Traumatic Brain Injury and Stem Cells: An Overview of Clinical Trials, the Current Treatments and Future Therapeutic Approaches.

Traumatic brain injury represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. The traumatic injury activates an important inflammatory response, followed by a cascade of events that lead to neuronal loss and further brain damage. Maintaining proper ventilation, a normal level of oxygenation, and adequate blood pressure are the main therapeutic strategies performed after injury. Surgery is often necessary for patients with more serious injuries. However, to date, there are no therapies that completely resolve the brain damage suffered following the trauma. Stem cells, due to their capacity to differentiate into neuronal cells and through releasing neurotrophic factors, seem to be a valid strategy to use in the treatment of traumatic brain injury. The purpose of this review is to provide an overview of clinical trials, aimed to evaluate the use of stem cell-based therapy in traumatic brain injury. These studies aim to assess the safety and efficacy of stem cells in this disease. The results available so far are few; therefore, future studies need in order to evaluate the safety and efficacy of stem cell transplantation in traumatic brain injury.

Effect of horse riding equipment in activity of trunk and lower limb muscles in equine-assisted therapy

Equine-assisted therapy uses the horse in rehabilitation and/or education of people, such as Down syndrome(SD), cerebral palsy(PC)and intellectual disability(DI). In context, the rehabilitation program and horse riding equipment should be usedaccording to the specific characteristics of each individual, becoming an ally in the quest for excellence in equine-assisted therapy programs. The aim was to evaluate the effect of riding equipment used in equine-assisted therapy on the muscular activityof trunk and lower limb of individuals with SD, PC and DI. The study included 15 individuals equally assigned to each group: SD, PC and DIwith a mean age of 16.2 (±1.10), 16 (±1.22)e 16 (±0) years,respectively. The analysis of muscle activity was performed through surface electromyography, using four variations of horse riding equipment: saddle with and without feet supported on the stirrups and blanket with and without feet supported on the stirrups. Sigma Stat 3.5®software was used for statistical analysis.The Shapiro Wilk's test was used for normality of the data, the Bartlett test for homogeneity of the variances and the Kruskal-Wallis test for repeated measures with no normal distribution.Statistically significant differences were observed forp<0.05.The SDgroup presented a greater muscular activity of trunk and lower limbs with blanket equipment without the feet supported in the stirrups (H = 15.078, p = 0.002), as in the DI group (H=8.302, p = 0.040), while inPCgroup was the saddle with feet supported in the stirrups (H=11.137,p = 0.011). The choice of riding equipment used in equine-assisted therapy interferes differently in the pattern of muscular activation of the trunk and the lower limbs, according to the pathological processes of the practitioners. It should be an important aspect to consider when planninga treatment.

Exercise-driven restoration of the alcohol-damaged brain.

There are vast literatures on the neural effects of alcohol and the neural effects of exercise. Simply put, exercise is associated with brain health, alcohol is not, and the mechanisms by which exercise benefits the brain directly counteract the mechanisms by which alcohol damages it. Although a degree of brain recovery naturally occurs upon cessation of alcohol consumption, effective treatments for alcohol-induced brain damage are badly needed, and exercise is an excellent candidate from a mechanistic standpoint. In this chapter, we cover the small but growing literature on the interactive neural effects of alcohol and exercise, and the capacity of exercise to repair alcohol-induced brain damage. Increasingly, exercise is being used as a component of treatment for alcohol use disorders (AUD), not because it reverses alcohol-induced brain damage, but because it represents a rewarding, alcohol-free activity that could reduce alcohol cravings and improve comorbid conditions such as anxiety and depression. It is important to bear in mind, however, that multiple studies attest to a counterintuitive positive relationship between alcohol intake and exercise. We therefore conclude with cautionary notes regarding the use of exercise to repair the brain after alcohol damage.

Predictors of Outcome Post Cardiac Arrest.

Early predictors of prognosis in comatose patients post cardiac arrest help inform decisions surrounding continuation or withdrawal of treatment and provide a framework on which to better inform relatives of the likely outcome. Markers defined prior to the widespread use of therapeutic hypothermia post arrest may no longer be reliable and an up-to-date analysis of the literature is presented.

Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications.

Lysosomal storage disorders (LSDs) are a broad class of monogenic diseases with an overall incidence of 1:7,000 newborns, due to the defective activity of one or more lysosomal hydrolases or related proteins resulting in storage of un-degraded substrates in the lysosomes. The over 40 different known LSDs share a life-threatening nature, but they are present with extremely variable clinical manifestations, determined by the characteristics and tissue distribution of the material accumulating due to the lysosomal dysfunction. The majority of LSDs lack a curative treatment. This is particularly true for LSDs severely affecting the CNS. Based on current preclinical and clinical evidences, among other treatment modalities, hematopoietic stem cell gene therapy could potentially result in robust therapeutic benefit for LSD patients, with particular indication for those characterized by severe brain damage. Optimization of current approaches and technology, as well as implementation of clinical trials for novel indications, and prolonged and more extensive follow-up of the already treated patients will allow translating this promise into new medicinal products.

Cerebral plasticity: Windows of opportunity in the developing brain.

BACKGROUND: Neuroplasticity refers to the inherently dynamic biological capacity of the central nervous system (CNS) to undergo maturation, change structurally and functionally in response to experience and to adapt following injury. This malleability is achieved by modulating subsets of genetic, molecular and cellular mechanisms that influence the dynamics of synaptic connections and neural circuitry formation culminating in gain or loss of behavior or function. Neuroplasticity in the healthy developing brain exhibits a heterochronus cortex-specific developmental profile and is heightened during "critical and sensitive periods" of pre and postnatal brain development that enable the construction and consolidation of experience-dependent structural and functional brain connections. PURPOSE: In this review, our primary goal is to highlight the essential role of neuroplasticity in brain development, and to draw attention to the complex relationship between different levels of the developing nervous system that are subjected to plasticity in health and disease. Another goal of this review is to explore the relationship between plasticity responses of the developing brain and how they are influenced by critical and sensitive periods of brain development. Finally, we aim to motivate researchers in the pediatric neuromodulation field to build on the current knowledge of normal and abnormal neuroplasticity, especially synaptic plasticity, and their dependence on "critical or sensitive periods" of neural development to inform the design, timing and sequencing of neuromodulatory interventions in order to enhance and optimize their translational applications in childhood disorders of the brain. METHODS: literature review. RESULTS: We discuss in details five patterns of neuroplasticity expressed by the developing brain: 1) developmental plasticity which is further classified into normal and impaired developmental plasticity as seen in syndromic autism spectrum disorders, 2) adaptive (experience-dependent) plasticity following intense motor skill training, 3) reactive plasticity to pre and post natal CNS injury or sensory deprivation, 4) excessive plasticity (loss of homeostatic regulation) as seen in dystonia and refractory epilepsy, 6) and finally, plasticity as the brain's "Achilles tendon" which induces brain vulnerability under certain conditions such as hypoxic ischemic encephalopathy and epileptic encephalopathy syndromes. We then explore the unique feature of "time-sensitive heightened plasticity responses" in the developing brain in the in the context of neuromodulation. CONCLUSION: The different patterns of neuroplasticity and the unique feature of heightened plasticity during critical and sensitive periods are important concepts for researchers and clinicians in the field of pediatric neurology and neurodevelopmental disabilities. These concepts need to be examined systematically in the context of pediatric neuromodulation. We propose that critical and sensitive periods of brain development in health and disease can create "windows of opportunity" for neuromodulatory interventions that are not commonly seen in adult brain and probably augment plasticity responses and improve clinical outcomes.

Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain.

Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment.

[Neurological diseases after lightning strike : Lightning strikes twice]. / Neurologische Erkrankungen nach Blitzschlag : Lightning strikes twice.

Lightning strikes rarely occur but 85 % of patients have lightning-related neurological complications. This report provides an overview about different modes of energy transfer and neurological conditions related to lightning strikes. Moreover, two case reports demonstrate the importance of interdisciplinary treatment and the spectrum of neurological complications after lightning strikes.

Realidade virtual como possibilidade terapêutica para adolescentes com encefalopatia crônica não progressiva da infância / Virtual reality as a therapeutic possibility for teenagers with chronic not-progressive encephalopathy of childhood

INTRODUÇÃO: A aprendizagem motora surge de um processo complexo de percepção/cognição/ação. Para a Fisioterapia, o conhecimento sobre aprendizado motor fornece bases neurofisiológicas que sustentam a intervenção terapêutica. Na área de ensino de Ciências, a realidade virtual pode se apresentar como um instrumental pelo qual possam ser alcançadas as adolescentes com paralisia cerebral, com déficit no desempenho motor. OBJETIVOS: O presente estudo propôs a inserção de conhecimentos do ensino de ciências por meio de recursos tecnológicos na prática fisioterapêutica direcionada a adolescentes portadores de paralisia cerebral. Essa abordagem foi mediada pela realidade virtual, visando ao incremento do aprendizado motor. MÉTODOS: O desenho experimental utilizado no presente estudo foi o de abordagem qualitativa participante, utilizando-se como instrumento de coleta de dados as oficinas pedagógicas que tratavam de conceitos da ciência para o aprendizado motor aliado à realidade virtual. A amostra analisada foi constituída de quatro adolescentes, entre 11 e 18 anos, portadores de paralisia cerebral, matriculados no ensino fundamental da rede de ensino do município de Teresópolis (RJ), em tratamento fisioterapêutico na Clínica-Escola de Fisioterapia do Unifeso. Foi utilizada, também, a escala de função motora grossa (GMFM) como escala avaliativa pré e pós-intervenção. RESULTADOS: Os sujeitos/pacientes apresentaram melhora em seu desempenho neuromotor associado com o ensino de ciências, demonstrando ser possível a potencialização do aprendizado motor com a aproximação do aprendizado científico. Em relação à escala GMFM, pode-se perceber aumento de 4% na média geral, confirmando o avanço motor dos participantes, percebido nessa análise qualitativa. CONCLUSÃO: A criação de subsídios para a construção do conhecimento científico por meio dos recursos do ambiente virtual aponta para o incremento do desempenho motor e para a formação de sujeitos histórico-sociais.

INTRODUCTION: Motor learning arises from a complex process of perception/cognition/action. For Physiotherapy, knowledge of motor learning provides neurophysiological bases that support therapeutic intervention. In the area of science education, virtual reality may represent an instrument by which adolescents with cerebral palsy and deficit in motor performance can be reached. OBJETIVES: The present study has as purpose the inclusion of knowledge of science education through technology in physical therapy practice directed at adolescents with cerebral palsy. This approach was mediated by virtual reality, aiming to increase motor learning. METHODS: The experimental design used was a qualitative participant study, using as instrument to collect data pedagogical workshops, which dealt with science concepts for motor learning combined with virtual reality. The sample consisted of four subjects, aged 11 and 18 years, with cerebral palsy, enrolled in primary schools in the municipality of Teresopolis (RJ), and on physiotherapy in the School of Physiotherapy Clinic Unifeso. The scale of motor function (GMFM) as pre- and post-intervention was also used for evaluation. RESULTS: Subjects/patients showed improvement in their neuromotor performance associated with the teaching of science, demonstrating the feasibility of the enhancement of motor learning with the scientific learning approach. Regarding the GMFM scale it could be perceived an increase of 4% in the overall average, confirming the motor progress of the participants, perceived by this qualitative analysis. CONCLUSION: The creation of subsidies for the construction of scientific knowledge, by means of virtual resources environment, point to the enhancement of the motor performance and for the formation of social-historical subjects.

Complications and follow up of subarachnoid hemorrhages.

Complications of subarachnoid hemorrhage are the major life threatening and functional components of the follow up of a ruptured aneurysm. Knowing how to identify these is a key challenge. They vary in type throughout the postoperative follow up period. The aim of this article is firstly to list the main complications of the acute phase (rebleeding, acute hydrocephalus, acute ischemic injury and non-neurological complications), the subacute phase (vasospasm) and the chronic phase of subarachnoid hemorrhages: (chronic hydrocephalus and cognitive disorders) and to describe their major clinical and radiological features. Secondly, we describe the long-term follow up strategy for patients who have suffered a subarachnoid hemorrhage and have been treated endovascularly or by surgery. This follow up involves a combination of clinical consultations, cerebral MRI and at least one review angiogram.

Isolated linear skull fractures in children with blunt head trauma.

BACKGROUND AND OBJECTIVE: Children and adolescents with minor blunt head trauma and isolated skull fractures are often admitted to the hospital. The objective of this study was to describe the injury circumstances and frequency of clinically important neurologic complications among children with minor blunt head trauma and isolated linear skull fractures. METHODS: This study was a planned secondary analysis of a large prospective cohort study in children <18 years old with blunt head trauma. Data were collected in 25 emergency departments. We analyzed patients with Glasgow Coma Scale scores of 14 or 15 and isolated linear skull fractures. We ascertained acute neurologic outcomes through clinical information collected during admission or via telephone or mail at least 1 week after the emergency department visit. RESULTS: In the parent study, we enrolled 43,904 children (11,035 [25%] <2 years old). Of those with imaging studies, 350 had isolated linear skull fractures. Falls were the most common injury mechanism, accounting for 70% (81% for ages <2 years old). Of 201 hospitalized children, 42 had computed tomography or MRI repeated; 5 had new findings but none required neurosurgical intervention. Of 149 patients discharged from the hospital, 20 had repeated imaging, and none had new findings. CONCLUSIONS: Children with minor blunt head trauma and isolated linear skull fractures are at very low risk of evolving other traumatic findings noted in subsequent imaging studies or requiring neurosurgical intervention. Hospital admission for neurologically normal children with isolated linear skull fractures after minor blunt head trauma for monitoring is typically unnecessary.

[Acute treatment of patients with severe traumatic brain injury]. / Akutversorgung des Patienten mit schwerem Schädel-Hirn-Trauma.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and permanent disability and a common and important global problem. The contribution of secondary posttraumatic brain damage to overall disability in TBI is significant, underlining the importance of prompt and comprehensive treatment for affected patients. METHODS: This article focuses on current concepts of prehospital and emergency room management of patients with severe TBI to prevent secondary brain injuries. RESULTS AND DISCUSSION: Preclinical prevention and treatment of hypoxia, hypotension and hypercarbia are essential, as they affect the long-term outcome in TBI patients. Prehospital intubation should be critically weighed and in the context of an individual decision. In general, prehospital intubation is more difficult than in the clinical setting. The combination of ketamine and benzodiazepines are commonly used to induce anesthesia before intubation in hemodynamic instable patients. The choice of a muscle relaxant for anesthesia induction is either a non-depolarizing neuromuscular blocking agent or succinylcholine. Administration of mannitol or hypertonic saline is effective to rapidly decrease intracranial pressure. Whenever possible the final destination for transport of TBI patients should be a level I center with round the clock neurosurgical expertise. Trauma-induced coagulopathy should be recognized and immediately treated using a point-of-care testing. CONCLUSION: Hypoxia, hypotension and hypercarbia should strictly be avoided to improve survival and neurological outcome in patients with severe TBI. The prehospital decision to intubate must be made on a case by case basis at the accident site. A level I trauma center should be the destination for this patient group.

Recognizing and managing concussion in school sport.

Every country around the world enjoys some sort of sport. The Olympics sees countries from all over the globe participate in elite sport, in both winter and summer competitions. Australia is widely known for cricket and rugby; America is known for baseball and gridiron football (among others). These sports are played at an elite level as well as beginners from early ages as young as 4 years in the backyard. Yet, it is also these sports that can deliver a ball at the speed of 100 km/h (football), 105 km/h (baseball), 112 km/h (rugby), 150 km/h (cricket), and 211 km/h (soccer). This is the same force that a car collision can produce. That force eventually finds a target, and in some cases, unfortunately, it is a head. Damage to the brain is not only from the impact of the ball hitting its target but rather also the shearing forces of acceleration-deceleration injury that can cause extensive injuries. There has been much discussion of late regarding concussion in sport and the accumulative effects of head blows resulting in varying degrees of memory loss and dementia later in life. The media have been saturated with heightened awareness of chronic traumatic encephalopathy. This, however, is still being researched. It is true that each concussion compounds the one before, but rather than focus on the injury, managers/coaches and sporting codes should be focusing on the identification and proper management of a suspected concussion and the return-to-play protocols. This is especially important in our schools where growing brains need nurturing. Neuroscience nurses are at the forefront of educating school children, teachers, and coaches through partnering with local schools. This article will focus on concussion recognition and management in school sport.

[The practices of withdrawing artificial nutrition and hydration in the neonatal intensive care unit: a preliminary study]. / Étude pilote sur les pratiques de l'arrêt de la nutrition/hydratation artificielle en réanimation néonatale.

INTRODUCTION: Prematurity is one of the etiologies for severe neurological complications. Decisions to withdraw therapeutics, including artificial nutrition and hydration (ANH), are sometimes discussed. But can one withdraw ANH if the patient is a child suffering from severe neurological conditions, based on his best interests? The aim of this study was to further the understanding of the complexity of the withdrawal of ANH and its implementation in the neonatal intensive care unit (NICU). METHOD: This qualitative preliminary study based on a questionnaire was conducted on the staff in the NICU of the Pontoise medical center (France) in February 2012. The results were compared with the current knowledge on this issue and sociological data. RESULTS: Ten of the hospital staff members responded to the questionnaire: 60% considered ANH as a treatment, but the status of ANH (i.e., treatment or care) remained undefined for several respondents. Comparison with the withdrawal of mechanical ventilation or adult practices seemed to be inadequate. The staff had little experience in the domain and therefore few certainties on practices. Half of the respondents indicated that terminal sedation needed to be used. For the other half, it depended on the patient's pain. Timing was also an important notion given that the newborn is a being developing and evolving each in its own way. CONCLUSION: The withdrawal of ANH remains controversial in the NICU. Humanity, culture, and the relationship to others are ever present in the decision-making process, creating a moral opposition above and beyond ethical reflection.