Results of direct and indirect revascularisation for adult European patients with Moyamoya angiopathy.

There is little information concerning clinical data and revascularization procedures in adult European patients with Moyamoya disease. More data are available on juvenile European Moyamoya angiopathy and its microsurgical therapies. This analysis summarizes our clinical experience in European adult patients with Moyamoya angiopathy. Nine adult European patients underwent surgical revascularization for Moyamoya angiopathy between 1997 and 2005. Direct intracranial-extracranial (EC-IC) bypass was considered the primary surgical modality. In case of unsuitable donor or recipient arteries, encephalo-myo-synangiosis (EMS) was chosen as an indirect modality. The current analysis confirms that direct EC-IC-bypass is a feasible option for most cases of adult European Moyamoya disease. Exact definition of long-term benefits would require a multicentric study. EMS appears to be of questionable value in the adult European population.

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.

Intraprocedural thrombus formation during coil placement in ruptured intracranial aneurysms: treatment with systemic application of the glycoprotein IIb/IIIa antagonist tirofiban.

BACKGROUND AND PURPOSE: When using detachable coils to treat intracranial aneurysms, thromboembolism is the most feared and frequently reported complication during or after endovascular therapy. The purpose of this study was to document the therapeutic effect of tirofiban on patency of the parent vessel, rate of rebleedings, and outcome of the patients in the setting of acute subarachnoidal hemorrhage. METHODS: A patient data base was retrospectively reviewed to identify patients in whom thrombus occurred during endovascular treatment of ruptured cerebral aneurysms within a 34-month period and who were treated with tirofiban. All patients underwent anticoagulation with heparin during endovascular treatment procedures. Sixteen patients (age range, 52.9 +/- 10.7 years; 10 women, 6 men) were identified with intraprocedural thrombus formation. The patency of the parent vessel was assessed in a retrospective analysis blinded to outcome. Eight patients received ventriculostomy and had a follow-up CT. RESULTS: Local nonocclusive thrombus at the coil surface was detected in 5 patients, in all of whom the thrombus was dissolved. In 10 patients, partial or total occlusion of the parent vessel occurred during the intervention; in 8 of these, the vessel was recanalized completely and in 2 drug administration was assisted by mechanical means. In 1 patient, however, the occlusion persisted. No periprocedural rebleedings of the ruptured aneurysm occurred; 3 of 8 ventriculostomies had clinically silent small local bleedings. CONCLUSION: The use of tirofiban in the setting of endovascular treatment of ruptured intracranial aneurysms to dissolve platelet aggregation seems relatively safe and effective.

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.

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.

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.

Neuroprotective efficacy of combination therapy with two different antioxidants in rats subjected to transient focal ischemia.

The vascular endothelium and parenchyma of the brain have both potential pathways to generate free radicals under pathological conditions. We evaluated the neuroprotective efficacy of two different antioxidants, a microvascularly acting 21-aminosteroid (U-74389G) and a brain-penetrating pyrrolopyrimidine (U-101033E) alone and in combination. Forty Sprague-Dawley rats were randomly assigned to one of four treatment groups: (1) vehicle-treated controls, (2) U-74389G, (3) U-101033E, (4) U-74389G+U-101033E. Drugs were administered in a dosage of 3x3 mg/kg i.v. before, during, and after ischemia. All animals were subjected to 90 min of middle cerebral artery occlusion. Local cortical blood flow (LCBF) was continuously recorded by bilateral laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. There were no significant differences in LCBF among groups. U-101033E improved neurological function from postoperative day 4 to 7, while U-74389G did not improve neurological recovery. Animals treated with both drugs showed significantly less deficits from postoperative day 1 to 7. U-101033E and combination therapy reduced total infarct volume by 53% and 54% (P<0.05). U-74389G non-significantly reduced total infarct volume by 25%. Cortical infarct volume was significantly reduced in all treatment groups but only U-101033E and combination therapy protected the basal ganglia from infarction. In conclusion, brain-penetrating antioxidants have superior neuroprotective properties compared to microvascularly acting agents. Combination therapy, affording antioxidation plus radical scavenging in blood vessels and brain parenchyma, might yield the highest degree of neuronal protection from peroxidative damage. The neuroprotective efficacy seems to be independent of CBF.

EEG burst suppression is not necessary for maximum barbiturate protection in transient focal cerebral ischemia in the rat.

Barbiturates have been demonstrated to reduce the cerebral metabolic rate (CMR) in a dose-dependent manner but investigations of a dose-response relationship for their neuroprotective efficacy are scant. It has been suggested that barbiturates possess other mechanism of action that may be critical to their protective effect. If so, it is conceivable that the peak effect of such mechanisms does not parallel the reduction in CMR. Thus, maximal neuroprotection may be achieved with a substantially lower dose of the drug. Thirty Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion while either anesthetized with (1) halothane (control) or (2) intravenous thiopental titrated to cause mild EEG suppression or (3) thiopental titrated to maintain EEG burst suppression. Cortical blood flow was recorded by continuous bilateral laser Doppler flowmetry (LDF). Infarct volume was assessed after 3 h of reperfusion. Low-dose thiopental decreased blood flow to 80% of baseline and high-dose thiopental to 70% of baseline. LDF did not indicate improvement of blood flow by thiopental in the ischemic area. Compared to controls, low-dose thiopental significantly decreased infarct volume by 28% and high-dose thiopental by 29%. The results of this study and a review of literature indicate that barbiturates provide cerebral protection but that the magnitude of this effect has been overestimated. Other mechanisms than CMR reduction seem to contribute to their beneficial effects, and high doses administered to the point of burst suppression may not be required to obtain maximal protection.

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.

Radical resection of meningiomas and arteriovenous fistulas involving critical dural sinus segments: experience with intraoperative sinus pressure monitoring and elective sinus reconstruction in 10 patients.

OBJECTIVE: Radical resection of meningiomas and dural arteriovenous fistulas involving functional major dural sinuses entails the risk of intracranial hypertension and venous infarction. Surgical reconstruction of dural sinuses and bridging veins increases the spectrum of dural sinus conditions that can be treated by complete resection, but indications for venous reconstructions and associated risks are still not well defined. We report our experience with sinus reconstruction based on the intraoperative assessment of collateral venous flow. METHODS: Radical resection of meningiomas (n = 5) or dural arteriovenous fistulas (n = 5) involving critical segments of dural sinuses was performed in 10 patients. All but two patients were suffering from recurrent disease after incomplete treatment. Tolerance of sinus occlusion was assessed intraoperatively by measuring stump pressure in the superior sagittal sinus during test clamping of the involved sinus segment. RESULTS: In five patients, the results of pressure monitoring suggested that occlusion of the sinus might not be tolerated. In two other patients, major bridging veins entered the diseased segment. In these patients, the resected sinus segment was reconstructed and bridging veins were reinserted as far as possible. Postoperative graft occlusion occurred in two patients. One patient who was managed without reconstruction sustained a transient postoperative neurological deficit resulting from venous congestion in the vein of Labbé. Postoperative imaging confirmed total elimination of the pathological process in all 10 patients. There was no recurrence of disease during follow-up periods of up to 8 years. CONCLUSION: The monitoring of sinus pressure, together with the possible reconstruction of the diseased sinus, allows complete surgical treatment of dural sinus abnormalities and involves acceptable risk.

Neuroprotective effects of combination therapy with tirilazad and magnesium in rats subjected to reversible focal cerebral ischemia.

OBJECTIVE: Cell death after cerebral ischemia is mediated by release of excitatory amino acids, calcium influx into cells, and generation of free radicals. We examined the hypothesis that concurrent administration of tirilazad, a well-known antioxidant, and magnesium, an antagonist of calcium and excitatory amino acids, would result in a synergistic neuroprotective effect. METHODS: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and assigned to one of four treatment arms (n = 10 in each): 1) vehicle, 2) tirilazad, 3) MgCl2, or 4) tirilazad and MgCl2. Cortical blood flow was recorded using laser Doppler flowmetry. Functional deficits were quantified by performing daily neurological examinations. Infarct volume was assessed after 7 days. RESULTS: There was no difference in cortical blood flow among groups. Animals that received tirilazad or MgCl2 monotherapy had significantly better neurological function compared with control animals only on postoperative Days 3 and 4, whereas animals treated with both drugs had significantly better neurological function than did control animals from postoperative Days 2 through 7. Magnesium reduced total infarct volume by 25% (nonsignificant), tirilazad by 48% (P<0.05), and combination therapy by 59% (P<0.05) compared with control data. CONCLUSION: Combined therapy with antagonists of excitatory amino acids and free radicals provides better neuroprotection from the effects of transient focal ischemia than does therapy with either antagonist alone. In contrast to many experimental agents, tirilazad and magnesium offer the advantage of being licensed for clinical use. This drug combination could be of great benefit when administered before temporary artery occlusion in patients undergoing cerebrovascular surgery.

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.

No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia.

OBJECT: Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses-the gold standard of neuroprotection during neurovascular procedures-provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question. METHODS: Thirty-two Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33 degrees C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy. CONCLUSIONS: The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.

Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter.

OBJECT: The aim of this retrospective study was to compare treatment results of surgery plus whole-brain radiation therapy (WBRT) with gamma knife radiosurgery alone as the primary treatment for solitary cerebral metastases suitable for radiosurgical treatment. METHODS: Patients who had a single circumscribed tumor that was 3.5 cm or smaller in diameter were included. Treatment results were compared between microsurgery plus WBRT (52 patients, median tumor dose 50 Gy) and radiosurgery alone (56 patients, median prescribed tumor dose 22 Gy). In case of local/distant tumor recurrence in the radiosurgery group, additional radiosurgical treatment was administered in patients with stable systemic disease. Survival time was analyzed using the Kaplan-Meier method, and prognostic factors were obtained from the Cox model. The patient groups did not differ in terms of age, gender, pretreatment Karnofsky Performance Scale (KPS) score, duration of symptoms, tumor location, histological findings, status of the primary tumor, time to metastasis, and cause of death. Patients who suffered from larger lesions underwent surgery (p < 0.01). The 1-year survival rate (median survival) was 53% (68 weeks) in the surgical group and 43% (35 weeks) in the radiosurgical group (p = 0.19). The 1-year local tumor control rates after surgery and radiosurgery were 75% and 83%, respectively (p = 0.49), and the 1-year neurological death rates in these groups were 37% and 39% (p = 0.8). Shorter overall survival time in the radiosurgery group was related to higher systemic death rates. A pretreatment KPS score of less than 70 was a predictor of unfavorable survival. Perioperative morbidity and mortality rates were 7.7% and 1.6% in the resection group, and 8.9% and 1.2% in the radiosurgery group, respectively. Four patients presented with transient radiogenic complications after radiosurgery. CONCLUSIONS: Radiosurgery alone can result in local tumor control rates as good as those for surgery plus WBRT in selected patients. Radiosurgery should not be routinely combined with radiotherapy.

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

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.

Neuroprotective properties of a novel antioxidant (U-101033E) with improved blood-brain barrier permeability in focal cerebral ischemia.

Many efforts have been undertaken to develop antioxidants against free radical induced brain damage, 21-aminosteroids, although accumulating in the cell membrane, thus protecting vascular endothelium from peroxidative damage hardly penetrate the blood-brain barrier. A novel group of antioxidants, the pyrrolopyrimidines, has a markedly improved ability to enter the brain parenchyma. In our current study the neuroprotective potential of the 21-aminosteroid U-74389G was compared with that of the pyrrolopyrimidine U-101033E in a rat model of reversible focal cerebral ischemia. Sprague-Dawley rats were subjected to unilateral occlusion of the middle cerebral artery with assignment to one of three treatment arms (n = 10 each), receiving either vehicle, U-74389G, or U-101033E. Regional CBF was recorded bilaterally by laser Doppler flowmetry. In addition, neurological examination was performed daily, with assessment of infarct volume at day seven. U-101033E reduced the infarct volume significantly by 51%, whereas U-74389G afforded non-significant attenuation only. U-101033E was found to improve neurological recovery promptly; animals with U-74389G began to recover only at the end of the experimental observation period. Differences in the regional CBF were not found in the contralateral hemispheres for either treatment group. We conclude that antioxidative compounds which cross the blood-brain barrier are more effective in focal cerebral ischemia than agents which predominantly act on the endothelium of cerebral microvessels.

[Proper diagnosis and treatment of carotid stenoses. Recommending surgery, when is it too risky?]. / Karotisstenosen richtig erkennen und behandeln. Wann rät man zur OP, wann ist sie zu riskant?

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.

[Therapy of subarachnoid hemorrhage. First aid already on site!]. / Therapie der Subarachnoidalblutung. Die fängt bereits auf der Strasse an!

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.