Staff at a leading law firm are to saddle up and drop 200 ft in memory of a Grimsby student. Robert Abba, 22, died after suffering an epileptic fit at home in Scartho.
His mother Rachel works for Bridge McFarland solicitors and colleagues will take in such landmarks as Lincoln Castle and Grimsby Dock Tower as they run, cycle, skydive and abseil to raise money in the memory of Robert. The money will go to help Epilepsy Research UK find out more about epilepsy and SUDEP – Sudden Unexpected (Unexplained) Death in Epilepsy. Around 87 people are diagnosed with epilepsy each day and SUDEP claims around 600 lives every year.
Seizures in epilepsy can be caused by genetic factors or they can be triggered by injury. While we know that all brains are capable of generating seizures we do not know why some brains do not develop them. A good example is epilepsy that develops as a result of an ischemic stroke. Only some of the people who have an ischemic stroke will develop epilepsy so it has long been conjectured that there are also other factors at play.
Researchers at the Hebrew University in Jerusalem believe they may have found one of these factors in the form of a micro-gene.
The research, that has been published in the journal Proceedings of the National Academy of Sciences, started out from the hypothesis that healthy brains do not have seizures when exposed to flashing lights or other triggers because of so-called short RNAs, otherwise known as rapidly inducible microRNAs.
MicroRNAs are a class of RNA – that is, one of the macromolecules needed for all forms of life, together with DNA and proteins – that have the ability to suppress the genetic expression of certain proteins.
Prof. Hermona Soreq and her team tested their hypothesis through a genetically designed a type of mouse that produces very large amounts of a microRNA called miR-211.
The overexpression of miR-211 taking place in the mice’s forebrain was engineered in such a way that it could be lowered with the antibiotic doxycycline. Soreq, along with colleagues at the Ben-Gurion University of the Negev in Israel and Dalhousie University in Canada, managed to suppress the excess of miR-211 in the transgenic mice by using doxycycline, which brought the levels to normal.
After 4 days, they recorded the mice’s brain activity using electrocorticography. They found that the mice reacted to the miR-211-suppressing doxycycline by having nonconvulsive seizures, as well as by accumulating miR-134 in the forebrain.
The new study revealed that once they had their levels of miR-211 lowered, the mice showed signs of epilepsy and a propensity for convulsions. They displayed a hypersensitivity to compounds that induce epilepsy, such as the miR-134.
This suggests that miR-211 has a neuroprotective role and is key in preventing epileptic seizures in genetically modified mice.
“Dynamic changes in the amount of miR-211 in the forebrains of these mice shifted the threshold for spontaneous and pharmacologically induced seizures, alongside changes in the cholinergic pathway genes,” Prof. Soreq explains.
“It is important to discover how only some people’s brains present a susceptibility to seizures, while others do not, even when subjected to these same stressors. In searching for the physiological mechanisms that allow some people’s brains to avoid epilepsy, we found that increased levels of microRNA 211 could have a protective effect.” Prof. Hermona Soreq
The scientists hope that their discovery will help the medical research community to develop new treatments for epilepsy. Such therapies might work by raising the levels of miR-211 in human brains.
Technology for localizing epileptogenic brain regions plays a central role in surgical planning. Recent improvements in acquisition and electrode technology have revealed that high-frequency oscillations (HFOs) within the 80–500 Hz frequency range provide the neurophysiologist with new information about the extent of the epileptogenic tissue in addition to ictal and interictal lower frequency events. Nevertheless, two decades after their discovery there remain questions about HFOs as biomarkers of epileptogenic brain and there use in clinical practice.Methods
In this review, we provide practical, technical guidance for epileptologists and clinical researchers on recording, evaluation, and interpretation of ripples, fast ripples, and very high-frequency oscillations.Results
We emphasize the importance of low noise recording to minimize artifacts. HFO analysis, either visual or with automatic detection methods, of high fidelity recordings can still be challenging because of various artifacts including muscle, movement, and filtering. Magnetoencephalography and intracranial electroencephalography (iEEG) recordings are subject to the same artifacts.Significance
High-frequency oscillations are promising new biomarkers in epilepsy. This review provides interested researchers and clinicians with a review of current state of the art of recording and identification and potential challenges to clinical translation.
Today – Friday 16th – we have been at the annual UCL (University College London) Neuroscience Symposium. It is immensely popular and attracts almost around 800 delegates. Epilepsy Research UK projects were in evidence and I had the opportunity to meet some of our current researchers as well as young researchers that we would like to encourage in order to keep their skills in the field of epilepsy.
You can find more details of the UCL Symposium and download the abstract booklet here.
Among the Epilepsy Research UK funded researchers was Dr Stephanie Schorge who was presenting some details of her work on gene therapy and refractory epilepsy. We also met Dr Gabriele Lignani who has just been awarded an Epilepsy Research UK Fellowship. Dr Ligani was presenting his work on how to increase promoter activity to treat intractable epilepsy. We also ran into Albert Snowball from the UCL Institute of Neurology who was presenting his work on gene therapy for epilepsy using non-integrating lentiviral delivery of an engineered potassium channel gene. The Institute of Neurology at UCL has a worldwide reputation and as an organisation, we are proud to help fund some of the fantastic work that is going on there.
To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam.Methods
Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters.Results
The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: −$3.8/SS), intramuscular midazolam (ICER: −$64/SS), and rectal diazepam (ICER: −$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters.Significance
For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States. Rectal diazepam is not a cost-effective alternative, and this conclusion remains extremely robust to wide variations of the input parameters.
Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol
Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding.
Epilepsy patients and others with damage in a part of the brain called the amygdala fail to recognise facial emotions, though they find faces looking sideways more memorable, a new study shows.
In the new study, researchers at tthe University of Bath, in collaboration with neurosurgeons and psychologists in Warsaw, Poland, sought to examine if gaze and emotional expression — both highly self-relevant social signals — affect the recollection accuracy of perceived faces in patients with mesial temporal lobe epilepsy (MTLE).
The researchers showed a series of faces with neutral or emotional expressions to 40 patients with MTLE and 20 healthy individuals. Half of the faces were looking straight ahead, and half sideways. They found that healthy participants had better recognition of emotional faces, while epileptics couldn’t remember emotional faces any better than neutral ones — but did find pictures of people gazing away more memorable than those looking straight ahead.
The findings add to the evidence that damage to the amygdala affects facial recognition and gaze perception — which is especially important since perception and understanding the facial cues of others is essential in human societies.
People with damage to the amygdala have deficits in emotion recognition while keeping the perception of others’ eye gaze direction intact. These patients often struggle with everyday communication, particularly with understanding social signals, which causes problems in relationships with others. These social problems often lead to lower levels of life satisfaction.
“Surprisingly, we found that individuals with amygdala damage remembered faces looking to the side more than those looking towards them. This effect was independent of the emotional content of the face,” the University of Bath’s Sylwia Hyniewska said in a news release. “This was unexpected given that all research so far focusing on other populations showed either an interaction effect between emotion and gaze, or an improved memory for faces looking towards the observer.”
Hyniewska added: “We expected our patients to remember faces better when they were looking at them — presented with the direct gaze. However for some reason patients seem to remember faces looking away better. This means that the interaction between the processing of emotions and gaze is more complex than we thought, and not only emotions but also gaze should be studied further in this specific population to develop treatments improving these patients’ well-being.”
What is the amygdala?