Archive for category Epilepsy

[Book Chapter] Pregnancy and Epilepsy

VD Kapadia – Medical Disorders in Pregnancy

Epilepsy is the most common neurological disorder, with 50 million people affected by it worldwide. Nearly 50% of these affected individuals are women. The burden of  epilepsy in women in India is to the tune of 2.73 million, with 52% of them being in …

Continue —> Pregnancy and Epilepsy [PDF]

 

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[ARTICLE] EFFICACY OF SHORT TERM VIDEO EEG IN DETECTING PSYCHOGENIC NON-EPILEPTIC SEIZURES – Full Text PDF

Abstract

Background: Short term video Electroencephalography (SVEEG) is a non-invasive diagnostic procedure typically last for about 1-5 hours. SVEEG can be utilize to differentiate epileptic from Psychogenic Non-epileptic Seizures (PNES).

Objective: To assess the yield of short term video EEG in detecting PNES.

Methods:Retrospective analysis of short term video EEG in a tertiary level hospital. Patient history, provisional diagnosis, previous EEG and imaging reports were tabulated. Various short term video EEG findings like epileptiform abnormalities, PNES and other non-epileptic events were analyzed in detail. According to the provisional diagnosis formed two groups; Suspecting NEE and suspecting seizure disorders. Change in the provisional diagnosis after SVEEGs were also studied.

Results: A total of 417 SVEEGs analyzed: 34(8.2%) patients developed events to suggest PNES, 16(3.8%) patients had other non-epileptic events; 96(23%) showed interictal epileptiform discharges, 15 (3.6%) showed seizures and 90(21.6%) patients showed non-specific EEG abnormalities. Around 60% SVEEGs were conclusive.

Conclusion: A diagnostic event was recorded during SVEEG in majority of patients in the PNES group. SVEEG is a cost effective and useful diagnostic procedure; especially to identify non-epileptic events.

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[Abstract] Pharmacology and epilepsy : update on the new antiepileptic drugs

New antiepileptic drugs are regularly approved for treatment and offer large therapeutic opportunities. Efficacy of these drugs is relatively similar on-label with different mechanisms to be combined for a synergic effect. Treatments such as cannabidiol have benefitted from large media coverage despite limited clinical evidence so far. The objective of antiepileptic drugs is to stop the recurrence of epileptic seizures with as few adverse events as possible. When confronted to a difficult-to-treat epilepsy, referral to a specialised centre is strongly advised. The aim is to confirm that the diagnosis is correct, that the treatment is well adapted (indication, pharmacokinetic and compliance) and to evaluate the indication for non-pharmacological treatments such as epilepsy surgery.

 

via [Pharmacology and epilepsy : update on the new antiepileptic drugs]. – Abstract – Europe PMC

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[Abstract] Driving rules : first seizure and epilepsy.

For patients with epilepsy, the occurrence of a traffic accident due to an epileptic seizure is a major problem. In order to reduce the risk of an accident, the Road Traffic Commission of the Swiss League against Epilepsy has issued guidelines concerning the driving ability of a vehicle in case of epilepsy. These directives were last modified in 2015. According to these directives, the waiting period differs according to the category of the vehicle concerned and the origin of the event (first crisis provoked or not provoked). At the occurrence of the first episode, an exhaustive evaluation is mandatory in order to avoid unnecessarily prolonged restrictions. These directives are available on : http://www.epi.ch/wp-content/uploads/flyer-Epilepsie_fuehrerschein-licence-conduire-2016.pdf

 

via [Driving rules : first seizure and epilepsy]. – Abstract – Europe PMC

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[BOOK] The Comorbidities of Epilepsy – Google Books

The Comorbidities of Epilepsy

Front Cover
Marco Mula
Academic PressApr 20, 2019 – Medical – 413 pages

Epilepsy is one of most frequent neurological disorders affecting about 50 million people worldwide and 50% of them have at least another medical problem in comorbidity; sometimes this is a the cause of the epilepsy itself or it is due to shared neurobiological links between epilepsy and other medical conditions; other times it is a long-term consequence of the antiepileptic drug treatment.

The Comorbidities of Epilepsy offers an up-to-date, comprehensive overview of all comorbidities of epilepsy (somatic, neurological and behavioral), by international authorities in the field of clinical epileptology, with an emphasis on epidemiology, pathophysiology, diagnosis and management. This book includes also a critical appraisal of the methodological aspects and limitations of current research on this field. Pharmacological issues in the management of comorbidities are discussed, providing information on drug dosages, side effects and interactions, in order to enable the reader to manage these patients safely.

The Comorbidities of Epilepsy is aimed at all health professionals dealing with people with epilepsy including neurologists, epileptologists, psychiatrists, clinical psychologists, epilepsy specialist nurses and clinical researchers.

  • Provides a comprehensive overview of somatic, neurological and behavioral co-morbidities of epilepsy
  • Discusses up-to-date management of comorbidities of epilepsy
  • Written by a group of international experts in the field

 

via The Comorbidities of Epilepsy – Google Books

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[WEB PAGE] When Will There Ever be a Cure for Epilepsy?

The three-pound organ that serves as command central for the human organism is certainly a marvel, just by virtue of the fact that the brain can appreciate its own awesomeness, even if it hasn’t quite perfected the flying car or even self-driving cars. Yet. Companies developing brain-computer interface technology are enabling humans to do things like send commands to computers by just flexing a bit of muscle. Still, there is much we don’t know about ourselves, no matter how much telepsychiatry we do. And that applies especially to medical conditions that affect the brain like epilepsy, a neurological condition for which there is no cure.

What is Epilepsy?

While most of us are probably familiar with some Hollywood-ized version of epilepsy in which someone starts flailing around after being hit by strobe lights on the disco floor, the reality is that epilepsy refers to a large group of neurological disorders that generally involve chronic, spontaneous seizures that vary greatly in how they manifest. The causes of epilepsy are also all over the place, from traumatic brain injuries and stroke to viral and bacterial infections to genetics.

A new set of classifications for epilepsy came out in 2017.

It is considered a brain disorder, according to the U.S. Centers for Disease Control (CDC), though some researchers have suggested it could be classified as a neurodegenerative disease like Parkinson’s or Alzheimer’s. In fact, there is research that suggests a genetic link between epilepsy and neurodegenerative diseases.

Not surprisingly, many of the companies developing therapies for neurodegenerative diseases are also working on treatments for epilepsy and vice versa. For example, a new, well-funded joint venture involving Pfizer (PFE) and Bain Capital called Cerevel, which we profiled in our piece on Parkinson’s disease, is also in advanced clinical trials for an epileptic drug. Its GABA A positive modulator drug candidate targets GABA (Gamma-Aminobutyric Acid) neurotransmitters that block impulses between nerve cells in the brain, helping keep the nervous system chill.

Impacts of Epilepsy

More than 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally, according to the World Health Organization (WHO). The CDC estimates about 3.4 million Americans live with the condition. Globally, an estimated 2.4 million people are diagnosed with epilepsy each year. Interestingly, the disorder seems to target those who can least afford it: WHO said nearly 80% of people with epilepsy live in low- and middle-income countries.

Impacts of epilepsy graphic

A 2015 study of a bunch of other studies that estimated the cost of epilepsy in the United States found that epilepsy-specific costs probably average out to about $10,000 based on the variety of ranges, which means epilepsy costs the United States healthcare system about $34 billion, though the numbers are widely debated. Conversely, WHO says low-cost treatments are available, with daily medication coming as cheaply as $5 per year, so another win for the U.S. healthcare system.

Treatments for Epilepsy

There are more than 20 antiepileptic drugs used to treat epilepsy, usually to help prevent or slow the occurrence of seizures. Other therapies include surgery and electroceutical treatment in which electrical stimulation is applied, usually to the vagus nerve, the longest cranial nerve in the body. While many find relief from one or more of these options, a third of those who suffer from epilepsy are not able to manage their seizures, according to the U.S. National Institutes of Health (NIH). Below we take a look at a range of innovative therapies designed to detect, stop, or find a cure for epilepsy.

Brain Stimulation Therapies

In our article on electroceutical treatments, we highlighted a London company called LivaNova (LIVN) that offers an implantable Vagus Nerve Stimulation (VNS) therapy that has been approved by the U.S. Food and Drug Administration (FDA) to help treat those with partial seizures who do not respond to seizure medications. A medical device company with a lengthy track record of returning value to investors, Medtronic (MDT) got FDA pre-market approval last year for its Deep Brain Stimulation (DBS) therapy for use in reducing partial-onset seizure for those who have proven to not respond to three or more antiepileptic medications. DBS therapy delivers controlled electrical pulses to an area in the brain called the anterior nucleus of the thalamus, which is part of a network involved in seizures. Yet another company offering a variation of brain stimulation therapy is NeuroPace, which markets its responsive neurostimulation device, or RNS system, as “the first and only brain-responsive neurostimulation system designed to prevent epileptic seizures at their source.”

Artificial Intelligence to Detect, Predict, and Control Epilepsy

The NIH is funding further research into implantable devices that can detect, predict, and stop a seizure before it happens, “working closely with industry partners to develop pattern-recognition algorithms,” which sounds an awful lot like artificial intelligence and machine learning will be at the forefront of some future diagnostics and treatment. AI in healthcare has been an ongoing theme around here, with a recent dive into AI and mental health. Back to AI and epilepsy: A group of neurologists at the Medical University of South Carolina developed a new method based on artificial intelligence to predict which patients will see success with surgical procedures designed to stop seizures. Sounds like a great idea to learn beforehand if it’s necessary to crack open your skull.

Click for company websiteA Boston area startup called Empatica, spun out from MIT in 2011, has raised $7.8 million for a smartwatch that detects possible seizures by monitoring subtle electrical changes across the surface of the skin. Other methods normally rely on electrical activity in the brain that tracks and records brain wave patterns called an electroencephalogram. Empatica’s seizure detection algorithm, on the other hand, can detect complex physiological patterns from electrodermal activity that is most likely to accompany a convulsive seizure. Psychology Today reportedthat the device, Embrace Watch, received FDA approval earlier this year for seizure control in children after getting the green light for the technology for adults in 2018.

The Empatica smartwatch can detect electrical currents in the skin to predict the onset of an epileptic seizure.

Click for company websiteAI and drug discovery for better epileptic drug candidates is yet another application that we would expect to see grow in the coming years. Silicon Valley-based startup System1 Biosciences raised $25 million last year, which included Pfizer among its dozen investors. System1 builds a sort of brain model for testing drug candidates using stem cell lines derived from patients with brain disease. The company uses robotic automation to develop these three-dimensional cerebral organoids, allowing it to generate huge datasets in a relatively short amount of time, then applying “advanced data analysis” (also AI?) to detect patterns that might match the characteristics of a neurological disease (what it refers to as deep phenotypes) such as epilepsy with novel treatments.

Cannabis for Controlling Seizures

We’ve written extensively about the suddenly booming hemp CBD market, noting that the FDA approved a CBD-based drug for epilepsy last year in our recent article on the best certified CBD oils on the market. However, we’ve only briefly profiled the company behind Epidiolex for treating rare forms of epilepsy, GW Pharmaceuticals (GWPH). Sporting a market cap just south of $5 billion, GW Pharmaceuticals has taken in about $300 million in post-IPO equity since our article, bringing total post-IPO equity funding to about $568 million. Aside from its successful epileptic drug, GW also developed the world’s first cannabis-based prescription medicine for the treatment of spasticity due to multiple sclerosis that is available in 25 countries outside the United States.

The forms of epilepsy that GW Pharmaceuticals can treat or can potentially treat.

Back on the epilepsy side, Epidiolex has been approved for two rare forms of epilepsy, with clinical trials underway for two more rare neurological disorders associated with seizures – tuberous sclerosis complex and Rett syndrome. Also in the pipeline is a drug dubbed CBDV (GWP42006) that’s also for treating epileptic seizures, though the results of a trial last year were not encouraging. The same compound is also being investigated for autism. Be sure to check out our article on Charlotte’s Web, a CBD company that came about because of epilepsy.

Helping Cells Get Their Vitamin K

Click for company websiteNeuroene Therapeutics is a small startup spun out of the Medical University of South Carolina that recently picked up $1.5 million in funding to tests its lead drug compounds, which are analogous to the naturally occurring form of vitamin K that is essential for brain health. In particular, the lab-developed vitamin K protects the integrity of the cell’s mitochondria, which serves as a sort of power plant for brain cells, helping the neural circuit fire better. Unfortunately, you can’t get the effect from simply eating a bowl of Special K each morning covered in an organic sugar substitute, so the company is developing a method to deliver the effects directly to the brain.

A Nasal Spray to Stop Seizures

Click for company websiteFounded in 2007 near San Diego, Neurelis licenses, develops, and commercializes treatments for epilepsy and other neurological diseases. It has raised $44.8 million in disclosed funding, most coming in a $40.5 million venture round last November. The company’s flagship product is called Valtoco, a formulation that incorporates diazepam, an existing drug used to control seizures and alcohol withdrawal, with a vitamin E-based solution that is delivered using a nasal spray when a sudden seizure episode occurs. The product uses an absorption enhancement technology called Intravail developed by another San Diego area company called Aegis Therapeutics that Neurelis acquired in December last year. Neurelis submitted Valtoco to the FDA for approval in September.

Conclusions

While many people with epileptic conditions can control their seizures with many of the current medications or other therapies available now, there’s a big chunk of the population that is living with uncertainty. Considering the strong link between neurological disorders like epilepsy and certain neurodegenerative disorders, expect to see some good synergies in the next five to 10 years, especially as automation and advanced analytics using AI start connecting the dots between genetics, biochemistry, and brain disorders.

via When Will There Ever be a Cure for Epilepsy? – Nanalyze

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[Editorial] Functional brain mapping of epilepsy networks: methods and applications – Neuroscience

This multidisciplinary research topic is a collection of contemporary advances in neuroimaging applied to mapping functional brain networks in epilepsy. With technology such as simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) now more readily available, it is possible to non-invasively map epileptiform activity throughout the entire brain at millimetre resolution. This research topic includes original research studies, technical notes and reviews of the field. Due to the multidisciplinary nature of the domain, the topic spans two journals: Frontiers in Neurology (Section: Epilepsy) and Frontiers in Neuroscience (Section: Brain Imaging Methods).
In this editorial we consider the outcomes of the multidisciplinary work presented in the topic. With the benefit of time elapsed since the original papers were published, we can see that the works are making a substantial impact in the field. At the time of writing, this topic had well over 27,000 full-paper downloads (including over 18,000 for the 15 papers in the Epilepsy section, and over 9,000 for the 8 papers in the Brain Imaging Methods section). Several papers in the topic have climbed the tier in Frontiers and received an associated invited commentary, demonstrating there is substantial interest in this research area.
Reviews
The topic’s review papers set the scene for the original research papers and synthesise contemporary thinking in epilepsy research and neuroimaging methods. We see that Epilepsy, whether of a “generalised” or “focal” origin, is increasingly recognised as a disorder of large-scale brain networks. At one level it is self-evident that otherwise healthy functional networks are recruited during epileptic activity, as this is what generates patient perceptions of their epileptic aura. For example, the epileptic aura of mesial temporal lobe epilepsy can include an intense sensation of familiarity (déjà vu) associated with involvement of the hippocampus, and unpleasant olfactory auras which may reflect involvement of adjacent olfactory cortex. As seizures spread more widely throughout the brain, presumably along pre-existing neural pathways, patients lose control of certain functions; for example, their motor system in the case of generalised convulsions, or aspects of awareness in seizures that remain localised to non-motor brain regions. Yet these functions return when the seizure abates, implying involved brain regions are also responsible for normal brain function. What has been less clear, and difficult to investigate until the advent of functional neuroimaging, is precisely which brain networks are involved (especially in ‘generalised’ epilepsy syndromes), and the extent to which functional networks are perturbed during seizures, inter-ictal activity, and at other times.
Functional imaging evidence of brain abnormalities in temporal lobe epilepsy is explored in (Caciagli et al., 2014), including evidence of dysfunction in limbic and other specific brain networks, as well as global changes in network topography derived from resting-state fMRI. Archer et al systematically review the functional neuroimaging of a particularly severe epilepsy phenotype, Lennox-Gastaut Syndrome (LGS), illustrating well how different forms of brain pathology can manifest in a similar clinical phenotype, simply by the nature of the healthy networks that the underlying pathology perturbs (Archer et al., 2014). Similarly, the mechanisms of absence seizure generation are reviewed by (Carney and Jackson, 2014), revealing that it too has a signature pattern of large-scale functional brain network perturbation. The ability to make such observations has considerable clinical significance, as highlighted in the review by (Pittau et al., 2014).
The tantalising proposition that there may be a common treatment target for all focal epilepsy phenotypes is also explored in a review of the piriform cortex by (Vaughan and Jackson, 2014). The piriform cortex was first implicated as a common brain region associated with spread of interictal discharges in focal epilepsy in an experiment that analysed the spatially normalised functional imaging data of a heterogeneous group of focal epilepsy patients (Laufs et al., 2011). This finding, since replicated (Flanagan et al., 2014), led Vaughan & Jackson to explore in detail what is known of the piriform cortex. Their findings reveal the piriform has several features that likely predispose it to involvement in focal epilepsy, and features that also explain many of the peculiar symptoms experienced by patients, from olfactory auras to the characteristic nose-wiping that many patients perform postictally. This work points to the need for future studies to determine whether the piriform might be an effective target for deep brain stimulation or other targeted therapy to prevent the spread of epileptiform activity.
Original research
Temporal lobe epilepsy is investigated in several papers in this topic. One of these studies also introduces a new exploratory method, Shared and specific independent component analysis (SSICA), that builds upon independent component analysis to perform between-group network comparison (Maneshi et al., 2014). In application to mesial temporal lobe epilepsy (MTLE) and healthy controls, three distinct reliable networks were revealed: two that exhibited increased activity in patients (a network including hippocampus and amygdala bilaterally, and a network including postcentral gyri and temporal poles), and a network identified as specific to healthy controls (i.e. effectively decreased in patients, consisting of bilateral precuneus, anterior cingulate, thalamus, and parahippocampal gyrus). These finding give mechanistic clues to the cognitive impairments often reported in patients with MTLE. Further clues are revealed in a study of the dynamics of fMRI and its functional connectivity (Laufs et al., 2014). Compared to healthy controls, temporal variance of fMRI was seen to be most increased in the hippocampi of TLE patients, and variance of functional connectivity to this region was increased mainly in the precuneus, the supplementary and sensorimotor, and the frontal cortices. More severe disruption of connectivity in these networks during seizures may explain patients’ cognitive dysfunction (Laufs et al., 2014). Yang and colleagues also show that it may be possible to use fMRI functional connectivity to lateralise TLE (Yang et al., 2015), which could be a useful clinical tool.
Mechanistic explanations of symptomatology beyond the seizure onset zone can also be revealed with conventional nuclear medicine techniques such as 18F-FDG-PET. This is demonstrated in a study of Occipital Lobe Epilepsy by Wong and colleagues, who observed that patients with automatisms have metabolic changes extending from the epileptogenic occipital lobe into the ipsilateral temporal lobe, whereas in patients without automatisms the 18F-FDG-PET was abnormal only in the occipital lobe (Wong et al., 2014).
The clinical significance of the ability to non-invasively study functional brain networks extends to understanding the impact of surgery on brain networks. This Frontiers research topic includes an investigation by Doucet and colleagues revealing that temporal lobe epilepsy and surgery selectively alter the dorsal, rather than the ventral, default-mode network (Doucet et al., 2014).
Another approach to better understand the mechanisms of seizure onset and broader symptomatology is computational modelling. It can track aspects of neurophysiology than cannot be readily measured: for example effective connectivity and mean membrane potential dynamics are shown by (Freestone et al., 2014) to be estimable using model inversion. In a proof-of-principle experiment with simulated data, they demonstrate that by tailoring the model to subject-specific data, it may be possible for the framework to identify a seizure onset site and the mechanism for seizure initiation and termination. Also in this topic, Petkov and colleagues utilise a computational model of the transition into seizure dynamics to explore how conditions favourable for seizures relate to changes in functional networks. They find that networks with higher mean node degree are more prone to generating seizure dynamics in the model, thus providing a mathematical mechanistic explanation for increasing node degree causing increased ictogenicity (Petkov et al., 2014).
Seizure prediction is an area of considerable research, and in this topic Cook and colleagues reveal intriguing characteristics in the long-term temporal pattern of seizure onset. They confirmed that human inter-seizure intervals follow a power law, and they found evidence of long-range dependence. Specifically, the dynamics that led to the generation of a seizure in most patients appeared to be affected by events that took place much earlier (as little as 30 minutes prior and up to 40 days prior in some patients) (Cook et al., 2014). The authors rightly note that this information could be valuable for individually-tuned seizure prediction algorithms.
Several methodological papers in this Frontiers Topic prove there remains considerable potential to improve neuroimaging methods as applied to the study of epilepsy. For example, (Mullinger et al., 2014) reveal the critical importance of the accuracy of physical models if one is to optimise lead positioning in functional MRI with simultaneous EEG. Confirming with computer modelling and phantom measurements that lead positioning can have a substantial effect on the amplitude of the MRI gradient artefact present on the EEG, they optimised the positions in a novel cap design. However, whilst this substantially reduced gradient artefact amplitude on the phantom, it made things worse when used on human subjects. Thus, improvement is required in model accuracy if one is to make accurate predictions for the human context.
Reduction of artefact, particularly cardioballistic and non-periodic motion artefact, remains a challenge for off-the-shelf MRI-compatible EEG systems. However, for over a decade, the Jackson group in Melbourne has dealt well with this issue using insulated carbon-fibre artefact detectors, physically but not electrically attached to the scalp (Masterton et al., 2007). In the present topic, they provide detailed instructions for building such detectors and interfacing them with a commercially available MRI-compatible EEG system (Abbott et al., 2015). This team also previously developed event-related ICA (eICA), to map fMRI activity associated with inter-ictal events observed on EEG (Masterton et al., 2013b). The method is capable of distinguishing separate sub-networks characterised by differences in spatio-temporal response (Masterton et al., 2013a). The eICA approach frees one from assumptions regarding the shape of the time-course of the neuronal and haemodynamic response associated with inter-ictal activity (which can vary according to spike type, can vary from conventional models and may include pre-spike activity (Masterton et al., 2010); issues explored further in the present topic by (Faizo et al., 2014) and (Jacobs et al., 2014)). However, the effectiveness of eICA can be affected by fMRI noise or artefact. In the present topic we see that application of a fully automated de-noising algorithm (SOCK) is now recommended, as it can substantially improve the quality of eICA results (Bhaganagarapu et al., 2014).
The ability to detect activity associated with inter-ictal events can also be improved with faster image acquisition. Magnetic Resonance Encephalography (MREG) is a particularly fast fMRI acquisition method (TR=100ms) that achieves its speed using an under-sampled k-space trajectory (Assländer et al., 2013; Zahneisen et al., 2012). This has now been applied in conjunction with simultaneous EEG, to reveal that the negative fMRI response in the default-mode network is larger in temporal compared to extra-temporal epileptic spikes (Jacobs et al., 2014).
The default mode network and its relationship to epileptiform activity is also examined in several other papers in this topic. In a pilot fMRI connectivity study of Genetic Generalised Epilepsy and Temporal Lobe Epilepsy patients, (Lopes et al., 2014) observed that intrinsic connectivity in portions of the default mode network appears to increase several seconds prior to the onset of inter-ictal discharges. The authors suggest that the default mode network connectivity may facilitate IED generation. This is plausible, although causality is difficult to establish and it is possible that something else drives both the connectivity and EEG changes (Abbott, 2015).
Complicating matters further is the question of what connectivity means. There are many ways in which connectivity can be assessed. Jones and colleagues have discovered that some of these do not necessarily correlate well with each other. They examined connectivity between measurements made with intracranial electrodes, connectivity assessed using simultaneous BOLD fMRI and intracranial electrode stimulation, connectivity between low-frequency voxel measures of fMRI activity, and a diffusion MRI measure of connectivity – an integrated diffusivity measure along a connecting pathway (Jones et al., 2014). They found only mild correlation between these four measures, implying they assess quite different features of brain networks. More research in this domain would therefore be valuable.
Whatever the measure of connectivity utilised, most evidence of alterations in connectivity in epilepsy has been obtained from comparison of a group of patients with a group of healthy controls. However, a new method called Detection of Abnormal Networks in Individuals (DANI) is now proposed by (Dansereau et al., 2014). This method is designed to detect the organisation of brain activity in stable networks, which the authors call modularity. The conventional definition of modularity refers to the degree to which networks can be segregated into distinct communities, usually estimated by maximising within-group nodal links, and minimising between group links (Girvan and Newman, 2002; Rubinov and Sporns, 2010). Dansereau take a novel approach to this concept, instead evaluating the stability of each resting state network across replications of a bootstrapped clustering method (Bellec et al., 2010). In the DANI approach, the degree to which an individual’s functional connectivity modular pattern deviates from a population of controls is quantified. Whilst application of the method to epilepsy patients is preliminary, significant changes were reported likely related to the epileptogenic focus in 5 of the 6 selected focal epilepsy patients studied. In several patients, modularity changes in regions distant from the focus were also observed, adding further evidence that the pervasive network effects of focal epilepsy can extend well beyond the seizure onset zone.
When it comes to application of EEG-fMRI to detect the seizure onset zone, there is typically a trade-off between specificity and sensitivity, with the added complication that activity or network changes may also occur in brain regions other than the ictal onset zone. The distant activity may be due to activity propagation from the onset zone, pervasive changes in functional networks creating a ‘permissive state’, or in some cases might be the brain’s attempt to prevent seizures. Specificity and sensitivity of EEG-fMRI to detect the ictal onset zone is explored by (Tousseyn et al., 2014). They determined how rates of true and false positives and negatives varied with voxel height and cluster size thresholds, both for the full statistical parametric map, and for the single cluster that contained the voxel of maximum statistical significance. The latter conferred the advantage of reducing positives remote from the seizure onset zone. As a result, it appeared to be more robust to variations in statistical threshold than analysis of the entire map. One needs to be cautious however, given the small numbers of patients studied, and the fact that the “optimal” settings were determined using receiver operator characteristic curves of the same study data. It remains to be seen how well this might generalise to a different study.
Perhaps the greatest potential for future advancement in EEG-fMRI is in methods to make the most of the all the information captured by each modality. This is highlighted by the work of Deligianni et al, demonstrating with a novel analysis framework the potential to obtain more information on the human functional connectome by utilising EEG and fMRI together (Abbott, 2016; Deligianni et al., 2014).
We hope that you enjoy this collection of papers providing a broad snapshot of advances in brain mapping methods and application to better understand epilepsy.

via Frontiers | Editorial: Functional brain mapping of epilepsy networks: methods and applications | Neuroscience

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[NEWS] New guidance on use of valproate in women, girls of child bearing age with epilepsy published

Apr 2 2019

 

New guidance to support regulations around the use of valproate in women and girls of child bearing age with epilepsy has been published by specialists from 13 UK healthcare bodies including seven Royal Colleges.

And NICE has published a summary of updated guidance for healthcare professionals bringing together all its recommendations and other safety advice on the drug valproate.

The use of sodium valproate during pregnancy is associated with up to a 40 per cent risk of neuordevelopmental disorders and a 10 per cent risk of physical disabilities for an unborn child.

In March 2018, the Medicines and Healthcare products Regulatory Agency published guidelines which meant that valproate could no longer be prescribed for girls and women of childbearing age unless no other effective treatment was available.

Any girl or woman prescribed valproate should also be fully informed of the risks associated with the medication and the need for effective contraception.

But a year on, implementation of the guidelines have thrown up specific challenges with complex issues and individual situations where the best interests of the patient did not always appear to be met.

Claire Glazebrook, Director of Fundraising, Marketing and External Affairs at Epilepsy Society, said:

Over the last year our Helpline has received multiple calls from women, parents and healthcare professionals, all struggling to interpret the guidelines and what they mean for them as individuals. And we know that this experience is replicated across other patient organizations and clinics.

I hope this guidance will help to answer some of their questions and provide clarity in what can be a very emotional and challenging decision.

For some girls and women, they have no option but to take sodium valproate as it may be the only drug that will control their seizures. But that of course means there are some very important and potentially heartbreaking issues to consider around planning a family.

All these women and girls deserve consistency in the advice and information that they receive.”

The new pan-college guidance has been drawn up by Judy Shakespeare of the Royal College of General Practitioners and Sanjay Sisodiya of the Association of British Neurologists and Royal College of Physicians. Sanjay Sisodiya is also Director of Genomics at Epilepsy Society and Professor of Neurology at UCL.

He said: This work has come together through much valued contributions from specialists across all the national bodies involved.

“In some cases the new regulations have lead to situations where the best interests of the patients may not appear to be best served. Some of the points raised by the regulations are also complex ethical issues. We do not attempt to address all these issues in this document but hope that it will bring greater clarity for clinicians  leading to better care for women and girls with epilepsy. All women and girls have individual needs and where possible should be involved in the choices they make about their own health and plans to start a family.”

Writing in the guidance, Professor Dame Sally Davies, Chief Medical Officer for England said:

I am very pleased that the Medical Royal Colleges have come together to produce this important and helpful guidance, so that doctors and other healthcare professionals across primary and secondary care are on the same page regarding the use of sodium valproate – including around instances where its use is still appropriate.”

via New guidance on use of valproate in women, girls of child bearing age with epilepsy published

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[WEB SITE] New epilepsy warning device detects more seizures than current methods – Video

epilepsy warning

A recent study developed and evaluated the effectiveness of a new device to detect epileptic seizures and act as an epilepsy warning.

Despite receiving medication, approximately 30% of people with epilepsy continue to have seizures. Seizures occurring during sleep can be especially dangerous and are often unwitnessed. These epileptic patients are also at high risk for sudden unexpected death in epilepsy (SUDEP), a major cause of death in epileptic patients. Also, patients with an intellectual disability and severe therapy-resistant epilepsy have an estimated 20% lifetime risk of dying from epilepsy. Therefore, the development of an epilepsy warning device could help not only improve the quality of care for patients but also help prevent SUDEP.

One of the current techniques to monitor epilepsy at night is a sensor that reacts to vibrations from rhythmic jerks. Despite techniques, many seizures are still being missed. However, a new device developed by scientists from the Netherlands may be the solution to help reduce the number of epileptic patient deaths occurring during the night. This new high-tech device is a bracelet known as Nightwatch.

Bracelet recognizes two warning signs of severe seizures

The researchers developed the bracelet to recognize two important warnings signs of severe epileptic seizures: an abnormally fast heartbeat and rhythmic jolting movements. When these seizure warnings are detected the bracelet will send an alert to the patient’s caretaker or nurse.

The researchers recently conducted a prospective trial to test the bracelet in 28 intellectually handicapped epilepsy patients. They observed the patients wearing the bracelet for an average of 65 nights. In the event of a severe seizure, the bracelet sounded an alarm. Patients were also filmed to see whether any false alarms occurred or if the bracelet missed any attacks. The results of the trial were recently published in Neurology.

The new technology performed better than current methods 

The bracelet was compared to bed sensors, which are the current standard detection method. The findings showed that the bed sensor only detected 21% of serious attacks and on average remained silent once every four nights per patient. In comparison, the Nightwatch bracelet only missed a serious attack every 25 nights (on average) per patient.

The comparison showed the bracelet detected 85% of all serious night-time epilepsy seizures and 96% of the most severe ones. These results show combining patterns that can trigger seizures, such as heart rate and movement, is a reliable method of detection for night-time seizures.  The care staff of patients during the study reported being positive about the use of the bracelet and patients did not experience discomfort from wearing the bracelet at night.

The researchers expect through the use of the bracelet, the number of SUDEP cases may be reduced by two-thirds and applied globally, this epilepsy warning device could save thousands of lives. However, saving the life of the patient also depends on how quickly caretakers or nurses respond to the alarm. The Nightwatch is now available and can be used by adults at home and in institutions.

Written by Lacey Hizartzidis, PhD

References:

  1. Johan Arends, Roland D. Thijs, Thea Gutter, Constantin Ungureanu, Pierre Cluitmans, Johannes Van Dijk, Judith van Andel, Francis Tan, Al de Weerd, Ben Vledder, Wytske Hofstra, Richard Lazeron, Ghislaine van Thiel, Kit C.B. Roes, Frans Leijten, and the Dutch Tele-Epilepsy Consortium. Multimodal nocturnal seizure detection in a residential care setting. Neurology Nov 2018, 91 (21) e2010-e2019; DOI:10.1212/WNL.0000000000006545.
  2. New epilepsy warning device could save thousands of lives. EurekAlert website https://www.eurekalert.org/pub_releases/2018-11/euot-new110518.php. Accessed January 12, 2019.
  3. Photo credit: LivAssured https://www.eurekalert.org/multimedia/pub/185082.php?from=411220

Disclaimer: Not a sponsored post.

via New epilepsy warning device detects more seizures than current methods – Medical News Bulletin | Health News and Medical Research

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[Abstract] Vagus Nerve Stimulation for the Treatment of Epilepsy

First page of article

Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.

via Vagus Nerve Stimulation for the Treatment of Epilepsy – Neurosurgery Clinics

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