Posts Tagged seizure

[BLOG POST] Mozart and epilepsy: the rhythm beats on

 

I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously.

By Barbara Krafft – The Bridgeman Art Library, Object 574471, Public Domain, Link

 

The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s diseasedementia and sleep disordersThe authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.

Public Domain, Link

The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called  ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elise doesn’t have this effect.

By W.J. Baker (held the expired copyright on the photograph) – Library of Congress[1]Contrairement à une erreur fréquemment répandue le buste a été réalisé par Hugo Hagen, non pas à partir du masque mortuaire mais, comme de nombreux autres, d’après le masque réalisé en 1812 par Franz Klein pour un buste qu’il devait réaliser ensuite., Public Domain, Link

So what does the structure of Mozart’s music do to the brain? One suggestion is that Mozart’s music enhances the body’s parasympathetic drive; this reduces the heart rate, and thereby inhibits the brain’s propensity to epileptic seizures. The suppression of this parasympathetic drive is of course the theory behind using vagus nerve stimulation (VNS) to treat drug-resistant epilepsy. For more on VNS, see my previous blog, Vagus nerve stimulation: from neurology and beyond!

By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0Link

You have surely wondered by now if K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you have not, because the authors of another interesting paper did. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors, Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.   

https://www.publicdomainpictures.net/en/view-image.php?image=76907&picture=dog-amp-child-painting

It therefore appears as if it all rosy in the garden of music and the brain. But it is not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.

By CLASSICNEYO – Own workCC BY-SA 4.0Link

So, is it time for neurologists to start prescribing music?

Or is it too much of a double-edged sword?

Music is #SimplyIrresistible. Luca Florio on Flickr. https://www.flickr.com/photos/elle_florio/29516744480

via Mozart and epilepsy: the rhythm beats on – The Neurology Lounge

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[Abstract] The Role of EEG in the Erroneous Diagnosis of Epilepsy

Summary

Errors in diagnosis are relatively common in medicine and occur in all specialties. The consequences can be serious for both patients and physicians. Errors in neurology are often because of the overemphasis on “tests” over the clinical picture. The diagnosis of epilepsy in general is a clinical one and is typically based on history. Epilepsy is more commonly overdiagnosed than underdiagnosed. An erroneous diagnosis of epilepsy is often the result of weak history and an “abnormal” EEG. Twenty-five to 30% of patients previously diagnosed with epilepsy who did not respond to initial antiepileptic drug treatment do not have epilepsy. Most patients misdiagnosed with epilepsy turn out to have either psychogenic nonepileptic attacks or syncope. Reasons for reading a normal EEG as an abnormal one include over-reading normal variants or simple fluctuations of background rhythms. Reversing the diagnosis of epilepsy is challenging and requires reviewing the “abnormal” EEG, which can be difficult. The lack of mandatory training in neurology residency programs is one of the main reasons for normal EEGs being over-read as abnormal. Tests (including EEG) should not be overemphasized over clinical judgment. The diagnosis of epilepsy can be challenging, and some seizure types may be underdiagnosed. Frontal lobe hypermotor seizures may be misdiagnosed as psychogenic events. Focal unaware cognitive seizures in elderly maybe be blamed on dementia, and ictal or interictal psychosis in frontal and temporal lobe epilepsies may be mistaken for a primary psychiatric disorder.

via The Role of EEG in the Erroneous Diagnosis of Epilepsy : Journal of Clinical Neurophysiology

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[NEWS] Predicting seizures before they happen

Date: June 10, 2019

Source: RCSI

Summary: A new study has found a pattern of molecules that appear in the blood before a seizure happens. This discovery may lead to the development of an early warning system, which would enable people with epilepsy to know when they are at risk of having a seizure.

FULL STORY

A new study has found a pattern of molecules that appear in the blood before a seizure happens. This discovery may lead to the development of an early warning system, which would enable people with epilepsy to know when they are at risk of having a seizure.

Researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted at RCSI (Royal College of Surgeons in Ireland) led the study, which is published in the current edition of the Journal of Clinical Investigation (JCI).

FutureNeuro and RCSI researchers have discovered molecules in the blood that are higher in people with epilepsy before a seizure happens. These molecules are fragments of transfer RNAs (tRNAs), a chemical closely related to DNA that performs an important role in building proteins within the cell. When cells are stressed, tRNAs are cut into fragments. Higher levels of the fragments in the blood could reflect that brain cells are under stress in the build up to a seizure event.

Using blood samples from people with epilepsy at the Epilepsy Monitoring Unit in Beaumont Hospital, Dublin and in a similar specialist centre in Marburg, Germany, the group found that fragment levels of three tRNAs “spike” in the blood many hours before a seizure.

“People with epilepsy often report that one of the most difficult aspects of living with the disease is never knowing when a seizure will occur,” said Dr Marion Hogg, FutureNeuro investigator, Honorary Lecturer at RCSI, and the study’s lead author.

“The results of this study are very promising. We hope that our tRNA research will be a key first step toward developing an early warning system.”

Approximately 40,000 people in Ireland have epilepsy and one third of those do not respond to current treatments, meaning they continue to experience seizures. The World Health Organisation estimates that more than 50 million people worldwide have epilepsy.

“New technologies to remove the unpredictability of uncontrolled seizures for people with epilepsy are a very real possibility,” said Professor David Henshall, Director of FutureNeuro and Professor of Molecular Physiology and Neuroscience at RCSI who was a co-author on the paper.

“Building on this research we in FutureNeuro hope to develop a test prototype, similar to a blood sugar monitor that can potentially predict when a seizure might occur.”

Story Source:

Materials provided by RCSINote: Content may be edited for style and length.


Journal Reference:

  1. Marion C. Hogg, Rana Raoof, Hany El Naggar, Naser Monsefi, Norman Delanty, Donncha F. O’Brien, Sebastian Bauer, Felix Rosenow, David C. Henshall, Jochen H.M. Prehn. Elevation of plasma tRNA fragments precedes seizures in human epilepsyJournal of Clinical Investigation, 2019; DOI: 10.1172/JCI126346

via Predicting seizures before they happen — ScienceDaily

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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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[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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[NEWS] Focused ultrasound offers potential new epilepsy treatment

29 Jan 2019 Tami Freeman
Clinical trial
Researchers at the Ohio State University College of Medicine are studying how well focused ultrasound can treat medication-refractory lobe focal onset epilepsy. (Courtesy: Ohio State University)

Focused ultrasound treatments use multiple ultrasound beams focused deep within the body to provide non-invasive, targeted therapy for a wide range of clinical applications. Now, researchers at The Ohio State University College of Medicine have begun a clinical trial investigating the use of transcranial focused ultrasound to control a specific type of epilepsy in which seizures are not controlled by medication.

The study will enrol up to 10 patients with medication-refractory lobe focal onset epilepsy. Patients will receive MR-guided focused ultrasound through an intact skull to ablate tissue deep in the brain. The treatment works by passing 1024 ultrasound beams through the scalp, skull and brain tissue (without causing any harm) until they converge at a focal point to ablate a specific part of the brain involved in epilepsy.

“We’re pursuing this clinical trial because we know there’s a large unmet clinical need. More than 20 million people worldwide live with uncontrollable seizures because no available treatment works for them,” explains neurosurgeon Vibhor Krishna, who is leading the study. “Our goals are to test the safety of this procedure and study changes in seizure frequency in these patients.”

Earlier this month, a 58-year-old man became the first patient to be treated with focused ultrasound for epilepsy at Ohio State. During the three-hour surgery in an intraoperative MRI-surgical suite, he remained awake and alert, providing real-time feedback to the treatment team. His feedback helped the team safely ablate the brain region involved in spread of his epilepsy without causing undesirable side effects.

After treatment, the research team plan to monitor all the patients closely for one year. They will use neurological exams and neuro-psychological exams to assess language, memory and executive functioning.

“This is an important step in the evolution of focused ultrasound as a mainstream therapy for disorders affecting the brain,” said Neal Kassell, founder and chairman of the Focused Ultrasound Foundation, which is funding the clinical trial. “Ultimately, the results of this study could lead to new, more effective therapies for certain patients with epilepsy.”

 

 

via Focused ultrasound offers potential new epilepsy treatment – Physics World

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[NEWS] Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

 

Elizabeth Delacruz can’t crawl or toddle around like most youngsters nearing their second birthday.

A rare metabolic disorder that decimated her mobility has also led to cortical blindness – her brain is unable to process images received from an otherwise healthy set of brown eyes. And multiple times a day Elizabeth suffers seizures that continually reduce her brain function. She can only offer an occasional smile or make soft bubbly sounds to communicate her mood.

“But a few months ago I heard her say, ‘Mama,’ and I started to cry,” said Carmen Mejia, a subtle quaver in her voice as she recalled the joy of hearing her daughter. “That’s the first time she said something.”

Ms. Mejia realizes it may also be the last, unless doctors can find a way to detect and prevent the epileptic seizures stemming from a terminal disease called pyruvate dehydrogenase deficiency (PDHD) – which occurs when mitochondria don’t provide enough energy for the cells.

A UT Southwestern study gives parents like Ms. Mejia renewed hope for their children: By monitoring the brain activity of a specific cell type responsible for seizures, scientists can predict convulsions at least four minutes in advance in both humans and mice. The research further shows that an edible acid called acetate may effectively prevent seizures if they are detected with enough notice.

Although the prediction strategy cannot yet be used clinically – a mobile technology for measuring brain activity would have to be developed – it signifies a potential breakthrough in a field that had only been able to forecast seizures a few seconds ahead.

“Many of the families I meet with are not just bothered by the seizures. The problem is the unpredictability, the not knowing when and where a seizure might occur,” said Dr. Juan Pascual, a pediatric neurologist with UT Southwestern’s O’Donnell Brain Institute who led the study published in Science Translational Medicine. “We’ve found a new approach that may one day solve this issue and hopefully help other scientists track down the root of seizures for many kinds of epilepsy.”

Debunked theory

The critical difference between the study and previous efforts was debunking the long-held belief among researchers that most cells in epilepsy patients have malfunctioning mitochondria. In fact, Dr. Pascual’s team spent a decade developing a PDHD mouse model that enabled them to first discover the key metabolic defect in the brain and then determine only a single neuron type was responsible for seizures as the result of the metabolic defect. They honed in on these neurons’ electrical activity with an electroencephalogram (EEG) to detect which brainwave readings signaled an upcoming seizure.

“It’s much more difficult to predict seizures if you don’t know the cell type and what its activity looks like on the EEG,” Dr. Pascual said. “Until this finding, we thought it was a global deficiency in the cells and so we didn’t even know to look for a specific type.”

Predicting seizures

The study shows how a PDHD mouse model helped scientists trace the seizures to inhibitory neurons near the cortex that normally keep the brain’s electrical activity in check.

Scientists then tested a method of calculating when seizures would occur in mice and humans by reviewing EEG files and looking for decreased activity in energy-deficient neurons. Their calculations enabled them to forecast 98 percent of the convulsions at least four minutes in advance.

Dr. Pascual is hopeful his lab can refine EEG analyses to extend the warning window by several more minutes. Even then, live, clinical predictions won’t be feasible unless scientists develop technology to automatically interpret the brain activity and calculate when a seizure is imminent.

Still, he said, the discovery that a single cell type can be used to forecast seizures is a paradigm-shifting finding that may apply to all mitochondrial diseases and related epilepsies.

Potential therapy

Dr. Pascual’s ongoing efforts to extend the prediction time may be a crucial step in utilizing the other intriguing finding from the study: the use of acetate to prevent seizures.

The study showed that delivering acetate into the blood stream of PDHD mice gave their neurons enough energy to normalize their activity and decrease seizures for as long as the acetate was in the brain. However, Dr. Pascual said the acetate would probably need more time – perhaps 10 minutes or more – to take effect in humans if taken by mouth.

Acetate, which naturally occurs in some foods, has been used in patients for decades – including newborns needing intravenous nutrition or patients whose metabolism has shut down. But it had not yet been established as an effective treatment for mitochondrial diseases that underlie epilepsy.

Among the reasons, Dr. Pascual said, is that labs have struggled to create an animal model of such diseases to study its effects; his own lab spent about a decade doing so. Another is the widespread acceptance of the ketogenic diet to reduce the frequency of seizures.

But amid a growing concern about potentially unhealthy side effects of ketogenic diets, Dr. Pascual has been researching alternatives that may refuel the brain more safely and improve cognition.

Frequent seizures

Elizabeth, among a handful of patients whose EEG data were used in the new study, has been prescribed a ketogenic diet and some vitamins to control the seizures. Her family has seen little improvement. Elizabeth often has more than a dozen seizures a day and her muscles and cognition continue to decline. She can’t hold her head up and her mother wonders how many more seizures her brain can take.

Elizabeth was only a few months old when she was diagnosed with PDHD, which occurs when cells lack certain enzymes to efficiently convert food into energy. Patients who show such early signs often don’t survive beyond a few years.

Ms. Mejia does what she can to comfort her daughter, with the hope that Dr. Pascual’s work can someday change the prognosis for PDHD. Ms. Mejia sings, talks, and offers stuffed animals and other toys to her daughter. Although her little girl can’t see, the objects offer a degree of mental stimulation, she said.

“It’s so hard to see her go through this,” Ms. Mejia said. “Every time she has a seizure, her brain is getting worse. I still hope one day she can get a treatment that could stop all this and make her life better.”

‘Big questions’

Dr. Pascual is already conducting further research into acetate treatments, with the goal of launching a clinical trial for patients like Elizabeth in the coming years.

His lab is also researching other epilepsy conditions – such as glucose transporter type I (Glut1) deficiency – to determine if inhibitory neurons in other parts of the brain are responsible for seizures. If so, the findings could provide strong evidence for where scientists should look in the brain to detect and prevent misfiring neurons.

“It’s an exciting time, but there is much that needs to happen to make this research helpful to patients,” Dr. Pascual said. “How do we find an automated way of detecting neuron activity when patients are away from the lab? What are the best ways to intervene when we know a seizure is coming? These are big questions the field still needs to answer.”

via Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

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[ARTICLE] SUPPORTIVE PRINCIPLES IN THE PHARMACOLOGICAL MANAGEMENT OF THE PATIENTS WITH EPILEPSY

Abstract

Background: Pharmacological management of patients with epilepsy is still a very challenging approach for the best outcome of these patients. When considering the appropriate treatment choice for patients it is necessary to take into account several factors that can influence the effectiveness and quality of life. Cancelling or changing treatment suddenly can lead to uncontrolled seizures. After a short period without seizures, many patients are tempted to abandon treatment. Cessation of treatment can be discussed after a seizure-free period for at least two years. Treatment should be discontinued gradually by reducing the dosage and constant supervision of the physician. This paper analyses briefly the general pharmacological and treatment methods in several forms of adult epilepsy.

Conclusions: Management of epilepsy means more than observing the medication prescribed by the specialist. It is also important for the patient to maintain his general health status, monitor the symptoms of epilepsy and response to treatment and take care of his safety. Involvement in the management of one’s own affection can help the patient to control his condition and to continue his routine in usual manner. The objective of antiepileptic treatment is to reduce epileptic seizures to zero without intolerable side effects. New treatments should focus not only on reducing the frequency and intensity of seizures but also improving the quality of life of patients. Key words: patient, epilepsy, therapy and dynamics.

Introduction

The analysis of the specialized literature reveals that many issues regarding differential treatment of epilepsy require subsequent clarification. As far as we are concerned, we have designed and developed therapeutic recommendations, in our opinion, effective, supporting the results of treating epilepsy in its various stages, from premonition to status variants. In this context, the main element in the choice of preparations, besides the trivial clinical signs, was the use of sub-curative monitoring data, including repeated EEG examinations, which fixed the subjective response of patients. Choosing the best possible medicine or an optimal combination of medicines is sometimes difficult. The perfect antiepileptic should be long, nonsedative, well tolerated, very active in various types of convulsive and with non-harmful effects on vital organs and functions. In addition, it must be effective in various forms of active epilepsy and in treating underlying epileptic seizures and capable of restoring the electroencephalogram between seizures to its normal form [5; 9; 10; 18; 23; 24; 27; 31; 38; 40; 41; 43].

It is still debatable whether such a drug will ever be discovered, and especially one that will control all types of epilepsy. The thorough study of pharmacological properties allows us to appreciate which of the existing antiepileptics will meet the current requirements of our patients under study. Due to the fact that patients differ considerably after clinical response to known anticonvulsants and the possibilities of treatment with associated drugs are insufficiently and superficially researched, testing of more efficient substances including new combinations continues. Due to the modern medication, which benefits from a wide and sufficiently efficient range of specific drugs, a large proportion of the recurrent and the disabling sequelae of the disease can be prevented. The adverse effects of drugs are low, so many of the past patients who have been labelled for life by this suffering can now live a productive life. The actual ability to control this disease effectively prevents more of its severe consequences [12; 13; 15; 22; 29; 46; 50].

General principles of pharmacotherapy of epilepsies

In the treatment of psychiatric disorders of our patients with epilepsy we have taken into account the following principles:

Appropriate selection of the remedy, its dosing, routes of administration and possible side effects. And we took into account the following:

  1. The syndrome of psychic state – the gradual expression of the disorders, the relationship between productive and negative alterations and the type of impairment of psychic processes.
  2. The dynamic characteristics of the psychic state – the duration of the disturbances, the changes in the presence of paroxysmal manifestations.
  3. The somatic and neurological condition of the patient with epilepsy. This parameter is important in the context

of the evidence of side effects of favorable and unfavorable preparations. Somatic mood dictates and the route of administration of drugs: parenteral in gastrointestinal disorders, endonasal or transorbital (by electrophoresis) when parenteral administration is not preferred.

Individual features of the patient with epilepsy (age, weight, response to anticonvulsant therapy and others) are also considered. It is often forgotten that lower doses are indicated for children and older people as the exchange of substances in them is slow and standard dose treatment leads to accumulation of preparations and adverse effects [6; 7; 14; 19].

We recommend the gradual increase of the doses, with the preference of the minimal effective doses of the drugs. All the above-described drugs are initially indicated at minimal doses, then the dose gradually increases until the first positive effects are displayed, the subsequent increase of the doses is made after a certain period of time to stabilize the positive effect.

Complex treatment – it is necessary to prescribe unimoment of anticonvulsant remedies from different classes and groups in combination with non-medication methods. Polipharmacologic treatment has certain priorities in comparison with monotherapy because it addresses different links of the pathological process. It is important to avoid the multidimensional effects of many drugs, the doubling of the mechanisms of action and the predilection of some and the same psychological processes.

Continuous therapy. The treatment of productive disorders is done until their complete jugulation (sometimes with the purpose of preventing relapse and longer), of the deficient ones by alternating the cures, with gradual modifications [28; 30; 34; 39; 42].

Principles of medication of psychosomatic syndromes in epilepsy

Criteria for the effectiveness of psychotropic remedies administered in epilepsy are those of improving the knowledge and behavioral processes. More differentiated treatment is based on syndrome of mental disorders.

  1. Deficient disorder (transient dementia, mental-mental diminution, etc.) The treatment is continuously practiced, alternating the belts. It is rational to indicate the preparations of different subgroups. The following criteria are taken into consideration when drawing up the treatment scheme:

a) Main mechanism of action: nootrop, general metabolism, cerebrovascular or actoprotector;

b) Predominant action on mediating processes: GABA (piracetam, fenibut, gamma-aminobutyric acid); cholin-ergic (gliatiline); dopaminergic (nakom); and combined (meclofenoxate, glycine, glutamic acid);

c) With predominant action on the function of the encephalic structures: the cerebral and subcortical (nakom), on the left hemisphere (gliatilline); on the right hemisphere (cortexil);

d) With action on psychomotor activity: major stimulation (piracetam, nakom vinpocetine), mean enhancement (aminalone, gamma-aminobutyric acid, cerebrolizine, nicergoline, tanakan), diminishment (fenibut, glycine, ci-narizine);

e) Route of administration: parenteral, internal, endo-nasal, transorbital (by electrophoresis), mixed. Duration of treatment: from 7 days to 4 months (nakom, fenibut). On the basis of this therapy it is also possible to indicate prophylactic doses of anticonvulsants.

  1. For different types of excitation (chaotic, twilight, delusional, manic, psychopathic, etc.) the support treatment are the sedative neuroleptics. Major tranquilizers, barbiturates and other anticonvulsants, may also be indicated sedative antidepressants.
  • Hallucinatory delusions. More rational are antipsy-chotic neuroleptics. In the case of neuroleptic syndrome with caution are added corrective remedies. That adjuvant preparations use daytime tranquilizers, in depressive or anxious states are used antidepressants.
  • Emotional productive disruptions. In the states of excitation are indicated predominantly sedative neuroleptics and tranquilizers, antidepressants – in depression, tranquilizers and antiepileptics – in dysphoria, in anxiety states -neuroleptics and tranquilizers.

  • Productive districts nearby. Psychoparticular depressions are typically treated with “inor” euroleptics, preferably “behavioral correctors” or low doses of risperidone and tranquilizers; in neurotic manifestations (asthenia, obsessions, hysteria, hypocondria) are used tranquilizers and low doses of antidepressants [1; 2; 3; 4; 8; 11; 25; 26].
    КиберЛенинка: https://cyberleninka.ru/article/n/supportive-principles-in-the-pharmacological-management-of-the-patients-with-epilepsy

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    Continue —> SUPPORTIVE PRINCIPLES IN THE PHARMACOLOGICAL MANAGEMENT OF THE PATIENTS WITH EPILEPSY – тема научной статьи по медицине и здравоохранению читайте бесплатно текст научно-исследовательской работы в электронной библиотеке КиберЛенинка

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    [NEWS] Brain-zapping implants that fight depression inch closer to reality | Science News

    Researchers are resetting the part of the brain that can shift mood

    BY LAURA SANDERS, FEBRUARY 10, 2019
    neural activity

    MOOD CHANGER  Neural activity in certain areas of the brain (brightly colored strands show connections emanating from those regions) can be measured to decode mood.

    Like seismic sensors planted in quiet ground, hundreds of tiny electrodes rested in the outer layer of the 44-year-old woman’s brain. These sensors, each slightly larger than a sesame seed, had been implanted under her skull to listen for the first rumblings of epileptic seizures.

    The electrodes gave researchers unprecedented access to the patient’s brain. With the woman’s permission, scientists at the University of California, San Francisco began using those electrodes to do more than listen; they kicked off tiny electrical earthquakes at different spots in her brain.

    Most of the electrical pulses went completely unnoticed by the patient. But researchers finally got the effect they were hunting for by targeting the brain area just behind her eyes. Asked how she felt, the woman answered: “Calmer in my nerves.”

    Zapping the same spot in other participants’ brains evoked similar responses: “I feel positive, relaxed,” said a 53-year-old woman. A 60-year-old man described “starting to feel a little more alive, a little more energy.” With stimulation to that one part of the brain, “participants would sit up a little straighter and seem a little bit more alert,” says UCSF neuroscientist Kristin Sellers.

    Such positive mood changes in response to light neural jolts, described in the Dec. 17 Current Biology, bring researchers closer to an audacious goal: a device implanted into the brains of severely depressed people to detect a looming crisis coming on and zap the brain out of it.

    It sounds farfetched, and it is. The project is “fundamental, pioneering, discovery neuroscience,” says Mark George, a psychiatrist and neurologist at the Medical University of South Carolina in Charleston. George has been studying depression for 30 years. “It’s like sending a spacecraft to the moon.”

    This video shows the location of brain regions involved in emotion processing: the orbitofrontal cortex (green), cingulate (red), insula (purple), hippocampus (yellow) and amygdala (blue). The dots show where electrodes were placed to monitor seizures in patients with epilepsy.

    Still, in the last several years, teams of scientists have made startling amounts of progress, both in their ability to spot the neural signatures that come with a low mood and to change a person’s feelings.

    With powerful computational methods, scientists have recently zeroed in on some key features of depressed brains. Those hallmarks include certain types of brain waves in specific locations, like the one just behind and slightly above the eyes. Other researchers are focused on how to correct the faulty brain activity that underlies depression.

    A small, implantable device capable of both learning the brain’s language and then tweaking the script when the story gets dark would be an immensely important clinical tool. Of the 16.2 million U.S. adults with severe depression, about a third don’t respond to conventional treatments. “That’s a huge number of people with a very disabling and probably underdiagnosed and underappreciated illness,” says neurologist Vikram Rao, who is working on the UCSF project with Sellers.

    A disease of circuits

    When George began studying depression decades ago, the field was still haunted by Sigmund Freud, who blamed the disorder on bad parenting and repressed anger. Soon after came the chemical imbalance concept, which held that the brain just needs a dash of the right chemical signal to fix itself. “It was the ‘brain is soup’ model,” George says. Toss in more of the crucial ingredient — serotonin, for instance — and the recipe would sing.

    “We have a very different view now,” George says. Thanks to advances in brain imaging, scientists see depression as a disorder of neural circuits — altered connections between important brain regions can tip a person into a depressed state. “We’ve started to define the road map of depression,” George says.

    Depression is a disorder, but one that’s tightly linked to emotion. It turns out that emotions span much of the brain. “Emotions are more widespread than we thought,” says cognitive neuroscientist Kevin LaBar. With his colleagues at Duke University, LaBar has used functional MRI scans to find signatures of certain emotions throughout the brain as people are feeling those emotions. He found the wide neural reach of sorrow, for instance, by prompting the emotion with gloomy songs and films.

    Some electrical arrays that researchers at the University of California, San Francisco are testing sit on the surface of the brain (top); others penetrate deep into brain tissue (bottom).

    Functional MRI allows scientists to see the entire scope of a working brain, but that wide view comes with the trade-off of lower resolution. And resolution is what’s needed to precisely and quickly sense — and change — brain activity. Implanting electrodes, like those used in the UCSF project, gives a more nuanced look into select brain areas. Those detailed recordings, taken from people undergoing epilepsy treatment, are what allowed neural engineer Maryam Shanechi to decode the brain’s emotions with precision.

    As seven patients spent time in the hospital with electrodes monitoring brain activity, their emotions naturally changed. Every so often, the participants would answer mood-related questions on a tablet computer so that researchers could measure when the patients shifted between emotions. Then Shanechi, of the University of Southern California in Los Angeles, and her colleagues matched the brain activity data to the moods.

    The task wasn’t simple. The implanted electrodes recorded an enormous pile of data, much of it irrelevant to mood. Shanechi and her team developed an algorithm to distill all that data into a few key predictive brain regions for each person. The resulting decoder could tell what mood a person was in based on brain activity alone, the team reported in the October Nature Biotechnology. “In every single individual, we can show how their mood changes in real time,” Shanechi says.[…]

    more —-> Brain-zapping implants that fight depression inch closer to reality | Science News

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