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Biomedical subjects

R Schmid-Elsaesser

Publications and source records attributed to R Schmid-Elsaesser.

At least 19 recordsLinked to original sources
PubMed2007

Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with 99mTc-ECD SPECT.

INTRODUCTION: Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information. METHODS: Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer ((99m)Tc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI. RESULTS: The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (-46.52%), negative rCBV increment (-13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student's t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection. CONCLUSIONS: Perfusion MRI before and after acetazolamide administration compares favourably with (99m)Tc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study.

Acetazolamide↗
PubMed2005

Neuroprotective effects of a postischemic treatment with a bradykinin B2 receptor antagonist in a rat model of temporary focal cerebral ischemia.

Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B2 receptors. In a rat model of focal cerebral ischemia, blockade of B2 receptors before initiation of ischemia with the B2 receptor antagonist, LF 16-0687 Ms, afforded substantial neuroprotection. In order to assess the potential clinical value of this approach, we evaluated the effect of LF 16-0687 Ms given at reperfusion following focal cerebral ischemia on local cerebral blood flow (LCBF), neurological outcome, and infarct size. Sprague-Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal filament. Animals were assigned to one of four treatment arms (n = 7 each): (1) vehicle, (2) LF 16-0687 Ms (1.0 mg/kg/day), (3) LF 16-0687 Ms (3.0 mg/kg/day), or (4) LF 16-0687 Ms (10.0 mg/kg/day) given at reperfusion and repetitively over 2 days. Neurological recovery was examined daily, and infarct volume was assessed histologically on day 7 after ischemia. Physiological parameters and local CBF were not influenced by the treatment. Significant improvement of neurological outcome was observed on postischemic day 3 in animals receiving 1.0 and 3.0 mg/kg/day of LF 16-0687 Ms (P < 0.05). Inhibition of B2 receptors significantly reduced infarct volume in all treated animals predominantly in the cortex. B2 receptor blockade with LF 16-0687 Ms showed neuroprotective effectiveness even when therapy was initiated upon reperfusion, i.e. 90 min after induction of ischemia. Therefore, blockade of B2 receptors seems to be a promising therapeutic approach after focal cerebral ischemia, which deserves further experimental and clinical evaluation.

Analysis of Variance↗
PubMed2005

Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats.

BACKGROUND: During many neurovascular procedures temporary occlusion of cerebral arteries is inevitable. Neuroprotective drugs may reduce the risk of cerebral infarction in this situation. Increasing evidence indicates neuroprotective properties of magnesium in cerebral ischemia. Previous experimental studies on the neuroprotective efficacy of magnesium-treatment in transient focal ischemia provide widely differing results using different magnesium doses and treatment-regimens. The present study was conducted to find the maximum protective dose of intravenous magnesium sulphate in a rat model of transient focal ischemia. METHODS: 45 male Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion (MCAO) by an intraluminal thread. Animals were randomly assigned to one of 4 treatment arms: (1) vehicle (2) MgSO(4) 1x0.75 mmol/kg (3) MgSO(4) 2x1 mmol/kg (4) MgSO(4) 1 mmol/kg+0.5 mmol/kg/h. Local cortical blood flow (LCBF) was continuously measured by laser-Doppler flowmetry. Functional deficits were quantified daily, infarct volumes were assessed histologically after 7 days. RESULTS: Magnesium serum levels below 3 mmol/l were well tolerated by the animals. Above 3 mmol/l cardiodepressive effects limited neuroprotection. Total infarct volumes in groups 3 and 4 were significantly reduced by 32% and 42%, respectively, compared to controls. Postoperative neurological recovery was significantly improved in magnesium-treated groups. CONCLUSION: Continuous magnesium-administration with stable serum concentrations between 2 and 3 mmol/l offered the best protection and was well tolerated. Serum concentrations above 3 mmol/l should not be exceeded. An elevation of magnesium serum levels could be useful for brain tissue protection during procedures which are prone to the risk of temporary vessel occlusion.

Animals↗
PubMed2005

Cranial and spinal dural arteriovenous malformations and fistulas: an update.

Awareness of a potential arteriovenous fistula is critical for diagnosis of cranial as well as spinal fistulas. The natural history of cranial and spinal dural arteriovenous fistulas has been clarified during the last decade and interdisciplinary therapies have experienced a substantial development recently. The classification of Cognard & Merland is now the most widely accepted one for cranial dural AVF. It is based on the degree of flow reversal in the sinuses and cortical veins and reflects well the natural history of the different lesions and serves as basis for therapeutic indications. Several studies have defined the annual bleeding risk of cranial dural fistulas between 1.8 and 15%, depending on the pattern of venous drainage and initial symptomatology. Surgical, endovascular and radiosurgical methods must be selectively chosen for the treatment. The risk associated with surgical or endovascular treatment of benign fistulas is higher than the risk of eliminating fistulas that have already led to cortical venous reflux. Transvenous endovascular occlusion or surgical disconnection of draining veins is the treatment of first choice for cranial and spinal dAVF with venous flow reversal. Benign cranial dural arteriovenous fistulas are a developing indication for radiosurgery.

Arteriovenous Fistula↗
PubMed2004

Congested residual nidus after preoperative intranidal embolization in midsize cerebral arteriovenous malformations of 3-6 cm in diameter.

BACKGROUND: Modern delicate microcatheters allow intranidal embolization of cerebral arteriovenous malformations (AVM). The aim of the current analysis was to assess effects of preoperative intranidal deployment of embolic material on surgical time and blood loss in cerebral arteriovenous malformations of 3-6 cm in diameter. METHODS: The case records of 38 cerebral AVM between 3 and 6 cm in maximum diameter were reviewed, that had been embolized intranidally with N-butyl 2-cyanoacrylate (Histacryl) and subsequently operated on. Surgical time and blood loss as well as particular intraoperative findings such as a congested nidus and thrombosis of draining veins were registered and correlated with the extent of embolization and the time interval between embolization and surgery. FINDINGS: Preoperative embolization occluded an estimated range of 10 to 90% of the nidus. Minor embolization related bleeding without clinical relevance occurred in 5 patients. Significant embolization related bleeding resulting in earlier than planned surgery occurred in another 5 patients. All embolization related haemorrhages occurred within 24 hours. Average total operating time was 343+/-106 min and average blood loss was 684+/-858 ml. Unequivocal bleeding difficulty from the nidus and a total blood loss of more than 1000 ml were encountered in 7 instances and dissection was tedious due to a bleeding AVM core in 5 other cases. A congested AVM core was the source of bleeding in 11 patients and paraventricular neovascularization in one. 6 of the 11 cases with a congested AVM core had suffered minor or substantial haemorrhage after a preoperative endovascular procedure. Intraoperative nidus congestion was noted in this series after an interval as long as 2 weeks after the last embolization. Combined management resulted in permanent morbidity in 6 of the 38 cases. In 4 of them the neurological deficit was associated with an intraoperative bleeding problem, in all due to congested nidus. Morbidity had to be correlated with major haemorrhage resulting from preoperative embolization in 2 instances. CONCLUSIONS: Intranidal embolization prior to surgical removal of AVM can lead to a congested residual nidus and intraoperative bleeding. Minor leakage after preoperative embolization is an inconsistent warning sign of nidus congestion. Nidus outflow after intranidal embolization appears to require a few weeks for normalization. Delay of surgery after embolization should be considered in cases of suspected congested residual nidus. The danger of major haemorrhage or arterial revascularization during this waiting period appears small.

Blood Loss, Surgical↗
PubMed2003

Ruptured intracranial dissecting aneurysms: management considerations with a focus on surgical and endovascular techniques to preserve arterial continuity.

BACKGROUND: The present retrospective analysis was undertaken to review an institutional experience with 13 intracranial dissecting aneurysms as source of subarachnoid haemorrhage (SAH) among a total of 585 ruptured intracranial aneurysms. METHODS AND RESULTS: In 6 patients the vertebral artery (VA) was affected, in 2 patients the basilar artery (BA), in 3 the internal carotid (ICA), in 1 the middle cerebral (MCA) and in 1 the postcommunicating (A2) segment of the anterior cerebral artery (ACA). Maintaining arterial patency was aimed at in all patients. Tangential clipping or circumferential wrapping were used as surgical methods. Endovascular stenting and/or coiling was applied in 2 instances. Four of the 6 VA dissecting aneurysms underwent surgical exploration between 1 and 22 days after haemorrhage. Two patients were in WFNS grade V and died subsequently with the aneurysms untreated, one after rehaemorrhage. In the patients with secured VA aneurysms the postoperative course was uncomplicated with the exception of additional caudal cranial nerve injury in 1 instance. Both BA aneurysms were initially treated by endovascular methods. In the first patient incomplete packing with Gugliemi detachable (GDC) coils was achieved. Follow-up angiography 6 months later showed growth and coil compaction and subsequent wrapping with Teflon fibres resulting in angiographic stabilization. The other BA aneurysm was treated by a combination of a coronary stent and GDC coils. The 3 dissecting ICA aneurysms were all explored surgically. In only 1 instance ICA continuity could be preserved by wrapping, in the other 2 cases a major portion of the vessel wall disintegrated upon removal of the surrounding clot. The only ACA dissecting aneurysm, on A2, was successfully treated with a Dacron cuff. In the single patient with a MCA aneurysm, a decision for conservative management was taken, because neither a surgical nor an endovascular solution was seen as a possibility that did not risk occlusion of lenticulostriate branches. The patient suffered a fatal rehaemorrhage 4 weeks later at her home. CONCLUSIONS: The reported experience suggests that in Western countries also dissecting aneurysms are an occasional source of SAH. The outcome in our conservatively managed patients confirms the poor prognosis of conservative management. Wrapping and endovascular stent based methods can achieve stabilization of the dissected artery without sacrificing the artery. Results of treatment appear to depend largely on the location of the dissecting aneurysm.

Aged↗
PubMed2003

Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia.

OBJECTIVE: Bradykinin has been identified as a mediator of secondary brain damage in acute insults. We currently studied neuroprotective properties of a bradykinin B2 receptor antagonist (LF16-0687 Ms) in transitory focal cerebral ischemia to assess infarct formation and the development of brain edema. MATERIAL AND METHODS: 55 Rats were subjected to 90 min of MCA-occlusion. The receptor antagonist was administered at two dose levels, given from 30 min prior to ischemia over two days after ischemia. Ischemic tissue damage was quantified at day 7 after MCA-occlusion together with assessment of brain edema in separate experiments. Neurological recovery was studied daily. RESULTS: Animals receiving treatment (low dose) had a better functional recovery, particularly at days 3 and 4 (P < 0.05). Infarct formation was significantly attenuated in these animals in both total and cortical brain tissue by 50, or 80%, respectively. Postischemic brain swelling was significantly lowered, i.e. by 62%. CONCLUSIONS: Our findings provide further support for a mediator role of bradykinin in ischemic brain damage including edema formation, obviously by ligand binding to the bradykinin B2 receptor. The availability of a receptor antagonist may afford opportunity for translation of this experimental treatment into stroke patients.

Animals↗
PubMed2003

Neuroprotective efficacy of intra-arterial and intravenous magnesium sulfate in a rat model of transient focal cerebral ischemia.

BACKGROUND: Many neurovascular procedures necessitate temporary occlusion of cerebral arteries. In this situation neuroprotective drugs may increase the safety of the procedures. Magnesium may inhibit ischemic damage by anti-excitotoxic, calcium channel blocking and vasodilatory action. Some evidence suggests that intra-arterial administration might provide a much higher degree of protection than intravenous treatment. In this study the neuroprotective efficacy of intra-arterial and intravenous magnesium administration was examined in a rat model of transient focal ischemia. METHODS: 34 male Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion (MCAO) by an intraluminal thread. Before ischemia, animals received an infusion of either (1) vehicle (0.9% NaCl) (2) MgSO4 intra-arterially or (3) MgSO4 intravenously. Local cortical blood flow (LCBF) was continuously measured by laser-Doppler flowmetry. Functional deficits were quantified daily, infarct volumes were assessed histologically after 7 days. FINDINGS: There was no difference between the treatment groups concerning LCBF. Magnesium serum levels increased from approximately 1 mmol/l to approximately 1.8 mmol/l by either route of administration. Both intra-arterial and intravenous treatment improved neurological recovery and equally reduced total infarct volume by approximately 25%. INTERPRETATION: The results indicate that there is no advantage of intra-arterial over intravenous magnesium administration. A comparison with previous studies suggests that even within the normal range of serum magnesium concentrations, low-normal levels may be hazardous and high-normal levels may be protective in transient focal ischemia.

Animals↗
PubMed2003

Neuronavigation based on CT angiography for surgery of intracranial aneurysms: primary experience with unruptured aneurysms.

Several reports have demonstrated the use of three-dimensional (3D) computed tomographic angiography (CTA) for preoperative planning in patients with intracranial aneurysms. Until now, there are no reports on the potential role of navigation systems in combination with CTA in aneurysm surgery. In the present study we report our experience with neuronavigation based on CTA in 16 patients with unruptured anterior circulation aneurysms for 1) planning craniotomy; 2) guided approach to the aneurysm; and 3) 3D presentation of the aneurysm and adjacent arteries in correct orientation. The reconstructed CTA images were analyzed preoperatively with regard to diameter of aneurysm neck and dome as well as projection and possible daughter aneurysms, and these parameters were compared with the intraoperative findings. In addition the accuracy of the navigator to locate the aneurysm neck was measured intraoperatively. Navigated approach planning resulted in variable keyhole craniotomies for the 7 middle cerebral artery aneurysms, but did not result in deviation from small standard craniotomies for the internal carotid and anterior communicating artery aneurysms. Precision of the indication of the navigator with regard to the aneurysm neck ranged from < 1 mm to 4 mm. Intraoperative assessment confirmed the CTA data with regard to aneurysm size and projection in all, and definition of daughter aneurysms and adjacent arteries in most cases. The computer assisted approach allowed a smaller, exactly placed craniotomy primarily in MCA aneurysms. 3D presentation of the aneurysms and the adjacent arteries in correct orientation facilitated identification and dissection the aneurysms. Current navigation systems are not precise enough to allow "blind" aneurysm clipping by placing a real clip on the virtual aneurysm neck.

Adult↗
PubMed2002

Effects of LF 16-0687 Ms, a bradykinin B(2) receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia.

Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B(2) receptors. LF 16-0687 Ms, a non-peptide competitive bradykinin B(2) receptor antagonist, was recently found to decrease brain swelling in various models of traumatic brain injury. We have investigated the influence of LF 16-0687 Ms on the edema formation, neurological outcome, and infarct size in temporary focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal filament. Local CBF was bilaterally recorded by laser Doppler flowmetry. Study I: animals were assigned to one of three treatment arms (n=11 each): (a) vehicle, (b) LF 16-0687 Ms (12.0 mg/kg per day), or (c) LF 16-0687 Ms (36.0 mg/kg per day) given repetitively s.c. over 3 days. The neurological recovery was examined daily. The infarct volume was assessed histologically 7 days after ischemia. Study II: brain swelling and bilateral hemispheric water content were determined at 48 h post ischemia in eight rats, subjected to the low dose regimen as described above, and in eight vehicle-treated control animals. All treated animals showed tendency to exhibit improved neurological recovery throughout the observation period as compared to the vehicle-treated controls, while this improvement was only significant within the low dose group from postischemic days 3 to 4. Low dose LF 16-0687 Ms significantly attenuated the total and cortical infarct volume by 50 and 80%, respectively. Furthermore, postischemic swelling (-62%) and increase in water content of the infarcted brain hemisphere (-60.5%) was significantly inhibited. The present findings provide strong evidence for an involvement of bradykinin-mediated secondary brain damage following from focal cerebral ischemia. Accordingly, specific inhibition of bradykinin B(2) receptors by LF 16-0687 Ms attenuated postischemic brain swelling, improved the functional neurological recovery, and limited ischemic tissue damage, raising its potential for clinical evaluation in patients with acute stroke.

Animals↗
PubMed2002

Anesthetic methods in rats determine outcome after experimental focal cerebral ischemia: mechanical ventilation is required to obtain controlled experimental conditions.

OBJECTIVE: Anesthetic agents, pH, blood gases and blood pressure have all been found to influence the pathophysiology of experimental stroke. In experimental research, rats are predominantly used to investigate the effects of focal cerebral ischemia. Chloral hydrate, applied intraperitoneally (i.p.), and halothane, applied via face-mask in spontaneously breathing animals or via endotracheal tube in mechanically ventilated animals are popular methods of anesthesia. We investigated the potential of these anesthetic methods to maintain physiologic conditions during focal cerebral ischemia and their influence on postischemic mortality and histological outcome. METHODS: Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery occlusion by insertion of an intraluminal thread and assigned to one of three groups (n=10 each): (A) chloral hydrate i.p./spontaneously breathing; (B) halothane in 70:30 (%) N2O/O2 via face-mask/spontaneously breathing; and (C) halothane in 70:30 (%) N2O/O2 via endotracheal tube/mechanically ventilated. Physiologic parameters were measured before, during, and after ischemia. Infarct volume was histologically assessed after 7 days. RESULTS: All anesthetic techniques except mechanical ventilation via an endotracheal tube resulted in considerably fluctuating blood gases levels, hypercapnia, acidosis and low blood pressure. All spontaneously breathing animals (groups A and B) exhibited a higher postischemic mortality and significantly larger infarct volumes than group C with intubated and ventilated animals. CONCLUSIONS: Intra- and postischemic physiologic parameters such as blood pressure, pH, and blood gases critically determine outcome after focal cerebral ischemia. Although anesthesia by halothane via face-mask allowed better control of depth of anesthesia than chloral hydrate, we have found this method to be unsatisfactory due to insufficient control of ventilation and waste of anesthetic gases. Experiments with rats requiring normal physiologic parameters should be performed under conditions of controlled mechanical ventilation and sufficient analgesia.

Acidosis, Respiratory↗
PubMed2001

[Proper diagnosis and treatment of carotid stenoses. Recommending surgery, when is it too risky?].

A number of multicentric randomized studies have been able to demonstrate a benefit from surgery in high-grade asymptomatic and symptomatic carotid artery stenosis. The benefits of carotid artery endarterectomy are greater in symptomatic than in asymptomatic patients. This means that, in the case of the latter, the benefits and risks of surgery must be considered with special care. The gold standard of the preoperative diagnostic work-up is selective angiography. Since this examination modality is associated with a complication rate of > 1% in this group of patients, there is an increasing tendency to content oneself with such noninvasive procedures as duplex sonography used in combination with cranial and cervical MRI. The life expectancy of patients undergoing carotid artery end-arterectomy is determined mainly by their concomitant cardiac problems. Constant surveillance and optimal treatment of vascular risk factors is therefore essential in these patients.

Carotid Stenosis↗
PubMed2001

Transorbital keyhole approach to anterior communicating artery aneurysms.

OBJECTIVE: The transorbital keyhole approach to anterior communicating artery aneurysms was developed as a minimally invasive method for safe control of the anterior communicating artery complex. This approach does not necessitate resection of the gyrus rectus. METHODS: The technique is described in detail. The transorbital keyhole approach provides more ventral access than the supraorbital approaches, and the anterior communicating artery complex can be controlled by splitting the basal aspect of the interhemispheric fissure. RESULTS: Since late 1998, the authors have used the transorbital keyhole approach routinely. During the initial experience with 33 patients, the only observed complication specific to this approach was transient diplopia in one patient. At follow-up examinations 2 to 15 months after surgery, the cosmetic results were favorable as compared with those of standard pterional craniotomy. CONCLUSION: We have designed a small, custom-tailored approach to the anterior communicating artery complex for routine use. The small orbitocranial approach is a step toward the ideal of purely extra-axial safe control of anterior communicating artery aneurysms. The orbitocranial keyhole approach seems to be substantially better than the craniotomy, although it requires additional effort and time.

Esthetics↗
PubMed2000

[Therapy of subarachnoid hemorrhage. First aid already on site!].

The age peak for spontaneous subarachnoidal bleeding from an aneurysm is 55-60 years, and two-thirds of the cases are women. The prognosis continues to be poor (50% early mortality rate). Early admission to a neurosurgical department/institution may be life-saving. Already in the out-of-hospital situation, lowering of the frequently elevated blood pressure needs to be achieved (e.g. with Adalat (nifedipine) 10 mg, sublingual). Depending on the stage presenting, either early surgery is indicated, or elective surgery when the patient has been stabilized. Here, two different schools of thought continue to exist. A new method is endovascular coiling involving the microcatheter placement of tiny platinum spirals in the aneurysm to effect local thrombosis. As a prophylactic measure, vasospasm may be prevented by the administration of Nimotop (nimodipine). But its treatment continues to be problematic.

Cerebral Angiography↗
PubMed2000

Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms.

The assessment of the functional outcome - in addition to the conventional endpoints as histomorphometry of the ischemic brain damage - for the evaluation of cerebroprotective therapies is increasingly recommended, although there is little consensus on appropriate procedures. We evaluated a battery of sensorimotor tasks in rats after transient middle cerebral artery occlusion (MCAO) to select those with the highest potential to discriminate between various degrees of neuronal damage. A total of 40 Sprague-Dawley rats were subjected to 90 min of MCAO and assigned to one of four treatment arms: (1) sham-operated controls, (2) vehicle-treated controls, (3) moderately effective neuroprotection by 2x100 mg/kg alpha-phenyl-N-tert-butyl nitrone (PBN), (4) highly effective neuroprotection by mild hypothermia (33 degrees C). Functional deficits were daily quantified using the beam balance task (1.5 cm, 2.5 cm diameter rectangular and 2.5 cm diameter cylindrical beam), the prehensile traction task, the rotarod, and a six-point neuro-score. Infarction of cerebral cortex and basal ganglia was assessed one week after ischemia. Treatment with PBN significantly reduced cortical infarction (-31%), while treatment with hypothermia resulted in a significantly smaller infarct volume of cortex (-94%) and basal ganglia (-27%). Beam balance, prehensile traction and rotarod failed to demonstrate any difference in motor performance. The six-point neuro-score showed a significant correlation with cortical infarction from day 2 and with total infarct volume from day 3. The smaller the reduction of infarct volume, the later the corresponding difference in neuro-score became apparent. Functional outcome after MCAO in rats can be assessed by a relatively simple measurement of neurological deficit. The slope of functional recovery is closely related with the degree of the morphological, particularly cortical damage. If expected treatment effects are small, an observation period of at least 3 days should be planned for the study design. The functional impairment from focal brain ischemia and its subsequent recovery could provide valuable information for future studies evaluating the neuroprotective potential of novel agents and procedures.

Animals↗
PubMed2000

Reconstructive surgery of the extracranial arteries.

The first carotid endarterectomy (CEA) is usually accredited to Eastcott who reported in 1954 the successful incision of a diseased carotid bulb with end-to-end anastomosis of the internal carotid artery (ICA) to the common carotid artery (CCA). During the following years surgeons were quick to adopt and improve the intuitively attractive procedure. But by the early to mid 1980s several leading neurologists began to question the growing number of CEAs performed at that time. Six major CEA trials were then designed which are now completed or nearing completion. Most conclusive data are available from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) for symptomatic carotid disease, and from the Asymptomatic Carotid Atherosclerosis Study (ACAS) for asymptomatic carotid disease. The key result of these studies is that CEA is beneficial to high grade symptomatic and asymptomatic carotid stenosis. While the benefit in symptomatic disease is clear, it may be negligible in asymptomatic patients suffering from other medical conditions, the most important being coronary artery disease. Since the conclusions from the different studies vary significantly, guidelines and recommendations with regard to CEA have been issued by a number of interest groups, so-called consensus conferences. The best known guidelines are published by the American Heart Association (AHA). However, the practice of interest groups to issue guidelines is currently being criticized, the main reason being that interest groups have different ideas and all claim the right to issue guidelines. At present we recommend CEA for symptomatic high-grade stenosis in patients without significant coincident disease. With regard to asymptomatic stenosis we suggest surgery to otherwise healthy patients if the stenosis is very narrow or progressive. Preoperative evaluation has changed over the years. Currently we recommend duplex sonography in combination with intra- and extracranial magnetic resonance angiography (MRA). Concurrent coronary artery disease is a major consideration in the perioperative management, and the use of a specific algorithm is recommended. Surgery is performed under general anaesthesia with intraoperative monitoring such as electroencephalography (EEG) and transcranial Doppler (TCD). A temporary intraluminal shunt is used selectively if after cross-clamping the flow velocity in the middle cerebral artery (MCA) falls to below 30 to 40% of baseline. For years we employed routine barbiturate neuroprotection during cross-clamping. At the present time we use barbiturate selectively, if the flow velocity in the MCA falls to below 30 to 40% of baseline and if the use of a temporary intraluminal shunt is not possible due to difficult anatomic conditions. The reason to abandon systematic barbiturate protection was to accelerate recovery from anaesthesia. Our patients are monitored overnight on the ICU or a surveillance unit. Routine hospitalization after surgery is 5 to 7 days with a control duplex sonography being performed prior to discharge. A number of details with regard to surgical technique and perioperative management are a matter of discussion. Our surgical routine is described here step by step. Such management resulted in 6 major complications among the 402 cases with 4 of cardiopulmonary and 2 of cerebrovascular origin. For the future we can expect the development of percutaneous transluminal techniques competing with standard carotid endarterectomy. At the present time several comparative studies are under way. Irrespective of the technical approach to treat carotid stenosis, several other issues have to be clarified before long. One of the major unresolved items is the timing of treatment after completed stroke. In this regard prospective trials need to be performed. Although numerically not as important as carotid stenosis, vertebral artery (VA) and subclavian artery (SA) stenoses are more and more accepted as indication for surgical

Carotid Arteries↗
PubMed2000

Neuroprotective effects of the novel brain-penetrating antioxidant U-101033E and the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN).

Literature on the therapeutic efficacy of free radical scavengers suggests that drugs that are able to cross the blood-brain barrier are more effective in protecting the brain from ischemic damage. However, the exact mechanisms by which brain-penetrating antioxidants act have yet not been delineated. We compared the neuroprotective potential of the newly discovered pyrrolopyrimidine U-101033E with that of alpha-phenyl-N-tert-butyl nitrone (PBN) and investigated their influence on cerebral blood flow. Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery (MCA) occlusion by an intraluminal filament. Local cerebral blood flow (LCBF) was bilaterally recorded by laser Doppler flowmetry. Neurological deficits were quantified daily. Infarct volume was assessed after 7 days. MCA occlusion reduced ipsilateral LCBF to 20-30% of baseline. After reperfusion, postischemic hyperemia was followed by a decrease in LCBF to about 70% of baseline. There was no difference in LCBF among groups. U-101033E improved neurological function and reduced infarct volume by 52% (P < 0.05). Improvement of neurological function and reduction of infarct volume (-25%) in animals treated with PBN was not significant. We conclude that U-101033E has superior neuroprotective properties compared with PBN. Neither drug improves blood flow during ischemia and 1 h of reperfusion. The mechanisms by which these brain-penetrating antioxidants act remain to be clarified.

Animals↗