Open versus Transcutaneous (Ultrasound-Guided and Based on Anatomic Landmarks) Tunneled Venous Access to the Right Internal Jugular Vein in Children: A Prospective Single-Center Study.

BACKGROUND: The purpose of this study was to compare the immediate and long-term complications that are associated with the utilized techniques for the insertion of indwelling central venous catheters, that is the open surgical technique, the ultrasound-guided technique, and the transcutaneous technique based on external anatomical landmarks in the right internal jugular vein, to a pediatric population. METHODS: This was a prospective randomized trial based on a pediatric patient population under 16 years of age of a tertiary pediatric-oncological hospital. The procedure was performed by a medical team with varying experience regarding the percutaneous and open insertion methods. We studied the outcome of our procedure, based on the immediate and delayed complication rate, as well as the needed time in order to complete the procedure and mean duration of line use. RESULTS: The patients that were inserted in our protocol were divided into three subgroups based on the selected technique for the insertion of the central venous catheter. A total number of 88 insertions (25.4%) (out of 346) were based on the technique that was using external anatomical landmarks, 121 insertions were based on the ultrasound-guided transcutaneous technique (34.9%), whereas in 137 cases (39.5%) the open surgical technique was preferred. All cases that were related to catheter re-insertion were excluded from our study. We performed a statistical analysis regarding the catheter dwell time between the three subgroups of patients and no significant difference was recorded. Moreover, the development of thrombosis was investigated, and we noted that a higher percentage of this complication was related to the transcutaneous external landmark and open surgical technique. Also, the incidence of infection was taken into consideration, which manifested an increased incidence when the transcutaneous technique based on external landmarks was used. CONCLUSIONS: Ultrasound-guided percutaneous insertion was considered to be a safe and effective technique for the insertion of central venous catheters. Our study also demonstrated a decrease in operating times when performed by operators with increasing expertise, increased preservation of the diameter of the venous lumen, and no increase in complication rates when the ultrasound-guided technique was selected.

Autoimmunity in Long Covid and POTS.

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.

An α-chloroaldehyde-based formal synthesis of eribulin.

Eribulin (Halaven) is the most structurally complex non-peptidic drug made by total synthesis and has challenged preconceptions of synthetic feasibility in drug discovery and development. However, despite decades of research, the synthesis and manufacture of eribulin remains a daunting task. Here, we report syntheses of the most complex fragment of eribulin (C14-C35) used in two distinct industrial routes to this important anticancer drug. Our convergent strategy relies on a doubly diastereoselective Corey-Chaykovsky reaction to affect the union of two tetrahydrofuran-containing subunits. Notably, this process relies exclusively on enantiomerically enriched α-chloroaldehydes as building blocks for constructing the three densely functionalized oxygen heterocycles found in the C14-C35 fragment and all associated stereocenters. Overall, eribulin can now be produced in a total of 52 steps, which is a significant reduction from that reported in both academic and industrial syntheses.

New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension.

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.

Shunt Over-drainage, Slit Ventricle Syndrome, Programmable Valves and Anti-Siphon Devices. A Narrative Review of a Multifactorial and Intractable Problem.

The current management strategy of hydrocephalus mainly involves the insertion of a ventriculoperitoneal shunt and is inherently related with a complication widely known as shunt over-drainage. Albeit this is a well-recognized complication, the true incidence and severity of this phenomenon remains undefined and most probably underdiagnosed, necessitating a more comprehensive pathophysiologic and therapeutic consideration. The slit ventricle syndrome is intimately related with the entity of shunt over-drainage, although who's the definition of the former is implicated by a lack of universally accepted inclusion criteria. Another point of controversy is related with the absence of widely accepted criteria that would be able to discriminate the existing differentiations between these two entities. This is reflected in the fact that there are many proposed, relevant, treatment protocols. The background for all this data is based on the uncertainty and ambiguity regarding the pathophysiological mechanisms that are implicated. Current efforts are centered on the implementation of precautionary measures, as well as on treatment of both of these entities. Currently, there are enough evidence that support the concept that prevention of siphoning via the use of gravitational valves or antisiphon devices is the most efficacious means contained in our current therapeutic armamentarium. We attempt to present an overview of this complex entity, emphasizing on the hydrodynamics of the cerebrospinal fluid circulation in conditions harboring a ventriculoperitoneal shunt, the effect of the siphoning effect and the role of programmable valves and anti-siphon devices in our effort to eliminate this phenomenon. Based on an extensive literature review and on expert opinion, we concluded that the insertion of an anti-siphon device (gravitational shunt valves) could reliably address the issue of over-drainage, when a patient assumes a vertical position. Besides that, there are ongoing prospective studies centered on the safety and efficacy of adjustable gravitational valves, whose results are of ultimate importance. It is of paramount importance to be recognized that, due to the complexity of the pathophysiology of shunted hydrocephalus, lifelong follow-up of patients with ventriculoperitoneal shunts is necessary.

The Role of Antisiphon Devices in the Prevention of Central Ventricular Catheter Obliteration for Hydrocephalus: A 15-Years Institution's Experience Retrospective Analysis.

Shunt over-drainage in patients harboring a ventriculoperitoneal shunt constitutes one of the most devastating, and difficult to manage, side effects associated with this operation. Siphoning is one of the most important contributing factors that predispose to this complication. Based on the fact that the predisposing pathophysiologic mechanism is considerably multiplicated, amelioration of that adverse condition is considerably difficult to achieve. A lot of evidence suggests that the widespread utilization of gravitational valves or antisiphon devices is of utmost importance, in order to minimize or even avoid the occurrence of such complications. The recent literature data highlight that gravity-related, long-lasting shunt over-drainage consists of a momentous factor that could be considered one of the main culprits of central shunt failure. A lot of efforts have been performed, in order to design effective means that are aimed at annihilating siphoning. Our tenet was the investigation of the usefulness of the incorporation of an extra apparatus in the shunt system, capable of eliminating the impact of the siphoning effect, based on the experience that was gained by their long-term use in our institution. A retrospective analysis was performed, based on the data that were derived from our institution's database, centered on patients to which an ASD was incorporated into their initial shunt device between 2006 and 2021. A combination of clinical, surgical, radiological findings, along with the relevant demographic characteristics of the patients were collected and analyzed. We attempted to compare the rates of shunt dysfunction, attributed to occlusion of the ventricular catheter, in a group of patients, before and after the incorporation of an anti-siphon device to all of them. A total number of 120 patients who have already been shunted due to hydrocephalus of different etiologies, were managed with the insertion of an ASD. These devices were inserted at different anatomical locations, which were located peripherally to the initially inserted valvular mechanism. The data that were collected from a subpopulation of 17 of these patients were subjected to a separate statistical analysis because they underwent a disproportionately large number of operations (i.e., >10-lifetime shunt revisions). These patients were studied separately as their medical records were complicated. The analysis of our records revealed that the secondary implementation of an ASD resulted in a decrease of the 1-year and 5-year central catheter dysfunction rates in all of our patients when compared with the relevant obstruction rates at the same time points prior to ASD insertion. According to our data, and in concordance with a lot of current literature reports, an ASD may offer a significant reduction in the obstruction rates that is related to the ventricular catheter of the shunt. These data could only be considered preliminary and need to be confirmed with prospective studies. Nevertheless, this study could be considered capable of providing supportive evidence that chronic shunt over-drainage is a crucial factor in the pathophysiology of shunt malfunction. Apart from that, it could provide pilot data that could be reviewed in order to organize further clinical and laboratory studies, aiming toward the assessment of optimal shunt valve systems that, along with ASD, resist siphoning.

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.

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.

"Be Careful What You Swallow": A Case Series of Swallow Syncope.

Swallow (deglutition) syncope is a rare form of neurally mediated cardioinhibitory reflex syncope occurring during swallowing. Patients may present to clinicians across multiple disciplines, so high awareness and careful evaluation are essential. We report 3 such individuals, describing our strategies in diagnosis, investigation and treatment, particularly focusing on conservative management. (Level of Difficulty: Intermediate.).

A diagnostic challenge in an unresponsive refugee child improving with neurosurgery-a case report.

An unresponsive paediatric patient may present a diagnostic challenge for health professionals, as rapid identification of the cause is needed to provide proper interventions. The following report details a challenging diagnosis of unresponsiveness in a refugee child. In the migratory context, observed unresponsiveness states are frequently attributed to psychologic factors, and overlapping psychiatric classifications (resignation syndrome, functional coma and catatonia) are common. Our patient fell into an unresponsive state for 6 months after witnessing a traumatic event. Diagnostic workup for multiple medical comorbidities led to surgical intervention for tethered cord syndrome. Shortly after that, the patient's responsiveness improved, putting to question her condition's underlying cause. This case highlights the need for a biopsychosocial approach in such cases, reflected in thorough clinical examination and diagnostic investigations. A multidisciplinary perspective and expertise proved crucial and may help in the rehabilitation of children in similar situations.

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.

Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics*.

Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure-activity relationships for this class of compounds.

Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.

The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.

Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.

Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant. Initial efforts resulted in the discovery of M4K2009, an analogue of the previously reported ALK2 inhibitor LDN-214117. Although highly selective for ALK2 over the TGF-ßR1 receptor ALK5, M4K2009 is also moderately active against the hERG potassium channel. Varying the substituents of the trimethoxyphenyl moiety gave rise to an equipotent benzamide analogue M4K2149 with reduced off-target affinity for the ion channel. Additional modifications yielded 2-fluoro-6-methoxybenzamide derivatives (26a-c), which possess high inhibitory activity against ALK2, excellent selectivity, and superior pharmacokinetic profiles.

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.

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.

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.