Posttraumatic epilepsy: Integrating clinical, inflammatory, and genetic profiles in traumatic brain injury patients.

OBJECTIVE: This study aims to assess the clinical, inflammatory, and genetic profiles of traumatic brain injury (TBI) patients over a 2-year follow-up period, focusing on the development of posttraumatic epilepsy (PTE). METHODS: Fifty-nine patients with acute TBI were recruited in the emergency unit of a hospital in Brazil. Clinical data and blood samples were collected after 10 days of hospitalization for posterior genetic profile (Apolipoprotein E- ApoE and Glutamic Acid Descarboxylase-GAD sequencing) analyses. A subset of 19 patients were assessed for cytokine markers (mRNA expression). The development of PTE was investigated for two years following TBI. Statistical analyses including univariate analysis, multiple correspondence analysis, and Mann-Whitney test were performed. RESULTS: Analysis revealed an association between severe TBI and requirement for neurosurgery and polytrauma (p<0.05), as well as the development of PTE over a two-year follow-up period (p<0.05). Multiple correspondence analysis identified two distinct profiles associated with PTE and Non-PTE outcomes. The PTE profile showed a higher prevalence of the ApoE genotype E3/E3 and GAD1 SNP (rs769391) genotype AA in our study, while the Non-PTE profile showed a higher presence of E3/E4. mRNA expression analysis demonstrated acute elevated levels of TNF-α in the PTE group as compared to Non-PTE patients (6.70±1.53 vs 5.31 ±0.33, p<0.01). SIGNIFICANCE: Our findings underscore the multifactorial nature of aspects potentially contributing to PTE. It is unlikely that any single factor might in isolation have a strong causative influence over the development of epilepsy after TBI. Our results provide a suggestion of potential clustering that might be relevant as prognostic factors for PTE.

Modeling of post-traumatic epilepsy and experimental research aimed at its prevention

Research on the prevention of post-traumatic epilepsy (PTE) has seen remarkable advances regarding its physiopathology in recent years. From the search for biomarkers that might be used to indicate individual susceptibility to the development of new animal models and the investigation of new drugs, a great deal of knowledge has been amassed. Various groups have concentrated efforts in generating new animal models of traumatic brain injury (TBI) in an attempt to provide the means to further produce knowledge on the subject. Here we forward the hypothesis that restricting the search of biomarkers and of new drugs to prevent PTE by using only a limited set of TBI models might hamper the understanding of this relevant and yet not preventable medical condition.

Modeling of post-traumatic epilepsy and experimental research aimed at its prevention.

Research on the prevention of post-traumatic epilepsy (PTE) has seen remarkable advances regarding its physiopathology in recent years. From the search for biomarkers that might be used to indicate individual susceptibility to the development of new animal models and the investigation of new drugs, a great deal of knowledge has been amassed. Various groups have concentrated efforts in generating new animal models of traumatic brain injury (TBI) in an attempt to provide the means to further produce knowledge on the subject. Here we forward the hypothesis that restricting the search of biomarkers and of new drugs to prevent PTE by using only a limited set of TBI models might hamper the understanding of this relevant and yet not preventable medical condition.

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.

Potential therapeutic implications of ergogenic compounds on pathophysiology induced by traumatic brain injury: A narrative review.

Traumatic brain injury (TBI) is a devastating condition that often triggers a sequel of neurological disorders that can last throughout lifespan. From a metabolic viewpoint, the compromising of the energy metabolism of the brain has produced evidence linking the severity of brain injury to the extent of disturbances in the cerebral metabolism. The cerebral metabolic crisis, however, displays that regional heterogeneity varies temporally post-injury. It is important to note that energy generation and mitochondrial function are closely related and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment, and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. One of the possible strategies may be the inclusion of ergogenic compounds, which is a class of supplements that typically includes ingredients used by athletes to enhance their performance. The combination of these compounds offers specific physiological advantages, which include enhanced energy availability/metabolism and improved buffering capacity. However, the literature on their effects in certain biological systems and neurological diseases, such as TBI, has yet to be determined. Thus, the present review aims to discuss the role of ergogenic compounds popularly used in secondary damage induced by this neurological injury. In this narrative review, we also discuss how the results from animal studies can be applied to TBI clinical settings.

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.

Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury.

Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI.

Epilepsia Traumática Temprana en Niños: Epidemiología y Pronóstico Inmediato / Early traumatic epilepsy in children: epidemiology and inmediate pronostic

El presente trabajo tiene como objetivo analizar 110 casos de Epilepsia Traumática Temprana (ETT) en niños hospitalizados en el Servicio de Neurocirugía del Instituto Nacional de Salud del Niño entre enero de 1982 a diciembre de 1986. Los casos correspondieron al 7.3% de 1448 niños hospitalizados con traumatismo craneoencefálico. Se usó el método descriptivo retrospectivo.El 65.52% presentaron la edad de 3 a 10 años. El 63.60% fueron de sexo masculino. La etiología predominante correspondió a caídas de altura y accidentes de transito. Los factores clínicos más importantes asociados a esta entidad fueron: pérdida de conciencia mayor de 24 horas, 35.41%; los signos focales 13.64%; hematoma intracraneano 4.55% y lesiones de duramadre, 1.85%. Además el 25.45% presentaron una lesión trivial craneoencefálica. El 23.64% presentó fracturas craneales. El 86.36% presentaron su primera crisis dentro de las primeras 24 horas post-traumatismo encéfalo craneano. No se encontró diferencia en el tipo de convulsiones; focal, focal-generalizada y generalizada. El 5.76% fallecieron.

[Post-traumatic epilepsy. Analysis of 70 cases]. / Epilepsia postraumática. Análisis de 70 casos.

A retrospective study of 70 cases of posttramatic epilepsy is undertaken. The clinical and electroencephalographic characteristics are analyzed and it is emphasized: (1) The predominance of generalized seizures over focal fits, and among these last, the higher incidence of motor seizures are stressed. (2) The incidence of early seizures was of 5% in this series. (3) The occurrence of epilepsy usually was within 2 years after head injury. (4) Frequent correlation between the clinical course and the EEG is noted. A brief bibliographical review on the subject is presented, and the importance of a prospective study in the value of anticonvulsive drugs in prevention of posttramatic epilepsy is underlined.