Epilepsy is a neurological disorder involving recurrent seizures. A seizure takes place when there is a sudden burst of electrical activity in the brain causing disruption to the way the brain functions normally.
Epilepsy is still poorly understood and patients have many unanswered questions. Many people cannot achieve freedom from seizures and for those that do quality of life can be affected by side effects from currently prescribed antiepileptic drugs (AEDs) such as tremors, agitation, and drowsiness.
Today is Epilepsy Awareness Day, and our Bill Holt shares more information about this difficult condition:
More than one-third of patients with newly diagnosed epilepsy do not respond to treatment with AEDs. In a large study conducted by the University of Melbourne, 1,795 patients with both newly diagnosed and previously treated epilepsy were followed for a minimum of two years or until death. The study took place between 1982 and 2014 and throughout the study period, seizure control rates did not improve.
Globally, an estimated 2.4 million people are diagnosed with epilepsy each year, meaning a potential 800,000 people are not responding to current treatments if we apply the learnings of the above study.
Despite the availability of more than a dozen new medications in the past two decades, the overall outcome for people with new-onset epilepsy has not changed fundamentally. Current antiepileptic drugs target seizure suppression and not disease modification. Future research may focus on novel treatments that can modify the development or progression of epilepsy.
What is epilepsy and how does it affect the individual?
There are different types of seizure which depend upon the area of the brain involved in the electrical activity. There are several types of seizure involving motor and non-motor symptoms. For example, a Tonic-clonic (grand mal) seizure causes a loss of consciousness and muscle contractions whereas an absence seizure (petit mal) can be brief and include momentary loss of consciousness.
What are the current treatments offered?
AEDs (anti-convulsant medications) are prescribed to control electrical activity in the brain. As previously mentioned these work for around two-thirds of patients. A patient will usually start on a low dose and work up until seizure control is attained. If seizure control is not achieved with the first regimen, a different AED will be prescribed and again dose escalated whilst the dose of the first regimen is decreased. Another possibility is to control seizures using a combination therapy.
For those who do not respond to anticonvulsants other options currently include deep-brain stimulation, surgery (only for certain candidates), Vagus nerve stimulation VNS) or a ketogenic diet (usually for pediatric epilepsy).
Why is it that approximately one third of patients do not respond to AEDs?
An AED must pass through the blood-brain barrier (BBB); a possible reason for drug-resistant epilepsy may be that the cells of the BBB transport larger amounts of the AED out of the brain meaning that it is less efficacious.
There are, however, other hypotheses, including misdiagnosis, there are several common imitators of seizures such as convulsive syncope (fainting), panic reactions, and dissociative states.
Why is epilepsy research important?
The underlying mechanisms of epilepsy are still only partially understood. It is, however, known that about 30%-40% is caused by genetic predisposition. Research will help scientists and drug developers understand the biological pathways which can be targeted for new epilepsy treatments. Areas of exploration are remarkably broad not only due to the complexity of the brain but also because different types of epilepsy have unique causes; seizures can be the result of many different types of brain malfunction.
Research into novel AEDs in pediatrics is also scarce, therefore, age- and disease-specific drug targets require identification and translation into innovative drug development strategies.
There are also social stigma/perceived social responses which affect patients. The University of Cambridge is currently running a Ph.D. research study titled “Young peoples’ perspectives on the impact of their long-term physical illness, disability or health condition.” This study looks at the impact on education, social life, and wellbeing of having a long-term physical illness, disability, or physical health condition. It also explores beliefs about illness and experiences in different contexts, such as at home, in education, and with health professionals. Researchers are particularly interested in epilepsy; for more information visit: https://cambridge.eu.qualtrics.com/jfe/form/SV_3pJ3SYh7ffgKUMB
What is on the horizon in epilepsy research?
Current AEDs are anti-convulsants which control seizures but have no effects on the underlying pathophysiology of epilepsy. There are a number of relevant animal models of epileptogenesis (how the brain develops epilepsy) which are being investigated to help scientists understand the epileptogenic process and potentially identify ways to prevent development of seizures or alter the course of the disease.
The search for biomarkers (e.g., metabolic, functional, molecular) is also vitally important, either to identify risk of epilepsy prior to first seizure for pre-symptomatic intervention (e.g., in those genetically predisposed) or in identifying patients already diagnosed with epilepsy for risk of severe brain damage caused by seizures.
How can an epilepsy patient stay abreast of developments in diagnostic techniques and treatments?
Patient advocacy groups such as the Epilepsy Society publish the latest in research papers/summaries to help patients stay informed of advances in epilepsy research.
The Epilepsy Foundation is committed to helping patients, families, and caregivers in advocating for funding for epilepsy programs and the protection of rights for those with disabilities. You can view their advocacy page here or clinical study information page here.