Epilepsy in Patients With Primary CNS Lymphoma: Prevalence, Risk Factors, and Prognostic Significance.

BACKGROUND AND OBJECTIVES: Epilepsy is a common comorbidity of brain tumors; however, little is known about the prevalence, onset time, semiology, and risk factors of seizures in primary CNS lymphoma (PCNSL). Our objectives were to determine the prevalence of epilepsy in PCNSL, to identify factors associated with epilepsy, and to investigate the prognostic significance of seizures in PCNSL. METHODS: We performed an observational, retrospective single-center study at a tertiary neuro-oncology center (2011-2023) including immunocompetent patients with PCNSL and no history of seizures. We collected clinical, imaging, and treatment data; seizure status over the course of PCNSL; and oncological and seizure outcome. The primary outcome was to determine the prevalence of epilepsy. Furthermore, we aimed to identify clinical, radiologic, and treatment-related factors associated with epilepsy. Univariate analyses were conducted using the χ2 test for categorical variables and unpaired t test for continuous variables. Predictors identified in the unadjusted analysis were included in backward stepwise logistic regression models. RESULTS: We included 330 patients, 157 (47.6%) were male, median age at diagnosis was 68 years, and the median Karnofsky Performance Status score was 60. Eighty-three (25.2%) patients had at least 1 seizure from initial diagnosis to the last follow-up, 40 (12.1%) as the onset symptom, 16 (4.8%) during first line of treatment, 27 (8.2%) at tumor progression and 6 (1.8%) while in remission. Focal aware seizures were the most frequent seizure type, occurring in 43 (51.8%) patients. Seizure freedom under antiseizure medication was observed in 97.6% patients. Cortical contact (odds ratio [OR] 8.6, 95% CI 4.2-15.5, p < 0.001) and a higher proliferation index (OR 5.7, 95% CI 1.3-26.2, p = 0.02) were identified as independent risk factors of epilepsy. Patients with PCNSL and epilepsy had a significantly shorter progression-free survival (median progression-free survival 9.6 vs 14.1 months, adjusted hazard ratio 1.4, 95% CI 1.0-1.9, p = 0.03), but not a significantly shorter overall survival (17 vs 44.1 months, log-rank test, p = 0.09). DISCUSSION: Epilepsy affects a quarter of patients with PCNSL, with half experiencing it at the time of initial presentation and potentially serving as a marker of disease progression. Further research is necessary to assess the broader applicability of these findings because they are subject to the constraints of a retrospective design and tertiary center setting.

Delayed traumatic intracranial aneurysms: literature review and case series.

Traumatic intracranial aneurysm (TICA) is a rare and aggressive pathology that requires prompt treatment. Nevertheless, early vascular imaging following head trauma may yield falsely negative results, underscoring the importance of subsequent imaging within the first week to detect delayed TICAs. This study aims to report our experience with delayed TICAs and highlight the clinical importance of repeated angiographic screening for delayed TICAs. In this retrospective analysis, we evaluated patients managed for a TICA at a tertiary care teaching institution over the last decade. Additionally, we conducted a systematic review of the literature, following the PRISMA guidelines, on previously reported TICAs, focusing on the time lag between the injury and diagnosis. Twelve delayed TICAs were diagnosed in 9 patients. The median time interval from injury to diagnosis was 2 days (IQR: 1-22 days), and from diagnosis to treatment was 2 days (IQR: 0-9 days). The average duration of radiological follow-up was 28 ± 38 months. At the final follow-up, four patients exhibited favorable neurological outcomes, while the remainder had adverse outcomes. The mortality rate was 22%. Literature reviews identified 112 patients with 114 TICAs, showcasing a median diagnostic delay post-injury of 15 days (IQR: 6-44 days), with 73% diagnosed beyond the first week post-injury. The median time until aneurysm rupture was 9 days (IQR: 3-24 days). Our findings demonstrate acceptable outcomes following TICA treatment and highlight the vital role of repeated vascular imaging after an initial negative computed tomography or digital subtraction angiography in excluding delayed TICAs.

Effect of ultrasound-mediated blood-spinal cord barrier opening on survival and motor function in females in an amyotrophic lateral sclerosis mouse model.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). METHODS: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.Cg-Tg(SOD1∗G93A)1Gur/J). The BSCB was disrupted using a 1 MHz ultrasound transducer coupled to the spinal cord, with and without injection of insulin-like growth factor 1 (IGF1), a neurotrophic factor that has previously shown efficacy in ALS models. FINDINGS: Results in wild-type (WT) animals demonstrated that the BSCB can be safely disrupted and IGF1 concentrations significantly enhanced after a single session of transient BSCB disruption (176 ± 32 µg/g vs. 0.16 ± 0.008 µg/g, p < 0.0001). Five repeated weekly US sessions performed in female ALS mice demonstrated a survival advantage in mice treated with IGF1 and US (US IGF1) compared to treatment with IGF1 alone (176 vs. 166 days, p = 0.0038). Surprisingly, this survival advantage was also present in mice treated with US alone vs. untreated mice (178.5 vs. 166.5 days, p = 0.0061). Muscle strength did not show difference among the groups. Analysis of glial cell immunoreactivity and microglial transcriptome showing reduced cell proliferation pathways, in addition to lymphocyte infiltration, suggested that the beneficial effect of US or US IGF1 could act through immune cell modulation. INTERPRETATION: These results show the first step towards a possible beneficial impact of transient BSCB opening for ALS therapy and suggest implication of immune cells. FUNDING: Fondation pour la Recherche Médicale (FRM). Investissements d'avenirANR-10-IAIHU-06, Société Française de Neurochirurgie (SFNC), Fond d'étude et de Recherche du Corps Medical (FERCM), Aide à la Recherche des Maladies du Cerveau (ARMC), SLA Fondation Recherche (SLAFR), French Ministry for High Education and Research (MENR), Carthera, Laboratoire de Recherche en Technologies Chirurgicales Avancées (LRTCA).

Management of entrapped temporal horn: Literature review and operative technique for endoscopic fenestration.

CONTEXT: Entrapment of the temporal horn (TH) is rare condition that can lead to increased intracranial pressure, but there is no consensus on a standard treatment. The aim of this study was to conduct a systematic literature review of the reported cases of TH entrapment and describe our operative technique for endoscopic fenestrations of the lateral ventricle into the basal cisterns. METHODS: We searched the databases Pubmed and Google scholar to find all studies reporting cases of entrapped TH and the subsequent treatment. Additionally, we report two illustrative cases of endoscopic fenestration with a step-by-step description of our surgical technique. RESULTS: Twenty-nine studies with a total of 67 patients were included in the analysis. The mean age was 36.5 years (SD± 21.9), and the female-to-male ratio was 1.5. The most frequent cause of TH entrapment was post-surgical scarring after tumor surgery (n= 30), and the most commonly reported treatment modality was endoscopic fenestration of the TH (n = 14). We observed an increasing use of endoscopic fenestration over time. CONCLUSION: Entrapped TH is a rare condition often requiring surgical treatment. Neuronavigation-guided endoscopic fenestration of the ventricle into the basal cisterns appears to be a safe, efficient, and device-free technique that has gained importance over the past years.

Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.

Safety and practicality study of using an exoskeleton in acute neurosurgery patients.

INTRODUCTION: Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in rehabilitation departments to help patients stand and walk. We report the first case series of exoskeleton use in acute neurosurgery and intensive care patients, evaluating safety, clinical feasibility and patients' satisfaction. METHODS: We report a retrospective observational study including individuals hospitalized in the neurosurgical intensive care and neurosurgery departments. We included patients with a medical prescription for an exoskeleton session, and who met no contraindication. Patients benefited from standing sessions using a self-balanced exoskeleton (Atalante, Wandercraft, France). Patients and sessions data were collected. Safety, feasibility and adherence were evaluated. RESULTS: Seventeen patients were scheduled for 70 standing sessions, of which 27 (39%) were completed. They were typically hospitalized for intracranial hemorrhage (74%) and presented with unilateral motor impairments, able to stand but with very insufficient weight shifting to the hemiplegic limb, requiring support (MRC 36.2 ± 3.70, SPB 2.0 ± 1.3, SPD 0.7 ± 0.5). The average duration of standing sessions was 16 ± 9 min. The only side effect was orthostatic hypotension (18.5%), which resolved with returning to seating position. The most frequent reason for not completing a session was understaffing (75%). All patients were satisfied and expressed a desire to repeat it. CONCLUSIONS: Physiotherapy using the exoskeleton is safe and feasible in the acute neurosurgery setting, although it requires adaptation from the staff to organize the sessions. An efficacy study is ongoing to evaluate the benefits for the patients.

Shark critical life stage vulnerability to monthly temperature variations under climate change.

In a 10-month experimental study, we assessed the combined impact of warming and acidification on critical life stages of small-spotted catshark (Scyliorhinus canicula). Using recently developed frameworks, we disentangled individual and group responses to two climate scenarios projected for 2100 (SSP2-4.5: Middle of the road and SSP5-8.5: Fossil-fueled Development). Seasonal temperature fluctuations revealed the acute vulnerability of embryos to summer temperatures, with hatching success ranging from 82% for the control and SSP2-4.5 treatments to only 11% for the SSP5-8.5 treatment. The death of embryos was preceded by distinct individual growth trajectories between the treatments, and also revealed inter-individual variations within treatments. Embryos with the lowest hatching success had lower yolk consumption rates, and growth rates associated with a lower energy assimilation, and almost all of them failed to transition to internal gills. Within 6 months after hatching, no additional mortality was observed due to cooler temperatures.

Quantifying larval dispersal portfolio in seabass nurseries using otolith chemical signatures.

The temporal asynchronies in larvae production from different spawning areas are fundamental components for ensuring stability and resilience of marine metapopulations. Such a concept, named portfolio effect, supposes that diversifying larval dispersal histories should minimize the risk of recruitment failure by increasing the probability that at least some larvae successfully settle in nursery. Here, we used a reconstructive approach based on otolith chemistry to quantify the larval dispersal portfolio of the European seabass, Dicentrarchus labrax, across six estuarine nursery areas of the northeast Atlantic Ocean. The analysis of natal and trajectory signatures indicated that larvae hatch in distinct environments and then dispersed in water masses featured by contrasting chemical signatures. While some trace elements appeared affected by temporal changes (Mn and Sr), others varied spatially during the larval stage but remained poorly affected by temporal fluctuation and fish physiology (Ba, Cu, Rb and Zn). We then proposed two diversity metrics based on richness and variations of chemical signatures among populations to reflect spatio-temporal diversity in natal origins and larval trajectories (i.e., estimates of dispersal portfolio). Along the French coast, the diversity estimates were maximum in nurseries located at proximity of offshore spawning sites and featured by complex offshore hydrodynamic contexts, such as the Mont St-Michel bay. Finally, our findings indicate that the dispersal portfolio was positively related with the local abundance of seabass juveniles, supporting the assumption that heterogeneity in dispersal history contributes to promote recruitment success in nurseries.

Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Northeast Atlantic elasmobranch community on the move: Functional reorganization in response to climate change.

While spatial distribution shifts have been documented in many marine fishes under global change, the responses of elasmobranchs have rarely been studied, which may have led to an underestimation of their potential additional threats. Given their irreplaceable role in ecosystems and their high extinction risk, we used a 24-year time series (1997-2020) of scientific bottom trawl surveys to examine the effects of climate change on the spatial distribution of nine elasmobranch species within Northeast Atlantic waters. Using a hierarchical modeling of species communities, belonging to the joint species distribution models, we found that suitable habitats for four species increased on average by a factor of 1.6 and, for six species, shifted north-eastwards and/or to deeper waters over the past two decades. By integrating species traits, we showed changes in habitat suitability led to changes in the elasmobranchs trait composition. Moreover, communities shifted to deeper waters and their mean trophic level decreased. We also note an increase in the mean community size at maturity concurrent with a decrease in fecundity. Because skates and sharks are functionally unique and dangerously vulnerable to both climate change and fishing, we advocate for urgent considerations of species traits in management measures. Their use would make it better to identify species whose loss could have irreversible impacts in face of the myriad of anthropogenic threats.