Novel Approaches to Prevent Epileptogenesis After Traumatic Brain Injury.

Traumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by an external force. When epilepsy develops following TBI, it is known as post-traumatic epilepsy (PTE). PTE occurs in a subset of patients suffering from different types and severities of TBI, occurs more commonly following severe injury, and greatly impacts the quality of life for patients recovering from TBI. Similar to other types of epilepsy, PTE is often refractory to drug treatment with standard anti-seizure drugs. No therapeutic approaches have proven successful in the clinic to prevent the development of PTE. Therefore, novel treatment strategies are needed to stop the development of PTE and improve the quality of life for patients after TBI. Interestingly, TBI represents an excellent clinical opportunity for intervention to prevent epileptogenesis as typically the time of initiation of epileptogenesis (i.e., TBI) is known, the population of at-risk patients is large, and animal models for preclinical studies of mechanisms and treatment targets are available. If properly identified and treated, there is a true opportunity to prevent epileptogenesis after TBI and stop seizures from ever happening. With that goal in mind, here we review previous attempts to prevent PTE both in animal studies and in humans, we examine how biomarkers could enable better-targeted therapeutics, and we discuss how genetic variation may predispose individuals to PTE. Finally, we highlight exciting new advances in the field that suggest that there may be novel approaches to prevent PTE that should be considered for further clinical development.

Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity.

Owing to the complexity of the pathophysiological mechanisms driving epileptogenesis following traumatic brain injury (TBI), effective preventive treatment approaches are not yet available for posttraumatic epilepsy (PTE). Neuroinflammation appears to play a critical role in the pathogenesis of the acquired epilepsies, including PTE, but despite a large preclinical literature demonstrating the ability of anti-inflammatory treatments to suppress epileptogenesis and chronic seizures, no anti-inflammatory treatment approaches have been clinically proven to date. TBI triggers robust inflammatory cascades, suggesting that they may be relevant for the pathogenesis of PTE. A major cell type involved in such cascades is the microglial cells-brain-resident immune cells that become activated after brain injury. When activated, these cells can oscillate between different phenotypes, and such polarization states are associated with the release of various pro- and anti-inflammatory mediators that may influence brain repair processes, and also differentially contribute to the development of PTE. As the molecular mechanisms and key signaling molecules associated with microglial polarization in brain are discovered, strategies are now emerging that can modulate this polarization, promoting this as a potential therapeutic strategy for PTE. In this review, we discuss the relevant literature regarding the polarization of brain-resident immune cells following TBI and attempt to put into perspective a role in epilepsy pathogenesis. Finally, we explore potential strategies that could polarize microglia/macrophages toward a neuroprotective phenotype to mitigate PTE development.

Clinical analysis on risk factors and prognosis of early post-traumatic epilepsy.

OBJECTIVE: To analyze the risk factors and prognosis related to early post-traumatic epilepsy (EPTE). METHODS: One hundred and eighty-six patients with traumatic brain injury were enrolled. Their full clinical data were collected. Single factor analysis and logistic regression analysis of risk factors related to EPTE were performed. The prognosis of patients was determined. RESULTS: Single factor analysis showed that there were significant differences of age (p = 0.011), epilepsy history (p < 0.001), injury site (p = 0.004), injury type (p < 0.001) and injury degree (p < 0.001) between the EPTE group (40 patients) and non-EPTE group (146 patients). Logistic regression analysis showed that the injury site, injury type and injury degree were the main risk factors for EPTE. The odds ratio values of injury site, injury type and injury degree were 1.977 (1.473-2.679), 2.096 (1.543-2.842) and 2.376 (1.864-3.609), respectively. The logistic regression equation was P = Exp (-1.473 + 0.698 × injury site + 0.717 × injury type + 0.935 × injury degree). The sensitivity and specificity of injury site, injury type and injury degree for predicting EPTE were 79.2% and 80.5%, 78.9% and 85.7% and 84.2% and 81.0%, respectively. The analysis of prognosis showed that the Glasgow Outcome Scale/Activity of Daily Living Scale scores in the EPTE group were significantly lower than those in non-EPTE group (p < 0.05). CONCLUSIONS: Injury site, injury type and injury degree are the main risk factors for EPTE. The prognosis of patients with traumatic brain injury can be affected by EPTE.

Different Clinical Expression of Anxiety Disorders in Children and Adolescents: Assessment and Treatment.

BACKGROUND: Fearful and anxious behaviour is especially common in children, when they come across new situations and experiences. The difference between normal worry and an anxiety disorder is in the severity and in the interference with everyday life and normal developmental steps. Many longitudinal studies in children suggest that anxiety disorders are relatively stable over time and predict anxiety and depressive disorders in adolescence and adulthood. For this reason, the early diagnostic and treatment are needed. Researchers supposed that anxiety is a result of repeated stress. Additionally, some genetic, neurobiological, developmental factors are also involved in the aetiology. METHODS AND SUBJECTS: The aim of this article is to summarize and to present our own results obtained with the assessment and treatment of different forms of anxiety disorders in children and adolescents such as: Posttraumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), Dental anxiety, General Anxiety Disorder (GAD), and Anxious-phobic syndrome. Some results are published separately in different journals. a) Post Traumatic Stress Disorder (PTSD) in 10 young children aged 9 ± 2, 05 y. is evaluated and discussed concerning the attachment quality. b) The group with OCD comprises 20 patients, mean age 14,5 ± 2,2 years, evaluated with Eysenck Personality Questionnaire (EPQ), Child behaviour Checklist (CBCL), K-SADS (Schedule for Affective Disorders and Schizophrenia for School age children), Beck Depression Inventory (BDI), SCWT (Stroop Colour Word task), WCST (Wisconsin Card Scoring test). c) Dental stress is evaluated in a group of 50 patients; mean age for girls 11,4 ± 2,4 years; for boys 10,7 ± 2,6 years, evaluated with (General Anxiety Scale (GASC), and Eysenck Personality Questionnaire (EPQ). d) Minnesota Multiphasic Personality Inventory (MMPI) profiles obtained for General Anxiety Disorder in 20 young females and 15 males aged 25,7± 5,35 years, and a group with Panic attack syndrome N=15 aged 19,3±4,9 years are presented and discussed by comparison of the results for healthy people. e) Heart Rate Variability (HRV) was applied for assessment and treatment in 15 anxious-phobic patients, mean age 12, 5±2,25 years and results are compared with other groups of mental disorder. RESULTS: Children with PTSD showed a high level of anxiety and stress, somatization and behavioural problems (aggression, impulsivity, non-obedience and nightmares), complemented by hypersensitive and depressed mothers and misattachment in the early period of infancy. Consequently, the explanation of the early predisposition to PTSD was related to be the non-developed Right Orbital Cortex. The later resulted from insecure attachment confirmed in all examined children. The obtained neuropsychological profile of children with OCD confirmed a clear presence of obsessions and compulsions, average intellectual capacities, but the absence of depressive symptoms. Executive functions were investigated through Event Related Potentials on Go/NoGo tasks. Results showed that no significant clinical manifestations of cognitive dysfunction among children with OCD in the early stage of the disorder are present, but it could be expected to be appearing in the later stage of the disorder if it is no treated. In a study of 50 children randomly selected, two psychometric instruments were applied for measuring general anxiety and personal characteristics. It was confirmed that there was presence of significant anxiety level (evaluated with GASC) among children undergoing dental intervention. The difference in anxiety scores between girls and boys was also confirmed (girls having higher scores for anxiety). Results obtained with EPQ showed low psychopathological traits, moderate extraversion and neuroticism, but accentuated insincerity (L scale). L scales are lower by increasing of age, but P scores rise with age, which can be related to puberty. No correlation was found between personality traits and anxiety except for neuroticism, which is positively correlated with the level of anxiety. The obtained profiles for MMPI-201 in a group of patients with general anxiety are presented as a figure. Females showed only Hy peak, but in the normal range. However, statistics confirmed significant difference between scores in anxiety group and control (t= 2, 25164; p= 0, 038749). Males showed Hs-Hy-Pt peaks with higher (pathological) scores, related to hypersensitivity of the autonomic nervous system, as well as with manifested anxiety. Calculation confirmed significant difference between control and anxiety in men (t= 15.13, p=0.000). Additionally, MMPI profiles for patients with attack panic syndrome are also presented as a figure. Control scales for females showed typical V form (scales 1 and 3) related to conversing tendencies. In addition, females showed peaks on Pt-Sc scales, but in normal ranges. Pathological profile is obtained in males, with Hy-Sc peaks; this profile corresponds to persons with regressive characteristics, emotionally instable and with accentuated social withdraw. Heart rate variability (HRV) is a measure of the beat to beat variability in heart rate, related to the work of autonomic nervous system. It may serve as a psychophysiological indicator for arousal, emotional state and stress level. We used HRV in both, the assessment and biofeedback training, in a group of anxious-phobic and obsessive-compulsive school children. Results obtained with Eysenck Personality Questionnaire showed significantly higher psychopathological traits, higher neuroticism and lower lie scores. After 15 session HRV training very satisfying results for diminishing stress and anxiety were obtained.

Clinical analysis on risk factors and prognosis of early post-traumatic epilepsy / Análise clínica de fatores de risco e prognóstico da epilepsia pós-traumática precoce

ABSTRACT Objective To analyze the risk factors and prognosis related to early post-traumatic epilepsy (EPTE). Methods One hundred and eighty-six patients with traumatic brain injury were enrolled. Their full clinical data were collected. Single factor analysis and logistic regression analysis of risk factors related to EPTE were performed. The prognosis of patients was determined. Results Single factor analysis showed that there were significant differences of age (p = 0.011), epilepsy history (p < 0.001), injury site (p = 0.004), injury type (p < 0.001) and injury degree (p < 0.001) between the EPTE group (40 patients) and non-EPTE group (146 patients). Logistic regression analysis showed that the injury site, injury type and injury degree were the main risk factors for EPTE. The odds ratio values of injury site, injury type and injury degree were 1.977 (1.473-2.679), 2.096 (1.543-2.842) and 2.376 (1.864-3.609), respectively. The logistic regression equation was P = Exp (-1.473 + 0.698 × injury site + 0.717 × injury type + 0.935 × injury degree). The sensitivity and specificity of injury site, injury type and injury degree for predicting EPTE were 79.2% and 80.5%, 78.9% and 85.7% and 84.2% and 81.0%, respectively. The analysis of prognosis showed that the Glasgow Outcome Scale/Activity of Daily Living Scale scores in the EPTE group were significantly lower than those in non-EPTE group (p < 0.05). Conclusions Injury site, injury type and injury degree are the main risk factors for EPTE. The prognosis of patients with traumatic brain injury can be affected by EPTE.

RESUMO Objetivo Analisar os fatores de risco e prognóstico relacionados à epilepsia pós-traumática precoce (EPTE). Métodos Cento e oitenta e seis pacientes com lesão cerebral traumática foram incluídos. Seus dados clínicos completos foram coletados. A análise fatorial única e a análise de regressão logística dos fatores de risco relacionados à EPTE foram realizadas. O prognóstico dos pacientes foi observado. Resultados A análise fatorial única mostrou que houve diferenças significativas de idade (p = 0,011), história de epilepsia (p < 0,001), local da lesão (p = 0,004), tipo de lesão (p < 0,001) e grau de lesão (p < 0,001) entre o grupo EPTE (40 casos) e o grupo não-EPTE (146 casos), respectivamente. A análise de regressão logística mostrou que o local da lesão, tipo de lesão e grau de lesão foram os principais fatores de risco para EPTE. Os valores de razões de chance do local da lesão, tipo de lesão e grau de lesão foram 1.977 (1.473-2.679), 2.096 (1.543-2.842) e 2.376 (1.864-3.609), respectivamente. A equação de regressão logística foi P = Exp (-1,473 + 0,698 × local de lesão + 0,717 × tipo de lesão + 0,935 × grau de lesão). A sensibilidade e especificidade do local da lesão, tipo de lesão e grau de lesão para a predição da EPTE foram de 79,2% e 80,5%, 78,9% e 85,7% e 84,2% e 81,0%, respectivamente. A análise do prognóstico mostrou que o escore da Escala de Desfechos de Glasgow / Atividade de Vida Diária no grupo EPTE foi significativamente menor do que no grupo não-EPTE (P <0,05). Conclusões O local da lesão, tipo de lesão e grau de lesão são os principais fatores de risco para EPTE. A EPTE pode afetar o prognóstico de pacientes com lesão cerebral traumática.

Epileptogenesis, traumatic brain injury, and biomarkers.

Epilepsy is one of the most common brain disorders, causing serious disability and premature death worldwide. Approximately 1.2% of the U.S. population has active epilepsy, and 30 to 40% have seizures that do not respond to antiseizure drugs. There currently is no treatment available that prevents epilepsy following a potential epileptogenic insult, and the search for disease or syndrome modifying interventions for epilepsy is a high priority of neurobiological research. This requires better understanding of neuronal mechanisms underlying the development of epilepsy, and biomarkers of this process that would permit cost-effective drug discovery, and validation in clinical trials, for potential antiepileptogenic compounds. EpiBioS4Rx is an NIH-funded Center without Walls consisting of collaborative investigations in the United States, Europe, and Australia of traumatic brain injury in patients, and a standardized animal model, to identify biomarkers of epileptogenesis and to determine their ability to assess the effectiveness of potential antiepileptogenic agents. Successful completion of this project is expected to result in design of an economically feasible, full-scale clinical trial of at least one antiepileptogenic intervention.

In search of antiepileptogenic treatments for post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) is diagnosed in 20% of individuals with acquired epilepsy, and can impact significantly the quality of life due to the seizures and other functional or cognitive and behavioral outcomes of the traumatic brain injury (TBI) and PTE. There is no available antiepileptogenic or disease modifying treatment for PTE. Animal models of TBI and PTE have been developed, offering useful insights on the value of inflammatory, neurodegenerative pathways, hemorrhages and iron accumulation, calcium channels and other target pathways that could be used for treatment development. Most of the existing preclinical studies test efficacy towards pathologies of functional recovery after TBI, while a few studies are emerging testing the effects towards induced or spontaneous seizures. Here we review the existing preclinical trials testing new candidate treatments for TBI sequelae and PTE, and discuss future directions for efforts aiming at developing antiepileptogenic and disease-modifying treatments.

A novel dissemination effort for prolonged exposure: Practice and dissemination curriculum.

OBJECTIVES: This study examines the effectiveness of a novel dissemination and implementation curriculum for prolonged exposure (PE). Predoctoral clinical psychology interns completed a sequential, four-part curriculum that culminated in a community-based practicum during which interns conducted a PE workshop. We hypothesized that workshop participants would report more favorable attitudes regarding PE after completing the intern-led workshop than endorsed at the outset of the workshop. METHOD: A total of 53 workshop participants attended and completed questionnaires. The majority of workshop participants had a master's-level degree or educational specialist degree (n = 28; 57.1%) and were currently a counselor or psychosocial rehabilitation worker (n = 21; 42.9%). We examined changes between pre- and posttraining time points for five self-report items related to negative attitudes toward PE and three self-report items related to intent to use PE. RESULTS: There was a significant effect of workshop training on four out of five items related to negative attitudes toward PE. The nonsignificant result of the fifth item may be due to a ceiling effect given that baseline scores for this item were very positive. There was a significant effect of workshop training on all three items related to intent to use PE. CONCLUSIONS: Results suggested that this sequential four-part curriculum may be an effective way of combining education, training, and dissemination efforts. Future research should examine if similar results can be achieved with a controlled research design and whether outcomes would generalize to actual PE delivery skills in routine clinical care. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Targeting neurodegeneration to prevent post-traumatic epilepsy.

In the quest for developing new therapeutic targets for post-traumatic epilepsies (PTE), identifying mechanisms relevant to development and progression of disease is critical. A growing body of literature suggests involvement of neurodegenerative mechanisms in the pathophysiology of acquired epilepsies, including following traumatic brain injury (TBI). In this review, we discuss the potential of some of these mechanisms to be targets for the development of a therapy against PTE.

Specialized Palliative and Hospice Care and the Importance of Mourning Our Nation's Veterans.

One aspect of palliative medicine that has been underexplored is the perspective of veterans either facing critical life-limiting illness or at the end of life. The needs of veterans differ not only because military culture affects how veterans cope with their illness but also because exposure-related factors (combat and environmental) differ between military branches. In this paper, we describe two cases involving end-of-life care for veterans with combat trauma and describe individualized approaches to their care.

Treatment options for posttraumatic epilepsy.

PURPOSE OF REVIEW: Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE) are common and debilitating consequences of traumatic brain injury (TBI). Early PTS result in secondary brain injury by raising intracranial pressure and worsening cerebral edema and metabolic crisis. PTE is a localization-related epilepsy strongly associated with TBI severity, but risk factors for PTE and epileptogenesis are incompletely understood and are active areas of research. Medical management of PTS in adults and children is reviewed. Surgical options for posttraumatic drug-resistant epilepsy are also discussed. RECENT FINDINGS: Continuous electroencephalography is indicated for children and adults with TBI and coma because of the high incidence of nonconvulsive seizures, periodic discharges, and associated secondary brain injury in this population. Neuroinflammation is a central component of secondary brain injury and appears to play a key role in epileptogenesis. Levetiracetam is increasingly used for seizure prophylaxis in adults and children, but variability remains. SUMMARY: PTS occur commonly after TBI and are associated with secondary brain injury and worse outcomes in adults and children. Current medical and surgical management options for PTS and PTE are reviewed.

Clinical approach to posttraumatic epilepsy.

Traumatic brain injury (TBI) is one of the most common causes of acquired epilepsy, and posttraumatic epilepsy (PTE) results in significant somatic and psychosocial morbidity. The risk of developing PTE relates directly to TBI severity, but the latency to first seizure can be decades after the inciting trauma. Given this "silent period," much work has focused on identification of molecular and radiographic biomarkers for risk stratification and on development of therapies to prevent epileptogenesis. Clinical management requires vigilant neurologic surveillance and recognition of the heterogeneous endophenotypes associated with PTE. Appropriate treatment of patients who have or are at risk for seizures varies as a function of time after TBI, and the clinician's armamentarium includes an ever-expanding diversity of pharmacological and surgical options. Most recently, neuromodulation with implantable devices has emerged as a promising therapeutic strategy for some patients with refractory PTE. Here, we review the epidemiology, diagnostic considerations, and treatment options for PTE and develop a roadmap for providers encountering this challenging clinical entity.

Clinical epidemiology of posttraumatic epilepsy in a group of Chinese patients.

OBJECTIVE: To explore the incidence, types of onset, and risk factors of posttraumatic epilepsy (PTE). METHODS: This is a retrospective follow-up study of patients discharged from the Affiliated Hospital of the Medical College of the Chinese People's Armed Police Forces between September 2004 and September 2008 with a diagnosis of traumatic brain injury (TBI). RESULTS: Complete clinical information was available on 2826 patients. Of the 2826 TBI patients, 141 developed PTE, providing an incidence rate of 5.0%. Twenty-four cases (0.8%) had posttraumatic seizures (PTS), of which 16 (66.7%) continued to experience after the acute phase of their TBI, accounting for 5.0% of the total PTE cases. A total of 125 cases (88.7%) were diagnosed as presenting with late-stage seizures, occurring from 10 days to three years after TBI (93/141 (66.0%) presented within six months after the TBI, 14/141 (9.9%) between six and twelve months, 22/141 (15.7%) between one and two years and only 12/141 (8.5%) between two and three years after the TBI. The severity of PTE was rated mild, medium, and severe in 3.6%, 6.9%, and 17% of the TBI patients. Multiple regression analysis was carried out to identify factors contributing to the risk of developing PTE. Five parameters contributed to the model: Older age, greater severity of brain injury, abnormal neuroimaging, surgical treatment, and early-stage seizures. CONCLUSION: Age, severity of brain injury, neuroimaging results, treatment methods, and early-stage seizures are independent risk factors of PTE.

Exercise augmentation compared to usual care for post traumatic stress disorder: a randomised controlled trial (the REAP study: Randomised Exercise Augmentation for PTSD).

BACKGROUND: The physical wellbeing of people with mental health conditions can often be overlooked in order to treat the primary mental health condition as a priority. Exercise however, can potentially improve both the primary psychiatric condition as well as physical measures that indicate risk of other conditions such as diabetes mellitus and cardiovascular disease. Evidence supports the role of exercise as an important component of treatment for depression and anxiety, yet no randomised controlled trials (RCT's) have been conducted to evaluate the use of exercise in the treatment of people with post traumatic stress disorder (PTSD). This RCT will investigate the effects of structured, progressive exercise on PTSD symptoms, functional ability, body composition, physical activity levels, sleep patterns and medication usage. METHODS AND DESIGN: Eighty participants with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of PTSD will be recruited. Participants will have no contraindications to exercise and will be cognitively able to provide consent to participate in the study. The primary outcome measures will be PTSD symptoms, measured through the PTSD Checklist Civilian (PCL-C) scale. Secondary outcome measures will assess depression and anxiety, mobility and strength, body composition, physical activity levels, sleep patterns and medication usage. All outcomes will be assessed by a health or exercise professional masked to group allocation at baseline and 12 weeks after randomisation. The intervention will be a 12 week individualised program, primarily involving resistance exercises with the use of exercise bands. A walking component will also be incorporated. Participants will complete one supervised session per week, and will be asked to perform at least two other non-supervised exercise sessions per week. Both intervention and control groups will receive all usual non-exercise interventions including psychotherapy, pharmaceutical interventions and group therapy. DISCUSSION: This study will determine the effect of an individualised and progressive exercise intervention on PTSD symptoms, depression and anxiety, mobility and strength, body composition, physical activity levels, sleep patterns and medication usage among people with a DSM-IV diagnosis of PTSD. TRIAL REGISTRATION: ACTRN12610000579099.

Military sexual trauma among U.S. female veterans.

Sexual abuse among female veterans reportedly occurs in significant numbers in the U.S. military and has been recognized to cause posttraumatic stress disorder (PTSD). PTSD, which stems from sexual abuse, has been called military sexual trauma (MST), which has only recently been recognized by the Department of Defense. Consequently, there has been scant research on the prevalence, impact, and treatment of MST. This article explores the phenomenon of sexual aggression against female veterans in the U.S. military, risk factors for MST, PTSD as a result of MST, a conceptual framework for treating PTSD stress, and treatment strategies for PTSD.

Wearable sensor platform and mobile application for use in cognitive behavioral therapy for drug addiction and PTSD.

We present a wearable sensor platform designed for monitoring and studying autonomic nervous system (ANS) activity for the purpose of mental health treatment and interventions. The mobile sensor system consists of a sensor band worn on the ankle that continuously monitors electrodermal activity (EDA), 3-axis acceleration, and temperature. A custom-designed ECG heart monitor worn on the chest is also used as an optional part of the system. The EDA signal from the ankle bands provides a measure sympathetic nervous system activity and used to detect arousal events. The optional ECG data can be used to improve the sensor classification algorithm and provide a measure of emotional "valence." Both types of sensor bands contain a Bluetooth radio that enables communication with the patient's mobile phone. When a specific arousal event is detected, the phone automatically presents therapeutic and empathetic messages to the patient in the tradition of Cognitive Behavioral Therapy (CBT). As an example of clinical use, we describe how the system is currently being used in an ongoing study for patients with drug-addiction and post-traumatic stress disorder (PTSD).

Post-traumatic seizure susceptibility is attenuated by hypothermia therapy.

Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available antiepileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and were then maintained at normothermic or moderate hypothermic temperatures for 4 h. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole, a GABA(A) receptor antagonist. Pentylenetetrazole elicited a significant increase in seizure frequency in TBI normothermic animals as compared with sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizures. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy.

Are the neurotrophic factors a suitable therapeutic target for the prevention of epileptogenesis?

Neurotrophic factors are involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors. Therefore, modulating their levels in lesion areas may exert favorable effects on seizure-induced damage. However, it is unclear if damage limitation or repair may prevent epileptogenesis; it is also uncertain which neurotrophic factor should be administered for limiting or repairing damage while avoiding possible proepileptic effects. We used viral vectors to locally supplement fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when an epileptogenic damage was already in place. These vectors were tested in the pilocarpine model of status epilepticus-induced neurodegeneration and epileptogenesis. FGF-2/BDNF expressing vectors increased neuronogenesis, limited neuronal damage, and reduced the occurrence of spontaneous seizures. These findings are discussed with consideration of the hurdles that will have to be overcome before clinical application.

Epilepsia postraumática, evaluación de los criterios de causalidad. A propósito de un caso / Posttraumatic epilepsy and its differential diagnosis in impairment evaluation. Case report

Objetivo: Se presenta un caso de valoración pericial de nexo de causalidad en una epilepsia postraumática, entre un traumatismo craneoencefálico (TCE) ocurrido cuatro años antes y una agresión con resultado de lesiones leves, en un varón de 21 años, consumidor ocasional de alcohol, cannabis y cocaína. El objetivo de este artículo es el análisis de los criterios médico-legales aplicables al caso y la correcta evaluación del estado anterior del paciente. La valoración pericial resulta afectada por la complejidad de los mecanismos desencadenados en el TCE, por la intervención de otros factores que pueden contribuir a la aparición de epilepsia, y por la existencia de una extensa literatura sobre el tema, en muchos casos con hallazgos dispares y contradictorios. Conclusiones: En el presente caso, evaluados los criterios de causalidad, la epilepsia se considera secundaria al TCE sufrido cuatro años antes (AU)

Introduction: This report shows a case of posttraumatic epilepsy related to head injury four years ago and aggression with result in mild injury, in a 21-year-old male, alcohol, cannabis and cocaine user. The aim of this report is to review the expert evaluation of the link between head injury or aggression and posttraumatic epilepsy by the analysis of the causal relationship factors and the influence of previously existing pathology. The expert evaluation is awkward and difficult to deal with, because of the different mechanisms of Traumatic Brain Injury (TBI) and other factors that could lead to epilepsy. Also the extensive bibliography on the subject is controversial. Conclusions: In this case the posttraumatic epilepsy can be reasonably linked to the TBI that had been undergone 4 years ago (AU)