What's Current?

Investigation of mechanisms of vagus nerve stimulation for seizure using finite element modeling

Epilepsy Research Journal - Wed, 07/27/2016 - 00:00
Vagus Nerve Stimulation (VNS) was FDA approved nearly 20 years ago in 1997, implanted in over 65,000 patients and yet its mechanisms of action in treating epileptic seizures remain unclear. While responder rates are over 50% for the 30–40% of patients who are resistant to anti-seizure medications, most responders do not become seizure-free, but rather have the severity and frequency of seizures reduced by approximately 40–50% on average (Amar et al., 2009; Wu and Sharan, 2013).
Categories: What's Current?

ERUK final report: A new technique to improve the diagnosis and treatment of epilepsy

Epilepsy Research - Tue, 07/26/2016 - 06:54

Background

Electroencephalography (EEG) is widely used in the diagnosis of epilepsy, but it relies on a person having a seizure whilst being monitored. This can lead to delays in diagnosis and treatment, unnecessary anxiety and reduced quality of life.

To try and address this problem, Professor John Terry, at the University of Exeter, has been working alongside neurologists in London to develop computer models that can detect ‘hidden’ information within brain networks, in short resting EEG recordings (during which no seizure has taken place), and accurately identify whether or not a person has generalised epilepsy.

The study

In 2012, Professor Terry and his team were awarded £139,595 to refine their models and find out whether they could:

  1. differentiate more accurately between people with and without generalised epilepsy.
  2. distinguish, based on differences in brain network properties, between people with focal and generalised epilepsy.
  3. identify, based the activity of neuronal networks, people who have responded to antiepileptic drug (AED) treatment and those who have not.

If successful, the models would have real potential  to enhance the diagnosis of epilepsy, and perhaps even allow neurologists to predict a) whether or not a person would respond to an AED, and b) what the best AED treatment for a person might be, thus reducing the time to optimal therapy.

This grant has now come to an end and the final report has been submitted.

Results

With regards to aims one and two above, the findings are extremely encouraging. The researchers now have a model that can distinguish with considerable accuracy, from resting EEG recordings, groups of people with generalised epilepsy from healthy controls (who do not have epilepsy). Professor Terry reports that in a test of 30 people with epilepsy and 38 without epilepsy, the model had a misdiagnosis rate of less than 5%. This is highly significant, and the team has already been exploring how they might incorporate the model into a clinical device. On the advice of feedback from commercial companies, they intend to develop a working prototype in the near future.

In terms of differentiating between people with focal and generalised epilepsy, the preliminary data obtained through this grant suggest that this should indeed be possible using computer network modelling. Professor Terry was awarded another ERUK project grant in 2015 to progress these findings and we look forward to hearing the outcome.

For a number of reasons, mainly an unexpected lack of viable resting EEG data from before and after AED treatment, it wasn’t possible to make a lot of progress on aim three. However, there has been significant follow-on funding generated from this grant, particularly from EPSRC, which will enable the team to carry out this research.

Significance

This grant has further highlighted the potential of computer models as clinical tools for the diagnosis and management of epilepsy. There is a lot more work to be done to establish their full potential, but the funding is in place and the preliminary evidence is encouraging. We are very excited about this work, as it stands to make a real difference to people’s treatment journeys and quality of life.

Click here to view our research portfolio.

Categories: What's Current?

A new genetic link to Temporal Lobe Epilepsy

Epilepsy Research - Tue, 07/26/2016 - 02:20

There may be an association between natural differences (known as polymorphisms) in a gene called ADAM10 and temporal lobe epilepsy, according to new research led by Dr Keshen Li from Jinan University in China.

The study, published in the scientific journal Frontiers in Neurology, is the first that shows such an association and suggests that by analysing these natural differences early on, it could be possible to predict someone’s risk of temporal lobe epilepsy.

The team of researchers examined the regulatory region of the ADAM10 gene in 496 people with temporal lobe epilepsy and in 528 healthy volunteers. They saw that in people with temporal lobe epilepsy the frequency of ‘component‘ A in the DNA was consistently increased compared to healthy controls, who had a higher frequency of component C at the same position on the DNA.

Further analyses suggested that the presence of A on both chromosomes at that location could be a factor that makes people more susceptible to temporal lobe epilepsy, whilst having one A and one C could be protective against generalised tonic-clonic seizures and drug resistant temporal lobe epilepsy.

It is important to note that all of the people recruited to this study were of Han Chinese decent and that the genetic polymorphisms might be different in other ethnic groups. The authors write: “Caution should be exercised before generalizing these findings to other ethnic populations.” However, at the very least these findings will guide future research that could ultimately lead to new diagnostic techniques and better treatments for temporal lobe epilepsy.

It is known that there are as many as 6,771 polymorphisms in the ADAM10 gene, which encodes for a cell-surface protein crucial in Alzheimer’s disease. Two of these differences, found in the regulatory region of the gene, are particularly important because they have been shown to decrease or ‘downregulate’ the expression* of the ADAM10 gene and give rise to epileptic seizures in Alzheimer’s disease.

Experiments in rodents have also shown that downregulating ADAM10 results in repetitive seizures, which may well mean that low levels of ADAM10 can also cause seizures in people. A ‘reverse’ experiment showed that in mice where ADAM10 was mildly overexpressed, induced seizures were less severe and recovery times were shorter, again suggesting that ADAM10 may be protective against seizures.

* The term ‘gene expression’ refers to the process by which information from a gene is used to create a functioning gene product, very often a protein.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

Categories: What's Current?

New findings could help scientists prevent the Development of Epilepsy

Epilepsy Research - Mon, 07/25/2016 - 14:14

Scientists at Louisiana State University, and at Spain’s University of Alcala, have developed compounds that can prevent seizures in a rodent model of epilepsy. They believe that so-called ‘neuroprotective’ compounds like these may also prevent epilepsy in humans in the future.

In earlier work, the team screened a range of compounds that block a specific inflammatory molecule in neurons, and discovered that one in particular, LAU-0901, stopped seizures in epilepsy models. In the current study they focused on LAU-0901, and a more refined version of it known as LAU-09021, to try and find out exactly how they work.

They found that the compounds’ actions preserved dendritic spines, which are vital to communication between neurons. Dendritic spines are damaged during seizures and other ‘insults’, causing a chain of events that make neurons hyperexcitable, which promotes the development of epilepsy. The team discovered that the animals were still protected from seizures up to 100 days after treatment with LAU-09021, suggesting that the process of epilepsy development had been arrested.

These findings, published in the journal Scientific Reports, indicate that, in the future, new therapies that preserve dendritic spines could potentially stop seizures and prevent the development of epilepsy.

Senior Author Dr Nicolas Bazan, at the Louisiana State University Health Sciences Center, said: “Most of the anti-epileptic drugs currently available treat the symptom – seizures – not the disease itself. Understanding the potential therapeutic usefulness of compounds that may interrupt the development process may pave the way for disease-modifying treatments for patients at risk for epilepsy.”

Click here for more articles about brain science including genetics.

 

Categories: What's Current?

Novel compounds arrested epilepsy development in mice

Medical News Today - Mon, 07/25/2016 - 03:00
A team led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans' Neuroscience Center of Excellence, has developed neuroprotective compounds that may prevent the...
Categories: What's Current?

US suicide rate for people with Epilepsy exceeds levels in general population

Medical News Today - Mon, 07/25/2016 - 03:00
Researchers at Columbia University's Mailman School of Public Health and the Centers for Disease Control studied the prevalence of suicide among people with epilepsy compared to the population...
Categories: What's Current?

New Method to look at Synapses in the Living Human Brain

Epilepsy Research - Sat, 07/23/2016 - 15:44

Researchers at Yale University have developed a new, non-invasive method to examine synapses – the points of communication between neurons. The work is published in the leading journal Science Translational Medicine.

In the future, this novel technique could improve the diagnosis and treatment of epilepsy, and of other neurological conditions.

In a press release, Dr Richard Carson, Professor of Radiology and Biomedical Imaging and Senior Author of the study, said: “This is the first time we have synaptic density measurement in live human beings. Up to now any measurement of synaptic density was post-mortem (after death).”

The researchers developed a radioactive tracer that binds to a protein called SV2A, found at synapses. They injected the tracer into the body and, using a type of imaging called positron emission tomography (PET), were able to visualise synapses in the brain of animals, healthy people and people with epilepsy. They then used mathematical tools to calculate synaptic density, the number of functional synapses per volume of brain tissue, to assess how much and how well the subjects’ neurons were communicating. They discovered that in the brains of people with temporal epilepsy, synaptic density measurements reflected damage to certain regions.

The scientists hope that this method can eventually be used routinely, to monitor the course of various neurological conditions, including epilepsy, and assess how well certain drugs are working. Its non-invasive nature will help make assessment a more comfortable and less daunting experience for patients, which is so important.

There are trillions of synapses in the brain, which transmit signals from one neuron to another. Changes in the density of synapses are associated with a number of neurological disorders, including epilepsy.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

Categories: What's Current?

Novel compounds arrested epilepsy development in mice

Science Daily - Fri, 07/22/2016 - 09:29
Neuroprotective compounds have been developed by scientists that may prevent the development of epilepsy. The researchers explained that the compounds prevented seizures and their damaging effects on dendritic spines, specialized structures that allow brain cells to communicate. In epilepsy, these structures are damaged and rewire incorrectly, creating brain circuits that are hyper-connected and prone to seizures, an important example of pathological plasticity.
Categories: What's Current?

The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts

Epilepsia - Thu, 07/21/2016 - 01:45
Summary Objective

Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage-gated sodium (NaV) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.

Methods

Immunocytochemistry was performed on primary calvarial osteoblasts extracted from neonatal C57BL/6J mice and additional RNA sequencing (RNASeq) was included to confirm expression of NaV. Whole-cell patch-clamp recordings were made to identify the native currents expressed and to assess the actions of carbamazepine (50 μm) or phenytoin (50 μm).

Results

NaV expression was demonstrated with immunocytochemistry, RNA sequencing, and functionally, with demonstration of robust tetrodotoxin-sensitive and voltage-activated inward currents. Application of carbamazepine or phenytoin resulted in significant inhibition of current amplitude for carbamazepine (31.6 ± 5.9%, n = 9; p < 0.001), and for phenytoin (35.5 ± 6.9%, n = 7; p < 0.001).

Significance

Mouse osteoblasts express NaV, and native NaV currents are blocked by carbamazepine and phenytoin, supporting our hypothesis that AEDs can directly influence osteoblast function and potentially affect bone strength.

Categories: What's Current?

Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE – Commission on European Affairs and the European Epilepsy Monitoring Unit Association

Epilepsia - Thu, 07/21/2016 - 01:45
Summary

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)—Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.

Categories: What's Current?

Scientists apply new imaging tool to common brain disorders

Science Daily - Wed, 07/20/2016 - 14:35
A new approach has been developed to scanning the brain for changes in synapses that are associated with common brain disorders. The technique may provide insights into the diagnosis and treatment of a broad range of disorders, including epilepsy and Alzheimer's disease, say authors of a new report.
Categories: What's Current?

FDA accepting comments on draft guidelines on compounding law

Clinical Neurology News - Wed, 07/20/2016 - 10:51

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A <a...

Categories: What's Current?

Erratum

Epilepsia - Wed, 07/20/2016 - 08:01
Categories: What's Current?

People with Epilepsy are more likely to be Smokers, Study Suggests

Epilepsy Research - Wed, 07/20/2016 - 05:15

There is a strong correlation between epilepsy and smoking according to a study of people living in French-speaking Switzerland.

Although it has yet to be established whether or not epilepsy actually causes smoking, there appears to be a genetic link between susceptibility to epilepsy and to nicotine addiction. There is also a more indirect association, as people find benefit in smoking to relieve stress or depression associated with epilepsy.

For the study, published in the Journal of Neurology, a team of scientists led by Dr Fabienne Picard, from University Hospitals and Medical School of Geneva, analysed 429 people, aged 16 years and older, who had epilepsy and who lived in French-speaking Switzerland.

The data were compared with those from the ‘Tabakmonitoring’ database, which provides annual, detailed information about tobacco use habits in Switzerland’s ‘general’ population, according to linguistic region.

For the epilepsy group, a questionnaire requesting information about their epilepsy type and smoking habits was sent to neurologists to complete with their epilepsy patients. Being a ‘current smoker’ was defined as having had at least one cigarette per day for the previous six months.

Sixteen of the questions were about tobacco consumption (frequency, amount, type, attempts at cessation), and 13 questions were about the type of epilepsy the person had. Four of the questions explored the possible link between epilepsy and smoking (two concerned the relationship between the timings of epilepsy onset and the starting smoking) and two looked at the possible subjective effect of tobacco consumption on seizure frequency. Three questions were about general health (including two screening questions about depression).

The results showed that 32.1% of people with epilepsy were smokers, compared to 19% of the ‘general’ French-speaking Swiss population. The highest prevalence of smoking was seen amongst people with idiopathic generalised epilepsy (44.3%) compared to 27.8% for other types of epilepsy.

These findings are important because they suggest that people with epilepsy may need additional education and support concerning the issue of smoking. Future studies will hopefully focus on understanding the mechanism underlying the relationship between tobacco smoking and epilepsy, so measures to ‘address’ it can be developed.

Author: Dr Özge Özkaya

Click here to read more stories about living with epilepsy.

 

Categories: What's Current?

Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury

Epilepsia - Tue, 07/19/2016 - 08:20
Summary 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 and to 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.

Categories: What's Current?

Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort

Epilepsia - Tue, 07/19/2016 - 08:15
Summary Objectives

To evaluate the effectiveness of lacosamide (LCM) in pediatric patients, using time to treatment failure as the outcome measure, and to assess the impact of concomitant sodium channel blocker (SCB) use on LCM retention.

Methods

This is a retrospective cohort study of patients <21 years old receiving LCM from 2010 to 2015. Kaplan-Meier survival curves were generated for time to LCM failure, defined as discontinuation of LCM or addition of another antiepileptic therapy. The impact of concomitant use of traditional SCB agents (phenytoin, carbamazepine, oxcarbazepine, and/or lamotrigine) and other factors including age, seizure types, fast drug titration, and prior antiepileptic drug history were evaluated using Cox regression.

Results

The analysis cohort included 223 patients, of whom 116 were taking one or more SCBs, with median follow-up of 7.4 months (1–53 months). For all patients, the probability of remaining on LCM without addition of another therapy was 44.7% at 12 months and 25.6% at 24 months. Concomitant SCB use was an independent predictor of time to LCM failure (hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.38–2.65, p < 0.001).Although treatment emergent adverse effects were reported more often in patients taking SCB (65% vs. 39%, p < 0.001), intolerability was rarely the sole reason cited for LCM discontinuation, and SCB use was strongly associated with LCM failure, even when controlling for presence of treatment emergent adverse effects (adjusted HR 1.99, 95% CI 1.36–2.90, p < 0.001).

Significance

This study provides observational evidence for treatment persistence of LCM in children, in a large cohort with long-term follow-up, using time to treatment failure as the outcome measure. Concomitant SCB use was a key factor increasing risk of LCM failure, but not due to treatment-emergent adverse effects alone.

Categories: What's Current?

New evidence that Nighttime Seizures Disrupt Memory Consolidation

Epilepsy Research - Tue, 07/19/2016 - 05:31

Nighttime seizures disrupt sleep-dependent memory consolidation, according to a pilot study published in the journal Clinical Neurophysiology.

This finding is important, because it will help scientists to better understand the effect of seizures on memory consolidation, and the factors that may influence this. There is currently only limited data in adults, and some conflicting data in children, regarding sleep dependent memory consolidation in epilepsy, although the association is not new.

For the current study, a team led by Dr Ellen Bubrick, from Harvard Medical School, in Boston, recruited 11 people with focal epilepsy aged between 21 and 56 years.

The researchers asked the subjects to complete a memory test, during which they were required to remember the positions of 15 pairs of coloured images of animals and everyday objects, on a 5 x 6 matrix. Participants were first shown where the object pairs were located (the ‘training’ stage), and then asked to remember this after either 12 hours of continuous wakefulness, or 12 hours that included sleep.

The results showed that memory retention after 12 hours of wakefulness was 62.7%, but this increased to 83.6% when the 12-hour period included sleep. This suggests that sleep enhances memory consolidation in epilepsy.

During the study, three of the participants had daytime seizures and three had nighttime seizures. The scientists found that the daytime seizures had no effect on memory, as assessed, but that nighttime seizures resulted in a drop in retention rates.

Memory difficulties are commonly seen in people with epilepsy, and these can sometimes be more debilitating than the seizures themselves. If the effects of seizures on sleep-dependent memory seen here are confirmed in larger studies, it may be possible to develop ways of managing them in the future.

Author: Dr Özge Özkaya

Click here to read more stories about living with epilepsy.

 

 

Categories: What's Current?

New Project Could Help reduce Memory Loss Following paediatric epilepsy Surgery

Epilepsy Research - Mon, 07/18/2016 - 05:09

The US National Institute of Health (NIH) has awarded Dr Noa Ofen and colleagues, at Wayne State University in Detroit, $1.9 million (almost £1.5 million), over five years, to examine the formation of memory networks in the developing brain.

Dr Ofen hopes her findings will be applied to paediatric epilepsy surgery, to help predict and reduce the risk of subsequent memory problems.

Dr Ofen comments: “Little is known about how memory systems develop in the human brain. In this project, we will use a combination of unique neuroimaging methodologies that allow us to add new insights about the neural basis of memory development. We also hope this project will be a first step toward clinical applications that can ultimately improve the quality of life of children with focal epilepsy.”

For the study, the researchers will take electrical recordings using electrodes directly implanted on the surface of the brain, whilst the person performs standard memory tasks. This method, known as electrocorticography (ECoG), is highly invasive, and so subjects will be children with focal epilepsy, who are undergoing pre-surgical assessment and need to have ECoG as part of this. The technique will allow the researchers to examine exactly what neurons are doing during memory formation, and study, in real time, information that is predictive of whether information/experiences will be remembered after surgery.

The team will use the information gained during ECoG to map memory networks within the brain. They will also collect functional MRI data from a subset of the children, and from a large number of healthy controls, to try and determine how age naturally affects the activation of and connections between major regions of memory networks.

This project will be instrumental in identifying, in great detail, the functions of memory networks in the developing brain. The team also hopes to extend the mapping of memory networks to key areas of the brain, so that measures can be taken to avoid damaging these during epilepsy surgery. This will help to reduce the risk of subsequent memory problems and greatly improve quality of life.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

Categories: What's Current?

Pages