Intractable epilepsy

Overview

Epilepsy is a neurological condition characterized by recurrent seizures. A seizure is a rapid, abnormal alteration in the electrical activity of the brain. Temporary symptoms include twitching, loss of consciousness, and blank gazing.

Antiepilepsy medications are the initial line of therapy (AEDs). However, AEDs are unable to control seizures in certain persons. This is referred to as intractable epilepsy.

 

Intractable epilepsy definition

When AEDs fail to ameliorate the intensity or frequency of seizures, this is referred to as intractable (or refractory) epilepsy. It is identified after you have tried at least two AEDs (alone or in combination) with no success.

As a result, the disease is frequently characterized by medication adjustments.

Intractable epilepsy can appear in several ways:

• You are given epilepsy medicine, but it does not work.
• Your current medicine, which was meant to manage your seizures, no longer works.
• You are experiencing severe adverse effects from AEDs, making it difficult for you to continue therapy.

Seizures with intractable epilepsy continue even when AEDs are used. This is understandably frustrating and unpleasant.

 

Epidemiology

Epilepsy is rather prevalent. It affects more than 70 million individuals worldwide. Approximately 30 to 40% of these persons 

 

Etiology

Normal epilepsy drugs may not work well for many reasons, including:

• When administered at a medically safe dosage, the seizures simply become greater than the drug.
• Poor compliance with medication (missing doses)
• Complicating factors, such as extreme stress, sleep deprivation, and illness
• Additional medical problems, such as syncope (a transient loss of consciousness caused by inadequate brain blood flow): evidence suggests that the two illnesses are frequently confused, although persons with both conditions do exist. According to one research published in BMC Neurology, up to 41.1 percent of people with epilepsy had drug-resistant epilepsy, and 65.9 percent of those had both syncope and epilepsy.
• Brain abnormalities
• Genetic causes
• Medicine tolerance: In this situation, a medication may be effective for a few months until symptoms recur. With a new drug, the cycle will begin again.
• Some people just do not respond to medications: Some patients may require more than one drug to control their seizures, although these extra medications may not always completely halt seizures.

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

 

Symptoms

The basic characteristic of intractable epilepsy is that seizures continue even when anti-seizure medications are used. Seizures can last minutes or seconds and vary in strength and frequency. Electrical imbalances in the brain and overactive neurons produce them.

Convulsions, or uncontrollable shaking, may occur in some patients with intractable epilepsy.

Seizure symptoms include:

• Convulsions, or shaking movements
• Loss of consciousness
• Loss of bowel or bladder control
• Staring into space
• Falling
• Muscle rigidness

If you still experience seizures after taking more than two antiepileptic medications, you may have intractable epilepsy.

 

What Does This Mean for Your Child?

Intractable epilepsy may last a lifetime. This can lead to many long-term issues.  Your child may have: 

• Trouble doing school work 
• A need for help with daily living skills 
• A greater risk of getting hurt
• Depression or anxiety
• Trouble sleeping
• Reproductive issues

 

How Do I Know If the Treatment Is Wrong?

Another cause of uncontrolled seizures is inadequate or suboptimal therapy. To put it another way, the 'wrong key' is being used to open the door! The following are some of the most common causes of poor therapy.

Reasons For Suboptimal Treatment Of Seizures

• Using the wrong medication
• Inadequate doses of medicine
• Polypharmacy and toxicity
• Missing doses (poor compliance)
• Complicating factors (illness, sleep deprivations, extreme stress)

 

Using the wrong medication. Many seizure drugs are effective against a variety of seizure types. However, certain medications are not appropriate for particular types of seizures. Carbamazepine (Tegretol), for example, is often effective in treating focal seizures but not absence or myoclonic seizures. Ethosuximide (Zarontin) is effective for absence seizures but not for focal seizures. Because absence and focal seizures can occasionally be confused, there is a risk of administering the incorrect medication.

 

Inadequate or incorrect doses of medicine. People's reactions to seizure medications vary greatly. Every drug has a recommended dosage range, but for some, it is too high, while for others, it is too low. A person will have too many adverse effects if a dose that is too high for them is utilized. Seizures may occur if the dosage is too low.

• When the medication daily dosages are raised, some persons with uncontrolled seizures may become seizure-free.
• Others, such as elderly people, may benefit from lower ASM dosages, resulting in fewer drug adverse effects.
• Measuring blood levels of antiseizure drugs (ASMs) can assist guide therapy in some cases, although levels are not as significant as carefully inquiring about side effects and seizure control. Newer seizure medications frequently have fewer negative effects than previous seizure medications.
• On epilepsy.com, you can find information on seizure medications.

 

Polypharmacy and toxicity. Polypharmacy is the use of several medications at once to treat the same condition. Some people require more than one drug to control their epilepsy, but additional medications rarely lead to complete freedom from seizures.

• Two key studies, one by Mattson and colleagues and the other by Kwan and Brodie, indicate that if a person is not seizure-free on a decent dose of a single ASM, adding a second will only make them seizure-free around 10% of the time.
• In youngsters, the effectiveness rate of a second drug is roughly 30%.
• Two medications have more adverse effects than one, and three drugs have more side effects than two.
• Patients who use polypharmacy may experience so many adverse effects that it is impossible to tolerate a greater dose of any of their ASMs.
• Furthermore, polypharmacy can result in medication interactions that restrict how effectively a treatment works or worsen the negative effects of another drug.
• Patients who use polypharmacy may experience so many adverse effects that it is impossible to tolerate a greater dose of any of their ASMs.
• Furthermore, polypharmacy can result in medication interactions that restrict how effectively a treatment works or worsen the negative effects of another drug.
• It can sometimes be beneficial to streamline or simplify medications, but this must be done under the guidance of your neurologist. Sometimes "less is more," especially if it reduces overall levels of side effects and allows for an increase in the most beneficial medicine. Making these modifications can be difficult, since there may be a time of seizures and side effects as the new and improved routine is established.

 

Diagnosis

When a person has endured years of uncontrollable seizures, they are classified with intractable epilepsy. This indicates that their medicine is no longer effective in controlling their seizures, and their seizures are frequent, severe, and harming their quality of life. According to research, up to 40% of persons with epilepsy will develop intractable epilepsy, also known as drug-resistant epilepsy or refractory epilepsy.

Typically, you must have epilepsy for a long period of time before it may be called intractable. Your healthcare practitioner will take into account things such as:

• How often do you have seizures
• How well you've stuck to your treatment regimen
• If you still have seizures when properly medicated

 

When your epilepsy is pronounced intractable, you may expect a battery of tests and scans, just as you did when it was first diagnosed. These are some examples:

• Electroencephalogram (EEG)
• Computerized tomography (CT) scan
• Magnetic resonance imaging (MRI)

These scans may assist your doctor in identifying previously unknown factors that may influence future treatment decisions, which may include surgery or an implant.

 

What Does Drug-Resistant Epilepsy Mean?

Antiseizure drugs do not always manage seizures. These can be described using a variety of phrases, such as "uncontrolled," "intractable," "refractory," or "drug resistant."

• According to studies, nearly one-third of adults and 20-25 percent of children have epilepsy that does not respond fast to medications.
• The International League Against Epilepsy (ILAE) has advocated that the term "drug resistant epilepsy" be used instead of "refractory epilepsy."

1. Drug-resistant epilepsy occurs when a person fails to achieve (and maintain) seizure-free status after appropriate trials of two antiseizure drugs
2. These seizure drugs must have been chosen suitably for the individual's seizure type, tolerated by the individual, and tried alone or in combination with other seizure medications.

 

• Whether you have drug-resistant epilepsy, you should contact an epilepsy expert (epileptologist) at a comprehensive epilepsy center to determine why and if there are better treatment choices.

 

Management

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

Treatment options include:

Changing antiepilepsy drugs

Your doctor may advise you to use a different AED alone or in combination with another medication. AEDs include the following:

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

However, if you've already used two AEDs and had no success, it's doubtful that another AED will work. This might be because of how your brain or body reacts with AEDs. In this scenario, you'll have to attempt other remedies.

Antiepileptic medications (AEDs), either alone or in combination, are the first-line therapy for seizures. When one drug fails to work, another is tried. Unfortunately, the success rate decreases after a number of AED failures.

In general, following numerous AED failures, healthcare practitioners will begin to consider alternative methods of treating and managing seizures. Following drug failure, other treatment options may include lifestyle modifications, VNS therapy, and surgery.

According to one study published in the New England Journal of Medicine, the success rate for the third therapy after two unsuccessful treatments is relatively low—around 4%.

 

Diet Changes

According to certain studies, the ketogenic diet may reduce the number of seizures in some persons. This is a high-fat, low-carbohydrate diet that is strictly monitored by a dietician. It is typically given to children whose seizures are not responding to medicines.

According to one research published in the Iranian Journal of Pediatrics, children with epilepsy who had previously not been well-managed with medication had a success rate of 58.4 percent.

 

Improving Sleep

Seizures are affected by sleep habits. When patients with epilepsy do not get enough sleep, they are more prone to experience seizures. Seizures may become more frequent and last longer if you don't get enough sleep.

As a result, it is critical to create regular sleep patterns, such as receiving at least eight hours of sleep every night and going to bed and waking up at the same time.

 

Vagus nerve stimulation Therapy

Vagus nerve stimulation (VNS) therapy is the use of a tiny electric device, similar to a pacemaker. The device is implanted beneath the skin of the chest and transmits electrical impulses to the brain via the vagus nerve in the neck. The therapeutic objective is to lessen the frequency and severity of seizures.

 

Surgery

Surgery is a viable option for persons with refractory epilepsy if the seizure origin in the brain can be pinpointed and that region is safe to remove. Seizure cessation or near-cessation success rates range from 50 to 90 percent, depending on the origin of the seizures and their location in the brain. Epilepsy surgery is considered elective, which means that it is done for personal reasons rather than medical necessity.

Surgery in the brain can control seizures and may involve:

• Implanting a device to treat seizures
• Removing the area of the brain causing seizures
• Disrupting nerve pathways that promote seizure impulses

Not everyone is a candidate for surgery to treat persistent epilepsy. It is only an option if the area of the brain producing the seizures can be pinpointed. Furthermore, the region to be eliminated must not interfere with critical capabilities such as voice, touch, or movement.

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 transections

Your doctor will be able to tell you if brain surgery is correct for you. Operation success rates for seizure eradication vary depending on the kind of surgery, but can range from 50 to 90 percent.

 

Coping

Seizures that are intractable are tough to live with. Because of your seizure risk, you may be unable to drive, go to work, or participate in activities you like. You may need to make significant lifestyle adjustments until you find medications that lessen your seizure frequency.

It is critical to establish healthy coping mechanisms for all elements of your life, including emotional, physical, social, and practical components.

Consider a diagnosis of intractable epilepsy to be a starting point, not a finish. It doesn't imply that therapies won't help you; it just means you haven't found the correct ones yet. Continue to collaborate with your healthcare practitioner to find a solution.

 

Consequences of Intractable Epilepsy

Intractable epilepsy is a very incapacitating disorder. This group has a high rate of premature mortality. According to some research, up to 1% of people with persistent epilepsy die each year. The probability of sudden unexpected death appears to be twice as high in this cohort as it is in the overall population. If seizures are not managed, sudden unexpected death appears to be more likely.

A greater number of people are seriously injured. In addition to the obvious physical harm, the social ramifications of uncontrollable seizures may be crippling. Psychosocial patterns and independence are not generally developed during the development and teenage years.

A patient with intractable seizures is unable to obtain a driver's license and so is unable to participate in many social activities and career possibilities. The public lack of physical control that happens with large seizures may be both mentally and socially damaging, both individually and professionally.

 

Surgical Treatment for Epilepsy

Surgery can be used to treat intractable epilepsy, and several trials have demonstrated that surgery can be more beneficial than long-term medication treatment in carefully selected patients with intractable epilepsy. Resection procedures, disconnection operations, and neuromodulation utilizing electrical stimulation are the three primary types of surgical possibilities.

Patients with concordant EEG and imaging data (for example, a lesion that corresponds with a seizure focal in a noneloquent region) are candidates for surgical resection. Patients who do not have concordant results may be candidates for palliative surgery, such as disconnection procedures, or they may be candidates for neuromodulation.

 

How Can Parents Help?

Consult your doctor to find out what therapies are available for your kid. Assure that your child takes his or her medications as directed and avoids recognized seizure triggers such as lack of sleep, antihistamine usage, or severe stress.

Always notify your doctor if you believe medication isn't working or if you don't observe any improvement. This enables the doctor to provide the best possible treatment for your kid. Keeping your child safe during a seizure is critical. Make sure that other adults and caregivers (family members, babysitters, teachers, coaches, and so on) are aware of what to do if this occurs.

 

Conclusion 

Intractable epilepsy occurs when a seizure medication does not work, stops working, or has significant adverse effects that make it difficult to use.

When medications fail to control a child's seizures, doctors may suggest a specific diet, such as the high-fat, low-carbohydrate ketogenic diet. They may prescribe vagus nerve stimulator (VNS) treatment on occasion. An implanted device (stimulator) provides moderate electrical pulses to the brain through the vagus nerve. 

About 50% of children with intractable epilepsy may be candidates for epilepsy surgery. The majority of them would benefit greatly from surgery.