Leptomeningeal Anastomoses Research Articles

Granulocyte Colony-Stimulating Factor Enhances Arteriogenesis and Ameliorates Cerebral Damage in a Mouse Model of Ischemic Stroke

Enhancing collateral artery growth is a potent therapeutic approach to treat cardiovascular ischemic disease from occlusive artery. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has gained attention for its ability to promote arteriogenesis, ameliorating brain damage, by the mechanisms involving monocyte upregulation. However, the recent clinical study testing its efficacy in myocardial ischemia has raised the question about its safety. We tested alternative colony-stimulating factors for their effects on collateral artery growth and brain protection. Brain hypoperfusion was produced by occluding the left common carotid artery in C57/BL6 mice. After the surgery, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, or GM-CSF (100 μg/kg/day) was administered daily for 5 days. The angioarchitecture for leptomeningeal anastomoses and the circle of Willis were visualized after the colony-stimulating factor treatment. Circulating blood monocytes and Mac-2-positive cells in the dorsal surface of the brain were determined. A set of animals underwent subsequent ipsilateral middle cerebral artery occlusion and infarct volume was assessed. Granulocyte colony-stimulating factor as well as GM-CSF promoted leptomeningeal collateral growth after common carotid artery occlusion. Both granulocyte colony-stimulating factor and GM-CSF increased circulating blood monocytes and Mac-2-positive cells in the dorsal brain surface, suggesting the mechanisms coupled to monocyte upregulation might be shared. Infarct volume after middle cerebral artery occlusion was reduced by granulocyte colony-stimulating factor, similarly to GM-CSF. Macrophage colony-stimulating factor showed none of theses effects. Granulocyte colony-stimulating factor enhances collateral artery growth and reduces infarct volume in a mouse model of brain ischemia, similarly to GM-CSF.

Cortex-sparing infarctions in patients with occlusion of the middle cerebral artery

BackgroundIn patients with a middle cerebral artery (MCA) occlusion, the involvement of the cortex may be affected by the presence of leptomeningeal anastomoses between the cerebral arteries.MethodsThe authors enrolled consecutive...

Moyamoya Disease Presenting with an Acute Confusional State in an Elderly Patient

Moyamoya disease is the angiographic diagnosis of a clinical syndrome showing bilateral stenosis or occlusion of the distal internal carotid arteries and their major branches with extensive parenchymal, leptomeningeal, or transdural anastomoses. The clinical features normally present as reversible ischemic neurologic deficits, sensory-motor attacks with acute hemiplegia, and motor convulsion. An acute confusional state (ACS) among hospitalized patients is a frequent and serious problem. It is characterized by an acute neurologic deficit with a fluctuating course of impaired attention span, unorganized thinking, and altered levels of consciousness. We report a case of 66-year-old woman who presented with an ACS in the emergency department. The subsequent workups including a neuroradiological examination revealed a rare case of moyamoya disease with bifrontal ischemic infarction. The recognition of an ACS as a manifestation of moyamoya disease should therefore be included in the differential diagnosis of elderly patients who present with an acutely altered neuropsychiatric state. A prompt diagnosis may help to select the most appropriate therapy for this rare disorder especially in elderly patients.

TRACING COLLATERAL CIRCULATION AFTER ISCHEMIA IN RAT CORTEX BY LASER SPECKLE IMAGING

The collateral circulation is crucial for the pathophysiology and outcome of acute cortical ischemia. Current understanding of collateral circulation still remains sparse, largely due to prior limitations of spatial or/and temporal resolution in methods to evaluate these diminutive redistributive routes of cerebral blood flow (CBF) especially in leptomeningeal anastomoses that connected cortical arteries. In the study, based on a mini-stroke model, laser speckle imaging with high spatiotemporal resolution was used to assess the dynamic evolution of the collateral circulation around a mini-ischemia in the rat cortex. We found that the blood flow and diameter in the intra-arterial anastomoses were enhanced immediately after the ligation of one branch of middle cerebral artery and recovered to baseline level as arterial recirculation was performed. Whereas the communicative flow-through of the posterior cerebral artery and the middle cerebral artery anastomoses was not significant enough to be determined. This is the evidence that intra-arterial anastomoses were the primary routes to restore blood flow into the ischemic territory during the acute phase of ischemia, and laser speckle imaging method was proven as a powerful tool to be potential for subserving further investigation of the collateral circulation.

Collateral Circulation Imaging: MR Perfusion Territory Arterial Spin-Labeling at 3T

Current knowledge of the collateral circulation remains sparse, and a noninvasive method to better characterize the role of collaterals is desirable. The aim of our study was to investigate the presence and distal flow of collaterals by using a new MR perfusion territory imaging, vessel-encoded arterial spin-labeling (VE-ASL). Fifty-six patients with internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis were identified by sonography. VE-ASL was performed to assess the presence and function of collateral flow. The perfusion information was combined with VE maps into high signal-intensity-to-noise-ratio 3-colored maps of the left carotid, right carotid, and posterior circulation territories. The presence of the anterior and posterior collateral flow was demonstrated by the color of the standard anterior cerebral artery/MCA flow territory. The distal function of collateral flow was categorized as adequate (cerebral blood flow [CBF] >/=10 mL/min/100 g) or deficient (CBF <10 mL/min/100 g). The results were compared with those of MR angiography (MRA) and intra-arterial digital subtraction angiography (DSA) in cross table, and kappa coefficients were calculated to determine the agreement among different methods. The kappa coefficients of the presence of anterior and posterior collaterals by using VE-ASL and MRA were 0.785 and 0.700, respectively. The kappa coefficient of the function of collaterals by using VE-ASL and DSA was 0.726. Apart from collaterals through the circle of Willis, VE-ASL showed collateral flow via leptomeningeal anastomoses. In patients with ICA or MCA stenosis, VE-ASL could show the presence, the origin, and distal function of collateral flow noninvasively.

Increased vessel diameter of leptomeningeal anastomoses after hypoxic preconditioning

Recently, cerebral blood flow changes were re-discussed to contribute to tissue protection after preconditioning. In the present study, we demonstrate increased vessel diameters of the leptomeningeal anastomoses after hypoxic preconditioning by visualization of the brain angioarchitecture using the latex perfusion technique. This finding may display the anatomical correlate to previously described perfusion changes after preconditioning.

Cortical Perfusion Measurement by Indocyanine-Green Videoangiography in Patients Undergoing Hemicraniectomy for Malignant Stroke

Assessment of cerebral perfusion during neurosurgical procedures would be beneficial to identify areas at risk and to guide placement of monitoring probes. Therefore, we have adapted near-infrared indocyanine-green (ICG) videoangiography to assess cortical perfusion intraoperatively. ICG videoangiography was performed intraoperatively in 6 patients after decompressive hemicraniectomy for middle cerebral artery stroke. Flow maps of cortical perfusion were generated with IC-CALC 1.1 software by calculating the ratio of difference in fluorescence intensity and rise time. Excellent visualization of cerebral arteries, cortical perfusion and collateral circulation via leptomeningeal anastomoses could be demonstrated in all cases. Flow maps revealed high spatial resolution and showed heterogeneous maple-leaf-shaped hypoperfusion. 26.5+/-13.7% and 29.0+/-9.1% of the exposed cortical surface (141+/-18 cm2) demonstrated core and penumbral flow, respectively. ICG videoangiography appears to be a valuable tool to precisely detect relative cortical tissue perfusion. Thus, it may provide useful research data on the pathophysiology of human stroke, help surgeons to maintain adequate brain perfusion intraoperatively, and simplify adequate placement of tissue probes to monitor critically hypoperfused brain tissue.

Relevance of Occlusion Test in Endovascular Coiling of Posterior Cerebral Artery (P2 Segment) Aneurysms

P2 segment aneurysms are located on the posterior cerebral artery (PCA) between the junction of the posterior communicating artery with the PCA and the quadrigeminal cisternal part of the PCA. We reviewed our experience with endovascular coiling in such aneurysms. Clinical and pre-procedural data from four patients, referred for endovascular treatment of P2 segment aneurysms, were retrospectively studied for factors influencing post-interventional neurological deficits caused by ischemia of the PCA distal territory. Balloon occlusion was done in three patients and patient tolerance was assessed using clinical and anatomic criteria. Embryologic and anatomic features of the PCA were reviewed. Balloon occlusion test and endovascular coiling of aneurysms was possible in three patients. Control angiogram after embolization showed elimination of aneurysms from the circulation and the distal PCA filled through leptomeningeal anastomoses. One patient deteriorated due to aneurysmal rupture soon after the balloon occlusion test and coiling could not be done. In the other three patients post-intervention CT and MRI images showed PCA territory infarcts in spite of demonstration of good collateral circulation distal to the occluded PCA. In conclusion, P2 aneurysms can be effectively treated by endovascular coiling without a balloon occlusion test. While the balloon occlusion test does not contribute to clinical decision-making it may be associated with potential morbidity and mortality.

Significance of establishing collateral circulation by leptomeningeal anastomoses in the occlusion of arteriae cerebri mediae

We have investigated establishment of collateral circulation in patients with cerebral circulation disorder. Thirty angiograms of patients treated at Neurological Department of Hospital Centre in Sarajevo suffering from arteriae cerebri mediae occlusion were used for this study. Cerebral anastomoses that included connections between arteriae cerebri anterior and arteriae cerebri mediae over leptomeningeal anastomoses occurred in some patients suffering from occlusion of this arteriae. It was concluded that the majority of anastomoses existed between big leptomeningeal branches of postcommunicant segment of a. cerebri anterior and branches of cerebri mediae. These collaterals are of great significance as their functional ability is sometimes of a high degree in cases of occlusion of one or the other artery. It can be concluded that anastomosing of the blood vessels increases their volume in the whole and therefore more blood can be provided, although physiological factors should not be neglected, as functional effectiveness of collateral circulation in postocclusive states depends also on the state of the whole cerebrovascular system, then on the speed of creation of occlusion (thrombosis or embolism), systemic arterial pressure, volume and viscosity of the blood.

Recurrent stroke in patients with symptomatic carotid artery occlusion is associated with high-volume flow to the brain and increased collateral circulation.

To investigate whether the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic carotid artery occlusion (CAO) is related to (1) volume flow in the contralateral internal carotid artery (ICA), basilar artery (BA), and middle cerebral arteries (MCAs), and (2) intracranial collateral flow to the symptomatic side, measured in the first 6 months after the qualifying symptoms occurred. We prospectively studied 112 patients with symptomatic CAO. Quantitative volume flow was measured with magnetic resonance angiography (MRA) and collateral flow via the circle of Willis with MRA, via the ophthalmic artery (OA) with transcranial Doppler sonography, and via leptomeningeal anastomoses with conventional angiography. During 49+/-14 months of follow-up (mean+/-SD), 7 patients had recurrent ipsilateral ischemic stroke. Compared with patients without recurrent stroke, these patients had significantly higher total flow to the brain, ie, ICA+BA flow (mean 536 mL/min versus 410 mL/min; P<0.05), and significantly higher contralateral ICA flow (355 mL/min versus 209 mL/min; P<0.001), whereas BA and MCA flow showed no significant differences. Also, they more often had Willisian collateral flow (P<0.05), mainly caused by increased collateral flow via the posterior communicating artery (PCoA; 71% versus 28%; P<0.05), whereas collateral flow via the OA and leptomeningeal anastomoses did not differ significantly. Recurrent ipsilateral ischemic stroke in patients with symptomatic CAO is associated with high volume flow to the brain and increased collateral PCoA flow.

Anatomy and functionality of leptomeningeal anastomoses: a review.

This review seeks to provide a structured presentation of existing knowledge of leptomeningeal anastomoses from anatomic and functional points of view and to identify problems and possible research directions to foster a better understanding of the subject and of stroke mechanisms. Available data show that leptomeningeal anastomoses may be important in understanding stroke mechanisms and that leptomeningeal anastomoses play an important role in penumbra outcome. However, the literature shows no consensus between statements on the existence of leptomeningeal anastomoses and compensatory capacity. By analyzing the available literature and identifying the factors that contribute to this confusion, we found that variability and the functional consequences thereof are important but that quantitative data are lacking. Moreover, vascular remodeling is an issue to consider.

Collateral hemodynamics after middle cerebral artery occlusion in Wistar and Fischer-344 rats

We investigated whether the difference in infarction volume after occlusion of a long proximal segment of the middle cerebral artery between Wistar and Fischer-344 rats, is caused by differences in collateral blood flow rate through leptomeningeal anastomoses. In view of the retrograde direction of collateral blood flow into the middle cerebral artery territory, we developed parasagittal laser-Doppler flowmetry. Using this method two laser-Doppler probes are placed on the cerebral cortex: probe 1 is placed near the anastomoses between the middle- and anterior cerebral artery, probe 2 is placed 2 mm further away from these anastomoses than probe 1. We found in both rat strains a comparable relation between the areas under the curve of the signal measured by both laser-Doppler probes for 2 h after middle cerebral artery occlusion. This relation is considered to be a measurement of the collateral blood flow rate into the middle cerebral artery territory through leptomeningeal anastomoses after middle cerebral artery occlusion. We conclude that collateral blood flow for the two strains were essentially similar for the initial 2 h after MCA occlusion. Although these collateral blood flows could have been different at a later time, it is unlikely that the interstrain difference in cerebral infarction volume between Wistar and Fischer-344 rats after proximal middle cerebral artery occlusion is caused by an apparent interstrain difference in the magnitude of collateral blood flow rate through leptomeningeal anastomoses. The parasagittal laser-Doppler flowmetry technique we developed for these experiments is currently successfully used in our laboratory to evaluate the efficacy of hemodynamically active pharmacotherapeutical agents in raising the collateral blood flow rate into the middle cerebral artery territory after middle cerebral artery occlusion.

Rat middle cerebral artery occlusion by an intraluminal thread compromises collateral blood flow

We compared in Wistar rats collateral blood flow through leptomeningeal anastomoses after middle cerebral artery occlusion using craniotomy (`extravasal occlusion'), which results in a small volume of cerebral infarction, and after intraluminal thread occlusion (`intravasal occlusion'), which produces a large volume of cerebral infarction. Simultaneous laser–Doppler flowmetry with two probes placed on the cerebral cortex was used to measure and compare collateral blood flow. Extravasal occlusion caused a cortical blood flow reduction along a gradient in lateral direction, whereas blood flow reduction after intravasal occlusion was more uniformly distributed. It is concluded that permanent intravasal occlusion compromises collateral blood flow and therefore may not be a suitable model for measuring the ability of pharmacotherapeutic agents, if any, to improve collateral blood flow acutely after middle cerebral artery occlusion. The two models can be useful for testing drugs on parenchymal neuroprotective properties. Thereby, the intraluminal technique is preferred because of the possibility to study reperfusion damage when transient occlusion is applied.

Predictability of extracranial/intracranial bypass function: a retrospective study of patients with occlusive cerebrovascular disease.

When the efficacy of extracranial/intracranial bypass surgery is discussed, can we include the patients with extensive collateral circulation through the bypass and those with poor collateral circulation in the same group? The bypass function should be determined not by the patency of the bypass but by the extent of collateral circulation through the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow can be predicted from the results of preoperative studies. In 51 hemispheres of 44 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the preoperative results of angiographic and stimulated cerebral blood flow studies were investigated. The bypass function is highly predictable with the aid of preoperative studies. In 11 hemispheres that showed both retrograde spontaneous circulation via leptomeningeal anastomoses and decreased reactivity to acetazolamide of cerebral blood flow in an area distal to the arterial lesion, collateral circulation through the bypass developed well and reactivity to acetazolamide improved. In all of 13 hemispheres that showed normal reactivity to acetazolamide, the bypass was patent but the collateral circulation did not develop well. In only 4 of 24 hemispheres with spontaneous antegrade circulation distal to the lesion was there satisfactory collateral circulation through the bypass. Our results indicate that improvement of the hemodynamic status by bypass surgery should be expected only in patients with both spontaneously developed leptomeningeal anastomoses and decreased reactivity to acetazolamide.

Vasomotor reactivity and pattern of collateral blood flow in severe occlusive carotid artery disease.

The compromise of cerebrovascular autoregulation in severe occlusive carotid artery disease depends on the functional capacity of collateral pathways. In previous reports correlating hemodynamic disturbances with collateral pathways, collateral blood supply was often evaluated by invasive cerebral angiography. In this study noninvasive transcranial Doppler ultrasound was used to determine both collateral pathways and vasomotor reactivity. With the use of blood flow direction, compression tests, and evident side-to-side asymmetries of blood velocities, the collateral supply through the anterior and posterior communicating arteries, the ophthalmic artery, and leptomeningeal anastomoses was evaluated by transcranial Doppler ultrasound in 48 patients (42 men, 6 women; mean +/- SD age, 59 +/- 9 years) with occlusion (n = 36) or stenosis of more than 90% (n = 12) of one internal carotid artery. Ipsilateral vasomotor reactivity was determined by the percent increase of middle cerebral artery mean blood velocity with the use of (1) the breath-holding maneuver and (2) acetazolamide (1 g IV) as vasodilatory stimulus. Additional stenoses (50% to < 90%) of the contralateral internal carotid artery were present in 20 of the 48 patients. Vasomotor reactivity was not affected by the presence of a contralateral internal carotid artery stenosis. Both vasodilatory stimuli similarly indicated poor vasomotor reactivity when an ophthalmic or a leptomeningeal pathway accompanied an anterior communicating artery pathway compared with a lone anterior communicating artery pathway (P < .05). The acetazolamide challenge indicated significantly better preserved vasomotor reactivity when blood supply was provided through a lone anterior communicating artery pathway (66 +/- 30%) than through an anterior and posterior communicating artery pathway (33 +/- 20%, P < .05), whereas the breathholding method failed to show such a difference. The presence of an ophthalmic artery pathway may provide the first evidence of disturbed vasomotor reactivity. The use of cerebral angiography to evaluate collateral pathways must be considered carefully since transcranial Doppler ultrasound is a reliable noninvasive alternative.

Percutaneous transluminal angioplasty for severe stenosis of the posterior cerebral artery: Case report

The Stealth dilation catheter was used for the intravascular treatment of a patient who had hemodynamically significant stenosis of the posterior cerebral artery and had a history of recurrent transient ischemic attacks associated with right hemiparesis and ipsilateral hemianopia dating from March 1993. Cerebral perfusion studies prior to and after the intravenous administration of acetazolamide demonstrated regions of moderately low perfusion and low hemodynamic reserve in the territories of the left middle and posterior cerebral arteries. Cerebral angiograms demonstrated severe stenosis of the left posterior cerebral artery and occlusions of both middle cerebral arteries, which had leptomeningeal anastomoses with the posterior cerebral arteries. Percutaneous transluminal angioplasty (PTA) was performed using the Stealth catheter on the stenotic segment of the left posterior cerebral artery after left superficial temporal artery-middle cerebral artery anastomosis. The patient manifested marked improvement in her neurologic condition just after PTA, in association with marked increase in cerebral perfusion and hemodynamic reserve in the territories of the left middle and posterior cerebral arteries. We have presented evidence that PTA can be used to treat patients with stenosis of the first segment of the posterior cerebral artery and hemodynamic compromise in the territory that artery supplies.

中大脳動脈M1部塞栓症に対する局所線溶療法施行後のレンズ核線条体動脈領域病巣の検討

Middle cerebral artery (MCA) occlusion can be treated successfully with local intraarterial infusion of tissue-type plasminogen activator (t-PA). If the M1 segment of MCA is occluded, the ischemia of lenticulostriate territory occurs. The lenticulostriate arteries are end-arteries, whereas the cortical branches of MCA have leptomeningeal anastomoses. The pathophysiological effect on the lentriculostriate arterial territory after quick reperfusion of the M1 by fibrinolytic therapy is, however, not yet well understood. We investigated changes in neuroradiological findings for the lenticulostriate arterial territory following fibrinolytic therapy for embolic M1 occlusion.The clinical and neuroradiological findings in nine patients treated with intra-arterial infusion of t-PA were reviewed. All patients had had computerized tomographic (CT) scans before and after fibrinolysis. Six (66.7%) had areas of increased attenuation on immediate postperfusion CT scans in the lenticulostriate arterial territory. Three patterns were categorized according to the changes in neuroradiological findings in the lenticulostriate arterial territory following sequential CT scans. In three cases (Group 1), the high density lesions as seen in the immediate postperfusion CT scans disappeared within 24 hours; they subsequently became low density areas. In three cases (Group 2), the high density lesions as seen in the immediate postperfusion CT scans persisted for several days. Only one of them was symptomatic. Three cases (Group 3) had normal findings on immediate postperfusion CT scans; all showed low density areas on the next day. All patients were observed to show hemorrhagic transformation within seven days.In Group 1, the rapid clearance of the high attenuation represented contrast that had entered into the disrupted blood-brain barrier (BBB). In Group 2, hemorrhagic extravasation had occurred in the lenticulostriate arterial territory since the vessel walls were damaged so badly that they no longer could resist the pressure of reperfusion. In Group 3, recirculation caused oligemia due to the no-reflow phenomenon.

The case of aphasia or neglect after striatocapsular infarction

The occurrence of aphasia or neglect was related to anatomo-structural (CT/MRI), functional [regional cerebral blood flow (rCBF)] and pathogenetic features [duration of middle cerebral artery (MCA) occlusion and degree of cortical leptomeningeal anastomoses] in 57 cases (26 with and 31 without aphasia or neglect) with strictly subcortical infarcts of one defined type, i.e. striatocapsular infarcts. No distinct pattern of language disturbances was found. Aphasic syndromes did not differ in the amount of involvement of the putamen, pallidum, head of caudate nucleus and white matter. Patients with aphasia or neglect had larger infarcts than those without. However, there was no specific involvement of the basal ganglia, the internal capsule or the deep white matter in patients with aphasia or neglect. Patients with aphasia or neglect had a significantly longer duration of MCA occlusion and mostly poor leptomeningeal collaterals. The cortical rCBF was significantly decreased in the cortical MCA territory in the patients with aphasia or neglect only. The rCBF remained low at follow-up after 1 year and corresponded to focal cortical atrophy on MRI, although neglect had subsided completely in all patients and aphasia had improved considerably in almost 75% of the cases. Aphasia or neglect after striatocapsular infarcts are most likely due to selective neuronal loss of the cerebral cortex due to prolonged MCA occlusion and insufficient collateral blood flow. Individual differences in recovery from aphasia after striatocapsular infarction can be explained in terms of the number of surviving cortical neurons.

Transcranial Doppler Sonography: Collateral Pathways in Internal Carotid Artery Obstructions

Fifty-four patients with stenoses and occlusions of the extracranial internal carotid artery (ICA) demonstrated by intravenous digital subtraction angiography (IVDSA) were studied by extracranial duplex and transcranial Doppler. Two hundred healthy volunteers served as control group. Intracranial collateralization was demonstrated in 32 patients with ICA stenoses greater than 80% and occlusions. Twelve patients with unilateral and 8 patients with bilateral ICA obstructions greater than 80% showed collateral supply via the anterior (ACA) and/or posterior cerebral artery (PCA). In 5 cases of unilateral ICA occlusion and in 7 patients with bilateral ICA stenoses greater than 80% and occlusions, the ophthalmic artery and ACA and/or PCA served as collateral vessels. Five patients with ICA occlusions showed leptomeningeal anastomoses in the region of the postocclusive middle cerebral artery (MCA). All 54 patients showed normal time-mean flow velocity in the post-obstructive MCA. In unilateral ICA stenoses greater than 80% and occlusions, the pulsatility index in the ipsilateral MCA was reduced in comparison with the contralateral side, indicating that this parameter is more sensitive to hemodynamic effects of ICA obstructions than time-mean velocity.

Transkranielle Doppler-Sonographie bei zerebrovaskulären Erkrankungen

A review of our 1 1/2 years' experience with transcranial Doppler sonography (TCD) is given. In total, 619 TCD examinations were performed. Considering physiological variations of blood flow velocities in the intracranial arteries, TCD findings in stenoses and occlusions of the extracranial and intracranial brain-supplying arteries as well as in intracranial vasospasms were evaluated. In patients with leptomeningeal anastomoses demonstrated by TCD in the region of the peripheral middle cerebral artery, the regional cerebral blood flow was measured by 99mTc-HMPAO-SPECT. The value and limitations of TCD in cerebrovascular diseases and the indications to TCD examination of the intracranial arteries are discussed.