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Biomedical subjects

Robert Schmid-Elsaesser

Publications and source records attributed to Robert Schmid-Elsaesser.

11 recordsLinked to original sources

Simultaneous bilateral laser Doppler fluxmetry and electrophysiological recording during middle cerebral artery occlusion in rats.

Laser Doppler fluxmetry (LDF) and electrocorticography (ECG) are techniques used to indicate successful occlusion of the middle cerebral artery (MCAO) in the intraluminal filament model of ischemic stroke. However, each method has several advantages and drawbacks. This article describes a simple technique to simultaneously and continuously monitor LDF and ECG over both cerebral hemispheres. We investigated the potential of this method to improve the reliability of the filament model. Thirty male Sprague-Dawley rats were subjected to transient MCAO under three different experimental conditions (n=10 each group): MCAO in [A] normothermic animals, in [B] animals treated with hypothermia and in [C] animals receiving barbiturate for induction of burst suppression. Cortical blood flow was continuously recorded bilaterally by LDF and the electrocorticogram was continuously recorded over both hemispheres. The results show that monitoring of cortical electrophysiological activity by ECG allows detection of subarachnoid hemorrhage (SAH) during normal electrophysiological status and provides continuous control of barbiturate induced burst suppression as well as information about postischemic electrophysiological recovery. ECG did not detect MCAO, premature reperfusion, or SAH during burst suppression induced by barbiturates. In contrast, MCAO, SAH and premature reperfusion were rapidly indicated by LDF. Our findings suggest that simultaneous bilateral LDF and ECG during MCAO are of complementary value, in particular if barbiturates are investigated.

Animals↗

Cavernous malformations of the brainstem: three-dimensional-constructive interference in steady-state magnetic resonance imaging for improvement of surgical approach and clinical results.

OBJECTIVE: The indications for resection of cavernous malformations (CMs) of the brainstem include neurological deficits, (recurrent) hemorrhage, and surgically accessible location. In particular, knowledge of the thickness of the parenchymal layer and of the CM's spatial relation to nuclei, tracts, cranial nerves, and vessels is critical for planning the surgical approach. We reviewed the operative treatment of 13 patients with 14 brainstem CMs, with special regard to refined three-dimensional (3D)-constructive interference in steady-state (CISS) magnetic resonance imaging (MRI). METHODS: Patients were evaluated neurologically and by conventional spin-echo/fast spin-echo and 3D-CISS MRI. Surgery was performed with the use of microsurgical techniques and neurophysiological monitoring. RESULTS: Eleven CMs were located in the pons/pontomedullary region; 10 of the 11 were operated on via the lateral suboccipital approach. Three CMs were located near the floor of the fourth ventricle and operated on via the median suboccipital approach, with total removal of all CMs. Results were excellent or good in 10 patients; one patient transiently required tracheostomy, and two patients developed new hemipareses/ataxia with subsequent improvement. Not only did 3D-CISS sequences allow improved judgment of the thickness of the parenchymal layer over the lesion compared with spin-echo/fast spin-echo MRI, but 3D-CISS imaging also proved particularly superior in demonstrating the spatial relation of the lesion to fairly "safe" entry zones (e.g., between the trigeminal nerve and the VIIth and VIIIth nerve groups) by displaying the cranial nerves and vessels within the cerebellopontine cistern more precisely. CONCLUSION: Surgical treatment of brainstem CMs is recommended in symptomatic patients. Especially in patients with lesions situated ventrolaterally, the 3D-CISS sequence seems to be a valuable method for identifying the CM's relation to safe entry zones, thereby facilitating the surgical approach.

Adolescent↗

Intravenous magnesium versus nimodipine in the treatment of patients with aneurysmal subarachnoid hemorrhage: a randomized study.

OBJECTIVE: The prophylactic use of nimodipine in patients with aneurysmal subarachnoid hemorrhage reduces the risk of ischemic brain damage. However, its efficacy seems to be rather moderate. The question arises whether other types of calcium antagonists offer better protection. Magnesium, nature's physiological calcium antagonist, is neuroprotective in animal models, promotes dilatation of cerebral arteries, and has an established safety profile. The aim of the current pilot study is to evaluate the efficacy of magnesium versus nimodipine to prevent delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. METHODS: One hundred and thirteen patients with aneurysmal subarachnoid hemorrhage were enrolled in the study and were randomized to receive either magnesium sulfate (loading 10 mg/kg followed by 30 mg/kg daily) or nimodipine (48 mg/d) intravenously until at least postoperative Day 7. Primary outcome parameters were incidence of clinical vasospasm and infarction. Secondary outcome measures were the incidence of transcranial Doppler/angiographic vasospasm, the neuronal markers (neuron-specific enolase, S-100), and the patients' Glasgow Outcome Scale scores at discharge and after 1 year. RESULTS: One hundred and four patients met the study requirements. In the magnesium group (n = 53), eight patients (15%) experienced clinical vasospasm and 20 (38%) experienced transcranial Doppler/angiographic vasospasm compared with 14 (27%) and 17 (33%) patients in the nimodipine group (n = 51). If clinical vasospasm occurred, 75% of the magnesium-treated versus 50% of the nimodipine-treated patients experienced cerebral infarction resulting in fatal outcome in 37 and 14%, respectively. Overall, the rate of infarction attributable to vasospasm was virtually the same (19 versus 22%). There was no difference in outcome between groups. CONCLUSION: The efficacy of magnesium in preventing delayed ischemic neurological deficits in patients with aneurysmal subarachnoid hemorrhage seems to be comparable with that of nimodipine. The difference in their pharmacological properties makes studies on the combined administration of magnesium and nimodipine seem promising.

Adult↗

Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats: a comparison between small volume resuscitation and mannitol.

OBJECTIVE: Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic-hyperoncotic saline solutions with the routinely used hyperosmotic agent-mannitol-and investigated their effects on ICP, CBF, neurological recovery and morphological damage after SAH in rats. METHODS: 60 dextran-resistant Wistar rats were subjected to SAH by an endovascular filament. ICP, MABP (mean arterial blood pressure) and bilateral local CBF were continuously recorded. All animals were randomly assigned to four groups: (I) NaCl 0.9% (4 ml/kg bw), (II) 7.5% NaCl+6% dextran 70 (4 ml/kg bw), (III) 7.2% NaCl+HES 200,000 (4 ml/kg bw) and (IV) 20% mannitol (9.33 ml/kg bw) given 30 min after SAH. Neurological deficits were assessed on days 1, 3 and 7 after SAH. The morphological damage was evaluated on day 7 after SAH. RESULTS: The induction of SAH resulted in an immediate ICP increase to 46.6+/-3.2 mm Hg (mean+/-S.E.M.) and 29.6+/-1.3 (mean+/-S.E.M.) mm Hg 90 min post-SAH. While a treatment with both hypertonic saline solutions (II, III) decreased ICP as well as the 20% mannitol solution, only the group treated with hypertonic saline and dextran 70 (II) showed an increase of ipsilateral CBF for 20 min after the infusion and significantly more surviving neurons in the motorcortex and caudoputamen. Mortality was reduced from 60% (I) and 73% (III and IV), respectively, to 40% in group II. CONCLUSION: Of all hypertonic solutions investigated, small volume resuscitation with NaCl 7.5% in combination with 6% dextran 70 evolved to be most effective in terms of reducing the initial harmful sequelae of SAH, leading to lowered ICP and less morphological damage after SAH in the rat.

Animals↗

Introducing a freely accessible internet database for identification of cerebral aneurysm clips to determine magnetic resonance imaging compatibility.

OBJECTIVE: Knowledge of the magnetic properties of cerebral aneurysm clips in patients undergoing magnetic resonance imaging (MRI) is imperative. In daily practice, however, it is often impossible to derive this information from previous medical records. The aim of this study was to develop a freely accessible internet database to identify unknown cerebral aneurysm clips on the basis of conventional x-ray images of the cranium and to provide reliable information about their magnetic properties to allow safe MRI investigations in these patients. METHODS: The 17 most commonly used clip series of the past 50 years were selected. The ferromagnetic properties of 47 example clips were examined by means of the Food and Drug Administration-approved "deflection angle test." An HTML-based database has been developed using standard x-ray images in two planes and photographs of the clips. Furthermore, details about alloy, ferromagnetic properties, MRI compatibility, year of construction, and other characteristics identifiable on x-rays were included. RESULTS: Seven aneurysm clips (of four clip models) were judged to be not MRI-compatible. The database named "ClipFinder" allows easy identification of cerebral aneurysm clips on standard cranial x-rays by comparing the films with the databank images supported by information on unique features of the clip design. CONCLUSION: On exemplary applications, ClipFinder provides a fast and easy-to-use database to identify unknown cerebral aneurysm clips via the internet and determine their MRI compatibility. The reliability of the identification system needs to be further evaluated in clinical practice before it can be recommended for widespread use.

Contraindications↗

Temporary aneurysm orifice balloon occlusion as an alternative to retrograde suction decompression for giant paraclinoid internal carotid artery aneurysms: technical note.

OBJECTIVE: Giant paraclinoid carotid artery aneurysms frequently require the temporary interruption of local circulation to facilitate safe clip occlusion. Owing to the brisk retrograde blood flow through the ophthalmic artery and cavernous branches, the simple trapping of the aneurysm by cervical internal carotid artery clamping and intracranial distal clipping may not adequately soften the lesion. Retrograde suction decompression aspiration of this collateral supply by a catheter introduced into the cervical internal carotid artery is a popular method to achieve aneurysm deflation. With a large collateral supply, the method is not effective enough. The advent of relatively long and maneuverable soft balloons allows temporary occlusion of the aneurysm orifice. METHODS: We applied this method in two instances of giant carotid ophthalmic aneurysms. In both instances, a 15- to 20-mm-long and 4-mm-wide occlusion balloon was inserted in the internal carotid artery at the level of the aneurysm before craniotomy. After craniotomy and dissection of the aneurysm neck, the balloon was inflated under intraoperative angiographic control. RESULTS: The aneurysm became soft enough in both cases without tapping and aspiration to allow safe clip occlusion. In the first case, the postoperative course was uneventful and visual acuity improved. A known additional infraclinoid part of the aneurysm was eliminated endovascularly 5 months later using balloon-protected injection of vinyl alcohol copolymer (Onyx; Micro Therapeutics, Inc., Irvine, CA). In the second case, a postoperative symptomatic vasospasm developed 15 hours after surgery. Hypertensive therapy resulted in the disappearance of symptoms and an otherwise uneventful course with improvement of vision. CONCLUSION: This preliminary experience suggests that this new method is a feasible alternative to retrograde suction decompression.

Balloon Occlusion↗

Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia.

We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO). Drugs were administered 30 min before and 1 h after MCAO. Hypothermia (33 degrees C) was maintained for 2 h. Infarct size was planimetrically determined after 6 h. In part II, 29 rats were assigned to the same treatment arms and subjected to 7 days of permanent MCAO. Neurological deficits and body weight were assessed daily. Infarct size was determined on day 7. In part I, MTH significantly reduced infarct formation by 52% after 6 h. In part II, high mortality within the first 3 days was observed in both groups. Treated animals showed a significantly better postoperative weight gain on day 7 and neurological recovery on days 6 and 7 compared to controls without significant differences in infarct volume. MTH seems to exert its neuroprotective properties even in a setting of permanent cerebral ischemia. High mortality and absence of infarct reduction after 7 days might be due to model limitations. Neurological recovery, the most important clinical outcome parameter, is significantly improved in 7-day survivors. Significant neuroprotection under conditions of permanent ischemia and former promising results in transient ischemia justify further investigations of MTH.

Animals↗

Dexamethasone in the treatment of subarachnoid hemorrhage revisited: a comparative analysis of the effect of the total dose on complications and outcome.

The benefit of dexamethasone in aneurysmal subarachnoid hemorrhage (SAH) is unproven. This actual study re-examined the impact on complications and outcome. Two hundred and forty-two patient records were analyzed. Dexamethasone had been prescribed individually. Group A consisted of patients in WFNS-grade I to III that were given at least 12mg/day dexamethasone for at least five days. All other patients in WFNS-grade I to III were assigned to group B. Groups C and D resulted from WFNS-grades IV and V, subdivided according to dexamethasone medication as groups A and B. Hydrocephalus and re-hemorrhage were significantly less frequent in group A than B (19% vs. 37%, P=0.011, and 3% vs. 13%, P=0.037, respectively). Favorable outcomes (Glasgow Outcome Scale, GOS 4 and 5) were more frequent in group A than B (99% vs. 85%; P=0.003). Frequencies of vasospasm and infections did not differ. In groups C and D significant differences were demonstrated for frequencies of hydrocephalus (C: 16%, D: 57%; P=0.006) and complications other than infection (C: 33%, D: 79%; P=0.002). Favorable outcomes were more frequent in group C than D (79% vs. 47%; P=0.046). Frequencies of vasospasm and infections did not differ.

Adult↗

Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats.

OBJECTIVE: Increased intracranial pressure (ICP) and decreased cerebral blood flow leading to global cerebral ischemia are the primary causes of death after severe subarachnoid hemorrhage (SAH). Hypertonic saline has been demonstrated to exert neuroprotective properties after traumatic brain injury by osmotic mobilization of parenchymal water and improvement of microcirculation. We used a rat model to investigate the effects of hypertonic fluid resuscitation after SAH on ICP, cerebral blood flow, body weight, neurological recovery, and morphological damage. METHODS: Sixty rats were subjected to SAH induced by an endovascular filament. ICP and local cerebral blood flow were recorded continuously. Animals were assigned to three groups: 1) NaCl 0.9%; 2) NaCl 7.5% (4 ml/kg); and 3) NaCl 7.5% plus 6% dextran 70 (4 ml/kg) given 30 minutes after SAH. Body weight and neurological deficits were assessed daily. Morphological damage was evaluated on Day 7. RESULTS: SAH resulted in an immediate increase of ICP to approximately 60 mm Hg initially, and then to approximately 30 mm Hg for the next 90 minutes. Although NaCl 7.5% alone and in combination with dextran led to an immediate, significant, and lasting decrease of ICP to 15 to 20 mm Hg, only the combined therapy significantly increased body weight and improved neurological recovery. Furthermore, the group that received combined therapy exhibited significantly more surviving neurons in hippocampus, cortex, caudoputamen, and cerebellum. Mortality was reduced nonsignificantly, from approximately 65% in groups I and II to 35% in Group III. CONCLUSION: Treatment with NaCl 7.5% plus 6% dextran 70 is significantly effective for reducing the initial harmful sequelae of SAH. The regimen resulted in lowered ICP, improved neurological recovery, and less morphological damage after SAH in the rat.

Animals↗

Combination drug therapy and mild hypothermia after transient focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: We have recently demonstrated that pretreatment with magnesium (calcium and glutamate antagonist) and tirilazad (antioxidant) in combination with intraischemic mild hypothermia (33 degrees C) (MTH) offers superior neuroprotective efficacy in a rat model of focal transient cerebral ischemia. In the present study, we investigated the time window of this treatment strategy with a posttreatment regimen to define its role for stroke patients. METHODS: We subjected 48 Sprague-Dawley rats to 90 minutes of middle cerebral artery occlusion by an intraluminal filament. Bilateral regional cerebral blood flow was continuously recorded by laser Doppler flowmetry. Combination therapy with MTH was started at 0, 1, 3, and 5 hours after induction of ischemia. Drugs were given in 1-hour intervals, and hypothermia was maintained for 2 hours. Neurological deficits were assessed daily. Infarct size was planimetrically determined on postoperative day 7. RESULTS: Combination therapy with MTH significantly reduced infarct volume compared with normothermic controls by -74%, -49%, and -45% when applied at 0, 1, and 3 hours after induction of ischemia. Furthermore, these treatment groups showed less neurological deficits on postischemic days 1 and 2 (P<0.05). Onset of treatment 5 hours after middle cerebral artery occlusion failed to significantly reduce infarct formation and neurological deficits. CONCLUSIONS: The therapeutic window of the new combination therapy is at least 3 hours after onset of ischemia, comparable to that of moderate hypothermia (30 degrees C), a grade of hypothermia associated with higher risks of severe side effects.

Animals↗

Neuroprotection in transient focal cerebral ischemia by combination drug therapy and mild hypothermia: comparison with customary therapeutic regimen.

BACKGROUND AND PURPOSE: A combined therapeutic approach has been advocated repeatedly for treatment of focal cerebral ischemia. A clinical example of combined therapy is administration of nimodipine, mannitol, dexamethasone, and barbiturates during temporary occlusion of a cerebral artery in neurovascular surgery. We have recently demonstrated outstanding neuroprotective properties of a combination therapy with magnesium (calcium antagonist and glutamate antagonist), tirilazad (antioxidant), and mild hypothermia (MTH). In this study we compared this treatment strategy with the customary treatment options in a rat model of transient focal cerebral ischemia. METHODS: Sprague-Dawley rats (n=120) were subjected to 90 minutes of middle cerebral artery occlusion by an intraluminal filament (n=10 per group). In experiment 1, the customary treatment options (nimodipine, mannitol, dexamethasone, methohexital) were evaluated as monotherapy and in combination. In experiment 2, the customary and the new combination therapy (MTH) were compared. Mild hypothermia (33 degrees C) was maintained for 2 hours. Neurological examinations were performed daily. Infarct size was assessed histologically after 7 days. RESULTS: In experiment 1, infarct volume was attenuated by 34% at maximum, with mannitol and methohexital being the most effective drugs given as monotherapy. In experiment 2, combined administration of the customary treatment options had no additive effect (infarct volume -36%). Combination therapy with MTH reduced total infarction by 73% and almost completely abolished cortical infarction (-91%). None of the animals of this group had any residual neurological deficit at the end of the observation period (P<0.05 versus all other groups). CONCLUSIONS: The efficacy of drugs (monotherapy or in combination) most commonly used for neuroprotection during neurovascular surgery is limited. The newly proposed combination therapy (magnesium, tirilazad, and mild hypothermia), which is based on pathophysiological considerations, seems to be a promising alternative for neuroprotection in cerebrovascular surgery.

Adrenal Cortex Hormones↗