Radiation exposure of the anesthesiologist in the neurointerventional suite.

BACKGROUND: Scatter radiation during interventional radiology procedures can produce cataracts in participating medical personnel. Standard safety equipment for the radiologist includes eye protection. The typical configuration of fluoroscopy equipment directs radiation scatter away from the radiologist and toward the anesthesiologist. This study analyzed facial radiation exposure of the anesthesiologist during interventional neuroradiology procedures. METHODS: Radiation exposure to the forehead of the anesthesiologist and radiologist was measured during 31 adult neuroradiologic procedures involving the head or neck. Variables hypothesized to affect anesthesiologist exposure were recorded for each procedure. These included total radiation emitted by fluoroscopic equipment, radiologist exposure, number of pharmacologic interventions performed by the anesthesiologist, and other variables. RESULTS: Radiation exposure to the anesthesiologist's face averaged 6.5 ± 5.4 µSv per interventional procedure. This exposure was more than 6-fold greater (P < 0.0005) than for noninterventional angiographic procedures (1.0 ± 1.0) and averaged more than 3-fold the exposure of the radiologist (ratio, 3.2; 95% CI, 1.8-4.5). Multiple linear regression analysis showed that the exposure of the anesthesiologist was correlated with the number of pharmacologic interventions performed by the anesthesiologist and the total exposure of the radiologist. CONCLUSIONS: Current guidelines for occupational radiation exposure to the eye are undergoing review and are likely to be lowered below the current 100-150 mSv/yr limit. Anesthesiologists who spend significant time in neurointerventional radiology suites may have ocular radiation exposure approaching that of a radiologist. To ensure parity with safety standards adopted by radiologists, these anesthesiologists should wear protective eyewear.

Current recommendations for endovascular interventions in the treatment of ischemic stroke.

Ischemic stroke remains one of the leading cause of adult death and disability in the United States. Reperfusion of the occluded vessel is the standard of care in the setting of acute ischemic stroke according to established guidelines. Since the introduction of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in the late 1990s, significant advances have been made in methods to deliver thrombolytic agents and in devices for mechanical recanalization of occluded vessels. Furthermore, improvements in patient selection contribute to achievement of good clinical outcomes after endovascular therapy. This article summarizes findings from recent clinical trials and presents evidence-based guidelines for endovascular interventions in the treatment of ischemic stroke.

Bedside use of a dual aortic balloon occlusion for the treatment of cerebral vasospasm.

BACKGROUND: Delayed ischemic neurological deficits (DIND) due to cerebral vasospasm remains a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Methods to prevent DIND remain limited both in safety and efficacy. A novel intra-aortic dual balloon catheter (NeuroFlo™: CoAxia, Maple Grove, MN) is under investigation for treatment of ischemic stroke, including DIND. Because this technique does not require cerebral artery navigation, it may be useful as a bedside procedure, outside of the conventional angiography suite. We report the first case of ultrasound-guided application of the NeuroFlo™ system at bedside in the Neurological Intensive Care Unit. METHODS: A 52-year-old woman presented with Hunt Hess IV aSAH complicated by medically refractory cerebral vasospasm. Despite surgical clipping of her aneurysm, the patient remained critically ill, failing maximal conventional medical therapy. For that reason, the NeuroFlo™ system was deployed using two-dimensional, spectral and color-flow Doppler ultrasound guidance at the patient's bedside while maintaining all forms of cerebral blood flow monitoring. RESULTS: The procedure was well tolerated and there was no complication. CONCLUSION: Bedside application of the NeuroFlo™ system may be safely performed in critically ill patients. The NeuroFlo™ system is under investigation for treatment of refractory cerebral vasospasm to prevent delayed ischemic neurological disease.

Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer's disease.

Neocortical beta-amyloid (Abeta) aggregates in Alzheimer's disease (AD) are enriched in transition metals that mediate assembly. Clioquinol (CQ) targets metal interaction with Abeta and inhibits amyloid pathology in transgenic mice. Here, we investigated the binding properties of radioiodinated CQ ([(125)I]CQ) to different in vitro and in vivo Alzheimer models. We observed saturable binding of [(125)I]CQ to synthetic Abeta precipitated by Zn(2+) (K(d)=0.45 and 1.40 nm for Abeta(1-42) and Abeta(1-40), respectively), which was fully displaced by free Zn(2+), Cu(2+), the chelator DTPA (diethylene triamine pentaacetic acid) and partially by Congo red. Sucrose density gradient of post-mortem AD brain indicated that [(125)I]CQ concentrated in a fraction enriched for both Abeta and Zn, which was modulated by exogenous addition of Zn(2+) or DTPA. APP transgenic (Tg2576) mice injected with [(125)I]CQ exhibited higher brain retention of tracer compared to non-Tg mice. Autoradiography of brain sections of these animals confirmed selective [(125)I]CQ enrichment in the neocortex. Histologically, both thioflavine-S (ThS)-positive and negative structures were labeled by [(125)I]CQ. A pilot SPECT study of [(123)I]CQ showed limited uptake of the tracer into the brain, which did however, appear to be more rapid in AD patients compared to age-matched controls. These data support metallated Abeta species as the neuropharmacological target of CQ and indicate that this drug class may have potential as in vivo imaging agents for Alzheimer neuropathology.

Mice transgenic for Alzheimer disease beta-amyloid develop lens cataracts that are rescued by antioxidant treatment.

Alzheimer disease is characterized by cerebral Abeta deposition, which we have recently discovered occurs also in the lens as cataracts in Alzheimer disease patients. Here we report the presence of significantly increased cataracts in the lenses of an Abeta-transgenic mouse model for Alzheimer disease and their amelioration upon treatment with EUK-189, a synthetic SOD/catalase mimetic. These data support an oxidative etiology for AD-associated lens cataracts and their potential to be treated preventatively with antioxidants.

Coil embolization of intracranial dissecting vertebral artery aneurysms with subclavian steal.

Subclavian steal phenomenon occurs when cerebral blood flow is diverted to supply the arm. We report 3 patients with asymptomatic subclavian steal phenomenon with retrograde blood flow in the vertebral artery who presented with subarachnoid hemorrhage due to dissecting aneurysms of the involved vertebral artery. The association of subclavian steal phenomenon complicated by subarachnoid hemorrhage due to dissecting vertebral aneurysms has not been previously described.

Pre-operative intracranial meningioma embolization.

Pre-operative embolization is a routinely utilized therapeutic adjunct to the resection of hypervascular lesions of the head and neck. In particular, pre-operative cerebral angiography and tumor embolization has become standard practice at many centers in the management of select intracranial meningiomas. However, controversy remains regarding its specific indications and clinical utility. In this article, we examine the principles of meningioma embolization, emphasizing the indications, risks and benefits associated with its use in the pre-operative setting.

Update on the natural history of intracranial atherosclerotic disease: A critical review.

Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some reports have suggested that disease processes and outcomes vary by vessel location, potentially altering the natural history and indications for intervention. Here we have performed a comprehensive, critical review of the natural history of ICAD by vessel in an attempt to assess the differences in disease specific to each of the vascular territories. Our assessment concludes that only minor differences exist between patients with different vessels affected in vessel-specific ICAD. We have found that middle cerebral artery disease confers a lower mortality than vessel-specific ICAD in other intracranial vessels, asymptomatic disease follows a more benign course than symptomatic disease, and that plaque progression or the detection of microemboli on transcranial Doppler may predict poor outcome. Given the expanding indications for treatment of ICAD and rapidly developing endovascular techniques to confront this disease, a thorough understanding of the natural history of ICAD aids the interventional neuroradiologist in determining when to treat and how to predict outcome in this patient population.

Training in endovascular surgical neuroradiology.

BACKGROUND: During the past few years, the field of endovascular surgical neuroradiology has been expanding. Neurosurgeons, radiologists, and neurologists are currently being trained. We analyzed data from a national survey of endovascular training programs to assess the current training status and future projections. METHODS: Survey participation requests were sent out to program directors and members of the Society of Endovascular Neurosurgery, the Society of Neurointerventional Surgery, and the Society of Vascular and Interventional Neurology. The format was an on-line survey designed by the authors, and completed through the SurveyMonkey.com website. Forty-three programs were identified and invited to participate. RESULTS: We achieved a response rate of 81% (n = 35). Twenty-seven (79%) of the 35 respondents listed their training program as academic, and 7 (20%) listed it as a mixture of academic with private practice. The training program faculty consisted of 57 radiologists, 39 neurosurgeons, and 10 neurologists. Length of fellowship offered was the same for all specialties in 43%, and differed based on clinical experience/background in 51%. Of the programs, 86% offered a 2-year fellowship, 49% had a mandatory resident rotation, 17% offered an infolded complete fellowship for residents, and 34% offered an infolded partial fellowship. Only 9% reported no resident exposure at all. There were 12% of respondents who reported to have knowledge of vascular surgeons or cardiologists performing intracranial procedures. At the time of the survey, there were 68 fellows in training, and most entered training immediately after residency (38%), whereas 26% entered after a fellowship and another 26% trained while in residency. There will be a 14% increase of graduates within the next 5 years. Comparing the past 5 years (2003-2007) with future 5-year projections (2008-2012), the number of radiologists is declining by 37% (73 vs. 46), whereas the number of neurosurgeons (74 vs. 106) and neurologists (20 vs. 37) is increasing by 42.5% and 112%, respectively. CONCLUSIONS: This survey suggests that there is a strong interest in endovascular surgical neuroradiology. The overall number of graduates is increasing, particularly in neurosurgery and neurology. Although the majority of current faculty is still comprised of neuroradiologists, the number of graduates in radiology will be decreasing during the next 5 years, reflecting a trend toward greater subspecialization within the fields of neurosurgery and neurology. Peer-Review Article.

Contribution of vascular pathology to the clinical expression of dementia.

Vascular lesions in the brain are common with advancing age; however, the independent and cumulative contributions of postmortem vascular lesions to antemortem cognitive status are not well established. We examined association of six vascular lesions (large infarcts, lacunar infarcts, leukoencephalopathy, microinfarcts, cribriform changes, and cerebral amyloid angiopathy) with antemortem diagnoses of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in 190 older adults from an autopsy series. We also developed a summary score based on three macroscopic vascular lesions: large infarcts (0, 1, and >or=2), lacunar infarcts (0, 1, and >or=2), and leukoencephalopathy (none, mild, and moderate-to-severe). Sixty-eight percent of cases had vascular lesions. Only leukoencephalopathy was associated with dementia (odds ratio (OR) 3.5, 95% CI 1.0-12.4), and only large infarcts were associated with VaD (OR 4.3, 95% CI 1.2-15.4). The vascular score was associated with dementia (OR 1.6, 95% CI 1.2-2.3), AD (OR 1.5, 95% CI 1.0-2.1) and VaD (OR 2.0, 95% CI 1.4-3.0). Leukoencephalopathy, large infarcts, and higher vascular burden is associated with the clinical expression of dementia and subtypes.

False positive CT angiography in brain death.

INTRODUCTION: Ancillary testing is frequently required in the determination of death by brain criteria, particularly in cases in which the clinical examination is drawn into question. Newer tests, such as computed tomographic angiography (CTA), have garnered enthusiasm for their ease of performance, but have not been validated as acceptable tests compared with a gold standard. CASE: We present a case of a 31-year-old patient who was felt to have cerebral circulatory arrest on CTA, but was subsequently found to have evidence of preserved cerebral blood flow on transcranial Doppler, thus precluding the diagnosis death by brain criteria. DISCUSSION: CTA is not a validated confirmatory test for cerebral circulatory arrest in brain death, and may be falsely positive. CONCLUSION: CTA should be studied further in comparison to validated tests, such as conventional angiography or single photon emission computed tomography (SPECT), before being accepted as a standard ancillary test in determining death by brain criteria.

Endovascular treatment of intracranial arteriovenous malformation.

Arteriovenous malformations (AVMs) of the brain are vascular lesions in which an abnormal tangle or nidus of vessels permits pathologic shunting of blood flow from the arterial to the venous tree without an intervening capillary bed. With brain imaging techniques, an increasing number of AVMs are detected before they hemorrhage, leading to new considerations and modifications of interdisciplinary management strategies. Treatment options include endovascular embolization, microsurgical resection, radiosurgery, medical management, or a combination of these. Neuroendovascular therapy is a critical component of this multidisciplinary and multimodal approach. The development and introduction of newer techniques and agents will continue to affect embolization treatments.

Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid.

Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Abeta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Abeta and biological metals in CSF. We assayed CSF copper, zinc, other metals and Abeta42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF Abeta42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Abeta42. In vitro, the degradation of synthetic Abeta substrate added to CSF was markedly accelerated by low levels (2microM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta degradation is normally promoted by physiological copper and zinc concentrations.

Sex hormones and neuropathology in elderly men: the HAAS.

Experimental studies suggest 17-beta estradiol (E2) and testosterone (T) may have neuroprotective properties that are associated with Alzheimer's and vascular pathology. However, there are limited studies correlating steroid hormones with autopsy findings in humans. In this community-based autopsy study of elderly men (n=232) participating in the Honolulu Asia Aging Study, we found a significant decrease of neurofibrillary tangles in the highest tertile of free serum estradiol [IRR=0.43 (0.3-0.7)] after controlling for age at blood draw, interval from blood draw until death, ApoE allele, and socio-demographic health factors. Higher Free-T levels were associated with a two-fold increased risk for micro infarcts [IRR=2.2; 95% CI (1.2-4.1)]. There was no association between sex hormones and amyloid plaques or cerebral amyloid angiopathy. This community-based autopsy study suggests that peripheral levels of sex hormones are associated with neurofibrillary tangles and micro-infarcts, but not with other neuropathologic markers of brain disease in elderly men.

Endogenous sex hormones, cognitive decline, and future dementia in old men.

OBJECTIVE: To estimate the association of endogenous levels of bioavailable testosterone and estradiol with risk for cognitive decline and dementia in old men. METHODS: Within the population-based, prospective Honolulu-Asia Aging Study, 2,974 men, aged 71 to 93 years, without dementia were reexamined 3 times over an average of 6 years for development of dementia and cognitive decline. Cognitive decline was measured with the Cognitive Abilities Screening Instrument. Incident dementia was diagnosed according to standard criteria. A total of 134 men experienced development of Alzheimer's disease (AD; including 40 cases with contributing cerebrovascular disease) and 44 experienced development of vascular dementia. RESULTS: Adjusting for age and other covariates, testosterone was not associated with risk for dementia (using Cox regression analyses) or cognitive decline (using random coefficient analyses). However, higher levels of estradiol were associated with risk for AD (hazard ratio per standard deviation increase, 1.25; 95% confidence interval, 1.05-1.47) and AD with cerebrovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38). Also, compared with the lowest tertile of estradiol, men in the middle and highest tertile of estradiol had 0.24 and 0.28 points lower Cognitive Abilities Screening Instrument scores, respectively, for each year increase in age. INTERPRETATION: In old men, endogenous testosterone levels are not associated with risk for cognitive decline and AD, whereas higher estrogen levels increase risk for cognitive decline and AD.