Steps in Providing Optimal Care for Patients With Drug-Resistant Epilepsy

Alex Whiting, MD

Epilepsy is a chronic neurologic disorder characterized by frequent seizures that affects over 70 million people worldwide. For a subgroup of patients who don’t respond to medication, otherwise known as drug-resistant, these individuals have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life. Developing novel treatments and management strategies for drug resistance has been a longstanding goal by several national organizations in the US, and represents one of the major challenges in epilepsy.

Over the years, the improvements in antiseizure medications have raised the standards for treating epilepsy, shifting the conversation around 75% and 100% seizure reduction rates instead of the traditional 50%. Advances in epilepsy surgery remain a significant part of this change as well, offering hope to subgroups of individuals with epilepsy who continue to fail with these medications.

Alex Whiting, MD, director of neurosurgery at Allegheny Health Network, is among those who see the impacts of drug-resistant epilepsy every day. He, along with his team of neurosurgeons, have been at the forefront of advocating for epilepsy surgery and the benefits it provides for certain individuals. In a recent interview with NeurologyLive®, Whiting provided a quick update on the state of treatment for patients with drug-resistant epilepsy, and the need to initiate tough conversations between patients, clinicians, and families on the potential treatment options available. He also touched on the challenges with understanding the pathophysiological mechanisms of the condition, as well as the steps following epilepsy surgery. 

NeurologyLive®: What are some of the earliest signs that a patient with epilepsy might be drug-resistant?

Alex Whiting, MD: The definition of drug-resistant epilepsy is now standardized. It refers to individuals who have not responded to multiple medications and continue to experience seizures. In most cases, a single seizure medication can effectively control seizures for patients. However, around one-third of individuals with epilepsy, after trying two different medicines, still experience seizures. These seizures typically manifest as staring spells, loss of consciousness, generalized tonic-clonic convulsions, among other seizure types. This definition is widely accepted by organizations like the American Academy of Neurology and the American Epilepsy Society. If a patient has tried multiple medications and continues to have seizures, they meet the criteria for drug-resistant epilepsy. At this point, it's advisable to undergo a surgical evaluation to explore potential options.

What types of conversations do you engage in with these patients, given their condition?

As a surgeon specializing in epilepsy, I primarily interact with patients who have not responded to medications. For individuals with epilepsy who have already attempted various medications without success, this can be a daunting and distressing period. They might feel like they've run out of options and are in a hopeless situation. During our discussions, I emphasize that seeking my expertise is a positive step. It allows us to explore an array of new treatment avenues and advanced technologies. Many times, our goal is to achieve a cure or find a way to attain seizure freedom. It's crucial for these patients to understand that despite medication failures or ongoing seizures, there's still hope and potential for improvement.

At the root of the issue, what is the mechanistic explanation for why certain patients develop drug-resistant epilepsy?

Unfortunately, epilepsy varies significantly among individuals, akin to unique fingerprints. No singular cause explains why some people are less responsive to medications. Genetic factors play a role for a subset of patients, as they might have a genetic predisposition that heightens the likelihood of seizures. For most patients, however, it's often attributed to random chance or unfortunate circumstances. I like to think of it as their epilepsy being more stubborn in nature. In epilepsy, a specific part of the brain is consistently triggering seizures, almost persistently attempting to initiate a seizure. For roughly two-thirds of patients, medications can effectively subdue this hyperactive brain region. However, for the remaining third, medications are insufficient, and seizures manage to overcome the medication barrier. In these cases, surgical intervention might be necessary to address the problematic brain region and potentially provide lasting seizure relief.

Does the location of the seizures influence your approach or choice of surgery?

Historically, our options for epilepsy treatment were relatively limited. Surgical intervention often involved removing a portion of the brain responsible for seizure activity. This approach was effective for individuals with isolated problematic brain areas. Yet, there was a significant subset of patients without viable surgical options. Their epilepsy might stem from critical brain regions or involve multiple areas simultaneously. Over the last two decades, the medical landscape has transformed with the introduction of innovative technologies such as laser ablation and stimulators. These advancements allow tailored surgical treatments for almost every patient with focal epilepsy. Consequently, our surgical approach is now influenced by the specific characteristics of each patient's condition.

Following epilepsy surgery, what steps are taken to customize patient management?

The post-surgery management plan depends on the type of surgery performed. For resective or ablative procedures, where the goal is to permanently halt the brain's seizure-causing area, a cautious approach is taken. We advise against abruptly discontinuing all medications right after surgery. It's preferable to allow time for the surgical effects to stabilize. As time passes and if the patient remains seizure-free, we gradually reduce their medication regimen. In cases involving stimulator implants, the approach varies depending on the type of stimulator used. Each type requires specific adjustments or titrations. We work closely with patients post-surgery to fine-tune their settings, aiming to optimize seizure control or achieve seizure freedom.

Looking ahead, what emerging concepts in epilepsy research hold significant promise? Where should our attention be focused?

We've made considerable strides in treating focal epilepsy—seizures originating from one or a few brain areas. Addressing generalized epilepsy, however, has proven more challenging, with limited effective options available. Neurostimulation—implanting devices to stimulate specific brain regions—is expected to play an increasingly crucial role in treating generalized epilepsy. While some patients may still lack suitable surgical options or require ongoing medication trials, advancements in neuromodulation offer hope. It's likely that within the next few years, nearly all patients who are unresponsive to medications will have a surgical option available. Keep an eye on developments in neuromodulation and related advancements as they shape the landscape of epilepsy treatment.

Transcript was edited with help of artificial intelligence.