October 2019, Volume XXXIII, No 7



Evolving diagnosis and treatment options

pilepsy, like so many medical conditions, is a mix of scientific truths and curiosities, diagnostic clarity and confusion, treatment successes, and profound treatment failures. The word “epilepsy” derives from the Greek verb epilambanein, meaning to be seized, to be overwhelmed by surprise. Epilepsy has historically been described as a disease, a magical curse—and even, at times, a sign of divinity. Increasing recognition of epilepsy as a disorder of brain electrical activity, combined with the development of more effective treatment, has begun to improve the disease course and lessen stigma.

Despite these advances, until the 1970s, it was legal in the United States to deny persons with seizures entry to restaurants, theaters, recreational centers, and other public places.

Defining epilepsy

Better understanding of epilepsy parallels a deepening understanding of brain physiology and anatomy. The brain is a complicated mix of collaborative cells organized in interwoven networks that work together to modulate consciousness, thought, and well-being. An epileptic seizure is a transient occurrence of symptoms due to abnormal excessive neuron firing in the brain.

Diagnostic terms have evolved. The terms “generalized” and “partial” seizures are still used by many to describe seizure, but the newest definition describes seizures as focal, generalized, or unknown onset, with modifiers that further describe seizure features.

“Seizure mimics”—symptoms that appear to be seizures—are common and can include panic attacks, sleep-related phenomena, migraine auras, and syncopal episodes characterized by fainting or passing out. Conditions like hypoglycemia, hyponatremia, and alcohol withdrawal can invoke seizures in earnest, but in such cases the seizure is provoked and not thought to represent a predisposition towards recurrent seizures qualifying for the diagnosis of epilepsy in the majority of such cases, although such events may “unmask” a cohort disposed to developing epilepsy.

Epilepsy is not an uncommon disease.

Utilizing the most current definition of epilepsy proposed in 2014 (Epilepsia, 55(4): 2014), Epilepsy is defined as being a diagnostic term when:

  1. At least two unprovoked (or reflex) seizures occur more than 24 hours apart.
  2. One unprovoked (or reflex) seizure and a probability that further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures will occur over the next 10 years.

The burden of epilepsy & SUDEP

Epilepsy is not an uncommon disease. The most recent data suggests that it affects one in 26 people. Per 2015 census data, an estimated 53,700 Minnesotans have epilepsy. In a more recent meta-analysis pooling 222 studies, the lifetime prevalence of active epilepsy was 7.60 per 1,000 persons with an annual cumulative incidence of epilepsy of 67.77 per 100,000 persons. The prevalence of epilepsy did not differ by age group, sex, or study quality. This exceeds the incidence of conditions such as colon cancer (38.0 diagnoses / 100,000 people) or lung cancer (57.5 diagnoses / 100,000 people), per 2015 CDC surveillance data.

Epilepsy burden can also affect employment. In a retrospective review of the Medical Expenditure Panel Survey using data from 1998–2009, 42% of people with epilepsy over age 18 reported employment, in comparison to 70% of people with no epilepsy. Epileptics missed an average of 12 days of work because of illness or injury, as compared with four days in the non-epileptic cohort. It was estimated that epileptics had a loss of productivity of $9,504 in 2011 dollars compared with people without epilepsy. In comparison, diabetes was associated with annual average lost productivity valued at $3,358 and depression at $3,182. Additionally, this data does not fully address the extension of burden for parents or caregivers whose work is interrupted to care for minors or loved ones with epilepsy.

Epilepsy is also associated with increased psychiatric diagnoses and diminished cognitive functioning in excess of the general population rates of adults without epilepsy. The interplay of memory and mood challenges induced by therapies to prevent seizures may even further compound such matters.

Part of epilepsy’s psychic impact may be due to the fact that sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related death in children and adults. SUDEP affects approximately 1 in 1,000 people with epilepsy each year. Risk mitigation strategies include reducing seizure frequency, optimizing therapy, and the use of nocturnal supervision/seizure detection devices.

Diagnostic challenges

While some patients may present with a clear seizure history and confirmatory testing (imaging plus neurodiagnostic testing), some epilepsies can be tough to diagnose. There are some with focal seizures who may only report recurrent paroxysmal psychic or sensory changes. Such events might occur and impair consciousness for the patient in a manner that would not be perceived to observers. The tests we rely on, such as electroencephalography (EEG) and brain imaging, cannot always help perfectly with diagnosis.

An EEG may consist of a 30-minute recording of brain activity using scalp electrodes. EEG after a first seizure shows an abnormality 12% to 73% of the time, yet a normal EEG may be seen in up to 50% of people with epilepsy. Brain imaging utilizing magnetic resonance imaging (MRI) as the preferred investigation in those with epilepsy may reveal causation of epilepsy, but also has a false negative rate, as the resolution of MRI still cannot tease out the detailed circuitry of the brain.

Our understanding of the role of genetics in epilepsy continues to advance. While the term “genetic” often makes people think of inherited disorders, many mutations causing epilepsy can happen spontaneously after conception in a manner that will lead to an affected child born to unaffected parents. It is thought that genetic factors account for 40% of epilepsy causes.

Medical treatment

The mix of options available to treat epilepsy has expanded considerably. No longer are we limited by a handful of medical options with, at times, intolerable side effects. The goal of treatment is to provide optimal seizure control with minimal drug side effects. At a very basic level, epileptic patients should have an emergency rescue medication available, such as a form of benzodiazepine to prevent prolonged seizures.

The mix of options available to treat epilepsy has  expanded considerably.

When judging the success of medical management of epilepsy, it is hoped that epileptics will attain seizure freedom in 47% of the cases with a first medication trial. An additional 14% will see seizure control with a second or third medication trial if the first trial fails. The current line of thought is that once two optimized medical trials have failed, an epileptic will be thought to have “intractable” epilepsy. For these patients, the hope is to contain, but perhaps not control seizures. In 3% of epileptics, two medications may completely control seizures. Despite the introduction of more than 15 new anti-epileptic drugs in the last 20 years, it is not clear that the treatment success rates with medications are substantially changing.

Lastly, compliance affects treatment failure. In a 2008 study of adults, 29% percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents.


Few topics have generated as much attention and excitement as has cannabis for the management of health conditions, including epilepsy. Recent research has shown benefit of cannabis fractionated into cannabidiol (CBD, one of many cannabinoids produced naturally in a cannabis plant) in treating severe epilepsy caused by Lennox Gastaut Syndrome (LGS) and Dravet Syndrome.

For Dravet Syndrome, CBD reduced median frequency of convulsive seizures per month from 12.4 to 5.9 versus placebo. Five percent of patients on CBD became seizure-free versus none with placebo. For LGS, the median percentage reduction in monthly drop seizure frequency from baseline in a study was 43.9% in the CBD group and 21.8% in the placebo group. While CBD shows benefit and promise for those with difficult epilepsy, we still need more data to show how this treatment modality will help those with other forms of epilepsy.

Dietary therapies for epilepsy

Ketogenic diets have been trialed for intractable epilepsy. In such patients, 90% of caloric intake may include fat as the main macronutrient of nourishment. Such a diet typically involves care by a multi-disciplinary team skilled in this modality. There are various other diets that can help epilepsy; see the Charlie Foundation website at https://charliefoundation.org/ for examples. In a recent study, it was found that those trialing a ketogenic diet or a modified Atkins diet saw a 63% response rate by one month and maintained a 41% response rate by 24 months.

Surgical options

When epilepsy becomes intractable, a patient should consider a surgical workup. While many neurology practices treat epilepsy, not all can provide a surgical opinion with advanced diagnostic testing that may lead to intervention upon the zone of seizure onset. In Minnesota, we are lucky to have multiple sites that can perform this expert evaluation. With advanced neurodiagnostic techniques, more patients are being considered for such surgical therapy than ever before. Control of seizures in the best of epilepsy surgery centers ranges from 15 to 75 percent.

Select surgical procedures can provide hope through electrical stimulation of the nervous system. Electrical nerve stimulation of the vagus nerve (VNS) in the neck via an implanted stimulating device can lessen seizure burden and provide a “rescue” intervention. VNS gives an electrical pulse when activated with a magnet passed over the device to help prevent a seizure from becoming prolonged. A recent VNS follow-up study found an increase in seizure reduction over time with this therapy by 38% after six months to 78% after 120 months in a long-term follow-up of 65 patients.

Responsive neurostimulation was approved in 2015. In this procedure, electrodes are placed in the brain to read patient brain activity and identify electrical signatures that may precede a seizure, allowing for a triggered electrical stimulation pulse to prevent seizure development. Five-year responder rates can be in excess of 60%. This therapy can be individualized to a patient’s needs.

In 2018 deep brain stimulation of the anterior nucleus of the thalamus was approved for treatment of epilepsy. In a randomized controlled trial, seizure reduction ranged from 21.3% following electrode insertion to 40.4% in the third month of treatment, compared to 14.5% in a non-stimulated control group. Long-term follow-up without a control group revealed a median seizure reduction at five years with treatment of 69%. The group of patients remaining on treatment declined from 105 after one year to 64 after five years.

The Future

Research in epilepsy continues to grow and expand as new drugs are developed, surgical options get refined, advances in genetic testing help us to better understand causes and tailor therapy, and stimulation parameters for newer electrical stimulation devices are optimized.

Tim Feyma, MD, is a child neurologist who specializes in medically complex children with neurologic conditions at Gillette Children’s Specialty Healthcare. He is also the current chair of the professional advisory board for the Epilepsy Foundation of Minnesota. 


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© Minnesota Physician Publishing · All Rights Reserved. 2019


Tim Feyma, MD, is a child neurologist who specializes in medically complex children with neurologic conditions at Gillette Children’s Specialty Healthcare. He is also the current chair of the professional advisory board for the Epilepsy Foundation of Minnesota.