El síndrome compartimental intracraneal: un modelo propuesto para la monitorización y el tratamiento de la lesión cerebral aguda

Durante décadas, uno de los principales objetivos en el tratamiento de la lesión cerebral aguda (LCA) grave ha sido el control de la hipertensión intracraneal (HIC). Sin embargo, la determinación de la HIC ha sufrido variaciones en sus umbrales a lo largo del tiempo sin que existan pruebas claras de ello. Mientras tanto, los avances en la comprensión de la dinámica del contenido intracraneal (cerebro, sangre y líquido cefalorraquídeo) y el desarrollo reciente de las técnicas de monitorización sugieren que centrarse en la distensibilidad intracraneal (CCI) podría ser un enfoque más fiable que guiar las acciones por valores predeterminados de presión intracraneal. Se sabe que el deterioro de la CCI pronostica la HI, ya que el volumen intracraneal puede aumentar rápidamente dentro del cráneo, una caja ósea cerrada con una expansibilidad irrisoria. Por lo tanto, puede producirse un síndrome compartimental intracraneal (ICCS) con efectos cerebrales deletéreos, precipitando una reducción de la perfusión cerebral, induciendo así una isquemia cerebral. El objetivo de la presente revisión en perspectiva es debatir el concepto de ICCS y sugerir un modelo integrador para la combinación de técnicas modernas invasivas y no invasivas para la evaluación de IH e ICC. La teoría y la lógica sugieren que la combinación de múltiples métodos auxiliares puede mejorar la predicción del deterioro de la ICC, señalando acciones proactivas y mejorando los resultados de los pacientes.For decades, one of the main targets in the management of severe acute brain injury (ABI) has been intracranial hypertension (IH) control. However, the determination of IH has sufered variations in its thresholds over time without clear evidence for it. Meanwhile, progress in the understanding of intracranial content (brain, blood and cerebrospinal fuid) dynamics and recent development in monitoring techniques suggest that targeting intracranial compliance (ICC) could be a more reliable approach rather than guiding actions by predetermined intracranial pressure values. It is known that ICC impairment forecasts IH, as intracranial volume may rapidly increase inside the skull, a closed bony box with derisory expansibility. Therefore, an intracranial compartmental syndrome (ICCS) can occur with deleterious brain efects, precipitating a reduction in brain perfusion, thereby inducing brain ischemia. The present perspective review aims to discuss the ICCS concept and suggest an integrative model for the combination of modern invasive and noninvasive techniques for IH and ICC assessment. The theory and logic suggest that the combination of multiple ancillary methods may enhance ICC impairment prediction, pointing proactive actions and improving patient outcomes

Cranioplasty Following Decompressive Craniectomy

Cranioplasty (CP) after decompressive craniectomy (DC) for trauma is a neurosurgical procedure that aims to restore esthesis, improve cerebrospinal fluid (CSF) dynamics, and provide cerebral protection. In turn, this can facilitate neurological rehabilitation and potentially enhance neurological recovery. However, CP can be associated with significant morbidity. Multiple aspects of CP must be considered to optimize its outcomes. Those aspects range from the intricacies of the surgical dissection/reconstruction during the procedure of CP, the types of materials used for the reconstruction, as well as the timing of the CP in relation to the DC. This article is a narrative mini-review that discusses the current evidence base and suggests that no consensus has been reached about several issues, such as an agreement on the best material for use in CP, the appropriate timing of CP after DC, and the optimal management of hydrocephalus in patients who need cranial reconstruction. Moreover, the protocol-driven standards of care for traumatic brain injury (TBI) patients in high-resource settings are virtually out of reach for low-income countries, including those pertaining to CP. Thus, there is a need to design appropriate prospective studies to provide context-specific solid recommendations regarding this topic

Management of intracranial hypertension following traumatic brain injury: a best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy. Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from "TBI Section" of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the "TBI Section" of the SINch and the 111 members of the Neuroanesthesia and Neurocritical Care Study Group of the SIAARTI. The aim of the survey was to test a preliminary evaluation of the grade of predictable future adherence of the recommendations following this intersociety proposal. The following recommendations are suggested as representing best clinical practice, nevertheless, adoption of local multidisciplinary protocols regarding thresholds of ICP values, drug therapies, hemostasis management and perioperative care of decompressed patients is strongly recommended to improve treatment efficiency, to increase the quality of data collection and to provide more powerful evidence with future studies. Thus, for this future perspective a rapid overview of the role of the multimodal neuromonitoring in the optimal severe TBI management is also provided in this document. It is reasonable to assume that the recommendations reported in this paper will in future be updated by new observations arising from future trials. They are not binding, and this document should be offered as a guidance for clinical practice through an intersociety agreement, taking in consideration the low level of evidence

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6–12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11–52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients

Insights into healthcare professionals’ perceptions and attitudes toward nanotechnological device application: What is the current situation in glioblastoma research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients’ quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians’ intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers’ knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians’ opinions and perspectives toward new technologies might be biased

The acute phase management of spinal cord injury affecting polytrauma patients : the ASAP study

Publisher Copyright: © 2022, The Author(s).Background: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. Methods: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. Results: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80–90 mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7 g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80–100 mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35–40 mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count > 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT) < 1.5 times the normal control [n = 85 (49.7%)] in patients needing spinal surgery. MRI [n = 160 (93.6%)] and spinal surgery [n = 158 (92.4%)] should be performed after intracranial, hemodynamic, and respiratory stabilization by most respondents. Corticosteroids [n = 103 (60.2%)], ISP/SCPP monitoring [n = 148 (86.5%)], and therapeutic hypothermia [n = 137 (80%)] were not utilized by most respondents. Conclusions: Our survey has shown a great worldwide variability in clinical practices for acute phase management of tSCI patients with polytrauma. These findings can be helpful to define future research in order to optimize the care of patients suffering tSCI.Peer reviewe

Snazer: the simulations and networks analyzer

<p>Abstract</p> <p>Background</p> <p>Networks are widely recognized as key determinants of structure and function in systems that span the biological, physical, and social sciences. They are static pictures of the interactions among the components of complex systems. Often, much effort is required to identify networks as part of particular patterns as well as to visualize and interpret them.</p> <p>From a pure dynamical perspective, simulation represents a relevant <it>way</it>-<it>out</it>. Many simulator tools capitalized on the "noisy" behavior of some systems and used formal models to represent cellular activities as temporal trajectories. Statistical methods have been applied to a fairly large number of replicated trajectories in order to infer knowledge.</p> <p>A tool which both graphically manipulates reactive models and deals with sets of simulation time-course data by aggregation, interpretation and statistical analysis is missing and could add value to simulators.</p> <p>Results</p> <p>We designed and implemented <it>Snazer</it>, the simulations and networks analyzer. Its goal is to aid the processes of visualizing and manipulating reactive models, as well as to share and interpret time-course data produced by stochastic simulators or by any other means.</p> <p>Conclusions</p> <p><it>Snazer </it>is a solid prototype that integrates biological network and simulation time-course data analysis techniques.</p

Casemix, management, and mortality of patients rreseceiving emergency neurosurgery for traumatic brain injury in the Global Neurotrauma Outcomes Study: a prospective observational cohort study.

BackgroundTraumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development.MethodsWe did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)-a composite of life expectancy, education, and income measures-into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation.FindingsOur study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24-51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34-69) and the youngest in the low HDI tier (median 28 years, IQR 20-38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6-32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55-5·2) and high HDI tier (2·26, 1·23-4·15), but not the low HDI tier (1·66, 0·61-4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17-2·49).InterpretationPatients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices.FundingNational Institute for Health Research Global Health Research Group