Jacobus J. van Overbeeke

Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review

We did a systematic review to address the added value of intraoperative MRI (iMRI)-guided resection of glioblastoma multiforme compared with conventional neuronavigation-guided resection, with respect to extent of tumour resection (EOTR), quality of life, and survival. 12 non-randomised cohort studies matched all selection criteria and were used for qualitative synthesis. Most of the studies included descriptive statistics of patient populations of mixed pathology, and iMRI systems of varying field strengths between 0·15 and 1·5 Tesla. Most studies provided information on EOTR, but did not always mention how iMRI affected the surgical strategy. Only a few studies included information on quality of life or survival for subpopulations with glioblastoma multiforme or high-grade glioma. Several limitations and sources of bias were apparent, which affected the conclusions drawn and might have led to overestimation of the added value of iMRI-guided surgery for resection of glioblastoma multiforme. Based on the available literature, there is, at best, level 2 evidence that iMRI-guided surgery is more effective than conventional neuronavigation-guided surgery in increasing EOTR, enhancing quality of life, or prolonging survival after resection of glioblastoma multiforme.

Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects

OBJECT In large vestibular schwannoma (VS), microsurgery is the main treatment option, and complete resection is considered the primary goal. However, previous studies have documented suboptimal facial nerve outcomes in patients who undergo complete resection of large VSs. Subtotal resection is likely to reduce the risk of facial nerve injury but increases the risk of lesion regrowth. Gamma Knife surgery (GKS) can be performed to achieve long-term growth control of residual VS after incomplete resection. In this study the authors report on the results in patients treated using planned subtotal resection followed by GKS with special attention to volumetric growth, control rate, and symptoms. METHODS Fifty consecutive patients who underwent the combined treatment strategy of subtotal microsurgical removal and GKS for large VSs between 2002 and 2009 were retrospectively analyzed. Patients with neurofibromatosis Type 2 were excluded. Patient charts were reviewed for clinical symptoms. Audiograms were evaluated to classify hearing pre- and postoperatively. Preoperative and follow-up contrast-enhanced T1-weighted MR images were analyzed using volume-measuring software. RESULTS Surgery was performed via a translabyrinthine (25 patients) or retrosigmoid (25 patients) approach. The median follow-up was 33.8 months. Clinical control was achieved in 92% of the cases and radiological control in 90%. One year after radiosurgery, facial nerve function was good (House-Brackmann Grade I or II) in 94% of the patients. One of the two patients who underwent surgery to preserve hearing maintained serviceable hearing after resection followed by GKS. CONCLUSIONS Considering the good tumor growth control and facial nerve function preservation as well as the possibility of preserving serviceable hearing and the low number of complications, subtotal resection followed by GKS can be the treatment option of choice for large VSs.

Gamma knife radiosurgery for vestibular schwannomas: Results of hearing preservation in relation to the cochlear radiation dose

This study was designed to evaluate hearing preservation after gamma knife radiosurgery (GKRS) and to determine the relation between hearing preservation and cochlear radiation dose in patients with a sporadic vestibular schwannoma (VS).

Management of large vestibular schwannoma. Part II. Primary Gamma Knife surgery: radiological and clinical aspects

OBJECT In large vestibular schwannomas (VSs), microsurgery is the main treatment option. A wait-and-scan policy or radiosurgery are generally not recommended given concerns of further lesion growth or increased mass effect due to transient swelling. Note, however, that some patients do not present with symptomatic mass effect or may still have serviceable hearing. Moreover, others may be old, suffer from severe comorbidity, or refuse any surgery. In this study the authors report the results in patients with large, growing VSs primarily treated with Gamma Knife surgery (GKS), with special attention to volumetric growth, control rate, and symptoms. METHODS The authors retrospectively analyzed 33 consecutive patients who underwent GKS for large, growing VSs, which were defined as > 6 cm(3) and at least indenting the brainstem. Patients with neurofibromatosis Type 2 were excluded from analysis, as were patients who had undergone previous treatment. Volume measurements were performed on contrast-enhanced T1-weighted MR images at the time of GKS and during follow-up. Medical charts were analyzed for clinical symptoms. RESULTS Radiological growth control was achieved in 88% of cases, clinical control (that is, no need for further treatment) in 79% of cases. The median follow-up was 30 months, and the mean VS volume was 8.8 cm(3) (range 6.1-17.7 cm(3)). No major complications occurred, although ventriculoperitoneal shunts were placed in 2 patients. The preservation of serviceable hearing and facial and trigeminal nerve function was achieved in 58%, 91%, and 86% of patients, respectively, with any facial and trigeminal neuropathy being transient. In 92% of the patients presenting with trigeminal hypesthesia before GKS, the condition resolved during follow-up. No patient- or VS-related feature was correlated with growth. CONCLUSIONS Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling.

Chordoma: the entity

Chordomas are malignant tumors of the axial skeleton, characterized by their locally invasive and slow but aggressive growth. These neoplasms are presumed to be derived from notochordal remnants with a molecular alteration preceding their malignant transformation. As these tumors are most frequently observed on the skull base and sacrum, patients suffering from a chordoma present with debilitating neurological disease, and have an overall 5-year survival rate of 65%. Surgical resection with adjuvant radiotherapy is the first-choice treatment modality in these patients, since chordomas are resistant to conventional chemotherapy. Even so, management of chordomas can be challenging, as chordoma patients often present with recurrent disease. Recent advances in the understanding of the molecular events that contribute to the development of chordomas are promising; the most novel finding being the identification of brachyury in the disease process. Here we present an overview of the current paradigms and summarize relevant research findings.

Intraobserver and Interobserver Agreement in Volumetric Assessment of Glioblastoma Multiforme Resection

BACKGROUND:The role of extent of tumor resection in improving outcome for patients with glioblastoma multiforme (GBM) is still under debate. OBJECTIVE:To analyze intraobserver and interobserver agreement of manual segmentation as a method for volumetric assessment of GBM resection. METHODS:Three observers performed volumetric assessment of preoperative tumor volume (PreTV) and postoperative tumor volume (PostTV) by manual segmentation on contrast-enhanced T1-weighted MRI data sets of 8 patients. Measurements were repeated after a minimum interval of 2 weeks. Intraobserver and interobserver agreement for PreTV, PostTV, and residual tumor volume (RTV) percentage were expressed in intraclass correlation coefficients (ICCs). RESULTS:Intraobserver agreement is high for PreTV (ICC = 0.99), PostTV (ICC = 0.73-0.94), and RTV (ICC = 0.89-0.94). Interobserver agreement is high for PreTV (ICC = 0.97), but low for PostTV (ICC = 0.54) and RTV (ICC = 0.52). CONCLUSION:Postoperative assessment of GBM volume seems to offer high intraobserver agreement, but low interobserver agreement. Using absolute RTV values to relate extent of tumor resection with survival may be unreliable. More research is needed before this method can be used as a valid end point for clinical studies. Computer-assisted tumor volume calculation may increase interobserver agreement in the future.

Neuromodulation in Psychiatric Disorders

Psychiatric disorders are worldwide a common cause of severe and long-term disability and socioeconomic burden. The management of patients with psychiatric disorders consists of drug therapy and/or psychotherapy. However, in some patients, these treatment modalities do not produce sufficient therapeutic effects or induce intolerable side effects. For these patients, neuromodulation has been suggested as a potential treatment modality. Neuromodulation includes deep brain stimulation, vagal nerve stimulation, and transcranial magnetic and electrical stimulation. The rationale for neuromodulation is derived from the research identifying neurobiologically localized substrates for refractory psychiatric symptoms. Here, we review the clinical data on neuromodulation in the major psychiatric disorders. Relevant data from animal models will also be discussed to explain the neurobiological basis of the therapy.

Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: A randomized controlled trial

Background: Although the added value of increasing extent of glioblastoma resection is still debated, multiple technologies can assist neurosurgeons in attempting to achieve this goal. Intraoperative magnetic resonance imaging (iMRI) might be helpful in this context, but to date only one randomized trial exists. Methods: We included 14 adults with a supratentorial tumor suspect for glioblastoma and an indication for gross total resection in this randomized controlled trial of which the interim analysis is presented here. Participants were assigned to either ultra-low-field strength iMRI-guided surgery (0.15 Tesla) or to conventional neuronavigation-guided surgery (cNN). Primary endpoint was residual tumor volume (RTV) percentage. Secondary endpoints were clinical performance, health-related quality of life (HRQOL) and survival. Results: Median RTV in the cNN group is 6.5% with an interquartile range of 2.5-14.75%. Median RTV in the iMRI group is 13% with an interquartile range of 3.75-27.75%. A Mann-Whitney test showed no statistically significant difference between these groups (P =0.28). Median survival in the cNN group is 472 days, with an interquartile range of 244-619 days. Median survival in the iMRI group is 396 days, with an interquartile range of 191-599 days (P =0.81). Clinical performance did not differ either. For HRQOL only descriptive statistics were applied due to a limited sample size. Conclusion: This interim analysis of a randomized trial on iMRI-guided glioblastoma resection compared with cNN-guided glioblastoma resection does not show an advantage with respect to extent of resection, clinical performance, and survival for the iMRI group. Ultra-low-field strength iMRI does not seem to be cost-effective compared with cNN, although the lack of a valid endpoint for neurosurgical studies evaluating extent of glioblastoma resection is a limitation of our study and previous volumetry-based studies on this topic.

A comparison of cell-cycle markers in skull base and sacral chordomas

OBJECTIVE Despite refinement of surgical techniques and adjuvant radiotherapy, the prognosis for patients with a chordoma remains poor. Identification of prognostic factors related to tumor biology might improve this assessment and result in molecular markers for targeted therapy. Limited studies have been performed to unravel the impact of cell-cycle markers in chordoma, and those performed have shown inconclusive results. In the current study, we aimed to discover the impact of cyclin-dependent kinase 4 (CDK4) expression and its relation to prognosis and other cell-cycle markers in chordoma. METHODS Twenty-five human formalin-fixed, paraffin-embedded chordoma specimens were examined by immunohistochemistry for the expression of CDK4, protein 53 (p53), and murine double minute 2 (MDM2). The MIB-1 labeling index and mitotic index were used for the examination of proliferation. We collected detailed demographic and clinical data. RESULTS Overexpression of CDK4, p53, and MDM2 was found in five (20%), seven (28%), and 14 (56%) of the cases, respectively. All three cell-cycle markers showed a significant correlation with MIB1 labeling index. Expression of CDK4 (P = 0.02) and p53 (P < 0.01) were both significantly correlated with poor overall survival. Also, histologically observed necrosis (P < 0.05) and a dedifferentiated tumor subtype (P < 0.01) were related to adverse patient outcome. CONCLUSION Our results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.

Assessment and Imaging of the Cerebrovascular Glycocalyx

The glycocalyx is a gel-like layer lining the luminal surface of the endothelium. The glycocalyx exerts an important barrier role because it prevents exposure of plasma components to the endothelial surface. Disruption of the glycocalyx by local inflammation or ischemia results in decreased glycocalyx thickness which is associated with a number of vascular diseases. The cerebrovascular glycocalyx has sparsely been studied, but is of great interest because of its potential role in cerebrovascular disease. In this review, we describe all existing techniques to visualize the glycocalyx and designate techniques that may be suitable for studying the cerebrovascular glycocalyx. A total of seven imaging techniques are discussed thoroughly, including transmission electron microscopy, intravital microscopy, micro-particle image velocimetry, confocal laser scanning microscopy, two-photon laser scanning microscopy, orthogonal polarization spectral imaging and sidestream dark field/oblique imaging. Measurement of serum concentrations of glycocalyx-specific constituents is another method for glycocalyx analysis. Also, we have reviewed the methods of glycocalyx analysis by using these imaging techniques. So far, the cerebrovascular glycocalyx has only been studied in vitro. However, other cerebral microcirculatory properties have been studied in vivo. This suggests that the cerebrovascular glycocalyx can be studied in vivo by using some of the described techniques, when specific software is subjoined to the analysis. In conclusion, we have summarized techniques available for glycocalyx assessment, and explained the significance and technical possibilities regarding cerebrovascular glycocalyx visualization. Cerebrovascular glycocalyx assessment would add valuable information to our understanding of the pathophysiology of cerebrovascular disease. Moreover, as a part of the blood-brain barrier, more knowledge on the cerebrovascular glycocalyx may lead to better understanding of neurodegenerative conditions that are caused by a compromised blood-brain barrier including Alzheimer`s disease, vascular dementia, multiple sclerosis and epilepsy.