Lauren Whetzel Siburkis

In an effort to improve the quality of life for patients and families affected by epilepsy, researchers at the American Epilepsy Society's (AES) 69th Annual Meeting unveiled personal monitoring devices in the works that aim to detect seizures before they even occur.

According to Mark Lehmkuhle, PhD, a neurosurgery professor at the University of Utah, random seizures are a harsh reality for the more than 1.2 million Americans with uncontrolled epilepsy.

 The fear of unpredictable episodes can shadow every part of these individuals’ lives because of the uncertainty of knowing when they might strike and cause them to lose consciousness.

Each of the devices presented at the meeting offer biometric recording technology that would allow individuals to monitor clinical and subclinical seizure activity in their everyday home environment and receive an advance warning before a seizure strikes.

Researchers say the most common method used to record seizure activity outside of the hospital is the seizure diary. However, Dr. Lehmkuhle said, seizure diaries merely serve as snapshots and do not produce complete, accurate records. That’s because the diaries, he said, minimize the occurrence of non-convulsive seizures and lack records of seizures that occur while an individual is asleep.

With the intent to revolutionize the detection and treatment of seizures, Dr. Lehmkuhle and his team of researchers from the University of Utah and Epitel Inc., developed an inexpensive, disposable, and discreet seizure-monitoring device called the EEG PatchTM. This waterproof patch relies on 2 electrodes to record electroencephalogram (EEG) data during all aspects of everyday life.

He explained that an epileptologist must place the device on a patient’s scalp at a known seizure-prone area of the brain identified by a traditional, wired EEG. This device can operate for 7 days on a single charge, and data can be downloaded anytime for review in the standard European Data Format. A small handheld device can also be used to wirelessly observe the EEG signal in real time.

 “Armed with 7-day, location-specific EEG data, an epileptologist will have a robust record of quantitative seizure counts to better treat patients, revolutionizing therapy,” said Dr. Lehmkuhle. This device is currently being tested in a small pilot feasibility study and follow-up data will be released in the future.

 a team of US researchers described a new device-designed to be worn around the arm-that is capable of detecting and recording generalized tonic-clonic seizures. Results from a phase 3 study revealed that this device, known as the Brain Sentinel: GTC Seizure Detection and Warning System, can detect seizure activity with 100% sensitivity and a very low rate of false detection, as compared to video EEG detection in epilepsy monitoring units at 11 level 4 epilepsy centers across the United States.

According to the authors, the system sends alerts within an average of a few seconds after the onset of the generalized tonic-clonic seizure. This device is currently under Food and Drug Administration review for market clearance.

 from the University of Texas at Dallas tested the accuracy of 2 commercially available wrist-worn devices that detect seizure activity based on changes in an individual’s heart rate, arterial oxygenation, and electrodermal activity. Their results found that seizure detection using heart rate, arterial oxygenation, and electrodermal activity signals is much more accurate than detection by heart rate changes alone.

“These findings may allow for the development of a comfortable, easy-to-manage wrist-worn device capable of recognizing seizures, alerting a caregiver, and creating an electronic diary for use by physicians,” said Diana Cogan, a graduate student and lead author of the study.

Because sudden expected death in epilepsy (SUDEP) cases most often occur during sleep, researchers agreed that individuals who experience seizures overnight could greatly benefit from having a monitoring device to let others know when and if a seizure occurs.

All three presenters discussed the issue of stigmatism in epilepsy. “I think all of us who are working on devices are acutely aware of the stigmatism of wearing the cap on the head,” said Cogan. “That’s why we chose the biosignals we did – so the device can be worn on the wrist.”

Dr. Cavazos agreed, stating, “The advantage of having the device on the arm is that it’s not stigmatized. It allows people to move and do things. It's an exciting time for people with epilepsy.” His company hopes to make their device smaller and even more unobtrusive.

The AES 2015 Annual Meeting was held December 4-8 in Philadelphia.

1. Lehmkuhle M, et al. Development of a discrete, wearable, EEG device for counting seizures. Abstract No 2.158, 2015. American Epilepsy Society Annual Meeting, 

2. Cavazos JE, et al. Automated EMG based seizure detection and quantification for the home and the epilepsy monitoring unit: a prospective multicenter study. Abstract No 3.088, 2015. American Epilepsy Society Annual Meeting, 

3. Cogan DL, et al. Seizure detection by multi-extracerebral biosignal analysis. Abstract No 3.084, 2015. American Epilepsy Society Annual Meeting, 

Articles

Researchers discussed external devices that would allow individuals to monitor clinical and subclinical seizure activity in their home environment

Future of Personal Monitoring Devices for Epilepsy

People with epilepsy face a number of related health challenges, including cognitive, physical, and psychological disorders. But new findings from international research presented at the American Epilepsy Society’s (AES) 69th Annual Meeting suggest other, less expected, consequences on the aging process.

 released by researchers from New York University (NYU) Langone Medical Center and Imperial College London, results indicated that patients with epilepsy who are unresponsive to medication have brains that appear older than would be expected for their age.

In the study, 58 participants were placed into 3 groups: 18 patients with intractable epilepsy were used in the study, along with 20 patients with new-onset focal epilepsy, and 20 healthy controls.

The authors used structural magnetic resonance imaging scans to predict the ages of participants with epilepsy and their healthy peers. A machine-learning algorithm was used to predict age based on data from healthy patients that had been gathered from large, publicly available imaging databases, including the Pattern Recognition for Neuroimaging Toolbox (commonly known as PRoNTo). Age prediction was carried out using the white matter and gray matter segmentation images separately, yielding two age estimates per subject.

The difference between predicted brain age and chronological age was, on average, 8.8 years older for patients with uncontrolled epilepsy than healthy participants, said Heath Pardoe, PhD, lead author and assistant professor of neurology at NYU Langone Medical Center. This finding, he stated during a press conference, “essentially highlights the importance of getting seizures under control.”

“The absence of similar changes in patients with new-onset epilepsy suggests that ongoing seizures may underlie the brain aging phenomenon observed in this study,” said Dr. Pardoe.

He further explained that this technique could potentially be used to diagnose patients with intractable epilepsy early in the course of their disease, and may also be useful for other applications, like measuring the protective effect of antiepileptic medication.

Related epilepsy and aging research was also presented by Matti Sillanpaa, MD, a professor and senior research scientist at the University of Turku, Finland.

Dr. Sillanpaa reported on a 50-year follow-up of 179 epilepsy patients (many of whom he treated throughout his career) who were diagnosed as children, using neuropsychological assessments and multimodality imaging techniques to gain insights into the aging process.

An analysis of the participants’ survival, seizure outcomes, social integration, and reproductive activity were deemed promising. At the 45-year follow-up,

 most of the participants achieved 10-year remission without medications, and most of those without comorbid illnesses graduated from school, obtained driver's licenses, and achieved a socioeconomic status comparable with healthy controls.

“People with epilepsy today have a bright future,” said Dr. Sillanpaa during a press conference. Treatments have improved and the stigmas associated with epilepsy are not what they once were.

The subjects with epilepsy did have abnormal neurological signs – 23% had amyloid deposits, compared to 7% in the control group.

Although the researchers note that fewer participants with epilepsy live in partnership and have children compared with healthy participants, both groups appear to enjoy a high quality of life.

Session: Epilepsy and Aging: Clinical, Cognitive and Basic Science Aspects of Aging and Epilepsy. Dec. 7, 2015.

1. Pardoe HR, et al. Do seizures age the brain?: machine learning analysis of structural MRI. Abstract No 1.146, 2015. American Epilepsy Society Annual Meeting, 

Clinical conditions of long-term cure in childhood-onset epilepsy: a 45-year follow-up study

Results of an MRI study and a 50-year follow-up study shed light on the effects of epilepsy on the brain’s aging process.

Consequences of Epilepsy on the Aging Brain

The generic versus brand-name drug debate has long been a hot-button issue in the epilepsy community. But 

the findings of research presented at the American Epilepsy Society’s Annual Meeting 

revealed that brand-name and generic formulations of anti-epileptic drugs (AED) are, for all intents and purposes, the same.

During a special Food and Drug Administration (FDA) Town Hall Update, speakers explained that neurologists, patients, and patient advocacy groups have been skeptical whether product bioequivalence established in healthy individuals can ensure the same result in AEDs used by people with epilepsy.

What is the reason for such doubt? The FDA determines bioequivalency of generic drugs based on single-dose studies in normal, healthy individuals. And until recently, a majority of uncontrolled studies have suggested lack of efficacy or increased adverse events when people with epilepsy switched from brand to generic AEDs

To address the epilepsy community’s concern, the FDA Office of Generic Drugs funded a series of brand-to-generic AED switching studies in epilepsy patients, including the Bioequivalence in Epilepsy Patients (BEEP) and Equivalence in Generic Drugs (EQUIGEN) studies.

In both US studies, lamotrigine was used as the study drug because of its pharmacokinetic parameters and accessible study population. The overall results from both studies indicated that the generic versions of lamotrigine are pharmacokinetically equivalent to the original drug.

Speakers addressed reasons why problems are occasionally reported among generic drug users, citing issues such as variation in color and appearance of the brand and generic drugs as well as the “nocebo” effect, when patients experience negative effects based on expectations and other psychological factors. One expert said that, for some patients, the mere suggestion of a drug’s side effects is enough to trigger negative symptoms, such as erectile dysfunction.

Michael Privitera, MD, Director of the Epilepsy Center at University of Cincinnati Epilepsy Center, said this new and promising data provide reassurance to both the prescribers of generic drugs and the users. More particularly, the findings arm health care providers with concrete facts to debunk the myths surrounding the use of generic drugs.

According to the FDA, approximately 80% of all prescriptions filled in the United States are for generic drugs. In 2010 alone, the use of FDA-approved generics saved $158 billion-an average of $3 billion every week.

In most states, unless a physician explicitly writes “dispense as written” or “no substitution,” pharmacists can switch a patient to a lower-cost generic drug without the consent or knowledge of either the patient or the physician.

Session:  FDA Town Hall Update: Generic Antiepileptic Drug Bioequivalence in Epilepsy Patients: From Anecdotes to Evidence. Dec. 7, 2015.

Important bioequivalence issues regarding anti-epileptic drugs were highlighted at the FDA Town Hall meeting held during AES 2015.

Generic vs Brand-Name Anti-Epileptic Drugs

Brain surgery is increasingly being used to control seizures when they occur repeatedly, despite antiepileptic medications. The challenge, however, is often pinpointing seizure-producing areas of the brain, according to several neurosurgeons at the American Epilepsy Society (AES) 2015 Annual Meeting in Philadelphia.

Presenters from prestigious medical institutions across the United States and Canada outlined some of their most challenging cases for which they were charged with analyzing patients’ seizures using stereo electroencephalogram (sEEG) depth electrodes, subdural strip and grid electrodes, or a combination of both.

Subdural electrodes are typically used if the seizure focus is believed to be on the surface of the brain. If the seizure focus is believed to be deep-such as within a lesion-invasive monitoring is done using sEEG depth electrodes. In both procedures, patients are observed in the electroencephalogram (EEG) video monitoring unit to locate the exact origin of the seizures.

David A. Steven, MD, a neurosurgeon at the University of Western Ontario, shared a complex case of his patient, a 27-year-old woman, who experienced hypermotor seizures several times per day since the age of 2. Her auras included heart 

sensations, and numbness in her left arm, face, and leg-mostly in the arm and face.

Although anti-seizure medications can successfully treat seizures in two-thirds of all people with epilepsy, surgical evaluation is recommended in the remaining one-third of people, like this patient, who continue to have seizures regardless of medications.

Dr. Steven said he was originally unable to determine where her 

 within the brain using a scalp EEG, but thought that they appeared to be frontal lobe seizures. After a magnetic resonance image revealed a lesion on the patient’s brain, Dr. Steven placed 1 sEEG electrode within the lesion and 10 strip and grid electrodes surrounding the area. By doing so, he was able to determine that the lesion was primarily responsible for her seizures and ultimately performed a lesionectomy on the patient.

In this particular case, Dr. Steven said the use of both types of electrodes was necessary because the precise location of the seizure focus was uncertain. Both methods also helped ensure that the patient’s seizure focus was surgically removed without causing damage to important nearby brain regions.

The overall consensus among the speakers was that the decision to use sEEG over subdural electrodes and vice versa must be made on a case-by-case basis. Data generated by each type of electrodes produce different results and the methods are not a catch-all approach to epilepsy care.

Session: Surgery: Battle Royale: Stereo EEG vs. Subdural Electrodes. Dec. 7, 2015.

1. Koubeissi M. Pre-surgery Intracranial Monitoring: Stereo-EEG Versus Subdural Electrodes. Epilepsy Foundation website 

http://www.epilepsy.com/information/professionals/diagnosis-treatment/surgery/presurgical-evaluation/pre-surgery

During pre-surgery planning, decisions regarding which electrode(s) to utilize must be made on a case-by-case basis. 

Seizure Analysis: Stereo EEG vs. Subdural Electrodes 

Hundreds of clinicians and health care providers from around the world gathered for a Spanish symposium on frontal lobe epilepsy, held during the American Epilepsy Society (AES) 2015 Annual Meeting in Philadelphia, to learn more about treatment options for the condition.

The group discussion, presented in Spanish, provided an overview of frontal lobe epilepsy, particularly the clinical semiology of seizures and comorbidities associated with intractable cases. The forum gave special reference to the neuropsychological aspects of frontal lobe epilepsy, which affect quality of life, including social and psychological development, in people with epilepsy.

Andres M. Kanner, MD, who is considered by many to be one of the world’s leading researchers on the behavioral aspects of epilepsy, discussed the psychiatric and neuropsychological aspects of frontal lobe epilepsy.

As the chief of the epilepsy division at the Miller School of Medicine at University of Miami, Dr. Kanner said that although psychiatric comorbidities are relatively common in patients with frontal lobe epilepsy, they are not specific to the condition. Examples of such psychiatric issues, he said, include attention deficit disorders, mood and anxiety disorders, and impulsive control disorders.

Similarly, Dr. Kanner explained that frontal lobe epilepsy may also be associated with characteristic cognitive disturbances, such as memory and verbal fluency, social cognition, and concept formation. However, he said these types of conditions may be identified in patients with other types of epilepsy as well.

He mentioned that, unlike temporal lobe epilepsy, frontal lobe epilepsy does not have a different impact on the verbal and visual mediated functions relative to the side of the epileptogenic area of the brain, nor does it affect the intelligence quotient of those with the condition. Furthermore, he said, the neuropsychological deficits of individuals with frontal lobe epilepsy do not correlate with the age of onset, duration of seizure disorder, or the severity of seizures.

Another global epilepsy expert, Jaime Parra, MD, from Madrid, Spain, shared his expertise regarding the semiology of frontal lobe seizures.

“Semiologic features in frontal lobe seizures depend neither on the anatomical origin of the ictal discharge nor the target areas of its propagation, alone, but on the dynamic interaction between both of them and are highly reproducible in an individual patient,” said Dr. Parra.

He further explained that the semiology of frontal lobe seizures follow “a propagation of the ictal discharge in a rostral-to-caudal axis.” No organization is clarified for the medial-lateral axis just yet, he said.

Session: SUDEP: Spanish Symposium: Frontal Lobe Epilepsy. Dec. 4, 2015.

Experts from around the globe met to discuss the neuropsychological aspects of frontal lobe epilepsy.

A Multicultural Assessment of Frontal Lobe Epilepsy

A key issue hindering the development of effective sudden unexpected death in epilepsy (SUDEP) prevention efforts is the lack of data on the incidence of such occurrence as well as the extent of its burden on public health, according to an expert speaker at the American Epilepsy Society (AES) Annual Meeting.

“Right now, we have the cart before the horse,” said Dale C. Hesdorffer, PhD, Professor of Epidemiology at the Columbia University Medical Center. “Sure, we can implement public health interventions but we have no known reliable outcomes [of those interventions].”

Gaps in knowledge of the risk of SUDEP, from both families and health care professionals, prohibit researchers from pinpointing target areas from which they could gather the most valuable information about SUDEP prevention.

In a 2014 study Hesdorffer had co-authored assessing the public health burden of SUDEP in the United States, results indicated that, although SUDEP requires autopsy for definitive diagnosis, most coroners and medical examiners do not use the diagnosis of SUDEP as an official cause of death.

 It is also common, she said, for a family or epitologist to forgo an autopsy of a decedent's body because they assume the death was a result of an epilepsy complication.

For the sake of advancing SUDEP research and awareness, Hesdorffer said medical examiners, coroners, and the general public need to make the decision to conduct thorough autopsies on individuals with epilepsy. They would provide valuable insight about modifiable risk factors and circumstances of death, which would, in turn, aid the development of successful prevention strategies and programs.

“Ultimately, we need intervention to prevent SUDEP and it should take place in the community in which all sudden deaths go to autopsy,” said Hesdorffer. “If this happens, an intervention could be implemented and we could look at the increase or decrease in SUDEP incidence over a period of time and evaluate pre-intervention as opposed to the post-intervention.”

According to the study, the limitations of existing data highlight the importance of gathering additional population-based studies from medical examiner and coroner offices with active protocols to identify epilepsy and SUDEP occurrence in decedents. Cross-referencing such information from clinical reports, vital records, and death certificates would offer vital information, such as modifiable risk factors and circumstances of death.

She further explained that a better understanding of the incidence and public health burden of SUDEP is necessary to recognize priorities in medical and prevention research as well as inform people with epilepsy more accurately of their risk.

Although Hesdorffer believes there is a lot of work to do to identify true SUDEP interventions, she is optimistic that research is headed in the right direction toward reducing the overall occurrence of SUDEP cases.

Session: SUDEP: Are we read for trials of SUDEP prevention in people with epilepsy? Dec 4, 2015.

1. Thurman DJ, Hesdorffer DC, French JA. 

Sudden unexpected death in epilepsy: Assessing the public health burden

How can the medical community advance research and tackle the difficult issue of sudden unexplained death in epilepsy (SUDEP)?