What Is Refractory Epilepsy and How Is It Treated?

Epilepsy affects approximately 600,000 people in the UK, making it one of the most common neurological conditions. While many individuals achieve good seizure control with medication, a significant number continue to experience seizures despite treatment. This condition is known as refractory epilepsy, and it presents unique challenges for both patients and healthcare providers.

Understanding Refractory Epilepsy

Refractory epilepsy, also called medication-resistant or intractable epilepsy, is defined as a failure to achieve seizure freedom despite adequate trials of two or more appropriately chosen and tolerated anti-seizure medications (ASMs). According to the International League Against Epilepsy (ILAE), approximately 30% of people with epilepsy fall into this category.

Living with uncontrolled seizures can have profound impacts on quality of life, including:

• Increased risk of injury and premature death
• Limitations on employment and education
• Restrictions on driving and independence
• Higher rates of anxiety, depression, and social isolation
• Cognitive impairment from frequent seizures
• Medication side effects without adequate seizure control

Why Does Epilepsy Become Refractory?

Several factors may contribute to medication resistance in epilepsy:

Underlying Cause: Certain causes of epilepsy are more likely to be medication-resistant, such as:

• Structural abnormalities (e.g., mesial temporal sclerosis, cortical dysplasia)
• Some genetic epilepsy syndromes
• Brain tumours or vascular malformations
• Extensive brain injuries

Incorrect Diagnosis: Some individuals may have been misdiagnosed with epilepsy or prescribed inappropriate ASMs for their specific seizure type.

Pharmacological Factors: Some patients develop tolerance to medications, while others have genetic variations affecting medication metabolism.

Lifestyle Factors: Poor medication adherence, sleep deprivation, stress, or alcohol consumption may reduce treatment effectiveness.

Comprehensive Assessment for Refractory Epilepsy

When epilepsy proves difficult to control, a comprehensive reassessment is essential, typically at a specialist epilepsy centre. This evaluation includes:

1. Detailed History Review: Confirming the epilepsy diagnosis and reviewing all previous treatments
2. Video-EEG Monitoring: Capturing actual seizures to confirm the diagnosis and seizure type
3. Advanced Neuroimaging: High-resolution MRI with epilepsy protocol to identify structural abnormalities
4. Genetic Testing: When appropriate, especially for suspected genetic epilepsy syndromes
5. Functional Neuroimaging: Tests like PET or SPECT scans to identify abnormal brain activity
6. Neuropsychological Assessment: Evaluating cognitive function and psychological wellbeing

Treatment Options for Refractory Epilepsy

1. Medication Strategies

Even when epilepsy is deemed refractory, medication adjustments remain important:

• Alternative ASMs: Trying newer medications or those with different mechanisms of action
• Combination Therapy: Using multiple ASMs with complementary mechanisms
• Precision Medicine Approach: Tailoring treatment based on specific epilepsy syndrome, genetic findings, or biomarkers
• Clinical Trials: Access to experimental treatments not yet widely available

2. Surgical Options

Surgery offers the best chance of seizure freedom for many patients with refractory epilepsy:

• Resective Surgery: Removing the area of the brain causing seizures, most commonly temporal lobe resection
• Laser Interstitial Thermal Therapy (LITT): Using laser technology to destroy small seizure-generating areas
• Corpus Callosotomy: Cutting the nerve connections between brain hemispheres to prevent seizure spread
• Lesionectomy: Removing specific structural abnormalities causing seizures

Surgical candidacy depends on several factors, including:

• Ability to clearly identify the seizure onset zone
• Location of the seizure focus relative to critical brain functions
• Patient’s overall health and ability to tolerate surgery

3. Neuromodulation Therapies

When medication fails and surgery isn’t suitable, neuromodulation offers alternative options:

• Vagus Nerve Stimulation (VNS): An implanted device that stimulates the vagus nerve, reducing seizure frequency over time
• Deep Brain Stimulation (DBS): Electrodes implanted in specific brain regions, approved for epilepsy in 2018
• Responsive Neurostimulation (RNS): A “brain pacemaker” that detects abnormal activity and delivers stimulation to prevent seizures

4. Dietary Therapies

Modified diets can be effective in controlling seizures for some individuals:

• Ketogenic Diet: A high-fat, low-carbohydrate diet that has shown effectiveness, particularly in children
• Modified Atkins Diet: A less restrictive version of the ketogenic diet
• Low Glycaemic Index Treatment: Focuses on consuming foods that produce smaller changes in blood glucose
• Medium-Chain Triglyceride (MCT) Diet: Incorporates specific types of fats for ketone production

5. Lifestyle Management

Complementary approaches that may help improve seizure control include:

• Stress Reduction: Techniques like mindfulness meditation and relaxation therapy
• Sleep Hygiene: Consistent sleep patterns and treatment of sleep disorders
• Trigger Identification and Avoidance: Keeping seizure diaries to identify patterns
• Regular Physical Activity: Appropriate exercise programs tailored to the individual

The Multidisciplinary Approach

Management of refractory epilepsy requires a team of specialists:

• Epileptologists (neurologists specialising in epilepsy)
• Neurosurgeons
• Neuroradiologists
• Neuropsychologists
• Epilepsy specialist nurses
• Dietitians
• Social workers
• Occupational therapists

Recent Advances and Future Directions

Several promising developments may improve outcomes for refractory epilepsy:

• Improved Surgical Techniques: Minimally invasive approaches reducing recovery time and complications
• Novel ASMs: Medications with new mechanisms of action targeting medication-resistant epilepsy
• Gene Therapy: For specific genetic epilepsy syndromes
• Closed-Loop Systems: More advanced responsive neurostimulation devices
• Biomarkers: Better prediction of which treatments will work for specific patients
• Cannabis-Based Treatments: Ongoing research into cannabidiol and related compounds

Living with Refractory Epilepsy

While the primary goal is seizure freedom, improved quality of life remains essential even when complete seizure control isn’t achieved. Support services play a crucial role:

• Epilepsy Specialist Nurses: Providing education, support, and care coordination
• Patient Support Groups: Connecting with others facing similar challenges
• Psychological Support: Addressing common comorbidities like anxiety and depression
• Vocational Rehabilitation: Assistance with employment challenges
• Benefits Advice: Navigating disability benefits and financial support options

Conclusion

Refractory epilepsy presents significant challenges, but advances in diagnosis and treatment continue to improve outcomes. A comprehensive, multidisciplinary approach is essential, focusing not only on seizure reduction but also on overall quality of life. With appropriate specialist care, many individuals with refractory epilepsy can achieve better seizure control and lead fulfilling lives.

If you or someone you care for is struggling with epilepsy that doesn’t respond to initial treatments, seeking referral to a specialist epilepsy centre is a crucial step toward exploring the full range of available options.