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Essential tremor (ET) is identified as the most prevalent movement disorder, primarily characterized by tremors in both upper extremities. The spectrum of surgical options for ET includes gamma knife radiosurgery (GKRS) and other stereotactic radiosurgery (SRS) modalities. Despite the limitations of these options, SRS is deemed an essential and indispensable approach. Our research aimed to assess the safety and efficacy of SRS, such as GKRS, on tremor control and the spectrum of associated adverse events in the treatment of ET, also focusing on long term outcomes of the procedure. We systematically conducted an extensive search across esteemed databases, which included PubMed, Cochrane Library, Embase, and Web of Science. We included studies involving individuals diagnosed with ET who had undergone GRKS treatment. A proportional rate was used to evaluate the outcomes in a 95% confidence interval. We included 12 studies comprising 414 patients. The treatment success rate with SRS was 86.6% (95% CI: 72.4-100%). Conversely, the overall failure rate was 13.4% (95% CI: 0.00 to 27.6%). Notably, post-procedure complications were observed in 9.7% of patients (95% CI: 5.8-13.6%). A meta-analysis of five studies revealed a statistically significant reduction of tremor from the FTM scale after treatment with GKRS (MD -2.1; 95% CI -2.5 to -1.6; p < 0.01; I² = 81%). A meta-analysis of eight studies revealed a statistically significant reduction in writing tremor from the FTM scale after treatment with GKRS (MD -1.7; 95% CI -2.3 to -1.2; p < 0.01; I² = 93%). A meta-analysis of six studies revealed a statistically significant reduction in drawing tremor from the FTM scale after treatment with GKRS (MD -1.9; 95% CI -2.5 to -1.4; p < 0.01; I² = 80%). Finally, a meta-analysis of three studies revealed a statistically significant reduction in drinking tremor from the FTM scale after treatment with GKRS (MD -1.6; 95% CI -1.9 to -1.3; p < 0.01; I² = 11%). Our findings show a high success rate and low failure of GKRS for ET. Thus, GKRS is a seemingly effective and safe option for managing these patients. The importance of this research lies in its contribution to the evolving landscape of radiosurgery, providing a robust basis for the clinical application of GKRS., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Over the last years, multiple studies have been dedicated to evaluate the efficacy of different treatment options for Neuromyelitis Optica Spectrum Disorder (NMOSD). However, there is a wide variety of endpoints employed across these studies. Our goal is to conduct a systematic review describing the endpoints utilized in studies related to NMOSD., Methods: Medline, Embase, and Cochrane were searched from inception to May 2023, to identify studies analyzing treatment options in patients with NMOSD. We collected data on baseline study characteristics and all efficacy outcomes available., Results: We included 127 studies and identified approximately 40 different efficacy endpoints, categorized into 1) relapse, 2) disability, 3) visual acuity, and 4) surrogate outcomes. Most studies were retrospective (54.3 %) and aimed at attack prevention (81.4 %). The most common relapse-related outcomes were annualized relapse rate (73.2 %), followed by relapse rate (50.4 %), and relapse-free rate (36.2 %). The relapse definition also varied widely among studies, with only 73 (57.4 %) studies explicitly addressing the definition used. The most common disability outcome was the Expanded Disability Scale (97.6 %), followed by the Modified Rankin Scale (7.9 %). Visual Acuity Score was employed in 14.2 % of studies, followed by Visual Evoked Potentials (6.3 %). Imaging was the most common surrogate (20.5 %), followed by the fraction of B cells (18.1 %)., Conclusion: Publications were heterogeneous in measuring efficacy, with different use of endpoints and relapse definitions. Standardization across studies would improve data analysis and application in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors have no conflict of interest to declare.

Introduction: Tirofiban is a fast-acting glycoprotein IIb-IIIa inhibitor that inhibits the final common pathway to platelet aggregation and has been studied as adjuvant therapy for acute ischemic stroke (AIS). Since the prior meta-analysis new randomized controlled trials (RCTs) have been published. This meta-analysis aimed to update the current knowledge on the efficacy of tirofiban for patients with AIS not submitted to reperfusion therapies., Methods: We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting the use of tirofiban in AIS. The efficacy outcomes were favorable functional outcome, functional disability, modified Rankin Scale change at 90 days, and changes in the National Institutes of Health Stroke Scale score after 24 hours and 7 days of the symptom onset. The safety outcomes include symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and all-cause mortality., Results: A higher rate of favorable functional outcome was associated with tirofiban administration (RR= 1.09; 95 % CI 1.04-1.14; p<0.001). The mRS after 90 days was significantly lower in the tirofiban group (MD= -0.55; 95 % CI -0.90 - [-0.20]; p<0.01). Tirofiban administration was not significantly associated with higher rates of sICH in AIS patients (RR= 0.85; 95 % CI 0.26-2.81; p = 0.79) or any ICH compared to the control group (RR= 1.01; 95 % CI 0.42-2.39; p = 0.98). All-cause mortality was similar between groups (RR= 0.64; 95 % CI 0.34-1.23; p = 0.18)., Conclusion: Tirofiban increases the number of patients achieving a favorable functional outcome in patients. There was no improvement in NIHSS after 24 hours and 7 days. Tirofiban did not increase the risk of sICH or any ICH, and mortality was similar between groups., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Temporal lobe epilepsy (TLE) is a prevalent form of epilepsy originating in the temporal lobes. A common pathological feature is hippocampal sclerosis (HS), characterized by the loss of neuronal cells, which is associated with the typical temporal mesial lobe epilepsy (MTLE). In this study, we aimed to analyze gray matter alterations in patients with MTLE with right and left hemisphere HS using voxel-based morphometry and compare them with control groups. A meta-analysis was performed based on the guidelines contained in the Protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the MEDLINE database, with the keywords: "gray matter" AND "temporal lobe epilepsy " AND ("hippocampal sclerosis" OR "hippocampal abnormalities") AND ("voxel-based morphometry" OR "VBM" OR "voxel-wise"). Of the 14 articles included in the review, 8 were added by the method, in which the meta-analysis was performed. Our results indicate that in the right hemisphere, the hippocampus, caudate nucleus, parahippocampal gyrus, thalamus, dorsalis medial nucleus, insula, and right claustrum were most commonly implicated. In the left hemisphere, a significant pattern of gray matter loss was observed in the putamen, lentiform nucleus, uncus, Brodmann areas 20 and 23, cingulate gyrus, caudate nucleus, cerebellum, and cuneus compared to healthy controls.Our study highlights distinct patterns of gray matter alteration in MLTE-HS and suggests that these regions may contribute to changes in verbal memory and visuospatial impairment based on their anatomical and hemispheric locations. Our findings can be potentially helpful for future diagnostic markers, therapeutic targets, and insights into disease progression, better understanding of these findings., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I 2  = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I 2  = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I 2  = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I 2  = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I 2  = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I 2  = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I 2  = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I 2  = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I 2  = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I 2  = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I 2  = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression - Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I 2  = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I 2  = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I 2  = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.Prospero registry: CRD42023486694., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Tremor-dominant Parkinson's Disease (TDPD) has a slower neurological decline compared to other phenotypes of the disease, but significantly impacts daily activities and is often less responsive to standard medications. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) lesioning of the Ventral Intermediate (VIM) nucleus of the thalamus may alleviate symptoms for these patients., Methods: A systematic review and meta-analysis of English-language studies from PubMed, Cochrane, and Embase were conducted, assessing the efficacy and safety of MRgFUS VIM thalamotomy in TDPD patients. Tremor scores were evaluated using the Clinical Scale Rating for Tremor and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRSIII). Neuropsychological outcomes were measured using the Parkinson Disease Questionnaire (PDQ) and the Montreal Cognitive Assessment. This analysis adhered to Cochrane and PRISMA guidelines., Results: Thirteen studies with 211 patients were included. MDS-UPDRSIII scores showed significant improvement at 1, 6, and 12 months post-MRgFUS, respectively: (MD -8.92 points, 95% CI: -15.44 to -2.40, p < 0.01; MD -7.39 points, 95% CI: -11.47 to -3.30, p < 0.01; MD -10.66 points, 95% CI: -16.89 to -4.43, p < 0.01). PDQ scores at baseline compared to 6 months post-treatment also indicated a significant improvement (SMD - 0.86, 95% CI: -1.21 to -0.50, p < 0.01). Neurological adverse events were generally mild and transient, with gait instability and sensory deficits being the most common., Conclusion: This meta-analysis demonstrates significant improvements in tremor and neuropsychological outcomes following MRgFUS VIM thalamotomy in TDPD patients, with adverse events being typically mild and transient., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aims to address the safety and efficacy of mechanical thrombectomy (MT) in acute ischemic stroke with an established infarction equal to or >50 mL with a significant difference between penumbra and established infarction detected by perfusion cerebral computed tomography (CT) with the Rapid ® system., Methods: This was a retrospective case-control study. Patients diagnosed with established and extensive ischemic stroke, defined by an ischemic volume equal to or >50 mL on CT or magnetic resonance imaging perfusion using the RAPID ® system, were examined. The intervention group received endovascular interventional treatment with or without recombinant tissue plasminogen activator (rt-PA) in addition to standard therapy, and the control group received conservative treatment with or without rt-PA plus standard therapy., Results: A total of 59 patients were enrolled, including 38 in the intervention group and 21 in the control group. Baseline characteristics were similar between groups. Patient National Institutes of Health Stroke Scale at discharge was significantly different between the control (median 30, interquartile range [IQR] 13) and intervention group (median 8, IQR 14) ( P < 0.001). Modified Rankin scale (mRS) scores were significantly different at discharge between intervention (median mRS 2, IQR 3) and controls (median mRS 5, IQR 1) ( P = 0.002). These mRS differences remained significant at 90 days, with median (IQR) values of 2 (2.75) and 5 (1), respectively ( P < 0.001)., Conclusion: MT is safe and effective for large-core ischemic strokes with significant perfusion mismatch, leading to better functional outcomes without significant complications compared to the best medical treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Background: Ischemic preconditioning (IP) is a powerful cellular protection mechanism. The cellular pathways underlying IP are extremely complex and involve the participation of cell triggers, intracellular signaling pathways, and end-effectors. Experimental studies have shown that sodium-glucose transport protein 2 (SGLT2) inhibitors promote activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main regulator of adenosine 5'-triphosphate homeostasis and energy metabolism in the body. Despite its cardioprotective profile demonstrated by numerous clinical trials, the results of studies on the action of SGLT2 inhibitors in IP are scarce. This study will investigate the effects of dapagliflozin on IP in patients with coronary artery disease (CAD). Methods: The study will include 50 patients with multivessel CAD, ischemia documented by stress testing, and preserved left ventricular ejection fraction (LVEF). Patients will undergo four exercise tests, the first two with a time interval of 30 min between them after washout of cardiovascular or hypoglycemic medications and the last two after 7 days of dapagliflozin 10 mg once a day, also with a time interval of 30 min between them. Discussion: The role of SGLT2 inhibitors on IP is not clearly established. Several clinical trials have shown that SGLT2 inhibitors reduce the occurrence cardiovascular events, notably heart failure. However, such studies have not shown beneficial metabolic effects of SGLT2 inhibitors, such as reducing myocardial infarction or stroke. On the other hand, experimental studies with animal models have shown the beneficial effects of SGLT2 inhibitors on IP, a mechanism that confers cardiac and vascular protection from subsequent ischemia-reperfusion (IR) injury. This is the first clinical study to evaluate the effects of SGLT2 inhibitors on IP, which could result in an important advance in the treatment of patients with stable CAD.

The diagnosis of Moyamoya disease (MMD) relies heavily on imaging, which could benefit from standardized machine learning tools. This study aims to evaluate the diagnostic efficacy of deep learning (DL) algorithms for MMD by analyzing sensitivity, specificity, and the area under the curve (AUC) compared to expert consensus. We conducted a systematic search of PubMed, Embase, and Web of Science for articles published from inception to February 2024. Eligible studies were required to report diagnostic accuracy metrics such as sensitivity, specificity, and AUC, excluding those not in English or using traditional machine learning methods. Seven studies were included, comprising a sample of 4,416 patients, of whom 1,358 had MMD. The pooled sensitivity for common and random effects models was 0.89 (95% CI: 0.85 to 0.92) and 0.92 (95% CI: 0.85 to 0.96), respectively. The pooled specificity was 0.89 (95% CI: 0.86 to 0.91) in the common effects model and 0.91 (95% CI: 0.75 to 0.97) in the random effects model. Two studies reported the AUC alongside their confidence intervals. A meta-analysis synthesizing these findings aggregated a mean AUC of 0.94 (95% CI: 0.92 to 0.96) for common effects and 0.89 (95% CI: 0.76 to 1.02) for random effects models. Deep learning models significantly enhance the diagnosis of MMD by efficiently extracting and identifying complex image patterns with high sensitivity and specificity. Trial registration: CRD42024524998 https://www.crd.york.ac.uk/prospero/displayrecord.php?RecordID=524998., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Head elevation is recommended as a tier zero measure to decrease high intracranial pressure (ICP) in neurocritical patients. However, its quantitative effects on cerebral perfusion pressure (CPP), jugular bulb oxygen saturation (SjvO 2 ), brain tissue partial pressure of oxygen (PbtO 2 ), and arteriovenous difference of oxygen (AVDO 2 ) are uncertain. Our objective was to evaluate the effects of head elevation on ICP, CPP, SjvO 2 , PbtO 2 , and AVDO 2 among patients with acute brain injury., Methods: We conducted a systematic review and meta-analysis on PubMed, Scopus, and Cochrane Library of studies comparing the effects of different degrees of head elevation on ICP, CPP, SjvO 2 , PbtO 2 , and AVDO 2 ., Results: A total of 25 articles were included in the systematic review. Of these, 16 provided quantitative data regarding outcomes of interest and underwent meta-analyses. The mean ICP of patients with acute brain injury was lower in group with 30° of head elevation than in the supine position group (mean difference [MD] - 5.58 mm Hg; 95% confidence interval [CI] - 6.74 to - 4.41 mm Hg; p < 0.00001). The only comparison in which a greater degree of head elevation did not significantly reduce the ICP was 45° vs. 30°. The mean CPP remained similar between 30° of head elevation and supine position (MD - 2.48 mm Hg; 95% CI - 5.69 to 0.73 mm Hg; p = 0.13). Similar findings were observed in all other comparisons. The mean SjvO 2 was similar between the 30° of head elevation and supine position groups (MD 0.32%; 95% CI - 1.67% to 2.32%; p = 0.75), as was the mean PbtO 2 (MD - 1.50 mm Hg; 95% CI - 4.62 to 1.62 mm Hg; p = 0.36), and the mean AVDO 2 (MD 0.06 µmol/L; 95% CI - 0.20 to 0.32 µmol/L; p = 0.65).The mean ICP of patients with traumatic brain injury was also lower with 30° of head elevation when compared to the supine position. There was no difference in the mean values of mean arterial pressure, CPP, SjvO 2 , and PbtO 2 between these groups., Conclusions: Increasing degrees of head elevation were associated, in general, with a lower ICP, whereas CPP and brain oxygenation parameters remained unchanged. The severe traumatic brain injury subanalysis found similar results., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Neuroendoscopy (NE) surgery emerged as a promising technique for the treatment of spontaneous intracerebral hemorrhage (ICH). A previous meta-analysis of randomized controlled trials (RCTs) analyzed the efficacy and safety of NE compared to craniotomy, but NE did not present a significant improvement in functional outcomes. However, a new study provided an opportunity to update the current knowledge. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting NE evacuation of spontaneous supratentorial ICH compared to craniotomy. The efficacy outcomes of interest were favorable functional outcome, functional disability, hematoma evacuation rate, and residual hematoma volume. The safety outcomes of interest were rebleeding, infection, and mortality. Seven RCTs were included containing 879 patients. The NE approach presented a significantly higher rate of favorable functional outcome compared with craniotomy (RR: 1.42; 95% CI 1.17, 1.73; p < 0.001). The evacuation rate was higher in patients who underwent the NE approach (MD: -8.36; 95% CI -12.66, -4.07; p < 0.001). NE did not show a benefit in improving the mortality rate (RR: 0.81, 95% CI 0.54, 1.22; p = 0.32). NE was associated with more favorable functional outcomes and lower rates of functional disabilities compared to craniotomy. Also, NE was superior regarding evacuation rate, while presenting a reduction in residual hematoma volume. NE might be associated with lower infection rates. Mortality was not improved by NE surgery. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy and safety of NE compared to craniotomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative., Aims: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms., Results: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality., Conclusions: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Delayed cerebral ischemia (DCI) is a common and severe complication after subarachnoid hemorrhage (SAH). Logistic regression (LR) is the primary method to predict DCI, but it has low accuracy. This study assessed whether other machine learning (ML) models can predict DCI after SAH more accurately than conventional LR. PubMed, Embase, and Web of Science were systematically searched for studies directly comparing LR and other ML algorithms to forecast DCI in patients with SAH. Our main outcome was the accuracy measurement, represented by sensitivity, specificity, and area under the receiver operating characteristic. In the six studies included, comprising 1828 patients, about 28% (519) developed DCI. For LR models, the pooled sensitivity was 0.71 (95% confidence interval [CI] 0.57-0.84; p < 0.01) and the pooled specificity was 0.63 (95% CI 0.42-0.85; p < 0.01). For ML models, the pooled sensitivity was 0.74 (95% CI 0.61-0.86; p < 0.01) and the pooled specificity was 0.78 (95% CI 0.71-0.86; p = 0.02). Our results suggest that ML algorithms performed better than conventional LR at predicting DCI.Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42023441586; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=441586., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Swallowing is a complex function that can be disrupted after stroke. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation therapy that recently has been tested to treat stroke-related dysphagia., Methods: The authors performed a search in the literature to review the described evidence of the use of tDCS in dysphagia after stroke. Three electronic databases were searched. The risk of bias evaluation was carried out through the RoB-2 tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was also implemented., Results: Of 265 articles, only nine studies were included in this review. The most common location of the tDCS stimulation was the unaffected hemisphere (44%). Regarding the outcome measure, the Dysphagia Outcome and Severity Scale (DOSS) was the most commonly used (55%). However, due to the high heterogeneity of the protocols, and considering the differences between the types of stroke, the authors opted not to perform a metanalysis. Instead, a systematic review with a thorough analysis of each individual study and the impact of the differences to the outcomes was preferred., Conclusions: The final considerations are that even though the majority of studies described benefits from tDCS in post-stroke dysphagia, as they present too many methodological differences, it is not possible to compare them. In addition, many articles included patients with less than 6 months after stroke, which is an important bias as the swallowing function can be recovered spontaneously within this period, turning the certainty of the evidence really low., (© 2023. Fondazione Società Italiana di Neurologia.)

Ruptured anterior communicating artery (ACoA) aneurysms are frequently associated with neuropsychological deficits. This review aims to compare neuropsychological outcomes between surgical and endovascular approaches to ACoA. We systematically searched PubMed, Embase, and Web of Science for studies comparing the endovascular and surgical approaches to ruptured ACoA aneurysms. Outcomes of interest were the cognitive function, covered by memory, attention, intelligence, executive, and language domains, as well as motor and visual functions. Nine studies, comprising 524 patients were included. Endovascularly-treated patients showed better memory than those treated surgically (Standardized Mean Difference (SMD) = -2; 95% CI: -3.40 to -0.61; p < 0.01). Surgically clipped patients had poorer motor ability than those with coiling embolization (p = 0.01). Executive function (SMD = -0.20; 95% CI: -0.47 to 0.88; p = 0.55), language (SMD = -0.33; 95% CI: -0.95 to 0.30; p = 0.30), visuospatial function (SMD = -1.12; 95% CI: -2.79 to 0.56; p = 0.19), attention (SMD = -0.94; 95% CI: -2.79to 0.91; p = 0.32), intelligence (SMD = -0.25; 95% CI: -0.73 to 0.22; p = 0.30), and self-reported cognitive status (SMD = -0.51; 95% CI: -1.38 to 0.35; p = 0.25) revealed parity between groups. Patients with ACoA treated endovascularly had superior memory and motor abilities. Other cognitive domains, including executive function, language, visuospatial function, attention, intelligence and self-reported cognitive status revealed no statistically significant differences between the two approaches. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42023461283; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=461283., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The neutrophil-lymphocyte ratio (NLR) is an easily accessible and inexpensive biomarker that has been shown to predict morbidity and mortality in congenital cardiac surgery. However, its regulatory mechanism remains unclear. This study aims to compare and correlate the tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 messenger RNAs (mRNAs) with the NLR in patients with tetralogy of Fallot (ToF) and ventricular septal defect (VSD)., Methods: A prospective translational study was conducted on 10 children with ToF and 10 with VSD, aged between 1 and 24 months. The NLR was calculated from the blood count taken 24 hours before surgery. The expression of these mRNAs was analyzed in the myocardial tissue of the right atrium prior to cardiopulmonary bypass., Results: Patients with ToF exhibited a higher NLR [ToF 0.46 (interquartile range; IQR) 0.90; VSD 0.28 (IQR 0.17); P=0.02], longer mechanical ventilation time [ToF 24 h (IQR 93); VSD 5.5 h (IQR 8); P<0.001], increased use of vasoactive drugs [ToF 2 days (IQR 1.75); VSD 0 (IQR 1); P=0.01], and longer ICU [ToF 5.5 (IQR 1); VSD 2 (IQR 0.75); P=0.02] and hospital length of stays [ToF 18 days (IQR 17.5); VSD 8.5 days (IQR 2.5); P<0.001]. A negative correlation was found between NLR and oxygen saturation (SaO 2 ) (r=-0.44; P=0.002). In terms of mRNA expression, the ToF group showed a lower expression of IL-10 mRNA (P=0.03). A positive correlation was observed between IL-10-mRNA and SaO 2 (r=0.40; P=0.07), and a negative correlation with NLR (r=-0.27; P=0.14)., Conclusions: Patients with ToF demonstrated a higher preoperative NLR and lower IL-10 mRNA expression by what appears to be a pro-inflammatory phenotype of cyanotic patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-513/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Background: Severe disorders of consciousness (sDoC) are a common sequela of aneurysmal subarachnoid hemorrhages (aSAH), and amantadine has been used to improve cognitive recovery after traumatic brain injury., Objective: This study evaluated the effect of amantadine treatment on consciousness in patients with sDoC secondary to aSAH., Methods: This double-center, randomized, prospective, cohort study included patients ≥ 18 years old with sDoC after aSAH from February 2020 to September 2023. Individual patient data of patients were pooled to determine the effect of amantadine, in comparison to placebo. The primary outcomes at 3 and 6 months after the ictus were evaluated using the modified Rankin scale (mRS) and Glasgow outcome scale (GOS). In addition to all-cause mortality, secondary endpoints were assessed weekly during intervention by scores on Rappaport's Disability Rating Scale (RDRS) and Coma Recovery Scale-Revised (CRSR)., Results: Overall, 37 patients with sDoC and initial Glasgow Coma Scale (GCS) varying between 3 and 11 were recruited and randomized to amantadine (test group, n = 20) or placebo (control group, n = 17). The average age was 59.5 years (28 to 81 year-old), 24 (65%) were women, and the mean GCS at the beginning of intervention was 7.1. Most patients evolved to vasospasm (81%), with ischemia in 73% of them. The intervention was started between 30 to 180 days after the ictus, and administered for 6 weeks, with progressively higher doses. Neither epidemiological characteristics nor considerations regarding the treatment of the aneurysm and its complications differed between both arms. Overall mortality was 10.8% (4 deaths). During the study, four patients had potential adverse drug effects: two presented seizures, one had paralytic ileus, and another evolved with tachycardia; the medication was not suspended, only the dose was not increased. At data opening, 2 were taking amantadine and 2 placebo., Conclusion: Despite some good results associated with amantadine in the literature, this study did not find statistically significant positive effects in cognitive recovery in patients with delayed post-aSAH sDoC. Further large randomized clinical trials in patients' subgroups are needed to better define its effectiveness and clarify any therapeutic window where it can be advantageous., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background:  In 2012, the Neurocritical Care Society launched a compilation of protocols regarding the core issues that should be addressed within the first hours of neurological emergencies - the Emergency neurological life support (ENLS)., Objective:  We aim to evaluate this repercussion through a bibliometric analysis., Methods:  We searched Scopus on October 2022 for articles mentioning ENLS. The following variables were obtained: number of citations; number of citations per year; number of publications per year; year of publication; research type; research subtype; country of corresponding author and its income category and world region; journal of publication and its 5-year impact factor (IF); and section where ENLS appeared., Results:  After applying eligibility criteria, we retrieved 421 articles, published from 2012 to 2022. The mean number of citations per article was 17.46 (95% Confidence Interval (CI) = 8.20-26.72), while the mean number of citations per year per article was 4.05 (95% CI = 2.50-5.61). The mean destiny journal 5-year IF was 5.141 (95% CI = 4.189-6.093). The majority of articles were secondary research (57.48%; n  = 242/421) of which most were narrative reviews (71.90%; n  = 174/242). High-Income countries were the most prominent (80.05%; n  = 337/421 articles). There were no papers from low-income countries. There were no trials or systematic reviews from middle-income countries., Conclusion:  Although still low, the number of publications mentioning ENLS is increasing. Articles were mainly published in journals of intensive care medicine, neurology, neurosurgery, and emergency medicine. Most articles were published by authors from high-income countries. The majority of papers were secondary research, with narrative review as the most frequent subtype., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Purpose: Temporary arterial occlusion (TAO) is a widespread practice in the surgical treatment of intracranial aneurysms. This study aimed to investigate TAO's role during ruptured aneurysm clipping as an independent prognostic factor on short- and long-term outcomes., Methods: This prospective cohort included 180 patients with ruptured intracranial aneurysms and an indication of microsurgical treatment. Patients who died in the first 12 hours after admission were excluded., Results: TAO was associated with intraoperative rupture (IOR) (odds ratio - OR = 10.54; 95% confidence interval - 95%CI 4.72-23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11-4.07; p = 0.01). The group with TAO and IOR had no significant difference in clinical (p = 0.06) and surgical (p = 0.94) complications compared to the group that had TAO, but no IOR. Among the 111 patients followed six months after treatment, IOR, number of occlusions, and total time of occlusion were not associated with Glasgow Outcome Scale (GOS) in the follow-up (respectively, p = 0.18, p = 0.30, and p = 0.73). Among patients who underwent TAO, IOR was also not associated with GOS in the follow-up (p = 0.29)., Conclusions: TAO was associated with IOR and surgical complications, being the latter independent of IOR occurrence. In long-term analysis, neither TAO nor IOR were associated with poor clinical outcomes.

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors., Objective: We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months., Methods: This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission., Results: A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm., Conclusion: Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear., Objective: To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia., Methods: The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs)., Results: We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02--10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42--14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89--11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%., Conclusion: Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Stereotactic radiosurgery (SRS) presents as a good treatment option for smaller, deep-seated brain metastases (BMs). This study aims to determine predictors of SRS failure for patients with non-small cell lung cancer BMs., Methods: This was a retrospective study of single non-small cell lung cancer BMs treated using SRS. We included patients >18 years with a single, previously untreated lesion. Primary outcome was treatment failure, defined as BMs dimension increase above the initial values. Demographic, clinical, and radiological data were collected to study potential predictors of treatment failure., Results: Worse rates of progression-free survival (PFS) were associated with heterogeneous contrast enhancement (18.1 ± 4.1 vs. 41.9 ± 4 months; P < 0.001). Better rates of PFS were associated with volumes <1.06 cm 3 (log-rank; P = 0.001). Graded prognostic assessment was significantly associated with survival at 120 months (log-rank; P < 0.001). Karnofsky Performance Scale was evaluated in 3 strata: 90-100, 80, and ≤70. Mean survival rates for these strata were 31.8 ± 3.9, 10.6 ± 2.2, and 9.8 ± 2.3 months, respectively (log-rank; P < 0.001). There were no differences regarding presence of extracranial metastases, age, or lesion location. A multivariable logistic regression found that volume <1.06 cm 3 was associated with higher survival rates at 10 years (odds ratio: 3.2, 95% confidence interval: 1.3-8.0)., Conclusions: Contrast-homogeneous metastases and lesions <1.06 cm 3 are associated with better rates of PFS. Karnofsky Performance Scale and graded prognostic assessment were associated with more favorable survival rates after 10 years. Volume <1.06 cm 3 was the only significant predictor of survival in the multivariable analysis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Neurocysticercosis (NCC) is considered a neglected infectious disease, but the most common parasitic disease of the central nervous system (CNS). Due to oral tendencies in childhood, it is hypothesized that individuals are infected around this age and develop symptoms as lately as during young adulthood. Although it is considered a benign disease, it may cause great impact in the patient's quality of life due to epilepsy, visual symptoms, and hydrocephalus, which eventually requires frequent hospitalizations. The treatment of hydrocephalus is the main challenge for neurosurgeons., Methods: We performed a concise review on neurocysticercosis in children and the main presentations of NCC in the neurosurgery practice and a systematic review on hydrocephalus secondary to extraparenchymal NCC., Results: Our review showed a rate of complete resolution of hydrocephalus secondary to NCC of around 80% with the first attempt of surgical treatment combined with medication therapy. Endoscopic removal of the intraventricular cysts with third ventriculostomy was the most common treatment modality. Patients previously managed with ventricular shunts are likely to have worse outcomes and complications., Conclusion: Endoscopic approach is the gold standard surgical treatment for hydrocephalus secondary to neurocysticercosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Torque Teno virus (TTV) is a recently discovered virus with high prevalence worldwide, that has been associated with vascular diseases. The aim of this study is to investigate the prevalence of TTV molecular DNA in the intracranial aneurysm (IA) artery walls., Method: Samples of IA walls were collected after microsurgical clipping from 35 patients with IA (22 ruptured/13 unruptured cases). The samples were submitted to molecular DNA extraction using the EasyMag automatized extractor and performed with Qiagen DNA extraction Minikit 250. The samples underwent PCR examination with primers for β-globin as internal control using the Nanodrop ® 2000 spectrophotometer. A quantitative (real-time) PCR with TTV-specific primers was performed. Clinical and radiological data of patients included was collected., Results: TTV was detected in 15 (42.85%) cases, being 10 (45.4%) ruptured and 5 (38.4%) unruptured ( p = 0.732) lesions. Multiple IAs accounted for 14 (40%) cases. Five cases (17.2%) had TTV+ and multiple aneurysms ( p = 0.73). Association between presence of virus and aneurysm rupture was not statistically significant ( p = 0.96)., Conclusion: This study demonstrated a relatively high prevalence of viral DNA in the walls of IAs. This is the first study to identify the presence of TTV DNA in IA's samples, which was found more often in ruptured lesions. This is an exploratory study, therefore, larger studies are required to clarify the relationships between inflammation, viral infection, IA formation and rupture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rabelo, Yoshikawa, Telles, Coelho, de Souza, de Oliveira, Mendoza, Braz-Silva, Boechat, Teixeira and Figueiredo.)

Background: Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections., Methods: We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death., Results: We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm 3 . Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p  = 0.021) and a higher rate of ICU admissions (14% versus 44%; p  = 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p  = 0.054)., Conclusion: Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Objective: Several studies on use of erenumab for migraine treatment have been published over recent years. However, its long-term safety and effectiveness have not been consistently established in the literature yet. We aimed to perform a qualitative and quantitative analysis of the long-term safety and effectiveness of erenumab for the treatment of migraine headaches., Methods: Long-term follow-up was defined as ≥ 1 year. PubMed, Embase and Cochrane Library were systematically searched from inception to 14 June 2022 for studies meeting the inclusion criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale., Results: Fourteen studies, comprising 3574 patients, were included. The total follow-up period ranged from 48 to 268 weeks (i.e., 1 year to 5.6 years). Pooled estimate rates for all adverse events (AEs) were 63% (95% CI 46-78); for serious AEs, 3% (95% CI 1-7); and for AEs leading to discontinuation of erenumab, 3% (95% CI 2-5). Reduction in monthly migraine days (MMDs) was -6.98 (95% CI -8.90 to -5.05) and in migraine-specific medication days (MSMDs) was - 6.09 (95% CI - 9.43 to - 2.75). More than half (57%; 95% CI 51-63) and around one-third (35%; 95% CI 28-42) of patients presented with reductions of ≥ 50% and ≥ 75% in MMDs, respectively. Headache Impact Test-6 (HIT-6) score was decreased by -9.68 points (95% CI - 12.03 to - 7.34). Nine studies were considered of poor methodological quality and five of fair quality., Conclusions: Erenumab has a favorable safety profile, with a low incidence of serious AEs, and sustained efficacy over ≥1 year of follow-up in the treatment of migraine., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Radiological indicators in head computed tomography (CT) scan have emerged as tools to evaluate sarcopenia using the sectional area and thickness of the temporal muscle. They can be obtained by standardized measurements in preoperative image assessment of patients with brain aneurysms. We aimed to evaluate the association between functional outcomes after interventions for intracranial aneurysms (IAs) and temporal muscle thickness (TMT) and area (TMA), as surrogates of sarcopenia., Methods: This is a prospective observational cohort study in patients who underwent microsurgery or embolization for ruptured or unruptured IA between January 2018 and December 2019, with a 6-month follow-up. Preoperative CT scans were analyzed to measure TMT and TMA. The functional outcome was assessed by the modified Rankin Scale (mRS). The main outcome was the relationship between sarcopenia and the postoperative functional outcome., Results: A total of 361 patients were included, of whom 199 (55.1%) had ruptured and 162 (44.9%) had unruptured lesions. Larger TMA significantly predicted better functional outcomes at discharge. TMT was associated with functional outcomes at both discharge and 6 months, adjusted for rupture and hypertension. Maximizing the sum sensitivity-specificity, an optimal TMT cutoff of 6.25 mm can predict unfavorable outcomes. Maximizing the positive predictive value × negative predictive value of a product, the cutpoint was 3.55 mm., Conclusions: Sarcopenia, represented by TMT and TMA, is associated with poorer functional results at discharge and 6-month follow-up in IA surgery. TMT below 6.25 mm was associated with unfavorable functional outcomes. These easily obtainable measurements may improve the decision-making process for patients with IAs., (© 2022 S. Karger AG, Basel.)

Purpose: To evaluate the risk factors for poor outcomes after surgical and endovascular treatment of aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Patients with ≥ 18-years of age and aSAH were included, while patients who died within 12 h of admission or lost follow-up were excluded. All participants underwent standardized clinical and radiological assessment on admission and were reassessed at discharge and at 6-months follow-up using the Glasgow Outcome Scale (GOS)., Results: Death at discharge was associated with female gender, anterior communication artery (ACoA) aneurysm location and presence of atherosclerotic plaque in the surgical group, and with age in the endovascular group. Both groups had clinical condition on follow-up associated with mFisher score on admission and hypertension. GOS on follow-up was also associated with presence of atherosclerotic plaque and multiple aneurysms in surgical group, and with age in endovascular group., Conclusions: Subjects treated surgically are prone to unfavorable outcomes if atherosclerotic plaques and multiple aneurysms are present. In patients with endovascular treatment, age was the main predictor of clinical outcome.

Background: High levels of homocysteine (Hct) have been associated with great risks of ischemic stroke. However, some controversy still exists. We performed a systematic review and meta-analysis to compare the levels of Hct between patients with ischemic stroke and controls., Methods: We performed a systematic literature search for articles reporting Hct levels of patients with occurrence of ischemic stroke. We employed a random-effects inverse-variance weighted meta-analytical approach in order to pool standardized mean differences, with estimation of τ2 through the DerSimonian-Laird method., Results: The initial search yielded 1361 studies. After careful analysis of abstracts and full texts, the meta-analysis included data from 38 studies, which involved almost 16 000 stroke events. However, only 13 studies reported means and standard deviations for cases and controls, and therefore were used in the meta-analysis. Those studies presented data from 5002 patients with stroke and 4945 controls. Standardized mean difference was 1.67 (95% CI 1.00-2.25, P < 0.01), indicating that Hct levels were significantly larger in patients with ischemic stroke compared to controls. Between-study heterogeneity was very large (I2 = 99%), particularly because three studies showed significantly large mean differences., Conclusion: This meta-analysis shows that patients with ischemic stroke have higher levels of Hct compared to controls. Whether this is a modifiable risk factor remains to be assessed through larger prospective cohorts., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Previous meta-analyses comparing microsurgery and coiling that include BRAT may be inaccurate to compare the outcomes of ruptured saccular aneurysms. This study aims to evaluate 10-year efficiency, safety, and advantages of coiling compared with clipping in patients with spontaneous saccular aneurismal SAH as a primary outcome. Also analyzed secondary outcomes: no-occlusion, mortality, rebleeding, and retreatment., Methods: A systematic search of the literature on microsurgical clipping versus coiling was done to identify RCTs with at least 10 years of follow-up published between 2000 and 2021. The primary outcome was favorable functional outcome, defined as a modified Rankin scale (mRS) score ≤ 2. Secondary outcomes were no-occlusion, mortality, rebleeding, and retreatment. Quality of the included trials was analyzed using the Risk of Bias 2.0 (RoB 2.0) tool. A random-effects meta-analysis was performed., Results: Two studies reported 10-year follow-up results, and the meta-analysis did not demonstrate significant differences between groups (OR 0.9, 95%CI 0.66-1.24, I 2  = 21%). No differences were observed compared clipping and coiling regarding occlusion rates (OR 5.3, 95%CI 0.8-36.3, I 2  = 89%). Mortality rates did not show significant differences between treatment modalities (OR 0.97, 95%CI 0.77-1.21, I 2  = 0%). Rebleeding rates were also similar between groups (OR 1.63, 95%CI 0.25-10.7, I 2  = 37%); however, significantly higher retreatment rates were associated with coiling (OR 10.6, 95%CI 2.1-52.5, I 2  = 80%). Overall, risk of bias was low., Conclusion: There are no long-term differences regarding no-occlusion, mortality, and rebleeding rates between coiling and clipping. Higher retreatment rates were associated with coiling., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: There are no guidelines on the management of surgical site infection (SSI) in neurosurgery. This study sought to analyze whether early debridement improved survival compared to antibiotic therapy alone in patients with postcraniotomy infections after oncological neurosurgeries., Methods: We retrospectively reviewed patient records from 2011 to 2019 to identify patients that had been reoperated for the debridement of SSI after brain tumor resection. If SSI was suspected but not clinically evident, the diagnosis was confirmed by cerebrospinal fluid (CSF) analysis or contrast-based imaging examinations. Immediately after diagnosis, broad-spectrum antibiotics were started for all patients., Results: Out of 81 SSI cases, 57 underwent debridement. Two patients were reoperated 3 times, and three had two surgeries, resulting in a total of 64 procedures. The number of days between SSI diagnosis and surgical intervention did not influence mortality in both univariate and multivariable analyses (Hazard ratio [HR] 1.03, 95% CI 0.93-1.13). Early debridement (<24 h) did not influence rates of antibiotic prescription at discharge ( P = 0.53) or hospital length of stay (LOS) ( P = 0.16). Higher neutrophil-lymphocyte ratios (NLRs) were associated with the lower survival (HR 1.05, 95% Confidence interval [CI] 1.01-1.08). Multiple cutoffs were tested and values above 3.5 are more significantly associated with worse outcomes (HR 2.2; 95%CI 1.1-4.2)., Conclusion: Early debridement does not seem to influence the survival, rates of antibiotic at discharge, or hospital LOS of patients presenting with SSI after neurosurgery for intracranial tumors. High NLRs are strong predictors of worse prognosis in this population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Objective: To compare the area of exposure to the cisternal thalamus associated with four surgical techniques: supracerebellar-infratentorial (SCIT), occipital interhemispheric (OI), transchoroidal (TC) and subtemporal before and after parahippocampal resection (ST and STh, respectively)., Methods: All approaches were performed on both sides of three heads. Qualitative anatomical analyses were performed to understand anatomical limits, advantages, and flaws of each technique. Quantitative analyses for multiple repeated dependent variables assessed significant differences between areas of exposure., Results: Exposure area was significantly more extensive using TC and STh approaches compared to ST, OI, and SCIT. STh achieved a significantly wider exposure compared to ST. Regarding dissection angle, surrounding structures and limitations, ST approaches do not provide adequate exposure, nor alignment with the thalamic axis. The OI and STh may provide a better field of exposure, but without adequate alignment and challenging deeper dissections. TC provides better exposure of the cisternal pulvinar with access to lateral pulvinar at the atrium's anterior wall but is a transcortical route that disrupts non-pathological tissue. SCIT provides an adequate area of exposure with the possibility of alignment with the thalamus axis, thus allowing an easier dissection of deeper lesions., Conclusions: For lesions at the pulvinar surface, OI and STh are adequate. For lesions restricted to medial pulvinar and deep along the thalamus axis, SCIT approaches are recommended. Lesions extending to the lateral pulvinar and ventricular atrium are best removed through TC approaches. The ST approach was not suitable to the cisternal pulvinar due to its limited angular exposure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Temporary arterial occlusion (TAO) is a technique widely used in cerebrovascular surgery. However, few studies have evaluated the independent long-term effects of TAO or given detailed information about the complications during in-hospital stay., Objective: This study aims to investigate the independent impact of TAO during unruptured intracranial aneurysm surgery on short and long-term outcomes., Methods: The study included surgical elective patients diagnosed with unruptured aneurysm and indication of microsurgical treatment. Outcome assessment included occurrence of intra-operative (IOC) and post-operative (POC) complications, as well as Glasgow Outcome Scale (GOS) score 6 months after discharge., Results: 114 patients were included and 36 were followed. TAO was associated with POC (OR = 2.08; CI 95% 1.12-3.96; p = 0.01). The group with TAO and intraoperative rupture (IOR) did not differ from the group with TAO without IOR in terms of POC (p = 0.65) and IOC (p = 0.78). IOR (p = 0.16) and number of occlusions (p = 0.23) did not change GOS, but the total time of occlusion was associated with neurologic worsening (p = 0.034) during follow-up. The TAO group had larger aneurysm size and higher frequency of irregular lesions, when compared to the entire study group. Aneurysm location was not associated with POC (p = 0.25), IOC (0.17) or GOS (p = 0.75)., Conclusion: The location of temporary clip placement and the number of clips did not influence the short- and long-term outcomes of patients with unruptured intracranial aneurysms. However, presence of temporary clips was associated with POC regardless of IOR occurrence and increased total time of occlusion was associated with poor outcomes after 6 months., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To analyze the role of serum creatinine levels as a biomarker of intracranial aneurysm outcomes., Methods: This is a prospective analysis of outcomes of patients with intracranial aneurysm. One hundred forty-seven patients with serum creatinine at admission and 6 months follow up were included. Linear and logistic regressions were used to analyze the data. Modified Rankin scale (mRS) was used to assess outcome., Results: Creatinine level was not directly related to aneurysm outcome nor aneurysm rupture (p > 0.05). However, patients with a glomerular filtration rate (GFR) lower than 72.50 mL·min-1 had an odds ratio (OR) of 3.049 (p = 0.006) for worse outcome. Similarly, aneurysm rupture had an OR of 2.957 (p = 0.014) for worse outcomes. Stepwise selection model selected 4 variables for outcomes prediction: serum creatinine, sex, hypertension and treatment. Hypertensive patients had, on average, an increase in 0.588 in mRS (p = 0.022), while treatment with microsurgery had a decrease in 0.555 (p = 0.038)., Conclusions: Patients with higher GFR had better outcomes after 6 months. Patients with higher GFR had better outcomes after 6 months. Creatinine presented an indirect role in GFR values and should be included in models for outcome prediction.

Surgical access to the middle fossa can be technically challenging. As neurosurgery evolves to minimally invasive approaches, the objective of this study is to demonstrate the extension of the Minipterional approach to access the middle fossa. We present a new surgical approach to the middle fossa for the treatment of secondary trigeminal neuralgia. Three cases are reported to illustrate the following techniques: a patient with petrotentorial meningioma and trigeminal neuralgia, a patient with an arachnoid cyst compressing the fifth nerve, and a patient with a middle cerebral artery aneurysm and a long history of TN (trigeminal neuralgia) refractory to medical and surgical treatments. All three experienced full symptom controls with no permanent neurological deficits. Therefore, the Minipterional technique might represent a feasible, effective, and safe option to treat refractory secondary TN. It also allows approaching these lesions when the posterior fossa approach is compromised by anatomical distortion and enables the simultaneous treatment of secondary trigeminal neuralgia and other lesions, such as aneurysms and meningiomas., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide's impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH)., Methods: Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS)., Results: A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2-4), 3 (IQR 3-4), and 3 (IQR 1-4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29-1.48], adjusted common OR 1.25 [95% CI 0.46-3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0-2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%)., Conclusions: In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.

Objective: To identify current evidence on the use of topiramate for refractory status epilepticus., Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used., Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects., Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Objectives: This study proposed a structured microsurgical training program and evaluated it with the assistance of a large sample of surgeons., Methods: The practical course comprised 16 sessions of approximately 4 hours each. This included two sessions for suturing rubber gloves and two sessions for suturing arteries, veins, and nerves in chicken thighs. The other sessions were performed on the femoral vessels of rats: 5 sessions for end-to-end arterial anastomosis, 5 for end-to-end venous anastomosis, 1 for arterial grafting, and 1 for end-to-side anastomosis. We conducted a structured assessment of the microsurgical skills in each training session., Results: In this study, 89 surgeons were evaluated. The mean scores for the different procedures were as follows: glove suturing, 33.3±0.59; chicken nerve end-to-end anastomosis, 40.3±0.49; chicken artery suturing, 40.9±0.36; chicken vein suturing, 42.3±0.36; graft interposition, 44.8±0.7; and end-to-side anastomosis, 43.7±0.63 (p<0.05 for all). The chicken thigh suturing scores were significantly higher than the rubber gloves suturing scores (p<0.01). There were no differences between scores of the rat artery and chicken thigh suturing procedures (p=0.24). The rat venous anastomosis scores were higher than the rat arterial anastomosis scores (p=0.02), as were graft interposition scores when compared with end-to-end venous anastomosis scores. The end-to-side anastomosis scores did not differ significantly from the grafting scores (p=0.85). The most common errors were inadequate knotting technique and suture rupture due to inadequate technique (both n=88 [98.9%])., Conclusion: We propose a 16-step, progressive microsurgical training program to learn the basic microsurgical techniques comprehensively and reliably. The program was evaluated in a large sample of trainees, and it demonstrated the adequacy of the training sequence and results.

Over the last few years, the role of early postoperative computed tomography (EPOCT) after cranial surgery has been repeatedly questioned, but there is yet no consensus on the practice. We conducted a systematic review to address the usefulness of EPOCT in association with neurological examination after elective craniotomies compared to the neurological examination alone. Studies were eligible if they provided information about the number of patients scanned, how many were asymptomatic or presented neurological deterioration before the scan and how many of each of those groups had their management changed due to imaging findings. CTs had to be performed in the first 48 h following surgery to be considered early. Eight studies were included. The retrospective studies enrolled a total of 3639 patients, with 3737 imaging examinations. Out of the 3696 CT scans performed in asymptomatic patients, less than 0.8% prompted an intervention, while 100% of patients with neurological deterioration were submitted to emergency surgery. Positive predictive values of altered scans were 0.584 for symptomatic patients and 0.125 for the asymptomatic. The number of altered scans necessary to predict (NNP) one change in management for the asymptomatic patients was 8, while for the clinically evident cases, it was 1.71. The number of scans needed to diagnose one clinically silent alteration is 134.75, and postoperative imaging of neurologically intact patients is 132 times less likely to issue an emergency intervention than an altered neurological examination alone. EPOCT following elective craniotomy in neurologically preserved patients is not supported by current evidence, and CT scanning should be performed only in particular conditions. The authors have developed an algorithm to help the judgment of each patient by the surgeon in a resource-limited context., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Fusiform intracranial aneurysms (FIA) are associated with significant morbidity and mortality. We carried out a systematic review and meta-analysis of individual participant data with propensity score adjustment to compare the functional and angiographic outcomes between surgical and endovascular approaches to FIA. We conducted a systematic review for articles on the treatment of FIA with individual patient-level detailing. Data from patients treated for FIA in our institution from 2010 to 2018 were also collected. The primary studied outcome was morbidity, and secondary outcomes were angiographic results and retreatment. Propensity score-adjusted mixed-effects logistic regression models evaluated treatment options, stratified by anatomical location. Compiling original and published data, there were 312 cases, of which 79 (25.3%) had open surgery, and 233 (74.5%) were treated with endovascular procedures. There were no differences between treatment groups, for neither cavernous ICA (OR 1.04, 95% CI 0.05-23.6) nor supraclinoid aneurysms (OR 7.82, 95% CI 0.65-94.4). Both size (OR 1.11, 95% CI 1.03-1.19) and initial mRS (OR 2.0, 95% CI 1.2-3.3) were risk factors for morbidity, independent of location. Neither age nor rupture status influenced the odds of posterior morbidity. Unfavorable angiographic outcomes were more common in the endovascular group for supraclinoid and vertebrobasilar aneurysms (χ 2 , P < 0.01). There were no differences between morbidity of surgical and endovascular treatments for FIA, regardless of aneurysm location. Size and initial mRS were correlated with functional outcomes, whereas age and rupture status were not. Microsurgery seems to yield better long-term angiographic results compared to endovascular procedures., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

One of the first attempts to define brain death (BD) dates from 1963, and since then, the diagnosis criteria of that entity have evolved. In spite of the publication of practice parameters and evidence-based guidelines, BD is still causing concern and controversies in the society. The difficulties in determining brain death and making it understood by family members not only endorse futile therapies and increase health care costs, but also hinder the organ transplantation process. This review aims to give an overview about the definition of BD, causes, physiopathology, diagnosis criteria, and management of the potential brain-dead donor. It is important to note that the BD determination criteria detailed here follow the AAN's recommendations, but the standard practice for BD diagnosis varies from one country to another., (© 2021. Fondazione Società Italiana di Neurologia.)

Background: The objective of this paper was to describe the arterial supply of the uncus and quantify the branches directed to the anteromedial aspect of the human temporal cortex., Methods: We studied 150 human cerebral hemispheres identifying main afferent arteries supplying the anteromedial temporal cortex with particular attention to the uncus, determining the territory supplied by each artery through either cortical or perforating branches., Results: The uncus was supplied by 419 branches of the anterior choroidal artery (AChA), 210 branches of the internal carotid artery (ICA), 353 branches of the middle cerebral artery (MCA), and 122 branches of the posterior cerebral artery (PCA). The total of supplying vessels was 1104 among the 150 hemispheres studied, which corresponds to 7.36 arteries per uncus. The average of branches per hemisphere was as follows: 2.79 from AChA, 1.40 from ICA, 2.35 from MCA, and 0.81 from PCA. The relative contribution of each artery for the total of specimens studied was as follows: 38% from AChA, 19% from ICA, 32% from the MCA, and 11% from the PCA. We identified cortical anastomoses mostly between the MCA and PCA (27 cases)., Conclusion: We described and quantified the uncus' vascularization, including anatomical variations. This updated, detailed description of the mesial temporal vascularization is paramount to improve the treatment of neurosurgical conditions., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Cellular response to TBI is a mixture of excitotoxicity, neuroinflammation, and cell death. Biomarkers that can track these lesions and inflammatory processes are being explored for their potential to provide objective measures in the evaluation of TBI, from prehospital care to rehabilitation. By understanding the pathways involved, we could be able to improve diagnostic accuracy, guide management, and prevent long-term disability. We listed some of the recent advances in this translational, intriguing, fast-growing field. Although the knowledge gaps are still significant, some markers are showing promising results and could be helping patients in the near future., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Congenital transsphenoidal encephalocele (CTE) surgical correction is a challenging procedure. Although rare, this anomaly, characterized with neural herniation elements, including the pituitary gland or optic pathway through the sphenoid bone with anatomical alteration, can be presented in many different ways and should be individually analyzed. Significant advances in medical technology and the 3D models may simulate the complex anatomical relations of the human body. Nowadays, medical education relies on the availability of standardized materials that can reliably emulate human anatomy. Therefore, realistic anatomical models have become an alternative for cadavers or animal specimens. In this technical note, the authors present a new technique to create personalized models that combine 3D printing, molding, and casting to create an anatomically and tactilely realistic model based on magnetic resonance and computerized tomography images. Produced from different silicon types, the model recreated the anatomic alterations precisely, allowing a multidisciplinary team to determine the adequate surgical approach for this patient. We describe a case of congenital transsphenoidal encephalocele of a 3-year-old boy, whose surgical correction was planned using a hybrid model. The technical description of the model is given in detail. This new hybrid model allowed a detailed discussion of the surgical approach aspects by having tissues of different consistencies and resistances and a very high prediction rate. This approach may allow a reduction in surgery time and possible complications after operative procedures.