Chronic Pediatric Headache as a Manifestation of Shunt Over-Drainage and Slit Ventricle Syndrome in Patients Harboring a Cerebrospinal Fluid Diversion System: A Narrative Literature Review.

The main subject of the current review is a specific subtype of headache, which is related to shunt over-drainage and slit ventricle syndrome, in pediatric patients harboring an implanted shunt device for the management of hydrocephalus. This clinical entity, along with its impairment regarding the quality of life of the affected individuals, is generally underestimated. This is partly due to the absence of universally agreed-upon diagnostic criteria, as well as due to a misunderstanding of the interactions among the implicated pathophysiological mechanisms. A lot of attempts have been performed to propose an integrative model, aiming at the determination of all the offending mechanisms of the shunt over-drainage syndrome, as well as the determination of all the clinical characteristics and related symptomatology that accompany these secondary headaches. This subcategory of headache, named postural dependent headache, can be associated with nausea, vomiting, and/or radiological signs of slim ventricles and/or subdural collections. The ultimate goal of our review is to draw clinicians' attention, especially that of those that are managing pediatric patients with permanent, long-standing, ventriculoperitoneal, or, less commonly, ventriculoatrial shunts. We attempted to elucidate all clinical and neurological characteristics that are inherently related to this type of headache, as well as to highlight the current management options. This specific subgroup of patients may eventually suffer from severe, intractable headaches, which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be incriminated as the cause of the headache, shunt over-drainage should not be overlooked. On the contrary, it should be seriously taken into consideration, and its management should be added to the therapeutic armamentarium of such cases, which are difficult to be handled.

Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology.

Polycystin-1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model.

Craniosynostosis is the premature fusion of skull sutures and has a severe pathological impact on childrens' life. Mechanical forces are capable of triggering biological responses in bone cells and regulate osteoblastogenesis in cranial sutures, leading to premature closure. The mechanosensitive proteins polycystin-1 (PC1) and polycystin-2 (PC2) have been documented to play an important role in craniofacial proliferation and development. Herein, we investigated the contribution of PC1 to the pathogenesis of non-syndromic craniosynostosis and the associated molecular mechanisms. Protein expression of PC1 and PC2 was detected in bone fragments derived from craniosynostosis patients via immunohistochemistry. To explore the modulatory role of PC1 in primary cranial suture cells, we further abrogated the function of PC1 extracellular mechanosensing domain using a specific anti-PC1 IgPKD1 antibody. Effect of IgPKD1 treatment was evaluated with cell proliferation and migration assays. Activation of PI3K/AKT/mTOR pathway components was further detected via Western blot in primary cranial suture cells following IgPKD1 treatment. PC1 and PC2 are expressed in human tissues of craniosynostosis. PC1 functional inhibition resulted in elevated proliferation and migration of primary cranial suture cells. PC1 inhibition also induced activation of AKT, exhibiting elevated phospho (p)-AKT (Ser473) levels, but not 4EBP1 or p70S6K activation. Our findings indicate that PC1 may act as a mechanosensing molecule in cranial sutures by modulating osteoblastic cell proliferation and migration through the PC1/AKT/mTORC2 cascade with a potential impact on the development of non-syndromic craniosynostosis.

Venous Thromboembolism Risk and Thromboprophylaxis in Pediatric Neurosurgery and Spinal Injury: Current Trends and Literature Review.

Although the entities of venous thromboembolism (VTE), deep venous thrombosis, pulmonary embolus, and thromboprophylaxis in adult patients undergoing brain tumor and spine surgery, traumatic brain injury and elective neurosurgical procedures are widely elucidated, the same is not valid when pediatric patients are under consideration. An attempt to review the peculiarities of these patients through a comprehensive bibliographic review is undertaken. We performed a narrative summary of the relevant literature dedicated to pediatric patients, centered on traumatic brain injury, the general incidence of thromboembolic disease in this patient population, the role of low molecular weight heparin (LMWH) in the treatment and prophylaxis of VTE, and its role in elective neurosurgical procedures, including spinal operations. Additionally, the risk of deep venous thrombosis in elective neurosurgical procedures is reviewed. Due to inherent limitations of the current studies, particularly a restricted number of patients, our data are underpowered to give a definitive protocol and guidelines for all the affected patients. Our current conclusions, based only on pediatric patients, argue that there is limited risk of VTE in pediatric patients suffering from brain tumors and that the possibility of VTE is very low in children undergoing elective neurosurgical procedures. There is no consensus regarding the exact incidence of VTE in traumatic brain injury patients. LMWH seems to be a safe and effective choice for the "at risk" pediatric patient population defined as being older than 15 years, venous catheterization, nonaccidental trauma, increased length of hospital stays, orthopaedic (including spinal) surgery, and cranial surgery.

The Entity of Cerebellar Mutism Syndrome: A Narrative Review Centered on the Etiology, Diagnostics, Prevention, and Therapeutic Options.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is an entity that entails a constellation of signs and symptoms which are recorded in a limited number of pediatric patients who have been operated on mainly for tumors involving the posterior cranial fossa, and more precisely, the region of the vermis. Medulloblastoma seems to constitute the most commonly recognized pathological substrate, associated with this entity. The most prevalent constituents of this syndrome are noted to be a, often transient, although protracted, language impairment, emotional lability, along with cerebellar and brainstem dysfunction. Apart from that, a definite proportion of involved individuals are affected by irreversible neurological defects and long-lasting neurocognitive impairment. A bulk of literature and evidence based on clinical trials exist, which reflect the continuous effort of the scientific community to highlight all perspectives of this complex phenomenon. There are several circumstances that intervene in our effort to delineate the divergent parameters that constitute the spectrum of this syndrome. In summary, this is implicated by the fact that inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty regarding risk factors and etiology are all constituents of a non-well-investigated syndrome. Currently, a preliminary consensus exists about the identification of a group of diagnostic prerequisites that are managed as sine qua non, in our aim to document the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. It is common concept that midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment should be accepted as the most determinant predisposing conditions for the establishment of this syndrome. A well-recognized pathophysiological explanation of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Despite the relative advancement that is recorded regarding the diagnostic section of this disease, no corresponding encouraging results are reported, regarding the available treatment options. On the contrary, it is mainly targeted toward the symptomatic relief of the affected individuals. The basic tenet of our review is centered on the presentation of a report that is dedicated to the definition of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Apart from that, an effort is made that attempts to elucidate the paramount priorities of the scientific forum, which are directed toward the expansion our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome.

Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach.

Epigenetic modifications are considered of utmost significance for tumor ontogenesis and progression. Especially, it has been found that miRNA expression, as well as DNA methylation plays a significant role in central nervous system tumors during childhood. A total of 49 resected brain tumors from children were used for further analysis. DNA methylation was identified with methylation-specific MLPA and, in particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6, GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray screening, as well as selected samples, were tested for their mRNA expression levels. CASP8, RASSF1 were the most frequently methylated genes in all tumor samples. Simultaneous methylation of genes manifested significant results with respect to tumor staging, tumor type, and the differentiation of tumor and control samples. There was no significant dependence observed with the methylation of one gene promoter, rather with the simultaneous presence of all detected methylated genes' promoters. miRNA expression was found to be correlated to gene methylation. Epigenetic regulation appears to be of major importance in tumor progression and pathophysiology, making it an imperative field of study.

Secondary mechanisms of injury and viable pathophysiological targets in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) can be divided into a primary and secondary phase. In the primary phase, hematoma volume is evaluated and therapies are focused on reducing hematoma expansion. In the secondary, neuroprotective phase, complex systemic inflammatory cascades, direct cellular toxicity, and blood-brain barrier disruption can result in worsening perihematomal edema that can adversely affect functional outcome. To date, all major randomized phase 3 trials for ICH have targeted primary phase hematoma volume and incorporated clot evacuation, intensive blood pressure control, and hemostasis. Reasons for this lack of clinical efficacy in the major ICH trials may be due to the lack of therapeutics involving mitigation of secondary injury and inflexible trial design that favors unilateral mechanisms in a complex pathophysiology. Potential pathophysiological targets for attenuating secondary injury are highlighted in this review and include therapies increasing calcium, antagonizing microglial activation, maintaining macrophage M1 versus M2 balance by decreasing M1 signaling, aquaporin inhibition, NKCCl inhibition, endothelin receptor inhibition, Sur1-TRPM4 inhibition, matrix metalloproteinase inhibition, and sphingosine-1-phosphate receptor modulation. Future clinical trials in ICH focusing on secondary phase injury and, potentially implementing adaptive trial design approaches with multifocal targets, may improve insight into these mechanisms and provide potential therapies that may improve survival and functional outcome.

Slit ventricle syndrome: Historical considerations, diagnosis, pathophysiology, and treatment review.

After the introduction of shunt treatment for the management of childhood hydrocephalus, a wide variety of complications related to this treatment modality have been recognized. The entity of slit ventricle syndrome (alternatively, symptomatic ventricular coaptation) is one of them, is frequently encountered in the pediatric population and its symptom complex resembles that of shunt failure. We conducted research on PubMed®, MEDLINE®, and Web of Science®, using the keywords: "slit ventricles," "slit ventricle syndrome," "SVS" and "ventricular coaptation." The aim of our review was to trace the advances made through the past decades, concerning our knowledge about the clinical characteristics, pathophysiology, and treatment options of this entity. The discrepancy among researchers about the offending etiology and the optimum treatment algorithm of this entity, as well as the necessity of an updated concept regarding shunt over drainage is analyzed. The multiple treatment modalities proposed and pathophysiologic mechanisms implicated for the treatment of slit ventricle syndrome illustrate the complexity of this entity. Consequently, the issue requires more detailed evaluation. In this review, we comment on all the main facets related to shunt over drainage and the resultant slit ventricle syndrome.

The entity of the trapped fourth ventricle: A review of its history, pathophysiology, and treatment options.

An isolated or trapped fourth ventricle is a relatively rare, although serious, adverse effect of hemorrhagic, infectious, or inflammatory processes that involve the central nervous system. This entity usually occurs after successful shunting of the lateral ventricles and may become clinically evident with the development of delayed clinical deterioration. This decline of the neurological status of the patient is evident after an initial period of improvement of the relevant symptoms. Surgical treatment options include cerebrospinal fluid shunting procedures, along with open surgical and endoscopic approaches. Complications related to its management are common and are related with obstruction of the fourth ventricular catheter, along with cranial nerve or brainstem dysfunction. We used the keywords: "isolated fourth ventricle," and "trapped fourth ventricle," in PubMed® and Web of Science®. Treatment of the trapped fourth ventricle remains a surgical challenge, although the neurosurgical treatment armamentarium has broadened. However, prompt recognition of the clinical and neurological findings that accompany any individual patient, in conjunction with the relevant imaging findings, is mandatory to organize our treatment plan on an individual basis. The current experience suggests that any individual intervention plan should be mainly based on the underlying pathological substrate of hydrocephalus. This could help us to preserve the patient's life, on an emergent basis, as well as to ensure an uneventful neurological outcome, maintaining at least the preexisting level of neurological function.

Glycemic variability of acute stroke patients and clinical outcomes: a continuous glucose monitoring study.

INTRODUCTION: Glycemic variability (GV) has been associated with worse prognosis in critically ill patients. We sought to evaluate the potential association between GV indices and clinical outcomes in acute stroke patients. METHODS: Consecutive diabetic and nondiabetic, acute ischemic or hemorrhagic stroke patients underwent regular, standard-of-care finger-prick measurements and continuous glucose monitoring (CGM) for up to 96 h. Thirteen GV indices were obtained from CGM data. Clinical outcomes during hospitalization and follow-up period (90 days) were recorded. Hypoglycemic episodes disclosed by CGM but missed by finger-prick measurements were also documented. RESULTS: A total of 62 acute stroke patients [48 ischemic and 14 hemorrhagic, median NIHSS score: 9 (IQR: 3-16) points, mean age: 65 ± 10 years, women: 47%, nondiabetic: 79%] were enrolled. GV expressed by higher mean absolute glucose (MAG) values was associated with a lower likelihood of neurological improvement during hospitalization before and after adjusting for potential confounders (OR: 0.135, 95% CI: 0.024-0.751, p = 0.022). There was no association of GV indices with 3-month clinical outcomes. During CGM recording, 32 hypoglycemic episodes were detected in 17 nondiabetic patients. None of these episodes were identified by the periodic blood glucose measurements and therefore they were not treated. CONCLUSIONS: Greater GV of acute stroke patients may be related to lower odds of neurological improvement during hospitalization. No association was disclosed between GV indices and 3-month clinical outcomes.

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.

An Updated Meta-Analysis of RCTs of Colchicine for Stroke Prevention in Patients with Coronary Artery Disease.

Emerging evidence from randomized controlled clinical trials (RCTs) suggests that colchicine has cardiovascular benefits for patients with coronary disease, including benefits for stroke prevention. We performed an updated systematic review and meta-analysis of all RCTs reporting on stroke outcomes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). We identified 6 RCTs including a total of 11,870 patients (mean age 63 years, 83% males) with a mean follow-up of 2 years. Colchicine treatment was associated with a lower risk of stroke during follow-up, compared to that of placebo or usual care (risk ratio = 0.49, 95% confidence interval: 0.31-0.80; p = 0.004), without heterogeneity across the included studies (I2 = 0%, p for Cochran's Q = 0.52). In the subgroup analysis, no heterogeneity (p = 0.77) was identified in the effect of colchicine on stroke prevention between patients with recent acute (RR = 0.55, 95% CI: 0.15-2.05) or chronic stable (RR = 0.43, 95% CI: 0.21-0.89) coronary artery syndromes. In conclusion, we found that colchicine treatment decreases the stroke risk in patients with a history of atherosclerotic cardiovascular disease.

Admission Neutrophil to Lymphocyte Ratio for Predicting Outcome in Subarachnoid Hemorrhage.

PURPOSE: We sought to evaluate the relationship between admission neutrophil-to-lymphocyte ratio (NLR) and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. MATERIAL AND METHODS: Consecutive patients with aSAH were treated at two tertiary stroke centers during a five-year period. Functional outcome was defined as discharge modified Rankin score dichotomized at scores 0-2 (good) vs. 3-6 (poor). RESULTS: 474 aSAH patients were evaluated with a mean NLR 8.6 (SD 8.3). In multivariable logistic regression analysis, poor functional outcome was independently associated with higher NLR, older age, poorer clinical status on admission, prehospital statin use, and vasospasm. Increasing NLR analyzed as a continuous variable was independently associated with higher odds of poor functional outcome (OR 1.03, 95%CI 1.00-1.07, p=0.05) after adjustment for potential confounders. When dichotomized using ROC curve analysis, a threshold NLR value of greater than 6.48 was independently associated with higher odds of poor functional outcome (OR 1.71, 95%CI 1.07-2.74, p=0.03) after adjustment for potential confounders. CONCLUSIONS: Higher admission NLR is an independent predictor for poor functional outcome at discharge in aSAH patients. The evaluation of anti-inflammatory targets in the future may allow for improved functional outcome after aSAH.

Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment: A Systematic Review and Meta-analysis of RCTs.

OBJECTIVE: To provide a critical appraisal on the evidence from randomized controlled clinical trials (RCTs) on the utility of direct endovascular treatment (dEVT) compared to the combination of endovascular treatment preceded by IV thrombolysis (bridging therapy [BT]) for patients with acute large vessel occlusion (LVO). METHODS: Eligible RCTs were identified by searching Medline and Scopus. We calculated the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) and pooled estimates using random-effects models. The primary outcome was the probability of modified Rankin scale (mRS) score of 0 to 2 at 3 months. RESULTS: We included 3 studies comprising 1,092 patients. No difference between the dEVT and BT groups was detected for the outcomes of mRS score of 0 to 2 (OR 1.08, 95% CI 0.85-1.38; adjusted OR 1.11, 95% CI 0.76-1.63), mRS score of 0 to 1 (OR 1.10, 95% CI 0.84-1.43; adjusted OR 1.16, 95% CI 0.84-1.61), and functional improvement at 3 months (common OR 1.08, 95% CI 0.88-1.34; adjusted common OR 1.09, 95% CI 0.86-1.37). Patients receiving dEVT had significantly lower likelihood of successful recanalization before the endovascular procedure compared to those receiving BT (OR 0.37, 95% CI 0.18-0.77). Patients receiving dEVT had lower intracranial bleeding rates compared to those receiving BT (OR 0.67, 95% CI 0.49-0.92) but without a significant difference in the probability of symptomatic intracranial hemorrhage. No differences in all-cause mortality, serious adverse events, or procedural complications between the 2 groups were uncovered. CONCLUSIONS: We detected no differences in functional outcomes of IV thrombolysis-eligible patients with an acute LVO receiving dEVT compared to BT. Because uncertainty for most endpoints remains large and the available data are not able to exclude the possibility of overall benefit or harm, further RCTs are needed.

Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model.

Craniosynostosis refers to the premature fusion of one or more cranial sutures leading to skull shape deformities and brain growth restriction. Among the many factors that contribute to abnormal suture fusion, mechanical forces seem to play a major role. Nevertheless, the underlying mechanobiology-related mechanisms of craniosynostosis still remain unknown. Understanding how aberrant mechanosensation and mechanotransduction drive premature suture fusion will offer important insights into the pathophysiology of craniosynostosis and result in the development of new therapies, which can be used to intervene at an early stage and prevent premature suture fusion. Herein, we provide evidence for the first time on the role of polycystin-1 (PC1), a key protein in cellular mechanosensitivity, in craniosynostosis, using primary cranial suture cells isolated from patients with trigonocephaly and dolichocephaly, two common types of craniosynostosis. Initially, we showed that PC1 is expressed at the mRNA and protein level in both trigonocephaly and dolichocephaly cranial suture cells. Followingly, by utilizing an antibody against the mechanosensing extracellular N-terminal domain of PC1, we demonstrated that PC1 regulates runt-related transcription factor 2 (RUNX2) activation and osteocalcin gene expression via extracellular signal-regulated kinase (ERK) signalling in our human craniosynostosis cell model. Altogether, our study reveals a novel mechanotransduction signalling axis, PC1-ERK-RUNX2, which affects osteoblastic differentiation in cranial suture cells from trigonocephaly and dolichocephaly patients.

Endovascular treatment for basilar artery occlusion: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Independent randomized controlled clinical trials (RCTs) have provided robust evidence for endovascular treatment (EVT) as the standard of care treatment for acute large vessel occlusions in the anterior circulation. We examined available studies specific to posterior cerebral circulation ischemic strokes to see if any conclusions can be drawn regarding EVT options. METHODS: We performed a systematic literature search to identify studies evaluating the safety and efficacy of EVT versus standard medical treatment for patients with acute basilar artery occlusion (BAO). We extracted data for outcomes of interest and presented associations between the two groups with the use of risk ratios (RRs) or odds ratios (ORs), with corresponding 95% confidence intervals (CIs). We used a random-effects model to pool the effect estimates. RESULTS: We identified five studies (two RCTs, three observational cohorts) including a total of 1098 patients. Patients receiving EVT had a higher risk of symptomatic intracranial hemorrhage (sICH) compared to those receiving non-interventional medical management (RR 5.42, 95% CI 2.74-10.71). Nonsignificant trends towards modified Rankin Scale (mRS) scores 0-2 (RR 1.02, 95% CI 0.74-1.41), mRS scores 0-3 (RR = 0.97, 95% CI 0.64-1.47), overall functional improvement (OR 0.93, 95% CI 0.57-1.51), and all-cause mortality (RR 1.03, 95% CI 0.78-1.35) at 3 months were seen. CONCLUSION: Although EVT increases the probability of sICH, the available data do not exclude the possibility of improved functional outcomes over standard therapy. As larger studies are challenged by the perceived lack of equipoise in this vulnerable patient population, results of ongoing RCTs are expected to provide substantial input for future meta-analyses.

Post-Traumatic Status Epilepticus Masquerading as Acute Ischemic Stroke: A Case Report and Literature Review.

BACKGROUND Advanced imaging is one of the main modalities utilized in the diagnostic investigation of a first-time epileptic ictus, as well as in the evaluation of a patient suspected of having an ischemic stroke. CASE REPORT We report the case of a 7-year-old boy who was admitted to our hospital because of a depressed skull fracture. Soon after its initial evaluation, he had an episode of generalized tonic-clonic seizures; therefore, a detailed diagnostic work up was scheduled, which raised the diagnostic dilemma of ischemic stroke versus imaging alterations related to status epilepticus. He underwent surgical exploration, and a few days later the repeat MRI verified that the initial signal changes should be attributed to the ictus. CONCLUSIONS Brain edema, most commonly affecting a cerebral hemisphere in its entirety, is a rare post-ictal imaging finding that is causally related to focal-onset status epilepticus. The aforementioned perfusion changes can aid in the differentiation of ictal-related brain abnormalities from acute ischemic stroke, if regional or more diffuse areas of increased perfusion are shown on MRI. Consequently, MRI should be considered the preferred imaging modality when we are confronted with cases of post-ictal signal changes that could masquerade as acute ischemic stroke.

Ruptured Arteriovenous Malformation Anterior to the Brainstem to a Child with Subsequent Spontaneous Thrombosis: Case Report and Literature Review.

BACKGROUND Cerebral arteriovenous malformations (AVMs) are considered to be abnormalities of congenital origin, presumably arising due to a disorder in the process of embryogenesis, in the phase of differentiation of premature vascular domes into mature arteries, capillaries, and veins. The end result of that process is the formation of direct arteriovenous communications, without intervening capillary beds. CASE REPORT We report the case of a 6-year-old female who suffered an abrupt deterioration of her level of consciousness due to a subarachnoid hemorrhage located in the basal cisterns. Radiological investigation with magnetic resonance arteriography-magnetic resonance venography (MRA-MRV) was negative, but digital subtraction angiography (DSA) revealed a micro-AVM in the vicinity of the brainstem. The patient subsequently developed communicating hydrocephalus and the repeat DSA, performed 1 month later, failed to re-imagine the lesion. Further workup with DSA 1 year after the ictus was negative for pathological findings. CONCLUSIONS There are a lot of controversies regarding the optimal imaging modality for surveillance of pediatric AVMs, the time period needed to follow-up a given lesion, even if it is considered treated, and the underlying mechanism of spontaneous thrombosis of untreated, yet ruptured, AVMs. All these issues, along with the unusual mode of evolution of the clinical picture of this lesion are discussed in detail, along with a review of the available literature.

Antithrombotics in intracerebral hemorrhage in the era of novel agents and antidotes: A review.

BACKGROUND: Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension, arteriovenous malformations, or trauma. However, it can also present in patients receiving antithrombotic drugs, either anticoagulants such as acenocoumarol/warfarin-novel oral anticoagulants or antiplatelets, for the prevention and treatment of thromboembolic disease. OBJECTIVE: The purpose of this review is to present current bibliographic data regarding ICH irrespective of the cause, as well as post-hemorrhage use of antithrombotic agents. Moreover, this review attempts to provide guidelines concerning the termination, inversion, and of course resumption of antithrombotic therapy. METHODS AND MATERIALS: We reviewed the most recently presented available data for patients who dealt with intracerebral hemorrhagic events while on antithrombotic agents (due to atrial fibrillation, prosthetic mechanical valves or recent/recurrent deep vein thrombosis). Furthermore, we examined and compared the thromboembolic risk, the bleeding risk, as well as the re-bleeding risk in two groups: patients receiving antithrombotic therapy versus patients not on antithrombotic therapy. CONCLUSION: Antithrombotic therapy is of great importance when indicated, though it does not come without crucial side-effects, such as ICH. Optimal timing of withdrawal, reversal, and resumption of antithrombotic treatment should be determined by a multidisciplinary team consisting of a stroke specialist, a cardiologist, and a neurosurgeon, who will individually approach the needs and risks of each patient.

Fetal subependymal giant cell astrocytoma: A case report and review of the literature.

BACKGROUND: Subependymal giant cell astrocytomas (SEGAs) appear approximately in 10% of patients with tuberous sclerosis. These tumors are most commonly diagnosed in childhood and adolescence, with in utero diagnosed SEGAs being an extremely rare entity. CASE DESCRIPTION: We present the case of a congenital SEGA detected in an antenatal ultrasound and further investigated with fetal magnetic resonance imaging (MRI) scans at 22 and 32 weeks of gestational age. At 9 days of age, the child underwent craniotomy and partial excision of the tumor, followed by a second more extensive operation 13 days later. The patient was subsequently administered mammalian target of rapamycin inhibitor (everolimus). CONCLUSION: In the latest follow-up MRI, at the age of two, the SEGA remained unchanged. Management of these tumors in neonates is challenging, mainly due to high morbidity and mortality of surgical treatment in these ages.