This spring James Brady, Jack Carr & James ‘Beans’ Low, Lyle’s very own #MarathonMen, are going to be running in the London marathon in memory of Tom Moulton in aid of Epilepsy Research UK.
So aside from training ahead of the marathon, the lads now need to raise some funds! Enter the #MarathonMen Charity Lunch.
On Sunday 12th February the boys will be hosting a lunch at Lyle’s,Tea Building, 56 Shoreditch High Street, London, E1 6JJ.
James Brady will be cooking a three-course set lunch, and you will receive the finest of service from the other two men, Jack Carr and James Low.
Tickets to the #MarathonMen Charity Lunch are £29 and include the menu and a drink on arrival. All profits go to support epilepsy research. For sample menus, dietary info and to book your tickets, please contact the boys via email.
Illustration by Florence Poppy Deary
Utility of gray-matter segmentation of ictal-Interictal perfusion SPECT and interictal F-FDG-PET in medically refractory epilepsy
Time to electroencephalography is independently associated with outcome in critically ill neonates and children
To identify factors associated with in-hospital mortality in neonates and children undergoing continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU).Methods
We performed a retrospective observational study in patients from birth to 21 years of age who underwent clinically indicated cEEG in the ICU from 2011 to 2013. The main outcome measure was in-hospital mortality.Results
Six-hundred and twenty-five patients (54.2% male) met eligibility criteria, of whom 211 were neonates (55% male, 24.8% premature) and 414 were pediatric patients (53.9% male). Electrographic seizures occurred in 176 patients (28.2%) and status epilepticus (SE) occurred in 20 (11.4%). The time from ICU admission to cEEG initiation was 16.7 (5.1–94.4) h. Eighty-nine patients (14.2%) (30 [14.2%] neonates, and 59 [14.3%] pediatric patients) died in the hospital. In neonates—after controlling for gender and prematurity—independent factors associated with mortality were prematurity (odds ratio [OR] 2.63. 95% confidence interval [CI] 1.06–6.5, p = 0.037), presence of status epilepticus (SE); OR 8.82, 95% CI 1.74–44.57, p = 0.008), and time from ICU admission to initiation of cEEG (OR 1.002, 95% CI 1.001–1.004 per hour, p = 0.008]. In pediatric patients—after controlling for gender and age—independent factors associated with mortality were the absence of seizures factors associated with mortality were absence of seizures (OR = 4.3, (95% CI: 1.5–12.4), p = 0.007), the presence of SE (OR 7.76, 95% CI 1.47–40.91, p = 0.016), and the time from ICU admission to initiation of cEEG (OR 1.001, 95% CI 1.0002–1.001, per hour, p = 0.005].Significance
Both presence of electrographic SE and time from ICU admission to cEEG initiation were independent factors associated with mortality in neonates and pediatric patients with cEEG in the ICU.
Researchers have shown for the first time that sleep-related memory consolidation is intact in a group of children with focal epilepsy.
It is known that children with epilepsy have high rates of impairment in both cognitive function (including memory) and sleep. Therefore doctors have previously assumed that sleep-dependent memory consolidation might be compromised in children with epilepsy. Not so, apparently.
“Our results suggest that sleep-related memory consolidation is an extremely robust mechanism,” wrote Dr Samantha Chan and co-authors of study that was conducted at Great Ormond Street Hospital (GOSH) in London and published in the journal Epilepsia.
The team analysed 22 children with focal epilepsy aged 6 to 16 years, and 21 children of the same age without epilepsy. In the evening, before bedtime, the children were taught groups of words (verbal task) and shown the location of objects on a flat surface (visuospatial task). The next morning, following a night’s sleep, the children were asked to remember the words and the position of the objects. The process was then repeated, this time with the initial training in the morning and recall at the end of the day. The team then compared the retention of memory in the morning and in the evening for each child.
In children without epilepsy, the researchers found that, as expected, memory retention was greater in the morning, after a night’s sleep, for both verbal and visuospatial tasks, when compared with recall at the end of the day. Moreover, children with longer periods of slow-wave sleep (when memory consolidation occurs) had better memory retention in the verbal task.
Interestingly, the scientists observed that memory retention was also greater after a night’s sleep in children with epilepsy. However, when the rate of abnormal electrical activity in the brain (recorded by EEG) was high at night, sleep-dependent memory consolidation in both verbal and visuospatial tasks were reduced.
The researchers also found that children with the longest duration of epilepsy and those whose seizures arose from the temporal lobe, an area of the brain that is important for making sense of speech, had poorer verbal and visuospatial memory consolidation during the day and were therefore more dependent on sleep for good overall memory retention.
The researchers concluded that sleep enhances memory consolidation to the same degree in children with focal epilepsy as in children without epilepsy and that the most likely factor affecting memory retention is night-time electrical discharges happening in-between seizures.
Author: Dr Özge Özkaya
Click here for more news articles about epilepsy in children.
People with Epilepsy Using Perampanel (FycompaTM) Should Be Closely Monitored due to Increased Risk of Falls, Study Suggests
People with epilepsy taking perampanel (FycompaTM) should be counselled and monitored against the risk of falls according to a study published in the journal Epilepsia.
The recommendation is based on the finding of three Phase 3 clinical trials testing the safety and efficacy of different doses of perampanel in people with drug resistant partial seizures and one Phase 3 clinical trial testing the drug in primary generalised tonic clonic seizures.
The study systematically reviewed the occurrence of falls in 1,480 people with drug resistant partial seizures and 163 people with primary generalised tonic clonic seizures aged 12 years and over. Falls that were the result of a seizure were not included in the analysis.
The results showed that 5.1% of people with drug resistant partial seizures experienced falls related to perampanel treatment, compared with just 3.4% of those treated with placebo (or dummy pill). For people with primary generalised tonic clonic seizures, these proportions were 2.5% and 1.2% respectively. Falls were also more common in those on higher doses of perampanel.
The researchers concluded that people with epilepsy taking perampanel should be closely monitored due to the increased risk of falls. “Clinicians need to be aware of and counsel patients about the potential for an increased risk of falls when treating with perampanel, especially at higher doses,” wrote Dr Ilo Leppik, who led the study.
However the authors added that in spite of the increased risk of falls, especially in the elderly, higher doses of perampanel could also provide a benefit in controlling seizures and reducing their frequency. “Appropriate treatment should be individualized by taking the patient profile into consideration,” they wrote.
Perampanel is sold under the trade name FycompaTM and used in combination with other antiepileptic drugs to treat partial seizures and generalized tonic clonic seizures in people with epilepsy aged 12 and over.
Side effects associated with the use of the drug include dizziness, somnolence, fatigue, aggression and irritability, as well as increased risk of falls.
Author: Dr Özge Özkaya
Click here for more articles about anti-epileptic drugs and pregnancy risks.
Surgery performed in an area of the brain called the posterior cortex is highly effective in controlling seizures and in leading to the discontinuation of antiepileptic drugs (AEDs) in children and adolescents with epilepsy, according to a study published in the scientific journal Epilepsia.
Interestingly, the sooner surgery is performed after the diagnosis of epilepsy, the more likely it is that patients will remain seizure free as a result.
According to the authors of the study, their findings emphasize the importance of considering brain surgery relatively early in young patients with drug resistant (or refractory) posterior cortex epilepsy.
The research team was led by Dr Thomas Bast at Epilepsy Center Kork in Germany and analysed data from 50 children and adolescents with drug resistant posterior cortex epilepsy who underwent surgery during which a portion of their brain was removed. All of the children apart from one had an area of abnormality (a lesion) in their brain that was visible in the MRI scan before surgery.
The patients were followed for eight years on average after surgery. Sixty percent of them remained seizure free in this period of time. Around one third of patients discontinued their AEDs following surgery and, one fifth reduced their use. In cases where seizures recurred, 70% happened in the first six months following surgery. Only three patients had a seizure recurrence two or more years after surgery.
Children for whom the seizure-causing region was on the left side of the brain or in a region called the parietal lobe were more likely to have recurrent seizures. Likewise, those with a longer duration between diagnosis and surgery were more likely to have a recurrence of their seizures after surgery.
“Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates”, wrote the authors. “Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy”.
Around one third of people with epilepsy do not respond to currently available AEDs. Some of these people with so-called drug resistant epilepsy can benefit from brain surgery.
Author: Dr Özge Özkaya
Click here for more articles about other treatments for epilepsy.
Shedding light on interictal epileptic spikes: An in vivo study using fast optical signal and electrocorticography
Interictal epileptic spikes (IESs), apart from being a key marker of epileptic neuronal networks, constitute a nice model of the widespread endogenous phenomenon of neuronal hypersynchronization. Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unresolved, but synaptic as well as nonsynaptic events are likely to be involved. In this study, changes in optical properties of neural tissues were observed in rats with penicillin-induced IES using fast optical signal (FOS) concomitantly with electrocorticography (ECoG).Methods
In this study, near-infrared optical imaging was used with ECoG to investigate variations in the optical properties of cortical tissue directly associated with neuronal activity in 15 rats. FOS changes correspond to variations of scattered light from neuronal tissue when neurons are activated. To independently evaluate our method, a control experiment on somatosensory was designed and applied to seven different rats. Time-frequency analysis was also used to track variations of (de)synchronization concomitantly with changes in optical signals during IES.Results
FOS responses revealed that changes in optical signals occurred 320 msec before to 370 msec after the IES peak. These changes started before any changes in ECoG signal. In addition, time-frequency domain electrocorticography revealed an alternating decrease-increase-decrease in the ECoG spectral power (pointing to desynchronization-synchronization-desynchronization), which occurred concomitantly with an increase-decrease-increase in relative optical signal during the IES. These results suggest a relationship between (de)synchronization and optical changes.Significance
These changes in the neuronal environment around IESs raise new questions about the mechanisms that induce changes in optical properties of neural tissues before the IES, which may provide suitable conditions for neuronal synchronization during IESs. FOS-ECoG constitutes a multimodal approach and opens new avenues to study the mechanisms of neuronal synchronization in the pathologic brain, which has clinical implications, at least in epilepsy.
Angus MacDonald is fundraising for Epilepsy Research UK. Angus, whose sister has epilepsy, has decided to cycle from London to Paris in June 2017 to support our research.
Angus says, “ My sister Sophie was first diagnosed with epilepsy 6 years ago, when she was 22. To be honest, I’d never really known much about epilepsy until then and witnessing that first seizure was a frightening, emotional experience.
I’d do anything for Sophie, so realising the lack of awareness around this condition and how many people it affects, I wanted to make a stand and raise awareness as soon as possible. I jumped at the chance both to challenge myself and raise money along the way so I did the London to Brighton cycle ride. I’m now taking this further by attempting the London to Paris one on June 1st this year.
Since Sophie was diagnosed, it’s obviously had a big impact on the family – we’re very close and, as with anyone you care for and love, there’s always that worry. However, we don’t let it affect our everyday lives – my sister wouldn’t want it and it’s important that it doesn’t define your life.
I was made aware of Epilepsy Research UK through a friend and, by reading through social media posts and all the news on their website, I made a decision that this was the charity I wanted to support; I’m now raising awareness and funds in whatever way I can.
I would say to anyone out there that suffers with epilepsy, don’t be afraid to come forward and talk to people about it. I’m lucky to have a fantastic bond with my sister and we love each a lot so putting the effort into this and raising money for research just makes sense to me and is easy to do. “
Angus has set up an online sponsor page, and has already gained a huge amount of support via twitter! If you’d like to support Angus in his fundraising you can do so here.
Our huge thanks go to Angus and his family for fundraising for our research, and we look forward to supporting him in his London to Paris cycle.
Researchers have managed to grow adult human neurons in the laboratory for the first time. According to the authors of a study published in Cell Reports, these cells could be used to understand the effect of antiepileptic drugs (AEDs) on the brain and might impact treatment of epilepsy in the future. They could also be used to understand how neurons connect with each other by regulating the expression of certain genes.
The tissues used in the study, which was led by Dr James Eberwine at the University of Pennsylvania, were donated by seven people who had undergone brain surgery either as a treatment for epilepsy or to remove brain tumours.
From these tissues, the researchers identified multiple different types of brain cells, including oligodendrocytes, microglia, endothelial cells, astrocytes and neurons, as well as the proteins that they produce. Of greatest significance was the ability to grow neurons, which had previously been thought impossible.
In a press release, Dr Eberwine said: “We were surprised that we could grow these neurons at all. The oldest tissue came from a donor who was in their mid-sixties. This is even more surprising because neurons don’t divide, so they need to last a lifetime. We are finally able to characterize adult aged cells from the most enigmatic organ of the body – the seat of learning and memory, as well as consciousness.”
The team identified more than 12,000 genes that were expressed in these various cells, hundreds of which were only expressed in certain cell types. Interestingly, the cells obtained from each donor had a different pattern of gene expression, which caused the authors to comment on “…the importance of taking a personalized medical approach for evaluating and treating each patient”.
The age of the people who provided the tissues ranged from 20 to 60 meaning that the cells could also help scientists understand how ageing affects the brain, something that has only been studied in animals so far.
Studying neurological conditions such as epilepsy and developing drugs to treat them is challenging. This is the first time that scientists have been able to generate a full range of brain cells, including neurons, from living donors and to use them to study how those cells connect and communicate.
Author: Dr Özge Özkaya
Click here for more articles about brain science including genetics.
Restless leg syndrome (RLS) or the urge to move the legs, is more common in people with epilepsy than the general public, according to a study published in the scientific journal Epilepsy and Behavior. The authors suggest that the syndrome could in fact be an early warning indicator for seizures.
The study also showed that RLS seems to occur more often in people with right temporal lobe epilepsy than in those with left temporal lobe epilepsy. This means that the presence of RLS could help doctors predict which the side of the brain is responsible for the epilepsy in some patients.
For the study, researchers led by Dr Paul Carney, a child neurologist at the University of North Carolina, screened epilepsy patients seen at an outpatient clinic between 2005 and 2015 for movement disorders. They evaluated the patients using the International Restless Legs Study Group questionnaire and the NIH RLS diagnostic criteria. They also measured iron levels in their blood, since a low level of iron is a risk factor for RLS, and performed a polysomnography, which is a comprehensive sleep-screening technique.
Almost 100 patients seen in the clinic in this period of time had focal-onset temporal lobe epilepsy. Half of these had right-sided temporal lobe epilepsy and half had left-sided temporal epilepsy. The results showed that moderate-to-severe RLS occurred in 21 of 50 (42%) people with right temporal lobe epilepsy and in 7 of 48 (15%) people with left temporal lobe epilepsy.
The researchers calculated that people who had right temporal lobe epilepsy were more than four times as likely to have RLS as those with left temporal lobe epilepsy. Interestingly, some patients experienced a sensation of worsening RLS before seizures. This is important because it could provide doctors with the opportunity to intervene at an earlier stage before a seizure develops.
RLS, also known as the Willis-Ekbom disease, is a disorder of the nervous system occurring in around 10% of the general population. Although scientists don’t know its exact cause, they think that it could be due to an imbalance in dopamine in the brain, a chemical that sends messages to control muscle movement.
Author: Dr Özge Özkaya
Click here for more articles about conditions related to epilepsy.
Adhering to antiepileptic drugs (AEDs) improves seizure control but can also enhance quality of life and sexual functioning in women with epilepsy, according to a study published in the journal Epilepsy and Behavior.
“Healthcare providers should be aware of these additional benefits of medication adherence and use these arguments to encourage female patients to take their medication, which can eventually increase their sexual satisfaction and overall [quality of life],” wrote Dr Chung-Ying Lin and the co-authors of the study.
The team assessed quality of life and sexual functioning in 576 Iranian women with epilepsy using the Quality of Life in Epilepsy questionnaire and the Female Sexual Function Index respectively. They also measured epilepsy severity using the Liverpool Seizure Severity Scale and medication adherence both subjectively (using the Medication Adherence Report Scale) and objectively (by measuring drugs levels in the participants’ blood).
The results showed a positive correlation between scores from the Medical Adherence Report Scale and those from the Quality of Life in Epilepsy questionnaire. In other words, greater adherence with medication was associated with improved quality of life. Medication adherence scores were also correlated with overall sexual functioning, and, in turn, improved sexual functioning was associated with improvements in quality of life.
The researchers recognised that there is a complex relationship between medication adherence, seizure control, quality of life, and sexual functioning. Nevertheless, their results indicate that the benefits of AED adherence extend beyond reduction of seizures into other aspects of well-being.
Sexuality is an important component of quality of life. It is estimated that around 20-30% of women with epilepsy experience some form of sexual dysfunction such as decreased sex drive or problems with arousal and infrequent orgasms. Factors that may influence sexual functioning in epilepsy include anxiety, stigmatization, and epileptic activity in the brain.
Author: Dr Özge Özkaya
Click here for more articles about anti-epileptic drugs and pregnancy risks.
There is some suggestion that microscopic infarct could be associated with invasive monitoring, but it is unclear if the microscopic infarct is also visible on imaging and associated with neurologic deficits. The aims of this study were to assess the rates of microscopic and macroscopic infarct and other major complications of pediatric epilepsy surgery, and to determine if these complications were higher following invasive monitoring.Methods
We reviewed the epilepsy surgery data from a tertiary pediatric center, and collected data on microscopic infarct on histology and macroscopic infarct on postoperative computed tomography (CT) or magnetic resonance imaging (MRI) done one day after surgery and major complications.Results
Three hundred fifty-two patients underwent surgical resection and there was one death. Forty-two percent had invasive monitoring. Thirty patients (9%) had microscopic infarct. Univariable analyses showed that microscopic infarct was higher among patients with invasive monitoring relative to no invasive monitoring (20% vs. 0.5%, respectively, p < 0.001). Eighteen patients (5%) had macroscopic infarct on CT or MRI. Univariable analysis showed no significant difference in macroscopic infarct between invasive monitoring and no invasive monitoring (8% vs. 3%, respectively, p = 0.085). One patient with microscopic infarct had transient right hemiparesis, and two with both macroscopic and microscopic infarct had unexpected persistent neurologic deficits. Thirty-two major complications (9.1%) were reported, with no difference in major complications between invasive monitoring and no invasive monitoring (10% vs. 7%, p = 0.446). In the multivariable analysis, invasive monitoring increased the odds of microscopic infarct (odds ratio [OR] 15.87, p = 0.009), but not macroscopic infarct (OR 2.6, p = 0.173) or major complications (OR 1.4, p = 0.500), after adjusting for age at surgery, sex, age at seizure onset, operative type, and operative location.Significance
Microscopic infarct was associated with invasive monitoring, and none of the patients had permanent neurologic deficits. Macroscopic infarct was not associated with invasive monitoring, and two patients with macroscopic infarct had persistent neurologic deficits.
Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population.Methods
Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]).Results
Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal).Significance
Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval.
Children with epilepsy have high rates of both cognitive impairment and sleep disruption. It is thus assumed that sleep-dependent memory consolidation is vulnerable to ongoing epileptic activity, but direct evidence of this is limited.Methods
We performed a within-subject comparison of memory retention across intervals of wake or overnight sleep. Healthy children (n = 21, 6–16 years, 12 female) and children with focal epilepsy (n = 22, 6–16 years, 9 female) performed verbal and visuospatial memory tasks under each condition. Sleep was assessed with electroencephalography (EEG) polysomnography during the overnight interval. Interictal discharges were quantified manually.Results
Memory retention was greater in the sleep condition in both the verbal (F1,39 = 10.8, p = 0.002, Cohen's d = 0.67) and the visuospatial (F1,36 = 4.23, p = 0.05, Cohen's d = 0.40) tasks, with no significant interaction of group by condition in either task. Across the total sample, gain in memory retention with sleep in the verbal task correlated with duration of slow wave sleep (r = 0.4, p = 0.01). In patients, sleep-dependent memory consolidation was negatively correlated with interictal discharge rate in both the verbal (ρ = −0.49, p = 0.04) and visuospatial (ρ = −0.45, p = 0.08) tasks. On post hoc analysis, a longer history of epilepsy (r = 0.53, p = 0.01) and a temporal (t10 = 1.8, p = 0.1, Cohen's d = 0.86) rather than an extratemporal seizure focus (t10 = 0.8, p = 0.4, Cohen's d = 0.30) was associated with greater contribution of sleep to verbal memory retention.Significance
We have demonstrated that memory consolidation in children with focal epilepsy benefits from sleep, showing the same correlation with slow wave sleep as in healthy children, but an inverse relationship with the interictal discharge load during sleep. This mechanism appears to be increasingly recruited with longer duration of illness, indicating a resilient homeostatic function which may be harnessed to aid learning.
Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII)
The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26–29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I–III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689). Overall, the results presented at the Conference show that considerable efforts are ongoing into discovery and development of AEDs with potentially improved therapeutic profiles compared with existing agents. Many of the drugs discussed in this report show innovative mechanisms of action and many have shown promising results in patients with pharmacoresistant epilepsies, including previously neglected rare and severe epilepsy syndromes.