Establishment of primary stroke centers: a survey of physician attitudes and hospital resources.

OBJECTIVES: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. METHODS: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. RESULTS: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. CONCLUSIONS: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment.

Educating the next generation of physicians about stroke: incorporating stroke prevention into the medical school curriculum.

BACKGROUND AND PURPOSE: In response to the need to educate physicians about stroke, we have implemented an educational program on stroke prevention for undergraduate medical students within the first-year neuroscience course. This study investigated whether first-year students learned and retained key information about stroke, and used students' feedback both to identify effective curricular components and to explore their attitudes regarding stroke prevention. METHODS: Stroke knowledge and self-assessed confidence in that knowledge before, immediately after, and 8 months after participation in the stroke curriculum were analyzed and compared for 3 classes, using paired t tests and repeated-measures ANOVA. Student feedback about the effectiveness of specific parts of the curriculum and about the importance of stroke prevention was solicited and evaluated. RESULTS: First-year medical students in 3 classes more than doubled their overall stroke knowledge scores (pretest total mean of 8.2; posttest mean 18.0), and retained significant improvement 8 months later (mean 15.7). Subscores in all 4 areas of stroke knowledge tested significantly increased (P<0.001). Students' confidence in their knowledge of stroke risk factors and warning signs, as well as in their knowledge itself, increased (P<0.001). Each of the 3 cohorts demonstrated similar improvements. Feedback indicated heightened awareness and interest in stroke prevention, which was maintained after completion of the curriculum. CONCLUSIONS: These results demonstrate that when instruction on stroke prevention is incorporated into the first-year curriculum, students learn and retain key information. Because entire classes of medical students are involved, this type of approach has the potential to reach all future physicians and therefore to meaningfully impact future stroke care.

Advances in the genetics of cerebrovascular disease and stroke.

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.

Experimental radiosurgery simulations using a theoretical model of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: A novel biomathematical arteriovenous malformation (AVM) model based on electric network analysis was used to investigate theoretically the potential role of intranidal hemodynamic perturbations in elevating the risk of rupture after simulated brain AVM radiosurgery. METHODS: The effects of radiation on 28 interconnected plexiform and fistulous AVM nidus vessels were simulated by predefined random or stepwise occlusion. Electric circuit analysis revealed the changes in intranidal flow, pressure, and risk of rupture at intervals of 3 months during a 3-year latency period after simulated partial/complete irradiation of the nidus using doses <25 and >/=25 Gy. An expression for risk of rupture was derived on the basis of the functional distribution of the critical radii of component vessels. The theoretical effects of radiation were also tested on AVM nidus vessels with progressively increasing elastic modulus (E:) and wall thickness during the latency period, simulating their eventual fibrosis. RESULTS: In an AVM with E=5. 0x10(4) dyne/cm(2), 4 (14.3%) of a total 28 sets of AVM radiosurgery simulations revealed theoretical nidus rupture (risk of rupture >/=100%). Three of these were associated with partial nidus coverage and 1 with complete treatment. All ruptures occurred after random occlusion of nidus vessels in AVMs receiving low-dose radiosurgery. Intranidal hemodynamic perturbations were observed in all cases of AVM rupture; the occlusion of a fistulous component resulted in intranidal rerouting of flow and escalation of the intravascular pressure in adjacent plexiform components. Risk of rupture was found to correlate with nidus vessel wall strength: a low E: of 1.9x10(4) dyne/cm(2) resulted in a 92.8% incidence of AVM rupture, whereas a higher E: of 7.0x10(4) dyne/cm(2) resulted in only a 3.6% incidence of AVM rupture. A dramatic reduction in rupture incidence was observed when increasing fibrosis of the nidus was modeled during the latency period. CONCLUSIONS: It was found that the theoretical occurrence of AVM hemorrhage after radiosurgery was low, particularly when radiation-induced fibrosis of nidus vessels was considered. When rupture does occur, it would appear from a theoretical standpoint that the occlusion of intranidal fistulas or larger-caliber plexiform vessels could be a significant culprit in the generation of critical intranidal hemodynamic surges resulting in nidus rupture. The described AVM model should serve as a useful research tool for further theoretical investigations of cerebral AVM radiosurgery and its hemodynamic sequelae.

Can induction of systemic hypotension help prevent nidus rupture complicating arteriovenous malformation embolization?: analysis of underlying mechanism achieved using a theoretical model.

BACKGROUND AND PURPOSE: Nidus rupture is a serious complication of intracranial arteriovenous malformation (AVM) embolotherapy, but its pathogenetic mechanisms are not well described. An AVM model based on electrical network analysis was used to investigate theoretically the potential role of hemodynamic perturbations for elevating the risk of nidus vessel rupture (Rrupt) after simulated AVM embolotherapy, and to assess the potential benefit of systemic hypotension for preventing rupture. METHODS: Five separate hypothetical mechanisms for nidus hemorrhage were studied: 1) intranidal rerouting of blood pressure; 2) extranidal rerouting of blood pressure; 3) occlusion of draining veins with glue; 4) delayed thrombosis of draining veins; and 5) excessively high injection pressures proximal to the nidus. Simulated occlusion of vessels or elevated injection pressures were implemented into the AVM model, and electrical circuit analysis revealed the consequent changes in intranidal flow, pressure, and Rrupt for the nidus vessels. An expression for Rrupt was derived based on the functional distribution of the critical radii of component vessels. If AVM rupture was observed (Rrupt > or = 100%) at systemic normotension (mean pressure [P] = 74 mm Hg), the theoretical embolization was repeated under systemic hypotension (minor P = 70 mm Hg, moderate P = 50 mm Hg, or profound P = 25 mm Hg) to assess the potential benefit of this maneuver in reducing hemorrhage rates. RESULTS: All five pathogenetic mechanisms under investigation were able to produce rupture of AVMs during or after embolotherapy. These different mechanisms had in common the capability of generating surges in intranidal hemodynamic parameters resulting in nidus vessel rupture. The theoretical induction of systemic hypotension during and after treatment was shown to be of significant benefit in attenuating these surges and reducing Rrupt to safer levels below 100%. CONCLUSION: The induction of systemic hypotension during and after AVM embolization would appear theoretically to be of potential use in preventing iatrogenic nidus hemorrhage. The described AVM model should serve as a useful research tool for further theoretical investigations of AVM embolotherapy and its hemodynamic sequelae.

Recommendations for the establishment of primary stroke centers. Brain Attack Coalition.

OBJECTIVE: To develop recommendations for the establishment and operation of primary stroke centers as an approach to improve the medical care of patients with stroke. PARTICIPANTS: Members of the Brain Attack Coalition (BAC), a multidisciplinary group of representatives from major professional organizations involved with delivering stroke care. Supplemental input was obtained from other experts involved in acute stroke care. EVIDENCE: A review of literature published from 1966 to March 2000 was performed using MEDLINE. More than 600 English-language articles that had evidence from randomized clinical trials, meta-analyses, care guidelines, or other appropriate methods supporting specific care recommendations for patients with acute stroke that could be incorporated into a stroke center model were selected. CONSENSUS PROCESS: Articles were reviewed initially by 1 author (M.J.A.). Members of the BAC reviewed each recommendation in the context of current practice parameters, with special attention to improving the delivery of care to patients with acute stroke, cost-effectiveness, and logistical issues related to the establishment of primary stroke centers. Consensus was reached among all BAC participants before an element was added to the list of recommendations. CONCLUSIONS: Randomized clinical trials and observational studies suggest that several elements of a stroke center would improve patient care and outcomes. Key elements of primary stroke centers include acute stroke teams, stroke units, written care protocols, and an integrated emergency response system. Important support services include availability and interpretation of computed tomography scans 24 hours everyday and rapid laboratory testing. Administrative support, strong leadership, and continuing education are also important elements for stroke centers. Adoption of these recommendations may increase the use of appropriate diagnostic and therapeutic modalities and reduce peristroke complications. The establishment of primary stroke centers has the potential to improve the care of patients with stroke. JAMA. 2000.

Transvenous retrograde nidus sclerotherapy under controlled hypotension (TRENSH): a newly proposed treatment for brain arteriovenous malformations--concepts and rationale.

PURPOSE: An alternative endovascular treatment to conventional transarterial embolization of cerebral arteriovenous malformations (AVMs) is proposed. CONCEPT: According to this proposed treatment, selected AVMs could undergo transvenous retrograde nidus sclerotherapy under controlled hypotensive anesthesia (TRENSH). RATIONALE: It is hypothesized that TRENSH may provide the means of avoiding delivery of embolic agents via arterial feeders (thus preventing ischemic complications), in addition to a possible more complete permeation of an AVM nidus with a sclerosant than can otherwise be obtained with current agents via arterial feeders. DISCUSSION: Instead of relying on access to an AVM nidus from the arterial side (with its usual complexity), TRENSH would require retrograde access to the lesion via much larger and anatomically simpler draining veins. Retrograde permeation of the AVM nidus may then be possible with a liquid sclerosant (to effect a "chemical embolization") provided that the arterial inflow is reduced sufficiently by temporary controlled systemic hypotension, with or without the aid of temporary balloon occlusion of the main arterial feeder(s). Retrograde spread of sclerosant within the nidus that falls short of filling arterial feeders and their branches to normal brain tissue may then be possible. Angioarchitectural and hemodynamic considerations are addressed, as are the potential role and limitations of TRENSH in the management of cerebral pial AVMs. Future implementation of this new technique in some specific selected cases in which the anatomic configuration of the AVM and its draining veins might be favorable could prove to be a potentially useful addition to the armamentarium of AVM therapies, which currently includes microsurgery, radiosurgery, and transarterial embolotherapy. Experimental studies directed at assessing the feasibility of TRENSH before potential future clinical application seem justified.

Theoretical modelling of arteriovenous malformation rupture risk: a feasibility and validation study.

PURPOSE: To explore the feasibility of using a theoretical computational model to simulate the risk of spontaneous arteriovenous malformation (AVM) haemorrhage. METHODS: Data from 12 patients were collected from a prospective databank which documented the angioarchitecture and morphological characteristics of the AVM and the feeding mean arterial pressure (FMAP) measured during initial superselective angiography prior to any treatment. Using the data, a computational model of the cerebral circulation and the AVM was constructed for each patient (patient-specific model). Two model risk (Risk(model)) calculations (haemodynamic- and structural-weighted estimates) were performed by using the patient-specific models. In our previously developed method of haemodynamic-weighted estimate, Risk(model) was calculated with the simulated intranidal pressures related to its maximal and minimal values. In the method of structural-weighted estimate developed and described in this paper, the vessel mechanical properties and probability calculation were considered in more detail than in the haemodynamic-weighted estimate. Risk(model) was then compared to experimentally determined risk which was calculated using a statistical method for determining the relative risk of having initially presented with AVM haemorrhage, termed Risk(exp). RESULTS: The Risk(model) calculated by both haemodynamic- and structural-weighted estimates correlated with experimental risks with chi2 = 6.0 and 0.64, respectively. The risks of the structural-weighted estimate were more correlated to experimental risks. CONCLUSIONS: Using two different approaches to the calculation of AVM haemorrhage risk, we found a general agreement with independent statistical estimates of haemorrhagic risk based on patient data. Computational approaches are feasible; future work can focus on specific pathomechanistic questions. Detailed patient-specific computational models can also be developed as an adjunct to individual patient risk assessment for risk-stratification purposes.

Anatomical and morphological factors correlating with rupture of intracranial aneurysms in patients referred for endovascular treatment.

The size of intracranial aneurysms is the only characteristic shown to correlate with their rupture. However, the critical size for rupture has varied considerably among previous accounts and remains a point of controversy. Our goal was to identify statistically significant clinical and morphological factors predictive of the occurrence of rupture and aneurysm size in patients referred for endovascular treatment. We retrospectively recorded the following factors from 74 patients who presented with ruptured (40) or unruptured (34) aneurysms: aneurysm morphology (uni/multilobulated), location (anterior/posterior), maximum diameter, diameter of the neck, and the patient's age and sex. We performed stepwise discriminant, and stepwise and logistic regression analysis to identify factors predicting rupture and the size of the aneurysm at rupture. The mean diameter of the ruptured aneurysms was 11.9+/-6.3 mm, range 3.0-33.0 mm, and that of the unruptured aneurysm 13.5+/-5.8 mm, range 5.0-30 mm. Stepwise discriminant analysis identified aneurysm morphology (P < 0.001) and location in the intracranial circulation (P < 0.001) as statistically significant factors in predicting rupture. Stepwise regression analysis revealed that aneurysm morphology and the size of the neck were predictors of aneurysm size at rupture.

Principles and philosophy of modeling in biomedical research.

Despite widespread applications in biomedical research, the role of models and modeling is often controversial and ill understood. It is usual to find that fundamental definitions, axioms, and postulates used in the modeling process have become tacit assumptions. What is essential, however, is a clear vision of the fundamental principles of modeling. This is even more compelling for new and emerging interdisciplinary fields that use techniques from previously separate scientific disciplines. This article outlines and reviews the central nature and philosophy of modeling, the rules that govern it, and its underlying key integral relationship to the 'scientific method'. A comprehensive understanding of these issues is indispensable to successful research and meaningful progress in all facets of biomedicine.

A nonlinear quasi-static model of intracranial aneurysms.

Biomathematical models of intracranial aneurysms can provide qualitative and quantitative information on stages of aneurysm development through elucidation of biophysical interactions and phenomena. However, most current aneurysm models, based on Laplace's law, are renditions of static, linearly elastic spheres. The primary goal of this study is to: 1. develop a nonlinear constitutive quasi-static model and 2. derive an expression for the critical size/pressure of an aneurysm, with subsequent applications to clinical data. A constitutive model of an aneurysm, based on experimental data of tissue specimens available in the literature, was incorporated into a time-dependent set of equations describing the dynamic behavior of a saccular aneurysm in response to pulsatile blood flow. The set of differential equations was solved numerically, yielding mathematical expressions for aneurysm radius and pressure. This model was applied to clinical data obtained from 24 patients presenting with ruptured aneurysms. Aneurysm development and eventual rupture exhibited an inverse relationship between aneurysm size and blood pressure. In general, the model revealed that rupture becomes highly probable for an aneurysm diameter greater than 2.0 mm and a systemic blood pressure greater than 125 mmHg. However, an interesting observation was that the critical pressure demonstrated a minimal sensitivity to the critical radius, substantiating similar clinical and experimental observations that blood pressure was not correlated, to any degree, with aneurysm rupture. Undulations in the aneurysm wall, presented by irregular multilobulated morphologies, could play an important role in aneurysm rupture. However, due to the large variation in results, more extensive studies will be necessary for further evaluation and validation of this model.