Significance of navigated transcranial magnetic stimulation and tractography to preserve motor function in patients undergoing surgery for motor eloquent gliomas.

Resection of gliomas in or close to motor areas is at high risk for morbidity and development of surgery-related deficits. Navigated transcranial magnetic stimulation (nTMS) including nTMS-based tractography is suitable for presurgical planning and risk assessment. The aim of this study was to investigate the association of postoperative motor status and the spatial relation to motor eloquent brain tissue in order to increase the understanding of postoperative motor deficits. Patient data, nTMS examinations and imaging studies were retrospectively reviewed, corticospinal tracts (CST) were reconstructed with two different approaches of nTMS-based seeding. Postoperative imaging and nTMS-augmented preoperative imaging were merged to identify the relation between motor positive cortical and subcortical areas and the resection cavity. 38 tumor surgeries were performed in 36 glioma patients (28.9% female) aged 55.1 ± 13.8 years. Mean distance between the CST and the lesion was 6.9 ± 5.1 mm at 75% of the patient-individual fractional anisotropy threshold and median tumor volume reduction was 97.7 ± 11.6%. The positive predictive value for permanent deficits after resection of nTMS positive areas was 66.7% and the corresponding negative predictive value was 90.6%. Distances between the resection cavity and the CST were higher in patients with postoperative stable motor function. Extent of resection and distance between resection cavity and CST correlated well. The present study strongly supports preoperative nTMS as an important surgical tool for preserving motor function in glioma patients at risk.

Influence of clinical and tumor-specific factors on the resting motor threshold in navigated transcranial magnetic stimulation.

OBJECTIVE: Preoperative non-invasive mapping of motor function with navigated transcranial magnetic stimulation (nTMS) has become a widely used diagnostic procedure. Determination of the patient-individual resting motor threshold (rMT) is of great importance to achieve reliable results when conducting nTMS motor mapping. Factors which contribute to differences in rMT of brain tumor patients have not been fully investigated. METHODS: We included adult patients with all types of de novo and recurrent intracranial lesions, suspicious for intra-axial brain tumors. The outcome measure was the rMT of the upper extremity, defined as the stimulation intensity eliciting motor evoked potentials with amplitudes greater than 50µV in 50 % of applied stimulations. RESULTS: Eighty nTMS examinations in 75 patients (37.5 % female) aged 57.9 ± 14.9 years were evaluated. In non-parametric testing, rMT values were higher in patients with upper extremity paresis (p = 0.024) and lower in patients with high grade gliomas (HGG) (p = 0.001). rMT inversely correlated with patient age (rs=-0.28, p = 0.013) and edema volume (rs=-0.28, p = 0.012) In regression analysis, infiltration of the precentral gyrus (p<0.001) increased rMT values. Values of rMT were reduced in high grade gliomas (p<0.001), in patients taking Levetiracetam (p = 0.019) and if perilesional edema infiltrated motor eloquent brain (p<0.001). Subgroup analyses of glioma patients revealed similar results. Values of rMT did not differ between hand and forearm muscles. CONCLUSION: Most factors confounding rMT in our study were specific to the lesion. These factors contributed to the variability in cortical excitability and must be considered in clinical work with nTMS to achieve reliable results with nTMS motor mapping.

Assessing the feasibility of mapping the tibialis anterior muscle with navigated transcranial magnetic stimulation in neuro-oncologic patients.

Mapping the lower extremity with navigated transcranial magnetic stimulation (nTMS) still remains challenging for the investigator. Clinical factors influencing leg mapping with nTMS have not been fully investigated yet. The aim of the study was to identify factors which influence the possibility of eliciting motor evoked potentials (MEPs) from the tibialis anterior muscle (TA). Patient records, imaging, nTMS examinations and tractography were retrospectively evaluated. 48 nTMS examinations were performed in 46 brain tumor patients. Reproducible MEPs were recorded in 20 patients (41.67%). Younger age (p = 0.044) and absence of perifocal edema (p = 0.035, Cramer's V = 0.34, OR = 0.22, 95% CI = 0.06-0.81) facilitated mapping the TA muscle. Leg motor deficit (p = 0.49, Cramer's V = 0.12, OR = 0.53, 95%CI = 0.12-2.36), tumor entity (p = 0.36, Cramer's V = 0.22), tumor location (p = 0.52, Cramer's V = 0.26) and stimulation intensity (p = 0.158) were no significant factors. The distance between the tumor and the pyramidal tract was higher (p = 0.005) in patients with successful mapping of the TA. The possibility to stimulate the leg motor area was associated with no postoperative aggravation of motor deficits in general (p = 0.005, Cramer's V = 0.45, OR = 0.63, 95%CI = 0.46-0.85) but could not serve as a specific predictor of postoperative lower extremity function. In conclusion, successful mapping of the TA muscle for neurosurgical planning is influenced by young patient age, absence of edema and greater distance to the CST, whereas tumor entity and stimulation intensity were non-significant.

A spinal epidural abscess due to Streptobacillus moniliformis infection following a rat bite: case report.

The authors describe the case of a 40-year-old man suffering from an epidural abscess in the thoracic spine due to a rarely isolated pathogen, Streptobacillus moniliformis, the causative agent of rat bite fever. Besides diffuse abdominal pain, ataxia, paresthesia, hypesthesia, and enhanced reflexes of the lower extremities, the patient suffered from a decreased sensation of bladder filling. His history was also positive for a rat bite 6 weeks earlier. Magnetic resonance imaging showed an epidural, space-occupying lesion compressing the spinal cord at the vertebral levels of T6-8. Neurosurgery revealed an epidural abscess, which was drained via laminectomy (T-7) and excision of the ligamentum flavum (T6-8). The etiological agent S. moniliformis was identified by 16S rRNA-based polymerase chain reaction and sequencing as well as by culture and mass spectrometry. Treatment with penicillin G led to complete resolution of the abscess and clinical recovery of the patient, who regained his bladder-filling sensation and free walking ability. This case demonstrates that careful attention to the patient's history is essential in suspecting unusual bacterial pathogens as the cause of an epidural abscess and initiating the optimal diagnostic procedure and antimicrobial therapy.

Collision Tumor Composed of Meningioma and Cavernoma.

A true collision tumor is a rare entity composed of two histologically distinct neoplasms coinciding in the same organ. This paper reports a unique case of cerebral collision tumor consisting of two benign components. On the first hand, meningioma which is usually a benign lesion arising from the meningothelial cell in the arachnoidal membrane. On the other, cerebral cavernoma which is a well-circumscribed, benign vascular hamartoma within the brain. To our knowledge, there is no previously documented case of cerebral collision tumor consisting of two benign components. A 56-year-old Caucasian male suffered in 2002 from an atypical meningioma WHO II° located in the left lateral ventricle. Three years after the tumor extirpation, the patient suffered from a hematoma in the fourth ventricle due to a recurrently haemorrhaged cavernoma. In 2008, a recurrence of the tumor in the left lateral ventricle was discovered. Additionally, another tumor located in the quadrigeminal lamina was detected. After surgical resection of the tumor in the left lateral ventricle, the pathological examination confirmed the diagnosis of a collision tumor consisting of components of a meningioma WHO II° and a cavernoma. Postoperatively, no adjuvant treatment was needed and no tumor recurrence is discovered up to the present. A possible explanation for the collision of those two different tumors may be migration of tumor cells mediated by the cerebrospinal fluid. After 5-years of follow-up, there is no sign of any tumor recurrence; therefore, surgical tumor removal without adjuvant therapy seems to be the treatment of choice.

Predictors for Recurrence of Chronic Subdural Hematoma.

AIM: This prospective study was designed to analyze the dependence of different factors on the recurrence rate of chronic subdural hematoma (cSDH) after surgical treatment. MATERIAL AND METHODS: Seventy-three consecutive patients, who were surgically treated at our department due to cSDH between 2009 and 2012, were included. The following parameters were analyzed: patient age and gender, occurrence of trauma, time between trauma and admission, neurological symptoms, presence of minor diseases, intake of anticoagulation medication. We classified the results of diagnostic imaging and determined the space-consuming effect via the cerebral midline shift. In addition, we scrutinized intraoperative findings and the dependence of the position of subdural drainage on the recurrence rate of cSDH. RESULTS: In our patient group, cSDH recurrence was significantly associated with aphasia (p=0.008). Moreover an increased cSDH recurrence rate was observed in the patient group that had a separated manifestation of the cSDH in the preoperative diagnostic imaging (p=0.048) and received no drainage implant (p=0.016). Homogeneous isodense cSDH was associated with no apparent recurrence (p=0.037). CONCLUSION: Within the scope of this study, we detected aphasia and separated cSDH as predictors of cSDH recurrence. Homogeneous isodense cSDH seems to be a good prognostic sign regarding the risk of recurrence development. Furthermore, our data clearly emphasize the importance of surgically applied drainage implants to prevent a recurrence of cSDH.

Aromatase inhibition by 15-deoxy-prostaglandin J(2) (15-dPGJ(2)) and N-(4-hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production.

Inhibition of aromatase activity is an established endocrine therapy in the treatment of hormone-dependent breast cancer. Recent studies on aromatase inhibition by the synthetic retinoid 4HPR, also known as fenretinide, and the PPARgamma agonist 15-dPGJ(2) have implicated a direct receptor-independent, redox-sensitive mechanism of action. The signalling molecule ceramide has also been previously implicated as a negative regulator of aromatase activity. In the present study, we have investigated a potential mediatory role for this sphingolipid during aromatase inhibition by fenretinide and 15-dPGJ(2) in the breast cancer cell line MDA MB 231 and JEG-3 choriocarcinoma cells. 4HPR and 15-dPGJ(2) caused a dose-dependent inhibition of aromatase activity associated with an increase in ceramide production. Both these actions were redox-sensitive as demonstrated by their abrogation in the presence of the anti-oxidant N-acetylcysteine. Exogenous ceramide analogue mimicked these inhibitory actions on aromatase, but in a redox-independent manner. Blockade of the de novo ceramide production pathway by fumonisin B(1) or myriocin inhibited the ceramide responses, but did not prevent aromatase inhibition by 15-dPGJ(2) or 4HPR. This study highlights a potential role for aromatase inhibition and the stress-response signal ceramide during the therapeutic actions of 15-dPGJ(2) and 4HPR in breast cancer treatment. However, these data do not support a mediatory role for this sphingolipid during aromatase inhibition by these agents.

Expression of ether à go-go potassium channels in human gliomas.

Ether à go-go (EAG) K(+) channels have been shown to be involved in tumor generation and malignant growth. Gliomas have not been investigated thus far. Using RT-PCR we investigated healthy human brain and human gliomas of different subtypes and malignancy grades for the expression of human EAG1 and eag-related gene (ERG) 1 channels. mRNA of both channels was detected in all tissues. Expression was strong in normal brain, moderate in high-grade and high in low-grade gliomas. Our findings suggest a differential expression of hEAG1 and hERG1 in gliomas depending on the malignancy grade and nature of the tumor cells. However, the hypothesis that EAG channels are related to the oncogenic process itself is only partly supported by this study.

Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas.

K(+) channels play an important role in glial cell proliferation and are functionally expressed in glial tumors. Because voltage-gated K(+) channel (Kv) subtypes Kv1.3 and Kv1.5 have been shown to contribute to growth-related properties of normal glia rather specifically, we investigated different human glioma samples for the expression of these channel subtypes using reverse transcriptase-PCR. Kv1.5 expression correlated with glioma entities and malignancy grades, i.e. expression was high in astrocytomas, moderate in oligodendrogliomas, and low in glioblastomas. No such correlation was evident for Kv1.3 expression. This study shows a clear differential expression of Kv1.5 in gliomas according to subtype and malignancy grade. This result corresponds to previous data on the expression of voltage-gated sodium channels in gliomas, which likewise showed a low or absent expression of channel subtypes in high-grade tumors.

Prostaglandin J2 metabolites inhibit aromatase activity by redox-sensitive mechanisms: potential implications for breast cancer therapy.

The mechanisms by which prostaglandin (PG)J(2) metabolites inhibit tumorigenicity are poorly understood but may involve thiol reactivity or peroxisome proliferator-activated receptor (PPAR)-dependent pathways. Because aromatase is an important therapeutic target in breast cancer treatment, we have investigated the effect of PGJ(2) metabolites on aromatase activity and evaluated a potential role for redox status during PGJ(2) metabolite action. 15-deoxy-Delta(12,14)PGJ(2) (15d-PGJ(2)) and 9-deoxy-Delta(9,12)13,14-dihydroPGD(2) (Delta(12)PGJ(2)) caused dose-dependent inhibition of both pre-induced aromatase activity in human breast fibroblasts and MDA MB 231 breast cancer cells and of constitutive aromatase activity in JEG-3 choriocarcinoma cells. Structure-activity studies showed that this inhibition was mimicked by 4-cyclopentene-1,3-dione but not by the PPARgamma agonist troglitazone nor the eicosanoids PGE(2) or arachidonic acid. The thiol oxidants diamide and H(2)O(2) simulated the inhibitory action of 15d-PGJ(2) on aromatase activity, whereas the glutathione (GSH) repletor and antioxidant N-acetyl-cysteine (NAC) reversed these actions of 15d-PGJ(2) and H(2)O(2) on aromatase. 15d-PGJ(2) also caused a direct dose-dependent inhibition of aromatase activity in JEG-3 cell sonicates, which was also reversed in the presence of GSH. Kinetic analysis of this 15d-PGJ(2)-induced inhibition of cell-free aromatase indicated the involvement of a non-competitive mechanism possibly resulting from direct thiol-targeted alkylation of the enzyme. These redox-sensitive, PPARgamma-independent actions of 15d-PGJ(2) on aromatase activity demonstrate a novel therapeutic potential for such cyclopentenone PGs in breast cancer treatment.

Molecular characterization of voltage-gated sodium channels in human gliomas.

Voltage-sensitive sodium channels appear to be an electrophysiological hallmark of gliomas. However, the expression of channel subtypes is unclear in these tumors. In this study different gliomas were investigated for the expression of sodium channel subtypes Na(v)1.1, Na(v)1.2, Na(v)1.3, Na(v)1.4, Na(v)1.6, and Na(x)(Na(v)2.1) using RT-PCR. At least one subtype of channels could be detected in each tumor. High-grade gliomas expressed fewer sodium channel subtypes and these at weaker levels than low-grade tumors. Expression of Na(v)1.6, the most abundant isoform in the CNS, was almost absent in the gliomas except the pilocytic variant. Our study gives clear evidence for a differential expression of sodium channel subtypes in gliomas and indicates a predominant expression of channels related to malignancy grades.