Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Focused ultrasound for brain metastases: an update on global clinical trials.

BACKGROUND: Despite advances in immunotherapy and targeted treatments for malignancies of the central nervous system (CNS), the treatment of brain metastases (BMs) remains a formidable challenge, due largely to difficulties in crossing the blood-brain barrier (BBB), drug resistance, and molecular discrepancies. Focused ultrasound (FUS) is a non-invasive tool for BBB breaching, tumor ablation, enhancing drug delivery, promoting the release of tumor biomarkers for liquid biopsy, or the tumor microenvironment disruption. This paper presents a comprehensive review of the current literature related to FUS and its application in the treatment of brain metastasis. METHODS: This review of the current literature via PubMed, Google Scholar, and Clincaltrials.gov focused on clinical trials in which FUS is used in the intracranial treatment of metastatic tumor, glioma, or GBM. RESULTS: FUS is safe and effective for treatment of primary or metastatic brain tumors. FUS-augmented drug delivery can open BBB to facilitate the transport of chemotherapeutic agents, immunotherapies, and targeted treatments. The integration of FUS with liquid biopsy has considerable potential for early tumor detection, precise gene profiling, and personalized therapy. Sonodynamic therapy can induce tumor cell apoptosis and could potentially be used to enhance the outcomes of other tumor treatments, such as surgery and chemotherapy. CONCLUSION: Further work is required to establish FUS as a standard therapy for BMs. FUS has the potential to transform brain tumor treatment, particularly when combined with immunotherapy and targeted therapy as a non-invasive alternative to surgery and radiation therapy.

Stereo-EEG for Epileptogenic Focus Localization in Schizencephaly: A Single-center Experience in Four Patients.

OBJECTIVE: Schizencephaly is a congenital cerebral malformation characterized by clefts in the hemispheres of the brain, where variations in semiology often make it difficult to localize epileptogenic focus. Here, we report on a series of patients who underwent stereo-encephalography (SEEG) for epileptogenic focus localization and subsequent SEEG-guided surgical intervention. METHODS: Four patients (ages 27, 33, 27, 25 years) with a mean seizure history of 16 years (range 8-22 years) were analyzed. Data pertaining to semiology, video encephalography (EEG), magnetic resonance imaging, positron emission tomography, and invasive EEG studies, surgical intervention and post-surgery outcome were collected and analyzed. RESULTS: All seizure onset zones were within the extent of schizencephaly; however, the limbic system (including the hippocampus, amygdala, cingulate gyrus, or insula) was involved in early spreading. Two patients underwent SEEG-guided radiofrequency thermo-ablation (RFTA) in the seizure onset zone, 1 patient underwent lesionectomy via craniotomy, and 1 underwent neither RFTA nor lesionectomy. At 2 years post-surgery, the outcomes were as follows: Engel grade Ia (n = 2), Ib (n = 1), and III (n = 1). CONCLUSIONS: This article reports on a precise approach to treating patients with schizencephaly dependent of seizure onset zone and functional cortex mapping. Subsequent SEEG-guided surgical interventions (radiofrequency thermo-ablation and lesionectomy) were shown to reduce seizure frequency, while preserving the neurologic functions in drug-resistant epilepsy patients with schizencephaly.

The Preliminary Results for Evaluating Cocoa Butter's Hepatoprotective Effects against Lipid Accumulation and Inflammation in Adult Male Rats Chronically Fed Ethanol.

The purpose of this study was to clarify the role of saturated fats from cocoa butter (plant source) compared with lard (animal source) on alcoholic liver damage in rats. Male Wistar rats were fed either a control diet (C) or an ethanol diet (E), and the dietary fats (corn oil, olive oil, and safflower oil) of these two diets were further replaced by lard (CL, EL) or cocoa butter (CC, EC). After 8-week feeding, plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic triglyceride (TG) levels, plasma intercellular adhesion molecular (ICAM)-1 levels, hepatic cytochrome P450 2E1 (CYP2E1) protein expression, and hepatic interleukin (IL)-1ß significantly increased in the E group compared to the C group. In addition, hepatic histopathological scores of fatty changes, inflammatory cell infiltration, and degeneration and necrosis in the E group were significantly higher compared to those in the C group. However, fatty changes were significantly inhibited only in the EC group as well as hepatic inflammatory cell infiltration, degeneration, and necrosis being significantly lower in the EL and EC groups. Plasma ICAM-1 and hepatic tumor necrosis factor (TNF)-α, IL-1ß, IL-6, and IL-10 levels were significantly lower in the EL and EC groups than those in the E group. Moreover, a correlation analysis showed that hepatic histopathological scores of degeneration and necrosis were significantly positively correlated with erythrocytic oleic acid (C18:1) and were negatively correlated with linoleic acid (C18:2). In conclusion, cocoa butter protected the liver against lipid accumulation and inflammation in rats chronically fed ethanol.

Cingulate gyrus epilepsy: semiology, invasive EEG, and surgical approaches.

OBJECTIVE: The semiology of cingulate gyrus epilepsy is varied and may involve the paracentral area, the adjacent limbic system, and/or the orbitofrontal gyrus. Invasive electroencephalography (iEEG) recording is usually required for patients with deeply located epileptogenic foci. This paper reports on the authors' experiences in the diagnosis and surgical treatment of patients with focal epilepsy originating in the cingulate gyrus. METHODS: Eighteen patients (median age 24 years, range 5-53 years) with a mean seizure history of 23 years (range 2-32 years) were analyzed retrospectively. The results of presurgical evaluation, surgical strategy, and postoperative pathology are reported, as well as follow-up concerning functional morbidity and seizures (median follow-up 7 years, range 2-12 years). RESULTS: Patients with cingulate gyrus epilepsy presented with a variety of semiologies and scalp EEG patterns. Prior to ictal onset, 11 (61%) of the patients presented with aura. Initial ictal symptoms included limb posturing in 12 (67%), vocalization in 5, and hypermotor movement in 4. In most patients (n = 16, 89%), ictal EEG presented as widespread patterns with bilateral hemispheric origin, as well as muscle artifacts obscuring the onset of EEG during the ictal period in 11 patients. Among the 18 patients who underwent resection, the pathology revealed mild malformation of cortical development in 2, focal cortical dysplasia (FCD) Ib in 4, FCD IIa in 4, FCD IIb in 4, astrocytoma in 1, ganglioglioma in 1, and gliosis in 2. The seizure outcome after surgery was satisfactory: Engel class IA in 12 patients, IIB in 3, IIIA in 1, IIIB in 1, and IVB in 1 at the 2-year follow-up. CONCLUSIONS: In this study, the authors exploited the improved access to the cingulate epileptogenic network made possible by the use of 3D electrodes implanted using stereoelectroencephalography methodology. Under iEEG recording and intraoperative neuromonitoring, epilepsy surgery on lesions in the cingulate gyrus can result in good outcomes in terms of seizure recurrence and the incidence of postoperative permanent deficits.

UPF1, a conserved nonsense-mediated mRNA decay factor, regulates cyst wall protein transcripts in Giardia lamblia.

The Giardia lamblia cyst wall is required for survival outside the host and infection. Three cyst wall protein (cwp) genes identified to date are highly up-regulated during encystation. However, little is known of the molecular mechanisms governing their gene regulation. Messenger RNAs containing premature stop codons are rapidly degraded by a nonsense-mediated mRNA decay (NMD) system to avoid production of non-functional proteins. In addition to RNA surveillance, NMD also regulates thousands of naturally occurring transcripts through a variety of mechanisms. It is interesting to know the NMD pathway in the primitive eukaryotes. Previously, we have found that the giardial homologue of a conserved NMD factor, UPF1, may be functionally conserved and involved in NMD and in preventing nonsense suppression. In this study, we tested the hypothesis that NMD factors can regulate some naturally occurring transcripts in G. lamblia. We found that overexpression of UPF1 resulted in a significant decrease of the levels of CWP1 and cyst formation and of the endogenous cwp1-3, and myb2 mRNA levels and stability. This indicates that NMD could contribute to the regulation of the cwp1-3 and myb2 transcripts, which are key to G. lamblia differentiation into cyst. Interestingly, we also found that UPF1 may be involved in regulation of eight other endogenous genes, including up-regulation of the translation elongation factor gene, whose product increases translation which is required for NMD. Our results indicate that NMD factor could contribute to the regulation of not only nonsense containing mRNAs, but also mRNAs of the key encystation-induced genes and other endogenous genes in the early-diverging eukaryote, G. lamblia.

Incomplete nonsense-mediated mRNA decay in Giardia lamblia.

Messenger RNAs containing premature translation stop codons are degraded by a nonsense-mediated mRNA decay (NMD) system. The NMD pathway is present in yeast, plants and mammals and is thought to protect cells from production of nonfunctional proteins by rapidly degrading mutant mRNAs. There is little understanding of the biology of the origins of eukaryotes, particularly of the NMD pathway. Searches using the BLAST program revealed that the protozoan Giardialamblia has only some of the components of the NMD pathway. We developed a luciferase reporter system with a nonsense mutation to monitor NMD in Giardia. The nonsense mutation triggered a decrease in luciferase mRNA levels and stability, suggesting that the NMD phenomenon could be present in Giardia. We also found a significant reduction of the mRNA levels of another system containing Giardia its own cyst wall protein 3 gene with a nonsense mutation. However, the reduction levels observed in these two systems are lower than that in late-branching eukaryotes, suggesting that the NMD system in Giardia may be less functional. Interestingly, the effect of G418 in promoting read-through of the nonsense mutation and inhibiting NMD in Giardia is similar to that in late-branching eukaryotes. We also characterised the giardial homologue of a conserved NMD factor, UPF1. Immunofluorescence assays revealed that giardial UPF1, like yeast UPF1, is expressed in the cytoplasm, but not in the nucleus. In addition, overexpression of UPF1 resulted in a reduction of the levels of nonsense-containing transcripts and enhanced translation termination at a nonsense codon. These results suggest that Giardia may have an incomplete NMD pathway and giardial UPF1 may be functionally conserved, involved in NMD and in preventing nonsense suppression.

Neomycin and puromycin affect gene expression in Giardia lamblia stable transfection.

Two systems for stable transfection of Giardia have been established using selection either by neomycin or by puromycin. We asked if these selection systems themselves influenced expression of endogenous giardial genes. Northern blot analysis showed a approximately 1.4 to approximately 7-fold increase in the encystation-induced cyst wall protein 1 (cwp1), cwp2, and gmyb2 gene transcripts in the drug selected cell lines during vegetative growth, compared with untransfected cells. However, the levels of the constitutive ran, lrp3, or alpha2-tubulin gene transcripts decreased slightly or did not change in these stably transfected cell lines. Part of the effect could be due to drug selection, since treatment of untransfected cells with G418 or puromycin also had similar effects. Nuclear run-on assays showed that part of the effect comes from an increase in transcription initiation rate. The levels of CWP and cyst formation during vegetative growth also increased in the transfected cell lines. Using proteomic technologies, we identified eight genes whose expression is upregulated in neomycin selected cell lines, including phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, ornithine carbamoyltransferase, carbamate kinase, orf 16424, cyclophilin, co-chaperone-like p21, and bip. Six of these are also upregulated in puromycin selected cell lines. Our results indicate that transfection and drug selection, per se, can alter expression of genes involved in metabolism, protein folding, and differentiation status in Giardia.