In one third of patients, seizures remain after epilepsy surgery, meaning that improved preoperative evaluation methods are needed to identify the epileptogenic zone. A potential framework for such a method is network theory, as it can be applied to noninvasive recordings, even in the absence of epileptiform activity. Our aim was to identify the epileptogenic zone on the basis of hub status of local brain areas in interictal magnetoencephalography (MEG) networks.Methods
Preoperative eyes-closed resting-state MEG recordings were retrospectively analyzed in 22 patients with refractory epilepsy, of whom 14 were seizure-free 1 year after surgery. Beamformer-based time series were reconstructed for 90 cortical and subcortical automated anatomic labeling (AAL) regions of interest (ROIs). Broadband functional connectivity was estimated using the phase lag index in artifact-free epochs without interictal epileptiform abnormalities. A minimum spanning tree was generated to represent the network, and the hub status of each ROI was calculated using betweenness centrality, which indicates the centrality of a node in a network. The correspondence of resection cavity to hub values was evaluated on four levels: resection cavity, lobar, hemisphere, and temporal versus extratemporal areas.Results
Hubs were localized within the resection cavity in 8 of 14 seizure-free patients and in zero of 8 patients who were not seizure-free (57% sensitivity, 100% specificity, 73% accuracy). Hubs were localized in the lobe of resection in 9 of 14 seizure-free patients and in zero of 8 patients who were not seizure-free (64% sensitivity, 100% specificity, 77% accuracy). For the other two levels, the true negatives are unknown; hence, only sensitivity could be determined: hubs coincided with both the resection hemisphere and the resection location (temporal versus extratemporal) in 11 of 14 seizure-free patients (79% sensitivity).Significance
Identifying hubs noninvasively before surgery is a valuable approach with the potential of indicating the epileptogenic zone in patients without interictal abnormalities.
A novel c132-134del mutation in Unverricht-Lundborg disease and the review of literature of heterozygous compound patients
Unverricht-Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132–134 of the coding sequence (c.132-134del) in the allele not including the dodecamer repetition. This mutation results in the loss of two amino acid residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn). Our patients presented a very different clinical picture. The male patient had a severe myoclonus, drug-resistant epilepsy and psychiatric comorbidity, while his affected sister had only very rare seizures and sporadic myoclonic jerks at awakening. The revision of literature about heterozygous compound EPM1 patients confirms this gender phenotypic expressivity, with female patients carrying less severe symptoms than male patients. These data lead to the hypothesis of complex gender-specific factors interacting with CSTB expressivity in EPM1 patients.
The burden of premature mortality of epilepsy in high-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy
Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
To evaluate treatment responses in benign familial neonatal epilepsy (BFNE).Methods
We recruited patients with BFNE through a multicenter international collaboration and reviewed electroclinical and genetic details, and treatment response. All patients were tested at minimum for mutations/deletions in the KCNQ2, KCNQ3, and SCN2A genes.Results
Nineteen patients were included in this study. A family history of neonatal seizures was positive in 16 patients, and one additional patient had a family history of infantile seizures. Mutations or deletions of KCNQ2 were found in 14, and of KCNQ3 in 2, of the 19 patients. In all patients, seizures began at 2–5 days of life and occurred multiple times per day. Four patients developed status epilepticus. Seizures were focal, alternating between hemispheres, and characterized by asymmetric tonic posturing associated with apnea and desaturation, followed by unilateral or bilateral asynchronous clonic jerking. Twelve of 19 patients were treated with multiple medications prior to seizure cessation. Seventeen of (88%) 19 patients were seizure-free within hours of receiving oral carbamazepine (CBZ) or oxcarbazepine (OXC). Earlier initiation of CBZ was associated with shorter hospitalization (p < 0.01). No side effects of CBZ were reported. All patients had normal development and remain seizure-free at a mean follow-up period of 7.8 years (6 months–16 years).Significance
This study provides evidence that CBZ is safe and rapidly effective in neonates with BFNE, even in status epilepticus. We propose that CBZ should be the drug of choice in benign familial neonatal seizures.
The maturation of adult-born granule cells and their functional integration into the network is thought to play a key role in the proper functioning of the dentate gyrus. In temporal lobe epilepsy, adult-born granule cells in the dentate gyrus develop abnormally and possess a hilar basal dendrite (HBD). Although morphological studies have shown that these HBDs have synapses, little is known about the functional properties of these HBDs or the intrinsic and network properties of the granule cells that possess these aberrant dendrites.Methods
We performed patch-clamp recordings of granule cells within the granule cell layer “normotopic” from sham-control and status epilepticus (SE) animals. Normotopic granule cells from SE animals possessed an HBD (SE+HBD+ cells) or not (SE+HBD− cells). Apical and basal dendrites were stimulated using multiphoton uncaging of glutamate. Two-photon Ca2+ imaging was used to measure Ca2+ transients associated with back-propagating action potentials (bAPs).Results
Near-synchronous synaptic input integrated linearly in apical dendrites from sham-control animals and was not significantly different in apical dendrites of SE+HBD− cells. The majority of HBDs integrated input linearly, similar to apical dendrites. However, 2 of 11 HBDs were capable of supralinear integration mediated by a dendritic spike. Furthermore, the bAP-evoked Ca2+ transients were relatively well maintained along HBDs, compared with apical dendrites. This further suggests an enhanced electrogenesis in HBDs. In addition, the output of granule cells from epileptic tissue was enhanced, with both SE+HBD− and SE+HBD+ cells displaying increased high-frequency (>100 Hz) burst-firing. Finally, both SE+HBD− and SE+HBD+ cells received recurrent excitatory input that was capable of generating APs, especially in the absence of feedback inhibition.Significance
Taken together, these data suggest that the enhanced excitability of HBDs combined with the altered intrinsic and network properties of granule cells collude to promote excitability and synchrony in the epileptic dentate gyrus.
Children with Epilepsy on the Ketonic Diet Should Have their Blood Selenium Levels Closely Monitored
An olive oil-based ketogenic-diet leads to a decline in selenium levels in children with drug-resistant epilepsy, according to a study published in the journal of Biological Trace Elements Research.
Previous research has shown that low amount of selenium, an element found in trace amounts in the blood that, may increase the risk of seizures. Therefore the levels of selenium in the blood of children with epilepsy who are on a ketogenic diet should be closely monitored.
For the study, the team led by Dr Orkide Guzel, at Behçet Uz Children Hospital in Izmir, Turkey, enrolled a total of 110 children with drug-resistant epilepsy, aged between three and 12 years, who were on ketogenic diet for at least 12 months.
The researchers measured the level of selenium in the children’s blood before the start of ketogenic diet treatment (baseline) and again at three, six and 12 months.
The results showed that although there were no significant differences in the level of selenium in the blood of the children after three months of treatment with ketogenic diet, selenium levels were significantly lower at six and 12 months compared with pre-treatment levels.
Almost half of the children (54 out of 110) were diagnosed with selenium deficiency, defined as selenium levels lower than 48 micrograms per litre, and treated with selenium supplements.
“The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element,” the authors wrote.
Author: Dr Özge Özkaya
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Neuroimaging offers a wide range of opportunities to obtain information about neuronal activity, brain inflammation, blood–brain barrier alterations, and various molecular alterations during epileptogenesis or for the prediction of pharmacoresponsiveness as well as postoperative outcome. Imaging biomarkers were examined during the XIII Workshop on Neurobiology of Epilepsy (XIII WONOEP) organized in 2015 by the Neurobiology Commission of the International League Against Epilepsy (ILAE). Here we present an extended summary of the discussed issues and provide an overview of the current state of knowledge regarding the biomarker potential of different neuroimaging approaches for epilepsy.
Impression Management Tactics May Positively Influence the Outcome of Job Interviews for People with Epilepsy
Impression management (IM) tactics, such as personal storytelling and self-promotion can have significant and positive effects on the outcome of job interviews for people with epilepsy, according to a study published in the scientific journal Epilepsia.
IM tactics could therefore be used as a “powerful strategy for empowering people with epilepsy to combat disability stigma, and offset negative perceptions of employers about the potential of this population to be productive workers,” according to the authors.
In order to determine the effect of assertive IM on the subjective impressions of the interviewers and outcome of job interviews, the team, led by Dr Fomg Chan, at the University of Wisconsin, carried out an experiment with 99 masters students in business or human resources.
They randomly assigned the students to one of three 15-minute videos of a job interview, where the candidate was applying for a position in computer sales. The candidate in the first video did not disclose any disability, the one in the second video had epilepsy but was not using any IM tactics and the candidate in the third video had epilepsy and was using IM tactics.
After watching the video, the researchers asked the students to rate the job applicant in terms of general impression and employability for the described position.
The results showed that IM tactics have a significant effect on the outcome of job interviews. The average rating of the students on both general impression and employability of an applicant with epilepsy who used IM tactics were significantly higher than for the applicant with epilepsy who did not use IM tactics.
It is important to note that the study has several limitations. For instance, the study participants were students and not actual business people. Moreover, the scenarios used in the study described an active athlete with epilepsy who had complete seizure control, however only a third of people with epilepsy actually have complete seizure control. “Hence, results should be interpreted with caution,” the authors wrote.
IM tactics are behaviours used by people to protect and promote their self-image and influence how they are perceived by others. Assertive IM tactics utilised in this study include actively constructing an image of oneself with a cohesive set of beliefs, opinions, characteristics, or experiences. Previous work has shown that IM tactics can influence the evaluation of a candidate by interviewers and the outcome of an interview including job offers.
Author: Dr Özge Özkaya
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A study published in the scientific journal, Epilepsia, shows that electronic diaries may help women with epilepsy who are planning a pregnancy adhere to treatment schedules.
The results of the study, conducted at New York University Langone Epilepsy Center, Mount Sinai School of Medicine and Brigham and Women’s Hospital, suggest that electronic diaries could be useful in clinical settings to enhance patient and medication management.
In a press release, the senior author of the study, Dr Jacqueline French, said: “Monitoring of medication adherence presents a tremendous challenge to clinicians and to clinical researchers. Poor adherence has been shown to negatively impact health care spending by resulting in more emergency room visits and hospitalizations, and may result in incomplete seizure control and increased risk of sudden death. Many times, patients do not report to their doctor about missed medication doses. This information could be used to discuss and improve compliance.”
Women with epilepsy who are pregnant are at particular risk of missing antiepileptic drug (AED) doses (e.g. due to sickness, or fear of harming their baby), but breakthrough seizures can be more harmful to both the mother and child (and so adherence to prescribed treatment is very important).
For the study, the researchers gave women with epilepsy who were planning to become pregnant an iPod Touch loaded with a customised mobile application called the WEPOD App that can track daily data.
A total of 86 women with epilepsy tracked their seizures and AED use and were included in the study. The researchers followed these women from the time of study enrolment throughout their pregnancy, and up to the birth of their child, or for women who did not become pregnant, for up to 12 months.
The results showed that 75% of women who used the electronic diary tracked their use of AEDs on a daily basis for more than 80% of the study period. These women were included in the data analysis and they showed a 97.7% adherence to medication. In addition, 44% of them admitted to missing an AED on at least one day.
Interestingly women who tracked their use of both AEDs and non-epilepsy medications reported a higher rate of adherence with AEDs than with other medications, suggesting that perceived importance of medications may influence adherence.
According to the authors the high rate of adherence may, in part, be a result of some of the electronic diary’s properties, such as daily reminders and real time feedback given to the provider.
Further research is needed to confirm these findings, and also to investigate how electronic diaries might help other groups of people with epilepsy (who aren’t women planning a pregnancy) adhere to their AED regimens.
Author: Dr Özge Özkaya
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A new imaging method could help predict which patients are likely to be free of seizures and which ones are likely to experience recurring seizures following brain surgery, according to a study published in the scientific journal Brain.
The authors state that there is very little information that can help predict the outcome of surgery in epilepsy, and that this study is the first to rigorously investigate the characteristics of the temporal lobe in a way that can help classify future seizures.
The team of international researchers, led by Dr Leonardo Bonilha, at the Medical University of South Carolina, analysed the tissue characteristics of certain areas of the temporal lobe known to be important in the generation and spread of temporal lobe seizures, using an MRI-based imaging technique called diffusion tensor imaging (DTI).
They studied 43 people with mesial temporal lobe epilepsy, who subsequently underwent surgery, and 44 healthy volunteers.
Approximately half of the patients (51.2%) were completely seizure-free following surgery, whilst the other 48.8% continued to experience seizures.
When they analysed the results of the DTI, the researchers saw that both the patients who were seizure-free and those who had recurrent seizures following surgery had abnormalities in white matter bundles (areas composed of nerve cell projections) in the temporal lobe, compared with healthy controls. However, certain abnormalities were only present in the brains of patients whose seizures persisted following surgery.
Surgery is a treatment option for some people with drug-resistant temporal lobe epilepsy, but in around half of the cases, it fails to prevent seizures. Being able to predict the outcome of brain surgery could be invaluable in deciding which patient should undergo surgery.
Author: Dr Özge Özkaya
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