What's Current?

Computer technology increasingly important in study of epilepsy

Epilepsy Research - Fri, 05/05/2017 - 11:37

Two recently published studies show just how important the use of computer technology and modelling have become in the study of epilepsy.

A study being carried out at Newcastle University is using a brain model to explore the cause of different epileptic seizure onset patterns. According to the study, at the onset of an epileptic seizure, differing characteristics of brain tissue surrounding the seizure’s origin site may determine which of two main patterns of brain activity will be seen. Electrical activity in the brain at the start of an epileptic seizure typically follows either a “low amplitude fast” pattern or a “high amplitude slow” pattern. Patients whose seizures follow the high amplitude slow pattern have a higher risk of continuing seizures after surgical treatment. However, the mechanisms underlying these different patterns are unclear.

To better understand the onset patterns, Yujiang Wang of Newcastle University, UK, and colleagues used a previously developed computer model that can simulate brain activity at the start of a seizure. The model output suggested that the onset pattern of a seizure may be determined not by brain tissue at the site where the seizure originates, but by characteristics of the surrounding “healthy” brain tissue.

The simulation showed that the high amplitude slow pattern occurs when surrounding brain tissue has higher excitability; that is, the brain cells have a stronger response to stimulation and can react immediately to the initiation of a seizure. Meanwhile, the low amplitude fast pattern is associated with tissue of lower excitability, which is only slowly penetrated by seizure activity.

These findings suggest why the different onset patterns are associated with different treatment outcomes. Surgical removal of seizure-triggering brain tissue may be enough to prevent seizure activity in nearby low-excitability tissue. However, high-excitability tissue may still be stimulated by alternative trigger sites after surgery, providing a possible explanation for the worse outcomes experienced by patients whose seizures follow the high amplitude slow pattern.

Next, the researchers plan to study seizure onset patterns in greater detail. “We hope to contribute towards the overall goal of associating patterns seen in seizures with an understanding of the underlying mechanism,” Wang says. “This would not only help our understanding of seizures in general, but may be useful for patient stratification in terms of treatment options.”

In a second study being carried out at Boston Children’s Hospital could enable more patients with epilepsy to benefit from surgery when medications do not help. The approach streamlines the seizure monitoring process required for surgical planning, making surgery a more feasible and less risky option for patients.

Currently, for some patients, pinpointing the diseased brain areas where their seizures originate requires invasive surgery to place grids of electrodes on the brain’s surface. This is followed by long-term electroencephalography (EEG) monitoring – typically for a week – while doctors wait for a seizure to happen. Then, patients must undergo a second brain operation to remove the diseased tissue.

The new technology, developed by Joseph Madsen, MD, Director of Epilepsy Surgery at Boston Children’s Hospital, and Eun-Hyoung Park, PhD, a computational biophysicist in the Department of Neurosurgery, could allow patients to be monitored in one short session, without the need to observe an actual seizure. Patients could then proceed directly to surgery, avoiding a second operation.

Effective use of this technology could cut the cost and risk by more than half by reducing the current two-stage procedure to one-stage, the researchers say.  “We know that the diseased brain network responsible for the seizures is there all along,” says Madsen. “So rather than wait for the patient to have a seizure, we set out to find patterns of interaction between various points in the brain that might predict where seizures would eventually start.”

To identify the brain areas causing the seizures, Madsen and Park applied a special algorithm to analyze patients’ interictal EEG data – data captured between their seizures. They randomly selected 25 patients with hard-to-treat epilepsy who previously had long-term EEG monitoring at Boston Children’s, and analyzed data from the first 20 seizure-free minutes of the patients’ EEGs.

Their algorithm, known as Granger causality analysis, is based on a statistical approach developed Sir Clive Granger (for which he won the Nobel Prize in Economics in 2003). Madsen and Park adapted the Granger method, originally used for economic forecasting, to calculate the probability that activity at one brain location predicts subsequent activity at other brain locations strongly enough to be considered causative. Their analysis generated a map of the causal relations in each patient’s epileptogenic network, which Park and Madsen superimposed over images of the brain.

They then showed that the brain regions predicted to be causing seizures strongly correlated with actual causative regions on seizure EEGs – as read by ten board-certified epileptologists, usually many days later.
Madsen and Park have shown that their calculations can be done quickly enough to allow data obtained in the operating room to potentially influence surgical decision-making. They now are investigating how the Granger causality method can best augment readings of EEGs by trained neurophysiologists.  “We still need to validate and refine our approach before it can be used clinically,” notes Madsen. “But we are hopeful that these advanced computer applications can help us treat more children with epilepsy – with less risk and lower cost.”

Article: Granger Causality Analysis of Interictal iEEG Predicts Seizure Focus and Ultimate Resection, Eun-Hyoung Park, PhD Joseph R. Madsen, MD, Neurosurgery, doi: 10.1093/neuros/nyx195, published 2 May 2017.

Article: Mechanisms underlying different onset patterns of focal seizures, Wang Y, Trevelyan AJ, Valentin A, Alarcon G, Taylor PN, Kaiser M, PLOS Computational Biology, doi: 10.1371/journal.pcbi.1005475, published 4 May 2017.

Categories: What's Current?

Brain model explores the cause of different epileptic seizure onset patterns

Medical News Today - Fri, 05/05/2017 - 03:00
At the onset of an epileptic seizure, differing characteristics of brain tissue surrounding the seizure's origin site may determine which of two main patterns of brain activity will be seen...
Categories: What's Current?

A thank you to West Lancashire Golf Club Ladies Captain Jackie Bickerstaffe

Epilepsy Research - Thu, 05/04/2017 - 12:24

Following a very successful Lady Captain’s Charity Evening on 11th March, a cheque for £4,858 was presented to Dr. Graeme Sills, Chairman of Epilepsy Research UK last weekend at the West Lancashire Golf Club.

Last year’s Ladies’ Captain Jackie Bickerstaffe introduced Dr. Sills to some of the main helpers at the fundraising event and presented the cheque totalling £4,858. She thanked everyone who had given so generously and Dr. Sills for coming to accept the Club’s donation.

Dr. Sills was delighted to attend and accept the cheque on behalf of Epilepsy Research UK and explained the work he does at Liverpool University into the understanding and treatment of epilepsy, a condition which affects a huge number of the population.

We in the Fundraising Office add our thanks to that of Dr. Sills to all at West Lancashire Golf Club, especially Jackie Bickerstaffe for nominating us as a beneficiary for such fantastic support of Epilepsy Research UK.

Pictured L to R are:
Paula Morris, Kiran Sharma, Linda Foy, Dr. Sills, Immediate Past Ladies’ Captain Jackie Bickerstaffe, Wayne Arands Asst. Catering Manager, Margaret McDowell and Immediate Past Captain Dr. Anil Sharma.

Categories: What's Current?

Reduced steroidogenesis in patients with PCDH19-female limited epilepsy

Epilepsia - Thu, 05/04/2017 - 08:35
Summary

Patients affected by protocadherin 19 (PCDH19)–female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age-matched controls. We also tested cortisol, estradiol, progesterone, and 17OH-progesterone using standard immunoassays. Apart from estradiol and progesterone, all the considered hormones were evaluated in basal condition and after stimulation with adrenocorticotropic hormone (ACTH). A generalized decrease in blood levels of almost all measured neuroactive steroids was found. When considering sexual development, cortisol and pregnenolone sulfate basal levels were significantly reduced in postpubertal girls affected by PCDH19-FE. Of interest, ACTH administration did not recover pregnenolone sulfate serum levels but restored cortisol to control levels. In prepubertal girls with PCDH19-FE, by challenging adrenal function with ACTH we disclosed defects in the production of cortisol, pregnenolone sulfate, and 17OH-progesterone, which were not apparent in basal condition. These findings point to multiple defects in peripheral steroidogenesis associated with and potentially relevant to PCDH19-FE. Some of these defects could be addressed by stimulating adrenocortical activity.

Categories: What's Current?

Pinpointing where seizures are coming from, by looking between the seizures

Medical News Today - Thu, 05/04/2017 - 03:00
A computational approach developed at Boston Children's Hospital, described in the journal Neurosurgery, could enable more patients with epilepsy to benefit from surgery when medications do not help.
Categories: What's Current?

Anxiety and depressive disorders in people with epilepsy: A meta-analysis

Epilepsia - Thu, 05/04/2017 - 00:30
Summary Objective

Comorbid anxiety and depressive disorders in people with epilepsy (PWE) are highly prevalent and associated with various adverse outcomes. However, the prevalence of anxiety disorders in PWE across studies is highly variable. Our aim was to estimate the prevalence and moderating factors of anxiety and depressive disorders in PWE.

Methods

Following prospective registration (PROSPERO; CRD42015027101), electronic databases were searched for studies that reported the prevalence of both anxiety and depressive disorders in samples of PWE up until July 2016. Data extracted included the prevalence of anxiety and depressive disorders, and moderators of interest (e.g., method of diagnosis, prevalence of drug-resistant epilepsy). Meta-analysis of the overall pooled prevalence of anxiety and depressive disorders was conducted.

Results

The search yielded 8,636 unique articles, with 27 studies meeting final inclusion criteria (3,221 PWE). The pooled prevalence of anxiety and depressive disorders was 20.2% (95% confidence interval [CI] 15.3–26.0%) and 22.9% (95% CI 18.2–28.4%), respectively. Method of diagnosis significantly moderated anxiety disorder prevalence (Q statistic with one degree of freedom [Q1] = 36.29, p < 0.0001); the prevalence of anxiety disorders based on unstructured clinician assessment was 8.1% (95% CI 5.7–11.4%), compared to a prevalence of 27.3% (95% CI 22.1–33.3%) based on a structured clinical interview. There were no significant moderators of depressive disorder diagnosis.

Significance

Findings suggest the prevalence of anxiety and depressive disorders in PWE are equivalent, and variability in prevalence of anxiety disorders across studies can be attributed partly to the method of diagnosis. These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy. Future research should aim to improve the detection and management of these comorbidities in PWE, particularly anxiety disorders, which have remained relatively neglected.

Categories: What's Current?

Long-term outcome in adolescent-onset generalized genetic epilepsies

Epilepsia - Tue, 05/02/2017 - 12:04
Summary Objective

Until now, it has been unclear if the three subsyndromes of adolescent-onset generalized genetic epilepsy (GGE) differ in long-term prognosis. Therefore, this study aimed to compare long-term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic–clonic seizures alone (EGTCS).

Methods

This retrospective study is based on the archive of an institutional tertiary care outpatient clinic for adult patients with epilepsy. Charts of 870 epilepsy outpatients were reviewed among whom 176 had adolescent-onset GGE (53 JAE, 66 JME, 57 EGTCS). Median patient age at investigation was 60 years; median follow-up time was 42.5 years. If possible, GGE patients were additionally interviewed on psychosocial and clinical variables.

Results

Age at first seizure was significantly higher in EGTCS patients (median 18 years) than in patients with JAE or JME (14 years each; p  0.001). Long-term seizure outcome hardly differed between the three subsyndromes. At the end of follow-up, 60% of all patients were in 5-year terminal seizure remission, and in 14%, epilepsy even had resolved (>10 years without seizures, >5 years without pharmacotherapy). Twenty percent of patients had persistent seizures during the last year of follow-up. Across all patients, 23% reported a psychiatric comorbidity, 87% had married, and 57% had achieved university entrance qualification.

Significance

Long-term outcome was shown to be highly similar across all subsyndromes of adolescent-onset GGE. Even in a selection of difficult-to-treat epilepsy patients still attending an adult epilepsy clinic, most become seizure-free. To confirm these findings, prospective studies are needed.

Categories: What's Current?

Electroclinical findings of minor motor events during sleep in temporal lobe epilepsy

Epilepsia - Tue, 05/02/2017 - 12:03
Summary Objective

It is well known that sleep-related motor seizures can originate from the temporal lobe. However, little is known about the clinical features of minor motor manifestations during sleep in patients with temporal lobe epilepsy. The main objective of our study was to verify the existence of minor motor events during sleep in patients with mesial temporal lobe epilepsy (MTLE) and to define their clinical features and electroencephalography (EEG) correlations.

Methods

We enrolled in the study patients with diagnosis of symptomatic MTLE and a group of healthy controls. All patients and controls underwent long-term video -EEG monitoring, including at least one night of nocturnal sleep. We analyzed all the movements recorded during nocturnal sleep of patients and controls and their electroencephalographic correlations.

Results

We analyzed the nocturnal sleep of 15 patients with symptomatic MTLE (8 males and 7 females; mean age ± standard deviation [SD]31.8 ± 14.9 years) and of 15 healthy controls (6 males and 9 females; mean age ± SD 32.8 ± 11.2 years). The analysis of movements during sleep revealed significant differences between groups, with the patients presenting significantly more movements in sleep than healthy controls (56.7 ± 39.2 vs. 15 ± 6.1; p < 0.001) with significant differences regarding oroalimentary automatisms, limb dystonia, straightening movements and gestural automatisms. EEG analysis showed that the proportion of movements preceded by EEG abnormalities was significantly higher in patients than in controls (57.8 ± 35.9 movements vs. 16.6 ± 13.4 movements; p < 0.001).

Significance

The results of our study demonstrated the presence of minor motor events during sleep in patients with MTLE, suggesting an epileptic origin of these episodes. The study of nocturnal sleep in MTLE patients is useful in helping the clinicians in the diagnostic and therapeutic workup of these patients.

Categories: What's Current?

Psychiatric and behavioral comorbidities in epilepsy: A critical reappraisal

Epilepsia - Tue, 05/02/2017 - 12:02
Summary

Psychiatric and behavioral disorders are important aspects of epilepsy and have received increasing attention in the last several years. The literature upon which most of the field relies contains some biases that must be carefully examined and resolved in future studies. First, in the pediatric epilepsy literature, many reports find that children with epilepsy have high levels of behavioral and psychiatric disorders when compared to appropriate controls. Most of these studies rely on parent-proxy completed instruments to assess these behavioral endpoints. Parents’ reports are not objective but reflect parents’ reactions and emotions. Increasing evidence suggests inherent biases in proxy reports and highlights the need to assess children directly. Second, periictal phenomena may be mischaracterized as underlying mood disorders. Third, many studies report elevated levels of psychiatric morbidity before and after the diagnosis of epilepsy, suggesting an inherent relation between the two types of disorders. Psychogenic nonepileptic seizures, while widely recognized as posing a diagnostic dilemma in the clinic, may account for some of these research findings. Diagnostic errors between epilepsy and psychogenic nonepileptic seizures need careful consideration when evaluating studies demonstrating associations between psychiatric disorders and epilepsy or poorer seizure control in association with psychiatric disorders in people who have epilepsy. Mental health concerns are important for everyone. An accurate, undistorted understanding of the relation between mental health disorders and epilepsy is essential to ensure appropriate therapy and to avoid unnecessary and potentially harmful treatments and common misconceptions.

Categories: What's Current?

Obstructive apnea due to laryngospasm links ictal to postictal events in SUDEP cases and offers practical biomarkers for review of past cases and prevention of new ones

Epilepsia - Tue, 05/02/2017 - 12:02
Summary

Seizure spread into autonomic and respiratory brainstem regions is thought to play an important role in sudden unexpected death in epilepsy (SUDEP). As the clinical dataset of cases of definite SUDEP available for study grows, evidence points to a sequence of events that includes postictal apnea, bradycardia, and asystole as critical events that can lead to death. One possible link between the precipitating seizure and the critical postictal sequence is seizure-driven laryngospasm sufficient to completely obstruct the airway for an extended period, but ictal laryngospasm is difficult to fully assess. Herein, we demonstrate in a rat model how the electrical artifacts of attempts to inspire during airway obstruction and features of the cardiac rhythm establish this link between ictal and postictal activity and can be used as practical biomarkers of obstructive apnea due to laryngospasm or other causes of airway obstruction.

Categories: What's Current?

Pinpointing where seizures are coming from, by looking between the seizures

Science Daily - Tue, 05/02/2017 - 08:41
A computational approach could enable more patients with epilepsy to benefit from surgery when medications do not help, report investigators.
Categories: What's Current?

Antidepressant may enhance drug delivery to the brain

Medical News Today - Tue, 05/02/2017 - 03:00
New research from the National Institutes of Health found that pairing the antidepressant amitriptyline with drugs designed to treat central nervous system diseases, enhances drug delivery to the...
Categories: What's Current?

Silent seizures recorded in the hippocampus of two patients with Alzheimer's disease

Science Daily - Mon, 05/01/2017 - 11:26
Investigators have identified silent, seizure-like activity in the hippocampus -- a brain structure significantly affected in Alzheimer's disease -- in two patients with Alzheimer's disease and no known history of seizures. These alterations in the brain's electrical activity could not be detected by standard EEG readings and primarily occurred during sleep, a time when memories are consolidated.
Categories: What's Current?

Pages