Posts Tagged seizure prevention
Researchers have successfully demonstrated how an electronic device implanted directly into the brain can detect, stop and even prevent epileptic seizures.
These thin, organic films do minimal damage in the brain, and their electrical properties are well-suited for these types of applications.
The researchers, from the University of Cambridge, the École Nationale Supérieure des Mines and INSERM in France, implanted the device into the brains of mice, and when the first signals of a seizure were detected, delivered a native brain chemical which stopped the seizure from progressing. The results, reported in the journal Science Advances, could also be applied to other conditions including brain tumours and Parkinson’s disease.
The work represents another advance in the development of soft, flexible electronics that interface well with human tissue. “These thin, organic films do minimal damage in the brain, and their electrical properties are well-suited for these types of applications,” said Professor George Malliaras, the Prince Philip Professor of Technology in Cambridge’s Department of Engineering, who led the research.
While there are many different types of seizures, in most patients with epilepsy, neurons in the brain start firing and signal to neighbouring neurons to fire as well, in a snowball effect that can affect consciousness or motor control. Epilepsy is most commonly treated with anti-epileptic drugs, but these drugs often have serious side effects and they do not prevent seizures in three out of 10 patients.
In the current work, the researchers used a neurotransmitter which acts as the ‘brake’ at the source of the seizure, essentially signalling to the neurons to stop firing and end the seizure. The drug is delivered to the affected region of the brain by a neural probe incorporating a tiny ion pump and electrodes to monitor neural activity.
When the neural signal of a seizure is detected by the electrodes, the ion pump is activated, creating an electric field that moves the drug across an ion exchange membrane and out of the device, a process known as electrophoresis. The amount of drug can be controlled by tuning the strength of the electric field.
“In addition to being able to control exactly when and how much drug is delivered, what is special about this approach is that the drugs come out of the device without any solvent,” said lead author Dr Christopher Proctor, a postdoctoral researcher in the Department of Engineering. “This prevents damage to the surrounding tissue and allows the drugs to interact with the cells immediately outside the device.”
The researchers found that seizures could be prevented with relatively small doses of drug representing less than 1% of the total amount of drug loaded into the device. This means the device should be able to operate for extended periods without needing to be refilled. They also found evidence that the delivered drug, which was in fact a neurotransmitter that is native to the body, was taken up by natural processes in the brain within minutes which, the researchers say, should help reduce side effects from the treatment.
Although early results are promising, the potential treatment would not be available for humans for several years. The researchers next plan to study the longer-term effects of the device in mice.
Malliaras is establishing a new facility at Cambridge which will be able to prototype these specialised devices, which could be used for a range of conditions. Although the device was tested in an animal model of epilepsy, the same technology could potentially be used for other neurological conditions, including the treatment of brain tumours and Parkinson’s disease.
The research was funded by the European Union.
Christopher M. Proctor et al. ‘Electrophoretic drug delivery for seizure control.’ Science Advances (2018). DOI: 10.1126/sciadv.aau1291
Dr Christopher Proctor is one of the first nine recipients of the Borysiewicz Biomedical Sciences Fellowship programme.
My research sets out to develop medical devices to treat and diagnose various health problems that have been difficult to address with conventional approaches such as epilepsy, Parkinson’s disease and brain tumours. As an engineer with expertise in electronics and materials, I work closely with biologists and clinicians in all stages of device development from early stage designing to late-stage testing.
The most exciting day I’ve had in research so far was when a concept that I took from a drawing on paper to a real device that I could hold in my hand, prevented a seizure for the third time. I say the third time because I am forever a sceptic, so I was hesitant to believe our initial results until we repeated it a couple times. Having seen that it was a repeatable result was very exciting because that is when you know you may really be on to something special.
I hope my research will ultimately lead to a better quality of life for people with health problems. I believe we are only scraping the surface of what is possible when we pair electronic devices with biology. It is difficult to project where early-stage research will go, but I suspect the way we address some of the most difficult to treat diseases may be radically different in the coming decades.
Cambridge is a great place to research and develop medical devices because this type of work is truly a team effort that requires expertise in everything from engineering to chemistry to medicine up to government regulations, finance and marketing. There is an ecosystem in and around the University of Cambridge that can bring all these experts together and that is exactly what is needed to take an early stage technology all the way to the patients that we are trying to help.
Traumatic brain injury (TBI) leads to many undesired problems and complications, including immediate and long-term seizures/epilepsy, changes in mood, behavioral, and personality problems, cognitive and motor deficits, movement disorders, and sleep problems.
Clinicians involved in the treatment of patients with acute TBI need to be aware of a number of issues, including the incidence and prevalence of early seizures and post-traumatic epilepsy (PTE), comorbidities associated with seizures and anticonvulsant therapies, and factors that can contribute to their emergence.
While strong scientific evidence for early seizure prevention in TBI is available for phenytoin (PHT), other antiepileptic medications, eg, levetiracetam (LEV), are also being utilized in clinical settings. The use of PHT has its drawbacks, including cognitive side effects and effects on function recovery. Rates of recovery after TBI are expected to plateau after a certain period of time. Nevertheless, some patients continue to improve while others deteriorate without any clear contributing factors.
Thus, one must ask, ‘Are there any actions that can be taken to decrease the chance of post-traumatic seizures and epilepsy while minimizing potential short- and long-term effects of anticonvulsants?’ While the answer is ‘probably,’ more evidence is needed to replace PHT with LEV on a permanent basis. Some have proposed studies to address this issue, while others look toward different options, including other anticonvulsants (eg, perampanel or other AMPA antagonists), or less established treatments (eg, ketamine). In this review, we focus on a comparison of the use of PHT versus LEV in the acute TBI setting and summarize the clinical aspects of seizure prevention in humans with appropriate, but general, references to the animal literature.