What's Current?

Stress a common seizure trigger in epilepsy, study affirms

Science Daily - Mon, 04/03/2017 - 12:35
The relationship between stress and seizures has been well documented over the last 50 years. A recent review article looks at the stress-seizure relationship and how adopting stress reduction techniques may provide benefit as a low risk form of treatment.
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Neurological diseases cost the U.S. nearly $800 billion per year

Medical News Today - Mon, 04/03/2017 - 09:00
A new paper published in the Annals of Neurology reports the most common neurological diseases pose a serious annual financial burden for the nation.
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Reasons for discontinuation of reversible contraceptive methods by women with epilepsy

Epilepsia - Mon, 04/03/2017 - 08:05
Summary Objective

To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE).

Methods

These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18–47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories.

Results

Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54–2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category.

Significance

Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.

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An examination of biochemical parameters and their association with response to ketogenic dietary therapies

Epilepsia - Mon, 04/03/2017 - 08:01
Summary Objective

In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were β-hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI).

Methods

Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up were obtained from 13 adults and 215 children with KDT response data from participating centers. One hundred thirty-two (57%) of 228 participants had some data at both baseline and 3 months; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months; and 22 (10%) of 228 had no data. KDT response was defined as ≥50% seizure reduction at 3-month follow-up.

Results

Acetyl carnitine at baseline was significantly higher in responders (p < 0.007). It was not associated with response at 3-month follow-up. There was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3-month follow-up in KDT responders. There was also a trend for greater differences in levels of propionyl carnitine and in β-hydroxybutyrate measured at baseline and 3-month follow-up in KDT responders. No other biochemical parameters were associated with response at any time point.

Significance

Our finding that certain carnitine fractions, in particular baseline acetyl carnitine, are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT.

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Sporadic periventricular nodular heterotopia: Classification, phenotype and correlation with Filamin A mutations

Epilepsy Research Journal - Mon, 04/03/2017 - 00:00
Heterotopia is defined by the presence of groups of normal neurons in an inappropriate location, which results from a primary failure of neuronal migration, including periventricular, subcortical and leptomeningeal glioneuronal varieties (Barkovich et al., 2001; Barkovich et al., 2005; Barkovich et al., 2012; Guerrini and Barba, 2010). The most common clinical manifestations of heterotopia are epileptic seizures, mainly resistant focal seizures, neurological deficits, systemic malformations and developmental delays (Barkovich et al., 2012; Guerrini and Parrini, 2010).
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Structural brain changes in medically refractory focal epilepsy resemble premature brain aging

Epilepsy Research Journal - Mon, 04/03/2017 - 00:00
Medically refractory focal epilepsy is associated with decreased brain-wide volumetric measures and cognitive function, both of which are also observed in normal aging (Dabbs et al., 2012; Hoppe et al., 2007; Sowell et al., 2003; Salthouse, 2004). Prior studies have noted that epilepsy-related neuroanatomical and cognitive changes are greater than those observed in normal aging and therefore may be conceptualized as accelerated aging (Breuer et al., 2016; Lin et al., 2012; Bernhardt et al., 2009; Helmstaedter et al., 2003).
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A big data approach to the development of mixed-effects models for seizure count data

Epilepsia - Thu, 03/30/2017 - 08:00
Summary Objective

Our objective was to develop a generalized linear mixed model for predicting seizure count that is useful in the design and analysis of clinical trials. This model also may benefit the design and interpretation of seizure-recording paradigms. Most existing seizure count models do not include children, and there is currently no consensus regarding the most suitable model that can be applied to children and adults. Therefore, an additional objective was to develop a model that accounts for both adult and pediatric epilepsy.

Methods

Using data from SeizureTracker.com, a patient-reported seizure diary tool with >1.2 million recorded seizures across 8 years, we evaluated the appropriateness of Poisson, negative binomial, zero-inflated negative binomial, and modified negative binomial models for seizure count data based on minimization of the Bayesian information criterion. Generalized linear mixed-effects models were used to account for demographic and etiologic covariates and for autocorrelation structure. Holdout cross-validation was used to evaluate predictive accuracy in simulating seizure frequencies.

Results

For both adults and children, we found that a negative binomial model with autocorrelation over 1 day was optimal. Using holdout cross-validation, the proposed model was found to provide accurate simulation of seizure counts for patients with up to four seizures per day.

Significance

The optimal model can be used to generate more realistic simulated patient data with very few input parameters. The availability of a parsimonious, realistic virtual patient model can be of great utility in simulations of phase II/III clinical trials, epilepsy monitoring units, outpatient biosensors, and mobile Health (mHealth) applications.

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Taking a “Selfie” Could Trigger Seizure-Like Activity in the Brain, Case Study Suggests

Epilepsy Research - Thu, 03/30/2017 - 05:30

Taking “selfies” may trigger seizure-like activities in the brain, suggests a case study published in the scientific journal Seizure. The authors of the study Dr Paula Brna and Elizabeth Gordon at Dalhousie University in Canada suggest that taking “selfies” may represent a new area of caution for people with photosensitive epilepsies.

While conducting a routine assessment of epilepsy in young people with electroencephalogram (EEG) monitoring, the researchers noticed two sudden bursts of activity typically associated with epileptic seizures on the recordings of one teenager. The bursts of activity corresponded to the moment when the teenager had taken “selfies” on her smartphone.

Photosensitivity is a well-described phenomenon affecting a small proportion of people with epilepsy. Affected people are at risk of having a seizure when exposed to shimmering day light, strobe lights, and to lights flickering with a certain frequencies on television or computer screens.

The young person described in this study had previously demonstrated photosensitive myoclonus, or brief, shock-like, involuntary movements caused by muscle contractions triggered by light stimulation, on routine EEG.

It is not clear what exactly triggered the photosensitivity in this case. According to the authors, it could either be the phone’s flash or more likely, the flashing red light designed to reduce red eyes in the picture.

“There’s a lot of data already about selfies being potentially dangerous in some circumstances because people don’t think,” said Dr Brna, in a press release. “There are even reports about people taking selfies while driving … If you induced a seizure behind the wheel, that would be a catastrophe, potentially.”

Although this is a study that has been published in a peer reviewed scientific journal, it is important to note that it is a single case and more studies are needed to confirm these findings. However, if the phenomenon observed in this case is proven, it might be worth counselling people with epilepsy about the risks, according to the authors.

Author: Dr Özge Özkaya

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Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial temporal lobe epilepsy

Epilepsy Research Journal - Thu, 03/30/2017 - 00:00
Recordings of electrical brain activity with EEG during epileptic seizures reveal abnormal cortical hypersynchronization. Between seizures the EEG often shows interictal depolarizing phenomena such as spikes generated by assemblies of hyperexcitable neurons. When interictal spikes appear in a part of cortex it is considered an irritative zone. Seizures arise from the seizure onset zone. Often these zones are in close spatial proximity (de Curtis and Avanzini, 2001).
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Childhood-Onset Epilepsy Could Be Linked to Accelerated Brain Ageing

Epilepsy Research - Wed, 03/29/2017 - 05:00

Childhood-onset epilepsy could be associated with accelerated brain ageing, according to a new study published in JAMA Neurology. According to the authors, childhood onset epilepsy could therefore be considered a neurobiological predisposition to cognitive disorders in later life.

In order to determine whether adults with a history of childhood-onset epilepsy have an increased risk of accelerated cognitive impairment in later life, researchers led by Dr Matti Sillanpää at the University off Turku in Finland analysed 41 adults with childhood-onset epilepsy who were followed for more than 50 years from the onset of the condition, and 46 matched controls.

They found that people with childhood-onset epilepsy had increased levels of amyloid loads in their brain. Amyloids are protein fragments that accumulate in the brain with age. While in a healthy brain these proteins are broken down and eliminated, in brain disorders such as Alzheimer’s disease, they stick together and form amyloid plaques which are neurotoxic.

Interestingly, the researchers of the presents study found that people who carried a certain type of genetic variant called ε4 in their apolipoprotein E (APOE) gene had a particularly increased risk of having amyloid load in their brain in late middle age, as measured by positron emission tomography (PET) scan.

They concluded that APOE ε4 could be a biomarker indicating accelerated brain ageing  in people with epilepsy.

“Childhood-onset epilepsy appears to be associated with increased amyloid accumulation in late middle age, even among individuals in remission without antiepileptic drug therapy for decades,” the authors wrote. “The findings suggest a link between epilepsy, APOE genotype, and amyloid pathology”

They added that these findings prompt more research into brain ageing in people with epilepsy and that further follow-up with frequent amyloid assessments are needed to confirm these results.

Author: Dr Özge Özkaya

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Research sheds light onto how cellular defects caused by genetic mutation may lead to epilepsy

Epilepsy Research - Mon, 03/27/2017 - 05:13

A new study published in the leading scientific journal Scientific Reports describes how cellular abnormalities caused by defects in a gene called GRIN2A may lead to epilepsy.  Understanding the exact mechanism of how seizures develop at the cellular level could help scientists design better treatments against them in the future.

It was already known that mutations in the GRIN2A gene are associated with different types of childhood epilepsies. However the exact effect of the mutations on brain cells was not well understood.

In the present study, researchers led by Dr Daniel Ursu, at Eli Lilly Research Centre in Windlesham, Surrey showed that mutations in the GRIN2A gene lead to the GRIN2A protein being trapped inside nerve cells. The GRIN2A protein is normally found on the cell surface at the junctions between two nerve cells. There, it functions as a “channel” allowing the passage of electrical signals form one nerve cell to the other.

The researchers think that in the absence of GRIN2A protein, or if the GRIN2A protein does not function properly, the passage of electrical activity is affected, increasing the risk of epilepsy.

Importantly, the team showed that it was possible to restore the activity of the GRIN2A protein using a chemical compound in cells carrying the same mutations in the GRIN2A gene as in people with epilepsy. This is an exciting finding as it suggests that it may also be possible to restore the function of the GRIN2A in patients, offering a potentially treatment against seizures.

“This study is important as it shows that mutations in GRIN2A cause the protein produced to malfunction in different ways, leading to epilepsy,” said the first author of the study, Dr Laura Addis in a press release. “By understanding exactly what is going wrong in children with defects in GRIN2A, we can now try to work out what medicines target the pathways in the nerve cells that aren’t working properly”.

Professor Deb Pal at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London and a co-author of the study added: “Personalised medicine is the future of epilepsy treatment and will involve prescribing treatments based on the specific effects of a patient’s genetic defect”. He said that scientists need to develop methods to screen different medicines to see if they can restore the function of the defective GRIN2A protein. “As the mutations cause the protein to malfunction in different ways, we will need to work out strategies for the different types of effect,” he explained. “Some medicines will need to be able to get the protein to the cell surface, whereas others will need to make the protein work more, or less effectively, depending on the type of mutation.”

Author: Dr Özge Özkaya

 



 

What is GRIN2A?  Information from the US National Library of Medicine

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The impact of seizures on epilepsy outcomes: A national, community-based survey

Epilepsia - Mon, 03/27/2017 - 03:25
Summary Objective

The aim of this study was to examine the impact of seizures on persons living with epilepsy in a national, community-based setting.

Methods

The data source was the Survey of Living with Neurological Conditions in Canada (SLNCC), a cohort derived from a national population-based survey of noninstitutionalized persons aged 15 or more years. Participants had to be on a seizure drug or to have had a seizure in the past 5 years to meet the definition of active epilepsy. The respondents were further stratified by seizure status: the seizure group experienced ≥1 seizure in the past 5 years versus the no seizure group who were seizure-free in the past ≥5 years regardless of medication status. Weighted overall and stratified prevalence estimates and odds ratios were used to estimate associations.

Results

The SLNCC included 713 persons with epilepsy with a mean age of 45.4 (standard deviation 18.0) years. Fewer people in the seizure group (42.7%) reported being much better than a year ago versus those in the no seizure group (70.1%). Of those with seizures, 32.1% (95% confidence interval [95% CI] 18.8–45.3) had symptoms suggestive of major depression (as per the Patient Health Questionnaire-9) compared to 7.7% (95% CI 3.4–11.9) of those without seizures. Driving, educational, and work opportunities were also significantly limited, whereas stigma was significantly greater in those with seizures.

Significance

This community-based study emphasizes the need for seizure freedom to improve clinical and psychosocial outcomes in persons with epilepsy. Seizure freedom has an important influence on overall health, as those with at least one seizure over the prior 5 years had an increased risk of mood disorders, worse quality of life, and faced significantly more stigma.

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Research team develops first-of-a-kind model to research post-malaria epilepsy

Science Daily - Thu, 03/23/2017 - 12:54
A first-of-its-kind mouse model could lead to an understanding of how cerebral malaria infection leads to the development of epilepsy in children, and to the prevention of seizures. The model -- a way for researchers to simulate the effects of malaria in children by using mice -- was developed in a collaboration between researchers of medicine, engineering, science and agriculture.
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Long-term white matter tract reorganization following prolonged febrile seizures

Epilepsia - Thu, 03/23/2017 - 07:46
Summary Objective

Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer-term evolution is unknown. We investigated a population-based cohort to determine white matter diffusion properties 8 years after PFS.

Methods

We used diffusion tensor imaging (DTI) and applied Tract-Based Spatial Statistics for voxel-wise comparison of white matter microstructure between 26 children with PFS and 27 age-matched healthy controls. Age, gender, handedness, and hippocampal volumes were entered as covariates for voxel-wise analysis.

Results

Mean duration between the episode of PFS and follow-up was 8.2 years (range 6.7–9.6). All children were neurologically normal, and had normal conventional neuroimaging. On voxel-wise analysis, compared to controls, the PFS group had (1) increased fractional anisotropy in early maturing central white matter tracts, (2) increased mean and axial diffusivity in several peripheral white matter tracts and late-maturing central white matter tracts, and (3) increased radial diffusivity in peripheral white matter tracts. None of the tracts had reduced fractional anisotropy or diffusivity indices in the PFS group.

Significance

In this homogeneous, population-based sample, we found increased fractional anisotropy in early maturing central white matter tracts and increased mean and axial diffusivity with/without increased radial diffusivity in several late-maturing peripheral white matter tracts 8 years post-PFS. We propose disruption in white matter maturation secondary to seizure-induced axonal injury, with subsequent neuroplasticity and microstructural reorganization as a plausible explanation.

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Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study

Epilepsia - Thu, 03/23/2017 - 07:35
Summary Objectives

To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients.

Methods

Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS.

Results

The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1–16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2–14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity.

Significance

These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

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