Prognostic value of scalp EEG ictal patterns in epilepsy surgery of hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is a surgically treatable epileptic syndrome. While the core of pre-surgical evaluations rely on video-EEG, recent studies question the necessity of recorded seizures denying a possible role of ictal EEG in surgical decision. This study aims to retrospectively assess the prognostic value of EEG ictal patterns in TLE-HS, in order to identify which patients need further investigations before offering surgery. METHODS: We included TLE-HS patients who underwent surgery with at least one captured seizure during non-invasive pre-surgical video-EEG recordings. They were classified in "mesial" and "lateral/mixed", according to the ictal EEG patterns, defined by the frequency of the discharge (mesial ≥ 5 Hz, lateral < 5 Hz). Seizure outcome was assessed by Engel's Class. Statistical analyses were performed to evaluate associations between EEG patterns and post-surgical outcomes. RESULTS: Sixty-nine exhibited a mesial pattern, forty- two displayed lateral/mixed patterns. Mesial pattern group had a significantly higher rate of postsurgical seizure freedom (82.7% vs. 28.6%). Gender, age of onset, age at surgery, duration of epilepsy, seizure frequency, and lateralization did not influence the outcome. Mesial pattern significantly correlated with favorable outcomes (p < 0.001), suggesting its potential predictive value. CONCLUSION: This retrospective study proposes ictal EEG patterns as possible predictors of postoperative prognosis in TLE-HS. A mesial pattern correlates with better outcomes, indicating a potentially more circumscribed epileptogenic zone. Patients with lateral/mixed patterns may benefit from additional investigations to delineate the epileptogenic zone. Further studies are warranted to validate and extend these findings.

From data to practice: brain meningioma treatment in elderly patients - a survey of the Italian Society of Neurosurgery (SINch®) and systematic review and meta-analysis.

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting.

Posterolateral approaches to the thoracic spine for calcific disc herniation: is wider exposure always better?

OBJECTIVE: To compare the costotransversectomy (CTV) and transpedicular (TP) approaches versus the transfacet (TF) approach for the surgical treatment of calcific thoracic spine herniations (cTDH), in terms of surgical and clinical outcomes. BACKGROUND: Surgical approaches for cTDH are debated. Anterior approaches are recommended, while posterolateral approaches are preferred for non-calcific, paramedian, and lateral hernias. Currently, there is limited evidence about the superiority of a more invasive surgical approach, such as CTV or TP, over TF, a relatively less invasive approach, in terms of neurological outcome, pain, and surgical complications, for the treatment of cTDH. METHODS: A retrospective, observational, monocentric study was conducted on patients who underwent posterolateral thoracic approaches for symptomatic cTDH, between 2010 and 2023, at our institute. Three groups were drafted, based on the surgical approach used: TF, TP, and CTV. All procedures were assisted by intraoperative CT scan, spinal neuronavigation, and intraoperative neuromonitoring. Analyzed factors include duration of surgery, amount of bone removal, intraoperative blood loss, CSF leak, need of instrumentation for iatrogenic instability, degree of disc herniation removal, myelopathy recovery. Afterwards, a statistical analysis was performed to investigate the bony resection of the superior posterior edge of the vertebral soma. The primary outcome was the partial or total herniation removal. RESULTS: This study consecutively enrolled 65 patients who underwent posterolateral thoracic surgery for cTDH. The TF approach taking the least, and the CTV the longest time (p < 0.01). No statistical difference was observed between the three mentioned approaches, in terms of intraoperative blood loss, dural leakage, post-resection instrumentation, total herniation removal, or myelopathy recovery. An additional somatic bony resection was successful in achieving total herniation removal (p < 0.01), and the extent of bony resection was directly proportional to the extent of hernia removal (p < 0.01). CONCLUSIONS: No statistically significant differences were highlighted between the TP, TF, and CTV regarding the extent of cTDH removal, the postoperative complications, and the neurological improvement. The described somatic bone resection achieved significant total herniation removal and was directly proportional to the preop against postop anteroposterior diameter difference.

Enhanced Mechanical and Electromechanical Properties of Compositionally Complex Zirconia Zr1-x(Gd1/5Pr1/5Nd1/5Sm1/5Y1/5)xO2-δ Ceramics.

Compositionally complex oxides (CCOs) or high-entropy oxides (HEOs) are new multielement oxides with unexplored physical and functional properties. In this work, we report fluorite structure-derived compositionally complex zirconia with composition Zr1-x(Gd1/5Pr1/5Nd1/5Sm1/5Y1/5)xO2-δ (x = 0.1 and 0.2) synthesized in solid-state reaction route and sintered via hot pressing at 1350 °C. We explore the evolution of these oxides' structural, microstructural, mechanical, electrical, and electromechanical properties regarding phase separation and sintering mechanisms. Highly dense ceramics are achieved by bimodal mass diffusion, composing nanometric tetragonal and micrometric cubic grains microstructure. The material exhibits an anomalously large electrostriction response exceeding the M33 value of 10-17 m2/V2 at room temperature and viscoelastic properties of primary creep in nanoindentation measurement under fast loading. These findings are strikingly similar to those reported for doped ceria and bismuth oxide derivates, highlighting the presence of a large concentration of point defects linked to structural distortion and anelastic behavior, which are characteristics of nonclassical ionic electrostrictors.

Parasagittal Meningiomas: The Impact of Sinus Opening and Grade of Resection on Clinical Outcome and Recurrence in a Consecutive Series of Patients.

BACKGROUND: Surgical management of parasagittal meningiomas (PMs) remains controversial in the literature. The need to pursue a resection as radical as possible and the high risk of venous injuries contribute to making the sinus opening a widely argued choice. This study aimed to analyze factors affecting the risk of recurrence and to assess clinical outcomes of patients who underwent surgical resection of PMs with conservative or aggressive management of the intrasinusal portion. METHODS: A single-institution retrospective review of all patients with PM surgically treated between January 2013 and March 2021 was conducted. RESULTS: Among 56 patients, the sinus was opened in 32 patients (57%), and a conservative approach was used in 24 patients (43%). The sinus opening was found to be a predictive factor of radical resection (Simpson grade [SG] I-II) (P = 0.007). SG was the only predictive factor of recurrence (P < 0.001). The radical resection group (SG I-II) showed recurrence-free survival at 72 months of about 90% versus 30% in the non-radical resection group (SG III-IV) (log-rank test = 14.21, P < 0.001). Aggressive management of the sinus and radical resection were not found to be related to permanent deficit (P = 0.214 and P = 0.254) or worsening of Karnofsky performance scale score (P = 0.822 and P = 0.933). CONCLUSIONS: Removal of the intrasinusal portion of the tumor using standard procedures is not associated with a higher risk of permanent deficit or worsening of Karnofsky performance scale and reduces the risk of recurrence.

Fasting duration impacts ribosome protein 6 phosphorylation in zebrafish brain: New insights in aquatic organisms' welfare.

BACKGROUND: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting. METHODS: Group-housed adult zebrafish were exposed to four and seven days of complete food withdrawal. At the end of the experimental period, Western blotting analyses were carried out to measure the expression levels of the phosphorylated S6 (pS6) by comparing the two experimental conditions versus the control group. The same antibody was then used to identify the distribution pattern of pS6 immunoreactive neurons in the whole brain and in the taste buds. RESULTS: We did not observe increased pS6 levels expression in the brain of animals exposed to short-term fasting compared to the control, whereas the expression increased in brain homogenates of animals exposed to mid-term fasting. pS6 immunoreactivity was reported in some hypothalamic neurons, as well as in the dorsal area of telencephalon and preoptic area, a neurosecretory region homolog to the mammalian paraventricular nucleus. Remarkably, we observed pS6 immunostaining in the sensory cells of taste buds lining the oral epithelium. CONCLUSIONS: Taken together, our data show that in zebrafish, differently from other fish species, seven days of fasting triggers neuronal activity. Furthermore, the immunostaining on sensory cells of taste buds suggests that metabolic changes may modulate also peripheral sensory cells. This event may have valuable implications when using zebrafish to design metabolic studies involving fasting as well as practical consequences on the animal welfare, in particularly stressful conditions, such as transportation.

A Study of Alternative TrkA Splicing Identifies TrkAIII as a Novel Potentially Targetable Participant in PitNET Progression.

Pituitary neuroendocrine tumors (PitNETs) are generally benign but comprise an aggressive, invasive, therapy-resistant, metastatic subset, underpinning a need for novel therapeutic targets. PitNETs exhibit low mutation rates but are associated with conditions linked to alternative splicing, an alternative oncogene pathway activation mechanism. PitNETs express the neurotrophin receptor TrkA, which exhibits oncogenic alternative TrkAIII splicing in other neuroendocrine tumors. We, therefore, assessed whether TrkAIII splicing represents a potential oncogenic participant in PitNETs. TrkAIII splicing was RT-PCR assessed in 53 PitNETs and TrkA isoform(s) expression and activation were assessed by confocal immunofluorescence. TrkAIII splicing was also compared to HIF1α, HIF2α, SF3B1, SRSF2, U2AF1, and JCPyV large T antigen mRNA expression, Xbp1 splicing, and SF3B1 mutation. TrkAIII splicing was detected in all invasive and most non-invasive PitNETs and was significantly elevated in invasive cases. In PitNET lineages, TrkAIII splicing was significantly elevated in invasive PIT1 PitNETs and high in invasive and non-invasive SF1 and TPIT lineages. Immunoreactivity consistent with TrkAIII activation characterized PitNET expressing TrkAIII mRNA, and invasive Pit1 PitNETs exhibited elevated HIF2α expression. TrkAIII splicing did not associate with SF3B1 mutations, altered SF3B1, SRSF2, and U2AF1 or JCPyV large T antigen expression, or Xbp1 splicing. Therefore, TrkAIII splicing is common in PitNETs, is elevated in invasive, especially PIT1 tumors, can result in intracellular TrkAIII activation, and may involve hypoxia. The data support a role for TrkAIII splicing in PitNET pathogenesis and progression and identify TrkAIII as a novel potential target in refractory PitNETs.

The anterior sylvian point as a reliable landmark for the anterior temporal lobectomy in mesial temporal lobe epilepsy: technical note, case series, and cadaveric dissection.

Introduction: Mesial temporal lobe epilepsy (MTLE) is one of the most prevalent forms of focal epilepsy in surgical series, particularly among adults. Over the decades, different surgical strategies have been developed to address drug-resistant epilepsy while safeguarding neurological and cognitive functions. Among these strategies, anterior temporal lobectomy (ATL), involving the removal of the temporal pole and mesial temporal structures, has emerged as a widely employed technique. Numerous modifications have been proposed to mitigate the risks associated with aphasia, cognitive issues, and visual field defects. Methods: Our approach is elucidated through intraoperative and cadaveric dissections, complemented by neuroradiological and cadaveric measurements of key anatomical landmarks. A retrospective analysis of patients with drug-resistant MTLE who were treated using our ATL technique at IRCCS Neuromed (Pozzilli) is presented. Results: A total of 385 patients were treated with our ATL subpial technique anatomically focused on the anterior Sylvian point (ASyP). The mean FU was 9.9 ± 5.4 years (range 1-24). In total, 84%of patients were free of seizures during the last follow-up, with no permanent neurological deficits. Transient defects were as follows: aphasia in 3% of patients, visual field defects in 2% of patients, hemiparesis in 2% of patients, and cognitive/memory impairments in 0.8% of patients. In cadaveric dissections, the ASyP was found at a mean distance from the temporal pole of 3.4 ± 0.2 cm (range 3-3.8) at the right side and 3.5 ± 0.2 cm (3.2-3.9) at the left side. In neuroimaging, the ASyP resulted anterior to the temporal horn tip in all cases at a mean distance of 3.2 ± 0.3 mm (range 2.7-3.6) at the right side and 3.5 ± 0.4 mm (range 2.8-3.8) at the left side. Discussion: To the best of our knowledge, this study first introduces the ASyP as a reliable and reproducible cortical landmark to perform the ATL to overcome the patients' variabilities, the risk of Meyer's loop injury, and the bias of intraoperative measurements. Our findings demonstrate that ASyP can be a safe cortical landmark that is useful in MTLE surgery because it is constantly present and is anterior to risky temporal regions such as temporal horn and language networks.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.