Drug delivery in diffuse intrinsic pontine glioma is significantly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), when combined with the administration of microbubbles can ...effectively open the BBB permitting the entry of drugs across the cerebrovasculature into the brainstem. Given that the utility of FUS in brainstem malignancies remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. A syngeneic orthotopic model was developed by stereotactic injection of PDGF-B
PTEN
p53
murine glioma cells into the pons of B6 mice. A single-element, spherical-segment 1.5 MHz ultrasound transducer driven by a function generator through a power amplifier was used with concurrent intravenous microbubble injection for tumor sonication. Mice were randomly assigned to control, FUS and double-FUS groups. Pulse and respiratory rates were continuously monitored during treatment. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen testing and sequential weight lifting measured motor function before and after sonication. A subset of animals were treated with etoposide following ultrasound. Mice were either sacrificed for tissue analysis or serially monitored for survival with daily weights. FUS successfully caused BBB opening while preserving normal cardiorespiratory and motor function. Furthermore, the degree of intra-tumoral hemorrhage and inflammation on H&E in control and treated mice was similar. There was also no difference in weight loss and survival between the groups (p > 0.05). Lastly, FUS increased intra-tumoral etoposide concentration by more than fivefold. FUS is a safe and feasible technique for repeated BBB opening and etoposide delivery in a preclinical pontine glioma model.
The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the transition to seizure is complex, potentially leading to imprecise delineation of ...epileptogenic brain areas. In particular, the pattern of interneuronal firing at seizure onset remains under debate, with some studies demonstrating increased firing and others suggesting reductions. Previous study of neocortical sites suggests that seizure recruitment occurs upon failure of inhibition, with intact feedforward inhibition in non-recruited territories. We investigated whether the same principle applies in limbic structures. We analysed simultaneous electrocorticography (ECoG) and neuronal recordings of 34 seizures in a cohort of 19 patients (10 male, 9 female) undergoing surgical evaluation for pharmacoresistant focal epilepsy. A clustering approach with five quantitative metrics computed from ECoG and multiunit data was used to distinguish three types of site-specific activity patterns during seizures, which at times co-existed within seizures. Overall, 156 single units were isolated, subclassified by cell-type and tracked through the seizure using our previously published methods to account for impacts of increased noise and single-unit waveshape changes caused by seizures. One cluster was closely associated with clinically defined seizure onset or spread. Entrainment of high-gamma activity to low-frequency ictal rhythms was the only metric that reliably identified this cluster at the level of individual seizures (P < 0.001). A second cluster demonstrated multi-unit characteristics resembling those in the first cluster, without concomitant high-gamma entrainment, suggesting feedforward effects from the seizure. The last cluster captured regions apparently unaffected by the ongoing seizure. Across all territories, the majority of both excitatory and inhibitory neurons reduced (69.2%) or ceased firing (21.8%). Transient increases in interneuronal firing rates were rare (13.5%) but showed evidence of intact feedforward inhibition, with maximal firing rate increases and waveshape deformations in territories not fully recruited but showing feedforward activity from the seizure, and a shift to burst-firing in seizure-recruited territories (P = 0.014). This study provides evidence for entrained high-gamma activity as an accurate biomarker of ictal recruitment in limbic structures. However, reduced neuronal firing suggested preserved inhibition in mesial temporal structures despite simultaneous indicators of seizure recruitment, in contrast to the inhibitory collapse scenario documented in neocortex. Further study is needed to determine if this activity is ubiquitous to hippocampal seizures or indicates a 'seizure-responsive' state in which the hippocampus is not the primary driver. If the latter, distinguishing such cases may help to refine the surgical treatment of mesial temporal lobe epilepsy.
Summary
Objective
Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance–guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug‐resistant ...mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS).
Methods
We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug‐resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS.
Results
Twelve patients with SEEG‐confirmed, non‐MTS MTLE and 18 patients with MRI‐confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non‐MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non‐MTS patients (58%, 95% confidence interval CI 30%‐86%) and 10 of 18 MTS patients (56%, 95% CI 33%‐79%), with no significant difference between groups (odds ratio OR 1.12, 95% CI 0.26‐4.91, P = .88). Length of stay was 1 day for most patients (range 0‐3 days). Procedural complications were rare and without long‐term sequelae.
Significance
We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG‐confirmed, non‐MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%‐80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first‐line surgical option for patients with both MTS and SEEG confirmed, non‐MTS MTLE.
Moyamoya and inflammation Mejia-Munne, Juan C., M.D; Ellis, Jason A., M.D; Feldstein, Neil A., M.D ...
World neurosurgery,
04/2017, Letnik:
100
Journal Article
Recenzirano
Abstract Background Over fifty years have elapsed since Moyamoya was initially described; however, the disease etiology remains unknown. Although certain genetic loci and immunological ...characteristics are associated with Moyamoya, this does not fully explain its pathophysiology. An association with inflammatory disease has been postulated but not rigorously explored. We sought to examine the epidemiological association of Moyamoya and inflammatory diseases by analyzing data from a large administrative database. Methods The National Inpatient Sample database for years 2009-2012 was obtained. Diagnosis of Moyamoya and inflammatory diseases were made using the International Classification of Disease, 9 th revision . Sample prevalence, sex, age, and admission type were recorded. Patients were grouped into inflammatory disease clusters based on the presence of diagnosis codes for atherosclerotic, adult-onset autoimmune, and juvenile-onset autoimmune diseases. Results There were 2,633 total admissions for Moyamoya. Atherosclerotic (p < 0.05) and juvenile-onset autoimmune disease (p < 0.05) were associated with Moyamoya in both pediatric and adult patient groups. Adult-onset autoimmune disease was associated with Moyamoya in pediatric (p < 0.05), but not adult groups. Conclusion Moyamoya is associated with inflammatory disease clusters in both pediatric and adult populations. Further studies are warranted to investigate the pathophysiological association between Moyamoya and inflammatory disease processes.
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•LVFA at ictal onset is associated with good surgical outcomes in children.•Consistent IOP morphology is associated with good surgical outcomes in children.•LVFA at ictal onset is ...less common in younger children during IEEG recording.
We aimed to classify ictal onset patterns (IOPs) in pediatric patients undergoing intracranial electroencephalography (IEEG) to guide surgery for refractory epilepsy. We aimed to determine if morphology of IOPs can predict surgical outcome.
We performed a retrospective review of pediatric patients who underwent epilepsy surgery guided by subdural IEEG from 2007 to 2016. IEEG seizures were reviewed by a blinded epileptologist. Data was collected on outcomes.
Twenty-three patients with 784 seizures were included. Age at seizure onset was 0.2–11 (mean 4.3, standard deviation 3.2) years. Age at time of IEEG was 4–20 (mean 13.5, standard deviation 4.4) years. Five distinct IOPs were seen at seizure onset: A) Low voltage fast activity (LVFA) with spread to adjacent electrodes (n = 7 patients, 30%), B) Burst of LVFA followed by electrodecrement (n = 12 patients, 52%), C) Burst of rhythmic spike waves (RSW) followed by electrodecrement (n = 9 patients, 39%), D) RSW followed by LVFA (n = 7 patients, 30%), E) Rhythmic spikes alone (n = 10 patients, 43%). Twelve patients (52%) had the same IOP type with all seizures. When the area of the IOP was resected, 14 patients (61%) had Engel I outcomes. Patients who had LVFA seen within their predominant IOP type were more likely to have good surgical outcomes (odds ratio 7.50, 95% confidence interval 1.02–55.0, p = 0.05). Patients who had only one IOP type were more likely to have good outcomes than patients who had multiple IOP types (odds ratio 12.6, 95% confidence interval 1.19–134, p = 0.04). Patients who had LVFA in their predominant IOP type were older than patients who did not have LVFA (mean age 15.0 vs. 9.9 years, p = 0.02).
LVFA at ictal onset and all seizures having the same IOP morphology are associated with increased likelihood of surgical success in children, but LVFA is less common in children who are younger at the time of IEEG.
Congenital basal meningoceles and encephaloceles are rare pathologies that may present in isolation or with characteristic-associated clinical features. Rarely, children with congenital midline ...defects may present with massive encephaloceles secondary to anterior cranial fossa agenesis. Traditionally, transcranial approaches with frontal craniotomies were used to reduce the herniated contents and repair the skull base defect. However, high rates of morbidity and mortality associated with craniotomies have favored the development and adoption of less-invasive techniques.
To present a novel technique for combined endoscopic endonasal and transpalatal repair of a giant basal meningocele through an extensive sphenoethmoidal skull base defect.
A representative case of congenital anterior cranial fossa agenesis with a giant meningocele was selected. Clinical and radiological presentations were reviewed, and the intraoperative surgical technique was documented and recorded.
A surgical video highlighting each surgical step was included to complement the description of the technique. The surgical outcome from the selected case is also presented.
This report describes a combined endoscopic endonasal and transpalatal approach to repair an extensive anterior skull base defect with herniation of intracranial content. This technique capitalizes on the advantages of each approach to address this complex pathology.
Objective
One of the clinical hallmarks of tuberous sclerosis complex (TSC) is radiologically identified cortical tubers, which are present in most patients. Intractable epilepsy may require surgery, ...often involving invasive diagnostic procedures such as intracranial electroencephalography (EEG). Identifying the location of the dominant tuber responsible for generating epileptic activities is a critical issue. However, the link between cortical tubers and epileptogenesis is poorly understood. Given this, we hypothesized that tuber voxel intensity may be an indicator of the dominant epileptogenic tuber. Also, via tuber segmentation based on deep learning, we explored whether an automatic quantification of the tuber burden is feasible.
Methods
We annotated tubers from structural magnetic resonance images across 29 TSC subjects, summarized tuber statistics in eight brain lobes, and determined suspected epileptogenic lobes from the same group using EEG monitoring data. Then, logistic regression analyses were performed to demonstrate the linkage between the statistics of cortical tuber and the epileptogenic zones. Furthermore, we tested the ability of a neural network to identify and quantify tuber burden.
Results
Logistic regression analyses showed that the volume and count of tubers per lobe, not the mean or variance of tuber voxel intensity, were positively correlated with electrophysiological data. In 47.6% of subjects, the lobe with the largest tuber volume concurred with the epileptic brain activity. A neural network model on the test dataset showed a sensitivity of .83 for localizing individual tubers. The predicted masks from the model correlated highly with the neurologist labels, and thus may be a useful tool for determining tuber burden and searching for the epileptogenic zone.
Significance
We have proven the feasibility of an automatic segmentation of tubers and a derivation of tuber burden across brain lobes. Our method may provide crucial insights regarding the treatment and outcome of TSC patients.
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