Application of nicardipine prolonged-release implants: analysis of 97 consecutive patients with acute subarachnoid hemorrhage.
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Biomedical subjects
Publications and source records attributed to Hans-Jakob Steiger.
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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.
OBJECTIVE: Despite recent advances in neurosurgical resection techniques, radiation therapy, and chemotherapy, malignant gliomas continue to have a dismal prognosis because relapses are unavoidable. METHODS: Dendritic cell vaccination has recently emerged as a promising type of active immunotherapy that aims to induce rather than transfer specific antitumor immune responses in patients. Active immunotherapy is the only type of immunotherapy able to induce immunological memory. RESULTS: Although an increasing number of small clinical trials show safety, feasibility, and immunological and clinical responses, this technology requires further clarification of some critical basic and clinical issues before its presumed place in the treatment of malignant gliomas can be specified. This article addresses the basic and clinical pitfalls that, more than with conventional therapies, may interfere with the potential benefits of this approach. CONCLUSION: Considering the particular mechanisms involved in the immune modulation of tumor biology using dendritic cell-based vaccinations, the authors summarize the arguments in favor of a further, appropriate assessment of this technology.
OBJECT: The extradural anterior petrosectomy approach to the pons and midbasilar artery (mid-BA) has the main disadvantage that the extent of resection of the petrous apex cannot be as minimal as desired given that the surgical target field is not visible during bone removal. Unnecessary or excessive drilling poses the risk of injury to the internal carotid artery, vestibulocochlear organ, and seventh and eighth cranial nerves. The use of a custom-tailored transdural anterior transpetrosal approach can potentially avoid these pitfalls. METHODS: A technique for a transdural anterior petrosectomy was developed in the operating theater and anatomy laboratory. Following a subtemporal craniotomy and basal opening of the dura mater, the vein of Labbé is first identified and protected. Cerebrospinal fluid ([CSF] 50-100 ml) is drained via a spinal catheter. The tent is incised behind the entrance of the trochlear nerve toward the superior petrosal sinus (SPS), which is coagulated and divided. The dura is stripped from the petrous pyramid. Drilling starts at the petrous ridge and proceeds laterally and ventrally. The trigeminal nerve is unroofed. The internal acoustic meatus is identified and drilling is continued laterally as needed. The bone of the Kawase triangle toward the clivus can be removed down to the inferior petrosal sinus if necessary. Anterior exposure can be extended to the carotid artery if required. It is only exceptionally necessary to follow the greater superior petrosal nerve toward the geniculate ganglion and to expose the length of the internal acoustic canal. The modified transdural anterior petrosectomy exposure has been used in nine patients-two with a mid-BA aneurysm, two with a dural arteriovenous fistula, one with a pontine glioma, three with a pontine cavernoma, and one with a pontine abscess. In one patient with a mid-BA aneurysm, subcutaneous CSF collection occurred during the postoperative period. No CSF fistula or approach-related cranial nerve deficit developed in any of these patients. There was no retraction injury or venous congestion of the temporal lobe nor any venous congestion due to the obliteration of the SPS or the petrosal vein. CONCLUSIONS: The custom-made transdural anterior petrosectomy appears to be a feasible alternative to the formal extradural approach.
OBJECT: Vaccination therapy that uses dendritic cells (DCs) is a promising immunotherapeutic approach. However, it relies on intact cellular immunity and efficient generation of mature DCs, both of which can be impaired in patients with glioma. Therefore, the immune status and ex vivo generation of DC in such patients were studied. METHODS: The frequencies of white blood cell subsets and monocyte-derived, mature DCs in patients with high-grade gliomas and healthy control volunteers were analyzed using flow cytometry. In the patients, frequencies of lymphocytes, T cells, and B cells were reduced in comparison with the volunteers in the control group, whereas frequencies of neutrophils and monocytes were increased. There were no differences between the two groups in terms of white blood cell counts or the frequency of NK cells and the major T-cell subsets. The responsiveness of T cells to lectin stimulation was normal. For monocytes, lower frequencies of CD80+ and CD86+ cells but not of CD40+ and HLA-DR+ cells were observed in patients. Ex vivo DC generation in a two-step culture protocol in autologous plasma-supplemented medium or in serum-free medium showed only minor differences in CD80 and HLA-DR expression between the patient and control groups. Frequencies of CD83+, CD1a+, CD14-, CD40+, and CD86+ cells were comparable. Overall, the serum-free medium was superior to the plasma-supplemented medium and allowed efficient ex vivo generation of CD83+, CD1a+, and CD14- mature DCs. CONCLUSIONS: Only minor defects in the immune status of patients with glioma were observed, which probably would not hamper immunotherapy. Mature DCs can be generated successfully in normal numbers and with typical immunophenotypes from monocytes of patients with glioma, particularly under serum-free conditions.
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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.
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.
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OBJECT: The purpose of this study was to determine the predictive value of [18F]fluoroethyl-L-tyrosine (FET)-positron emission tomography (PET) and magnetic resonance (MR) spectroscopy for tumor diagnosis in patients with suspected gliomas. METHODS: Both FET-PET and MR spectroscopy analyses were performed in 50 consecutive patients with newly diagnosed intracerebral lesions supposed to be diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET uptake greater than 1.6 were considered positive, that is, indicative of tumor. Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA) was decreased in conjunction with an absolute increase of choline (Cho) and an NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and signal abnormalities on MR images were compared with histological findings in neuronavigated biopsy specimens. The FET lesion/brain ratio and the NAA/Cho ratio were identified as significant independent predictors for the histological identification of tumor tissue. The accuracy in distinguishing neoplastic from nonneoplastic tissue could be increased from 68% with the use of MR imaging alone to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy. Sensitivity and specificity for tumor detection were 100 and 81% for MR spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological studies did not reveal tumor tissue in any of the lesions that were negative on FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of the lesions that were positive with both methods. CONCLUSIONS: In patients with intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies.
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.
OBJECTIVE: Changes of major cerebral vessels in patients with subarachnoid hemorrhage (SAH) are well known from routine cerebral angiography. Data on changes in the microcirculation do not exist. This study sought to provide a qualitative and quantitative analysis of the cortical microcirculation after SAH. METHODS: By means of orthogonal polarization spectral imaging, a qualitative and quantitative analysis of cortical microcirculation was performed during aneurysm surgery in 3 patients with an incidental intracerebral aneurysm and 10 patients with SAH. Vessel diameters, red blood cell velocity, and functional capillary density were analyzed before and after the aneurysm was clipped. RESULTS: Initial capillary density in patients with an incidental aneurysm was 91.5 +/- 36.5 cm(-1) (mean +/- standard deviation) compared with 30.5 +/- 13.8 in patients with SAH (P < 0.05). In patients with SAH, capillary density increased significantly to 53.9 +/- 29.1 cm(-1) (P < 0.05) during the operation, as did the frequency of venules with a red blood cell velocity greater than 2 mm/s (P < 0.05). No significant change of arteriolar or venular diameters was observed. However, in patients with SAH, mono- and multisegmental microvasospasms in arterioles were observed, with a reduction of vessel diameters up to 75.1%. CONCLUSION: Orthogonal polarization spectral imaging is a suitable method to study cerebral microcirculation during surgery. In patients with SAH, capillary density is significantly decreased and small arteries and arterioles of the cortical surface exhibit vasospasm that cannot be detected by angiography or transcranial Doppler sonography. These changes may contribute to the initial clinical symptoms and may have an influence on the clinical postoperative course.
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