What You Should Know About Intractable (Drug-Resistant) Epilepsy

Intractable (or refractory) epilepsy occurs when AEDs fail to improve the severity or frequency of seizures. It’s diagnosed after you’ve tried at least two AEDs (alone or together) without positive results.

As a result, the condition is often characterized by frequent medication changes.

Intractable epilepsy can appear in several ways:

• You receive medication for epilepsy, but it doesn’t work.
• Your existing medication, which used to control your seizures, stops working.
• You have severe side effects to AEDs, making it difficult to continue treatment.

Epilepsy is common. More than 70 million people in the world have it. Of these people, approximately 30 to 40 percent have intractable epilepsy.

The exact cause of intractable epilepsy is unknown. However, there are some theories behind the condition:

• Pharmacokinetic hypothesis. Efflux transporters are proteins that move toxic substances out of cells. This hypothesis proposes efflux transporters in the organs are overactive and reduce AED levels in the body, which decreases the drugs’ effectiveness.
• Neural network hypothesis. This theory says that seizures suppress the body’s natural antiseizure network and prevent AEDs from reaching the correct neurons.
• Intrinsic severity hypothesis. In this hypothesis, it’s said that severe forms of epilepsy are more resistant to AEDs.
• Gene variant hypothesis. This hypothesis states that genes linked to the transportation of AEDs in the body lead to drug resistance.
• Target hypothesis. AEDs work by targeting specific pathways and receptors in the brain. This hypothesis states that changes in these targets reduce the effects of drugs.
• Transporter hypothesis. This hypothesis proposes that efflux transporters in the blood-brain barrier are overactive, reducing the amount of drug entering he brain.

Sometimes, a person’s seizures might seem intractable even if they actually aren’t. This is called apparent pharmacoresistance.

In this case, drugs can’t control seizures due to the following reasons:

• incorrect use
• wrong dosage
• other medications cause interactions, decreasing effectiveness
• non-epileptic condition causing the seizures
• wrong diagnosis of seizure type or epilepsy syndrome
• lifestyle factors, like illegal drug use or stress

Intractable epilepsy causes seizures despite taking antiseizure medications. The symptoms of these seizures are the same as with seizures in general.

Possible symptoms include:

• convulsions
• stiffness
• twitching
• shaking
• loss of consciousness or awareness
• loss of bladder or bowel control
• blank staring
• falling

Your doctor will use several methods to diagnose intractable epilepsy:

• Medical history. Since intractable epilepsy involves frequent medication changes, your doctor will ask questions about the drugs you’ve taken.
• Electroencephalogram. An electroencephalogram (EEG) measures the electrical activity of your brain. This lets your doctor identify abnormal electrical patterns.
• Imaging scans. Imaging scans, like a CT scan or MRI scan, can show where the seizures are happening in your brain.

The goal of treatment for intractable epilepsy, like epilepsy in general, is to manage seizures.

Treatment options include:

Changing antiepilepsy drugs

Your doctor might recommend taking a different AED alone or with another drug. Examples of AEDs include:

• gabapentin
• lamotrigine
• zonisamide
• levetiracetam
• oxcarbazepine
• topiramate
• lacosamide

However, if you’ve previously taken two AEDs without positive results, it’s unlikely that another AED will work. This may be due to the way your brain or body interacts with AEDs. In this case, you’ll need to try other treatments.

Brain surgery

During brain surgery for epilepsy, your surgeon removes the part of the brain where seizures are happening.

Surgery can be divided into two categories:

• Curative. The goal is to get rid of the seizures.
• Palliative. The goal is to reduce the number and severity of seizures.

Examples of curative procedures used for epilepsy include:

• anterior temporal lobectomy
• hemispherectomy
• lensionectomy (used for tumors, cortical malformations, venous malformations; the surgeon will remove a lesion thought to be causing the seizures)
• amygdalohippocampectomy

Examples of palliative procedures used for epilepsy include:

• corpus callosotomy
• multiple subpial transection

Your doctor can determine if brain surgery is right for you. Surgery success rates — the elimination of seizures — depend on the kind of surgery you have, but could range from 50 to up to 90 percent.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) uses a device to simulate your vagus nerve, which may improve seizures. The device is implanted beneath your skin in your chest.

VNS may cause side effects like:

• hoarse voice
• coughing
• difficulty breathing

Other neurostimulation devices include:

• responsive neuro stimulation (RNS), which involves an electric generator implanted in the skull
• deep brain stimulation (DBS), where an electrode is implanted in the brain and a stimulator is implanted under chest skin

Dietary changes

A doctor might recommend following a seizure diet like the modified Atkins diet or ketogenic diet. The more restrictive keto diet is commonly prescribed for children who don’t respond to AEDs.

These diets can be difficult to follow successfully because they often require precise measurement of fats and carbohydrates.

If you’re following a low carbohydrate diet for epilepsy, be sure to work with a registered dietitian. They can help you get the nutrients you need.

Side effects of a seizure diet may include stomach upset and constipation.

Lifestyle changes

Along with the treatments above, it’s important to minimize seizure triggers.

Common triggers include:

• lack of sleep
• hunger
• alcohol
• caffeine
• nicotine
• drugs
• mental and emotional stress
• overstimulation, like bright lights

If AEDs aren’t helping your seizures, see a doctor. They might suggest a different dosage or drug.

Seek medical help if you have:

• worsening seizures
• more frequent seizures
• longer seizures than usual
• loss of consciousness for a long time
• difficulty waking up after a seizure

The outlook of intractable epilepsy varies from person to person.

Generally, you can expect a better outlook when intractable epilepsy is diagnosed early. That’s because it can take time to find effective alternative treatments when AEDs fail to work.

To improve your long-term outlook, visit your doctor regularly and follow their instructions. Take note of your seizure triggers and do your best to avoid them.

This can help prevent or minimize long-term effects, such as:

• permanent disability
• cognitive issues
• dependence on family and friends
• reduced quality of life

Trying different treatments can be expensive, even if you have health coverage. If you need assistance, talk to your healthcare professional. They might be able to suggest resources or organizations that provide financial aid.

Intractable epilepsy can take a toll on your physical, emotional, and mental health. This is normal. If you need support, visit an epilepsy center. These centers often have support services that can help improve your outlook.

If AEDs are unable to control your seizures, it’s called intractable epilepsy. It occurs when AEDs fail to work, stop working, or cause side effects that make it hard to keep taking the medication. There are some theories about why this occurs, but the exact cause is unknown.

The goal of treatment is to find effective alternative therapies. This might include nerve stimulation, brain surgery, or lifestyle changes. Your doctor may also suggest additional medications or different doses.

If AEDs don’t improve your seizures, ask for a referral to a comprehensive epilepsy center where medical professionals have special training in diagnosing and treating intractable epilepsy.

The outlook is generally better when intractable epilepsy is diagnosed early.