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OBJECTIVE: Seizures can be difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). We previously observed that brief apnea with hypoventilation (A&H) in our severe TBI model acutely interrupted seizures. The current study is designed to determine the effect of A&H on subsequent seizures and whether A&H has potential therapeutic implications. METHODS: Piglets (1 week or 1 month old) received multifactorial injuries: cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, and seizures induced with kainic acid. A&H (1 min apnea, 10 min hypoventilation) was induced either before or after seizure induction, or control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, and mechanically ventilated, and epidural electroencephalogram was recorded for an average of 18 h after seizure induction. RESULTS: In our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures, although most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8-10 h, seizures transitioned to interictal epileptiform discharges regardless of A&H or timing of A&H. SIGNIFICANCE: Even brief A&H may alter traumatic seizures. In our preclinical model, we will address the possibility of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI.
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Apnea , Lesiones Traumáticas del Encéfalo , Modelos Animales de Enfermedad , Hipoventilación , Convulsiones , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Porcinos , Convulsiones/etiología , Convulsiones/fisiopatología , Hipoventilación/terapia , Hipoventilación/fisiopatología , Hipoventilación/etiología , Apnea/fisiopatología , Electroencefalografía , Factores de Tiempo , Ácido Kaínico , MasculinoRESUMEN
INTRODUCTION: Post-traumatic seizures (PTSs) contribute to morbidity after traumatic brain injury (TBI). Early PTS are rare in combat casualties sustaining TBI, but the prevalence of late PTS is poorly described. We sought to define the prevalence and risk factors of late PTS in combat casualties with computed tomography evidence of TBI. METHODS: From 2010 to 2015, 687 combat casualties were transferred to a military treatment facility and included in the Department of Defense Trauma Registry. 71 patients with radiographic evidence of TBI were analyzed. Data collection included demographics, injury characteristics, interventions, medications, and outcomes. RESULTS: Of the 71 patients with evidence of TBI, 66 patients survived hospitalization and were followed. No patients had early PTS, and most received antiepileptic drugs (AEDs) for prophylaxis. At a median follow-up of 7.4 y, late PTS occurred in 25.8% of patients. Patients with late PTS were more severely injured (median Injury severity score 30 versus 24, P = 0.005) and required more blood products (18 units versus 2, P = 0.045). Patients with late PTS were more likely to have had a penetrating TBI (76.5% versus 38.8%, P = 0.01), multiple types of intracranial hemorrhage (94.1% versus 63.3%, P = 0.02), and cranial decompression (76.5% versus 28.6%, P = 0.001). Six-month Glasgow outcome scores were worse (3.5 versus 4.1 P = 0.001) in the late PTS population. No significant relationship was observed between administration of AEDs for early PTS prophylaxis and late PTS. CONCLUSIONS: Combat casualties with TBI suffering late PTS are more severely injured and require more blood products. Penetrating TBI, intracranial hemorrhage, and need for cranial decompression are correlated with late PTS, and associated with worse Glasgow Outcome Score. The administration of prophylactic AEDs for early PTS was not associated with a difference in rates of late PTS.
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Lesiones Traumáticas del Encéfalo , Humanos , Masculino , Adulto , Lesiones Traumáticas del Encéfalo/complicaciones , Femenino , Factores de Riesgo , Adulto Joven , Estudios Retrospectivos , Epilepsia Postraumática/etiología , Epilepsia Postraumática/epidemiología , Epilepsia Postraumática/prevención & control , Epilepsia Postraumática/diagnóstico , Convulsiones/etiología , Convulsiones/epidemiología , Convulsiones/prevención & control , Convulsiones/diagnóstico , Anticonvulsivantes/uso terapéutico , Prevalencia , Personal Militar/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Sistema de Registros/estadística & datos numéricos , Estudios de Seguimiento , Guerra de Irak 2003-2011 , Puntaje de Gravedad del TraumatismoRESUMEN
AIM: This study aimed to determine the frequency of traumatic brain injury (TBI) on neuroimaging and the need for emergency neurosurgery in children with normal mental status following a post-traumatic seizure (PTS). METHODS: We searched six electronic databases from inception to October 15, 2018, to identify studies including children under 18 years with head injury and a Glasgow Coma Score of 15 after an immediate PTS. Relevant non-English articles were translated to determine eligibility. RESULTS: We performed random effect meta-analyses and assessed heterogeneity with I2 . The pooled estimate of the frequency of TBI, from seven studies, was 13.0% (95% CI: 4.0-26.1; I2 = 81%). Data on the need of emergency neurosurgery were reported in four studies and the pooled estimate of its frequency was 2.3% (95% CI: 0.0-9.9; I2 = 86%). Two studies reported on children with isolated PTS without any other signs of head injury, representing 0.1% of patients in both studies, for a total of 76 children. Of these, only three had TBI and one underwent neurosurgery. CONCLUSION: Children with immediate PTS and normal mental status frequently have TBI with a substantial need for neurosurgery. Clinicians should strongly consider neuroimaging for these children, although prolonged observation may be considered for those with isolated PTS.
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Lesiones Traumáticas del Encéfalo/complicaciones , Convulsiones/etiología , Lesiones Traumáticas del Encéfalo/cirugía , Humanos , Neuroimagen , Procedimientos Neuroquirúrgicos , Convulsiones/diagnóstico por imagenRESUMEN
BACKGROUND: Traumatic brain injury (TBI) is a well-known risk factor for seizures. We aimed to identify the frequency and risk factors for seizure occurrence during hospitalization for TBI. METHODS: We used ICD-9-CM codes to identify patients 18 years of age or older from the National Trauma Data Bank who were admitted with TBI. We also used ICD-9-CM codes to identify the subset who had seizures during hospitalization. Patient demographics, comorbidities, Glasgow Coma Scale (GCS) score, Injury Severity Score Abbreviated Injury Scale (ISSAIS), in-hospital complications, and discharge disposition were compared in the seizure group (SG) and no-seizure group (NSG). RESULTS: A total of 1559 patients had in-hospital seizures, comprising 0.4% of all patients admitted with TBI. The mean age of SG was 3 years older than NSG [51 vs. 48; p < 0.0001]. African-American ethnicity (20 vs. 12%, p < 0.0001) and moderate TBI (8 vs. 4%, p < 0.0001) were more common in SG. History of alcohol dependence was more common in the SG (25 vs. 11%, p < 0.0001). Fall was the most common mechanism of injury in SG (56 vs. 36% in NSG; p < 0.0001). Subdural hematoma was more common in SG (31 vs. 21%, p < 0.0001). SG had higher rates of pneumonia, ARDS, acute kidney injury, and increased ICP. The average length of hospital stay was significantly higher in SG (10 vs. 6 days, p < 0.0001), and these patients had higher rate of discharge to nursing facility (32 vs. 25%, p < 0.0001). CONCLUSION: In-hospital seizures occur in 0.4% of all TBI patients. Although infrequent, seizure occurrence is associated with higher rates of hospital complications such as pneumonia and ARDS and is an independent predictor of longer hospital stay and worse hospital outcome.
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Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/epidemiología , Evaluación de Resultado en la Atención de Salud , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/etiología , Lesiones Traumáticas del Encéfalo/etnología , Bases de Datos Factuales , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Convulsiones/etnologíaRESUMEN
BACKGROUND: Much debate exists on the optimal medication for posttraumatic seizure prophylaxis after traumatic brain injury (TBI). There is some evidence that levetiracetam (LEV) could be neuroprotective and provide long-term benefits in this patient population. OBJECTIVE: The primary objective was to compare the Glasgow Outcome Scale-Extended (GOS-E) 6 months or more after severe TBI. Secondary end points were presence of early seizures (0 to 7 days post-TBI) or late seizures (8 days post-TBI to phone interview), use of anticonvulsant medication when interviewed, medication-related hospital complications, and a summary of phenytoin (PHT) and LEV dosing regimens. METHODS: This was an IRB-approved, single-center, prospective cohort analysis. Patients were identified by cross-referencing a list of patients receiving LEV or PHT, with a list of patients with ICD-9 code consistent with TBI. After study inclusion, patients were contacted by telephone, and the GOS-E was administered. Data for secondary end points were gathered by retrospective chart review. RESULTS: In all, 19 patients were included in the final analysis. There was no difference in the GOS-E score assessed ≥6 months after injury (5.07±1.69 vs 5.60±2.07, P=0.58). There was no difference in the secondary end points of early seizures (P=0.53) or late seizures (P=0.53). However, the PHT group experienced a higher rate of hospital days with recorded fever (0.20±0.22 vs 0±0; P=0.014). CONCLUSIONS: Long-term functional outcome in patients who experienced a TBI was not affected by treatment with PHT or LEV; however, patients treated with PHT had a higher incidence of fever during hospitalization.
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Anticonvulsivantes/uso terapéutico , Lesiones Encefálicas/tratamiento farmacológico , Fenitoína/uso terapéutico , Piracetam/análogos & derivados , Convulsiones/prevención & control , Adulto , Anciano , Lesiones Encefálicas/complicaciones , Femenino , Humanos , Levetiracetam , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Piracetam/uso terapéutico , Estudios Prospectivos , Convulsiones/etiologíaRESUMEN
A precise understanding of the latency to post-traumatic epilepsy (PTE) following a traumatic brain injury (TBI) is necessary for optimal patient care. This precision is currently lacking despite a surprising number of available data sources that could address this pressing need. Following guidance from the Cochrane Collaboration and Joanna Briggs Institute, we conduct a systematic review to address the research questions: What is the cumulative incidence of PTE following mild TBI (mTBI; concussion), and what is the distribution of the latency to onset? We designed a comprehensive search of medical databases and gray literature sources. Citations will be screened on both abstract and full-text levels, independently and in duplicate. Studies will be evaluated for risk of bias independently and in duplicate using published instruments specific to incidence/prevalence studies. Data will be abstracted independently and in duplicate using piloted extraction forms. Disagreements will be resolved by consensus or third-party adjudication. Evidence synthesis will involve pairwise and individual participant data meta-analysis with heterogeneity explored via a set of predetermined subgroups. The robustness of the findings will be subjected to sensitivity analyses based on the risk of bias, outlier studies, and mTBI definitional criteria. The overall certainty in the estimates will be reported using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). This protocol presents an innovative and impactful approach to build on the growing body of knowledge surrounding post-mTBI PTE. Through a precise understanding of the latency period, this study can contribute to early detection, tailored interventions, and improved outcomes, leading to a substantial impact on patient care and quality of life.
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A late post-traumatic seizure (LPTS), a consequence of traumatic brain injury (TBI), can potentially evolve into a lifelong condition known as post-traumatic epilepsy (PTE). Presently, the mechanism that triggers epileptogenesis in TBI patients remains elusive, inspiring the epilepsy community to devise ways to predict which TBI patients will develop PTE and to identify potential biomarkers. In response to this need, our study collected comprehensive, longitudinal multimodal data from 48 TBI patients across multiple participating institutions. A supervised binary classification task was created, contrasting data from LPTS patients with those without LPTS. To accommodate missing modalities in some subjects, we took a two-pronged approach. Firstly, we extended a graphical model-based Bayesian estimator to directly classify subjects with incomplete modality. Secondly, we explored conventional imputation techniques. The imputed multimodal information was then combined, following several fusion and dimensionality reduction techniques found in the literature, and subsequently fitted to a kernel- or a tree-based classifier. For this fusion, we proposed two new algorithms: recursive elimination of correlated components (RECC) that filters information based on the correlation between the already selected features, and information decomposition and selective fusion (IDSF), which effectively recombines information from decomposed multimodal features. Our cross-validation findings showed that the proposed IDSF algorithm delivers superior performance based on the area under the curve (AUC) score. Ultimately, after rigorous statistical comparisons and interpretable machine learning examination using Shapley values of the most frequently selected features, we recommend the two following magnetic resonance imaging (MRI) abnormalities as potential biomarkers: the left anterior limb of internal capsule in diffusion MRI (dMRI), and the right middle temporal gyrus in functional MRI (fMRI).
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Biomarcadores , Lesiones Traumáticas del Encéfalo , Aprendizaje Automático , Neuroimagen , Humanos , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/complicaciones , Neuroimagen/métodos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Adulto , Algoritmos , Epilepsia Postraumática/diagnóstico por imagen , Epilepsia Postraumática/etiología , Imagen Multimodal/métodos , Convulsiones/diagnóstico por imagen , Teorema de Bayes , Persona de Mediana EdadRESUMEN
OBJECTIVE: Traumatic brain injury (TBI) and the subsequent Post-traumatic seizure (PTS) is a growing public health concern. Generally, anti-seizure drugs (ASDs) are recommended for PTS prophylaxis and treatment. This meta-analysis aimed to review the current state of knowledge and the evidence for the efficacy and safety of Levetiracetam (LEV) on the incidence of seizure in TBI patients compared to Phenytoin (PHT). METHODS: A search was carried out based on PubMed, MEDLINE, Europe PMC database, and Cochrane Library up to November 2023. A total of 16 studies (3 randomized clinical trials, 10 retrospective cohort studies, and 3 prospective cohort studies) including 5821 TBI patients included in our meta-analysis. We included studies comparing LEV and PHT after brain injury in both adults and children. Risk of bias assessment was done for randomized controlled trials (RCTs) with a risk-of-bias tool (RoB-2) and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort studies. Two RCTs in our meta-analysis had a high risk of bias, therefore we applied sensitivity analysis to evaluate the robustness of our results. RESULTS: The most commonly reported dosage for LEV was 500â¯mg twice daily and for PHT it was 5â¯mg/kg. There was no significant difference between LEV and PHT groups in reducing the early seizure incidence (OR = 0.85; 95% CI = [0.60, 1.21]; p = 0.375, fixed-effect, I2 = 21.75%). The result of sensitivity analysis for late seizure showed no significant difference between LEV and PHT in reducing the late seizure occurrence after TBI (OR = 0.87; 95% CI = [0.21, 3.67]; p = 0.853, fixed-effect, I2 = 0%). The mortality in TBI patients treated with LEV was not statistically significant compared to the PHT group (OR = 1.11; 95% CI = [0.92, 1.34], p = 0.266). The length of stay in the hospital was not significantly different between the LEV and PHT groups (MD = -1.33; 95% CI = [-4.55, 1.90]; p = 0.421). However, in comparison to PHT, LEV shortened the length of ICU stay (MD = -2.25; 95% CI = [-3.58, -0.91]; p =0.001). In terms of adverse effects, more patients in the PHT group have experienced adverse events compared to LEV but the difference was not significant (OR = 0.69; 95% CI = [0.44, 1.08]; p = 0. 11). CONCLUSION: The results of our meta-analysis showed LEV and PHT have similar effects on the occurrence of early and late seizures in TBI patients. Therefore, none of the drugs is superior to the other in reducing PTS. However, treating TBI patients with LEV did not shorten the length of hospital stay in comparison to PHT but reduced the length of ICU stay significantly. The analysis showed that patients in the LEV experienced fewer side effects than in the PHT group, while it was not sufficiently clear whether all reported side effects were related to the drug alone or other factors. The mortality was similar between the LEV and PHT groups. Finally, we recommend more high-quality randomized controlled trials to confirm the current findings before making any recommendations in practice.
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Anticonvulsivantes , Lesiones Traumáticas del Encéfalo , Levetiracetam , Fenitoína , Convulsiones , Humanos , Anticonvulsivantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Levetiracetam/uso terapéutico , Fenitoína/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/prevención & control , Convulsiones/etiología , Convulsiones/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: Levetiracetam (LEV) and valproic acid (VPA) are two anti-epileptic drugs (AEDs) routinely used for post-traumatic seizure (PTS) prophylaxis at our institution. In our practice, VPA is used for its beneficial effects on behavioral agitation and headaches, but it is also associated with abnormal liver function tests (LFTs). Both medications may be associated with thrombocytopenia. There is less literature comparing the adverse effect profiles and discontinuation rates of LEV and VPA in the context of PTS prophylaxis. We conducted a quality improvement (QI) analysis to determine the safety of LEV and VPA for traumatic brain injury (TBI) patients at our institution. In particular, our QI analysis involved calculating the rates of discontinuation or change of drug regimen due to the adverse effects. METHODS: Our QI analysis focused on patients treated for TBI at our institution during a six-year period. We recorded the AED used and if the AED was discontinued or switched due to thrombocytopenia, behavioral agitation, headaches, or elevated LFTs (including elevated aspartate aminotransferase or alanine aminotransferase values). We also recorded the incidence of early PTS, defined as seizures within seven days of the TBI. RESULTS: Our QI analysis included patients with a mean age of approximately 49 years with nearly 75% males. The mean Glasgow Coma Scale (GCS) score was 12.88, with 73.11% of patients having a mild GCS. The three leading injury mechanisms were fall, assault, and motor vehicle collision. The three leading types of TBI were traumatic subarachnoid hemorrhage, subdural hematoma, and cerebral contusion. Among patients with no prior history of seizures, we found an early PTS incidence of 7.28%. For patients administered LEV and VPA, 0.11% (1/898) and 3.85% (4/104) had the medication discontinued or changed because of thrombocytopenia (p < 0.001), respectively. For patients on LEV, 4.01% (36/898) and 1.78% (16/898) had the medication discontinued or changed because of behavioral agitation and headaches, respectively. For patients on VPA, 2.88% (3/104) had the medication discontinued or changed because of hepatotoxicity. In total, 5.90% versus 6.73% (p > 0.5) of patients on LEV and VPA, respectively, had their medication regimens changed due to the adverse effects. CONCLUSIONS: The incidence of early PTS in our patients is within the range of what has been reported in the literature. The rate of discontinuation of LEV and VPA on account of adverse events is low in the context of PTS prophylaxis. Both medications had similar overall rates of discontinuation. VPA was discontinued more frequently than LEV due to thrombocytopenia, but discontinuation was not common in either case. LEV is associated with behavioral agitation and headaches, which makes VPA a desirable alternative for patients suffering from these symptoms.
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Background: Post traumatic seizures (PTS) and post traumatic epilepsy (PTE) are potential consequences of traumatic brain injury (TBI). There is no consensus regarding its management among treating doctors. Purpose: We have undertaken a global survey to assess the variability of management practices of PTS and PTE and highlight the pressing need to formulate uniform practice guidelines. Methods: A questionnaire consisting of sixteen questions were developed with the help of Google survey and sent through e-mail, or social media platforms like WhatsApp, Facebook messenger or Telegram, to practicing Neurologists and Neurosurgeons round the world. Results: There were a total of 220 responses. Majority of our responders (n = 202; 91.8%) would start an anti-epileptic (AED) prophylaxis to prevent PTS; 18 people (8.18%) told that they would not start AED prophylaxis for TBI. Phenytoin (n = 98; 48.5%) followed by Levetiracetam (n = 78; 38.6%) was the preferred drug, although the latter was significantly preferred by high and upper middle-income countries (p<.001). Majority (n = 99; 49%) would not use it beyond two weeks. Most clinicians would manage PTE with a single drug (n = 160; 72.7%) either Phenytoin (n = 69; 31.3%) or levetiracetam (n = 67; 30.4%). Most of them (n = 174; 86%) would treat for less than one year. Conclusions: Practices in the management of PTS and PTE vary widely among clinicians. Our study point towards the need for the development of a more robust and comprehensive practice guidelines for the management of the same.
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Background: Traumatic brain injury (TBI) is a common cause of paediatric intensive care unit (PICU) admissions in South Africa. Optimal care of these patients includes the prevention and control of post-traumatic seizures (PTS) in order to minimise secondary brain injury. Objectives: To describe the demographics of children admitted to a South African PICU, to describe the characteristics of PTS, and to describe the prophylactic and therapeutic management of PTS within the unit. Methods: A 3-year retrospective chart review was conducted at the PICU of the Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg, from 1 July 2015 to 30 June 2018. Results: Seventy-eight patients were admitted to the PICU, all with severe TBI. A total of 66 patient files were available for analysis. The median age of admission was 6 years (interquartile range (IQR) 4 - 9) with the majority of trauma secondary to mechanical injury (89%). Prophylactic anti-epileptic drugs (AEDs) were initiated in 44 (79%) patients. Early PTS occurred in 11 (25%) patients who received prophylaxis and 4 (33%) who did not. Three (5%) patients developed late PTS, resulting in an overall incidence of PTS of 43%. The most common seizure type was generalised tonic clonic (82%). Children diagnosed with PTS were a median of 2 years younger than those without PTS, with increased prevalence of seizures (83% v. 38%) in children below 2 years of age. Maintenance therapy was initiated in all patients consistent with recommended dosages. Of the total 167 anti-epileptic levels taken during maintenance, only 56% were within target range. Of the initial 78 patients, 8 died (10%). The median length of stay was 7 (IQR 5 - 12) and 8 (IQR 8 - 24) days longer in ICU and hospital respectively, in children with PTS. Conclusion: PTS is a frequent complication of severe TBI in children. There was considerable variation in the approach to both prophylaxis and maintenance therapy of PTS in terms of choice of agent, dosage, frequency of drug monitoring and approach to subtherapeutic levels. It is clear that more high-level studies are required in order to better inform these practices. Contributions of the study: To the best of our knowledge, this article represents the first description of incidence and management practices of paediatric post traumatic seizures.
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Post-traumatic seizures (PTS) have become an emerging challenge for neurologists worldwide with the rise of brain injuries. Trauma can lead to various outcomes, ranging from naive spasms to debilitating post-traumatic epilepsy (PTE). In this article, we will explore the pathogenesis of convulsions following a concussion. We will look at multiple studies to explain the various structural, metabolic, and inflammatory changes leading to seizures. Additionally, we will explore the association between severity and location of injury and PTE. PTE's pathophysiology is not entirely implicit, and we are still in the dark as to which anti-epileptic drugs will be useful in circumventing these attacks. The purpose of this narrative review is to explain the post-traumatic brain changes in detail so that such attacks can be either thwarted or treated more resourcefully in the future.
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BACKGROUND: This study aimed to re-establish a Population Pharmacokinetic (PPK) model of oral phenytoin to further optimize the individualized medication regimen based on our previous research. METHODS: Patients with intracranial malignant tumor requiring craniotomy were prospectively enrolled according to the inclusion criteria. Genotypes of CYP2C9*1 or *3 and CYP2C19*1, *2 or *3 were determined by real time PCR (TaqMan probe) method. Serum concentrations of phenytoin on the 4th and 7th day after oral administration were determined using fluorescence polarization immunoassay. The PPK parameters were estimated using Nonlinear Mixed Effects Models (NONMEM) and internal validation was performed using bootstraps. The predictive performance of the final model was evaluated by Normalized Predictive Distribution Errors (NPDEs) and diagnostic goodness- of-fit plots. RESULTS: A total of 390 serum samples were collected from 170 patients in PPK model building group. The population typical values for Vm, Km and the apparent volume of distribution (V) in the final model were 17.5 mg/h, 6.41 mg/L and 54.8 L, respectively. Internal validation by bootstraps showed that the final model was stable and reliable. NPDEs with a normal distribution and a scatterplot with symmetrical distribution showed that the final model had good predictive capability. Individualized dose regimens of additional 40 patients in the external validation group were designed by the present final PPK model. The percentages of patients with serum concentrations within the therapeutic range were 61.53% (24/39) on the 4th day and 94.87% (37/39) on the 7th day, which were higher than the 39.33% (59/150) and 52.10% (87/167) of above 170 patients (P < 0.0001). CONCLUSION: The present PPK final model for oral phenytoin may be used to further optimize phenytoin individualized dose regimen to prevent early seizure in patients after brain injury if patient characteristics meet those of the population studied.
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Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapéutico , Fenitoína/farmacocinética , Fenitoína/uso terapéutico , Convulsiones/genética , Convulsiones/prevención & control , Administración Oral , Adulto , Anciano , Anticonvulsivantes/sangre , Lesiones Encefálicas , Craneotomía , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenitoína/sangre , Periodo PosoperatorioRESUMEN
BACKGROUND: Current international guidelines for traumatic brain injury (TBI) recommend the use of phenytoin for the prevention of early post traumatic seizures (PTS) when the benefits are thought to outweigh the risks. In practice however, alternative antiepileptic drugs (AEDs) such as levetiracetam and valproate are being used as they are believed to have a more favourable risk profile. This is despite there being insufficient evidence to support their efficacy. The purpose of this study was to identify which AED was prescribed to patients presenting with a TBI at a single institution, and to determine the rate of early PTSs. METHODS: This was a retrospective case-note review study done at the Flinders Medical Centre including patients admitted from May 2013 to June 2017. All patients with traumatic intracranial haematomas were included. Patients were excluded if they had seizures prior to presentation to hospital or died within 24â¯h of injury. The primary outcomes were rate of early PTSs and the type of prophylactic AED prescribed. RESULTS: During this study period, 610 patients presented with a mild, moderate or severe traumatic brain injury. Overall, 16% of patients were prescribed an AED, with more than 90% of these patients being prescribed levetiracetam. Overall, the rate of early PTSs for patients prescribed AEDs was 2.9% compared with 3.5% for patients not prescribed AEDs (OR 0.83 CI 0.24-2.85 pâ¯=â¯1). CONCLUSIONS: This study showed that levetiracetam was the most commonly prescribed AED. It also demonstrated no statistically significant difference in the rate of early PTSs in patients with TBI, with or without prophylactic AEDs. This is in keeping with other contemporary studies, and therefore the routine administration of prophylactic AEDs may need to be re-examined.
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Anticonvulsivantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Epilepsia Postraumática/etiología , Epilepsia Postraumática/prevención & control , Pautas de la Práctica en Medicina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: The incidence of sport-related concussion (SRC) continues to rise. Presentations of concussed athletes vary from subtle symptoms to notable signs. Between the 4th and 5th iterations of the Concussion in Sport Group (CISG) guidelines, concussive convulsions were removed as a modifying factor, but little evidence or discussion supported this change. While considerable research exists regarding post-traumatic epilepsy in moderate to severe traumatic brain injury, convulsions following SRC are relatively understudied. There is no clear consensus on the prevalence of convulsions, seizures, or the management of these entities following SRC. The aim of this review was to assess the state of the literature, describe the management trends of concussive convulsions and post-traumatic epilepsy in the SRC population, and provide evidence and guidance for the management of these athletes. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adapted for a review of heterogeneous literature. English-language titles and abstracts published prior to June 2017 were searched systematically across four electronic databases. Primary peer-reviewed journal articles were included if they reported individuals of any age or gender who suffered a concussion or mild traumatic brain injury that was associated with seizure activity during a sports/recreational event. RESULTS: Of 852 records screened for review, 58 full-text articles were assessed for eligibility. Eight studies with 130 athletes total met the inclusion criteria. Of these individuals suffering a SRC convulsion or a post-concussive seizure, 0.8% received antiepileptic medications, 24.6% underwent electroencephalography, and 30.8% underwent brain imaging. The mean time until the participant returned to play was 14.8 days. Only 6.9% developed long-term sequelae over a mean follow-up time of 3.3 years. CONCLUSIONS: The current literature describing concussive convulsions and post-concussion seizure in sports is limited. A void of primary literature concerning the management of patients with concussive convulsions or seizures and the long-term sequelae among this population remains. However, the evidence available suggests that concussive convulsions do not need to be a primary modifying factor in the management of SRC.
Asunto(s)
Traumatismos en Atletas/terapia , Conmoción Encefálica/terapia , Encéfalo , Epilepsia Postraumática , Medicina Deportiva , Deportes , Traumatismos en Atletas/complicaciones , Encéfalo/patología , Conmoción Encefálica/complicaciones , Epilepsia Postraumática/tratamiento farmacológico , Epilepsia Postraumática/etiología , Femenino , Humanos , Masculino , PrevalenciaRESUMEN
BACKGROUND: To explore the incidence and risk factors, including type of seizures for post-traumatic epilepsy (PTE) after severe traumatic brain injury (TBI). SUBJECTS AND METHODS: This was a retrospective follow-up study of patients discharged from Liaocheng People's Hospital between March 2011 and June 2015 with a diagnosis of post-traumatic seizures. Risk factors for PTE were evaluated in 68 inpatients by using Kaplan-Meier curves and the Cox model. RESULTS: Complete clinical information was available for 68 patients. A total of 54 cases (79.4%) were diagnosed as presenting with PTE, occurring from 10 days to 179 months after severe TBI. Nineteen out of 54 cases (35.2%) had been defined as PTE within the first 6 months after the trauma, 17 cases (31.5%) within 7-12 months, 8 cases (14.8%) within 13-24 months, 2 cases (3.7%) within 25-36 months, and 8 cases (14.8%) within 37-179 months after the TBI. The Kaplan-Meier curves demonstrated that simple partial seizures, surgical treatment, and onset of seizures occurring within 6 months after injury were associated with PTE. CONCLUSIONS: The Cox model indicated that, for patients aged >34 years at the time of injury, the PTE risk was 2.55 times greater than for those aged ≤34 years. In addition, simple partial seizures, surgical treatment and onset of seizures occurring within 6 months after injury were significant risk factors for the development of PTE.
RESUMEN
Traumatic brain injury (TBI) is the leading cause of death and disability in children, and can lead to long lasting functional impairment. Many factors influence outcome, but imaging studies examining effects of individual variables are limited by sample size. Roughly 20-40% of hospitalized TBI patients experience seizures, but not all of these patients go on to develop a recurrent seizure disorder. Here we examined differences in structural network connectivity in pediatric patients who had sustained a moderate-severe TBI (msTBI). We compared those who experienced early post-traumatic seizures to those who did not; we found network differences months after seizure activity stopped. We also examined correlations between network measures and a common measure of injury severity, the Glasgow Coma Scale (GCS). The global GCS score did not have a detectable relationship to brain integrity, but sub-scores of the GCS (eyes, motor, verbal) were more closely related to imaging measures.
RESUMEN
Traumatic brain injury (TBI) is an important public health concern plagued by high rates of mortality and significant long-term disability in many survivors. Post-traumatic seizures (PTS) are not uncommon following TBI, both in the early (within 7 days post-injury) and late (after 7 days post-injury) period. Due to the potential of PTS to exacerbate secondary injury following TBI and the possibility of developing post-traumatic epilepsy (PTE), the medical community has explored preventative treatment strategies. Prophylactic antiepileptic drug (AED) administration has been proposed as a measure to reduce the incidence of PTS and the ultimate development of PTE in TBI patients. In this topical review, we discuss the pathophysiologic mechanisms of early and late PTS and the development of PTE following TBI, the pharmacodynamic and pharmacokinetic properties of AEDs commonly used to prevent post-traumatic seizures, and summarize the available clinical evidence for employing AEDs for seizure prophylaxis after TBI.