Epilepsy and Seizures
Epilepsy is a broad class of disorders resulting in recurring seizures (abnormal electrical activity in the brain)8. There are many different causes for various forms of epilepsy, including genetics, acute illness, substance withdrawal, acute injury, and electrolyte imbalance8.
Although children and older adults are most susceptible to seizures, they can occur in people of any age group or demographic8. However, 80% of people living with epilepsy are from low and middle-income countries. With the limited accessibility to proper medical treatment that characterizes this at-risk demographic, it has been proposed that up to 70% of people with epilepsy could live seizure-free1.
Individual seizure events are complex and heterogeneous, but generally fit in one of three broad categories8:
- Partial seizures begin with excessive synchronized firing in one portion of the cortex7. People undergoing a partial seizure are awake and may display irregular movements, have inappropriate autonomic responses, and experience sensory hallucinations such as visual aura9.
- Particularly in adult individuals, these partial seizures can transition into generalized seizures and spread across the entire cortex8,9. When a seizure begins or spreads over the entire cortex, an individual loses consciousness and exhibits tonic-clonic rhythmic movements.
- The third class of seizures is partial-complex seizures, which cause minimal motor symptoms, but leave the individual in an altered, hallucinatory state of consciousness8.
Current Treatment Options for Epilepsy
A wide range of anti-epileptic medications have been developed which counter and suppress the onset of seizures in epilepsy. Broadly, these medications work by suppressing neural activity, primarily within epileptogenic foci and networks.
While these medications are effective in 60-70% of patients in abolishing recurrent seizures, they can consequently induce negative psychological and physiological side effects22,23. In the 30-40% of drug-resistant epilepsy patients in which these medications are ineffective, two alternate treatment options exist: surgical resection, and vagal nerve stimulation.
The most prominent Resection surgery for treatment-resistant epilepsy is Laser Interstitial Thermal Therapy (LITT). This minimally-invasive surgery requires ablating discrete regions of epileptogenic foci, and can give patients life-changing relief from their seizures. However, successful remission of seizures is not guaranteed, and personalizing treatment strategy is quickly becoming a goal of modern neurosurgery.
Solutions such as connectomics have emerged as useful for epilepsy patient-selection and identifying those likely to respond to resective surgery, and will be discussed in the following sections24.
Alternative to neurosurgery, deep brain stimulation (DBS) and vagus nerve stimulation (VNS) seeks to treat epilepsy symptoms by regulating neurological activity to the brain. These treatments are generally less invasive than resective and ablative surgery, reducing costs associated with treatment as well as recovery time. However, their effectiveness is highly variable between individuals, and produces a gradual response, reducing seizures to a greater extent over time from beginning treatment25,26.
Connectomics holds utility in neuromodulatory treatments of epilepsy in both identifying accurate targets for DBS27, as well as tracking the treatment response through changes in underlying brain function over time26.
Figure 2: Common epilepsy DBS treatment sites
The Future of Epilepsy Therapy Through Connectomics
Recent research leveraging connectomic techniques not only demonstrates its potential in identifying where epilepsy is located in the brain, but also in predicting who will respond to different types of treatments24,34,35.
Alongside seizures, epilepsy has numerous cognitive symptoms, such as impaired motor, emotional, and executive function. These symptoms are directly tied to brain networks, namely the sensorimotor, limbic, and central-executive networks. Indeed, comorbid depression afflicts between 20-55% of epilepsy patients, and has shown to be directly tied with limbic system dysfunction36.
However within the context of epilepsy, brain networks and symptoms outside of seizures themselves have received relatively little attention. With advanced neuroimaging and connectomics, it may be possible to identify and better understand the brain network alterations associated with non-seizure components of epilepsy, enabling a more tailored and personalized continuum of epilepsy treatment and care35,36.
Connectomics enables a detailed structural and functional view of brain changes associated with the wide variety of symptoms which afflict epilepsy patients. Already demonstrating both predictive and therapeutic value, connectomic-approaches are beginning to be used to better understand and treat the symptoms of epilepsy, and in the future may help progress personalized treatment options6, 13, 24, 27, 29, 34, 36.