Epilepsy and Malnutrition Seminar by Dr. Adetola Hammed Hassan

Both epilepsy and malnutrition are important public health problems in sub-Saharan Africa with major medical, sociocultural, and economic implications.

Malnutrition can be responsible for electrolytic and vitamin deficiencies which affects neuronal excitability thereby enhancing epileptic activities.

People with epilepsy in developing countries are challenged by stigmatization and rejection giving them less access to appropriate meals resulting in poor nutritional status. This depicts a vicious relationship between malnutrition and epilepsy.

This seminar is generously supported by the Nussenbaum-Vogelstein Family.


Jeanne Paz from Gladstone Institutes, University of California, San Francisco at NYU Langone Health

Traumatic brain injury (TBI) is a leading cause of disability in children and adults. TBI affects 69 million people worldwide yearly and can lead to cognitive dysfunction, difficulty with sensory processing, sleep disruption, and epilepsy. Although TBI acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. Our work aims to understand where, when, and how secondary injuries develop, which is crucial for preventing or disability following TBI. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities. Dr. Paz will present the ongoing work in her laboratory that aims to identify the cellular and circuit mechanisms behind complement-mediated neural plasticity after TBI and its role in post-traumatic epileptogenesis.

This seminar is generously supported by the Nussenbaum-Vogelstein Family.


Michael A. Rogowski, MD/PhD on Role of AMPA Receptors in Epilepsy and as a Target for Antiseizure Medications

Dr. Rogawski will discuss on five key aspects of glutamate-based neurotherapeutics: (1) ionotropic glutamate receptors, (2) the function of AMPA receptors in excitatory synaptic transmission, (3) the role of AMPA receptors in focal and generalized seizures, (4) the mechanism of action of the antiseizure medication perampanel as a noncompetitive AMPA receptor blocker, and (5) the use of perampanel in the treatment of seizures and epilepsy.

This seminar is generously supported by the Nussenbaum-Vogelstein Family.


Clinical and Research Advances in Non-Epileptic Seizures Seminar

Because the signs and symptoms of non-epileptic seizure (NES) can resemble epileptic seizures, patients are often empirically treated for presumed epilepsy and receive anti-seizure medications and invasive treatments, which do not treat NES. Up to 20% of patients diagnosed with epilepsy have NES, making this a common condition, frequently seen in neurology clinics and units.


You will hear

This seminar described research advances in the diagnosis and treatment of patients with NES, including biomarker studies examining data from bioengineering and from structural and functional neuroimaging.


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About the Speaker

W. Curt LaFrance Jr., MD, MPH, is Director of Neuropsychiatry and Behavioral Neurology at Rhode Island Hospital (RIH) and Professor of Psychiatry and Neurology at Alpert Medical School, Brown University. He is Staff Physician at the Providence VAMC, and Clinical Lead for the VA National Telemental Health Center Tele-Seizures clinic. His research focuses on developing new biomarkers and treatments for neuropsychiatric aspects of epilepsy, conversion disorders and TBI.

This seminar is part of CURE Epilepsy’s Frontiers in Research Seminar Series. This program is generously supported by the Nussenbaum-Vogelstein Family and aims to help educate and expose researchers, clinicians, and students to exciting epilepsy research and also provide opportunities for young investigators to interact with leaders in the field.

Q&A with W. Curt LaFrance Jr., MD, MPH

If non-epileptic seizures reoccur, are epileptic seizures are also likely to reoccur?

We follow people over the course of time, and what we found, interestingly, is there can be periods… what we call periods of quiescence, or quiet periods, where there’s no seizures. This can be for epilepsy or for non-epileptic seizures. In taking the history, in talking with people, we’ll say… They’ll come back, and they’ll say, oh, I just had a flurry of seizures again. This could be epileptic or nonepileptic seizures. The question is, anything different recently?

More times than not, what we’ll hear is actually, I was getting ready for a final, and I pulled an allnighter. And then after the final, I had the seizures again. Non epileptic Seizures Diagnosis, Treatment, and Strategies Page 13 of 22 Again, this could be for epileptic or for non-epileptic seizures. As you’re aware, sleep deprivation is one of the ways that we actually induce seizures, whether epileptic or non-epileptic seizures. So, I’ll see what we’ll call environmental changes. That can be after a period of a quiet period, and then a flurry again, or recurrence, sometimes environmental. Sometimes it can be physiologic changes in the person. I see this from kids, to adolescents, to adults, I see this with other medications being added, bodily changes happening, all kinds of things.

There were some questions that came in, asking about whether there could be age-related, from childhood to adulthood, can that induce more nonepileptic seizures? There was also a question about whether trauma, for example, having wisdom teeth taken out, can that induce? That’s a pretty big stressor in a young person’s life.

Yes. You said a very important word there, you said stressors in their life. So, I’ll hear this from some people, they’ll say, but doc, I wasn’t even stressed, and I had the seizure. So, I’m not talking about stress-induced seizures, I’m talking about life stressors contributing to the formation. What I mean by that is, sometimes it’s not in the ramped-up period, where a lot of things are happening in life, or somebody just had a procedure, or a surgery, or something like that. They do happen postoperatively. I’ve seen them coming out of anesthesia, nonepileptic seizures.

But also, after procedure, like wisdom teeth extraction. But it also happens in what I call the letdown period. What I mean by that is, I’m on the beach, and I’m with my family, and it’s wonderful, and I had a seizure there. What’s that all about doctor? So sometimes people, when they’re in the ramped-up stage, they’ve got their defenses up, and then they’re when they’re in the letdown stage, then their defenses are down, and that’s where the seizure may occur. So, there’s not a one-to-one relationship of, I was stressed out, I had a seizure. It could be in different types of environments. So, I refer to life stressors, life events… we’ve all got life events.

Another thing that people hear, is that well, we’re not seeing an EEG signature, but it’s because the seizure is occurring deep in the brain, and we just can’t pick it up. How would you respond to that??

There are some locations, or foci, in the brain that elude scalp EEG signal. So, what I mean by that is if you’ve got a what we call mesial temporal, or some frontal lobe seizures, epileptic seizures, they actually… you can have the epileptic seizure, and the scalp EEG is not going to pick up that abnormal brain cell firing, epileptiform activity. So, in that case, it’s not that it’s not epilepsy, it’s that the focus eluded the scalp electrode. So we’ve got a clue there, though.

So just because you haven’t a normal EEG doesn’t mean it’s not epileptic seizures. We’ve got a clue, though, and we use the term semiology, ictal semiology, and all that means is the physical characteristics of the seizure. There are certain ways that frontal lobe epileptic seizures present, characteristically, that differ from psychogenic non-epileptic seizures. Even though both of those might have scalp negative EEG, we can look at the ictal semiology, the physical characteristics of the seizure, and we can make a comparison.

So that’s why you heard me say earlier, the right history, with the right witnessed seizure, with the right EEG, those are the ways that we get the documented… That’s how we get documented non-epileptic seizures. If we have the seizure characteristics, even though it’s a scalp negative EEG we may say, hmm, this looks more like frontal lobe epilepsy than it does psychogenic non-epileptic seizure, just because I’m watching the seizure myself. That’s the importance of the video EEG.

How do we find providers were trained to provide these therapies in our states or regions?

I would say start with your local epilepsy center, and say, do you have people who are trained in treatment for non-epileptic seizures? Now, that doesn’t mean that they were trained with taking control of your seizures workbook, they may have their own approach. What I showed you was just one of a number of approaches. So, this is not the be all and end all for everybody. There may be places around Non epileptic Seizures Diagnosis, Treatment, and Strategies Page 15 of 22 the country, who say yeah, we’ve got somebody who’s been treating people for 20 years, and they use this approach.

So I would say start with your local seizure, with your local epilepsy center, your local epileptologist. If there’s a neuropsychiatry department, sometimes they’ll do overlap brain and behavior, and you can contact them. I would say start locally.

Are non-epileptic seizures ever a diagnosis that can be removed from a patient’s problem list? This is something that needs to be on the radar now and indefinitely.

I view seizures, whether epileptic or non-epileptic seizures, as a chronic medical illness.

I’m thinking now of the International League Against Epilepsy’s more recent definitions for epilepsy. Before, there wasn’t a great definition for resolved, but now there’s a category for resolved epilepsy. So just as there’s a category for resolved epilepsy, you can have a category for non-epileptic seizures. That’s not official from the ILA per se, but I’m thinking, in parallel, what’s been done for the new diagnostic criteria for epilepsy and terminology, that could also be done for nonepileptic seizures.

Here’s what I will say. Life events are still going to keep happening, life is going to keep happening. Somebody is going to get sick in the family, a bill is going to come due that you didn’t expect, the car is going to break on the day that you don’t want it. That’s always going to keep happening. The tools that patients get with the workbook; they have to keep applying those tools.

The way that I demonstrate that to patients is, if they have readers, then at the end of the treatment, I’ll say, okay, read this sentence, and they’ll read it. And I’ll say, now take off your glasses and read the next sentence, and they can’t read the sentence. And I’ll say, the glasses didn’t cure you. You have to have the glasses on for you to be able to read, you have to keep using the tools for you to be able to address the stressors, the ongoing life stressors.

So people can go for extended periods… They’ve come back two or three years later, and they’ve said, the stuff came back. And I said, how are you doing… what’s going on in life, and how are you using the tools? And they said, life has gotten a lot harder, I just had two kids, and I’m not using the tools. I forgot about. So, there’s a little booster, and that booster is the thing that helps them to get back on track to use the tools again to address life events that are going to keep happening.

A couple of people have asked about the role of psychogenic seizures, non-epileptic seizures, and posttraumatic stress. I think you’ve already touched on this a bit. It’s not just the current life events that are happening, but the sequelae, as well, and using these tools to address that. Correct?

Yeah. So, people will refer to the various comorbidities or cooccurring illnesses. I didn’t put the slide in, but you’re probably already familiar. We’re talking about epilepsy now. Anywhere from a third to a half of patients with epilepsy also have depression. Anywhere from 20 to 40% of individuals with epilepsy also have anxiety. Anywhere from a third to a half have cognitive issues with epilepsy. So, these are comorbidities, neuropsychiatric comorbidities that occur with epilepsy, very similar in non-epileptic seizures.

So you’ve got about half of the people have comorbid depression with non-epileptic seizures, about half have anxiety, about half of… 40% of civilians, and up to 70% of veterans have PTSD, as you would expect, with non-epileptic seizures. So, a lot of comorbidities. So, it’s not just about treating the seizure. That’s why I was saying earlier, you’ve really got to treat the whole patient.

Can there be a false diagnosis of non-epileptic seizures? Why and how?

The answer is yes, and it can go either way. You can be diagnosed with non-epileptic seizures, and it can be epilepsy, or you can be diagnosed with epilepsy, and it can be non-epileptic seizures. I’ve seen both of those. I’ve mentioned with one of my early distance mentors was Orrin Devinsky, and he said early on, Curt, you have to approach a patient with seizure with humility, because you can be fooled either way. So, people can say, oh, well, I’ve seen that ictal semiology, I’ve seen the physical characteristics of that seizure, and that… That’s got to be a pseudo seizure, they said in a dismissive manner.

You know what? Number one, it’s not a pseudo procedure, and number two, it was actually a very odd manifestation of a frontal lobe epileptic seizure. Conversely, you can have somebody it’s like, wow, that’s a story for epilepsy, I’m going to treat them for two or three years with anti-seizure medications for presumed epilepsy. Nope. This was not epileptic seizures. The AED’s are not going to help the individual.

Do none-epileptic seizures present during sleep?

The answer is yes. The devils in the details here. So, epileptic seizures can arise out of physiologic sleep. Non-epileptic seizures can occur during the nighttime when a person is sleeping. Those are two different statements… So, both of them can occur at night, both of them can occur while people are sleeping. But what I mean by that is, we look at the tracing on the EEG. As many of the individuals know, the EEG changes when we’re in sleep and out of sleep stages.

So what happens is, we’re watching somebody, and then there’s an arousal, so they become awake, out of sleep, and then they have their non-epileptic seizure. That’s how we see that. But we really need the EEG that corresponds to the video to be able to say, oh, you know what, there was an arousal, so they were awake, even though it was at nighttime, when they were sleeping, and it was a non-epileptic seizure, as opposed to literally coming out of physiologic sleep and treated to a seizure. More times than not, it’s going to be epilepsy.

Do you have to have regular events in order for them to be classified as non-epileptic seizures, or can very infrequent events still be characterized as such?

I’ve seen people who have them once a year, and I’ve seen people who have 30 in a day. So, I wish it was that simple, it would make my job a lot easier. But no, it’s never that simple. So, we really have to pay attention to how often are these occurring? When are they occurring? In the workbook, we have a thing called a seizure log, and that’s where the individual really pays attention to their symptoms. So, every day, they’re documenting, I had one seizure at 12:00 PM, 12 noon, in the kitchen, after I was preparing breakfast, and it had this effect on me. So, we get them to start paying attention, whether it’s an epileptic or nonepileptic seizure.

And then when they start to pay attention to what’s happening, and what might be a precipitant to the seizures, then they can use some of the tools to go back and say, when I have my aura, number one, I want to get to a safe place, first thing, I want to let somebody know, if I can, if I have the ability to do that, and then I want to use some of the tools that I’ve been learning to
apply, to, hopefully, prevent the progression of the seizure into the full blown seizure. We’ve seen people with epilepsy and with non-epileptic seizures be able to take that approach.

If there’s nobody in the area in somebody’s region that’s an epilepsy specialist, what can they do? What can this person do? How can they find either remote resources, or is that possible? There are there lots of people in rural areas, or unable to get to an epilepsy center and see a specialist. What do they do?

They keep being an advocate for themselves. Here’s what I mean by that. I tell people, my patients and family members, you are your best advocate. I’ll hear statements like… sometimes they’ll say, doctor, can you write me a letter, I’ll say I Non epileptic Seizures Diagnosis, Treatment, and Strategies Page 21 of 22 can, but I want you to write the letter, and I want you to write the letter to your doctor, your hospital, your congressman. I want you to write letters to the licensing boards. The reason why I say this is because I live in two different worlds on a number of fronts, so in neurology and psychiatry. I live in two different worlds at the same time. In the VA and in the civilian world, I live in two different worlds at the same time.

So interestingly, with the VA system, being trained in telemedicine, I can treat veterans around the country. I go to my office in Providence, Rhode Island, and I see veterans all around the country, because the VA is a national system. So, one of the reasons that people can’t treat across state lines is because for me to treat somebody in Georgia or Arizona, I have to have a license in the state of Arizona, and I’m not going to get 50 licenses to be able to do that. So that’s why I’m saying, lobby. Go to the boards and say, you know what, telehealth has been helping people around the country and around the world, let’s make sure that people who have specialties can treat people, or people who are primary care can treat across state lines, and not have that burden of the system that exists in the civilian world. That would be a way to really push the envelope, which I’m a big fan of.

So that’s what I would say, keep being an advocate for yourself, but also keep asking around. A lot of times people will say, well, I’ve got a local clinician, they’re familiar. I view us in medicine as eternal students. So, some people will say, I’ll see you, and I’ll read the workbook, and we’ll work through this together. That’s another option, is have the local people, whoever it is, to get equipped using the resources that are available. Keep advocating for yourself, is what I would say.

Are non-epileptic seizures less dangerous to the brain than epileptic seizures?

People will ask, am I going to get brain damage from these? What I will say is that… sometimes people who have certain types of epileptic seizures, they can drop their oxygen level, and they can become hypoxic, and that can actually affect the brain, as you’re aware, we don’t see those same oxygen level drops in people who have generalized tonic-clonic non-epileptic seizures. So over time, we don’t see the same brain energy risks that may be associated with some types of epileptic-seizures that we do with non-epileptic seizures.

Serotonergic Mechanisms of Seizure-Induced Central Apnea Seminar

Respiratory dysfunction following generalized convulsive seizures is proposed as a causal mechanism in SUDEP. Central chemosensitivity to carbon dioxide, or CO2, drives ventilation in response to hypercapnia, especially during sleep. Dr. Richerson and colleagues have found that this response may be impaired in people with epilepsy, and that convulsive seizures lead to prolonged inhibition of the ventilatory response to hypercapnia.


You will hear

In a mouse model of Dravet syndrome, Dr. Richerson’s team has obtained evidence that seizures inhibit serotonin neurons that detect changes in CO2 levels. Defining the mechanisms of seizure-induced central apnea may lead to novel preventative treatments for SUDEP.



About the Speaker

The seminar was presented by George Richerson, MD, PhD, Professor and DEO/Roy J Carver Chair in Neuroscience at the University of Iowa, Carver College of Medicine.

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This seminar is part of CURE Epilepsy’s Frontiers in Research Seminar Series. This program is generously supported by the Nussenbaum-Vogelstein Family and aims to help educate and expose researchers, clinicians, and students to exciting epilepsy research and also provide opportunities for young investigators to interact with leaders in the field.