An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

A Clinical Practice Guideline for Prevention, Diagnosis and Management of Intraoperative Spinal Cord Injury: Recommendations for Use of Intraoperative Neuromonitoring and for the Use of Preoperative and Intraoperative Protocols for Patients Undergoing Spine Surgery.

STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Neurovascular Interventions for Neurotrauma: From Treatment of Injured Vessels to Treatment of the Injured Brain?

Traumatic brain injury is often associated with a direct or secondary neurovascular pathology. In this review, we present recent advancements in endovascular neurosurgery that enable accurate and effective vessel reconstruction with emphasis on its role in early diagnosis, the expanding use of flow diversion in pseudoaneurysms, and traumatic arteriovenous fistulas. In addition, future directions in which catheter-based interventions could potentially affect traumatic brain injury are described: targeting blood brain barrier integrity using the advantages of intra-arterial drug delivery of blood brain barrier stabilizers to prevent secondary brain edema, exploring the impact of endovascular venous access as a means to modulate venous outflow in an attempt to reduce intracranial pressure and augment brain perfusion, applying selective intra-arterial hypothermia as a neuroprotection method mitigating some of the risks conferred by systemic cooling, trans-vessel wall delivery of regenerative therapy agents, and shifting attention using multimodal neuromonitoring to post-traumatic vasospasm to further characterize the role it plays in secondary brain injury. Thus, we believe that the potential of endovascular tools can be expanded because they enable access to the "highways" governing perfusion and flow and call for further research focused on exploring these routes because it may contribute to novel endovascular approaches currently used for treating injured vessels, harnessing them for treatment of the injured brain.

Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES).

BACKGROUND: Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. METHODS: A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. RESULTS: A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations to support clinician's decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

Intracranial pressure: current perspectives on physiology and monitoring.

Intracranial pressure (ICP) monitoring is now viewed as integral to the clinical care of many life-threatening brain insults, such as severe traumatic brain injury, subarachnoid hemorrhage, and malignant stroke. It serves to warn of expanding intracranial mass lesions, to prevent or treat herniation events as well as pressure elevation which impedes nutrient delivery to the brain. It facilitates the calculation of cerebral perfusion pressure (CPP) and the estimation of cerebrovascular autoregulatory status. Despite advancements in our knowledge emanating from a half century of experience with this technology, important controversies remain related even to fundamental aspects of ICP measurements, including indications for monitoring, ICP treatment thresholds, and management of intracranial hypertension. Here, we review the history of ICP monitoring, the underlying pathophysiology as well as current perspectives on why, when and how ICP monitoring is best used. ICP is typically assessed invasively but a number of emerging, non-invasive technologies with inherently lower risk are showing promise. In selected cases, additional neuromonitoring can be used to assist in the interpretation of ICP monitoring information and adapt directed treatment accordingly. Additional efforts to expand the evidence base relevant to ICP monitoring, related technologies and management remain a high priority in neurosurgery and neurocritical care.

The human anti-ganglioside GM1 autoantibody response following traumatic and surgical central nervous system insults.

Predictors of the central nervous system (CNS) directed autoantibody response after acute CNS injury are poorly understood. We analyzed titers of IgG and IgM autoantibodies to ganglioside GM1 in serial serum specimens collected from human patients following acute spinal cord injury (SCI), traumatic brain injury (TBI) and brain tumor resection. We also assessed putative predictors of the autoantibody titers. We enrolled 19 patients with acute SCI, 14 patients with acute severe TBI, and 19 patients undergoing brain tumor resection. We also enrolled 25 control subjects. Some SCI, TBI and tumor patients exhibited elevated IgG titers as compared with control values; some SCI and TBI patients exhibited an acute peak in IgG titers, most commonly 14 days after insult. Some clinical and radiographic measures of injury severity correlated with IgG titer elevation in SCI and TBI patients but not tumor patients. Our study demonstrates that diverse CNS insults are followed by increased IgG autoimmune antibody titers to the CNS antigen ganglioside GM1, however the response inherent to each insult type is unique. IgG autoimmune antibody titers to GM1 merit further study as a biomarker of traumatic injury severity that can be measured in delayed fashion after CNS insult. These human data help to inform which patients with CNS insults are at risk for CNS-directed autoimmunity as well as the time course of the response.

Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations.

When the fourth edition of the Brain Trauma Foundation's Guidelines for the Management of Severe Traumatic Brain Injury were finalized in late 2016, it was known that the results of the RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) randomized controlled trial of decompressive craniectomy would be public after the guidelines were released. The guideline authors decided to proceed with publication but to update the decompressive craniectomy recommendations later in the spirit of "living guidelines," whereby topics are updated more frequently, and between new editions, when important new evidence is published. The update to the decompressive craniectomy chapter presented here integrates the findings of the RESCUEicp study as well as the recently published 12-mo outcome data from the DECRA (Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury) trial. Incorporation of these publications into the body of evidence led to the generation of 3 new level-IIA recommendations; a fourth previously presented level-IIA recommendation remains valid and has been restated. To increase the utility of the recommendations, we added a new section entitled Incorporating the Evidence into Practice. This summary of expert opinion provides important context and addresses key issues for practitioners, which are intended to help the clinician utilize the available evidence and these recommendations. The full guideline can be found at: https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/.

Rescatando al RescueICP: ¿Quién decide que es favorable o no? / Rescuing the RescueICP: Who decides what is favorable or not?

Tipo de Estudio: Internacional, multicéntrico, controlado y randomizado, Objetivo: Evaluar efectividad de la craniectomía descompresiva (CD) en el manejo de la hipertensión intracraneal refractaria en pacientes con lesión cerebral traumática. Material y Métodos: Incluyó 408 pacientes entre 10 y 65 años desde el 2004 hasta 2014. 202 pacientes en el grupo quirúrgico y 196 en el grupo de manejo médico fueron enrolados, 10 pacientes fueron excluidos por falta de consentimiento informado válido y retiro voluntario. Una vez enrolados se randomizó en 02 grupos: 1) craniectomía descompresiva (CD), debía realizarse 4 a 6 horas después de la randomización (hemicraniectomía frontotémporoparietal o craniectomía bifrontal) y 2) tratamiento médico, la cual dentro sus medidas de manejo (línea 1 y línea 2) incluía también el uso de barbitúricos e hipotermia. Resultados: La mortalidad en grupo quirúrgico fue 26,9% vs 48,9% en el grupo médico, estado vegetativo 8,5% vs 2,1%, dependencia completa de otros 21,9% vs 14,4%, buena recuperación sin déficit 4% vs 6,9% a los 6 meses. Mortalidad en grupo quirúrgico a 12 meses fue 30,% vs 52% en el grupo médico, estado vegetativo 6,2% vs 1,7%, dependencia completa de otros 18% vs 14%, buena recuperación sin déficit 9,8% vs 8,4%. Conclusión: La CD como tratamiento de la hipertensión endocraneana grave y refractaria, disminuyó la mortalidad en un 22%, comparado con el grupo de tratamiento médico (p< 0,001), pero se asoció con mayores casos de pacientes en estado vegetativo y discapacidad severa. Las tasas de discapacidad moderada y buena recuperación, fueron similares en ambos grupos.

Surgical Treatment of Vestibular Schwannoma: Does Age Matter?

OBJECTIVE: For older patients (>65 years) who undergo surgical treatment of vestibular schwannoma (VS), the reported rates of facial nerve preservation, hearing preservation, and complications are inconsistent. Many surgeons believe that older patients have worse outcomes than their younger counterparts and advise against surgical treatment. We analyzed a consecutive series of patients with VS treated with surgery to determine whether age was a factor in outcome. METHODS: We retrospectively reviewed all patients treated for VS at our institution from January 1, 2000, to July 1, 2012. We examined how sex, age (≥65 years and <65 years), race, tumor size, tumor laterality, body mass index, Charlson Comorbidity Index, smoking status, surgical approach, and preoperative hearing and symptoms were associated with outcomes. RESULTS: Two-hundred forty-three patients underwent resection of VS, including 23 patients ≥65 years (mean 68 ± 4 years) and 220 patients <65 years (mean 47 ± 11 years). The average tumor size was 16.5 mm. Older patients had a significantly lower body mass index of 26.6 vs. 29.8 (P = 0.03) and were more likely to have a CCI ≥2 (52.2% vs. 18.2%, P ≤ 0.00, preoperative facial numbness (34.8% vs. 10.1%, P = 0.03), and dizziness (78.3% vs. 49.3%, P = 0.03). There were no significant differences after surgery in facial nerve outcome, hearing preservation outcome, or general surgical complications between the 2 cohorts. CONCLUSIONS: With no difference in surgical complications, facial nerve outcome, or hearing preservation rates between older and younger patients in our series, age alone may not be an absolute contraindication to surgical management of VS.

Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

Classification of traumatic brain injury: past, present, and future.

Disease classification is central to the practice of medicine; it systematizes clinical knowledge and experience. Classification is essential for diagnosis and effective treatment of human disease. Progress in classifying traumatic brain injury (TBI) for targeted treatment has lagged behind other diseases such as cancer, and has contributed to a lack of progress in the field. Today TBI is most frequently classified as mild, moderate, or severe using the Glasgow Coma Scale (GCS). However, the GCS is symptoms-based and does not allow for targeting of specific pathology. Here we review general schemas for disease classification and how they have evolved over time. We discuss the characteristics of an ideal classification system and the unique challenges inherent to achieving such a system for TBI. Current means of classifying TBI are reviewed, as are the strengths and limitations of these approaches. Generating the data required to modernize TBI classification and to perhaps facilitate a targeted, precision medicine approach to its management will require a highly collaborative international effort. Fortunately these efforts are underway and will benefit from the lessons and tools that have come from other areas of medicine that have already found success with this approach.

An examination of the mechanisms by which neural precursors augment recovery following spinal cord injury: a key role for remyelination.

The mechanisms by which neural precursor cells (NPCs) enhance functional recovery from spinal cord injury (SCI) remain unclear. Spinal cord injured rats were transplanted with wild-type mouse NPCs, shiverer NPCs unable to produce myelin, dead NPCs, or media. Most animals also received minocycline, cyclosporine, and perilesional infusion of trophins. Motor function was graded according to the BBB scale. H&E/LFB staining was used to assess gray and white matter, cyst, and lesional tissue. Mature oligodendrocytes and ED1(+) inflammatory cells were quantitated. Confocal and electron microscopy were used to assess the relationship between the transplanted cells and axons. Pharmacotherapy and trophin infusion preserved gray matter, white matter, and oligodendrocytes. Trophin infusion also significantly increased cyst and lesional tissue volume as well as inflammatory infiltrate, and functional recovery was reduced. Animals transplanted with wild-type NPCs showed greatest functional recovery; animals transplanted with shiverer NPCs performed the worst. Wild-type NPCs remyelinated host axons. Shiverer NPCs ensheathed axons but did not produce MBP. These results suggest that remyelination by NPCs is an important contribution to functional recovery following SCI. Shiverer NPCs may prevent remyelination by endogenous cells capable of myelin formation. These findings suggest that remyelination is an important therapeutic target following SCI.

In vitro characterization of trophic factor expression in neural precursor cells.

In cellular transplantation strategies for repairing the injured central nervous system, interactions between transplanted neural precursor cells (NPCs) and host tissue remain incompletely understood. Although trophins may contribute to the benefits observed, little research has explored this possibility. Candidate trophic factors were identified, and primers were designed for these genes. Template RNA was isolated from 3 NPC sources, and also from bone marrow stromal cells (BMSCs) and embryonic fibroblasts as comparative controls. Quantitative polymerase chain reaction was performed to determine the effect of cell source, passaging, cellular differentiation, and environmental changes on trophin factor expression in NPCs. Results were analyzed with multivariate statistical analyses. NPCs, BMSCs, and fibroblasts each expressed trophic factors in unique patterns. Trophic factor expression was similar among NPCs whether harvested from rat or mouse, brain or spinal cord, or their time in culture. The expression of neurotrophin NT-3, NT-4/5, glial-derived neurotrophic factor, and insulin-like growth factor-1 decreased with time in culture. Induced differentiation of NPCs led to a marked and statistically significant increase in the expression of trophic factors. Culture conditions and environmental changes were also associated with significant changes in trophin expression. These results suggest that trophins could contribute to the benefits associated with transplantation of NPCs as well as BMSCs. Trophic factor expression changes with NPC differentiation and environmental conditions, which could have important implications with regard to their behavior after in vivo transplantation.

An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury.

Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-ß1 (TGF-ß1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion. Trophins may contribute to the benefits associated with cell-based repair strategies for spinal cord injury.