Computed Tomographic Scans in Posttraumatic Epilepsy

D’Alessandro, Roberto; Ferrara, Raffaele; Benassi, G; Lenzi, P

doi:10.1001/archneur.1988.00520250048019

Cited by 26 publications

(3 citation statements)

References 9 publications

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“…Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) have allowed for non-invasive analysis of molecular and structural alterations of white matter and other neural structures at high spatial resolution. MRI may be used to identify specific abnormalities associated with increased susceptibility to epileptogenesis, including focal lesions (D'Alessandro et al, 1982; Dalessandro et al, 1988), intracerebral hemorrhage (D'Alessandro et al, 1982), biparietal contusions (Englander et al, 2003) and dural penetration from bone or metal fragments (Englander et al, 2003). In a lateral FPI model, diffusion tensor trace alterations in the hippocampus acquired 3 hours after injury were found to predict seizure susceptibility and number of spikes 12 months later (Kharatishvili et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Analytic Tools for Post-traumatic Epileptogenesis Biomarker Search in Multimodal Dataset of an Animal Model and Human Patients

Duncan

Barisano

Cabeen

et al. 2018

Front. Neuroinform.

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Epilepsy is among the most common serious disabling disorders of the brain, and the global burden of epilepsy exerts a tremendous cost to society. Most people with epilepsy have acquired forms of the disorder, and the development of antiepileptogenic interventions could potentially prevent or cure epilepsy in many of them. However, the discovery of potential antiepileptogenic treatments and clinical validation would require a means to identify populations of patients at very high risk for epilepsy after a potential epileptogenic insult, to know when to treat and to document prevention or cure. A fundamental challenge in discovering biomarkers of epileptogenesis is that this process is likely multifactorial and crosses multiple modalities. Investigators must have access to a large number of high quality, well-curated data points and study subjects for biomarker signals to be detectable above the noise inherent in complex phenomena, such as epileptogenesis, traumatic brain injury (TBI), and conditions of data collection. Additionally, data generating and collecting sites are spread worldwide among different laboratories, clinical sites, heterogeneous data types, formats, and across multi-center preclinical trials. Before the data can even be analyzed, these data must be standardized. The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a multi-center project with the overarching goal that epileptogenesis after TBI can be prevented with specific treatments. The identification of relevant biomarkers and performance of rigorous preclinical trials will permit the future design and performance of economically feasible full-scale clinical trials of antiepileptogenic therapies. We have been analyzing human data collected from UCLA and rat data collected from the University of Eastern Finland, both centers collecting data for EpiBioS4Rx, to identify biomarkers of epileptogenesis. Big data techniques and rigorous analysis are brought to longitudinal data collected from humans and an animal model of TBI, epilepsy, and their interaction. The prolonged continuous data streams of intracranial, cortical surface, and scalp EEG from humans and an animal model of epilepsy span months. By applying our innovative mathematical tools via supervised and unsupervised learning methods, we are able to subject a robust dataset to recently pioneered data analysis tools and visualize multivariable interactions with novel graphical methods.

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Section: Introductionmentioning

confidence: 99%

Analytic Tools for Post-traumatic Epileptogenesis Biomarker Search in Multimodal Dataset of an Animal Model and Human Patients

Duncan

Barisano

Cabeen

et al. 2018

Front. Neuroinform.

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“…CT scans have been used for decades to assess global structural damage after TBI ( D’Alessandro et al, 1988 ). Characterization of early CT scans have identified an increased risk of PTE development in patients with depressed skull fracture, dural penetration, and intraparenchymal, subdural, or epidural hemorrhage.…”

Section: Emerging Biomarkers Of Post-traumatic Epilepsymentioning

confidence: 99%

Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions

Golub

Reddy

2022

Pharmacol Rev

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Post-traumatic epilepsy (PTE) is one of the most devastating long-term, network consequences of traumatic brain injury (TBI). There is currently no approved treatment that can prevent onset of spontaneous seizures associated with brain injury, and many cases of PTE are refractory to antiseizure medications. Post-traumatic epileptogenesis is an enduring process by which a normal brain exhibits hypersynchronous excitability after a head injury incident. Understanding the neural networks and molecular pathologies involved in epileptogenesis are key to preventing its development or modifying disease progression. In this article, we describe a critical appraisal of the current state of PTE research with an emphasis on experimental models, molecular mechanisms of post-traumatic epileptogenesis, potential biomarkers, and the burden of PTE-associated comorbidities. The goal of epilepsy research is to identify new therapeutic strategies that can prevent PTE development or interrupt the epileptogenic process and relieve associated neuropsychiatric comorbidities. Therefore, we also describe current preclinical and clinical data on the treatment of PTE sequelae. Differences in injury patterns, latency period, and biomarkers are outlined in the context of animal model validation, pathophysiology, seizure frequency, and behavior. Improving TBI recovery and preventing seizure onset are complex and challenging tasks; however, much progress has been made within this decade demonstrating disease modifying, anti-inflammatory, and neuroprotective strategies, suggesting this goal is pragmatic. Our understanding of PTE is continuously evolving, and improved preclinical models allow for accelerated testing of critically needed novel therapeutic interventions in military and civilian persons at high risk for PTE and its devastating comorbidities. Significance Statement Post-traumatic epilepsy is a chronic seizure condition after brain injury. With few models and limited understanding of the underlying progression of epileptogenesis, progress is extremely slow to find a preventative treatment for PTE. This study reviews the current state of modeling, pathology, biomarkers, and potential interventions for PTE and comorbidities. There’s new optimism in finding a drug therapy for preventing PTE in people at risk, such as after traumatic brain injury, concussion, and serious brain injuries, especially in military persons.

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“…Risk factors for posttraumatic epilepsy (PTE) are still debated; however, the extensive use of computed tomography (CT) scanning in patients with traumatic brain injury (TBI) has confirmed the important role of documented focal brain lesions not only in military, but also in civilian TBI (1–17). This means that a precise neuroradiologic diagnosis is of paramount value in determining the individual PTE risk.…”

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confidence: 99%

Predicting Posttraumatic Epilepsy with MRI: Prospective Longitudinal Morphologic Study in Adults

et al. 2005

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Summary:Purpose: Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments ≤2 years after traumatic brain injury (TBI).Methods: Brain MRI hyperintense (gliosis) or hypointense (hemosiderin) areas or both were assessed in the images of 135 adult TBI inpatients who completed a 2-year clinical, EEG, and MRI study protocol. Overall clinical follow-up for the development of PTE was 5-10 years (median, 102 months). Morphologic risk factors for PTE were evaluated by using Kaplan-Meier curves and Cox regression analysis.Results: In 20 patients, PTE developed. Kaplan-Meier curves showed that gliomesenchymal sequelae of focal brain lesions (subdural hematomas/contusions) that required surgical treatment (sSDH-C) were a PTE risk factor (p < 0.001), as were sequelae of nonsurgical hemorrhagic contusions with gliosis wall incompletely surrounding hemosiderin dregs (IW) (p = 0.039) and mainly those with time-related changes from incomplete to complete gliosis wall around hemosiderin (I/CW) (p = 0.005); those with early hemosiderin completely surrounded by gliosis (CW) were not (p = 0.821). Cox regression analysis showed that for patients with sequelae of sSDH-C, the PTE risk was 4.38 (p = 0.023) times higher than for those who did not require surgical treatment or underwent surgery because of purely extradural hematoma; for those with IW and I/CW lesions, considered pooled, it was 6.61 times higher (p = 0.014) than for those with CW lesions.Conclusions: MRI follow-up examination in the early chronic stage can differentiate among low-, intermediate-, and high-risk sequelae of TBI. These findings yield new evidence for, but do not resolve, the debate on posttraumatic epileptogenesis. Key Words: Posttraumatic epilepsy-Brain MRI-HemosiderinGliosis.Risk factors for posttraumatic epilepsy (PTE) are still debated; however, the extensive use of computed tomography (CT) scanning in patients with traumatic brain injury (TBI) has confirmed the important role of documented focal brain lesions not only in military, but also in civilian TBI (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). This means that a precise neuroradiologic diagnosis is of paramount value in determining the individual PTE risk.Magnetic resonance imaging (MRI) has become the imaging method of choice for evaluation of TBI patients in the chronic stage because of its exquisite capability in showing posttraumatic brain abnormalities, provided that the appropriate pulse sequences are used. However, the relation between PTE and brain damage as revealed by MRI has not been established (18). A few years ago, our group participated in a joint prospective longitudinal study to evaluate risk factors for PTE in adults by using clini-

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Computed Tomographic Scans in Posttraumatic Epilepsy

Cited by 26 publications

References 9 publications

Analytic Tools for Post-traumatic Epileptogenesis Biomarker Search in Multimodal Dataset of an Animal Model and Human Patients

Analytic Tools for Post-traumatic Epileptogenesis Biomarker Search in Multimodal Dataset of an Animal Model and Human Patients

Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions

Predicting Posttraumatic Epilepsy with MRI: Prospective Longitudinal Morphologic Study in Adults

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