Academic literature on the topic 'Posttraumatic epilepsy'

Suite aux traumatismes crâniens pénétrants, le cerveau devient graduellement hyperexcitable et génère des activités paroxystiques spontanées. Les mécanismes qui sous-tendent l’épileptogénèse demeurent cependant peu connus. La ligne directrice de nos travaux consiste en l'hypothèse que la diminution de l'activité corticale engendrée par la déafférentation déclenche des mécanismes homéostatiques agissant tant au niveau cellulaire qu’au niveau du réseau cortical, et qui mènent à une excitabilité neuronale accrue culminant en crises d’épilepsie. Nous avons testé cette hypothèse chez des chats adultes, lors de différents états de vigilance ou sous anesthésie, ayant subits une déafférentation partielle du gyrus suprasylvien. Nous avons évalué les effets de la déafférentation corticale aigue et chronique sur la survie des neurones et des cellules gliales et nous avons investigué comment la privation chronique d'afférences neuronales pourrait modifier les propriétés du réseau cortical et déclencher des crises d’épilepsie. Après la déafférentation du gyrus suprasylvien, les neurones situés dans les couches corticales profondes, en particulier les neurones inhibiteurs GABAérgiques, dégénèrent progressivement et parallèlement à une fréquence croissante des activités paroxystiques, notamment pendant le sommeil à ondes lentes. La privation chronique d'afférences neuronales et la perte de neurones activent les mécanismes homéostatiques de plasticité qui favorisent une plus grande connectivité neuronale, une efficacité plus élevée des connexions synaptiques excitatrices et des changements des propriétés neuronales intrinsèques. Ensemble, ces facteurs favorisent une excitation accrue du réseau cortical. L'activité corticale spontanée, mesurée par les taux moyens de décharge, augmente progressivement, en particulier pendant le sommeil à ondes lentes, caractérisé par des périodes silencieuses alternant avec des périodes actives. Ceci soutient, en outre, notre hypothèse concernant la participation des mécanismes de plasticité homéostatique. La dégénération des neurones des couches corticales profondes produit des changements importants dans la distribution laminaire de l'activité neuronale, qui est déplacée vers les couches plus superficielles, dans la partie déafferenté du gyrus. Ce changement dans la distribution de profils de profondeurs de décharges neuronales modifie également le déclenchement de l'activité corticale spontanée. Dans le cortex normal et dans la partie relativement intacte du gyrus suprasylvien, l'activité corticale est générée dans les couches corticales profondes. Pourtant, dans le cortex chroniquement déafferenté, l'oscillation lente et les activités ictales sont générées dans les couches superficielles et puis diffusent vers les couches plus profondes. Le traumatisme cortical induit également une importante gliose réactive et une altération de la fonction normale des cellules gliales, ce qui cause l’enlèvement dysfonctionnel du K+ extracellulaire et qui augmente l'excitabilité des neurones favorisant ainsi la génération d’activités paroxystiques. En conclusion, les mécanismes de plasticité homéostatique déclenchés par le niveau diminué d'activité dans le cortex déafferenté produisent une hyperexcitabilité corticale incontrôlable et génèrent finalement les crises d’épilepsie. Dans ces conditions, l’augmentation de l'activité corticale plutôt que la diminution avec des médicaments antiépileptiques pourrait être salutaire pour empêcher le développement de l'épileptogenèse post-traumatique.
After penetrating cortical wounds, the brain becomes gradually hyperexcitable and generates spontaneous paroxysmal activity, but the progressive mechanisms of epileptogenesis remain virtually unknown. The guiding line of our experiments was the hypothesis that the reduced cortical activity following deafferentation triggers homeostatic mechanisms acting at cellular and network levels, leading to an increased neuronal excitability and finally generating paroxysmal activities. We tested this hypothesis either in anesthetized adult cats, or during natural sleep and wake, using the model of partially deafferented suprasylvian gyrus to induce posttraumatic epileptogenesis. We evaluated the effects of acute and chronic cortical deafferentation on the survival of neurons and glial cells and how long-term input deprivation could shape up the properties of neuronal networks and the initiation of spontaneous cortical activity. Following cortical deafferentation of the suprasylvian gyrus, the deeply laying neurons, particularly the inhibitory GABAergic ones, degenerate progressively in parallel with an increased propensity to paroxysmal activity, mainly during slow-wave sleep. The chronic input deprivation and the death of neurons activate homeostatic plasticity mechanisms, which promote a gradual increased neuronal connectivity, higher efficacy of excitatory synaptic connections and changes in intrinsic cellular properties favoring increased excitation. The spontaneous cortical activity quantified by means of firing rate augments also progressively, particularly during slow-wave sleep, characterized by periods of silent states alternating with periods of active states, which supports furthermore our hypothesis regarding the involvement of homeostatic plasticity mechanisms. The degeneration of neurons in the deep cortical layers generates important changes in the laminar distribution of neuronal activity, which is shifted from the deeper layers to the more superficial ones, in the partially deafferented part of the gyrus. This change in the depth profile distribution of firing rates modifies also the initiation of spontaneous cortical activity which, in normal cortex, and in the relatively intact part of the deafferented gyrus, is initiated in the deep cortical layers. Conversely, in late stages of the undercut, both the cortical slow oscillation and the ictal activity are initiated in the more superficial layers and then spread to the deeper ones. Cortical trauma induces also an important reactive gliosis associated with an impaired function of glial cells, responsible for a dysfunctional K+ clearance in the injured cortex, which additionally increases the excitability of neurons, promoting the generation of paroxysmal activity. We conclude, that the homeostatic plasticity mechanisms triggered by the decreased level of activity in the deafferented cortex, generate an uncontrollable cortical hyperexcitability, finally leading to seizures. If this statement is true, augmenting cortical activity rapidly after cortical trauma rather than decreasing it with antiepileptic medication, could prove beneficial in preventing the development of posttraumatic epileptogenesis.
Inscrite au Tableau d'honneur de la Faculté des études supérieures

Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized mossy fiber reorganization ipsilateral to the injury that was absent in control mice or sections contralateral to the injury. Extracellular field and whole-cell patch clamp recordings were performed in acute brain slice preparations of the dentate gyrus. Dentate granule cells displayed spontaneous and evoked activity that was consistent with network synchronization and the formation of recurrent excitatory network only in slices that had posttraumatic mossy fiber sprouting. The excitability of surviving hilar GABAergic interneurons, which provide important feedback inhibition to granule cells, was examined at similar time points. Cell-attached and whole-cell voltage-clamp recordings revealed increased spontaneous and glutamate photostimulation-evoked excitatory input to hilar GABA neurons ipsilateral to the injury, versus control and contralateral slices. Despite increased excitatory synaptic input to interneurons, whole-cell voltage-clamp recordings revealed a reduction in inhibitory synaptic input to granule cells. These findings suggest that there are alterations in excitatory and inhibitory circuits in mice with posttraumatic mossy fiber sprouting and seizures after cortical contusion head injury.

碩士
國立臺灣師範大學
社會教育學系
98
Women with traumatic experiences of epilepsy are studied in the life story of recovery and of post-traumatic growth, using longitudinal life history in time sequence and horizontal approaching to the overall narratives. To integrate with the research-based self-narrative of women with epilepsy and the recall narrative of close relatives, the collected information is arranged according to the time table to render a macro epilepsy career. To record patient’s microscopic life story, using qualitative research methods in the "overall-content" approach for data processing and analysis reflects physical experience and stress adaptation. After all, we probe thoroughly into the feminine epilepsy patient and their close relatives with the process of traumatic experience to reveal the strategies of mental adaption and the reacting responses for problems in order to understand the significant change and impact after suffering epilepsy. The results showed: (A) Study of the life history makes a new interpretation of the meaning behind the traumatic events and inspiration to the researcher to re-define herself. (B) Women with epilepsy need to learn trust and share, and explore the positive values of traumatic experiences to become aware of their meaning and growth in the events. (C) "Recognition" from others and “Self-identification" possess decisive and importance meanings, and support from others can encourage the patient to have the positive attitude to generate post-traumatic growth. (D) Trauma patients can be self-identification from the traumatic experience written, and can depend on the positive personality of optimistic philosophy and self-affirmation to get cross over the trauma, resulting in self-transformation.

Indiana University-Purdue University Indianapolis (IUPUI)
Posttraumatic epilepsy, the development of temporal lobe epilepsy (TLE) following traumatic brain injury, accounts for 20% of symptomatic epilepsy. Reorganization of mossy fibers within the hippocampus is a common pathological finding of TLE. Normal mossy fibers project into the CA3 region of the hippocampus where they form synapses with pyramidal cells. During TLE, mossy fibers are observed to innervate the inner molecular layer where they synapse onto the dendrites of other dentate granule cells, leading to the formation of recurrent excitatory circuits. To date, the molecular mechanisms contributing to mossy fiber sprouting are relatively unknown. Recent focus has centered on the involvement of tropomycin-related kinase receptor B (TrkB), which culminates in glycogen synthase kinase 3β (GSK3β) inactivation. As the neurite outgrowth promoting collapsin response mediator protein 2 (CRMP2) is rendered inactive by GSK3β phosphorylation, events leading to inactivation of GSK3β should therefore increase CRMP2 activity. To determine the involvement of CRMP2 in mossy fiber sprouting, I developed a novel tool ((S)-LCM) for selectively targeting the ability of CRMP2 to enhance tubulin polymerization. Using (S)-LCM, it was demonstrated that increased neurite outgrowth following GSK3β inactivation is CRMP2 dependent. Importantly, TBI led to a decrease in GSK3β-phosphorylated CRMP2 within 24 hours which was secondary to the inactivation of GSK3β. The loss of GSK3β-phosphorylated CRMP2 was maintained even at 4 weeks post-injury, despite the transience of GSK3β-inactivation. Based on previous work, it was hypothesized that activity-dependent mechanisms may be responsible for the sustained loss of CRMP2 phosphorylation. Activity-dependent regulation of GSK3β-phosphorylated CRMP2 levels was observed that was attributed to a loss of priming by cyclin dependent kinase 5 (CDK5), which is required for subsequent phosphorylation by GSK3β. It was confirmed that the loss of GSK3β-phosphorylated CRMP2 at 4 weeks post-injury was likely due to decreased phosphorylation by CDK5. As TBI resulted in a sustained increase in CRMP2 activity, I attempted to prevent mossy fiber sprouting by targeting CRMP2 in vivo following TBI. While (S)-LCM treatment dramatically reduced mossy fiber sprouting following TBI, it did not differ significantly from vehicle-treated animals. Therefore, the necessity of CRMP2 in mossy fiber sprouting following TBI remains unknown.

THE ABSTRACT The thesis deals with sibling relationships of twins and triplets when one or more siblings suffer from some health disability or handicap. It outlines the way of life in sibling constellations of twins and triplets. It deals with the topic of a disabled person who has brothers or sisters. It defines family as a pillar of person's life and it focuses on the sibling relationships. The thesis explains the connection between multiple births and the occurrence of disability, and it considers certain aspects of family life, with the main focus on siblings, when one of the siblings suffers from some health limitation. It also describes twins and triplets and their specific features. For example, it shows the development of the identity of each of the siblings, the role of their birth order, the types of relationships that occur in a family with twins and triplets, and the way the siblings may experience the separation from one another. It draws on publications and other sources that deal with sibling constellations and the resulting relationships among the siblings, on the publications on twins and triplets, on children and adults with disability or handicap. Last not least, it draws on personal experience of the author and on the research interviews. Apart from that, the thesis clarifies how twins...

In children with epilepsy and traumatic brain injury (TBI), the content of autoantibodies (aAb) to glutamate receptors (NMDA and AMPA subtypes) and the level of nitric oxide products - nitrothyrosine (NT) and nitrates/ nitrites (NOx) in the blood were studied. The obtained data make it possible to reveal the specificity of damage to AMPA and NMDA subtypes of glutamate receptors in convulsive states and posttraumatic brain injuries. The participation of NO and its products in the development of autoimmune response was revealed.

Background: Medical cannabis is available to patients by physician order in two-thirds of the United States (U.S.) as of 2020, but remains classified as an illicit substance by federal law. States that permit medical cannabis ordered by a physician typically require a diagnosed medical condition that is considered qualifying by respective state law. Objectives: To identify and map the most recently (2016-2019) published clinical and scientific literature across approved conditions for medical cannabis, and to evaluate the quality of identified recent systematic reviews. Methods: Literature search was conducted from five databases (PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov), with expansion and update from the National Academies of Sciences, Engineering, and Medicine’s (NASEM) comprehensive evidence review through 2016 of the health effects of cannabis on several conditions. Following consultation with experts and stakeholders, 11 conditions were identified for evidence evaluation: amyotrophic lateral sclerosis (ALS), autism, cancer, chronic pain, Crohn’s disease, epilepsy, glaucoma, HIV/AIDS, multiple sclerosis (MS), Parkinson’s disease, and posttraumatic stress disorder (PTSD). The following exclusion criteria were imposed: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome, intervention, sample size, study setting, and reported effect size. Studies classified as systematic reviews with or without meta-analysis were graded using the AMSTAR-2 tool by two raters to evaluate the quality of evidence, with additional raters to resolve cases of evidence grade disagreement. Results: A total of 438 studies were included after screening. Five completed randomized controlled trials (RCTs) were identified, and an additional 11 trials were ongoing, and 1 terminated. Cancer, chronic pain, and epilepsy were the most researched topic areas, representing more than two-thirds of all reviewed studies. The quality of evidence assessment for each condition suggests that few high-quality systematic reviews are available for most conditions, with the exceptions of MS, epilepsy, and chronic pain. In those areas, findings on chronic pain are mostly in alignment with the previous literature, suggesting that cannabis or cannabinoids are potentially beneficial in treating chronic neuropathic pain. In epilepsy, findings suggest that cannabidiol is potentially effective in reducing seizures in pediatric patients with drug-resistant Dravet and Lennox-Gastaut syndromes. In MS, recent high-quality systematic reviews did not include new RCTs, and are therefore not substantially expanding the evidence base. In sum, the most recent clinical evidence suggests that for most of the conditions assessed, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic pain), with the higher quality of evidence for epilepsy driven by FDA-approved formulations for cannabis-based seizure treatments. Conclusion: The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.