In Context
Can technology reveal the natural history of epilepsy? Technological innovations and refinements to existing techniques are providing researchers with new insights into the natural history of epilepsy. David Holmes reports.
www.thelancet.com/neurology Vol 13 April 2014
seizure. But this system has several important drawbacks. Patients can only be monitored for a few hours at a time, which limits the odds of a seizure being captured, and for some time now there has been a clinical impression that patients have fewer seizures in hospital than they do at home, Brunnhuber explains. This could perhaps be because of the stress of the hospital environment, which can be particularly problematic for patients with learning difficulties, or perhaps because they are in an artificial situation divorced from their usual routine and environment. From a purely practical point of view, beds being taken up by acute admissions can often mean that scheduled telemetry appointments have to be cancelled at short notice, which can be a huge inconvenience to patients.
“We’re reaching out to new patient groups…Particularly some psychiatric patients who normally wouldn’t go near a hospital.” “From the outset our idea was to replicate the gold standard; we wanted to see if we could have the same quality of recording at home as we have in the hospital setting”, explains Brunnhuber. Patients still have a face-to-face consultation with a neurologist, although this can now be done remotely, but a technician travels to the patient’s home to set up the EEG and video equipment, returning each day for the 5-day monitoring period to ensure the equipment is running smoothly, to download and prune data, and to review any seizure data with the patient and any family and carers. The system has been a huge success
in terms of patient satisfaction and the high quality of data captured, and from a practical perspective it has insulated patients and staff from the unpredictable disruption caused by acute admissions. Importantly, it seems to be satisfying an unmet clinical need. “We’re reaching out to new patient groups”, says Brunnhuber. “Particularly some psychiatric patients who normally wouldn’t go near a hospital, so that’s a patient group we would naturally not see.” But it has also raised some fascinating scientific questions. After two small studies comparing home video telemetry with hospitalbased telemetry, a larger comparative study is starting to provide a statistical underpinning for that earlier clinical impression that patients have fewer seizures in hospital. “It appears that 50% of patients who are referred for diagnostic telemetry have seizures in hospital, whereas 85% of the same patients have seizures at home. That’s a huge difference, and it’s something we don’t really understand”, notes Brunnhuber. His team also did an audit to assess the diagnostic yield of repeat telemetry when the first session does not capture a seizure. For patients who had repeat telemetry in
For more on the feasibility of predicting seizures see Articles Lancet Neurol 2013; 12: 563–71 For more on the NHS Innovation Challenge see http://www.nhschallengeprizes. org/wp-content/uploads/NHS_ ICP_Booklet-Feb-2013.pdf
A J Photo/Hop American/Science Photo Library
In July, 2013, Mark Cook (St Vincent’s Hospital, Melbourne, Australia) and colleagues reported in The Lancet Neurology the feasibility of the use of a device that, through implanted intracranial electrodes, could warn patients of impending epileptic seizures with a simple light display on a handheld console. For many of the 15 patients who tested it, being able to predict imminent seizures allowed them to exercise a degree of control over their disease. But in the long term the device could turn out to have even broader implications. Although NeuroVista, the Seattlebased company that manufactured the device has now ceased to trade, the insights provided by constant year-round recordings of the electrical activity of patients’ brains are still changing the understanding of the natural history of epilepsy. And over the next few years, a combination of cutting-edge technologies and innovative ways of using tried and tested techniques look set to revolutionise the way epilepsy is diagnosed and managed. Franz Brunnhuber and his team at King’s College Hospital (London, UK) are playing their own part in the effort to unravel the complexity of epilepsy. In 2013, his team won an NHS Innovation Challenge prize for their pioneering use of home video telemetry to record patients’ seizure activity away from the stressful surroundings of the hospital ward. Usually, when patients are referred for diagnostic telemetry they have to be admitted to hospital, where they will have electrodes attached to their scalp to record their brain’s electrical activity with electroencephalography (EEG). They can also be put under constant video surveillance to capture visual evidence of any
347
Sovereign, ISM/Science Photo Library
In Context
For more on the responsive neurostimulation device see Neurology 2011; 77: 1295–304
348
hospital, only 12% of cases resulted in a diagnosis, compared with 40% when the repeat telemetry was done at home. What might explain these discrepancies, Brunnhuber explains, is the failure of hospital tests to recreate the “ecology of epilepsy”. Being able to study patients in their natural environment, he says, will in the long term enable researchers to start to piece together individuals’ trigger factors in a way that has not been possible before, and probe how the environment affects the presentation of seizures. “My hunch is that in a few years we’ll start to see things on the video that we don’t know to look for at the moment. This may sound trivial, but even the distance to furniture, to walls, may all have an impact”, says Brunnhuber. “I don’t think seizures just arise in isolation: every patient with epilepsy has an idea about their own trigger factors, but they can be very hard to establish, and the scientific evidence is pretty lousy.” Getting at good evidence to inform diagnosis and treatment has always been a problem with epilepsy: even something as seemingly routine as finding out how often a patient is having seizures is beset with difficulties. “Sometimes the seizures themselves erase the memory of the seizure”, explains Jacqueline French (NYU Comprehensive Epilepsy Center, New York, NY, USA), “so by the time the patient recovers to the point where
they could write something down, they’ve forgotten they’ve had a seizure. We see in the monitoring unit all the time that people deny they’ve had a seizure right after they’ve had one.” It’s not uncommon for patients to sleep through seizures, and even the way patients are asked to record seizures can cause problems. “We’re still in the age of using paper diaries that people may not be in the same place as, or they misplace it, or say they’ll write it down later and then they forget”, says French. One of the most startling findings of the pilot study by Cook and colleagues was the mismatch between the number of seizures patients reported and the number their implanted devices recorded, which could be verified from audio recordings captured by their device. “There was enormous discrepancy between what patients were reporting and what they were having”, says Cook. “Getting that sort of information changes the whole game, because it affects the way we study new drugs, and how we assess the efficacy of any new therapy we introduce.”
“Sometimes the seizures themselves erase the memory of the seizure, so by the time the patient recovers…they’ve forgotten they’ve had a seizure.” The study was done in Australia partly because the US Food and Drug Administration (FDA) wouldn’t approve a trial for a device that didn’t have a therapeutic component, which was “incredibly short-sighted”, says Cook, “because clearly the prediction is a therapy of a sort, or might lead to a better therapy”. But he is far from despondent about the prospects of similar technologies shaking things up in the near future. Cyberonics, the company based in Houston (TX, USA) that acquired many of NeuroVista’s assets, already has FDA approval for a device that stimulates the vagus nerve to try to prevent seizures from
manifesting in patients with refractory epilepsy. Medtronic (Minneapolis, MN, USA) have a deep-brain stimulation device approved in Europe and Canada that delivers controlled electrical pulses to the anterior nucleus of the thalamus in patients with severe treatment-refractory epilepsy. And NeuroPace, based in Mountain View (CA, USA) have recently had premarket approval from the FDA for their responsive neurostimulation device in patients with refractory epilepsy. The device consists of a base unit, which replaces part of the skull, connected by two leads to electrodes implanted near the patient’s epileptic foci, and responds to abnormal electrical activity to curtail seizures before clinical symptoms appear. With those approvals, Cook contends, “we’ll see other consequences of having access to the data that these systems provide. The NeuroPace approval is very important in that respect, because although they don’t do seizure prediction they do keep lots of other data about the seizures, which can give valuable and unique insights into the natural history of the condition that just wasn’t available before”. The amount of data produced by these devices is staggering: the study by Cook and colleagues alone produced more than 20 terabytes’ worth that are still being analysed. That’s a lot of hard drives, but with advances in computing power and increasingly advanced algorithms capable of unearthing the “deep rhythms” buried in the numbers, there is optimism about what the future holds. “Every system, if you can measure it accurately and monitor its responses to changes in the environment, you can control it better, and we just don’t have that ability now with most neurological illnesses, yet the potential is there”, says Cook. “These sorts of devices will change everything.”
David Holmes www.thelancet.com/neurology Vol 13 April 2014
Can technology reveal the natural history of epilepsy? Technological innovations and refinements to existing techniques are providing researchers with new insights into the natural history of epilepsy. David Holmes reports.
www.thelancet.com/neurology Vol 13 April 2014
seizure. But this system has several important drawbacks. Patients can only be monitored for a few hours at a time, which limits the odds of a seizure being captured, and for some time now there has been a clinical impression that patients have fewer seizures in hospital than they do at home, Brunnhuber explains. This could perhaps be because of the stress of the hospital environment, which can be particularly problematic for patients with learning difficulties, or perhaps because they are in an artificial situation divorced from their usual routine and environment. From a purely practical point of view, beds being taken up by acute admissions can often mean that scheduled telemetry appointments have to be cancelled at short notice, which can be a huge inconvenience to patients.
“We’re reaching out to new patient groups…Particularly some psychiatric patients who normally wouldn’t go near a hospital.” “From the outset our idea was to replicate the gold standard; we wanted to see if we could have the same quality of recording at home as we have in the hospital setting”, explains Brunnhuber. Patients still have a face-to-face consultation with a neurologist, although this can now be done remotely, but a technician travels to the patient’s home to set up the EEG and video equipment, returning each day for the 5-day monitoring period to ensure the equipment is running smoothly, to download and prune data, and to review any seizure data with the patient and any family and carers. The system has been a huge success
in terms of patient satisfaction and the high quality of data captured, and from a practical perspective it has insulated patients and staff from the unpredictable disruption caused by acute admissions. Importantly, it seems to be satisfying an unmet clinical need. “We’re reaching out to new patient groups”, says Brunnhuber. “Particularly some psychiatric patients who normally wouldn’t go near a hospital, so that’s a patient group we would naturally not see.” But it has also raised some fascinating scientific questions. After two small studies comparing home video telemetry with hospitalbased telemetry, a larger comparative study is starting to provide a statistical underpinning for that earlier clinical impression that patients have fewer seizures in hospital. “It appears that 50% of patients who are referred for diagnostic telemetry have seizures in hospital, whereas 85% of the same patients have seizures at home. That’s a huge difference, and it’s something we don’t really understand”, notes Brunnhuber. His team also did an audit to assess the diagnostic yield of repeat telemetry when the first session does not capture a seizure. For patients who had repeat telemetry in
For more on the feasibility of predicting seizures see Articles Lancet Neurol 2013; 12: 563–71 For more on the NHS Innovation Challenge see http://www.nhschallengeprizes. org/wp-content/uploads/NHS_ ICP_Booklet-Feb-2013.pdf
A J Photo/Hop American/Science Photo Library
In July, 2013, Mark Cook (St Vincent’s Hospital, Melbourne, Australia) and colleagues reported in The Lancet Neurology the feasibility of the use of a device that, through implanted intracranial electrodes, could warn patients of impending epileptic seizures with a simple light display on a handheld console. For many of the 15 patients who tested it, being able to predict imminent seizures allowed them to exercise a degree of control over their disease. But in the long term the device could turn out to have even broader implications. Although NeuroVista, the Seattlebased company that manufactured the device has now ceased to trade, the insights provided by constant year-round recordings of the electrical activity of patients’ brains are still changing the understanding of the natural history of epilepsy. And over the next few years, a combination of cutting-edge technologies and innovative ways of using tried and tested techniques look set to revolutionise the way epilepsy is diagnosed and managed. Franz Brunnhuber and his team at King’s College Hospital (London, UK) are playing their own part in the effort to unravel the complexity of epilepsy. In 2013, his team won an NHS Innovation Challenge prize for their pioneering use of home video telemetry to record patients’ seizure activity away from the stressful surroundings of the hospital ward. Usually, when patients are referred for diagnostic telemetry they have to be admitted to hospital, where they will have electrodes attached to their scalp to record their brain’s electrical activity with electroencephalography (EEG). They can also be put under constant video surveillance to capture visual evidence of any
347
Sovereign, ISM/Science Photo Library
In Context
For more on the responsive neurostimulation device see Neurology 2011; 77: 1295–304
348
hospital, only 12% of cases resulted in a diagnosis, compared with 40% when the repeat telemetry was done at home. What might explain these discrepancies, Brunnhuber explains, is the failure of hospital tests to recreate the “ecology of epilepsy”. Being able to study patients in their natural environment, he says, will in the long term enable researchers to start to piece together individuals’ trigger factors in a way that has not been possible before, and probe how the environment affects the presentation of seizures. “My hunch is that in a few years we’ll start to see things on the video that we don’t know to look for at the moment. This may sound trivial, but even the distance to furniture, to walls, may all have an impact”, says Brunnhuber. “I don’t think seizures just arise in isolation: every patient with epilepsy has an idea about their own trigger factors, but they can be very hard to establish, and the scientific evidence is pretty lousy.” Getting at good evidence to inform diagnosis and treatment has always been a problem with epilepsy: even something as seemingly routine as finding out how often a patient is having seizures is beset with difficulties. “Sometimes the seizures themselves erase the memory of the seizure”, explains Jacqueline French (NYU Comprehensive Epilepsy Center, New York, NY, USA), “so by the time the patient recovers to the point where
they could write something down, they’ve forgotten they’ve had a seizure. We see in the monitoring unit all the time that people deny they’ve had a seizure right after they’ve had one.” It’s not uncommon for patients to sleep through seizures, and even the way patients are asked to record seizures can cause problems. “We’re still in the age of using paper diaries that people may not be in the same place as, or they misplace it, or say they’ll write it down later and then they forget”, says French. One of the most startling findings of the pilot study by Cook and colleagues was the mismatch between the number of seizures patients reported and the number their implanted devices recorded, which could be verified from audio recordings captured by their device. “There was enormous discrepancy between what patients were reporting and what they were having”, says Cook. “Getting that sort of information changes the whole game, because it affects the way we study new drugs, and how we assess the efficacy of any new therapy we introduce.”
“Sometimes the seizures themselves erase the memory of the seizure, so by the time the patient recovers…they’ve forgotten they’ve had a seizure.” The study was done in Australia partly because the US Food and Drug Administration (FDA) wouldn’t approve a trial for a device that didn’t have a therapeutic component, which was “incredibly short-sighted”, says Cook, “because clearly the prediction is a therapy of a sort, or might lead to a better therapy”. But he is far from despondent about the prospects of similar technologies shaking things up in the near future. Cyberonics, the company based in Houston (TX, USA) that acquired many of NeuroVista’s assets, already has FDA approval for a device that stimulates the vagus nerve to try to prevent seizures from
manifesting in patients with refractory epilepsy. Medtronic (Minneapolis, MN, USA) have a deep-brain stimulation device approved in Europe and Canada that delivers controlled electrical pulses to the anterior nucleus of the thalamus in patients with severe treatment-refractory epilepsy. And NeuroPace, based in Mountain View (CA, USA) have recently had premarket approval from the FDA for their responsive neurostimulation device in patients with refractory epilepsy. The device consists of a base unit, which replaces part of the skull, connected by two leads to electrodes implanted near the patient’s epileptic foci, and responds to abnormal electrical activity to curtail seizures before clinical symptoms appear. With those approvals, Cook contends, “we’ll see other consequences of having access to the data that these systems provide. The NeuroPace approval is very important in that respect, because although they don’t do seizure prediction they do keep lots of other data about the seizures, which can give valuable and unique insights into the natural history of the condition that just wasn’t available before”. The amount of data produced by these devices is staggering: the study by Cook and colleagues alone produced more than 20 terabytes’ worth that are still being analysed. That’s a lot of hard drives, but with advances in computing power and increasingly advanced algorithms capable of unearthing the “deep rhythms” buried in the numbers, there is optimism about what the future holds. “Every system, if you can measure it accurately and monitor its responses to changes in the environment, you can control it better, and we just don’t have that ability now with most neurological illnesses, yet the potential is there”, says Cook. “These sorts of devices will change everything.”
David Holmes www.thelancet.com/neurology Vol 13 April 2014
