What Are the Treatment Options for Drug-Resistant Epilepsy?

Epilepsy, a common brain disorder that causes seizures, affects about 3 million adults and 470,000 kids in the U.S., according to the Centers for Disease Control and Prevention. While medications are often effective in controlling seizures, around a third, or roughly 1 million people, with the disorder have drug-resistant epilepsy that doesn’t respond to treatment with medication.

When seizures aren’t controlled it can greatly undermine quality of life and — though most people don’t die from epilepsy — significantly raise mortality risk, from things like seizure-related accidental injuries to what’s called sudden unexplained death in epilepsy. “In this condition, a person with epilepsy dies from a seizure, sometimes witnessed and sometimes not, and no other cause than the seizure is able to explain the death,” the Epilepsy Foundation notes. “Experimental evidence points to seizure-provoked heart rhythm abnormalities, breathing problems, or brain swelling during a seizure as possible causes.”

Even occasional seizures can limit a person’s ability to drive, be independent and live life to the fullest, says Dr. Deborah Holder, director of the Comprehensive Epilepsy Program at Children’s Hospital Los Angeles. For children, uncontrolled epileptic seizures can also inhibit development, making it especially crucial to get those under control quickly. If a toddler experiences frequent seizures, for example, it can get in the way of learning basic skills, be it walking, talking, reading or writing, Holder says. “Children have a critical time where their brain is developing, and if we don’t control seizures during that critical developmental time, they may not reach those developmental milestones,” she says.

Experts recommend individuals suspected of having epilepsy — and those for whom treatment doesn’t adequately control seizures — go to a specialized epilepsy center to undergo a comprehensive evaluation and receive a proper diagnosis. Along with monitoring electrical activity in the brain during a seizure with an electroencephalogram, or EEG, and performing brain scans, epilepsy centers have specialized multidisciplinary teams consisting of neurologists, clinical neurophysiologists, neurosurgeons, psychologists, psychiatrists, social workers and counselors who evaluate each patient, notes says Dr. Dawn Eliashiv, a professor of neurology at the David Geffen School of Medicine at UCLA and co-director of the UCLA Seizure Disorder Center.

[See: Was That a Seizure?]

Not all seizures are caused by epilepsy, and there are various theories as to why it might be that for a sizable minority of people with epilepsy it’s drug-resistant — also called intractable or refractory. But as noted in a 2017 review of research on various hypotheses in the journal Frontiers in Neurology, the reasons many people aren’t responsive to medication still aren’t altogether clear. Notably, there’s an overarching concern that in some cases not enough of the medication is able to pass through the so-called blood-brain barrier — going from the bloodstream into brain tissue — and therefore it isn’t effective in stopping seizures. There’s also conjecture that the severity of a person’s epilepsy may play a role in the effectiveness of medications. But rather than a single explanation satisfying questions, as with the variable nature of epilepsy itself, various factors may contribute to drug-resistance. “You have to take multiple things into consideration,” says Björn Bauer, an associate professor of pharmaceutical sciences at the University of Kentucky College of Pharmacy. “One patient’s seizures and refractory epilepsy might be different from another patient’s.” As a result, experts say, therapy has to be individualized.

Fortunately, clinicians say patients whose epilepsy doesn’t respond to medications have other options to get seizures under control. One key distinction that can be made with a closer evaluation, which can have implications for treatment, is whether a person with epilepsy has focal or generalized seizures. “We have patients who have focal seizures that start in one spot in the brain and spread; and then patients who have generalized seizures, where it looks like the brain fires altogether,” Holder explains.

If, for example, a patient has a brain tumor or a brain infection, like encephalitis, that results in intractable epilepsy, traditional surgery or so-called laser ablation — using light to destroy cells — to target focal areas in the brain where seizures start may be the answer. If the patient is a candidate for surgery, and we can identify the area of the brain where the seizures are coming from, then we can surgically remove or treat that, that’s a chance to cure the epilepsy,” Holder says, where surgery can render a person “seizure-free,” or stop them from occurring the future. “We have very high success rates with epilepsy surgery, both in adults and children,” she adds.

Risks for brain surgery to treat epilepsy vary depending on the type of surgery. “The most common type of epilepsy surgery is removal of part of the temporal lobe,” according to the Epilepsy Society. “Possible risks of this type of surgery include problems with memory, a partial loss of sight, depression or other mood problems.”

[See: These Medicines May Cause Bone Loss.]

In other patients it’s possible to identify a seizure focus, but it may be one that can’t be removed. “An example would be if your seizure focus is too close to your motor area or your language area and it’s not safe to remove because you would leave the patient with a deficit — they’d lose their motor skills or their language skills,” Holder explains. In such instances, there are several options involving neurostimulation or neuromodulation, “where we treat the brain without taking part of the brain out,” she says.

One called vagus nerve stimulation involves implanting a device that stimulates the namesake nerve in the neck. “By stimulating that nerve it sends a signal to the brain, changes the way the brain works, and seizures get better,” Holder says. She adds that the treatment can be used for a person with focal or generalized seizures. Another type of neuromodulation to specifically treat focal seizures, where the problem area can’t be removed, is called responsive neurostimulation, or RNS. That involves placing an EEG electrode on the brain in the area of the seizure focus, and a generator in the skull. “That little generator monitors the brain waves 24-7, and when it [detects] a seizure, it turns on and stimulates the brain directly to stop the seizure,” Holder explains. And deep brain stimulation — a treatment most commonly used to control tremors in people with Parkinson’s disease — is now also used in some adults with epilepsy to control seizures. While treatments and patient experiences differ, neuromodulation can decrease seizures, their duration and the fatigue people feel afterward. The risks for neuromodulation vary but generally include infection and bleeding.

As with surgery that stops seizures, Eliashiv notes says there’s some evidence that even neurostimulators decrease the risk of a sudden unexplained death in epilepsy — especially patients with drug-resistant epilepsy.

Apart from medications, surgery and neurostimulation, another option for tackling intractable epilepsy is dietary changes. “We can actually stop your seizures by changing the food you eat,” Holder says. A ketogenic diet or modified Atkins diet, which is a high-fat, low-carb diet, is used. “When we switch you to one of these high-fat diets, your brain switches from using sugar for energy to using ketones, which is a breakdown product of fat; and as long as your brain stays in ketosis, your seizures get better,” Holder says. “Two-thirds of patients respond to this diet.”

Patients aren’t just turned out to make changes on their own, either, but closely monitored to ensure they receive all the vitamins and nutrients they need and limit unintended ill effects. “There is a risk of kidney stones on the diet,” Holder notes. A k etogenic diet can over time, in some people, also cause damage to the heart. “So we monitor these patients — checking routinely for labs. We also monitor their heart yearly and their kidneys yearly to make sure that we’re not causing any permanent problems for these patients, and if we start to see signs of that, then we alter the diet,” she says.

Besides diet, other lifestyle factors can also have an impact. For example: “A lot of seizures get worse with sleep deprivation and stress,” Eliashiv says.

[See: 12 Medical Emergencies You Need to Address Right Away.]

More than anything, clinicians urge individuals with epilepsy to fully explore treatment options and work with specialists to find a suitable alternative to medication when drugs fail to stop seizures. “I still think that there is stigma associated with epilepsy,” Eliashiv says, “and I really want patients to come forward and to know that there is hope and they can be evaluated.” Adds Holder: “That’s really critical that anybody with epilepsy who is still having seizures get a comprehensive evaluation — and explore which option might be best for them.”

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What Are the Treatment Options for Drug-Resistant Epilepsy? originally appeared on usnews.com

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