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
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.
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.
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.
Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury
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.
Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort
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.
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.
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.
An integrative in silico system for predicting dysregulated genes in the human epileptic focus: Application to SLC transporters
Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource-intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier (SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy.Methods
Using our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls.Results
There was a highly significant (p < 9.99 × 10−7) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability.Significance
The identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families.
Recent reports define temporal lobe epilepsy with amygdala enlargement (TLE-AE) as a distinct electroclinical syndrome comparable to TLE with hippocampal sclerosis. In this retrospective observational study, we present the largest consecutive series of patients with new-onset TLE-AE to date and describe clinical characteristics and seizure outcome, and we aim to explore underlying autoimmune mechanisms within this syndrome.Methods
We reviewed all consecutive patients between 2004 and 2014 at our tertiary epilepsy center at the University of Bonn, Germany, with new-onset (<5 years) TLE-AE, negative serum antibody (ab) test results, and with available follow-up data for at least 12 months.Results
We identified 40 patients (23 male) with TLE-AE with a median age at epilepsy onset of 51 years (range 10–73) and a median disease duration of 11 months (range 0.5–55) at first presentation. At follow-up, 50% of the entire cohort achieved seizure freedom. Of interest, patients with remittent features of AE at follow-up (N = 24) had a superior outcome compared to those with stable magnetic resonance imaging (MRI) features of AE (N = 16): 17 (71%) of 24 were seizure-free for at least 6 months compared to 3 (19%) of 16, respectively (p = 0.003). MRI volumetry confirmed significantly enlarged amygdalae in TLE-AE in relation to healthy controls, and additionally showed significantly greater volume reductions in patients with remittent AE compared to those with stable AE.Significance
TLE-AE is a clinical syndrome beginning mostly in middle age, and in addition to its known association with ab-positive limbic encephalitis, it occurs in an ab-negative condition. Remission of AE in the course of the disease could be identified as a predictor for a favorable clinical outcome and is suspicious of an autoimmune etiology, although we could not confirm this hypothesis unequivocally with currently available noninvasive diagnostic tools.
Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy.Methods
Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis.Results
Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3–3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0–4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3–3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8–5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0–2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1–2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0–3.5, p = 0.04) remained significantly associated with the presence of epilepsy.Significance
The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies.
Children with epilepsy and febrile seizures have a higher risk of developing attention deficit and hyperactivity disorder (ADHD), according to a new study published in the scientific journal Pediatrics.
This finding suggests that the parents of children with epilepsy or febrile seizures should be told to be vigilant about ADHD symptoms and pay close attention to academic performance, a factor easily influenced by ADHD. It also indicates that paediatricians should monitor all children with epilepsy or febrile seizures for ADHD. These measures will allow ADHD to be identified early and hopefully treated before symptoms develop further.
In a press release, Dr Josiane LaJoie, a paediatric neurologist at New-York University Langone Comprehensive Medical Center (who wasn’t involved this particular research), said: “It is vital that, when caring for a child with epilepsy, some of the medical visit involves attention to academic achievement and psychosocial functioning.”
During the study, a team from Aarhus University, in Denmark, alongside colleagues in Norway, collated medical data from more than 900,000 people born in Denmark between 1990 and 2007, for between five and 22 years (up to 2012). Approximately 13,500 (1.5%) were diagnosed with epilepsy and almost 34,000 (3.8%) experienced febrile seizures. More than 21,000 (2.3%) developed ADHD in this time period.
The researchers found that children with epilepsy were almost three times as likely to develop ADHD than those without epilepsy. The risk of developing ADHD was also approximately 20% to 35% higher in children with febrile seizures compared to children without.
The analysis took into account other risk factors that may have contributed to the development, such as socioeconomic status, low birth weight and a family history of epilepsy, febrile seizures or psychiatric disorders.
These results are striking, however the researchers were not able to show that epilepsy and febrile seizures actually caused ADHD in these people.
Previous studies have shown similar associations between epilepsy and febrile seizures, but the current one analysed a much larger number of subjects, over a longer period of time.
Epilepsy, febrile seizures, and ADHD are all conditions of the central nervous system. It is therefore not surprising that there is a link between them. All three conditions may share common genetic and environmental risk factors that may explain these associations, but further research is needed to confirm this.
Author: Dr Özge Özkaya
Click here to read more stories about living with epilepsy.
We investigated clinical factors associated with seizure clustering in patients with drug-resistant focal epilepsy and any association between seizure clustering and outcome after surgery. We performed a retrospective study including patients with a diagnosis of drug-resistant focal epilepsy who underwent epilepsy surgery. Patients were prospectively registered in a database from 1986 until 2015. Seizure cluster was defined as two or more seizures occurring within 2 days. Potential risk factors for seizure clustering were assessed. To investigate any potential association between seizure clusters and seizure outcome after surgery, time to event analysis was used to produce a Kaplan-Meier estimate of seizure recurrence. We studied 764 patients. Seizure clusters were reported in 23.6% of patients with temporal lobe epilepsy (TLE) and 16.9% of extratemporal patients (p = 0.2). We could not identify any significant clinical factors associated with seizure clustering. Among patients with TLE, those who had history of seizure clusters fared better after surgery (p < 0.01). We found that seizure clusters relate to prognosis after temporal lobe surgery in drug-resistant TLE. These data may provide added value for surgical prognostication when combined with other data types. A better understanding of the neurobiology underlying seizure clusters is needed.
Suicide rates are higher in people with epilepsy compared to the general population, according to results published in the journal Epilepsy and Behaviour. Suicide prevention measures should therefore be put in place to prevent such deaths.
Rosemarie Kobau, one of the authors of the study, commented: “Caregivers of people with epilepsy and other members of the public can participate in programs such as Mental Health First Aid, an evidence-based program available in many U.S. communities that teaches people about mental illness symptoms, and how to recognize and intervene during a mental health crisis.”
The programme also exists in England, and more information about it can be found on the Mental Health First Aid England webpage.
During the study, scientists from the US Centers for Disease Controls and Prevention (CDC) used data collected over eight years, between 2003 and 2011, to determine how often and in what circumstances suicide occurs in people with epilepsy.
They found that an average of 17 out of 100,000 people with epilepsy, aged 10 years and older, died from suicide each year during the study period, compared to 14 out of 100,000 in the general population.
The team then focused on people aged 40-49 years, and discovered that the suicide rates were 29% amongst those with epilepsy and 22% in the general population.
Looking at the relationships between suicide rate and a) race/ethnicity, b) education and c) marital status, there were no significant differences between the epilepsy and general population ‘groups’. In both, approximately one-third of suicides were committed by people with the lowest level of education.
When the researchers examined the locations in which the suicides occurred most, they found that 81% of people with epilepsy committed suicide in residential settings, compared to 76% of people without epilepsy.
This result suggests that it may be beneficial that caregivers, relatives, and others living with people with epilepsy to assess the availability of potentially harmful materials in the home to reduce the risk of suicide.
According to Samaritans, there were more than 6.500 suicides in the UK and Republic of Ireland in 2014. It is thought that there might be a link between epilepsy, psychiatric disorders and suicide.
If you feel that you, or someone you know is at risk of suicide, you can contact Samaritans any time, from any phone, on 116 123.
Author: Dr Özge Özkaya
Click here to read more stories about living with epilepsy.
Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes
The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions.Methods
We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]).Results
We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable.Significance
Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA.