Christopher C. Giza

Summary of evidence-based guideline update: Evaluation and management of concussion in sports Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To update the 1997 American Academy of Neurology (AAN) practice parameter regarding sports concussion, focusing on 4 questions: 1) What factors increase/decrease concussion risk? 2) What diagnostic tools identify those with concussion and those at increased risk for severe/prolonged early impairments, neurologic catastrophe, or chronic neurobehavioral impairment? 3) What clinical factors identify those at increased risk for severe/prolonged early postconcussion impairments, neurologic catastrophe, recurrent concussions, or chronic neurobehavioral impairment? 4) What interventions enhance recovery, reduce recurrent concussion risk, or diminish long-term sequelae? The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: We systematically reviewed the literature from 1955 to June 2012 for pertinent evidence. We assessed evidence for quality and synthesized into conclusions using a modified Grading of Recommendations Assessment, Development and Evaluation process. We used a modified Delphi process to develop recommendations. Results: Specific risk factors can increase or decrease concussion risk. Diagnostic tools to help identify individuals with concussion include graded symptom checklists, the Standardized Assessment of Concussion, neuropsychological assessments, and the Balance Error Scoring System. Ongoing clinical symptoms, concussion history, and younger age identify those at risk for postconcussion impairments. Risk factors for recurrent concussion include history of multiple concussions, particularly within 10 days after initial concussion. Risk factors for chronic neurobehavioral impairment include concussion exposure and APOE ε4 genotype. Data are insufficient to show that any intervention enhances recovery or diminishes long-term sequelae postconcussion. Practice recommendations are presented for preparticipation counseling, management of suspected concussion, and management of diagnosed concussion.

The molecular pathophysiology of concussive brain injury.

Concussion or mild traumatic brain injury (mTBI) is a condition that affects hundreds of thousands of patients worldwide. Understanding the pathophysiology of this disorder can help manage its acute and chronic repercussions. Immediately following mTBI, there are several metabolic, hemodynamic, structural, and electric changes that alter normal cerebral function. These alterations can increase the brains vulnerability to repeat injury and long-term disability. This review evaluates current studies from the bench to the bedside of mTBI. Acute and chronic effects of concussion are measured in both animal and clinical studies. Also, the effect of repeat concussions is analyzed. Concussion-induced pathophysiology with regards to glucose metabolism changes, mitochondrial dysfunction, axonal injury, and structural damage are evaluated. Translational studies such as functional magnetic resonance imaging, magnetic resonance spectroscopy and diffusion tensor imaging prove to be effective clinical tools for both prognostic and treatment parameters. Understanding the neurobiology of concussion will lead to development and validation of physiological biomarkers of this common injury. These biomarkers (eg, laboratory tests, imaging, electrophysiology) will then allow for improved detection, better functional assessment and evidence-based return to play recommendations.

The New Neurometabolic Cascade of Concussion

Objective: To review the underlying pathophysiologic processes of concussive brain injury and relate these neurometabolic changes to clinical sports-related issues such as injury to the developing brain, overuse injury, and repeated concussion. Data Sources: Over 100 articles from both basic science and clinical medical literature selected for relevance to concussive brain injury, postinjury pathophysiology, and recovery of function. Data Synthesis: The primary elements of the pathophysiologic cascade following concussive brain injury include abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function. These alterations can be correlated with periods of postconcussion vulnerability and with neurobehavioral abnormalities. While the time course of these changes is well understood in experimental animal models, it is only beginning to be characterized following human concussion. Conclusions/Recommendations: Following concussion, cerebral pathophysiology can be adversely affected for days in animals and weeks in humans. Significant changes in cerebral glucose metabolism can exist even in head-injured patients with normal Glasgow Coma Scores, underscoring the need for indepth clinical assessment in an effort to uncover neurocognitive correlates of altered cerebral physiology. Improved guidelines for clinical management of concussion may be formulated as the functional significance and duration of these postinjury neurometabolic derangements are better delineated.

Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in Berlin, October 2016

The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement. This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps. A series of specific clinical questions were developed as part of the consensus process for the Berlin 2016 meeting. Each consensus question was the subject of a specific formal systematic review, which is published concurrently with this summary statement. Readers are directed to these background papers in conjunction with this summary statement as they provide the context for the issues and include the scope of published research, search strategy and citations reviewed for each question. This 2017 consensus statement also summarises each topic and recommendations in the context of all five CISG meetings (that is, 2001, 2004, 2008, 2012 as well as 2016). Approximately 60 000 published articles were screened by the expert panels for the Berlin …

Repeated Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability

Among the 3.5 million annual new head injury cases is a subpopulation of children and young adults who experience repeated traumatic brain injury (TBI). The duration of vulnerability after a single TBI remains unknown, and biomarkers have yet to be determined. Decreases in glucose metabolism (cerebral metabolic rate of glucose [CMRglc]) are consistently observed after experimental and human TBI. In the current study, it is hypothesized that the duration of vulnerability is related to the duration of decreased CMRglc and that a single mild TBI (mTBI) increases the brains vulnerability to a second insult for a period, during which a subsequent mTBI will worsen the outcome. Postnatal day 35 rats were given sham, single mTBI, or two mTBI at 24-h or 120-h intervals. (14)C-2-deoxy-D-glucose autoradiography was conducted at 1 or 3 days post-injury to calculate CMRglc. At 24 h after a single mTBI, CMRglc is decreased by 19% in both the parietal cortex and hippocampus, but approached sham levels by 3 days post-injury. When a second mTBI is introduced during the CMRglc depression of the first injury, the consequent CMRglc is depressed (36.5%) at 24 h and remains depressed (25%) at 3 days. In contrast, when the second mTBI is introduced after the metabolic recovery of the first injury, the consequent CMRglc depression is similar to that seen with a single injury. Results suggest that the duration of metabolic depression reflects the time-course of vulnerability to second injury in the juvenile brain and could serve as a valuable biomarker in establishing window of vulnerability guidelines.

Repeat Traumatic Brain Injury in the Juvenile Rat Is Associated with Increased Axonal Injury and Cognitive Impairments

Among the enormous population of head-injured children and young adults are a growing subpopulation who experience repeat traumatic brain injury (RTBI). The most common cause of RTBI in this age group is sports-related concussions, and athletes who have experienced a head injury are at greater risk for subsequent TBI, with consequent long-term cognitive dysfunction. While several animal models have been proposed to study RTBI, they have been shown to either produce injuries too severe, were conducted in adults, involved craniotomy, or failed to show behavioral deficits. A closed head injury model for postnatal day 35 rats was established, and single and repeat TBI (1-day interval) were examined histologically for axonal injury and behaviorally by the novel object recognition (NOR) task. The results from the current study demonstrate that an experimental closed head injury in the rodent with low mortality rates and absence of gross pathology can produce measurable cognitive deficits in a juvenile age group. The introduction of a second injury 24 h after the first impact resulted in increased axonal injury, astrocytic reactivity and increased memory impairment in the NOR task. The histological evidence demonstrates the potential usefulness of this RTBI model for studying the impact and time course of RTBI as it relates to the pediatric and young adult population. This study marks the first critical step in experimentally addressing the consequences of concussions and the cumulative effects of RTBI in the developing brain.

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

Summary: Purpose: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long‐term seizure control.

Is Being Plastic Fantastic? Mechanisms of Altered Plasticity after Developmental Traumatic Brain Injury

Traumatic brain injury (TBI) is predominantly a clinical problem of young persons, resulting in chronic cognitive and behavioral deficits. Specifically, the physiological response to a diffuse biomechanical injury in a maturing brain can clearly alter normal neuroplasticity. To properly evaluate and investigate developmental TBI requires an understanding of normal principles of cerebral maturation, as well as a consideration of experience-dependent changes. Changes in neuroplasticity may occur through many age-specific processes, and our understanding of these responses at a basic neuroscience level is only beginning. In this article, we will particularly discuss mechanisms of TBI-induced altered developmental plasticity such as altered neurotransmission, distinct molecular responses, cell death, perturbations in neuronal connectivity, experience-dependent ‘good plasticity’ enhancements and chronic ‘bad plasticity’ sequelae. From this summary, we can conclude that ‘young is not always better’ and that the developing brain manifests several crucial vulnerabilities to TBI.

Experience-dependent behavioral plasticity is disturbed following traumatic injury to the immature brain

Traumatic brain injury (TBI) is most prevalent in children and young adults. The long-term effects of pediatric TBI include cognitive and behavioral impairments; however, over time, it is difficult to distinguish individual variability in intellect and behavior from sequelae of early injury. Postnatal day (PND) 19 rats underwent lateral fluid percussion (FP) injury, followed by rearing in either standard (STD) or enriched environment (EE) conditions. The hypothesis was that the traditional enhancement of cognitive functioning following EE rearing would be attenuated when this rearing is preceded by TBI at PND19. Thirty days after injury, Morris water maze (MWM) acquisition and subsequent probe trial retention were used to assess the behavioral effects of injury on experience-dependent plasticity induced by housing in EE at two different time windows. MWM acquisition demonstrated improvements following early EE rearing in both sham and injured animals; however, the degree of improvement was greater for uninjured animals. When EE rearing was delayed for 2 weeks after injury, the injury effect was absent and the effect of rearing even stronger. Memory testing in the early EE groups using a delayed probe trial showed an effect of injury and housing, with the sham EE animals benefiting the most. After the delayed EE, sham EE animals again showed more probe target hits, while FPEE animals did not, demonstrating an enduring memory deficit. These data confirm that early TBI has effects on experience-dependent plasticity resulting in long-term neurobehavioral deficits. In addition, the ability to benefit from environmental stimulation following TBI is dependent upon time after injury.

The pathophysiology of traumatic brain injury at a glance

Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson’s disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel. This increased public awareness has uncovered a number of unanswered questions concerning TBI, and we are increasingly aware of the lack of treatment options for a crisis that affects millions. Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI. Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention.