Posts Tagged epileptogenesis

[Abstract] Big data sharing and analysis to advance research in post-traumatic epilepsy – Review


  • We have created the infrastructure for a centralized data repository for multi-modal data.
  • Innovative image and electrophysiology processing methods have been applied.
  • Novel analytic tools are described to study epileptogenesis after traumatic brain injury.


We describe the infrastructure and functionality for a centralized preclinical and clinical data repository and analytic platform to support importing heterogeneous multi-modal data, automatically and manually linking data across modalities and sites, and searching content. We have developed and applied innovative image and electrophysiology processing methods to identify candidate biomarkers from MRI, EEG, and multi-modal data. Based on heterogeneous biomarkers, we present novel analytic tools designed to study epileptogenesis in animal model and human with the goal of tracking the probability of developing epilepsy over time.


via Big data sharing and analysis to advance research in post-traumatic epilepsy

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[Abstract] Post-stroke epilepsy


Post-stroke epilepsy (PSE) is a major complication after stroke.

It is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention.

The current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE are covered in this review.


Post-stroke epilepsy (PSE) is a common complication after stroke, yet treatment options remain limited. While many physicians prescribe antiepileptic drugs (AED) for secondary prevention of PSE, it is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention. This review discusses the current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE.

Source: Post-stroke epilepsy

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[WEB SITE] Researchers Reveal New Possible Cause of Epilepsy – Neuroscience News

A team of researchers from Sanford-Burnham and SUNY Downstate Medical Center has found that deficiencies in hyaluronan, also known as hyaluronic acid or HA, can lead to spontaneous epileptic seizures. HA is a polysaccharide molecule widely distributed throughout connective, epithelial, and neural tissues, including the brain’s extracellular space (ECS). Their findings, published on April 30 in The Journal of Neuroscience, equip scientists with key information that may lead to new therapeutic approaches to epilepsy.

The multicenter study used mice to provide the first evidence of a physiological role for HA in the maintenance of brain ECS volume. It also suggests a potential role in human epilepsy for HA and genes that are involved in hyaluraonan synthesis and degradation.

While epilepsy is one of the most common neurological disorders—affecting approximately 1 percent of the population worldwide—it is one of the least understood. It is characterized by recurrent spontaneous seizures caused by the abnormal firing of neurons. Although epilepsy treatment is available and effective for about 70 percent of cases, a substantial number of patients could benefit from a new therapeutic approach.

Epilepsy is a brain disorder that causes seizures that disturb brain activity. Credit Sanford-Burnham Medical Research Institute.

“Hyaluronan is widely known as a key structural component of cartilage and important for maintaining healthy cartilage. Curiously, it has been recognized that the adult brain also contains a lot of hyaluronan, but little is known about what hyaluronan does in the brain,” said Yu Yamaguchi, M.D., Ph.D., professor in our Human Genetics Program.

“This is the first study that demonstrates the important role of this unique molecule for normal functioning of the brain, and that its deficiency may be a cause of epileptic disorders. A better understanding of how hyaluronan regulates brain function could lead to new treatment approaches for epilepsy,” Yamaguchi added.

The extracellular matrix of the brain has a unique molecular composition. Earlier studies focused on the role of matrix molecules in cell adhesion and axon pathfinding during neural development. In recent years, increasing attention has been focused on the roles of these molecules in the regulation of physiological functions in the adult brain.

In this study, the investigators examined the role of HA using mutant mice deficient in each of the three hyaluronan synthase genes (Has1, Has2, Has3).

“We showed that Has-mutant mice develop spontaneous epileptic seizures, indicating that HA is functionally involved in the regulation of neuronal excitability. Our study revealed that deficiency of HA results in a reduction in the volume of the brain’s ECS, leading to spontaneous epileptiform activity in hippocampal CA1 pyramidal neurons,” said Sabina Hrabetova, M.D., Ph.D., associate professor in the Department of Cell Biology at SUNY.

“We believe that this study not only addresses one of the longstanding questions concerning the in-vivo role of matrix molecules in the brain, but also has broad appeal to epilepsy research in general,” said Katherine Perkins, Ph.D., associate professor in the Department of Physiology and Pharmacology at SUNY.

“More specifically, it should stimulate researchers in the epilepsy field because our study reveals a novel, non-synaptic mechanism of epileptogenesis. The fact that our research can lead to new anti-epileptic therapies based on the preservation of hyaluronan adds further significance for the broader biomedical community and the public,” the authors added.


Contact: Susan Gammon, Ph.D. – Sanford-Burnham Medical Research Institute
Source: Sanford-Burnham Medical Research Institute press release
Image Source: The image is adapted from the Sanford-Burnham Medical Research Institute press release
Original Research: Abstract for “Hyaluronan Deficiency Due to Has3 Knock-Out Causes Altered Neuronal Activity and Seizures via Reduction in Brain Extracellular Space” by Amaia M. Arranz, Katherine L. Perkins, Fumitoshi Irie, David P. Lewis, Jan Hrabe, Fanrong Xiao, Naoki Itano, Koji Kimata, Sabina Hrabetova, and Yu Yamaguchi in Journal of Neuroscience. Published online April 30 2014 doi:10.1523/JNEUROSCI.3458-13.2014

Source: Researchers Reveal New Possible Cause of Epilepsy – Neuroscience News

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[Abstract] Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury – Epilepsia

Epilepsia. 2016 Jul 19. doi: 10.1111/epi.13470. [Epub ahead of print]

OBJECTIVE: Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified,but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury.METHODS: Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models andto internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism).RESULTS: The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747,and 0.716 for acute hospitalization, year 1, and year 2 models, respectively.SIGNIFICANCE: The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility.

Source: Traumatic Brain Injury Resource Guide – Research Reports – Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury

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[WEB SITE] Study explores development of epilepsy after brain injury – Health News

27/05/2015 10:15:00

Scientists at Newcastle University will carry out a pioneering study to look at the development of epilepsy following a serious brain injury.

Epilepsy can be triggered after traumatic brain damage such as a stroke, head trauma and some infections, yet no-one knows why some people go on to develop the life-threatening condition and others do not.

A team at Newcastle University has now been awarded more than £147,000 from leading charity, Epilepsy Research UK, to study epileptogenesis – a term used to describe how epilepsy arises after an injury to the brain.

Epileptogenesis involves a long and complex cascade of events, and what little is known about it mainly focuses on the latter stages, as seizures start to occur. Identifying what happens at the beginning, however, could lead to important breakthroughs and, ultimately, treatments to stop the serious condition developing.

The two-year project is being led by Dr Andrew Trevelyan, from Newcastle University’s Institute of Neuroscience, and it is one of only nine schemes nationwide in 2015 to receive a grant from the charity.

Dr Trevelyan (pictured) said: “We are delighted that Epilepsy Research UK are continuing to support our work.  Several years ago they provided me with the fellowship that helped to start my research group at Newcastle University, and which now includes eight people working full-time trying to understand what goes wrong during an epileptic seizure. That work led to key insights into how we identify from where in the brain the seizures arise.

“Now we want to understand how epilepsy might develop after an injury to the brain. This is a huge clinical problem because following such injuries, which include head trauma, strokes and some kinds of infection, there is a high risk of developing epilepsy.  But we cannot identify which people are at most risk, and even we could do so, we have no drugs to help them. What we need is the equivalent of the ‘morning after’ pill, to give people who have had a head injury or infection.”

Continue —>  Health News – Study explores development of epilepsy after brain injury.



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[WEB SITE] 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.

more –> Clinical Approach to Posttraumatic Epilepsy.

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