Trabectedin has promising antineoplastic activity in high-grade meningioma.

BACKGROUND: Meningiomas are common intracranial tumors arising from the meninges and usually are benign. However, a few meningiomas have aggressive behavior and, for such patients, effective treatment options are needed. Trabectedin is a novel, marine-derived, antineoplastic agent that has been approved and is used routinely as therapy for advanced soft tissue sarcoma and ovarian cancer. METHODS: The authors investigated the in vitro effects of trabectedin alone and in combination with hydroxyurea, cisplatin, and doxorubicin in primary cell cultures of benign (n = 9), atypical (n = 6), and anaplastic (n = 4) meningiomas using chemosensitivity assays (3-[4,5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT]), Western blot analysis, cell cycle analysis, and immunofluorescent staining. RESULTS: Strong antimeningioma activity of trabectedin was observed and was characterized by distinct cell cycle arrest, down-regulation of multiple cyclins, deregulated expression of cell death-regulatory genes, and massive apoptosis induction. Cytotoxic activity was especially intense in higher grade meningiomas with a half-maximal inhibitory concentration <10 nM. Combination with trabectedin synergistically enhanced the antimeningioma activity of hydroxyurea but also enhanced the activity of doxorubicin and cisplatin. On the basis of these findings, trabectedin was given to 1 patient who had heavily pretreated, anaplastic meningioma, and a favorable response was observed with radiologic disease stabilization, marked reductions in brain edema and requirement for corticosteroids, and improvement of clinical symptoms. However, treatment had to be discontinued after 5 cycles because of adverse drug effects. CONCLUSIONS: The current results indicated that trabectedin may represent a promising new therapeutic option for patients with aggressive meningioma and should be evaluated in prospective clinical studies.

Susceptibility-weighted imaging at 7 T: Improved diagnosis of cerebral cavernous malformations and associated developmental venous anomalies.

BACKGROUND AND AIM: In the diagnosis of cerebral cavernous malformations (CCMs) magnetic resonance imaging is established as the gold standard. Conventional MRI techniques have their drawbacks in the diagnosis of CCMs and associated venous malformations (DVAs). The aim of our study was to evaluate susceptibility weighted imaging SWI for the detection of CCM and associated DVAs at 7 T in comparison with 3 T. PATIENTS AND METHODS: 24 patients (14 female, 10 male; median age: 38.3 y (21.1 y-69.1 y) were included in the study. Patients enrolled in the study received a 3 T and a 7 T MRI on the same day. The following sequences were applied on both field strengths: a T1 weighted 3D GRE sequence (MP-RAGE) and a SWI sequence. After obtaining the study MRIs, eleven patients underwent surgery and 13 patients were followed conservatively or were treated radio-surgically. RESULTS: Patients initially presented with haemorrhage (n = 4, 16.7%), seizures (n = 2, 8.3%) or other neurology (n = 18, 75.0%). For surgical resected lesions histopathological findings verified the diagnosis of CCMs. A significantly higher number of CCMs was diagnosed at 7 T SWI sequences compared with 3 T SWI (p < 0.05). Additionally diagnosed lesions on 7 T MRI were significantly smaller compared to the initial lesions on 3 T MRIs (p < 0.001). Further, more associated DVAs were diagnosed at 7 T MRI compared to 3 T MRI. CONCLUSION: SWI sequences at ultra-high-field MRI improve the diagnosis of CCMs and associated DVAs and therefore add important pre-operative information.

Contrast-enhanced, high-resolution, susceptibility-weighted magnetic resonance imaging of the brain: dose-dependent optimization at 3 tesla and 1.5 tesla in healthy volunteers.

OBJECTIVES: We sought to determine the optimal dose of a contrast agent with known high relaxivity on 1.5 and 3 Tesla scanners that would achieve the best compromise between image quality and scan time for the clinical application of contrast-enhanced susceptibility-weighted imaging (CE-SWI). METHODS: Pre- and postcontrast SWI was performed with different contrast agent doses (0.05, 0.1, and 0.2 mmol/kg gadobenate dimeglumine) at both 1.5 and 3 T in 6 healthy volunteers, resulting in 72 examinations. Venograms were created from minimum intensity projection reconstructions over specified deep white matter volumes to enhance the visual appearance of connected venous structures. Three independent radiologists blindly rated the visibility of the veins on a continuous scale of 1 to 10. A general linear model was used for statistical evaluation, with fixed effects of the contrast agent dose, the field strength, the rater and the patients as a random effect. RESULTS: With CE-SWI, we found significant differences in the visibility of the deep veins dependent on the contrast media dose (P=0.02). At 3 T, the visibility of deep venous vessels, with regard to susceptibility effect, image quality, and scan time reduction after a standard contrast agent dose 0.1 mmol/kg was significantly better than that achieved with 0.05 mmol/kg. The visibility was considered equal with 0.1 mmol/kg of the contrast agent to the precontrast images and a dose of 0.2 mmol/kg. At 1.5 T, no significant difference was found between the 4 contrast agent doses. We found no difference in the visibility of the veins with the shorter sequences at 3 T compared with the sequences at 1.5 T. CONCLUSIONS: Only a standard dose (0.1 mmol/kg) of gadobenate dimeglumine is required to achieve the optimum susceptibility effect and image quality at 3 T, together with a reduced scan time. This result can be attributed to the higher relaxivity of gadobenate dimeglumine, compared with conventional gadolinium chelates.

Endoscopic anterior cervical foraminotomy for unilateral radiculopathy: anatomical morphometric analysis and preliminary clinical experience.

OBJECT: Cervical radiculopathy is typically caused by posterolateral disc herniation or spondylotic foraminal stenosis, either of which may compress the ventral aspect of the nerve root. The authors undertook a study to establish the feasibility of performing an endoscopic approach for anterior cervical foraminotomy (ACFor) in a clinical setting. METHODS: Application of this method on cadavers was conducted to verify the practicability of this technique. The clinical study included 16 patients (eight men and eight women; mean age 46.6 years) all presenting with unilateral radicular symptoms (one at two adjacent ipsilateral levels), which were associated with various degrees of neck pain. Disc herniations and/or uncovertebral osteophytes were confirmed on magnetic resonance imaging and high-resolution computerized tomography scanning. A total of 17 endoscopic ACFors (one two-level procedure) were performed using a rigid glass endoscope (25 degrees angled, 3-mm diameter, 10-mm length) mounted on a tubular retractor. No major surgery-related complications were encountered. During a mean follow-up period of 13.8 months an average absolute improvement of 44% (p > 0.05) in the neck disability index score and of 96% (p > 0.05) in the visual analog scale score for radicular pain (compared with the preoperative score) was observed. During the follow-up period strength improved to normal in 84% and sensory deficit in 80% of the patients. The overall subjective patient satisfaction rate was 87.6%; the return-to-work rate after 4 weeks was 81.4%. CONCLUSIONS: The advantages of endoscopic ACFor include minimial surgical exposure, improved intraoperative visualization, direct decompression of the nerve root, and the preservation of the intervertebral disc and the motion segment.

Social and economic outcome after posterior microforaminotomy for cervical spondylotic radiculopathy.

Between 1993 and 1998, the surgical technique of posterior cervical foraminotomy as described by Frykholm, with individual cervical nerve root decompression had been applied at the Neurosurgical Department of the University of Vienna. We conducted a retrospective study to assess the functional and socio-economic outcome. Thirty-two patients were included in this study, 21 men and 11 women with a median age of 48 years (range 30 to 70 years). Prior to surgical management, median duration of symptoms had been 7 weeks (range 1-50 weeks), with cervicobrachialgia in 28 of the patients, 27 of the patients had sustained radicular sensory loss, and in 25 of the patients radicular paresis occurred. Measured by the Prolo Functional Economic Outcome Rating Scale, 64% of the patients were classified with a good outcome (scale 8-10), 18% of the patients were classified with a moderate outcome (scale 5-7), and 18% of the patients were classified with a poor outcome (scale < 5). Two of the patients required additional anterior cervical discectomy and one patient suffered a superficial wound infection which needed surgical drainage. This study confirms that posterior microforaminotomy is a useful technique for degenerative disease causing cervical radiculopathy with the advantage of avoiding fusion and immobilisation. Criteria for evaluating the results of treating cervical spinal disorders vary widely. Comparative analyses of outcome among different therapy protocols are compromised by the diversity among the groups studied, as well as by the varying methods of measuring success. We propose a scale based on the socio-economic and functional status of the patient before and after treatment This scale is easily applicable and can delineate pre- and postoperative conditions of patients. A more universal acceptance of common criteria for judging the outcome of spinal operations should facilitate comparisons among various methods of treatment.

Traumatic arteriovenous fistula of the vertebral artery.

A 22-year-old woman sustained a stab wound injury of the right vertebral artery. Initial treatment with endovascular embolization using platinum coils in a local hospital could not stop the bleeding. The patient was transferred to our department in hypovolemic shock. Further angiography revealed an arteriovenous fistula. Open surgical revision occluded the vertebral artery and the patient recovered without neurological deficit.