Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for ...treatment or prophylaxis of central nervous system infections are rare. Six patients suffering subarachnoid hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were included in this study. Free interstitial concentrations of cefuroxime after intravenous application of 1,500 mg were measured by microdialysis in brain tissue, as well as in plasma at steady-state (
= 6) or after single-dose administration (
= 1). At steady state, free area under the concentration-time curve from 0 to 24 h (AUC
) values of 389.0 ± 210.3 mg/liter·h and 131.4 ± 72.8 mg/liter·h were achieved for plasma and brain, respectively, resulting in a brain tissue penetration ratio (AUC
/AUC
) of 0.33 ± 0.1. Plasma and brain tissue concentrations at individual time points correlated well (
= 0.59,
= 0.001). At steady-state time over MIC (
>MIC) values of >40% of dosing interval were achieved up to an MIC of 16 mg/liter for plasma and 4 mg/liter for brain tissue. Although MIC
values could not be achieved in brain tissue for relevant bacteria, current dosing strategies of cefuroxime might be sufficient to treat pathogens with MIC values up to 4 mg/liter. The activity of cefuroxime in brain tissue might be overestimated when relying exclusively on plasma levels. Although currently insufficient data after single dose administration exist, lower brain-plasma ratios observed after the first dose might warrant a loading dose for treatment and perioperative prophylaxis.
The management of ruptured C6 aneurysms remains controversial. Detailed long-term outcome data are still lacking. Thus the present study provided a detailed long term follow-up for a ...multidisciplinary approach combining microsurgical clipping, endovascular embolisation and parent artery occlusion with/without bypass protection.
In our single centre analysis of 64 consecutive patients, indications for microsurgery were: superior aneurysm projection, giant/large or wide necked aneurysms and aneurysms at branching sites. Indications for embolisation were: narrow necks, neck calcification, close aneurysm relation to the clinoid process or adhesion to the distal dural ring, and aneurysm location in the concavity of the carotid siphon curve.
23 patients (35.9%) underwent microsurgery, 38 patients (59.4%) embolisation and three patients (4.7%) parent artery occlusion under bypass protection. Retreatment was required in 20.9% (surgery 8.7%, endovascular 31.6%). Procedure related transient complications occurred in 10.9% (surgery 13.0%, endovascular 10.5%). Procedure related permanent morbidities occurred in 6.3% (surgery 8.7%, endovascular 5.3%), including visual deficits in 4.7% (surgery 4.4%, endovascular 5.3%). One endovascular patient died. Angiographic follow-up (29.2 (SD 31.9) months) revealed total aneurysm occlusion in 94.4% of the surgical and 82.9% of the endovascular patients. Clinical follow-up (58.7 (SD 47.6) months) showed 73.4% of the population reaching Glasgow Outcome Scale 4-5, these data being equivalent to the International Subarachnoid Aneurysm Trial (ISAT) outcomes.
Based on favourable neuroradiological and ophthalmological outcomes, microsurgery is recommended for superiorly projecting aneurysms, especially aneurysms involving the ophthalmic artery, and for giant/large or wide necked aneurysms. Based on stable aneurysm occlusion and excellent clinical outcomes, embolisation can be recommended for inferiorly/medially projecting small, narrow necked aneurysms.
miR-200a has been implicated in the pathogenesis of meningiomas, one of the most common central nervous system tumors in humans. To identify how miR-200a contributes to meningioma pathogenesis at the ...molecular level, we used a comparative protein profiling approach using Gel-nanoLC-MS/MS and identified approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma cells. Following the bioinformatic analysis to identify potential genes targeted by miR-200a, we focused on the non-muscle heavy chain IIb (NMHCIIb), and showed that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in cell division and cell migration, we aimed to identify whether miR-200a regulated these processes through NMHCIIb. We found that NMHCIIb overexpression partially rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression resulted in a similar migration phenotype in these cells and inhibited meningioma tumor growth in mice. Taken together, these results suggest that NMHCIIb might serve as a novel therapeutic target in meningiomas.
This report describes the management of a fusiform peripheral middle cerebral artery aneurysm by endovascular parent artery occlusion under bypass protection. Localization of the recipient cortical ...artery was accomplished after craniotomy by superselective injection of diluted ICG dye via a microcatheter positioned proximal to the aneurysm. This report demonstrates that superselective ICG angiography can be a beneficial alternative technique to identify the best anastomosis site intraoperatively.
The aim of this study was the evaluation of the normal sellar anatomy in vitro and in vivo with high-field MRI and its application in the diagnosis of sellar pathologies in comparison to standard ...MRI.
All high-field MR images were obtained using a 3
T Bruker Medspec 30/80 Scanner with a head birdcage transmit/receive coil and an actively shielded gradient system with a maximum gradient strength of 45
mT/m. Firstly an in vitro study of the sella turcica was performed to depict normal pituitary and sellar anatomy at high field. After a pilot-study this sequence-protocol was established: A RARE sequence (TR/TE = 7790/19
ms; matrix size, 512 × 512; RARE factor = 8, FOV, 200
mm) was used for T2-weighted coronal, axial and sagittal images. A 3D gradient echo sequence with magnetization-preparation (MP-RAGE, TR/TE/TI = 33.5/7.6/800
ms, matrix size, 512 × 512; FOV, 200
mm, effective slice thickness, 1.88
mm; 3 averages) was used for acquisition of T1-weighted pre- and post-contrast images. Between January 2002 and March 200458 patients were enrolled in this study. Seven patients were examined for suspected microadenoma and in 51 patients 3T MRI was used to obtain additional information about the sellar lesion already known to be present from standard MRI.
In 21 cases the accuracy of the imaging findings was assessed afterwards by comparison with intraoperative findings. The infiltration of the medial cavernous sinus wall was suspected on standard MRI on 15 sides (47%), on high-field MRI on 9 sides (28%) and could be verified by intraoperative findings on 6 sides (19%). Accordingly, sensitivity to infiltration was 83% for 3
T and 67% for standard MRI. Specificity was 84% for 3
T and 58% for standard MRI. Moreover, high-field MRI revealed microadenomas in 7 patients with a median diameter of 4
mm (range 2–9
mm). The segments of the cranial nerves were seen as mean 4 hypointense spots (range 2–5 spots) on high-field MRI in contrast to 3 spots (range 0–4 spots) on standard MRI. This difference was considerably significant (
P < 0.001, Wilcoxon rank sum test). The histopathological results revealed pituitary adenoma in 16 patients and non-adenomatous sellar pathologies such as Rathke's cleft cyst, sarcoidosis, meningeoma and metastasis in 5 patients.
High-field MRI is superior to standard MRI for the prediction of invasion of adjacent structures in patients with pituitary adenomas and improves surgical planning of sellar lesion.
Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for ...cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.
•First investigation about possible ultra highfield MR benefits for studying cognitive networks•Ultra highfield benefits for cognitive Network activations depend on the brain area.•High field (3T) and ultra high field (7T) first hand comparison
Objectives: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor ...cortex stimulation (MCS). Methods: Twenty two patients (10 males, 12 females, mean age 39 years, range 10–65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. Results: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). Conclusions: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.
The purpose of this work was to demonstrate susceptibility effects (SusE) in various types of brain tumors with 3T high-resolution (HR)-contrast-enhanced (CE)-susceptibility-weighted (SW)-MR imaging ...and to correlate SusE with positron-emission tomography (PET) and histopathology.
Eighteen patients with brain tumors, scheduled for biopsy or tumor extirpation, underwent high-field (3T) MR imaging. In all of the patients, an axial T1-spin-echo (SE) sequence and an HR-SW imaging sequence before and after IV application of a standard dose of contrast agent (MultiHance) was obtained. Seven patients preoperatively underwent PET. The frequency and formation of intralesional SusE in all of the images were evaluated and correlated with tumor grade as determined by PET and histopathology. Direct correlation of SusE and histopathologic specimens was performed in 6 patients. Contrast enhancement of the lesions was assessed in both sequences.
High-grade lesions demonstrated either high or medium frequency of SusE in 90% of the patients. Low-grade lesions demonstrated low frequency of SusE or no SusE. Correlation between intralesional frequency of SusE and histopathologic, as well as PET, tumor grading was statistically significant. Contrast enhancement was equally visible in both SW and SE sequences. Side-to-side comparison of tumor areas with high frequency of SusE and histopathology revealed that intralesional SusE reflected conglomerates of increased tumor microvascularity.
3T HR-CE-SW-MR imaging shows both intratumoral SusE not visible with standard MR imaging and contrast enhancement visible with standard MR imaging. Because frequency of intratumoral SusE correlates with tumor grade as determined by PET and histopathology, this novel technique is a promising tool for noninvasive differentiation of low-grade from high-grade brain tumors and for determination of an optimal area of biopsy for accurate tumor grading.
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