Advancing thalamic neuromodulation in epilepsy: Bridging adult data to pediatric care.

Thalamic neuromodulation has emerged as a treatment option for drug-resistant epilepsy (DRE) with widespread and/or undefined epileptogenic networks. While deep brain stimulation (DBS) and responsive neurostimulation (RNS) depth electrodes offer means for electrical stimulation of the thalamus in adult patients with DRE, the application of thalamic neuromodulation in pediatric epilepsy remains limited. To address this gap, the Neuromodulation Expert Collaborative was established within the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Special Interest Group. In this expert review, existing evidence and recommendations for thalamic neuromodulation modalities using DBS and RNS are summarized, with a focus on the anterior (ANT), centromedian(CMN), and pulvinar nuclei of the thalamus. To-date, only DBS of the ANT is FDA approved for treatment of DRE in adult patients based on the results of the pivotal SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) study. Evidence for other thalamic neurmodulation indications and targets is less abundant. Despite the lack of evidence, positive responses to thalamic stimulation in adults with DRE have led to its off-label use in pediatric patients. Although caution is warranted due to differences between pediatric and adult epilepsy, the efficacy and safety of pediatric neuromodulation appear comparable to that in adults. Indeed, CMN stimulation is increasingly accepted for generalized and diffuse onset epilepsies, with recent completion of one randomized trial. There is also growing interest in using pulvinar stimulation for temporal plus and posterior quadrant epilepsies with one ongoing clinical trial in Europe. The future of thalamic neuromodulation holds promise for revolutionizing the treatment landscape of childhood epilepsy. Ongoing research, technological advancements, and collaborative efforts are poised to refine and improve thalamic neuromodulation strategies, ultimately enhancing the quality of life for children with DRE.

Pediatric neuromodulation for drug-resistant epilepsy: Survey of current practices, techniques, and outcomes across US epilepsy centers.

Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

A Multicenter Study of Adherence to Best Practices and Application of Epilepsy Quality Metrics in a Pediatric Telemedicine Encounter.

Objective: To assess Epilepsy Quality Metrics (EQM) and guideline implementation in new pediatric patients seen in telemedicine. Methods: Multicenter, cross sectional, retrospective analysis. Results: Patients were similar across 3 centers for age, gender, and insurance type. Eighty-one percent presented for spells. One hundred sixty patients with epilepsy formed the EQM cohort. Results: Seizures described: 95%; frequency: 67%, last seizure documented: 81%, epilepsy syndrome documented: 67%; epilepsy diagnosis: 77%, medications reviewed: 56%, adverse events discussed: 73%. Quality of life discussed: 3%. Anticipatory guidance was described as follows: seizure safety, 57%; driving, 47%; SUDEP, 11%; vitamin D discussion, 19%; pregnancy and folic acid counseling, 4% and 10%. Epileptologists were 4 times as likely as generalists in discussing driving safety (odds ratio 3.93, 95% confidence interval 1.7-8.9; P = .001) for all ages. Significance: Performance on EQM and guideline implementation in pediatric epilepsy telemedicine encounters can be improved.

Quality and Safety Analysis of 2,999 Telemedicine Encounters During the COVID-19 Pandemic.

OBJECTIVE: To examine whether telemedicine remains safe and of high quality despite rapid expansion of services by comparing telemedicine encounters before and during the COVID-19 pandemic. METHODS: Pre-post study investigating 2,999 telemedicine encounters: February 1, 2020-May 15, 2020, was performed. A total of 2,919 completed visits before and after strict social distancing implementation were analyzed for patient and provider characteristics, encounter characteristics (e.g., history and physical examination), and quality and safety metrics (phone calls ≤ 7 days postvisit, visit-cause-specific hospital admission or mortality ≤ 30 days after visit). Stratified analysis of 3 groups for outcomes (young age, neuromuscular diagnosis, and new encounters) was performed. RESULTS: Patients ranging from 1 month to 33 years of age were seen. Rural patients were less likely to be seen during the pandemic compared with urban patients (8% vs 90%; p < 0.0001); teaching clinic and specialty clinic encounters increased significantly during the pandemic (8% vs 3%; p = 0.005), and documentation of at least 2 systems on examination was noted significantly more frequently during the pandemic (13% vs 7%; p = 0.009). No deaths were reported. There were no differences before/during the pandemic in safety or telemedicine failure metrics within the entire group and high-risk subgroups. CONCLUSIONS: Despite a markedly and rapidly expanded scope of ambulatory telemedicine care during the COVID-19 pandemic, telemedicine remained a safe and high-quality option for pediatric neurology patients. In addition, populations perceived as high risk for telemedicine (the very young, new patients, and those with neuromuscular diagnoses) can benefit from telemedicine visits, particularly when access to in-person care is limited.

"Chance Takers Are Accident Makers": Are Patients With Epilepsy Really Taking a Chance When They Drive?

This review compiles scientific data about the real dangers faced by people with epilepsy (PWE) who drive. Those include risks of motor vehicle accidents (MVA) in PWE as compared with controls (individuals without epilepsy) and as compared with persons with other medical conditions that impact fitness to drive. Data regarding Accident rates as related to seizure free intervals (SFI), single vs. multiple seizure events, and/or antiseizure drug (ASD) taper and reintroduction are discussed. Variation in state, national, and international laws and guidance for non-commercial and commercial drivers is highlighted, along with some related reasons for driving restrictions. The review concludes by emphasizing the importance of physicians educating patients about local driving laws and about risks of ASD non-adherence. The need for a broader, multi-stakeholder re-examination of driving regulations for PWE is noted.

Semiautomated Spike Detection Software Persyst 13 Is Noninferior to Human Readers When Calculating the Spike-Wave Index in Electrical Status Epilepticus in Sleep.

PURPOSE: Our objective was to use semiautomatic methods for calculating the spike-wave index (SWI) in electrical status epilepticus in slow-wave sleep (ESES) and to determine whether this calculation is noninferior to human experts (HEs). METHODS: Each HE marked identical 300-second epochs for all spikes and calculated the SWI in sleep EEGs of patients diagnosed with ESES. Persyst 13 was used to mark spikes (high sensitivity setting) in the same 300-second epochs marked by HEs. The spike-wave index was calculated. Pairwise HE differences and pairwise Persyst 13 (P13)-HE differences for the SWI were calculated. Bootstrap resampling (BCa, N = 3,000) was performed to better estimate mean differences and their 95% confidence bounds between HE and P13-HE pairs. Potential noninferiority of P13 to HEs was tested by comparing the 95% confidence bounds of the mean differences between pairs for the SWI. RESULTS: Twenty EEG records were analyzed. Each HE marked 100 minutes of EEG. HEs 1, 2, 3, and 4 marked 10,075, 8,635, 9,710, and 9,898 spikes, respectively. The highest and lowest 95% confidence bound of the mean difference in the SWI between HE pairs was: High: 10.3%; Low: -10.2%. Highest and lowest 95% confidence bound of the mean difference in the SWI between P13 and HE pairings was as follows: high, 9.5% and low, -6.7%. The lack of a difference between P13 and HEs supports that the algorithm is not inferior to HEs. CONCLUSIONS: Persyst 13 is noninferior to HEs in calculating the SWI in ESES, thus suggesting that an automated approach to SWI calculation may be a useful clinical tool.

DNM1 encephalopathy: A new disease of vesicle fission.

OBJECTIVE: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. METHODS: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. RESULTS: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. CONCLUSIONS: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

Ketogenic diet in Alpers-Huttenlocher syndrome.

We report on a young girl with Alpers-Huttenlocher syndrome, as confirmed by mitochondrial polymerase gamma sequencing, who was treated with the classic (4 parts fat:1 part each of carbohydrate and protein) ketogenic diet after she presented with epilepsia partialis continua. She improved clinically, and her electroencephalogram improved dramatically. This is the first detailed report on the efficacy of the ketogenic diet in treating the epileptic encephalopathy of Alpers-Huttenlocher syndrome. We present a literature review of the utility of a ketogenic diet in mitochondrial disorders, and speculations as to why the diet may be helpful in Alpers-Huttenlocher syndrome.

Postictal psychosis in a child.

Postictal psychosis is a state of psychosis following repeated or prolonged complex partial seizures with or without secondary generalization and is well described in adult epilepsy literature. It is sparsely reported in the pediatric literature. This report describes a 12-year-old male presenting with status epilepticus who developed psychotic symptoms. Diagnosis of postictal psychosis was made after correlating clinical symptoms with video-electroencephalographic monitoring. The clinical course of this illness is profiled, and the literature reviewed.