Tag Archives: #seizures

3-D ‘Heat Map’ Animation Shows How Seizures Spread in the Brains of Patients with Epilepsy (Neuroscience)

For 29 years, from the time she was 12, Rashetta Higgins had been wracked by epileptic seizures – as many as 10 a week – in her sleep, at school and at work. She lost four jobs over 10 years. One seizure brought her down as she was climbing concrete stairs, leaving a bloody scene and a bad gash near her eye.

A seizure struck in 2005 while she was waiting at the curb for a bus. “I fell down right when the bus was pulling up,” she says. “My friend grabbed me just in time. I fell a lot. I’ve had concussions. I’ve gone unconscious. It has put a lot of wear and tear on my body.”

Rashetta Higgins after surgery in the UCSF Medical Center
Rashetta Higgins at the UCSF Helen Diller Medical Center at Parnassus Heights after surgery to implant more than 150 electrodes to monitor her seizures. Photo courtesy of Rashetta Higgins

Then, in 2016, Higgins’ primary-care doctor, Mary Clark, at La Clinica Vallejo, referred her to UC San Francisco’s Department of Neurology, marking the beginning of her journey back to health and her contribution to new technology that will make it easier to locate seizure activity in the brain. Medication couldn’t slow her seizures or diminish their severity, so the UCSF Neurology epilepsy team recommended surgery to first record and pinpoint the location of the bad activity and then remove the brain tissue that was triggering the seizures.

In April, 2019, Higgins was admitted to UCSF’s 10-bed Epilepsy Monitoring Unit at UCSF Helen Diller Medical Center at Parnassus Heights, where surgeons implanted more than 150 electrodes. EEGs tracked her brain wave activity around the clock to pinpoint the region of tissue that had triggered her brainstorms for 29 years.

In just one week, Higgins had 10 seizures, and each time, the gently undulating EEG tracings recording normal brain activity jerked suddenly into the tell-tale jagged peaks and valleys indicating a seizure.

To find the site of a seizure in a patient’s brain, experts currently look at brain waves by reviewing hundreds of squiggly lines on a screen, watching how high and low the peaks and valleys go (the amplitude) and how fast these patterns repeat or oscillate (the frequency). But during a seizure, electrical activity in the brain spikes so fast that the many EEG traces can be tough to read.

“We look for the electrodes with the largest change,” says Robert Knowlton, MD, professor of Neurology, the medical director of the UCSF Seizure Disorders Surgery Program and a member of the UCSF Weill Institute of Neurosciences. “Higher frequencies are weighted more. They usually have the lowest amplitude, so we look on the EEG for a combination of the two extremes. It’s visual – not completely quantitative. It’s complicated to put together.”

Measuring the Lines

Enter Jonathan Kleen, MD, PhD, assistant professor of Neurology and a member of the UCSF Weill Institute of Neurosciences. Trained as both a neuroscientist and a computer scientist, he quickly saw the potential of a software strategy to clear up the picture – literally.  

“The field of information visualization has really matured in the last 20 years,” Kleen said. “It’s a process of taking huge volumes of data with many details – space, time, frequency, intensity and other things – and distilling them into a single intuitive visualization like a colorful picture or video.”

Kleen developed a program that translates the hundreds of EEG traces into a 3-D movie showing activity in all recorded locations in the brain. The result is a multicolored 3-D heat map that looks very much like a meteorologist’s hurricane weather map.

Video: This video shows the OPSCEA (or “Ictal Cinema”) technology developed at the UCSF Epilepsy Center. It converts the usual complex “traced-based” recordings of brain waves that doctors see (on the right) into an intuitive heat map projected on the patient’s own 3D reconstructed brain (right hemisphere of brain show in main view). Each trace (line) on the right is from a single intracranial electrode (black dots in the brain view). The seizure intensity is calculated automatically from the traces (specifically from the location of the arrow) and converted into color intensity (using a “line length” algorithm), revealing how activity in a given seizure moves in space and time. The technology also applies “slice views” (example shown halfway through the video) so that activity from electrodes deep in the brain can be seen in addition to the brain surface. © UCSF

The heat map’s cinematic representation of seizures, projected onto a 3-D reconstruction of the patient’s own brain, helps one plainly see where a seizure starts and track where, and how fast, it spreads through the brain.

The heat map closely aligns with the traditional visual analysis, but it’s simpler to understand and is personalized to the patient’s own brain.

“To see it on the heat map makes it much easier to define where the seizure starts, and whether there’s more than one trigger site,” Knowlton said. “And it is much better at seeing how the seizure spreads. With conventional methods, we have no idea where it’s spreading.”

Researchers are using the new technology at UCSF to gauge how well it pinpoints the brain’s seizure trigger compared with the standard visual approach. So far, the heat maps have been used to help identify the initial seizure site and the spread of a seizure through the brain in more than 115 patients.

Kleen’s strategy is disarmingly simple. To distinguish seizures from normal brain activity, he added up the lengths of the lines on an EEG. Seizures show up as high peaks and low valleys that make their cumulative length quite long, while gently undulating brain waves make much shorter lines. Kleen’s software translated these lengths into different colors, and the visualization was born.

The technology proved pivotal in Higgins’ treatment.

“Before her recordings, we had feared that Rashetta had multiple seizure-generating areas,” Kleen said. “But her video made it plainly obvious that there was a single problem area, and the bad activity was rapidly spreading from that primary hot spot.”

The journal Epilepsia put Kleen’s and Knowlton’s 3-D heat map technology on the cover, and the researchers made their software open-source, so others can improve upon it.

“It’s been a labor of love to get this technology to come to fruition” Kleen said. “I feel very strongly that to make progress in the field we need to share technologies, especially things that will help patients.”

A Fresh Start

Higgins has been captivated by the 3-D heat maps of her brain.

“It was amazing,” she said. “It was like, ‘That’s my brain. I’m watching my brain function.’”

And the surgery has been a life-changing success. Higgins hasn’t had a seizure in more than two years, feels mentally sharp, and is looking for a job.

“When I wake up, I’m right on it every morning,” she said. “I waited for this day for a long, long time.”

Featured image: Animation shows a 3D heat map of a where a seizure is occuring in the brain © UCSF


Reference: Kleen, J.K., Speidel, B.A., Baud, M.O., Rao, V.R., Ammanuel, S.G., Hamilton, L.S., Chang, E.F. and Knowlton, R.C. (2021), Accuracy of omni-planar and surface casting of epileptiform activity for intracranial seizure localization. Epilepsia, 62: 947-959. https://doi.org/10.1111/epi.16841


Provided by UCSF

New Dietary Treatment For Epilepsy Well Tolerated and Reduced Seizures (Food / Neuroscience)

The first clinical trial of a new dietary treatment for children and adults with severe forms of epilepsy, co-developed by UCL researchers and based on the ketogenic diet, has been successfully completed.

For the study, published in Brain Communications, clinicians evaluated the use of K.Vita®,  (also known as Betashot), an oral liquid dietary supplement developed by UCL in collaboration with Royal Holloway, University of London, and Vitaflo International Ltd.

The ketogenic diet (KD) consists of high-fat, low-carbohydrate and adequate protein consumption and mimics the fasting state, altering the metabolism to use body fat as the primary fuel source. This switch from carbohydrates to fat for body fuel is known as ketosis.

It is widely used to treat drug resistant epilepsies. However, the highly restrictive diet, which can cause constipation, low blood sugar, and stomach problems, can have poor compliance and is not suitable for everyone. Some KD supplements are also known to be unappetising.

K.Vita is based on novel findings by UCL researchers*, who discovered a different underlying mechanism to explain why the KD is effective against epilepsy; in developing a new treatment, researchers also sought to reduce the adverse side effects caused by KD.

Corresponding author Professor Matthew Walker (UCL Queen Square Institute of Neurology) said: “The ketogenic diet has been used for 100 years to treat epilepsy, helping reduce seizures in both children and adults.  

“It has long been thought the diet was effective due to its production of ketones**, however we now believe the increase in levels of the fatty acid, decanoic acid, also produced by the diet, may provide the powerful antiseizure effects.

“In this study we evaluated a newly developed medium chain triglyceride (type of dietary fat) supplement, designed to increase levels of decanoic acid, while also reducing the adverse side effects, and to be more palatable.”

For the feasibility trial, researchers wanted to establish participants’ tolerance (side effects such as bloating or cramps) to the treatment, acceptability (flavour, texture, taste) and compliance (how easy it is to use K.Vita at the advised quantity, as part of their daily diet). 

As secondary outcomes, they also monitored the frequency of epileptic seizures or paroxysmal events (fits, attacks, convulsions) and whether ketone production was decreased.  

In total, 35 children (aged 3 to 18) with genetically caused epilepsy and known to be unresponsive to drugs, and 26 adults with drug-resistant epilepsy*** (DRE), were given K.Vita liquid supplements (a drink), to be taken with meals. They were also asked to limit high-refined sugary food and beverages from their diets.

The trial lasted 12 weeks with K.Vita treatments increasing incrementally over time, taking into account individuals’ tolerance to the treatment.

In total, 23/35 (66%) children and 18/26 (69%) adults completed the trial i.e they were continuing to take K.Vita at 12 weeks. Gastrointestinal disturbances were the primary reason for discontinuation, and their incidence decreased over time

Over three-quarters of participants/caregivers reported favourably on sensory attributes, such as taste, texture and appearance, and ease of use.

In regards to the secondary outcomes, there was a mean 50% reduction in seizures or paroxysmal events, and fewer than 10% of people on the diet produced significant ketones.

Commenting on the findings, Professor Walker, who is also a consultant neurologist at the National Hospital for Neurology and Neurosurgery, said: “Our study provides early evidence of the tolerability and effectiveness of a new dietary supplement in severe drug-resistant epilepsies in adults and children and provides a further treatment option in these devastating conditions.

“It also offers an alternative, more liberal, diet for those who cannot tolerate or do not have access to ketogenic diets.”

He added: “While this study was not designed to include enough patients to fully assess the supplement’s effects on seizures, it is exciting to report that there was a statistically significant reduction in the number of seizures in the group overall after three months of treatment.

“Furthermore, high ketone levels were not observed in over 90% of the participants. This indicates that the effect of the diet was independent from ketosis; this is important because high ketone levels in the ketogenic diets contribute to both short- and longer-term side effects.”

First author, Dr Natasha Schoeler, Research Dietitian at UCL Great Ormond Street Institute of Child Health, commented: “This novel dietary approach for epilepsy management involves following the principles of a healthy balanced diet alongside use of K.Vita, allowing greater dietary freedom compared to ketogenic diets. Our approach also requires much less input from a specialist dietician than is required by traditional ketogenic diets, and so may allow more widespread access to people with drug-resistant epilepsy.”

Researchers say larger, controlled studies of K.Vita are now needed to determine the precise epilepsies and conditions in which the supplement is most effective.

Patients were recruited from Great Ormond Street Hospital, Chalfont Centre for Epilepsy and The National Hospital for Neurology and Neurosurgery, part of UCLHThe study was funded by VitaFlo International Ltd.

*It has been traditionally thought that the KD helps prevent seizures through the breakdown of fats, mimicking starvation. However, over the last decade, researchers at UCL and Royal Holloway, University of London, have shown that the fats themselves in the diet can prevent seizures. This has enabled the development of a novel dietary treatment for epilepsy that does not depend on a strict dietary regimen. Review published in Lancet Neurology

**Ketone is the chemical that your liver produces when it breaks down fats. The body uses ketones for energy typically during fasting, long periods of exercise, or when you don’t have as many carbohydrates

*** Drug resistant epilepsy (DRE) is a term used to describe when adequate trials of two anti-epileptic drugs (AEDs) have failed to control a person’s seizures. Some people also refer to this as “refractory”, “intractable” or “uncontrolled” epilepsy. 

Links

Image

‘Old woman helping a fainted girl to get back on her feet’, Credit, Madrolly on iStock


Reference: Natasha E Schoeler, Michael Orford, Umesh Vivekananda, Zoe Simpson, Baheerathi Van de Bor, Hannah Smith, Simona Balestrini, Tricia Rutherford, Erika Brennan, James McKenna, Bridget Lambert, Tom Barker, Richard Jackson, Robin S B Williams, Sanjay M Sisodiya, Simon Eaton, Simon J R Heales, J Helen Cross, Matthew C Walker, K.Vita Study Group, K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy, Brain Communications, 2021;, fcab160, https://doi.org/10.1093/braincomms/fcab160


Provided by UCL

Case Western Reserve Researchers Identify Potential Approach to Controlling Epileptic Seizures (Neuroscience)

Researchers from Case Western Reserve University have identified a potential new approach to better controlling epileptic seizures.

Lin Mei, professor and chair of the Department of Neurosciences at the Case Western Reserve School of Medicine, who led the new study in mouse models, said the team found a new chemical reaction that could help control epileptic seizures.

Their findings were recently published in The Journal of Clinical Investigation.

Epilepsy is a neurological disorder in which abnormal brain activity causes seizures or periods of unusual behavior, sensations and sometimes loss of awareness.

A human brain contains about 86 billion nerve cells, also known as neurons. Eighty percent of them–known as excitatory neurons–send messages to bundles of nerves that control muscles, typically calling on them to do something. In a healthy brain, activity that excitatory neurons inspire is managed by the remaining 20% of nerve cells, called inhibitory neurons.

“This balance between excitatory and inhibitory neurons is absolutely important for everything that we do,” Mei said. “When the balance is tilted, so that excitatory neurons are super active, there will be a problem. It’s highly likely there will be epilepsy.”

Two mechanisms cause epilepsy: One is genetic; the other is environmental.

In Dravet syndrome, a genetic type of epilepsy that is among the more severe forms of the condition, the sodium channel–a membrane pore critical for inhibiting neuron activation–is mutated and allows excitatory neurons to misfire, causing seizures.

Lin Mei © Case Western Reserve University

“It would be great if you could find a mechanism to make the sodium channels more stable,” Mei said.

He and his colleagues found that a chemical reaction in the brain, called neddylation, stabilizes the sodium channel in mouse models. When the researchers produced a mouse that lacked the protein required for neddylation in inhibitory neurons, it developed epilepsy. The surprising emergence of the condition inspired the team to explore the neddylation process in more depth; eventually they discovered that neddylation plays a critical role of for the sodium channel.

“If we have that chemical reaction in check,” he said, “you could help control epilepsy.”

Mei said the research provided evidence that a mutation in patients with epilepsy had a problem with neddylation, suggesting “neddylation theory” may apply to human patients.

The next step in their research, he said, is to identify drugs or approaches that can manipulate this chemical reaction to stabilize the sodium channel. The researchers are also conducting further experiments to determine whether this applies to patients with other types of epilepsy, not just Dravet patients.

“Our finding that neddylation can prevent epilepsy in mouse models represents a new direction for future research,” he said. “With this new lead, scientists or pharmaceutical companies can look for chemicals to boost neddylation. The concept is still in an early stage and much needs to be done to make a difference for patients.”

This chemical reaction–neddylation–has also been considered a target for cancer research, Mei said, so it could have applications beyond epilepsy.

Featured image: Image of epilepsy nerves © CASE


Reference: Wenbing Chen, … , Wen-Cheng Xiong, Lin Mei, “Neddylation stabilizes Nav1.1 to maintain interneuron excitability and prevent seizures in murine epilepsy models”, J Clin Invest. 2021;131(8):e136956. https://doi.org/10.1172/JCI136956


Provided by Case Western Reserve University

UVA Develops Imaging Approach to Help Stop Epilepsy Seizures (Neuroscience)

An advanced imaging approach developed at the School of Medicine could let surgeons determine the best target in the brain to stop epilepsy seizures, new research suggests.

UVA’s approach could improve patient outcomes and open the underused surgery to patients who are now ineligible, the research team reports.

“This imaging approach is significant as it creates 4D brain maps which offer additional sensitivity over standard-of-care imaging by revealing rates of glucose uptake rather than final absolute glucose uptake,” said imaging expert Bijoy Kundu, PhD, of UVA’s Department of Radiology and Medical Imaging and UVA’s Department of Biomedical Engineering. “This imaging approach might be beneficial as it may offer non-invasive localization of potential epileptic foci.”

Preventing Epilepsy Seizures

UVA’s new approach uses an enhanced form of positron-emission tomography (PET) to measure glucose use in the brain. This allows doctors to pinpoint the trouble spot in the brain that is triggering seizures. Once that spot is identified, it can be removed surgically, stopping the seizures.

PET scans have been used in the past to identify epilepsy trouble spots, but such scans have limited accuracy and often fail to identify an appropriate target. So a team of UVA researchers, backed by the UVA Brain Institute, developed the new approach, called “parametric dynamic FDG-PET imaging” (p-dFDG-PET).

To assess if the new approach offers improved sensitivity and accuracy, Kundu and UVA neurologist Mark Quigg, MD, launched a small pilot study. They performed scans on seven participants for whom traditional PET imaging had failed to identify a target. The results were encouraging: The technique located appropriate trouble spots in all seven.

“In the one patient who underwent successful surgery, p-dFDG-PET predicted the surgical target,” the researchers write in a new scientific paper outlining their findings. “In contrast, in the one patient who underwent unsuccessful surgery, p-dFDG-PET indicated a different surgical target than the one undertaken.”

The researchers say a larger study is needed to more fully assess the potential of UVA’s new approach. But if the technique works as well as the early results suggest, it could transform epilepsy care for many patients. Any hospital with a PET scanner could easily adopt UVA’s approach, the researchers say.

“Too often patients with intractable epilepsy turn away from transformative epilepsy surgery when invasive procedures are required to locate the ‘bad spot’ or the epileptic focus,” Quigg said. “Dynamic PET, as an addition to the noninvasive toolkit, can expand the number of epilepsy surgery candidates.”

About the Epilepsy Research

The researchers shared their findings at October’s World Molecular Imaging Congress and are preparing a manuscript for peer-reviewed publication. The research team consisted of Vikram Seshadri, Katherine A. Zarroli, Robert S. Schetlick, James C. Massey, Jose M. Reyes, Thomas J. Eluvathingal Muttikal, James T. Patrie, Stuart S. Berr, Nathan B. Fountain, Kundu and Quigg.

The work received financial support from the UVA Brain Institute. UVA’s Department of Biomedical Engineering is a collaboration of the School of Medicine and the School of Engineering and Applied Sciences.

Featured image: A brain map, created by a new approach developed at UVA, to guide surgery to prevent epilepsy seizures. © UVA Health


Provided by UVA Health

Epilepsy Discovery Reveals Why Some Seizures Prove Deadly (Neuroscience)

New research from the School of Medicine has shed light on the No. 1 cause of epilepsy deaths, suggesting a long-sought answer for why some patients die unexpectedly following an epileptic seizure.

The researchers found that a certain type of seizure is associated with sudden death in a mouse model of epilepsy and that death occurred only when the seizure induced failure of the respiratory system.

The new understanding will help scientists in their efforts to develop ways to prevent sudden unexpected death in epilepsy (SUDEP). Based on their research, the UVA team has already identified potential approaches to stimulate breathing in the mice and prevent death after a seizure. The team believe that this new approach could one day help save lives.

“SUDEP is a major concern for patients with epilepsy and their loved ones,” said Manoj Patel, PhD, of UVA’s Department of Anesthesiology. “Our study has identified a sequence of events that takes place during a seizure which can progress and lead to death. Furthermore, we show that intervention during a seizure can rescue death in mice with epilepsy. This project is a long time in the making, and we are excited to share it with the scientific community.”

SUDDEN UNEXPECTED DEATH IN EPILEPSY

Many people were unfamiliar with sudden unexpected death in epilepsy when it took the life of young Disney Channel star Cameron Boyce in 2019. He was only 20 years old. SUDEP, however, is the most common cause of epilepsy-related death. Estimates suggest it is responsible for 8% to 17% of all epilepsy deaths, increasing to 50% in patients whose seizures do not respond to treatment.

Scientists have suggested a variety of potential causes for SUDEP, but UVA’s researchers have brought clarity to why some seizures lead to death while others do not and how we may be able to prevent progression to death.

The researchers found that breathing disruption, known as apnea, began during seizures, as muscles start to stiffen. This stiffening included contraction of the diaphragm, the major breathing muscle, that prevented exhalation, stopping the normal breathing process.

Not all instances of this seizure-induced apnea were fatal; it was only when breathing did not recover immediately after the seizure that the mice died, the researchers found. The UVA team reasoned that artificially stimulating breathing would help prevent sudden death after a seizure. Indeed, in a mouse model of epilepsy, they determined that death could be prevented by directly ventilating the mouse.  

While their work was in lab mice, they confirmed their findings by monitoring breathing frequency and patterns in a human patient with epilepsy. They found there were breathing disruptions, or apneas, during seizures that were very similar to those seen in their mice.

“These results implicate respiratory arrest as a major factor in SUDEP and give us targets for future research on intervention,” said researcher Ian Wenker, PhD. 

Using their innovative new SUDEP model, the UVA researchers have identified potential avenues for preventing SUDEP. One might be to target “adrenergic” receptors that regulate the body’s response to adrenaline and other neurotransmitters. These receptors, the scientists found, are vital to restarting breathing after a seizure and preventing death.

“By identifying some of the receptors involved in stimulating breathing recovery following a seizure, we believe our findings will fuel other approaches to help reduce the risk of death in epilepsy patients,” said researcher Eric Wenger, a graduate student. “We’re eager for other researchers to use our new model to expand our understanding and ability to prevent SUDEP.”

FINDINGS PUBLISHED

The researchers have published their findings in a pair of new papers in the scientific journals Annals of Neurology and Frontiers in Neuroscience. The former was authored by Ian C. Wenker, Frida A. Teran, Eric R. Wengert, Pravin K. Wagley, Payal S. Panchal, Elizabeth A. Blizzard, Priyanka Saraf, Jacy L. Wagnon, Howard P. Goodkin, Miriam H. Meisler, George B. Richerson and Manoj K. Patel. The latter was authored by Eric R. Wengert, Ian C. Wenker, Elizabeth L. Wagner, Pravin K. Wagley, Ronald P. Gaykema, Jung-Bum Shin and Manoj K. Patel.

The research was supported by the National Institutes of Health, grants R01NS103090, 1F31NS115451-01, R01DC014254 and F31DC017370; the National Institute of Neurological Disorders and Stroke, grants NS034509, NS090414, NS103090 and NS110333; Citizens United for Research in Epilepsy; Wishes for Elliot and the UVA Department of Anesthesiology.

Featured image: School of Medicine researchers Eric Wengert (from left), Manoj Patel and Ian Wenker have shed light on what causes Sudden Unexpected Death in Epilepsy (SUDEP).

REFERENCES

(1) Wenker, I.C., Teran, F.A., Wengert, E.R., Wagley, P.K., Panchal, P.S., Blizzard, E.A., Saraf, P., Wagnon, J.L., Goodkin, H.P., Meisler, M.H., Richerson, G.B. and Patel, M.K. (2021), Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy. Ann Neurol, 89: 1023-1035. https://doi.org/10.1002/ana.26053 (2) Eric R. Wengert, Ian Wenker et al., “Adrenergic Mechanisms of Audiogenic Seizure-Induced Death in a Mouse Model of SCN8A Encephalopathy”,Front. Neurosci., 04 March 2021 | https://doi.org/10.3389/fnins.2021.581048


Provided by UVA Health

COVID-19–associated Seizures May Be Common, Linked to Higher Risk Of Death (Medicine)

Key Takeaways

  • Some hospitalized patients with COVID-19 experience “nonconvulsive” seizures detected through electrode tests.
  • Among hospitalized patients with COVID-19, those who had seizures were more likely to need lengthy hospital stays and faced a higher risk of dying.

“There is increasing evidence that non-convulsive seizures can damage the brain and make outcomes worse, similar to convulsions.”

— M. Brandon Westover, MD, PhD, Department of Neurology, Massachusetts General Hospital

COVID-19 can have damaging effects on multiple organs in the body, including the brain. A new study led by investigators at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) indicates that some hospitalized patients with COVID-19 experience nonconvulsive seizures, which may put them at a higher risk of dying. The findings are published in the Annals of Neurology.

“Seizures are a very common complication of severe critical illness. Most of these seizures are not obvious: Unlike seizures that make a person fall down and shake, or convulse, seizures in critically ill patients are usually nonconvulsive,” explains co–senior author M. Brandon Westover, MD, PhD, an investigator in the Department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. “There is increasing evidence that non-convulsive seizures can damage the brain and make outcomes worse, similar to convulsions.”

Westover notes that there have been only a few small reports of seizures in patients with severe COVID-19 illness, and it was previously unclear whether such seizures primarily occur in patients who already have a seizure disorder or whether they can arise for the first time because of COVID-19. The effects of such seizures on patients’ health was also unknown.

To provide insights, Westover and his colleagues analyzed medical information for 197 hospitalized patients with COVID-19 who underwent electroencephalogram (EEG) monitoring—tests that detect electrical activity of the brain using small metal discs attached to the scalp—for various reasons at nine institutions in North America and Europe.

The EEG tests detected nonconvulsive seizures in 9.6% of patients, some of whom had no prior neurological problems. Patients who had seizures needed to be hospitalized for a longer time, and they were four times more likely to die while in the hospital than patients without seizures—suggesting that neurological complications may be an important contributor to the morbidity and mortality associated with COVID-19.

“We found that seizures indeed can happen in patients with COVID-19 critical illness, even those without any prior neurologic history, and that they are associated with worse outcomes: higher rates of death and longer hospital stay, even after adjusting for other factors,” says co-senior author Mouhsin Shafi, MD, PhD, an investigator in the Department of Neurology at BIDMC, medical director of the BIDMC EEG laboratory, and director of the Berenson-Allen Center for Noninvasive Brain Stimulation. “Our results suggest that patients with COVID-19 should be monitored closely for nonconvulsive seizures. Treatments are available and warranted in patients at high risk; however, further research is needed to clarify how aggressively to treat seizures in COVID-19.”

Westover is an associate professor of Neurology at Harvard Medical School (HMS) and Shafi is an assistant professor of Neurology at HMS.

This work was supported by the National Institutes of Health, the Football Players Health Study at Harvard University, the Glenn Foundation for Medical Research and the American Federation for Aging Research, the American Academy of Sleep Medicine, the Department of Defense, and the Eleanor and Miles Shore Fellowship.


Reference: Lin, L., Al‐Faraj, A., Ayub, N., Bravo, P., Das, S., Ferlini, L., Karakis, I., Lee, J.W., Mukerji, S.S., Newey, C.R., Pathmanathan, J., Abdennadher, M., Casassa, C., Gaspard, N., Goldenholz, D.M., Gilmore, E.J., Jing, J., Kim, J.A., Kimchi, E.Y., Ladha, H.S., Tobochnik, S., Zafar, S., Hirsch, L.J., Westover, M.B. and Shafi, M.M. (2021), Electroencephalographic Abnormalities are Common in COVID‐19 and are Associated with Outcomes. Ann Neurol. https://doi.org/10.1002/ana.26060


Provided by Massachusetts General Hospital


About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of “America’s Best Hospitals.”

GOSH-led Metformin Trial Dramatically Reduces Seizures For People With Tuberous Sclerosis (Medicine)

A team of researchers led by UCL Great Ormond Street Institute of Child Health (ICH) and Great Ormond Street Hospital (GOSH) has found that metformin – a drug commonly used to treat Type 2 diabetes – can successfully reduce symptoms associated with tuberous sclerosis complex (TSC), including reduction in the frequency of seizures and the size of brain tumours.

The study, which also included teams from Royal United Hospitals Bath NHS Foundation Trust (RUH) and University Hospitals Bristol and Weston NHS Foundation Trust, recruited 51 patients with TSC who were randomly assigned a placebo or metformin for one year on a dose similar to that given for Type 2 diabetes.

TSC is a genetic disorder characterised by the development of benign tumours due to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. As a result, people with the condition may develop tumours (hamartomas) throughout the body that can affect the heart, kidneys, brain, skin and nails. Although some with the condition may experience few issues, for others it can be disfiguring or even have life threatening complications. As tumours can form in the brain, 75% of people with TSC will have epilepsy, which can lead to daily seizures.

Throughout the study, the research team wanted to see if metformin could limit the tumour growth and epilepsy associated with TSC.

Over the course of the year, the team found a 21% reduction in the size of brain tumours of those who were given metformin, compared to a 3% increase in tumour size for those taking the placebo. Patients with epilepsy and taking metformin saw a 44% drop in the frequency of their seizures, compared to a drop of only 3% for those on the placebo.

Metformin has been gaining attention in cancer research, with large population studies starting to show reduced rates of cancers in those regularly taking it.

Finbar O’Callaghan, professor of paediatric neuroscience at ICH and consultant paediatric neurologist at GOSH and lead investigator of the study said: “This is the first time a cheap, readily available, safe drug has been found to improve the symptoms of TSC. And we found metformin to be even more effective in treating young people. Some patients, who were having multiple seizures a day or week became seizure free after 12 months of treatment, while others are having far fewer seizures than before. We’re excited by what this could mean for the day-to day management of tuberous sclerosis patients.”

“We remain optimistic about the impact we’ve seen on the treatment of brain tumours and epileptic seizures, and believe this is a very promising step forward in improving quality of life for the children and adults living with TSC. Next steps for this work will be to conduct further large-scale trials in Tuberous sclerosis patients to determine the best doses to use and to demonstrate that the effect we have seen is repeatable in a larger population.”

It is estimated that between 3,700 – 11,000 people in the UK live with TSC. There is currently no cure, and only its symptoms can be treated with regular monitoring by a specialist doctor. Although the tumours in TSC patients are benign, the symptoms are not, and current treatments are not only expensive but have toxic side effects as they are immunosuppressants. GOSH treats 150 children with this condition and works closely with the two other hospitals with specialist TSC. The study team run specialist TS clinics at GOSH, the Royal United Hospital in Bath, and Bristol Royal Hospital for Children. These clinics follow up the largest number of TSC patients in the UK.

Zoe Bull, pictured above, was 18 months old when she was diagnosed with TSC, following some seizures. Doctors found benign tumours in her brain, kidneys and on her skin. After her diagnosis, Zoe was seizure-free until she had a focal-aware seizure, aged 10 on a family holiday to Disney World. “It was an unsettling wave-like sensation and what a remember feeling was a loss of control. It’s not something I could openly discuss with anyone, although eventually I was able to tell one friend and then another, until I developed a strong support network,” she said.

Zoe’s condition had been managed with medication to prevent and control her seizures but, as one of the tumours in Zoe’s kidneys was larger than 1cm, she was approached to see if she would like to be involved in the Metformin trial. Although Zoe didn’t know it at the time, she was one of the patients receiving metformin. Her results were encouraging, with a 38% reduction in brain tumour volume and a 75% reduction in seizure frequency during the course of the study.

“My hope is that medicines like this open the door for more treatment options and even a cure for TSC one day. I was fortunate enough to pass my driving test during a time when I was seizure-free but have since surrendered my licence. Hopefully, I will be able to drive again in the future, even if it was just to the shops!”


Featured image: Zoe Bull © GOSH


Reference: Sam Amin, Andrew A Mallick, Hannah Edwards et al., “The metformin in tuberous sclerosis (MiTS) study: A randomised double-blind placebo-controlled trial”, Volume 32, 100715, February 01, 2021. DOI: https://doi.org/10.1016/j.eclinm.2020.100715


Provided by GOSH for Children

Preventing Seizures After Brain Injury Could Stave Off Dementia (Neuroscience)

U of A study shows that measures to prevent post-injury seizures could slow or stop the onset of dementia.

Blocking seizures after a head injury could slow or prevent the onset of dementia, according to new research by University of Alberta biologists. 

“Traumatic brain injury is a major risk factor for dementia, but the reason this is the case has remained mysterious,” said Ted Allison, co-author and professor in the Department of Biological Sciences in the Faculty of Science. “Through this research, we have discovered one important way they are linked—namely, post-injury seizures.” 

“There is currently no treatment for the long-term effects of traumatic brain injury, which includes developing dementia,” added lead author Hadeel Alyenbaawi, who recently completed her PhD dissertation on this topic in the Department of Medical Genetics in the Faculty of Medicine & Dentistry

Traumatic brain injuries are a major risk factor for certain types of dementia, such as Alzheimer’s disease and chronic traumatic encephalopathy. Because seizures are common for patients who have suffered these injuries, neurologists often prescribe anti-epileptic treatments to prevent the seizures. 

Allison said the new research reveals the potential to refine this approach to treatment with the new goal of preventing dementia.

“Our data suggest that, at least in animal models, blocking these seizures also could have a benefit later in life by slowing or preventing the onset of dementia,” he explained. “A prophylactic treatment to prevent dementia is an exciting possibility, though there is much work to be done to develop our concept.”

“We are excited to see that our research and the tools we developed resolved some of the mystery around the link between traumatic brain injury and dementia.”

— Hadeel Alyenbaawi, lead author of the study

Dementia affects more than 432,000 Canadians over the age of 65, two-thirds of whom are women. The Government of Canada estimates that by 2031, dementia will cost our health-care system $16.6 billion each year.

“Dementia is devastating for patients and families, and it is growing in prevalence in our aging demographics,” added Allison. “These findings open the exciting possibility of refining the anti-epileptic treatments to be a prevention not only of seizures, but also dementia.”

“We are excited to see that our research and the tools we developed resolved some of the mystery around the link between traumatic brain injury and dementia,” added Alyenbaawi. “Our data regarding post-traumatic seizure could also help further investigation into promising preventive measures of these incurable diseases.”

Allison and the research team are members of the U of A’s Centre for Prions & Protein Folding Disease. Allison is also an adjunct professor in the Department of Medical Genetics in the Faculty of Medicine & Dentistry, and a member of the U of A’s Neuroscience and Mental Health Institute

The research was funded by the Alzheimer Society of Alberta & Northwest Territories and the Alberta Prion Research Institute, as well as philanthropic donations to the Faculty of Science

The study, “Seizures are a druggable mechanistic link between TBI and subsequent tauopathy,” was published in eLife.

Featured image: The study’s lead author, Hadeel Alyenbaawi, says understanding the link between traumatic brain injury and dementia could help further research into preventive measures. (Photo: Supplied)


Provided by University of Alberta

Innovative Treatment Brings Relief to Man Who Experienced Hundreds of Seizures Daily (Neuroscience)

Since he was a child, Eric Berg, 49, has had seizures due to epilepsy. This past year, his seizures increased in frequency, affecting his day-to-day life and his ability to work. With encouragement from his fiancee, Eric sought treatment at Mayo Clinic.

Watch: Man who experienced hundreds of seizures a day find relief thanks to innovative treatment.

Journalists: Broadcast-quality video (3:27) is in the downloads at the end of this post. Please “Courtesy: Mayo Clinic News Network.” Read the script.

“There was a point that I told Tina (his fiancee), ‘I think I’ve had more seizures in the last couple weeks than I’ve had my whole life.’ It was getting to the point where I was like: ‘OK, this is my brain. Something’s wrong,'” says Eric.

When Eric came to Mayo Clinic, he thought he was experiencing 50 to 60 seizures a day, but he soon learned that he was experiencing around 200 seizures daily.

“It was very clear that he was having very frequent seizures, about 12 an hour,” says Dr. Jeffrey Britton, chair of the Division of Epilepsy at Mayo Clinic. “Eric was found to have a growth in the back left part of his brain, which is a fairly common cause of medically intractable focal onset epilepsy.”

Dr. Britton says surgery wasn’t a good option for Eric, and medications to stop the seizures weren’t working. But at Mayo Clinic, experts are using a new way to treat some seizure disorders: repetitive transcranial magnetic stimulation, or rTMS.

This treatment uses a magnetic field to stimulate certain areas of the brain. While often used to treat depression, repetitive transcranial magnetic stimulation also is showing promise in treating seizures.

Dr. Brian Lundstrom, a neurologist and key figure in developing these treatments in patients with epilepsy, was brought in to see if Eric would be a good candidate for repetitive transcranial magnetic stimulation. “We have used rTMS for other purposes ― for depression, for mapping of epilepsy patients ― but he was the first patient where we used rTMS as a treatment for his epilepsy,” says Dr. Lundstrom.

Eric received his first repetitive transcranial magnetic stimulation treatments in June 2020.

“It might have scared me a little bit more to know that I’m the first one to try something, but now looking back, I mean, it was the best thing that’s probably ever happened in my life, aside from meeting Tina,” says Eric.

“There was a noticeable reduction in seizures that occurred even in the initial few days of the treatment, and then they stopped,” says Dr. Britton.

“June 24 was the last seizure that, you know, I can recall ― the last seizure activity that I had,” says Eric.

Eric returns to Mayo Clinic in Rochester every few months for repetitive transcranial magnetic stimulation treatments.

“The real benefit of something like rTMS, and noninvasive brain stimulation, is just that it is such a low-risk approach,” explains Dr. Lundstrom. Even if it only helps a minority of patients, we think that it may be a reasonable option for many patients.

For Eric, it feels like he has his life back, and he is looking forward to all the new opportunities this treatment has given him.

“Every day that goes by that he doesn’t have a seizure is a victory,” says his fiancee.

Featured image: Eric with his fiancee © Mayo Clinic


Provided by Mayo Clinic