Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

ICAR: endoscopic skull‐base surgery

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Delayed re-opening of an STA-MCA bypass graft

We describe the case of a 47-year-old female with symptomatic right MCA stenosis who had undergone cerebral revascularization through a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass. Despite clear patency in the operating room, post-operative angiography showed no flow in the bypass. Her ipsilateral internal carotid artery (ICA) was widely patent. She remained asymptomatic and follow-up angiography four years later showed a widely patent bypass graft in the setting of critical stenosis of the ipsilateral ICA. That the graft was found opened up and supplying the hemisphere was presumably stimulated by an increased demand and flow gradient promoting its patency. © Springer-Verlag 2006

Differential macrophage responses in the peripheral and central nervous system during wallerian degeneration of axons.

We characterized quantitatively the macrophage response following axonal injury in both the peripheral (PNS) and central nervous system (CNS) of adult mammals. A monoclonal antibody (ED-1) which stains monocytes, macrophages, and activated microglia was employed. In one model, Wallerian degeneration of the sciatic nerve was studied. An increase in the number of macrophages was seen as early as 1 day following nerve transection. Macrophage number increased synchronously along the length of degenerating nerve over a 21-day period. In a second model, transection of a spinal dorsal sensory root allowed us to compare and contrast the macrophage response along the PNS and CNS portions of a single axonal pathway. An increased number of macrophages restricted to the PNS portion of this pathway was seen by 3 days and continued to increase over a 14-day period. Myelin breakdown occurred in association with an increase in the number of macrophages by 3 days in the PNS but not the CNS portion of the degenerating dorsal root axon pathway. Low-affinity nerve growth factor receptor immunohistochemical staining increased by Day 1 in the PNS but not the CNS portion of this pathway, occurring prior to the invasion of macrophages. In both models, the morphology of infiltrating macrophages changed over time from small slender ramified cells to large elongated multivacuolated cells. In conclusion, our results demonstrate that the macrophage response during Wallerian degeneration of axons in adult mammals is much more rapid and robust in the PNS, where axonal regeneration occurs, than in the CNS, where axonal regeneration is far more limited

Radiosurgery for Cushing\u27s disease after failed transsphenoidal surgery

Object. Although transsphenoidal surgery has become the standard of care for Cushing\u27s disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing\u27s disease after failed transsphenoidal surgery. Methods. The records of all patients who underwent GKRS at the authors\u27 institution after unsuccessful transsphenoidal surgery for Cushing\u27s disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications. Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3-48 months). Three patients had a recurrence of Cushing\u27s disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract. Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing\u27s disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up

Blood use in cerebrovascular neurosurgery

Background and Purpose: This study reviews the perioperative use of red blood cell transfusion in cerebrovascular neurosurgery. The current algorithm for preoperative ordering of red cells is historical and dated. More blood is ordered than is actually transfused, and considerable variability exists between different institutions. We determine the use of blood transfusion in cerebrovascular surgery to develop a rational blood ordering practice. Methods: Records of 301 patients undergoing cerebrovascular neurosurgery at the University of Virginia were reviewed to quantitatively evaluate red blood cell transfusion practices. The amount and reason for transfusion were noted in each case. Results: In 126 patients undergoing carotid endarterectomy, there were no preoperative or intraoperative transfusions and 5 postoperative transfusions (4.0%). In 71 ruptured aneurysm patients, there were 2 preoperative blood transfusions (2.8%), 4 intraoperative transfusions (5.6%), and 15 postoperative transfusions (21.1%). Forty-seven patients underwent surgery for unruptured aneurysms, with no preoperative transfusions, 2 intraoperative transfusions (4.3%), and 8 postoperative blood transfusions (17.0%). Of the 54 patients undergoing surgery for arteriovenous malformations, 5 patients (9.3%) were transfused preoperatively, 4 were transfused intraoperatively (7.4%), and 22 were transfused postoperatively (40.7%). None of the 3 patients undergoing surgery for concomitant arteriovenous malformations and aneurysms received intraoperative blood transfusions, but 1 received blood both preoperatively and postoperatively, and another received a transfusion postoperatively only. The overall ratio of perioperative cross-match to transfusion in this series is 41.4. Conclusions: In vascular neurosurgery at our institution, blood has routinely been ordered excessively. We recommend an ABO-Rh type and antibody screen for aneurysm and arteriovenous malformation surgery and no screen for carotid endarterectomy to efficiently utilize transfusion therapy in cerebrovascular surgery

Basilar tip aneurysm - Adenosine induced asystole for the treatment of a basilar tip aneurysm following failure of temporary clipping

We report on a giant basilar tip aneurysm in a 48-year-old woman that could not be clipped despite temporary occlusion of the basilar trunk. Adenosine induced cardiac asystole reduced the aneurysm\u27s wall tension and coupled with increased exposure resulting from brain relaxation allowed for the aneurysm to be satisfactorily occluded via an extended right pterional craniotomy. In difficult vascular cases, adenosine induced cardiac standstill is a useful technique which may allow for technical success when other methods such as temporary clipping fail. It acts to both reduce aneurysm wall tension and increase operative exposure by reducing vascular, and hence brain volume. © 2007 Springer-Verlag

The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery

OBJECT: Pituitary adenomas are considered benign tumors; however, they may infiltrate surrounding tissues including the dura mater. In this paper the authors analyze the clinical significance of microscopically confirmed dural invasion by comparing a range of variables (age and sex of patients, adenoma type, adenoma size on magnetic resonance [MR] images, remission, residual pituitary disease, recurrence, survival, and disease-free interval after surgery) between patients with noninvasive adenomas and those with invasive ones. METHODS: Between 1992 and 1997 dural specimens were obtained in 354 patients with pituitary adenomas who underwent transsphenoidal surgery performed by the senior author (E.R.L.). Dural specimens were examined using routine histological methods and assessed for invasion by pituitary adenoma tissue. The dura was invaded by the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no evidence of dural invasion was found. Dural invasion was present significantly more frequently in the repeated surgery group (69%, 55 patients) than in the primary transsphenoidal surgery group (41%, 291 patients). The mean age of patients undergoing primary transsphenoidal surgery was significantly older in cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas (43 years), and these age differences also correlated with adenoma size. Women tend to develop clinically evident, smaller adenomas at a younger age than men. Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of 154 were women, whereas of the patients with adenomas that were larger than 20 mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with increasing size of the pituitary adenoma as measured on MR images. In 291 patients who underwent primary pituitary surgery, the frequency of dural invasion according to adenoma size was 24% (\u3c or = 10 mm), 35% (\u3e 10 to \u3c or = 20 mm), 55% (\u3e 20 to \u3c or = 40 mm), and 70% (\u3e 40 mm). In patients who underwent primary transsphenoidal surgery, dural invasion was present in more than 50% of those with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell adenomas was significantly larger than that of each of the endocrinologically active adenomas. In 58 (20%) of 291 patients who underwent primary pituitary surgery there was residual pituitary disease postsurgery, and 20% of this subset of patients showed clinical improvement to such an extent that no further management was recommended. After pituitary surgery, residual tumor tissue was demonstrable significantly more frequently in patients with invasive adenomas than in those with noninvasive adenomas. Recurrences after initial remission (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and 79 months after primary pituitary surgery (median 25 months). The recurrence rate was not related to dural invasion in a consistent or significant fashion. Seven patients died between 14 and 79 months after pituitary surgery and all had invasive adenomas identified on gross observation at surgery and on microscopy. The survival rate was slightly but significantly decreased for patients with invasive adenomas (91%) compared with patients with noninvasive adenomas (100%) at 6 years postsurgery. CONCLUSIONS: The principal significance of dural invasion by pituitary adenoma is the persistence of tumor tissue after transsphenoidal surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The increase in adenoma size with time and the concurrent development of dural invasion are the major factors that determine an incomplete adenomectomy. When the adenoma remains restricted to the sellar compartment or shows only moderate suprasellar extension, dural invasion may not yet have developed and conditions for complete selective adenomectomy are improved

Characterization of genetically defined types of Charcot-Marie-Tooth neuropathies by using magnetic resonance neurography

OBJECT: Charcot-Marie-Tooth (CMT) disease is a collection of related genetic disorders affecting peripheral nerves with an incidence of one in every 2500 individuals. A diagnosis of CMT disease has classically relied on a medical history, examination, and measurement of nerve conduction velocities. Advancements in genetic testing and magnetic resonance (MR) imaging techniques may provide clinicians with a more precise diagnostic armamentarium. The authors investigated MR neurography as a possible method to characterize CMT subtypes. METHODS: The authors performed MR neurography to evaluate sciatic nerves in the mid-thigh area of seven patients with genetically defined subtypes of CMT, one patient with chronic inflammatory demylinating polyneuropathy, and one patient without neuropathy. The authors correlate their findings with normal nerve conduction velocities (NCVs) and present their results as a descriptive case series. Although MR neurography could not be used to distinguish subtypes of CMT disease on nerve area or fascicle number, it appears to characterize phenotypic features and disease progression noninvasively in patients with some subtypes. CONCLUSIONS: In conjunction with NCV measurements, MR neurography may be useful in the diagnosis of CMT neuropathies and in monitoring disease progression