The Many Challenges of Drug-Resistant Epilepsy

For approximately two-thirds of people who have epilepsy, sustained freedom from seizures is achieved with antiseizure medications (ASMs). Sustained seizure freedom is defined as no seizures within 12 months or a period that is 3 times a person's longest interval between seizures, whichever is longer. Approximately one-third of people with epilepsy, in contrast, have drug-resistant epilepsy (DRE), in which seizure freedom is not attained with ASMs.

DRE is defined by the International League Against Epilepsy as lack of sustained seizure freedom after 2 adequate trials of ASMs. The rationale for this comes from epidemiologic studies showing there is an extremely low likelihood of responding to a third ASM after 2 others have failed. Adequate ASM trials require uptitration to a therapeutic dose with a tolerable medication, which can take several months.

Nonpharmaceutical treatment options, however, are available for people with DRE. Unfortunately, because of diagnostic delays—both for epilepsy itself and for identification of DRE—there are typically years-long delays in referral to comprehensive epilepsy centers where candidacy for treatments can be determined and treatments can be delivered. This makes recognition of DRE and understanding of the potential treatments paramount for clinicians treating people with epilepsy.

In this issue we present a range of cases of DRE, first with Drs. Rajarshi Mazumdar and Jessica Pasqua, who highlight Diagnostic and Treatment Delays in Temporal Lobe Epilepsy, and from Drs. Brin Freund, Anteneh Feyissa, Sanjeet Grewal, and Erik Middlebrooks, the clinical decision-making process for Neurostimulation for Drug-Resistant Epilepsy, a treatment of choice for DRE when seizures arise from more than 1 location. Next, we present case reports and discussion showcasing various DRE etiologies with Early-Onset Drug-Resistant Epilepsy Due to Gene Variants from Drs. Imane Abdelmoumen and Eiman Ali, Focal Status Epilepticus 9 Years After Brain Abscess from Dr. Natalie Ullman, Autoimmune-Associated Epilepsy by Evan McNeil and Drs. Middlebrooks and Feyissa. Progressive Drug-Resistant Epilepsy & Behavior Changes from Drs. Natalie Baner and Mark Fitzgerald presents the possibly autoimmune Rasmussen syndrome, and Drs. Charlene Gunasekera, David Burkholder, Lily Wong-Kisiel, Middlebrooks, and Feyissa share the neurocutaneous Parry-Romberg Syndrome With Drug-Resistant Epilepsy.

We are grateful to all contributors for sharing the stories of patients from our practices. In some cases, the treatment journey was as brief as 6 months and in other cases, over 20 years. We hope the material presented will assist Practical Neurology readers in speeding their own patient's journeys to what will hopefully be eventual seizure freedom as often as possible.