Current status of pediatric neurocritical care in Argentina. / Estado actual del soporte neurológico crítico en pediatría en la Argentina.

INTRODUCTION: Patients with neurocritical injuries account for 10-16 % of pediatric intensive care unit (PICU) admissions and frequently require neuromonitoring. OBJECTIVE: To describe the current status of neuromonitoring in Argentina. METHODS: Survey with 37 questions about neuromonitoring without including patients' data. Period: April-June 2017. RESULTS: Thirty-eight responses were received out of 71 requests (14 districts with 11 498 annual discharges). The PICU/hospital bed ratio was 21.9 (range: 4.2-66.7). Seventy-four percent of PICUs were public; 61 %, university-affiliated; and 71 %, level I. The availability of monitoring techniques was similar between public and private (percentages): intracranial pressure (95), electroencephalography (92), transcranial Doppler (53), evoked potentials (50), jugular saturation (47), and bispectral index (11). Trauma was the main reason for monitoring. CONCLUSION: Except for intracranial pressure and electroencephalography, neuromonitoring resources are scarce and active neurosurgery availability is minimal. A PICU national registry is required.

Introducción. Los pacientes con lesiones neurocríticas representan el 10-16 % de los ingresos a unidades de cuidados intensivos pediátricas (UCIP) y, frecuentemente, requieren neuromonitoreo. Objetivo. Describir el estado actual del neuromonitoreo en la Argentina. Métodos. Encuesta con 37 preguntas sobre neuromonitoreo sin incluir datos de pacientes. Período: abril-junio, 2017. Resultados. Se recibieron 38 respuestas a 71 solicitudes (14 distritos con 11 498 egresos anuales). La relación camas de UCIP/hospitalarias fue 21,9 (rango: 4,2-66,7). El 74 % fueron públicas; el 61 %, universitarias, y el 71 %, nivel 1. La disponibilidad fue similar entre públicas y privadas (porcentajes): presión intracraneana (95), electroencefalografía (92), doppler transcraneano (53), potenciales evocados (50), saturación yugular (47) e índice bispectral (11). El principal motivo de monitoreo fue trauma. Conclusión. Excepto la presión intracraneana y la electroencefalografía, los recursos de neuromonitoreo son escasos y la disponibilidad de neurocirugía activa es mínima. Se necesita un registro nacional de UCIP.

Developing a Guideline for Neurotrauma in Nigeria.

BACKGROUND: The Nigerian Academy of Neurological Surgeons in 2019 resolved to standardize the practice of neurosurgery in Nigeria. It set up committees to standardize the various aspects of neurosurgery, such as neurotrauma, pediatrics, functional, vascular, skull base, brain tumor, and spine. The Committee on Neurotrauma convened and resolved to study most of the available protocols and guidelines in use in different parts of the world. OBJECTIVE: To formulate a standard protocol for the practice of neurotrauma care within the Nigerian locality. METHODS: The Committee split its membership into 3 subcommittees to cover the various aspects of the Neurotrauma Guidelines, such as neurotrauma curriculum, standard neurotrauma management protocols, and neurotrauma registry. Each subcommittee was to research on available models and formulate a draft for Nigerian neurotrauma. RESULTS: All the 3 subcommittees had their reports ready on schedule. Each concurred that neurotrauma is a major public health challenge in Nigeria. They produced 3 different drafts on the 3 thematic areas of the project. The subcommittees are: 1. Subcommittee on Fellowship, Training and Research Curriculum; 2. Subcommittee on Standard Protocols and Management Guidelines; and 3. Subcommittee of the Nigerian Neurotrauma Registry. CONCLUSION: The committee concluded that a formal protocol for neurotrauma care is long overdue in Nigeria for the standardization of all aspects of neurotrauma. It then recommended the adoption of these guidelines by all institutions offering services in Nigeria using the management protocols, opening a registry, and mounting researches on the various aspects of neurotrauma.

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis.

INTRODUCTION: The immuno-microenvironment of injured nerves adversely affects mesenchymal stem cell (MSC) therapy for neurotmesis. Magnetic resonance imaging (MRI) can be used noninvasively to monitor nerve degeneration and regeneration. The aim of this study was to investigate nerve repair after MSC transplantation combined with microenvironment immunomodulation in neurotmesis by using multiparametric MRI. METHODS: Rats with sciatic nerve transection and surgical coaptation were treated with MSCs combined with immunomodulation or MSCs alone. Serial multiparametric MRI examinations were performed over an 8-week period after surgery. RESULTS: Nerves treated with MSCs combined with immunomodulation showed better functional recovery, rapid recovery of nerve T2, fractional anisotropy and radial diffusivity values, and more rapid restoration of the fiber tracks than nerves treated with MSCs alone. DISCUSSION: Transplantation of MSCs in combination with immunomodulation can exert a synergistic repair effect on neurotmesis, which can be monitored by multiparametric MRI.

Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration.

Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.

Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models.

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

An update on the management of adult traumatic nerve injuries-replacing old paradigms: A review.

Acute nerve injuries are routinely encountered in multisystem trauma patients. Advances in surgical treatment of nerve injuries now mean that good outcomes can be achieved. Despite this, old mantras associated with management of nerve injuries, including "wait a year to see if recovery occurs" and "there's nothing we can do", persist. Practicing by these mantras places these patients at a disadvantage. Changes begin to occur in the nerve, neuromuscular junction, and muscle from the moment a nerve injury occurs. These changes can become irreversible approximately 18 to 24 months following denervation. Thus, it is a race to reestablish a functional nerve-muscle connection before these irreversible changes. Good outcomes rely on appropriate acute management and avoiding delays in care. Primary nerve surgery options include direct primary repair, nerve graft repair, and nerve transfer. Acute management of nerve injuries proceeds according to the rule of 3's and requires early cooperation between trauma surgeons who recognize the nerve injury and consultant nerve surgeons. Care of patients with acute traumatic nerve injuries should not be delayed. Awareness of current management paradigms among trauma surgeons will help facilitate optimal upfront management. With the ever-expanding surgical options for management of these injuries and the associated improvement of outcomes, early multidisciplinary approaches to these injuries have never been more important. Old mantras must be replaced with new paradigms to continue to see improvements in outcomes for these patients. The importance of this review is to raise awareness among trauma surgeons of new paradigms for management of traumatic nerve injuries.

Peripheral nerve injuries in the pediatric population: a review of the literature. Part I: traumatic nerve injuries.

OBJECTIVE: This article reviews the clinical results that can be obtained after repair of a traumatic peripheral nerve injury in the pediatric population. METHODS: A systematic review of the published literature has been made. RESULTS: Functional outcome after major nerve injuries is sometimes disappointing in adults. However, children have been reported to experience much better functional results after nerve repair than adults. Moreover, recovery generally is faster in children. The superior capacity of children's central nervous system to adapt to external or internal environmental changes (neural plasticity) and the shorter recovery distance from the axon repair site to the target muscle are claimed to be crucial determinants of their favorable outcomes. Moreover, even in the pediatric population, it has been demonstrated that functional results are better the younger the patient is, including better clinical results in those injured in early childhood (< 6 years old) than in those injured in adolescence. Other favorable prognostic factors include the type of nerve injury (with complete transections doing less well than crush injuries) and the timing of surgery (with better outcomes after early repairs). CONCLUSIONS: All efforts should be done to repair in a timely and adequate fashion traumatic peripheral nerve injuries in children, as the results are good.

Rotary jet-spun porous microfibers as scaffolds for stem cells delivery to central nervous system injury.

Stem cell transplantation is a promising strategy to treat brain injuries. However, cell-based therapies are limited because poor local cell engraftment. Here, we present a polylactic acid (PLA) scaffold to support mesenchymal stem cells (MSCs) delivery in stroke. We isolated bone marrow MSCs from adult C57/Bl6 mice, cultured them on PLA polymeric rough microfibrous (PRM) scaffolds obtained by rotary jet spinning, and transplanted over the brains of adult C57/Bl6 mice, carrying thermocoagulation-induced cortical stroke. No inflammatory response to PRM was found. MSCs transplantation significantly reduced the area of the lesion and PRM delivery increased MSCs retention at the injury site. In addition, PRM upregulated α6-integrin and CXCL12 production, which may be the cause for greater cell retention at the lesion site and may provide additional benefit to MSCs transplantation procedures. We conclude that PRM scaffolds offer a promising new system to deliver stem cells to injured areas of the brain.

Predictive value of a diagnostic block in focal nerve injury with neuropathic pain when surgery is considered.

OBJECT: In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief. We evaluated the predictive value of a block on the outcome of surgery. METHODS: In total, three blocks were performed at two week intervals. Patients were blinded to injections containing lidocaine 1% and a placebo was included. Surgery was offered regardless of the effect of the blocks. Twenty-four patients received 72 blocks. Sixteen patients opted for surgery, 5 patients refrained from surgery, and in 3 the blocks provided permanent pain relief. The predictive ability of the block on the outcome of surgery was assessed by calculating the area under a Receiver Operating Characteristic curve (AUC). RESULTS: The AUC of the first lidocaine block was 0.35 with a 95% confidence interval from 0.077 to 0.62. At 95% confidence (two-sided), the AUC is less than 0.62, and hence the predictive ability of the block was poor. The outcome of the second lidocaine block and saline block did not change the conclusion of the first block. CONCLUSIONS: We conclude that the use of blocks to select patients for surgery should be critically appraised. PERSPECTIVE: A pain relieving response to one open block is currently considered mandatory before patients with focal nerve injury and neuropathic pain are offered surgery. Blinded blocks including a placebo show that responses for selection should be carefully interpreted because they may not be as predictive as generally presumed.

A three-layered hollow tubular scaffold as an enhancement of nerve regeneration potential.

A significant clinical challenge in the surgery of peripheral nervous system injured via accidents and natural disease is development of biomimetic grafts which could potentially promote nerve repair and regeneration. Although various engineered neural tissue scaffolds have been proposed to support the neural cell functions, they have not been able to instantaneously mimic the whole characteristics of endogenous microenvironment. In this study, we proposed a three-layered tubular scaffold which could provide appropriate electrical, mechanical and biological properties for peripheral nerve engineering. While the inter layer was graphene (Gr) embedded alginate-polyvinyl alcohol (AP-Gr) fibrous scaffold with well-defined anisotropy, the outer layer was double network scaffold of polycaprolactone fumarate (PCLF) and eggshell membrane (ESM). These two layers were attached together using a polycaprolactone (PCL) fibrous membrane, a middle layer, via a simple melting process. Results showed that while the electrical conductivity of the three-layered scaffold was similar to that of AP-Gr fibrous layer, the strength of the three-layered scaffold was significantly improved compared to AP-Gr and ESM-PCLF (1.5 and 1.1 times, respectively) attributed to well attachment of the two layers. As a proof-of-concept, PC12 cell attachment, proliferation, and alignment were studied on the developed three-layered scaffold. The majority of the cells (55%) aligned (<20°) along the major axis of fibers features. Furthermore, electrical stimulation revealed positive effect on the alignment of PC12 cells and change in the cell morphology. With the ease of fabrication and mechanical robustness, the three-layered scaffold of AP-Gr and ESM-PCLF might be utilized as a versatile system for the engineering of peripheral nerve tissue.

Establishing an Organotypic System for Investigating Multimodal Neural Repair Effects of Human Mesenchymal Stromal Stem Cells.

Human mesenchymal stromal stem cells (hMSCs) hold regenerative medicine potential due to their availability, in vitro expansion readiness, and autologous feasibility. For neural repair, hMSCs show translational value in research on stroke, spinal cord injury (SCI), and traumatic brain injury. It is pivotal to establish multimodal in vitro systems to investigate molecular mechanisms underlying neural actions of hMSCs. Here, we describe a platform protocol on how to set up organotypic co-cultures of hMSCs (alone or polymer-scaffolded) with explanted adult rat dorsal root ganglia (DRGs) to determine neural injury and recovery events for designing implants to counteract neurotrauma sequelae. We emphasize in vitro hMSC propagation, polymer scaffolding, hMSC stemness maintenance, hMSC-DRG interaction profiling, and analytical formulas of neuroinflammation, trophic factor expression, DRG neurite outgrowth and tropic tracking, and in vivo verification of tailored implants in rodent models of SCI. © 2018 by John Wiley & Sons, Inc.

Cellular therapy for traumatic neurological injury.

Neurological injury is the primary lethal mechanism of injury in children, and the primary etiology of long-term disability after trauma. Laboratories and clinical/translational teams have sought to develop stem/progenitor cell therapies to improve recovery in a clinical setting in which there is no significant reparative option. While none of these treatments are currently standard therapeutics, phase IIb clinical trials are underway in both adults and children in severe traumatic brain injury (TBI) and phase I/IIa trials in spinal cord injury. This review will characterize the cell therapy strategies: cell replacement and tissue integration vs. immunomodulation/enhanced endogenous tissue repair. TBI is somewhat different from other central nervous system injuries (spinal cord injury and stroke), in that TBI is a diffuse injury, whereas spinal cord injury and stroke are anatomically discrete. Importantly, this drives cell therapy approaches, as TBI is less apt to be treatable with a local cell replacement intervention. More localized injuries may be more amenable to local approaches and cell replacement to bridge focal gaps. This review focuses on a few reports in the field that highlight areas of progress, but is not intended to be a comprehensive survey of the state of regenerative medicine for neurological injuries.

Palliative Care Needs Assessment in the Neuro-ICU: Effect on Family.

BACKGROUND: Examine the association of a daily palliative care needs checklist on outcomes for family members of patients discharged from the neurosciences intensive care unit (neuro-ICU). METHODS: We conducted a prospective, longitudinal cohort study in a single, thirty-bed neuro-ICU in a regional comprehensive stroke and level 1 trauma center. One of two neuro-ICU services that admit patients to the same ICU on alternating days used a palliative care needs checklist during morning work rounds. Between March and October, 2015, surveys were mailed to family members of patients discharged from the neuro-ICU. RESULTS: Nearly half of surveys (n = 91, 48.1%) were returned at a median of 4.7 months. At the time of survey completion, mean Modified rankin scale score (mRS) of neuro-ICU patients was 3.1 (SD 2). Overall ratings of quality of care were relatively high (82.2 on a 0-100 scale) with 32% of family members meeting screening criteria for depressive syndrome. The primary outcome measuring family satisfaction, consisting of eight items from the Family Satisfaction in the ICU questionnaire, did not differ significantly between families of patients from either ICU service nor did family ratings of depression (PHQ-8) and post-traumatic stress (PCL-17). CONCLUSIONS: Among families of patients discharged from the neuro-ICU, the daily use of a palliative care needs checklist had no measurable effect on family satisfaction scores or long-term psychological outcomes. Further research is needed to identify optimal interventions to meet the palliative care needs specific to family members of patients treated in the neuro-ICU.

Serum-free bioprocessing of adult human and rodent skin-derived Schwann cells: implications for cell therapy in nervous system injury.

Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long-lived permanent disability, despite nerve repair surgery. Autologous Schwann cell (SC) therapy currently provides an exciting avenue for improved outcomes for these patients, particularly with the possibility to derive SCs from easily-accessible adult skin. However, due to current challenges regarding the efficient expansion of these cells, further optimization is required before they can be seriously considered for clinical application. Here, a microcarrier-based bioreactor system is proposed as a means to scale-up large numbers of adult skin-derived SCs for transplantation into the injured nerve. Bioprocessing parameters that allow for the expansion of adult rodent SCs have been identified, whilst maintaining similar rates of proliferation (as compared to static-grown SCs), expression of SC markers, and, importantly, their capacity to myelinate axons following transplant into the injured sciatic nerve. The same bioprocessing parameters can be applied to SCs derived from adult human skin, and like rodent cells, they sustain their proliferative potential and expression of SC markers. Taken together, this dataset demonstrates the basis for a scalable bioprocess for the production of SCs, an important step towards clinical use of these cells as an adjunct therapy for nerve repair. Copyright © 2017 John Wiley & Sons, Ltd.

An Initiative to Standardize the Identification of and Acute Response to Postoperative Lower-Extremity Neurological Deficits: Effects on Provider Knowledge, Confidence, and Communication Skills.

BACKGROUND: Although relatively uncommon, neurological deficits following hip and knee arthroplasty can have permanent and debilitating consequences. This study was conducted to quantify the effectiveness of an educational curriculum aimed at standardizing the identification of and acute response to postoperative neurological deficits in the inpatient setting, specifically with respect to improvements in clinician knowledge, confidence levels, and communication skills. METHODS: A multidisciplinary committee at a single, high-volume academic institution created an algorithm delineating the appropriate clinical actions and escalation procedures in the setting of a postoperative neurological deficit for each clinical practitioner involved in care for patients who undergo arthroplasty. An educational curriculum composed of online learning modules and an in-person "boot camp" featuring simulations with standardized patients was developed, along with assessments of clinician knowledge, confidence levels, and communication skills. Nurses, physical therapists, physician assistants, residents, fellows, and attending surgeons were encouraged to participate. The intervention spanned a 5-month period in 2015 with a mean time of 18.4 weeks between baseline assessments and the time of the latest follow-up. RESULTS: Online modules were completed by 322 individuals, boot camp was completed by 70 individuals, and latest assessments were completed by 38 individuals. The percentage correct on the knowledge assessment increased from 74.5% before the learning modules to 89.5% immediately after (p < 0.001) but degraded over time such that there was no significant difference between baseline and the latest follow-up scores (p = 0.11). Over the course of the boot camp, physician assistants and residents successfully performed approximately 91% of the indicated actions on the scoring rubric; physical therapists and nurses successfully performed 78%. Scores on the communication skills assessment showed a significant mean increase (p = 0.02) over the course of the intervention from 30.32 to 32.50, and the mean self-assessed confidence survey scores increased by 16.7%, from 7.2 to 8.4 (p < 0.001). CONCLUSIONS: A multimodality educational curriculum aimed at quality improvement can produce significant knowledge improvements, but these gains may not be maintained over time without further instruction. Gains in confidence and communication skills appear to be more long-lasting.

Retrospective analysis of a case series of patients with traumatic injuries to the craniocervical junction / Análise retrospectiva de série de casos com lesões traumáticas da junção craniocervical

ABSTRACT Objective To evaluate the correlation between the treatment, the characteristics of the lesions and the clinical outcome of patients with traumatic injuries to the craniocervical junction. Methods This was a retrospective study of patients treated conservatively or surgically between 2010 and 2013 with complete data sets. Results We analyzed 37 patients, 73% were men with mean age of 41.7 years. Of these, 32% were submitted to initial surgical treatment and 68% received conservative treatment. Seven (29%) underwent surgery subsequently. In the surgical group, there were seven cases of odontoid type II fractures, two cases of fracture of posterior elements of the axis, one case of C1-C2 dislocation with associated fractured C2, one case of occipitocervical dislocation, and one case of combined C1 and C2 fractures, and facet dislocation. Only one patient had neurological déficit that improved after treatment. Two surgical complications were seen: a liquoric fistula and one surgical wound infection (reaproached). In the group treated conservatively, odontoid fractures (eight cases) and fractures of the posterior elements of C2 (five cases) were more frequent. In two cases, in addition to the injuries of the craniocervical junction, there were fractures in other segments of the spine. None of the patients who underwent conservative treatment presented neurological deterioration. Conclusion Although injuries of craniocervical junction are relatively rare, they usually involve fractures of the odontoid and the posterior elements of the axis. Our results recommend early surgical treatment for type II odontoid fractures and ligament injuries, the conservative treatment for other injuries.

RESUMO Objetivo Avaliar a correlação entre o tratamento, as características das lesões e o resultado clínico em pacientes com lesões traumáticas na junção craniocervical. Métodos Estudo retrospectivo de pacientes maiores de 18 anos tratados de forma conservadora ou cirúrgica, entre 2010 e 2013. Resultados Foram analisados 37 pacientes, 73% eram do sexo masculino e a média de idade foi de 41,7 anos. Inicialmente 32% dos pacientes foram submetidos a tratamento cirúrgico, e 68% foram submetidos a tratamento conservador. Sete pacientes (29%) do grupo conservador foram submetidos posteriormente à cirurgia. No grupo cirúrgico, houve sete casos de fratura de odontóide tipo II, dois casos de fratura de elementos posteriores do áxis, um caso de luxação C1-C2, um caso de deslocamento occipito-cervical e um caso de fraturas de C1 e C2 e luxação facetária. Um paciente apresentava déficit neurológico, melhorando após o tratamento. Houve duas complicações pós-cirúrgicas, uma fístula liquórica e uma infecção de ferida operatória (reabordada). No grupo conservador, predominaram as fraturas do odontóide (oito) e dos elementos posteriores de C2 (cinco). Em dois casos, havia também fraturas em outros segmentos da coluna. Nenhum dos pacientes deste grupo apresentou deterioração neurológica. Conclusão As lesões da junção craniocervical são raras, sendo mais frequentes as fraturas do odontóide e dos elementos posteriores do áxis. Nossos resultados recomendam o tratamento cirúrgico precoce para os pacientes com fraturas do odontóide tipo II e lesões ligamentares, e tratamento conservador para os demais pacientes.

Retrospective analysis of a case series of patients with traumatic injuries to the craniocervical junction.

OBJECTIVE: To evaluate the correlation between the treatment, the characteristics of the lesions and the clinical outcome of patients with traumatic injuries to the craniocervical junction. METHODS: This was a retrospective study of patients treated conservatively or surgically between 2010 and 2013 with complete data sets. RESULTS: We analyzed 37 patients, 73% were men with mean age of 41.7 years. Of these, 32% were submitted to initial surgical treatment and 68% received conservative treatment. Seven (29%) underwent surgery subsequently. In the surgical group, there were seven cases of odontoid type II fractures, two cases of fracture of posterior elements of the axis, one case of C1-C2 dislocation with associated fractured C2, one case of occipitocervical dislocation, and one case of combined C1 and C2 fractures, and facet dislocation. Only one patient had neurological déficit that improved after treatment. Two surgical complications were seen: a liquoric fistula and one surgical wound infection (reaproached). In the group treated conservatively, odontoid fractures (eight cases) and fractures of the posterior elements of C2 (five cases) were more frequent. In two cases, in addition to the injuries of the craniocervical junction, there were fractures in other segments of the spine. None of the patients who underwent conservative treatment presented neurological deterioration. CONCLUSION: Although injuries of craniocervical junction are relatively rare, they usually involve fractures of the odontoid and the posterior elements of the axis. Our results recommend early surgical treatment for type II odontoid fractures and ligament injuries, the conservative treatment for other injuries. OBJETIVO: Avaliar a correlação entre o tratamento, as características das lesões e o resultado clínico em pacientes com lesões traumáticas na junção craniocervical. MÉTODOS: Estudo retrospectivo de pacientes maiores de 18 anos tratados de forma conservadora ou cirúrgica, entre 2010 e 2013. RESULTADOS: Foram analisados 37 pacientes, 73% eram do sexo masculino e a média de idade foi de 41,7 anos. Inicialmente 32% dos pacientes foram submetidos a tratamento cirúrgico, e 68% foram submetidos a tratamento conservador. Sete pacientes (29%) do grupo conservador foram submetidos posteriormente à cirurgia. No grupo cirúrgico, houve sete casos de fratura de odontóide tipo II, dois casos de fratura de elementos posteriores do áxis, um caso de luxação C1-C2, um caso de deslocamento occipito-cervical e um caso de fraturas de C1 e C2 e luxação facetária. Um paciente apresentava déficit neurológico, melhorando após o tratamento. Houve duas complicações pós-cirúrgicas, uma fístula liquórica e uma infecção de ferida operatória (reabordada). No grupo conservador, predominaram as fraturas do odontóide (oito) e dos elementos posteriores de C2 (cinco). Em dois casos, havia também fraturas em outros segmentos da coluna. Nenhum dos pacientes deste grupo apresentou deterioração neurológica. CONCLUSÃO: As lesões da junção craniocervical são raras, sendo mais frequentes as fraturas do odontóide e dos elementos posteriores do áxis. Nossos resultados recomendam o tratamento cirúrgico precoce para os pacientes com fraturas do odontóide tipo II e lesões ligamentares, e tratamento conservador para os demais pacientes.

Emerging potential of exosomes and noncoding microRNAs for the treatment of neurological injury/diseases.

Recent discoveries of cellular generation of exosomes, small (∼ 30 - 100 nm) complex lipid membrane structures which encapsulate and transport proteins, RNAs, including microRNAs (miRNAs) have provided new insight in how cells within organisms communicate. These discoveries will likely have a major impact on the treatment of disease, with cancers and neurological diseases as evident targets. Exosomes provide a major medium of intercellular communications and thereby, there being a potential by altering communications and instructions for protein production, we can employ exosomes to treat diseases. We now have an opportunity to treat neurological disease by modifying intercellular communication networks. Recent work demonstrating that the therapeutic benefit provided by stem cells for the treatments of stroke and traumatic brain injury depend on their generation and release of exosomes provides a foundation for exosome-based therapy. Cell-free exosomes have also been recently employed to effectively treat stroke and brain trauma. The content of exosomes, particularly their miRNA cargo which can concurrently impact the post-transcriptional regulation of many genes, can be regulated. We are at the cusp of capitalizing on this important means of intercellular communications for the treatment of diseases, such as cancers and neurological diseases, among many others.

Stem cell-based approaches to improve nerve regeneration: potential implications for reconstructive transplantation?

Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cell-based therapies have been postulated and tested in pre-clinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues for regenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patient-specific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across "gaps" in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration.