OBJECTIVE:To examine time delays and identify factors that affect wait times from index neurological event to carotid endarterectomy in patients with symptomatic carotid stenosis treated at a regional neurosurgical referral centre.METHODS:We performed a retrospective audit over two years of all patients who underwent a carotid endarterectomy at University Hospital, London, Ontario. The number of days was calculated from first neurological event through until surgery.RESULTS:Eighty-nine carotid endarterectomies (CEAs) were performed by four surgeons during the years 2006 and 2007. From the first neurological event, the median wait time for surgery was 111 days, while from the last event the median wait time was 83 days. There was 19 days' wait between specialist / TIA clinic appointment and the receipt of neurosurgical referral. Median wait time for diagnostic imaging was eight days for carotid Doppler ultrasound and 15 days for CT or MR angiography. There was a 44 day wait from receipt of neurosurgical referral to the date of surgery. Only three patients (4%) received CEA within two weeks of their last neurological event. There was a trend towards a difference in wait times between inpatients and outpatients, but no difference between females compared with males, or between patients presenting with stroke versus TIA.DISCUSSION:Median wait times for CEA after first neurological event was over three months at our center, reflecting the diagnostic workup required in TIA as well as the lack of a systematic approach. This is the subject of continued study at our institution.

Erosion and rupture of surface layers in atherosclerotic plaque can cause heart attack and stroke; however, changes in luminal surface composition are incompletely defined. Laser-induced fluorescence spectroscopy (LIFS), with limited tissue penetration, was used to investigate the surface of unstable carotid plaque and correlated with microscopy, birefringence and gene expression. Arterial matrix collagens I, III and elastin were assessed in unstable plaques (n = 25) and reference left internal mammary arteries (LIMA, n = 10). LIFS in addition to selective histological staining with picrosirius red, Movat pentachrome and immunostaining revealed decreased elastin and increased collagen I and III (P < 0.05) in carotid plaque when compared with LIMA. Within plaque, collagen I was elevated in the internal carotid region versus the common carotid region. Polarized light microscopy detected layers of aligned collagen and associated mechanical rigidity of the fibrous cap. Microarray analysis of three carotid and three LIMA specimens confirmed up-regulation of collagen I, III and IV, lysyl oxidase and MMP-12. In conclusion, LIFS analysis coupled with microscopy revealed marked regional differences in collagen I, III and elastin in surface layers of carotid plaque; indicative of plaque instability. Birefringence measurements demonstrated mechanical rigidity and weakening of the fibrous cap with complementary changes in ECM gene expression.

A 59 year old male teacher developed symptoms of panhypopituitarism. MRI revealed a solid homogeneously enhancing mass in the sella measuring 1.8 cm extending into the suprasellar cistern causing mild compression of the optic chiasm. The resected specimen consisted of a fascicular and storiform arrangement of elongated cells with abundant eosinophilic cytoplasm lacking granularity. No mitotic figures were seen. Immunohistochemical studies for chromogranin and pituitary hormones were negative. The lesional cells expressed GFAP, PGP9.5, and S100. Electron microscopy showed lesional cells bearing abundant intermediate filaments and rare neurosecretory granules. The final diagnosis was pituicytoma. Pituicytomas are rare primary tumors of the neurohypophysis. The putative cell of origin is the pituicyte, which is a glial cell normally residing in the posterior pituitary and pituitary stalk, the function of which is thought to be the regulation of hormone secretion from the neurohypophysis. The natural history of the pituicytoma is not well understood due to their rarity, although the largest case series in recent years suggests that complete resection may be curative. However, there is a chance of recurrence following sub-total resection with the role of adjuvant therapies being uncertain at this time. Correspondence 622 Brain Pathology 18 (2008) 620–622 © 2008 The Authors; Journal Compilation © 2008 International Society of Neuropathology

OBJECTIVE The aim of this study was to present the clinical and radiological characteristics, surgical management, and outcome in a large series of patients with aneurysms of the distal anterior cerebral artery (DACA) managed in the microsurgical era. METHODS The records of 1109 patients with anterior circulation aneurysms managed at the authors' institution between 1970 and 1998 were reviewed. RESULTS Fifty-nine patients (5.3%) were identified with 67 DACA aneurysms. Seventy-three percent of the patients were women. The mean age of all patients was 47 years. Multiple aneurysms were identified in 51% of all patients, most commonly on the middle cerebral artery. Thirty-six patients had ruptured DACA aneurysms and 23 had unruptured aneurysms. In those with ruptured aneurysms, the admission grade was Grade I in 10 patients (27.8%), Grade II in three patients (8.3%), Grade III in 10 patients (27.8%), Grade IV in seven patients (19.4%), and Grade V in six patients (16.7%). Frontal lobe hematomas occurred in 28% of the patients with ruptured aneurysms and carried a poor prognosis. In those with unruptured aneurysms, 11 were incidental and 12 were identified after a subarachnoid hemorrhage from another aneurysm. The mean diameter was 10 mm in ruptured aneurysms and 5.8 mm in unruptured aneurysms. Fifty-eight patients underwent surgery and one patient was treated with endovascular coiling. Six patients, all with ruptured aneurysms, died. Seventy percent of survivors with ruptured aneurysms had a favorable outcome. CONCLUSION DACA aneurysms possess a number of characteristics that distinguish them from the more common intracranial aneurysms. With modern neurosurgical and endovascular techniques, an acceptable operative morbidity and mortality can be achieved.

Saccular aneurysms are balloon-like expansions developing from the branching region of a major brain artery; a small fraction are at risk of rupture with severe clinical consequences. Their wall integrity is related to both collagen fibre strength and orientation. Our approach involved serial section histology and polarized light microscopy, including 3D orientation and birefringence measurements. Results show a marked difference in fibre birefringence across the wall, with strength mainly in the outer layers. Directional and strength measurements on medial gap fibres of major brain artery bifurcations reveal an exceptional structural anisotropy - the apex having a tendon-like backbone.

Background and Purpose— Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. Methods— Patients with carotid stenosis of ≥60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. Results— 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P <0.0001) and were more likely to have a stroke during the first year of follow-up (15.6%, 95% CI, 4.1 to 79; versus 1%, 95% CI, 1.01 to 1.36; P <0.0001). Conclusions— Our findings indicate that TCD− ACS will not benefit from endarterectomy or stenting unless it can be done with a risk <1%; TCD+ may benefit as much as SCS if their surgical risk is not higher. These findings suggest that ACS should be managed medically with delay of surgery or stenting until the occurrence of symptoms or emboli.

Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (p<0.05) of collagen type I distal to the bifurcation compared to proximal tissue in the carotid specimens. Conclusion: Fluorescence spectroscopy is an effective method for evaluating ECM (collagen and elastin) associated with vascular remodeling despite the considerable variability in the plaque structure. Consistent regional differences were detected in the carotid specimens.

We have demonstrated that in vitro fluorescence spectroscopic analysis of diseased carotid arteries can identify clinically relevant compositional changes in connective tissue (collagen type I, III, IV and elastin) associated with plaque remodeling and instability.

BACKGROUND:Dural cavernous angiomas are uncommon benign vascular malformations which may present intraoperative difficulties in hemostasis when the diagnosis is not suspected preoperatively. Preoperative diagnosis can be difficult when angiomas show atypical features and share imaging characteristics with other entities.METHODS:A patient presented with a radiographically aggressive lesion, subsequently identified as a dural cavernous angioma. The lesion is reviewed and its clinical, radiographic, and pathological features are compared with other vascular malformations.CASE REPORT:A 40-year-old man presented with new onset seizures and an enhancing lesion infiltrating the floor of the right middle cranial fossa. Due to its aggressive radiographic appearance, initial considerations included chondrosarcoma, meningioma or metastasis. Pathological examination, however, revealed the lesion to be a cavernous angioma of dura.CONCLUSION:This uncommon lesion may present a diagnostic challenge with significant intraoperative implications. T2 sequence hyperintensity in a relevant lesion should raise suspicion of an hemangioma. It is important to be aware of this entity and its potential to mimic other entities on radiographic grounds.

The aim of this prospective study was to assess the feasibility and diagnostic relevance of repetitive dynamic (contrast-enhanced) CT measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in the first 3 weeks after aneurysmal subarachnoid hemorrhage (SAH). In 15 patients with SAH, 59 dynamic CT studies including 944 regions of interest (ROI) were analyzed. The results were correlated with the clinical course and time after the event and the occurrence of vasospasm. Values for the entire series were 33.8 ± 19.3 ml/100 g/min (CBF), 3.3 ± 1.3 ml/100 g (CBV), and 7.3 ± 3.9 s (MTT). Significant differences in CBF and CBV were found between ROI in grey and white matter, with time after the event, between patients with significant and absent or minor vasospasm, and between patients with and without a presumed vasospasm-related infarct.

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Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada

carotid stenosis, but benefits are lessened by perioperative surgical risk. Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke. We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy.Methods In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months. We recorded occurrences of stroke, myocardial infarction, and death. We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses.Findings Surgery was cancelled in 45 patients, none were lost to follow-up by 30 days, and two were lost by 3 months. The combined rate of stroke, myocardial infarction, and death was lower in the low-dose groups than in the high-dose groups at 30 days (5.4 vs 7.0%, p=0.07) and at 3 months (6.2 vs 8.4%, p=0.03). In an efficacy analysis, which excluded patients taking 650 mg or more acetylsalicylic acid before randomisation, and patients randomised within 1 day of surgery, combined rates were 3.7% and 8.2%, respectively, at 30 days (p=0.002) and 4.2% and 10.0% at 3 months (p=0.0002).Interpretation The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients laking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg.

BACKGROUND Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

The purpose of this study was to examine how the prognosis of patients who presented with a recent ischemic event referable to a 70% to 99% stenosis of one carotid artery (ipsilateral) was altered by stenosis and occlusion of the contralateral carotid artery. The benefit of performing carotid endarterectomy on the recently symptomatic artery, in the presence of contralateral artery disease, was also examined.A total of 659 patients were grouped into one of three categories according to the extent of stenosis in the contralateral carotid artery: less than 70% (559 patients), 70% to 99% (57 patients), and occlusion (43 patients). Strokes that occurred during the follow-up period were designated as ipsilateral if they arose from the same carotid artery as the symptom for which the patient had been entered into the study. Medically treated patients with an occluded contralateral artery were more than twice as likely to have had an ipsilateral stroke at 2 years than patients with either severe (hazard ratio: 2.36; 95% confidence interval (CI): 1.00-5.62) or mild-to-moderate (hazard ratio: 2.65; 95% CI: 1.43-4.90) contralateral artery stenosis. The perioperative risk of stroke and death was higher in patients with an occluded contralateral artery (4.0% risk) or mild-to-moderate (5.1% risk) contralateral stenosis. Regression analyses indicated that the results were not affected by other risk factors.An occluded contralateral carotid artery significantly increased the risk of stroke associated with a severely stenosed ipsilateral carotid artery. Despite higher perioperative morbidity in the presence of an occluded contralateral artery, the longer-term outlook for patients who had endarterectomy performed on the recently symptomatic, severely stenosed ipsilateral carotid artery was considerably better than for medically treated patients.

OBJECTIVE To determine whether carotid endarterectomy prevents deterioration of functional status among patients with transient ischemic attacks or nondisabling strokes and ipsilateral carotid stenosis of 70% to 99%. DESIGN Multicentered randomized controlled trial with an average 18-month follow-up. SETTING Fifty clinical centers in North America. PATIENTS A total of 659 patients presenting with recent transient attacks of nondisabling stroke and ipsilateral atherosclerotic carotid stenosis of 70% to 99% were included. Patients were stable neurologically at the time of entry. No patient was lost to follow-up. INTERVENTION Vascular surgeons and neurosurgeons were prescreened for low perioperative complication rates. Patients were randomly allocated to carotid endarterectomy plus continuing medical care (n = 328) or medical care alone (n = 331), including antiplatelet therapy. MAIN OUTCOME MEASURES All patients were assessed by neurologists for the occurrence of stroke and functional status at scheduled intervals after entry. RESULTS In addition to a previously reported risk reduction for ipsilateral stroke for patients assigned to carotid endarterectomy, there was an absolute risk reduction (and relative risk reduction [RRR]) for functional status impairment of 5.6% (RRR, 69%) for vision, 4.6% (RRR, 87%) for comprehension of language, 8.3% (RRR, 88%) for fluency of speech, 4.3% (RRR, 84%) for swallowing, 6.0% (RRR, 53%) for lower-limb function, 9.3% (RRR, 75%) for upper-limb function, 7.4% (RRR, 60%) for shopping, and 10.5% (RRR, 50%) for visiting outside usual residence (P < .05, two-tailed, for all items). CONCLUSIONS Carotid endarterectomy reduced the risk for impairment of function among patients with recent symptomatic cerebral ischemia and ipsilateral high-grade carotid stenosis.

Hunterian proximal artery occlusion was used in the treatment of 160 of 335 patients harboring giant aneurysms of the anterior circulation. One hundred and thirty-three of these aneurysms arose from the internal carotid arteries, 20 from the middle cerebral arteries, and seven from the anterior cerebral arteries. Ninety percent of the patients had satisfactory outcomes. The safety of internal carotid artery occlusion has been greatly enhanced by preoperative flow studies and by test occlusion with an intracarotid balloon to identify those patients who require preliminary extracranial-to-intracranial bypass, which was used in all of the middle cerebral occlusions. The anterior cerebral artery had magnificent leptomeningeal collateral flow that prevented infarction even without cross flow. Obliteration of the aneurysm by thrombosis was complete, or nearly so, in all but four patients whose treatment was completed. Analysis of poor outcome in 16 patients revealed that hemodynamic ischemic infarction was known to occur after only two of the carotid occlusions.