Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Objective: The vagus nerve has important immunological functions that may be relevant for its anticonvulsive action. We postulate that this anticonvulsive action is activated by a shift in the immune system resulting in a reduction of neurotoxic and an increase of neuroprotective tryptophan metabolites. Methods: Eleven patients with refractory epilepsy and 11 controls matched for age and gender were included in this study. The primary outcome measure was a 50% seizure reduction. Other variables were pro-inflammatory cytokines IL-6 and TNF-alpha, anti-inflammatory cytokine IL-10, cortisol, and the tryptophan metabolites 3-hydroxykynurenine (3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled during baseline, and in week 28 of add-on treatment. Results: IL-6 levels were higher in the responders than in the control group, and decreased after vagus nerve stimulation (VNS), whereas IL-10 was low and increased after VNS. In nonresponders, VNS resulted in an increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol concentrations are higher in the epilepsy group than in the control group. After VNS, these concentrations decreased. The concentrations of the tryptophan metabolites were lower in the epilepsy group than in the control group. The KYNA ratios are defined as the ratio of neuroprotective KYNA versus neurotoxic 3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were lower in epilepsy patients than in controls, and they both moderately increased after VNS. Conclusion: The outcome of this preliminary study indicates that VNS causes a rebalancing of the immune system. This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels. Copyright (C) 2010 S. Karger AG, Base

Implementation of a mobile 0.15-T intraoperative MR system in pediatric neuro-oncological surgery: feasibility and correlation with early postoperative high-field strength MRI

INTRODUCTION: We analyze our preliminary experience using the PoleStar N20 mobile intraoperative MR (iMR) system as an adjunct for pediatric brain tumor resection. METHODS: We analyzed 11 resections in nine children between 1 month and 17 years old. After resection, we acquired iMR scans to detect residual tumor and update neuronavigation. We compared final iMR interpretation by the neurosurgeon with early postoperative MR interpretation by a neuroradiologist. RESULTS: Patient positioning was straightforward, and image quality (T1 7-min 4-mm sequences) sufficient in all cases. In five cases, contrast enhancement suspect for residual tumor was noted on initial postresection iMR images. In one case, a slight discrepancy with postoperative imaging after 3 months was no longer visible after 1 year. No serious perioperative adverse events related to the PoleStar N20 were encountered, except for transient shoulder pain in two. CONCLUSIONS: Using the PoleStar N20 iMR system is technically feasible and safe for both supra- and infratentorial tumor resections in children of all ages. Their small head and shoulders favor positioning in the magnet bore and allow the field of view to cover more than the area of primary interest, e.g., the ventricles in an infratentorial case. Standard surgical equipment may be used without significant limitations. In this series, the use of iMR leads to an increased extent of tumor resection in 45 % of cases. Correlation between iMR and early postoperative MR is excellent, provided image quality is optimal and interpretation is carefully done by someone sufficiently familiar with the system

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

BACKGROUND: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. METHODS: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care. RESULTS: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. CONCLUSION: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial

The lumbosacral angle does not reflect progressive tethered cord syndrome in children with spinal dysraphism

Purpose: Our goal was to validate the hypothesis that the lumbosacral angle (LSA) increases in children with spinal dysraphism who present with progressive symptoms and signs of tethered cord syndrome (TCS), and if so, to determine for which different types and/or levels the LSA would be a valid indicator of progressive TCS. Moreover, we studied the influence of surgical untethering and eventual retethering on the LSA. Methods: We retrospectively analyzed the data of 33 children with spinal dysraphism and 33 controls with medulloblastoma. We measured the LSA at different moments during follow-up and correlated this with progression in symptomatology. Results: LSA measurements had an acceptable intra- and interobserver variability, however, some children with severe deformity of the caudal part of the spinal column, and for obvious reasons those with caudal regression syndrome were excluded. LSA measurements in children with spinal dysraphism were significantly different from the control group (mean LSA change, 21.0° and 3.1° respectively). However, both groups were not age-matched, and when dividing both groups into comparable age categories, we no longer observed a significant difference. Moreover, we did not observe a significant difference between 26 children with progressive TCS as opposed to seven children with stable TCS (mean LSA change, 20.6° and 22.4° respectively). Conclusions: We did not observe significant differences in LSA measurements for children with clinically progressive TCS as opposed to clinically stable TCS. Therefore, the LSA does not help the clinician to dete

Confirmation of a metastasis-specific microRNA signature in primary colon cancer

The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (l et-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate m iR-30b expression with axon guidance and l et-7i expression with cell adhesion, migration, and motility

Increased Number of Cerebellar Granule Cells and Astrocytes in the Internal Granule Layer in Sheep Following Prenatal Intra-amniotic Injection of Lipopolysaccharide

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies