[7] Some clinical factors that are thought to be predictive of DRE include the female sex, focal epilepsy, developmental delay, status epilepticus, earlier age of onset of epilepsy, neurological deficits, having an abnormal EEG and/or imaging findings, genetic predisposition, association with the ABCB1 gene, and inborn errors of metabolism.
Typically patients are admitted to hospital for prolonged EEG monitoring with video technology used to capture clinical events as they occur.
[10] Typically patients are taken off their anti-seizure medications in order to characterize the evolution of seizure symptoms and their relation with changes in electrical activity of brain.
Identification of common lesions associated with epilepsy, like focal cortical dysplasia, mesial temporal sclerosis, microencephalocele, and heterotopia, require thorough review of images by trained clinicians, as the changes can be very subtle and easily missed if not specifically evaluated for.
Oftentimes findings on PET scan are often correlated with other diagnostic workup that has already/concurrently been obtained to further localize an epileptogenic area of the brain, particularly in the case of focal epilepsy.
[15][16] Single-Photon Emission Computerized Tomography (SPECT scan) is another radiotracer based imaging technique that uses an oxygen radio-isotope to assess blood flow in the brain.
This imaging is performed during inpatient video EEG monitoring in which the tracer is injected into the patient's bloodstream as soon as a seizure starts.
[16][17][11] Magnetoencephalography (MEG): A newer non-invasive imaging technique that measures the magnetic field associated with neuronal firing in the brain.
If there is poor performance in measures of specific cognitive domains like verbal memory, naming, or visual-spatial orientation, it may point to areas of the brain that are dysfunctional and likely related to seizure onset.
Besides helping assess the likely area of seizure onset, this testing can be informative post surgical intervention and/or epilepsy therapy.
[11][19] If epilepsy surgery is being considered, testing is often performed to determine the hemisphere of the brain involved in language and memory function.
Once the patient is fully recovered from the injection on the first side, the catheter is withdrawn and threaded up the contralateral middle cerebral artery with neuropsychological testing repeated.
This testing informs the "reserve" for memory and language function in each hemisphere and the potential for impairment with resective surgery on a given side.
In some cases additional testing with selective injection of the posterior cerebral artery (that supplies the mesial temporal region including hippoampus) can be done.
Functional MRI (fMRI) measures the change in blood flow and oxygenation in different parts of the brain in response to an activity.
While the term drug-resistant epilepsy implies ineffectiveness of pharmacologic therapy, recent advances in the pharmaceutical industry have introduced new drugs that have proven to be effective in the management of DRE patients.
Approved by the FDA in 2019 for treatment of epilepsy in adults, cenobamate is primarily used to treat patients with focal onset seizures.
There have been at least three separate clinical trials involving cenobamate with results showing a reduction in seizure burden by at least 50% in the experimental groups, especially at higher doses of the drug.
No adverse cardiac events have been reported with the use of fenfluramine for epilepsy treatment, with the main side effects being diarrhea, weight loss, and fatigue.
The mechanism of action of cannabidiol is unclear but hypothesized to be related to Ca channels, adenosine signaling, and overall modulation of neuronal hyperexcitability.
[26] Similar to fenfluramine, there has been evidence of improvements in cognition, emotional regulation, and communication in addition to seizure control for patients taking cannabidiol.
This state is called ketosis and it changes several biochemical processes in the brain in a way that inhibits epileptic activity.
Side effects of the ketogenic diet include constipation, fatigue, weight loss, and kidney stones (typically after long-term adherence).
[37] Some physicians recommend the modified Atkins diet because they assume that patients will adhere to it on the long-term because it is more compatible with daily life and the meals are more enjoyable.
Rapid fluctuations in glucose levels both high and low is thought to be a trigger for seizures in some patients with epilepsy.
In most cases, epilepsy surgery is only an option when the area of the brain that causes the seizures – the so-called epileptic focus – can be clearly identified and is not responsible for critical functions such as language.
This procedure is mostly carried out on patients with so-called drop attacks that come with a very high risk of injury and in which the epileptic focus is not clearly delimitable.
Surgical intervention is considered a viable option for infants with drug-resistant epilepsy, particularly when anti-seizure medications fail to achieve seizure control.
[63][64] Deep brain stimulation of the anterior nuclei of the thalamus is approved for DRE in some countries in Europe, but has been and continues to only be used in a very few patients.
Responsive neurostimulation (RNS) is approved for DRE in the US and involves stimulation directly to 1 or 2 seizure foci when abnormal electrocorticographic activity is detected by the device's software.