Practical Drug Treatment Recommendations on the Drug Refractory Epilepsy Patients: 2021 Clinical Guideline Subcommittee for Epilepsy in the Korean Neurological Association

One third of the overall epilepsy population are estimated to be a drug refractory epilepsy (DRE), defined as the patients who failed to control seizure reduction, even tried two or more appropriate antiepileptic drugs (AEDs) trials. Those people need additional AEDs trials or other treatment options (resective surgery, neuromoulation, etc.). Here, we, clinical guideline committee of the Korean Neurological Association (KNA) introduce the recommendations of AEDs treatments including not only old and new AEDs currently available in Korea but also AEDs planned to be launched in the new future for DRE patients with literature review to help efficient decision of the clinician. The authors reviewed literatures and assessed efficacy and tolerability on 12 currently available and four newly introduced/or planned AEDs applied to DRE patients, published from November 2015 to July 2021. Brivaracetam, eslicarbazepine, canabidiol and cenobamate are the four AEDs that are newly introduced or planned to be launched soon. The reviewed articles are publications after November 2015, 2018 American Association of Neurology guideline, new AEDs which were introduced or planned to be launched as of 2021. All AEDs are classified based on the therapeutic rating scheme, generating recommendations. Overall 173 papers have been reviewed and analyzed for recommendation rationales. KNA introduce additional add-on treatment or conversional monotherapy guidelines on the drug refractory focal and generalized epilepsy. We hope these guidelines or recommendations to help clinical decision for the treatment of drug refractory epilepsy patients

Epilepsy in children with perinatal arterial ischemic stroke

Purpose: Perinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. Material: We studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed. Results: From the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%). Discussion: Our study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.

Case Report: Rapid Treatment of Uridine-Responsive Epileptic Encephalopathy Caused by CAD Deficiency

We present two unrelated Chinese patients with CAD deficiency manifesting with a triad of infantile-onset psychomotor developmental delay with regression, drug-refractory epilepsy, and anaemia with anisopoikilocytosis. Timely translation into uridine supplementation, within 2-months of disease onset, allowed us to stop conventional anti-epileptic drugs and led to dramatic improvement in the clinical symptoms, with prompt cessation of seizures, resolution of anaemia, developmental progress, and prevention of development of severe and non-reversible manifestations. The remarkable recovery and prevention of advanced disease with prompt treatment, highlights the need to act immediately upon genetic diagnosis of a treatable disease. This further reinforces CAD deficiency as a treatable neurometabolic disorder and emphasises the need for a biomarker or genetic new born screening for early identification.

Pyridoxine Therapy: Not Just the Dose, the Duration Matters Too

Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. The prototypical presentation is intractable neonatal seizures that do not respond to conventional antiseizure medication but are well controlled by pyridoxine supplementation. Atypical forms account for one-third of the PDE spectrum and may escape early diagnosis. The common atypical presentations include the prenatal onset of seizures, seizures onset as delayed as 3 years of age, autism, arrested hydrocephalus, and fetal ventriculomegaly. Herein, we describe a 9-month-old child with neonatal-onset refractory seizures who failed two short trials of pyridoxine therapy and was later diagnosed with PDE by molecular studies. Regardless of the therapeutic response, a prolonged course of pyridoxine therapy is justified to identify delayed responders in infants with drug-refractory epilepsy of no apparent etiology.

Contributions of Imaging to Neuromodulatory Treatment of Drug-Refractory Epilepsy

Epilepsy affects about 1% of the world’s population, and up to 30% of all patients will ultimately not achieve freedom from seizures with anticonvulsive medication alone. While surgical resection of a magnetic resonance imaging (MRI) -identifiable lesion remains the first-line treatment option for drug-refractory epilepsy, surgery cannot be offered to all. Neuromodulatory therapy targeting “seizures” instead of “epilepsy” has emerged as a valuable treatment option for these patients, including invasive procedures such as deep brain stimulation (DBS), responsive neurostimulation (RNS) and peripheral approaches such as vagus nerve stimulation (VNS). The purpose of this review is to provide in-depth information on current concepts and evidence on network-level aspects of drug-refractory epilepsy. We reviewed the current evidence gained from studies utilizing advanced imaging methodology, with a specific focus on their contributions to neuromodulatory therapy.