How are seizures detected and prevented in epilepsy?

By Eva Borras

According to the World Health Organization, epilepsy is one of the most common neurological diseases on the planet, with roughly 50 million people affected by it, including of age and gender. Epilepsy is a chronic disease characterised for causing recurring seizure episodes of involuntary movements of the body that can lead to unconsciousness, meaning that premature death is three times more likely for epilepsy patients than the general population. Although there is an estimate that 70% of those suffering from it could live seizure free if diagnosed and treated, that still leaves 15 million patients in pain. In addition, the frequency of such unwanted seizures seems to be impossible to fixate, as some people experience once every day and others various on the daily. For this reason, scientists have been researching for decades on how to stop seizures or at least predict when they might occur.

At the moment Anti-epileptic drugs (AEDs) are the most used treatment for epilepsy, approximately effective in 7 out of 10 people, as the NHS reported. However, AEDs have possible side effects such as headaches, drowsiness and rashes and it is important to emphasize this treatment is not a cure as seizures are not controlled completely. Furthermore, the WHO highlighted in 2004 that 80-90% epilepsy patients in low-income countries are not receiving the appropriate AEDs to successfully stop seizures due to unavailability of medications. The alternative treatment is surgery, for patients whose seizures continue happening after taking AEDs. But that is not the end of research, as several patients are both unsuitable for AEDs and brain surgery, so since the 1990s there has been a new promising therapeutic option for epilepsy without having to risk the patients life in surgery: neurostimulation. (Niriayo et al., 2018)

There are three invasive methods for neurostimulation approved: deep brain stimulation (DBS), Responsive Neurostimulator System (RNS) and Vagus nerve stimulation (VNS). The latter, VNS is the only approved method of stimulation therapy in the USA since 1997. (Fisher, 2012) Taking advantage of the fact that seizures happen via electrical signals sent to unrequested areas of the brain, the VNS consists of an implant that is placed under the chest’s skin and is connected to the left Vagus nerve in the neck. Using an external program the generator is adjusted by the physician. When abnormal electrical impulses are detected, the electrical device stimulates the peripheral Vagus nerve by means of electrical signals to finalize the seizure. One hypothesis of how seizures are reduced is because brain metabolism, mainly the thalamus increases;another is that VNS might modify synaptic connections in the brain. Although it doesn’t prevent the seizure, it is possible to use a programmed magnet over the implant to do so as soon as it is detected. Approximately in 30-40% of the cases have been reported as useful. Therefore electrical signals recorded by the implant in VNS allows early detection and, at times, anticipation of seizures. (Ben-Menachem, 2012)

Similarly, electrodes are implanted in the anterior nuclei of the thalamus in DBS. Using a pacemaker-like device, that was successful in treatment of Parkinson’s disease, DBS was adapted for epilepsy patient in the 1970s. The way DBS works is by inhibition or excitation target brain part to stop propagation of electrical connections causing seizures. In the future, DBS research is focused on identification of optimal target areas on the brain to increase effectivity. (Zangiabadi et al., 2019) With DBS, 40% of seizures were reduced after a 3 month period of carrying the implant, whilst after two years the seizures were reduced by 56% making DBS one of the most effective ways to prevent and stop seizures.  (Ben-Menachem, 2012)

In a study carried out in 2018, 10 out of 11 patients receiving both VNS and DBS had progressive similar responses with the two techniques. Additionally, both methods have risk of causing an infection as well as after surgery speech disorders development.(Kulju et al., 2018)

More recently, RNS has been proven to be very effective in cases where the precise area of the brain that causes seizures are identified. Four electrodes are implanted in the seizure foci along with a neurostimulator in each patient. The neurostimulator continuously monitors electrocorticographic activity and in response to abnormal patters it provides responsive electrical stimulation through the four electrodes. Combining three clinical trials, patients were found to have 600-2000 detections leading to stimulations per day and calculated to last almost 9 years before the need to replace the battery. In addition, other benefits such as improvement in learning were outlined when seizures onset from mesial temporal lobe, as well as improvement in verbal fluency when onset of seizures was in frontal lobe. (Skarpaas, Jarosiewicz and Morrell, 2019)

Nonetheless, over the last decade non-invasive techniques that don’t require a brain implant are being developed, and new doors, such as genetic strategies, to treat epilepsy hav opened. (11 different inherited genes have been identified for monogenic forms of epilepsy.) 

Lastly, optogenetics (the use of light sensitive proteins) is being considered as an exciting research tool. By modulating neural activity, scientists are able to inhibit and activate different neurones associated with the propagation of seizures. (Zangiabadi et al., 2019) This gives hope to find a non-invasive way in the near future to detect and prevent seizures.

References:

Ben-Menachem, E., 2012. Neurostimulation—Past, Present, and Beyond. Epilepsy Currents, 12(5), pp.188-191.

Fisher, R., 2012. Therapeutic devices for epilepsy. Annals of Neurology, 71(2), pp.157-168.

Kulju, T., Haapasalo, J., Lehtimäki, K., Rainesalo, S. and Peltola, J., 2018. Similarities between the responses to ANT-DBS and prior VNS in refractory epilepsy. Brain and Behavior, 8(6), p.e00983.

Niriayo, Y., Mamo, A., Kassa, T., Asgedom, S., Atey, T., Gidey, K., Demoz, G. and Ibrahim, S., 2018. Treatment outcome and associated factors among patients with epilepsy. Scientific Reports, 8(1).

Skarpaas, T., Jarosiewicz, B. and Morrell, M., 2019. Brain-responsive neurostimulation for epilepsy (RNS® System). Epilepsy Research, 153, pp.68-70.

Tefera, G., Woldehaimanot, T. and Angamo, M., 2015. Poor treatment outcomes and associated factors among epileptic patients at Ambo Hospital, Ethiopia. Gaziantep Medical Journal, 21(1), p.9.

Zangiabadi, N., Ladino, L., Sina, F., Orozco-Hernández, J., Carter, A. and Téllez-Zenteno, J., 2019. Deep Brain Stimulation and Drug-Resistant Epilepsy: A Review of the Literature. Frontiers in Neurology, 10.