Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia.

The clinical management of aneurysmal subarachnoid hemorrhage (SAH)-associated vasospasm remains a challenge in neurosurgical practice, with its prevention and treatment having a major impact on neurological outcome. While considered a mainstay, nimodipine is burdened by some non-negligible limitations that make it still a suboptimal candidate of pharmacotherapy for SAH. This narrative review aims to provide an update on the pharmacodynamics, pharmacokinetics, overall evidence, and strength of recommendation of nimodipine alternative drugs for aneurysmal SAH-associated vasospasm and delayed cerebral ischemia. A PRISMA literature search was performed in the PubMed/Medline, Web of Science, ClinicalTrials.gov, and PubChem databases using a combination of the MeSH terms "medical therapy," "management," "cerebral vasospasm," "subarachnoid hemorrhage," and "delayed cerebral ischemia." Collected articles were reviewed for typology and relevance prior to final inclusion. A total of 346 articles were initially collected. The identification, screening, eligibility, and inclusion process resulted in the selection of 59 studies. Nicardipine and cilostazol, which have longer half-lives than nimodipine, had robust evidence of efficacy and safety. Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics. Combinations between different drug classes have been studied to a very limited extent. Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical.

Impact of augmented reality fiber tractography on the extent of resection and functional outcome of primary motor area tumors.

OBJECTIVE: This study aimed to evaluate the impact of augmented reality intraoperative fiber tractography (AR-iFT) on extent of resection (EOR), motor functional outcome, and survival of patients with primary motor area (M1) intra-axial malignant tumors. METHODS: Data obtained from patients who underwent AR-iFT for M1 primary tumors were retrospectively analyzed and compared with those from a control group who underwent unaugmented reality intraoperative fiber tractography (unAR-iFT). A full asleep procedure with electrical stimulation mapping and fluorescein guidance was performed in both groups. The Neurological Assessment in Neuro-Oncology (NANO), Medical Research Council (MRC), and House-Brackmann grading systems were used for neurological, motor, and facial nerve assessment, respectively. Three-month postoperative NANO and MRC scores were used as outcome measures of the safety of the technique, whereas EOR and survival curves were related to its cytoreductive efficacy. In this study, p < 0.05 indicated statistical significance. RESULTS: This study included 34 and 31 patients in the AR-iFT and unAR-iFT groups, respectively. The intraoperative seizure rate, 3-month postoperative NANO score, and 1-week and 1-month MRC scores were significantly (p < 0.05) different and in favor of the AR-iFT group. However, no difference was observed in the rate of complications. Glioma had incidence rates of 58.9% and 51.7% in the study and control groups, respectively, with no statistical difference. Metastasis had a slightly higher incidence rate in the control group, without statistical significance, and the gross-total resection and near-total resection rates and progression-free survival (PFS) rate were higher in the study group. Overall survival was not affected by the technique. CONCLUSIONS: AR-iFT proved to be feasible, effective, and safe during surgery for M1 tumors and positively affected the EOR, intraoperative seizure rate, motor outcome, and PFS. Integration with electrical stimulation mapping is critical to achieve constant anatomo-functional intraoperative feedback. The accuracy of AR-iFT is intrinsically limited by diffusion tensor-based techniques, parallax error, and fiber tract crowding. Further studies are warranted to definitively validate the benefits of augmented reality navigation in this surgical scenario.

Surgical management of symptomatic hemangioma of the geniculate ganglion: fascicular-sparing resection or grafting?

Geniculate ganglion hemangioma (GGH) is rarely presented in the neurosurgical literature. It extends extradurally on the middle fossa floor and displaces the intratemporal part of the facial nerve. Surgical treatment is advisable at early symptoms. Proposed techniques include fascicular-sparing resection or nerve interruption with grafting. No definitive conclusions exist about the superiority of a certain technique in preserving facial nerve integrity and function. Through the description of a surgically managed symptomatic GGH, we herein discuss literature data about the surgical results of fascicular-sparing resection versus grafting. A PRISMA-based literature search was performed on the PubMed database. Only articles in English and published since 1990 were selected and furtherly filtered based on the best relevance. Statistical comparisons were performed with ANOVA. One hundred sixteen GGHs were collected, 56 were treated by fascicular-sparing resection, and 60 were treated by grafting. The facial function was improved, or unchanged, in 53 patients of the fascicular-sparing group and 30 patients of the grafting one. Sixty-five patients achieved a good (House-Brackmann (HB) grade III) postoperative facial outcome, of which 47 and 18 belonged to the fascicular-sparing and grafting group, respectively. Greater efficacy of the fascicular-sparing technique in the achievement of a better facial outcome was found (p = 0.0014; p = 0.0022). A surgical resection at the earliest symptoms is critical to preserve the facial nerve function in GGHs. Fascicular-sparing resection should be pursued in symptomatic cases with residual facial function (I-III HB). Conversely, grafting has a rationale for higher HB grades (V-VI). Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.

Novel "T-Dimension" Therapies for Pediatric Optic Pathway Glioma: A Timely, Targeted, and Tailored Treatment Trend.

INTRODUCTION: Novel targeted and tailored therapies can substantially improve the prognosis for optic pathway glioma (OPG), especially when implemented in a timely manner. However, their tremendous potential remains underestimated. Therefore, in this study, we provide an updated overview of the clinical trials, current trends, and future perspectives for OPG's novel therapeutic strategies. METHODS: We completed an extensive literature review using the PubMed, MEDLINE, and ClinicalTrials.gov databases. We analyzed and reported the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Thioguanine, procarbazine, lomustine, and vincristine/vinblastine, as well as cisplatin-etoposide, provided excellent results in advanced-phase trials. Selumetinib and trametinib, two oral MEK inhibitors, have been approved for recurrent or refractory OPGs in association with the angiogenetic inhibitor bevacizumab. Among the mTOR inhibitors, everolimus and sirolimus showed the best results. Stereotactic radiosurgery and proton beam radiation therapy have advantages over conventional radiotherapy regimens. Timely treatment is imperative for acute visual symptoms with evidence of tumor progression. This latest evidence can help define a novel "T-Dimension" for pediatric OPG therapies. CONCLUSION: The novel "T-Dimension" for pediatric OPGs is based on recent evidence-based treatments, including combination chemotherapy regimens, molecular targeted therapies, stereotactic radiosurgery, and proton beam radiation therapy. Additional clinical trials are essential for validating each of these new therapies.

A Dedicated Tool for Presurgical Mapping of Brain Tumors and Mixed-Reality Navigation During Neurosurgery.

Brain tumor surgery requires a delicate tradeoff between complete removal of neoplastic tissue while minimizing loss of brain function. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) have emerged as valuable tools for non-invasive assessment of human brain function and are now used to determine brain regions that should be spared to prevent functional impairment after surgery. However, image analysis requires different software packages, mainly developed for research purposes and often difficult to use in a clinical setting, preventing large-scale diffusion of presurgical mapping. We developed a specialized software able to implement an automatic analysis of multimodal MRI presurgical mapping in a single application and to transfer the results to the neuronavigator. Moreover, the imaging results are integrated in a commercially available wearable device using an optimized mixed-reality approach, automatically anchoring 3-dimensional holograms obtained from MRI with the physical head of the patient. This will allow the surgeon to virtually explore deeper tissue layers highlighting critical brain structures that need to be preserved, while retaining the natural oculo-manual coordination. The enhanced ergonomics of this procedure will significantly improve accuracy and safety of the surgery, with large expected benefits for health care systems and related industrial investors.

Rating the incidence of iatrogenic vascular injuries in thoracic and lumbar spine surgery as regards the approach: A PRISMA-based literature review.

PURPOSE: To assess the rate, timing of diagnosis, and repairing strategies of vascular injuries in thoracic and lumbar spine surgery as their relationship to the approach. METHODS: PubMed, Medline, and Embase databases were utilized for a comprehensive literature search based on keywords and mesh terms to find articles reporting iatrogenic vascular injury during thoracic and lumbar spine surgery. English articles published in the last ten years were selected. The search was refined based on best match and relevance. RESULTS: Fifty-six articles were eligible, for a cumulative volume of 261 lesions. Vascular injuries occurred in 82% of instrumented procedures and in 59% during anterior approaches. The common iliac vein (CIV) was the most involved vessel, injured in 49% of anterior lumbar approaches. Common iliac artery, CIV, and aorta were affected in 40%, 28%, and 28% of posterior approaches, respectively. Segmental arteries were injured in 68% of lateral approaches. Direct vessel laceration occurred in 81% of cases and recognized intraoperatively in 39% of cases. CONCLUSIONS: Incidence of iatrogenic vascular injuries during thoracic and lumbar spine surgery is low but associated with an overall mortality rate up to 65%, of which less than 1% for anterior approaches and more than 50% for posterior ones. Anterior approaches for instrumented procedures are at risk of direct avulsion of CIV. Posterior instrumented fusions are at risk for injuries of iliac vessels and aorta. Lateral routes are frequently associated with lesions of segmental vessels. Suture repair and endovascular techniques are useful in the management of these severe complications.

Microneurosurgical Management of Posterior Inferior Cerebellar Artery Aneurysms: Results of a Consecutive Series.

Aneurysms of the posterior inferior cerebellar artery (PICA) are uncommon. The complex anatomy of PICA and its intimate relationships with medulla, lower cranial nerves, and jugular tubercle makes the surgical treatment of these aneurysms fascinating. The reported is study aimed at a critical review of the overall results of a personal series of PICA aneurysms, treated by the senior author, R. Galzio. Demographics, charts, videos, outcome, and follow-up of a cohort of PICA aneurysms managed in the last 10 years were retrospectively analyzed, focusing only upon those treated with microneurosurgery. Twenty-five patients, harboring a single aneurysm, were operated on. Fifteen aneurysms were ruptured. Nineteen were proximal, all of these being been treated through a far-lateral approach. Trans-condylar or trans-tubercular variants were rarely necessary and however reserved to peculiar cases. Twenty-three aneurysms underwent direct treatment consisting of clip ligation. At 6-month follow-up, 60% of patients had a modified Rankin Score (mRS) of 0-2. Given the high anatomical variability of both PICA and patients' bony anatomy, a case-by-case meticulous preoperative imaging evaluation is mandatory for the choice of the most suitable and tailored surgical corridor which, in turn, is pivotal to achieve the best outcome.

Posterior Circulation Aneurysms: A Critical Appraisal of a Surgical Series in Endovascular Era.

The advent of the endovascular era has apparently decreased the role of microneurosurgery for many of the posterior circulation aneurysms. This study consists of a critical appraisal of a retrospective surgical series regarding posterior circulation aneurysms, targeted to define whether microneurosurgery still has a role for some of these. In 28 years, 157 aneurysms were surgically treated, 98 of which ruptured. The Average patient age was 56.7 ± 14.2 years, while in hemorrhagic cases, the mean Hunt-Hess score was 2.17 ± 0.8. Basilar tip, vertebral artery and proximal posterior inferior cerebellar artery were the most frequently involved sites. The treatment consisted of 128 clippings, 19 trappings, 7 wrappings, and 3 bypasses. A total exclusion was achieved in 88.5% of the aneurysms. An average follow-up of 67.1 ± 61.3 months proved no recurrences. The best results were observed in patients <65 years old who harbored small-to-regular aneurysms of the basilar tip, distal cerebellar arteries, or vertebral artery.Clipping proved to be a definitive and durable treatment for a large part of posterior circulation aneurysms, whereas bypass allows for treating aneurysms not amenable for coiling, stenting, or clipping. The present study confirms that microneurosurgery continues to have a paramount role within neurovascular pathology.

Microneurosurgery for Paraclinoid Aneurysms in the Context of Flow Diverters.

The advent of flow diverter (FD) stents has apparently reduced the role of microneurosurgery for paraclinoid aneurysms despite sparse high-quality evidence about their long-term effects.The present study critically reviews the overall results of a microneurosurgical series of 57 paraclinoid aneurysms.Of these aneurysms, 47.4% were regular in size while 19.3 were giant. Barami type I was predominant. In 21 aneurysms a hemorrhagic onset occurred. Pterional approach with intradural anterior clinoidectomy was preferred by far. Clipping was possible in 91.2% of aneurysms and a high-flow bypass was the choice in five cases. An mRS of 0-2 was achieved in 77.3% of patients, typically <50 years old.Visual field appeared improved or unchanged in 36.3% and 63.6% of the symptomatic patients, respectively. In 76.1% of incidental aneurysms, campimetry was unaffected by surgery.A complete aneurysm exclusion was achieved in 93% of cases using a single procedure. No recurrences were documented on an average follow-up of 54.1 ± 34 months.Microneurosurgery is still a valuable, definitive, and durable option for Barami type Ia, Ib, or II paraclinoid aneurysm, especially in patients <50 years old and visually symptomatic. Conditions other than these are ideal candidates for FD stents.

The Preoperative Functional Downgrading of Brain AVMs.

The actual role of preoperative embolization of brain arteriovenous malformations (AVMs) is undervalued.The present study aims to describe the effectiveness, safety, technics, and results of the endovascular-based functional downgrading of brain AVMs.Data regarding 31 Spetzler-Martin (SM) grade III AVMs that consecutively underwent a combined endovascular-surgical treatment were reviewed. Clinical and radiological outcomes were evaluated according to modified Ranking Scale score (mRS) and postoperative angiography, respectively.Low-density Onyx was used in all cases, and the timeframe between the embolizations was 10-15 days. Procedures were 1.6 (±0.6) on average. Superselective nidal catheterization was essential to reach the deepest parts of the AVMs, which were the targets. Onyx made the nidus compact and easier to dissect. The Average obliteration rate was 29.6%, with negligible morbidity. Surgery was performed after 3.7 days on average and the AVM exclusion was complete in 83.4% of cases. An mRS score between 0 and 2 was reported in 77.5% of patients, while the best outcome was achieved in small and medium-deep malformations.An effective and safe functional downgrading of brain AVMs must be based upon specific technical key aspects, which make surgery easier and, ultimately, allow for the achievement of the best outcome.

Supratentorial high-grade gliomas: maximal safe anatomical resection guided by augmented reality high-definition fiber tractography and fluorescein.

OBJECTIVE: The theoretical advantages of augmented reality (AR) with diffusion tensor imaging (DTI)-based high-definition fiber tractography (HDFT) and sodium fluorescein (F) in high-grade glioma (HGG) surgery have not been investigated in detail. In this study, the authors aimed to evaluate the safety and efficacy profiles of HDFT-F microscope-based AR cytoreductive surgery for newly diagnosed supratentorial HGGs. METHODS: Data of patients with newly diagnosed supratentorial HGGs who underwent surgery using the AR HDFT-F technique were reviewed and compared with those of a cohort of patients who underwent conventional white-light surgery assisted by infrared neuronavigation. The safety and efficacy of the techniques were reported based on the postoperative Neurological Assessment in Neuro-Oncology (NANO) scores, extent of resection (EOR), and Kaplan-Meier curves, respectively. The chi-square test was conducted for categorical variables. A p value < 0.05 was considered statistically significant. RESULTS: A total of 54 patients underwent surgery using the AR HDFT-F technique, and 63 underwent conventional white-light surgery assisted by infrared neuronavigation. The mean postoperative NANO scores were 3.8 ± 2 and 5.2 ± 4 in the AR HDFT-F group and control group, respectively (p < 0.05). The EOR was higher in the AR HDFT-F group (p < 0.05) than in the control group. With a mean follow-up of 12.2 months, the rate of progression-free survival (PFS) was longer in the study group (log-rank test, p = 0.006) than in the control group. Moreover, the complication rates were 9.2% and 9.5% in the study and control groups, respectively. CONCLUSIONS: Overall, AR HDFT-F-assisted surgery is safe and effective in maximizing the EOR and PFS rate for patients with newly diagnosed supratentorial HGGs, and in optimizing patient functional outcomes.

Shedding the Light on the Natural History of Intracranial Aneurysms: An Updated Overview.

The exact molecular pathways underlying the multifactorial natural history of intracranial aneurysms (IAs) are still largely unknown, to the point that their understanding represents an imperative challenge in neurovascular research. Wall shear stress (WSS) promotes the genesis of IAs through an endothelial dysfunction causing an inflammatory cascade, vessel remodeling, phenotypic switching of the smooth muscle cells, and myointimal hyperplasia. Aneurysm growth is supported by endothelial oxidative stress and inflammatory mediators, whereas low and high WSS determine the rupture in sidewall and endwall IAs, respectively. Angioarchitecture, age older than 60 years, female gender, hypertension, cigarette smoking, alcohol abuse, and hypercholesterolemia also contribute to growth and rupture. The improvements of aneurysm wall imaging techniques and the implementation of target therapies targeted against inflammatory cascade may contribute to significantly modify the natural history of IAs. This narrative review strives to summarize the recent advances in the comprehension of the mechanisms underlying the genesis, growth, and rupture of IAs.

Microsurgical Clipping of Carotid-Ophthalmic Tandem Aneurysms: Case Report and Surgical Nuances.

Tandem intracranial aneurysms (TandIAs) are rare but inherently complex, and special technical considerations are required for their surgical management. The present case highlights the key surgical aspects of two carotid-ophthalmic TandIAs incidentally found in a 60-year-old female. Both the aneurysms were superiorly projecting, regular in size, and involved the left ophthalmic segment of the internal carotid artery (ICA). The minimum distance between the necks was 3 mm. The patient underwent microsurgery because of the reported major complications rate of the endovascular treatment in the case of a very short minimum distance between the TandIAs. After cervical ICA exposure, both the aneurysms were excluded through a pterional approach. Intradural anterior clinoidectomy and unroofing of the optic canal allowed the mobilization of the left optic nerve. The more distal aneurysm was clipped before the opening of the distal dural ring of the ICA. The proximal aneurysm was clipped with two straight clips stacked perpendicular to the ICA. A small remnant was intentionally left to avoid the stenosis of the ophthalmic artery. Postoperative angiography showed the exclusion of both the aneurysms with a small dog-ear of the more proximal one. The patient was discharged neurologically intact and, after one year, the remnant remained stable. Microsurgical clipping is a definitive and durable treatment for carotid-ophthalmic TandIAs. In the case of a very short minimum distance between the aneurysms, the distal one should be clipped first to make the anterior clinoidectomy, opening of the distal dural ring of the ICA, and clipping of the more proximal aneurysm easier.

Mild Head Trauma (MHT) and Antiplatelet Therapy. Reply to Lorenzati et al. Comment on "Savioli et al. Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications? Medicina 2021, 57, 357".

We read your data with interest, and we truly appreciate the similar experience [...].

Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications?

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient's condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

Pai syndrome: a review.

BACKGROUND: Pai syndrome is a rare idiopathic developmental condition characterized by midline craniofacial abnormalities. It was originally described as the presence of a median cleft lip, cutaneous polyps of the nasal mucosa and face, and midline lipomas of the central nervous system, mostly at the corpus callosum. However, there is great phenotypical variability and these characteristics are rarely all present at once. OBJECTIVE: The aim of this review was to analyze the available evidence regarding Pai syndrome in order to better delineate this rare condition and its features. METHODS: We analyzed the PubMed database using the words "Pai syndrome", "frontonasal dysplasia", "cleft lip", "nasal polyp", "facial polyp", and "corpus callosum lipoma", including reviews, case reports and case series. CONCLUSION: There is no consensus regarding the diagnostic criteria of Pai syndrome up to date. It is usually diagnosed at birth, and its incidence is often underestimated. At present, the etiology of Pai syndrome is unknown. Several hypotheses regarding its genetic background have been made; however, there are not enough data yet to elucidate this point. An improved awareness could help in diagnosing the condition and performing the necessary investigations. These patients should have a multidisciplinary follow-up.

Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery.

Trauma Coagulopathy and Its Outcomes.

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was >10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE <-6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy.

Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.

INTRODUCTION: During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. METHODS: This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic-clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. RESULTS: A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). CONCLUSIONS: The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.

NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.

The relevance of nitric oxide synthase 2 (NOS2) as a prognostic factor in Glioblastoma Multiforme (GBM) malignancy is emerging. We analyzed the effect of NOS2 inhibitor 1400W on the autophagic flux and extracellular vesicle (EV) secretion in U87MG glioma cells. The effects of glioma stem cells (GSC)-derived EVs on adherent U87MG were evaluated. Cell proliferation and migration were examined while using Cell Counting Kit-8 assay (CCK-8) and scratch wound healing assay. Cell cycle profile and apoptosis were analyzed by flow cytometry. Autophagy-associated acidic vesicular organelles were detected and quantified by acridine orange staining. The number and size of EVs were assessed by nanoparticle tracking analysis. EV ultrastructure was verified by transmission electron microscopy (TEM). WB was used to analyze protein expression and acid sphingomyelinase was determined through ceramide levels. 1400W induced autophagy and EV secretion in both adherent U87MG and GSCs. EVs secreted by 1400W-treated GSC, but not those from untreated cells, were able to inhibit adherent U87MG cell growth and migration while also inducing a relevant level of autophagy. The hypothesis of NOS2 expression as GBM profile marker or interesting therapeutic target is supported by our findings. Autophagy and EV release following treatment with the NOS2 inhibitor could represent useful elements to better understand the complex biomolecular frame of GBM.