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Refractory Epilepsy: Causes, Risk Factors, Treatment And Role Of Keto Diet

| Reviewed By Karthika Thirugnanam

People with epilepsy have seizures due to abnormal electrical activity in the brain. A seizure is a sudden and uncontrolled disturbance in the brain which can lead to changes in one's behaviour, feelings, movements, and levels of consciousness. Each seizure may not only be life-threatening to the patient, but repeated seizures can also cause significant brain damage.

An individual is said to have refractory epilepsy when the medications fail to bring their seizures under control. Refractory epilepsy is also known as uncontrolled, intractable, or drug-resistant epilepsy. Studies have shown as much as 10 percent of the world's population experiences seizure at least once in their lifetime, one-third of whom develop epilepsy [1].

Most newly diagnosed epileptic patients will become seizure-free on their initial anti-epileptic drug therapy; however, about 30 per cent continue to experience seizures despite trials with multiple anti-epileptic drugs and are diagnosed as having refractory epilepsy [2].

Refractory epilepsy can adversely impact one's life in various ways, interrupting the quality of life not only for the patient but also for those around them.

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Causes Of Refractory Epilepsy

The reasons that lead to uncontrolled seizures are as follows [3]:

  • Incorrect diagnosis
  • Wrong treatment
  • Certain triggers or lifestyle factors also affect seizure control despite the best treatment
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Risk Factors Of Refractory Epilepsy

The commonly reported risk factors of the condition are as follows [4]:

  • Epilepsy with structural lesions in the brain - certain specific lesions, certain developmental abnormalities in the brain
  • Early epilepsy onset
  • High seizure frequency
  • Absence of response to the first 2 AEDs (Anti-Epileptic Drugs)
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Treatment For Refractory Epilepsy

Patients with refractory epilepsy are usually treated with multiple anti-epileptic drugs and because of the chronic nature of this disease, comprehensive care for these individuals should include their socio-psychological needs as well as the management of the chronic side effects of these medications [5].

When the seizures persist even after the application of the treatment measures, other medical methods will be used to treat and manage the condition, such as epilepsy surgeries, vagal nerve stimulation (VNS) and a ketogenic diet [6].

1. Brain surgery

The most common form of treatments applied for refractory epilepsy is brain surgery. It is regarded as an alternative treatment for patients with refractory epilepsy [7]. The best candidates for surgery are individuals with focal epilepsy whose seizures arise from one area that is not critical for brain function. Brain surgery is further classified into two types, callosotomy and resective surgery [8].

  • Callosotomy: Also known as corpus callosotomy, the palliative surgical procedure treats refractory epilepsy. In this procedure, the corpus callosum (it connects the left side of the brain to the right side) is cut through to limit the spread of epileptic activity between the two halves of the brain. When the corpus callosum is disconnected, the progression and generalisation of the seizure are prevented [9][10].
  • Resective surgery: Resective surgery, the most common epilepsy surgery, is the removal of a small portion of the brain. In severely refractive cases an entire half of the brain may need to be resected [11]. The surgeon cuts out brain tissues in the area of the brain where seizures originate, usually the site of a tumour, brain injury or malformation [12].

2. Vagus nerve stimulation (VNS)

VNS is a nonpharmacologic tool that can be considered as adjunctive therapy for patients with refractory partial seizures, who are not candidates for epilepsy surgery or are unwilling to undergo the procedure [13][14]. The pulse generator of the VNS device is implanted beneath the skin in the left upper chest region and is connected to the left vagus nerve. Studies show 50 per cent improvement in seizure frequency in 37 per cent of patients in their first year of therapy [15].

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Management Of Refractory Epilepsy

What is a keto diet?

With surgeries and therapies laid out for the management of the condition, health experts and doctors suggest the adoption of a keto or ketogenic diet.

The ketogenic diet (or keto diet, for short) is a low-carb, high-fat diet which can help improve one's health [16]. Ketogenic diets, studies assert, have benefits against diabetes, cancer, epilepsy and Alzheimer's disease. Keto diet involves drastically reducing carbohydrate intake and replacing it with fat, which puts your body into a metabolic state called ketosis [17][18].

When ketosis happens, your body becomes incredibly efficient at burning fat for energy. It also turns fat into ketones in the liver, which can supply energy for the brain [19]. Along with that, it can result in high reductions in blood sugar and insulin levels [20].

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Keto diet and refractory epilepsy

The high-fat, low-carbohydrate diet has shown efficacy in the treatment of refractory epilepsy [21]. Although the mechanism of its anti-epileptic activity is not completely understood, new evidence suggests that the production of ketone bodies may diminish the hyperexcitability of neurons and improve seizure control [22]. Doctors usually recommend the ketogenic diet for children whose seizures have not responded to several different seizure medicines due to its effectiveness in managing the condition [23].

The ketogenic diet has been shown in many studies to be particularly helpful for some epilepsy conditions [24]. These include infantile spasms, Rett syndrome, tuberous sclerosis complex, Dravet syndrome, Doose syndrome, and GLUT-1 deficiency [25]. The studies further state that using a formula-only keto diet for infants and gastrostomy-tube fed children may lead to better compliance and possibly even improved efficacy [26].

Studies go on to point out that not only do the ketogenic diet formulas help in children with epilepsy on the ketogenic diet, but work better than a solid food ketogenic diet [27]. According to the study published in the journal Epilepsia, out of the 61 children who were on all-liquid ketogenic diets, 59 per cent of these children had a >90 per cent reduction in seizures, which is near twice the average response for children receiving the ketogenic diet overall [28].

However, there are side effects which should be discussed before considering the keto diet.

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On A Final Note…

Polymers, electrical brain stimulation and prediction of seizures may be available in the future for treating patients with refractory epilepsy. Cell transplantation and gene therapy, although holding great promise, are still far from routine clinical use. Along with accurate medical treatment, it is very crucial to make conscious lifestyle changes including that in diet, sleep, self-care, stress-reduction, etc. While the patient along with the doctor figures out what works best for them, the person must not hesitate in reaching out for emotional support.

With inputs from Dr. Sowmya M Consultant Neurologist, Aster RV Hospital.

Karthika ThirugnanamClinical Nutritionist and Dietitian
MS, RDN (USA)
Karthika Thirugnanam
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