Tractography Verified by Intraoperative Magnetic Resonance Imaging and Subcortical Stimulation During Tumor Resection Near the Corticospinal Tract.

BACKGROUND: Tractography is a popular tool for visualizing the corticospinal tract (CST). However, results may be influenced by numerous variables, eg, the selection of seeding regions of interests (ROIs) or the chosen tracking algorithm. OBJECTIVE: To compare different variable sets by correlating tractography results with intraoperative subcortical stimulation of the CST, correcting intraoperative brain shift by the use of intraoperative MRI. METHODS: Seeding ROIs were created by means of motor cortex segmentation, functional MRI (fMRI), and navigated transcranial magnetic stimulation (nTMS). Based on these ROIs, tractography was run for each patient using a deterministic and a probabilistic algorithm. Tractographies were processed on pre- and postoperatively acquired data. RESULTS: Using a linear mixed effects statistical model, best correlation between subcortical stimulation intensity and the distance between tractography and stimulation sites was achieved by using the segmented motor cortex as seeding ROI and applying the probabilistic algorithm on preoperatively acquired imaging sequences. Tractographies based on fMRI or nTMS results differed very little, but with enlargement of positive nTMS sites the stimulation-distance correlation of nTMS-based tractography improved. CONCLUSION: Our results underline that the use of tractography demands for careful interpretation of its virtual results by considering all influencing variables.

Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.

OBJECTIVE: Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery. METHODS: nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions. RESULTS: Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P < 0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization. CONCLUSIONS: Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization.

Positive influence of partial resection on overall survival of patients with overlapping glioblastomas.

OBJECTIVES: Patients with overlapping glioblastomas (former known as gliomatosis cerebri according to the 2007 WHO classification) have a poor prognosis. Most of the patients undergo biopsy to confirm histopathological diagnosis. Treatment comprises chemotherapy, radiation and combination of both. We determined whether resection of the contrast enhancing tumor parts leads to a prolonged survival. PATIENTS AND METHODS: We performed a retrospective analysis and included 31 patients with overlapping glioblastomas (OG) who showed WHO IV in the initial histopathological examination. All patients fulfilled criteria of overlapping glioblastomas in the MRI according to WHO criteria (3 or more lobes were affected). We evaluated Karnofsky performance score (KPS), gender, age, IDH-1_R132H status, MGMT promotor methylation status, proliferation index, postoperative therapy, biopsy vs. partial resection and extent of resection as possible factors affecting overall survival (OAS). A matched pair analysis was performed between the biopsy and resection group on basis of age, KPS and combined radio-chemotherapy. RESULTS: 10 Patients underwent resection of the contrast enhancing tumor parts, 21 patients underwent stereotactic biopsy. All included patients showed contrast enhancing lesions in the MRI. Median age was 61 years in the biopsy-group and 53 in the partial resection (PR) group. We found a significant correlation between OAS and age <50 (p=0.02). Median KPS was 80 in the STX group vs. 100 in the PR group. KPS above 80 was significantly associated with longer OAS (p=0.02). Median survival was 174days in the STX group compared to 446days in the PR group (p=0.05). Also the matched pair analysis showed significant p-values for resection. CONCLUSION: Partial resection might have a positive impact on overall survival of patients with overlapping glioblastomas (former known as gliomatosis cerebri), although the prognosis remains limited.

Noninvasive epicutaneous transfontanelle intracranial pressure monitoring in children under the age of 1 year: a novel technique.

Monitoring of intracranial pressure (ICP) may be indicated in children with traumatic brain injury, premature intraventricular hemorrhage, or hydrocephalus. The standard technique is either a direct measurement with invasive intracranial insertion of ICP probes or indirect noninvasive assessment using transfontanelle ultrasonography to measure blood flow. The authors have developed a new technique that allows noninvasive epicutaneous transfontanelle ICP measurement with standard ICP probes. They compared the ICP measurements obtained using the same type of standard probe used in 2 different ways in 5 infants (age < 1 year) undergoing surgery for craniosynostosis. The first ICP probe was implanted epidurally (providing control measurements) and the second probe was fixed epicutaneously on the skin over the reopened frontal fontanelle. ICP values were measured hourly for the first 24 hours after surgery and the values obtained with the 2 methods were compared using Bland-Altman 2-methods analysis. A total of 110 pairs of measurements were assessed. There was no significant difference between the ICPs measured using the epicutaneous transfontanelle method (mean 13.10 mm Hg, SEM 6.68 mm Hg) and the epidural measurements (mean 12.46 mm Hg, SEM 6.45 mm Hg; p = 0.4643). The results of this analysis indicate that epicutaneous transfontanelle measurement of ICP is a reliable method that allows noninvasive ICP monitoring in children under the age of 1 year. Such noninvasive ICP monitoring could be implemented in the therapy of children with traumatic brain injury or intraventricular hemorrhage or for screening children with elevated ICP without invasive intracranial implantation of ICP probes.

Immature teratoma of the tectum mesencephali with histopathological detection of rudimentary eye anlage in a 3-year-old boy: Report of a rare case.

Intracranial teratoma is a rare neoplasm derived from omnipotent germinal cells that can contain mesoderm, endoderm and/or ectoderm layer tissue. Histologically teratomas are characterized by abnormal structures like teeth or bone that can be further subdivided into mature and immature according to the presence of incompletely differentiated tissue. Characteristic intracranial teratomas are space-occupying lesions in the pineal region and often present with hydrocephalic symptoms due to aqueduct stenosis. A 3-year-old boy presented with a peracute hemiparesis, fatigue and speech deficit. MRI diagnostics showed a cystic, partially solid, inhomogeneous contrast-enhancing formation at the top of the tectum mesencephali with consecutive aqueduct compression. The patient underwent a sub-occipital craniotomy via a supracerebellar approach and complete resection was achieved. The histopathological examination mainly showed mature tissue of ectodermal, mesodermal and endodermal origin. However, small areas of undifferentiated neuroectodermal tissue within an optic vesicle formation were detected, leading to the diagnosis of an immature teratoma. In due course, the patient was discharged in good health without neurological deficits. To our knowledge, optic vesicle-containing intracranial germ cell tumors are extremely rare. Here we report a unique case with immature neuroectodermal tissue within an optic vesicle formation in an otherwise mature teratoma.

CCL2 Chemokine as a Potential Biomarker for Prostate Cancer: A Pilot Study.

PURPOSE: Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa. MATERIALS AND METHODS: Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested. RESULTS: The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading. CONCLUSION: Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.

Chemokines involved in tumor promotion and dissemination in patients with renal cell cancer.

BACKGROUND: Chemokines play a critical role in tumor initiation, progression, and metastasis and have been associated with poor prognosis in diverse malignancies. The prognostic impact of chemokines for renal cell cancer (RCC) remains to be defined. METHODS: Patients diagnosed with RCC and operated between 07/07 and 05/11 were differentially assessed for expression profiles of a series of chemokines and their receptors by RT-qPCR and Western Blot analysis (tumor and adjacent normal tissue, n=37) and by Luminex for corresponding serum expression levels. Results were statistically correlated with clinicopathologic parameters. RESULTS: Gene expression of CCL2, CCR7, CXCL12, CXCR3, CXCR5 and CX3CL1 chemokines was significantly down-regulated in tumor compared to normal tissue. The gene profile for CCR6 was positively correlated with tumor size and stage. A positive linear correlation was found between CXCL12 and tumor stage as well as between CX3CR1 and C-reactive protein. In contrast to clear cell RCCs those of a chromophobe type showed a significantly down-regulated gene expression for CCR6, CCL20, and CXCL12. The CXCR7 serum level was significantly increased in patients with tumor-related mortality during postoperative follow-up. CONCLUSIONS: Chemokines may serve as novel diagnostic and prognostic biomarkers for RCC. Studies on larger collectives are required for further assessment of potential clinical application.