image not only the brain but also the spine. Using a balloon-occlusion catheter, we confirmed that the DAVF arterial feeding vessel could be safely embolized. We then proceeded to effectively treat the DAVF with balloon–catheter-assisted Onyx-18 embolization. Conclusion Based on our report and an analysis of the literature, we propose that pediatric patients presenting with nontraumatic SAH should undergo at least a magnetic resonance imaging of the brain and cervical spine as part of their initial workup. In addition, we describe a balloon-occlusion catheter embolization technique that allows not only excellent embolic penetration of the fistula but also prevention of microcatheter reflux and lessening of the need for a tedious plug-and-stack technique.

Extracranial carotid artery stenosis represents a local manifestation of systemic cardiovascular disease, specifically at the bifurcation of the common carotid artery. It affects roughly half of all patients over 60 years of age and has been strongly correlated with 10–20 % of all strokes. The first resort of extracranial carotid artery stenosis management must be prevention, including the treatment of hypertension, hyperlipidemia, and diabetes, as well as smoking prevention/cessation. However, in the case of symptomatic and asymptomatic disease, several high-quality randomized controlled trials have demonstrated that aspirin and statins can reduce the risk of future ischemic events, while severe stenosis (>50 %) is best treated via carotid endarterectomy. For those patients who become candidates for carotid surgery, thorough perioperative workups must be tended to and vigilant postoperative care provided. In the hands of quality surgical teams, carotid endarterectomy offers the greatest 5-year reductions in extracranial carotid artery stenosis associated with cerebral ischemia and death.

Purpose To investigate whether improved clinical history allows the radiologist to better predict the pretest probability of obtaining a positive or negative result from a magnetic resonance (MR) examination. Materials and Methods Six neuroradiologists prospectively reviewed 100 consecutive requests for brain MR examinations and sequentially assessed 1) quality of written history, 2) degree of indication for requested study, and 3) any pertinent new information found during chart review that may have altered the degree of indication. MR yield was correlated with the degree of indication assessed before and after chart review. Results Most request form histories were judged as poor (63%), and chart review reduced the overall indications for MR examinations, as there was a tendency for high-indication requests to migrate to the low-indication category. Based on request form history alone, the yields for low- and high-indication studies were 13% and 37%, respectively. Correlations between MR yield and indication after chart review improved significantly (P < 0.05) with 2% and 61% for low and high indications, respectively. Sensitivity and specificity for a positive MR yield were 71% and 62%, respectively, for the indication judged by the request history alone, and 96% and 80%, respectively, after chart review. Positive and negative prediction rates were 37% and 87%, respectively, for the indication judged by the request history alone, and 61% and 98%, respectively, for the indication judged after chart review. Conclusion Based on our limited data, most request form histories were inadequate, and essential information available in the chart before MR examinations was frequently missing from the request forms. When adequate information was provided, the indication for the studies as judged by the radiologists predicted the MR yield more accurately, particularly for those requests with low indication. Therefore, our study suggests that MR imaging (MRI) may be used more effectively when pertinent clinical history is available. However, our study is limited and further studies are needed to confirm our results. J. Magn. Reson. Imaging 2004;20:228–232. © 2004 Wiley-Liss, Inc.

High-risk carotid surgery means that the likelihood of a complication is increased over the levels that are customarily accepted for carotid reconstruction. There are many instances where a high-risk operation should be performed, and where the increased risk is acceptable to the patient and the physician. In this presentation, I will identify the cases that I consider to be in high-risk groups and will present my evaluation and management strategy for these patients. Clearly, the surgeon considering a high-risk operation should have a good understanding of the natural history of carotid disease and the risks of surgery compared to the expected risks of medical treatment. I divide high-risk operations into several major categories. These include predictably difficult operations, cases with high risk for medical complications, cases with high risk for intraoperative ischemia, and cases with high risk for postoperative occlusion/stroke. Predictably, difficult operations include those with peculiar anatomical variants, reoperation, irradiated carotids, or extreme high exposures. With special emphasis on technique, these cases can be well performed surgically and the presentation will illustrate such cases. Patients with high-risk for medical complications include those with recent myocardial infarction, unstable angina, diabetic patients, patients with severe pulmonary disease, and patients who require continued postoperative anticoagulation (usually for heart valves). In many cases, these patients can undergo successful surgery; some such cases may also be suitable for endovascular treatment, particularly for recent myocardial disease. Patients with high-risk for intraoperative ischemia require that the surgeon have a solid knowledge of shunt placement and other strategies for cerebral protection. These include patients with contralateral occlusion, difficult shunt placements, high or difficult exposures, unstable neurological deficits, and propagating intraluminal thrombus high up the internal carotid. Patients with high risk for postoperative occlusion or stroke include diabetic patients, high focal lesions in the ICA, patients with postoperative hypotension, and hypertensive patients with headache following opening of a tight stenosis (dysautoregulated brain). In the majority of these cases, the use of a Hemashield patch graft will reduce or eliminate the chances of postoperative problems. Carotid surgery can be well performed by an experienced surgeon even in high-risk groups, and at present it remains the best-proven treatment for these cases. In the future, endovascular treatments may become common for some of these cases, but the scientific evidence to support this must still be proven. The most important factors in assuring a successful operation are careful planning, experience, and a high skill level for the operating surgeon.

The history of carotid surgery begins not with the detailing of the various surgical procedures, as might be imagined, but with a history of the understanding of the nature of carotid occlusive disease. It was only through an understanding of the basis of this disease that a rational surgical treatment could be formulated. Following a well-characterized disease process, surgical strategies were developed and refined during the first half of the twentieth century. After these surgical techniques had been refined, a number of national and international trials were performed to better determine which patients were candidates for surgical intervention. Currently, endovascular treatment stands on the horizon as a new therapeutic modality with which carotid occlusive disease may be treated.

Object. Exogenous progesterone has been shown to reduce brain edema and ischemia-induced cell damage and to improve physiological and neurological function during the early stage of focal cerebral ischemia. In the present study, the authors assessed the neuroprotective potential of progesterone during the late stage of ischemia in a transient middle cerebral artery (MCA) occlusion model in the rat.Methods. Forty-eight male spontaneously hypertensive rats were randomly assigned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accomplished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion volume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group.Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with control rats.Conclusions. Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.

In this article, the authors describe their standard technique for carotid endarterectomy and discuss the various surgical options and different variations of the procedure. Although there are numerous ways to perform carotid endarterectomy, several basic principles of carotid reconstruction must be adhered to. The surgeon must have complete preoperative knowledge of the patient's vascular anatomy, must maintain complete vascular control at all times, must have sufficient working anatomic knowledge to prevent harm to adjacent structures, and must assure the patient a patent repair that is free of technical errors. The most important factor in assuring a technically acceptable carotid surgery is the availability of a skilled cerebrovascular surgeon who has demonstrable morbidity and mortality rates below 3% and a proper understanding of both vascular principles and cerebral physiology.

Objective This study compared the electroencephalographic (EEG) changes occurring during carotid occlusion in 225 consecutive patients undergoing carotid endarterectomies performed by two surgeons, one using local and the other using general anesthesia. Methods A retrospective review of patients undergoing carotid endarterectomies for carotid occlusive disease was conducted. EEG changes associated with intraoperative ischemia (decreased amplitude, generalized slowing, and loss of fast activity) resulting in the need for an indwelling arterial shunt were recorded for the two anesthesia groups. To determine the similarities or differences between the two groups, the groups were compared regarding age, risk factors, and indications for surgery. Results Significant EEG changes were noted in 6 of 96 patients (6.3%) in the local anesthesia group versus 19 of 121 patients (15.7%) in the general anesthesia group. EEG changes consisted solely of generalized slowing in the local anesthesia group, whereas a more varied spectrum was observed in the general anesthesia group. The two groups were similar regarding age and risk factors. Although the local anesthesia group had more asymptomatic patients, symptomatic patients did not have a greater incidence of EEG changes. Conclusion There is a large difference in EEG changes potentially requiring shunt placement in patients undergoing surgery while under local (6.3%) versus general (15.7%) anesthesia. This could not be explained based on age, risk factors, interpretation of EEG findings, or indications between the two groups. We conclude that EEG monitoring may be insensitive and may fail to detect ischemia in patients who are under regional anesthesia. Alternately, the presence of general anesthetics may alter the character of the EEG findings and increase the sensitivity of EEG monitoring to ischemic events.

OBJECTIVE: Augmentation of blood flow to collateral-dependent tissue (CDT) as a result of selective vasodilation of collateral vessels has been shown to occur with various stimuli after middle cerebral artery occlusion. Etomidate, a carboxylated imidazole derivative, is a nonbarbiturate anesthetic that is used clinically both as an anesthetic and as a neuroprotective agent. The effect etomidate has on collateral cerebral vessels is unknown. The purpose of our studies was to test whether etomidate selectively augmented cerebral blood flow (CBF) to CDT during ischemia as an additional mechanism of neuroprotection. METHODS: A left craniotomy was performed in each of 14 dogs, with the animals under halothane anesthesia. A branch of the middle cerebral artery was occluded and cannulated distally for determination of CDT using a shadow flow technique. CBF and vascular pressures were measured and used to calculate vascular resistance. An etomidate infusion (0.1 mg/kg of body weight/min administered intravenously) was started, and CBF and vascular pressures were measured at 10 and 40 minutes. Hypotension was then induced, and CBF and pressures were again measured. RESULTS: CBF was significantly reduced in all regions of the brain, including CDT, when etomidate was infused. CDT showed a 53.7% reduction in flow, whereas normal CBF was reduced by at least 63.4%. During hypotension, blood flow to CDT was reduced by an additional 42.7%, whereas normal cerebrum was reduced by at least 22.7%. Vascular resistance was increased in all vessels during etomidate infusion. CONCLUSION: The neuroprotective effects of etomidate do not seem to be through the augmentation of collateral or global CBF.

PURPOSE: In this report, we describe a new multimodality device concept for occluding giant aneurysms. The device is designed to exploit the advantages, and avoid the disadvantages, of conventional microneurosurgery and interventional neuroradiology methods. CONCEPT: Our device concept involves surgically placing small permanent magnets, incorporated into a partially occluded magnetic clip, about the extraluminal neck without mechanically compromising the perforating vessels. These magnets serve as optimally positioned anchor points for ferromagnetic materials subsequently introduced via the endovascular route. RATIONALE: Currently, neurosurgical extraluminal obliteration of giant aneurysms is achieved by mechanically closing the aneurysm neck with metal clip blades, which is a technique that risks inadvertent occlusion of critical perforating vessels. Perforating vessel strokes can largely be avoided using endovascular aneurysm occlusion methods. However, in the setting of the giant aneurysm, these endovascular techniques are associated with high rates of incomplete occlusion. DISCUSSION: Preliminary feasibility tests of this concept were conducted using a simple prototype constructed in our laboratories.

OBJECTIVE To study the role of N-methyl-D-aspartate (NMDA) receptor activation and selective inhibition of neuronal nitric oxide synthase with 7-nitroindazole (7-NI) on blood flow to collateral-dependent tissue (CDT) after middle cerebral artery (MCA) occlusion. METHODS A left craniotomy was performed in each of 11 dogs with the animals under halothane anesthesia. A branch of the MCA was occluded and cannulated distally for determination of CDT, using a "shadow flow" technique. Cerebral blood flow (CBF) and vascular pressures were measured and used to calculate vascular resistance. TECHNIQUE Our shadow flow model has the ability to identify an area of CDT, with minimal contamination from overlap flow within a morphologically identified "risk area" for MCA branch occlusion. RESULTS NMDA increased blood flow to CDT by 56.2%, while normal ipsilateral and contralateral cerebrum increased by at least 35% from baseline. 7-NI caused a significant drop in regional CBF, with the greatest drop of 41.7% occurring in the CDT. Normal ipsilateral and contralateral CBF was reduced by 31.7 and 23.9%, respectively. The dilator response to NMDA was significantly attenuated after 7-NI administration, except in CDT where flow increased ("inverse steal"). Cerebral vascular resistance decreased in response to NMDA and increased with 7-NI. CONCLUSION Neuronal nitric oxide production seems to play an important role in regulating vascular tone and CBF to CDT after MCA occlusion. Selective preservation of blood flow to CDT seems to be mediated by NMDA receptor activation but independent of neuronal nitric oxide production.

✓ Serotonin (5-HT) produces constriction of peripheral collateral blood vessels. Using an animal model, the authors tested the hypothesis that 5-HT constricts collateral vessels in the cerebrum. A branch of the middle cerebral artery (MCA) was occluded proximally and cannulated distally in anesthetized dogs. Blood flow to the area at risk for infarction was detected by perfusing the cannulated MCA branch with microsphere-free blood during systemic injection of radioactive microspheres (shadow flow technique). Blood flow to collateral-dependent and normal cerebrum was measured during intravenous infusion of 5-HT (10 and 40 mg/kg/minute). Serotonin produced a dose-related reduction of blood flow to collateral-dependent cerebrum, increased collateral vessel resistance in large cerebral arteries and collateral vessels, and decreased cerebral artery perfusion pressure. In contrast, blood flow to normal cerebrum was not altered because a decrease in small vessel resistance effectively compensated for a decrease in MCA perfusion pressure. These findings indicate that 5-HT produces constriction of collateral vessels in the cerebrum. This response is clearly different from normal small cerebral vessels, which dilate during 5-HT infusion.

Surgical presence in the treatment of acute stroke patients is becoming increasingly aggressive. This article presents the current standards for stroke surgery in the acute setting, and defines those patient groups that represent appropriate candidates for such intervention.

therosclerotic cervical carotid artery disease is a significant contributor to the annual incidence of ischemic A stroke, which remains a leading cause of death, and was responsible for almost 130,000 fatalities in the United States in 2011 alone (14). A recent meta-analysis suggests that the prevalence of moderate and severe carotid stenosis (>50% luminal stenosis) is relatively common (6). Almost two decades ago, the Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial defined the 5-year cumulative risk of ipsilateral ischemic stroke among asymptomatic patients with more than 60% stenosis to be as high as 12% (8, 12). Among the symptomatic patient population—defined as those patients who have previously experienced a hemispheric transient ischemic attack, nondisabling stoke, or amaurosis fugax—the cumulative risk of ipsilateral ischemic stroke within 3e5 years of diagnosis was even higher, approximately 20%e25%, if the degree of luminal stenosis was greater than 70% (9, 19).

Stroke is a life threatening condition and remains the most common neurologic cause of hospital admission. Approximately 500,000 new or recurrent strokes are recorded each year in the United States. Behind cardiovascular disease and cancer, stroke remains the third leading cause of death in the United States, accounting for approximately 150,000 fatalities per year. Approximately 15%-20% of strokes are hemor-rhagic. This article focuses on intracerebral hemorrhage, which accounts for approximately half of stroke-related deaths.

Adenosine is a potent cerebral vasodilator. We tested the hypothesis that dilatation of collateral vessels in cerebrum, in response to topical adenosine and 2-chloroadenosine (2-CAD), would increase blood flow to collateral-dependent cerebrum. In dogs anesthetized with halothane, a branch of the middle cerebral artery (MCA) was occluded proximally and cannulated distally. The collateral-dependent area at risk for infarction was perfused from a reservoir with microsphere-free blood, and blood flow to normal cerebrum and to cerebrum dependent on collateral flow was measured with radioactive microspheres injected into the left ventricle through a femoral artery catheter. Perfusion through the cannulated MCA branch was stopped, and flow to normal and collateral-dependent cerebrum was measured after adenosine (10−2 M) or 2-CAD (10−4 M) was added to the superfusate over the cerebrum. In normal cerebrum, topical application of adenosine increased flow to outer but not inner layers. Topical application of adenosine had little effect on flow to collateral-dependent tissue. In normal cerebrum, 2-CAD increased flow to outer layers, whereas flow to inner layers tended to increase. During 2-CAD, flow to outer cortical layers of collateral-dependent cerebrum increased from 140 ± 20 ml/100 g/min (mean ± SD) to 231 ± 68, whereas flow to the inner collateral-dependent tissue did not change. The findings indicate that, after occlusion of a cerebral artery, topical 2-CAD increases blood flow to outer layers of collateral-dependent and normal cerebrum. The findings suggest also that, after arterial occlusion, collateral circulation to cerebrum has dilator reserve, and flow to tissues that are dependent on collaterals may be augmented.

TWO CASES OF delayed posterior interosseous nerve palsy after brachiocephalic arteriovenous fistula creation are presented. Both patients suffered from end-stage renal disease, necessitating chronic hemodialysis. After fistula construction, both developed progressive weakness of the muscles innervated by the posterior interosseous nerve. One patient also demonstrated sensory loss in the distribution of the superficial radial nerve. Electrophysiological studies confirmed posterior interosseous mononeuropathies in both cases. Surgical exploration demonstrated posterior interosseous nerve continuity, with severe compression from the hypertrophied venous limb of the arteriovenous fistula. The superficial radial nerve was also compressed in one patient. After neurolysis and fistula revision, both patients recovered neurological function.

In reviews in the 1980s, we discussed both indications for and surgical techniques in carotid endarterectomy. Significant changes in the practice of extracranial cerebrovascular reconstruction have occurred over the past few years. The newest indications and cooperative study data have recently been discussed by Camarata and Heros in this topic review series. In this article, we aim to review the advances in operative monitoring and surgical techniques of the last decade. We would be remiss, however, not to note that the latest Asymptomatic Carotid Atherosclerosis Study data, released in September 1994, indicate that carotid endarterectomy is significantly superior to medical therapy for asymptomatic stenosis of > 60%. These data, along with the North American Symptomatic Carotid Endarterectomy Trial results, will revitalize and lend scientific validity to carotid artery reconstruction.