What is Byteflies Building for People with Epilepsy and Why?
A personalizable seizure monitoring wearable for home use that extends the capabilities of specialized hospital equipment.
Epilepsy is a chronic neurological condition characterized by recurrent unprovoked seizures. Although epilepsy can sometimes be linked to a specific cause such as brain injury or certain genetic syndromes, often its origin (etiology) is unknown.
Epilepsy is more common than you may think. An estimated 65 million people of all ages have epilepsy and in the US one in 26 people will develop epilepsy at some point in their lifetime. About one in 3 people in countries with high access to expert care are treatment resistant. Low to middle-income countries account for up to 80% of all cases, the large majority of whom lack access to appropriate care.
Seizures are the hallmark symptom of epilepsy (even though having seizures does not necessarily mean you have epilepsy!). They are caused by an imbalance in electrochemical signaling in the brain. In turn, this can trigger additional symptoms that range from hardly noticeable to extremely disabling. Although various antiepileptic strategies exist, in most cases, they do not cure epilepsy but merely suppress the occurrence of seizures.
Because epilepsy is a chronic condition, because seizures are unpredictable and can be very disabling, because antiepileptic drugs have side-effects, epilepsy can have a profoundly negative impact on someone’s quality of life. In addition, many people must deal with stigma and discrimination in addition to their disease.
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What is the unmet need in epilepsy?
If it was not clear from the introduction, there are quite a few unmet medical needs for people with epilepsy, ranging from:
- Delivering state-of-the-art care to a broader demographic and larger geographic areas, especially where comprehensive epilepsy centers are not available.
- Developing new treatment options for treatment resistant epilepsy.
- Reducing the unpredictability of epilepsy and the associated stress caused by not knowing when the next seizure will occur.
- Managing psychosomatic stress, treatment side effects and epilepsy comorbidities.
The last bullet point may seem like a grab bag of issues, but the overarching theme is to maintain or improve someone’s quality of life when developing a care path.
We did not identify these unmet needs in a vacuum. Byteflies interacts on a nearly daily basis with a network of experts, including people with epilepsy, neurologists, and pharma and academic researchers. Recently, we organized the Byteflies Epilepsy Day which included multiple panel discussions that touched on these topics. You can find the full event recording here and a teaser video below.
Byteflies develops wearable health solutions. In other words, medical applications that derive data from small wearable sensors and turn that long-term data into actionable clinical insights for healthcare professionals and patients. We are a digital medicine company that takes pride in creating patient value. That means we let our technology development (the What) be driven by the need of the patient and healthcare professional (the Why).
The “Why” should always guide the “What”.
In that spirit, before diving into some of the specifics of Byteflies’s technology in the next section, let’s focus first on these unmet needs.
Most people with a suspected or confirmed diagnosis of epilepsy will at some point undergo a video-electroencephalography (video-EEG) observation. This test requires admission to a specialized epilepsy monitoring unit (EMU) for 1–7 days. During that time, the following data is typically recorded continuously:
- Twenty or more channels of electroencephalography (EEG), i.e. brain activity as measured on the scalp
- Video-audio feed
- Electrocardiography (ECG), i.e. heart activity to derive heart rate and sometimes heart rate variability
- Electromyography (EMG), i.e. muscle activity
All this biopotential data is sampled at a high frequency (typically 250 times per second and higher) and then reviewed by EEG readers to identify potential epileptic events.
Since epileptic seizures originate in the brain, EEG is obviously an important signal to evaluate. However, it is often not enough. Seizures come in many shapes and sizes and detecting them on the EEG signal is not always straightforward. They may originate in deep brain structures that are not readily picked up by a scalp EEG measurement or the signal could be obscured by motion artifacts*. Because many seizures will provoke involuntary and rhythmic movements patterns (known as motor patterns), the video feed is an important secondary signal, as is the EMG signal. Additionally, some seizures may evoke certain involuntary stereotypical behaviors, such as lip smacking, chewing, or pacing, known as automatisms. These automatisms are also easy to recognize on video. Finally, the seizure may also affect the autonomic nervous system, which is responsible for regulating many unconscious bodily functions, including the heart and respiratory rate. By recording the ECG, any changes in heart rate during the seizure can be evaluated.
*Entire books have been written on this subject and it is beyond the scope of this post to go into more detail. In case you are interested, the Atlas of Sleep Medicine and Ambulatory EEG Monitoring are useful sources.
When applied correctly, video-EEG can be a powerful diagnostic tool but –as always– there are some downsides too:
- A (potentially long) hospital admission is required.
- It requires access to a hospital with a specialized epilepsy monitoring unit and it can be expensive.
- There is no guarantee someone will have a seizure during their stay.
- The person is monitored under artificial conditions that do not reflect their usual environment and activities.
After that moment of intense observation, the patient goes back home, and all that fancy equipment is replaced by self-reporting via a seizure diary, which can be a phone application or simply pen-and-paper. Seizure diaries require an active effort to track seizures and symptoms, and despite people’s best efforts, they are known to be inaccurate (some examples: 1, 2). Consequently, many neurologists will not pay much attention to them.
So, what is our Why (unmet need) driver? People with epilepsy and their healthcare professionals are missing data when video-EEG equipment is not available. Either because no epilepsy monitoring units are available within a reasonable distance and –if they are– the hassle or expense of repeatedly coming to the hospital is simply too large. That missing data could have been used to:
- More quickly identify an optimal and personalized treatment strategy
- Understand if the dosing of a drug is right
- Find a balance between seizure freedom and side effects
- Track changes in quality of life and comorbidities over extended periods of time
The resulting What is our ability to record seizures objectively for prolonged periods of time with unobtrusive and cost-effective equipment outside the hospital, either because advanced equipment is not available or to fill in the gaps between video-EEG observations.
Several options already exist or are being developed to make this possible:
- Ambulatory EEG: Similar to the EEG equipment used in the hospital but typically in a more portable format so people can move around at home.
- Subcutaneous EEG: One or two EEG channels are recorded under the scalp which holds promise for making ultra-long-term EEG recordings but requires a surgical intervention.
- Consumer wearables: Fitness trackers or wellness devices may in some cases complement seizure diaries.
- Specialized medical wearables: Medical devices that come in a wide variety of shapes, sizes, and functionality that are purposely built for people with epilepsy for mid-to-ultra long-term use.
Each of these innovations have their pros and cons and we may dedicate a future post to exploring those in more detail. Byteflies Sensor Dot fits in the “specialized medical wearables” category. We aim to fill the gap between the hospital video-EEG and home seizure diary with user-friendly wearable devices that can record analogous signals compared to the video-EEG reference standard at home. More on that below!
Recent improvements in cost-effective and unobtrusive seizure monitoring devices are extending state-of-the-art epilepsy care to the home environment and geographic areas without access to specialized facilities.
New treatment options
Many different types of epilepsy and seizures are known but even in the most recent effort to improve their classification, an “unknown” category remains. As discussed previously, seizures vary in their location of onset and migration patterns in the brain, as well as the symptoms they elicit and their duration. Many occur without warning, but they can also be triggered by environmental factors, such as sleep quality, stress, alcohol, medication, hormonal changes, and the list goes on. Although most seizures only last for a few seconds to minutes, their effect on a person’s well-being can linger for hours (known as the post-ictal phase).
Suffice it to say, epilepsy is complex and can be extremely hard to treat effectively because of interindividual but also intraindividual differences (e.g., driven by lifestyle factors). Despite massive investments in the development of new antiepileptic drugs, as well as therapies such as vagal nerve stimulation (VNS) and responsive neurostimulation (RNS) devices, the last four decades have brought about little meaningful improvement in our ability to control seizures for people with epilepsy.
Echoing this from the patient’s perspective, one of the most common remarks noted in a survey conducted by the Epilepsy Foundation in 2016 was “Frustration of trying different medications and their side effects with no improvement”.
Where does that leave us when we repeat our Why → What exercise? Pharma and academia are still investing considerable resources in the identification of novel drugs and mechanisms of action. The latter is especially important because our understanding of what specifically causes epilepsy (down to the neurochemical signaling level) is still incomplete. These efforts should continue, but two important improvements can be made right now:
- In many cases, treating epilepsy is more than treating seizures, especially for treatment resistant individuals. Put differently: existing care paths can be made more holistic with an increased focus on long-term outcomes and quality of life.
- Collection of real-world data (i.e. RWD, data that is collected outside the lab or clinical trial) has a lot of potential to improve our ability to efficiently match existing treatments to the right individuals. Put differently: existing care paths can be made more personalized.
Continuing with the What, these ideas are not unique to epilepsy and similar efforts are underway for other chronic conditions and rare diseases (background reading: 1, 2, 3). Here, we can keep it brief: to collect RWD on seizures, triggers, side effects, and quality of life, on a sufficiently large scale, the same technological innovations as mentioned in the previous paragraph apply. Currently, there is no hard evidence that this will lead to immediate improvements in the standard of care but considering the advantages discussed in the previous section, there appears to be little downside exploring these strategies further. A secondary more long-term effect may be the identification of novel therapeutic targets based on the collection of all this data.
To understand how to make existing care paths more personalized and holistic with the treatment strategies currently available, we need to improve our ability to capture relevant long-term data unobtrusively in the real-world.
In that same survey mentioned previously, the unpredictability of seizures is one of the main factors identified as impacting quality of life by people experiencing frequent seizures.
Predicting when a seizure is about to happen is often considered the “Holy Grail” because it would return some control to people with epilepsy. It could also make certain acute forms of treatment more plausible: they would be administered just before a seizure hits, either manually or automatically, in the hope of preventing it from occurring altogether or at the very least reducing its severity (example). Finally, it could help reduce or even prevent SUDEP, sudden mortality associated with uncontrolled seizures.
You may have noticed the overuse of conditionals in that last paragraph. Attempts to predict seizures date back to the 1970s and recently have gone through a revival due to the availability of larger datasets and machine learning methods to process them (examples: 1, 2). Active large-scale efforts include My Seizure Gauge, RADAR-CNS, SeizeIT2, as well as improvements in our understanding of cyclical seizure patterns based on ultralong-term EEG monitoring (examples: 1, 2, 3). These recent efforts are important, but it is unlikely they will lead to a rapid breakthrough in our ability to forecast seizures for a large group of people with epilepsy.
The Why is again straightforward: not knowing when a seizure is about to hit leads to anxiety and stress, which in turn may increase people’s chances of having a seizure. Having uncontrolled seizures may cost someone their driving license and limit their professional opportunities. Knowing that clinically applicable seizure prediction is still quite far off and may only work for specific people or seizure types, does it even make sense to discuss it now?
It is a typical chicken-egg problem. Recent advances in wearable sensor technology and data analytics may improve our seizure prediction capabilities but to do so, we need to collect lots and lots of high-quality data. However, more short-term benefits may arise. Many people with epilepsy will experience certain telltale symptoms (“auras”) that alert them a seizure may be coming. Similarly, a lot of information about seizure triggers and risk factors may be hidden in daily activities. The only people qualified to identify those are people with epilepsy or their most trusted relations, but technology can help. Providing user-friendly seizure and symptom cataloguing apps and devices may allow people to uncover a lot of these patterns themselves while creating trust in the healthcare community that the information is backed up by objective verifiable seizure monitoring data.
The unpredictability of seizures is an especially insidious part of living with epilepsy. New seizure monitoring technology can play a crucial role in removing some of that unpredictability on the level of the individual. Over time, these data collection efforts may turn into more generalizable takeaways and pave the way to more robust seizure predicting capabilities.
Improving quality of life
Last but not least, a lot of the devices discussed in the state-of-the-art care section can also capture other objective digital measures such as sleep quality, stress levels, and even environmental parameters such as exposure to loud noise or light patterns. Overlaying this information on top of seizure patterns and other epilepsy symptoms may play a key role in tackling the three other unmet needs. Exactly how that information can be collected as unobtrusively as possible and integrated into care pathways, remains to be seen, and it will take an active effort from healthcare providers to not only reward the treating of core symptoms, but also long-term outcomes, including quality of life.
Adding objective quality of life measures to routine clinical care for people with epilepsy will require an active effort from the entire community, including regulators and payers.
How can Byteflies Sensor Dot meet this need?
We set the stage on some of the unmet clinical needs in epilepsy that could be met by advances in digital medicine and specifically remote monitoring technology. The number of devices and applications is diverse, and many already have or hopefully will soon have a positive impact on the management of epilepsy.
At Byteflies, we develop medical wearable devices that bring the quality of equipment traditionally used inside the hospital to the home environment in a user and home-friendly package. Over the last couple of years, we have been hard at work to build a wearable solution that replicates relevant video-EEG capabilities for use at home.
How it works
Sensor Dot is our multipurpose wearable that can record biopotential and motion (inertial) signals. It is cleared in the EU (CE) and US (FDA 510(k)) as a prescription medical device.
Sensor Dot is compatible with the biopotential electrodes that are used for hospital EEG but we are also developing disposable patches (adhesives with embedded biopotential electrodes) that are easier to use at home and allow longer monitoring periods.
The setup shown in the image above is recording two channels of EEG, one behind each ear (but other configurations are possible), as well as motion via the inertial sensors. A second Sensor Dot can add ECG, EMG, and an additional set of motion sensors.
The setup with two Sensor Dots measures signals that are the same or equivalent to what is recorded during a video-EEG observation, with the notable difference that the number of EEG channels is lower than what is used in the hospital. In other words, Sensor Dot is not meant to be a replacement for video-EEG equipment. On the contrary, it is meant to complement it by:
- Making the recording of relevant medical-grade signals possible in a form factor that is small enough for use in daily life.
- Making a cost-effective device available that can be used in locations or under circumstances where video-EEG equipment is not available.
- Increasing the number of day-to-week long seizure observation periods that can be made.
- Recording data that is compatible with existing diagnostic video-EEG data review workflows, as well as future automated data processing pipelines.
The current generation of Sensor Dot is ready to tackle these goals in the real-world. At the time of writing (January 2021), we have monitored over 150 people with this set up (and counting), accounting for more than 2000 focal and generalized seizures. Of course, we continue to improve our technology and work with all stakeholders to make sure the Why keeps fitting the What. For instance, with increased data recording capabilities comes the need to automate the data review process to avoid overloading neurologists with datasets they do not have the time to review.
The current generation of Sensor Dot is ready to tackle these goals in the real-world. Sensor Dot has monitored more than 150 people with epilepsy accounting for more than 2000 seizures.
We hope this post helps in clarifying why we are developing Sensor Dot for epilepsy the way we are. A seizure monitoring tool that extends the capabilities of the traditional video-EEG set up beyond the walls of the hospital a few weeks at a time.
We are incredibly excited to continue our work with the epilepsy community to get Sensor Dot in the right hands. Please follow us on this blog, Twitter, LinkedIn, or any of our other social media channels to stay up to date, and feel free to reach out via our website!
The introduction of this post only touches briefly on some important topics. If you are interested in learning more, we recommend the following sources:
- The basics of epilepsy by the American Epilepsy Foundation (and basically all other educational materials on their website).
- The Epilepsy Fact Sheet by the World Health Organization (WHO).
- The Education section on the website of the International League Against Epilepsy (ILAE), including https://www.epilepsydiagnosis.org.
- The Seizure First Aid training organized by the American Epilepsy Foundation. Everyone at Byteflies has completed this course and it is a fantastic way to learn more about epilepsy and become seizure first aid certified in the process!
The information contained in this article represents the views and opinions of the writer(s) and does not necessarily represent the views or opinions of other parties referenced or mentioned therein.
The article is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you read in this article.