Treatment Of Refractory Epilepsy Research Articles

Efficacy of add-on Cenobamate treatment in refractory epilepsy due to Rasmussen's encephalitis.

To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis. Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy which had been pharmacoresistant to more than 10 prior treatment regimens. Assessment included at least 1 year of follow-up after cenobamate introduction and included seizure frequency, seizure severity (in particular status epilepticus) and changes in co-medication. In the three patients, cenobamate add on treatment proved superior to all prior antiseizure and immunomodulatory treatments which had been individually applied. Not only were focal to bilateral tonic-clonic seizure completely controlled, but also focal motor status epilepticus no longer occurred. Co-medication could be reduced in all patients. This case series in a rare and highly pharmacoresistant epilepsy syndrome suggests high efficacy of cenobamate add-on treatment for seizure control. This may be a valuable information in epilepsy related to Rasmussen encephalitis and calls for further elucidation of the mechanism involved in superior seizure control also compared to prior treatments including sodium channel blockers and benzodiazepines. Rasmussen's encephalitis is a rare type of epilepsy that gets worse over time and doesn't respond well to most seizure medications. We describe three patients who tried many treatments without much success, but when they added cenobamate to their treatment, it worked better than the other medications. This also let them lower the overall amount of medication they were taking.

The effectiveness and safety of bevacizumab in improving the efficacy of antiseizure medication in treating refractory epilepsy induced by stereotactic radiosurgery in meningiomas

Background: Refractory epilepsy (RE) increases rapidly after stereotactic radiosurgery (SRS), but the reports on RE treatment are rare, with various methods and efficacy. In recent years, bevacizumab (BEV) has been widely used as it is effective in eliminating intracranial oedema and reducing radioactive damage. The aim of this study was to evaluate the application of additional BEV to RE after SRS in the real world. Methods: Seizure freedom and seizure response were defined as 100% and > 50% reduction in seizure frequency at baseline and 6-, 9- and 12-month follow-ups. The sustained seizure-free (SSF), sustained seizure response (SSR) was used to assess the effectiveness of BEV. The number of anti-seizure medications (ASM), seizure severity (NH3), and epilepsy quality of life rating scale (QOLIE-31) scores were compared before and 12 months after treatment. Results: Forty-one patients were included from January 2020 to December 2022. During the 1-year follow-up, 5 patients (12.2%) achieved SSF lasting 12 months, and 4.9% and 7.3% enjoyed SSF more than 6 months and 9 months, respectively. Twelve patients (29.3%) achieved SSR lasting for 12 months, and 19.5% and 24.4% of the study cohort achieved SSR more than 6 months and 9 months, respectively. Patients’ ASM, NH3, and QOLIE-31 scores significantly improved 12 months after treatment, and the adverse reactions were controllable. Conclusion: This study is the first to explore and report the additional use of BEV in the treatment of RE after SRS in meningiomas. BEV was effective and safe in the treatment of SRS-induced RE.

Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease.

Telemedicine for Ketogenic Dietary Treatment in Refractory Epilepsy and Inherited Metabolic Disease: State of Play and Future Perspectives.

Ketogenic dietary therapies (KDT) are diets that induce a metabolic condition comparable to fasting. All types of KDT comprise a reduction in carbohydrates whilst dietary fat is increased up to 90% of daily energy expenditure. The amount of protein is normal or slightly increased. KDT are effective, well studied and established as non-pharmacological treatments for pediatric patients with refractory epilepsy and specific inherited metabolic diseases such as Glucose Transporter Type 1 Deficiency Syndrome. Patients and caregivers have to contribute actively to their day-to-day care especially in terms of (self-) calculation and (self-) provision of dietary treatment as well as (self-) measurement of blood glucose and ketones for therapy monitoring. In addition, patients often have to deal with ever-changing drug treatment plans and need to document occurring seizures on a regular basis. With this review, we aim to identify existing tools and features of telemedicine used in the KDT context and further aim to derive implications for further research and development.

488 National Trends in the Treatment of Refractory Epilepsy: A Nationwide Inpatient SampleBased Propensity Score Matching Analysis

INTRODUCTION: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. METHODS: Using the NIS database from 2010-2020, patients with focal intractable epilepsy who underwent Laser Interstitial Thermal Therapy (LITT), open surgical resection, Vagal Nerve Stimulation (VNS), or Responsive Neuro-Stimulation (RNS) were identified. Outcomes such as discharge disposition, length of stay, complications, and mortality were analyzed. Propensity score matching was used to compare outcomes between pre-pandemic and pandemic (first peak of COVID-19) periods. RESULTS: A total of 33,969 focal intractable epilepsy cases were found with 3,343 patients receiving different treatment modalities including surgical resection (77.83%), VNS (8.21%), RNS (7.83%), and LITT (6.13%). Most of these patients (89.32%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (10.67%) underwent treatment during the COVID pandemic (2020). Among all treated patients, 2.7% had postoperative neurologic complications and 0.3% died. After propensity-score matching, 658 patients (329 in each group) were included. During the pandemic period, 7% presented with preoperative paralysis/aphasia, and 0.6% had subarachnoid hemorrhages, which was significantly higher than the pre-pandemic rate (1.8%; p < 0.001). There were no statistical differences in neurologic complications, discharge disposition, or LOS between the pre-pandemic and pandemic periods. On the other hand, the mortality rate was slightly higher during the pandemic compared to the pre-pandemic period (N = 4; 1.2% vs. N = 1; 0.2%; p = 0.026). CONCLUSIONS: Our study shows an increase in the diagnosis of focal intractable epilepsy and a decrease in resections, while LITT and RNS usage is rising. Improving access to surgery and encouraging newer treatment modalities for DRE is crucial. Further research is needed to optimize patient outcomes and identify factors that influence treatment choices.

A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity.

A ketogenic diet (KD) is often used in the treatment of refractory epilepsy. Many studies have found that it also has a positive impact on cognitive comorbidities, but the specific mechanism remains unclear. In many disease models, endoplasmic reticulum stress (ERS) and synaptic plasticity is considered a new therapeutic target for improving cognitive impairment, and it has become a research focus in recent years. Recently, studies have found that a KD has a certain regulatory effect on both ERS and synaptic plasticity, but this result has not been confirmed in epilepsy. To investigate the effect of a KD on ERS and synaptic plasticity. In this study, a rat model of temporal lobe epilepsy (TLE) induced by lithium chloride-pilocarpine was used. After the model was successfully established, the rats in each group were fed a normal diet or a KD for 28 days, and the effect of a KD on the latency and seizure frequency of spontaneous recurrent seizures (SRSs) was observed via video monitoring. Subsequently, a Morris water maze was used to evaluate the spatial learning and memory abilities of the rats in each group; the ultrastructure of the ER and the synapses of the hippocampus were observed by transmission electron microscopy, and the dendritic spine density of the hippocampus was analysed by Golgi staining. Long-term potentiation (LTP) was used to detect the synaptic plasticity of the rats' hippocampi, and the expression of ERS-related proteins and synapse-related proteins was detected by Western blotting. A KD effectively reduced the frequency of SRSs in rats with TLE and improved their learning and memory impairment. Further investigations found that a KD inhibited the up-regulation of glucose-regulated protein 78, phospho-protein kinase-like ER kinase, phosphorylated α subunit of eukaryotic initiation factor 2, activating transcription factor 4 and C/EBP homologous protein expression in the hippocampi of rats with TLE and protected the ultrastructure of the neuronal ER, suggesting that a KD suppressed excessive ERS induced by epilepsy. Concurrently, we also found that a KD not only improved the synaptic ultrastructure and increased the density of dendritic spines in rats with TLE but also reversed the epilepsy-induced LTP deficit to some extent. More importantly, the expression of postsynaptic density protein 95, synaptotagmin-1 and synaptosomal-associated protein 25 in the hippocampi of rats with epilepsy was significantly increased after KD intervention. The study findings indicate that a KD improves learning and memory impairment in rats with epilepsy, possibly by regulating ERS and synaptic plasticity.

Treatment of Refractory Epilepsy With MEK Inhibitor in Patients With RASopathy

BackgroundSeveral specific syndromes within the RASopathies spectrum lead to an increased risk of seizures up to developing refractory epileptic encephalopathy. Management remains symptomatic. MethodsHere we report two patients treated with trametinib, a MEK1-2 inhibitor, as a precision strategy for drug-resistant epilepsy. Patient 1 is a six-year-old girl with cardiofaciocutaneous syndrome (BRAF p.F595L, germline mutation), and Patient 2 is a 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation). Trametinib was initiated at a dosage of 0.025 mg/kg/day. ResultsPatient 1 had multiple seizures per day, multifocal motor to bilateral tonic-clonic. Electroencephalography (EEG) showed a dramatic reduction in EEG discharges three months after trametinib onset, while a marked clinical improvement occurred after about five months, at the same dosage, and the girl is currently seizure-free for more than six months.Patient 2 had left cerebral hemiatrophy leading to right focal motor seizures, multiple per week to multiple per day, since the age of three months. On trametinib, he experienced an early benefit, remaining seizure-free for more than three months. However, after six months we observed recurrence of seizures. After 22 months of treatment, trametinib was discontinued because of a suspected drug-induced inflammatory colitis. After discontinuation, we observed a significant clinical and EEG “rebound effect.” ConclusionsWe provide proof of concept that MEK inhibition is a promising approach for the treatment of patients with refractory epilepsy with selected germline and mosaic RASopathies. Future trials are encouraged to better investigate their potentials and limitations.

Effects of ketogenic diet on the classification and functional composition of intestinal flora in children with mitochondrial epilepsy.

The ketogenic diet (KD) has shown excellent performance in the treatment of refractory epilepsy, but how it works is not yet fully understood. Gut microbiota is associated with various neurological disorders through the brain-gut axis. Different dietary patterns have different effects on the composition and function of gut microbiota. Here, by analyzing fecal samples from some patients with mitochondrial epilepsy before and after KD treatment through 16SrRNA sequencing, we found that KD intervention reduced the abundance of Firmicutes in the patient's gut, while the abundance of Bacteroidota increased in the KD group. LefSe analysis showed that Actinobacteriota, Phascolarctobacterium had significant advantages in the control group, while Bacteroides increased significantly after KD intervention, especially Bacteroides fragilis. Functional analysis showed that there were significant differences in 12 pathways in level 3. These changes suggest that KD can change the composition and diversity of the gut microbiota in patients and affect their function. Changes in specific bacterial groups in the gut may serve as biomarkers for the therapeutic effects of KD on epilepsy.

Cannabidiol for the treatment of refractory epilepsy in children: a critical review of the literature.

Objective:The aim of this current report was to present a critical review of the use of cannabidiol (CBD) in the treatment of refractory epilepsies in the pediatric population.Data source:Literature review was carried out in the Medline (PubMed), Cochrane, and Scientific Electronic Library Online (SciELO) databases with the descriptors “Cannabidiol” and “Epilepsy.” The search was not limited by the date of publication, language, or study design. A total of 69 articles were included in the review.Data synthesis:The efficacy of CBD in treating epileptic seizures has been confirmed by randomized controlled trials for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. The incidence of side effects reported in subjects of the studies is high. However, most studies indicate a good safety profile and tolerance to the drug, with most of the adverse effects being mild to moderate and transient.Conclusions:There is no consensus on the release of CBD as a therapeutic tool by the drug regulatory agencies worldwide. However, the use of CBD is promising since it has presented satisfactory results in crisis control in well-designed studies. In addition, this drug has a good safety and tolerance profile. However, further studies with a long follow-up period are needed to confirm its usefulness and the long-term safety in pediatric patients.

New Progress in the Treatment of Refractory Epilepsy

New Progress in the Treatment of Refractory Epilepsy

The KDEP Trial: Protocol for a phase II, multicenter, open label, randomized controlled trial to evaluate the efficacy of ketogenic diet for symptomatic improvement of moderate to severe Major Depressive Disorder

Introduction: Major depressive disorder (MDD) is a disease with a high economic burden across the world, mainly secondary to a decrease in work performance and pill burden. Ketogenic diet is a type of non-pharmacological intervention that is employed in the treatment of refractory epilepsy and has shown promise for the treatment of other psychiatric disorders, including depression. Up to the date, there is a limited number of investigations regarding this topic, making the knowledge very scarce; therefore, our study will assess the clinical efficacy of ketogenic diet, particularly Modified Atkins Diet, as compared to control diet in adults with diagnostic of MDD on standard treatment without resolution of symptoms as a difference in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline at the third month follow-up visit. Methods: This is a phase II, multicenter, randomized, controlled, open-label, parallel-group, superiority trial with blinded endpoints. Sample size was calculated as 132 participants (66 participants per arm) to maintain a power of 80% and a two-sided significance level of 0.05. The primary endpoint is the improvement in MDD symptomatology measured by MADRS scale at 3 months from baseline. Discussion: There is evidence to support the notion that ketogenic diet improves patients symptoms by increasing levels of several molecules resulting in a decrease of neuroinflammation and an increase of neurogenesis, improving mood disorders. We hypothesize that a ketogenic diet will improve depressive symptoms in patients with moderate to severe depression when compared to patients on a control diet.

Silencing of miR-132-3p protects against neuronal injury following status epilepticus by inhibiting IL-1β-induced reactive astrocyte (A1) polarization.

Mesial temporal lobe epilepsy (MTLE) is one of the most common refractory epilepsies and is usually accompanied by a range of brain pathological changes, such as neuronal injury and astrocytosis. Naïve astrocytes are readily converted to cytotoxic reactive astrocytes (A1) in response to inflammatory stimulation, suppressing the polarization of A1 protects against neuronal death in early central nervous system injury. Our previous study found that pro-inflammatory cytokines and miR-132-3p (hereinafter referred to as "miR-132") expression were upregulated, but how miR-132 affected reactive astrocyte polarization and neuronal damage during epilepsy is not fully understood. Here, we aimed to explore the effect and mechanism of miR-132 on A1 polarization. Our results confirmed that A1 markers were significantly elevated in the hippocampus of MTLE rats and IL-1β-treated primary astrocytes. In vivo, knockdown of miR-132 by lateral ventricular injection reduced A1 astrocytes, neuronal loss, mossy fiber sprouting, and remitted the severity of status epilepticus and the recurrence of spontaneous recurrent seizures. In vitro, the neuronal cell viability and axon length were reduced by additional treatment with A1 astrocyte conditioned media (ACM), and downregulation of astrocyte miR-132 rescued the inhibition of cell activity by A1 ACM, while the length of axons was further inhibited. The regulation of miR-132 on A1 astrocytes may be related to its target gene expression. Our results show that interfering with astrocyte polarization may be a breakthrough in the treatment of refractory epilepsy, which may extend to the research of other astrocyte polarization-mediated brain injuries.

Neurostimulation as a Method of Treatment and a Preventive Measure in Canine Drug-Resistant Epilepsy: Current State and Future Prospects.

Modulation of neuronal activity for seizure control using various methods of neurostimulation is a rapidly developing field in epileptology, especially in treatment of refractory epilepsy. Promising results in human clinical practice, such as diminished seizure burden, reduced incidence of sudden unexplained death in epilepsy, and improved quality of life has brought neurostimulation into the focus of veterinary medicine as a therapeutic option. This article provides a comprehensive review of available neurostimulation methods for seizure management in drug-resistant epilepsy in canine patients. Recent progress in non-invasive modalities, such as repetitive transcranial magnetic stimulation and transcutaneous vagus nerve stimulation is highlighted. We further discuss potential future advances and their plausible application as means for preventing epileptogenesis in dogs.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy.

Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy. A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data. After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, P=0.013), whereas different ages (P=0.382), gender (P=0.824), types of seizure (P=0.829), and MRI features (P=0.791) showed no correlation with efficacy. None patients developed permanent complication postoperatively. VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Cannabinoids in the Treatment of Epilepsy: A Review

Cannabinoids have been studied for their role in the treatment of epilepsy for many years. The U.S. Food and Drug Administration (FDA) approved them for the treatment of some refractory syndromes in 2018. Cannabidiol and tetrahydrocannabinol are the most commonly studied cannabinoids and have been studied in great depth vis-à-vis their pharmacokinetics and pharmacodynamics. Studies have shown the efficacy of cannabinoids in the treatment of refractory epilepsy. A substantial amount of research has been performed exploring the interactions between cannabinoids and other conventional antiseizure medications. The exact mechanisms by which cannabinoids exert their effects on seizure control remain unclear and research into these mechanisms continues in great earnest. Cognitive changes from cannabinoids are constantly being studied and add to potential benefits from the use of these compounds. Cultural and social misconceptions and roadblocks about the use of cannabinoids persist and represent an ongoing obstacle to increasing research and therapeutic use of these compounds. This review focuses on all these aspects and of the use of these cannabinoids in the treatment of epilepsy and seeks to offer a fairly comprehensive description of the facets of cannabinoid therapy for refractory epilepsy.

Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways.

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

78 Physiologic Monitoring for Central Nervous System Oxygen Toxicity in Working Divers

The risk of central nervous system oxygen toxicity (CNSOT) limits diving operations for US Navy and occupational divers. CNSOT has variable and potentially deadly consequences such as seizures while underwater. Its pathophysiology is incompletely understood and its only current mitigation strategy is adhering to oxygen partial pressure (PO2) and time limits. Nutritional ketosis (NK) is used in the treatment of refractory epilepsy, and animal studies suggest it may delay onset of CNSOT. Primary objectives of this analysis are to better understand the pathophysiology and manifestations of CNSOT, and identify possible practical warning methods.

The efficacy and safety of Topiramate in the Treatment of Refractory Epilepsy in children in Paediatric Neurology clinic at Izzat Ali Shah Hospital

Objectives: This study has been performed to observe the efficacy & safety of Topiramate in refractory epilepsies in children in Pakistan.Materials and Methods: A cross-sectional prospective consecutive series of children age between (1-14 years) with refractory epilepsy were recruited from the Paediatric Neurology clinic of Izzat Ali Shah Hospital. Epilepsy was classified into Generalized, Focal, and Unknown based on ILAE Classification. Topiramate was added in patients who were refractory to at least two anti-epileptic drugs. The outcome was recorded in four categories i.e total remission, >50% seizure reduction, <50% seizure reduction, and no improvement.Results: Fifty-eight patients were enrolled in the study, but 5 patients were dropped out due to significant side effects. Most of the children were in the age group ranging from 5 to 10 years with predominant boys (n=32). The major type of epilepsy was 53% (n=28) was Unknown, while 36% (n=19) children had Generalized epilepsy and 11% (n=6) had Focal epilepsy. 25% children had total remission, 38% had >50% seizure reduction, 28% had < 50% seizure reduction and 9% had no improvement. Total remission was mostly seen in Focal epilepsy (50%) and least shown in Unknown type (14%) and the difference was significant (Chi-Square test p=0.039). Adverse effects to Topiramate were found in 33 (62%) of the total enrolled patients. Common adverse effects were weight loss in 14(26%), poor appetite in 13(24.5%), and behavioral issues in 6(22.5%) children.Conclusion: Topiramate is an effective anti-epileptic drug (AED) in refractory epilepsy especially with Focal and Generalized onset but is not as effective in other types of Refractory epilepsy. Weight loss and poor appetite were the commonest adverse effects that were reversible after dose reduction.

Epilepsy and cannabidiol - a new perspective for seizures treatment

BACKGROUND: Despite the fact that the number of antiepileptic drugs is constantly increasing, epilepsy can still be a therapeutic challenge. Approximately one-third of patients with epilepsy have persistent seizures refractory to treatment. The limited number of effective alternatives motivates researchers to seek new solutions. There is some hope for cannabidiol (CBD) preparations.AIM OF THE STUDY: The purpose of this study was to review the most recent available literature on the use of cannabidiol in the treatment of refractory epilepsy in children and adults. For this purpose, the PubMed and Google Scholar databases were reviewed. The phrase "cannabidiol and epilepsy" was used to search the database. After Screening titles and abstracts a total of 19 papers and articles cited in them were received and analyzed in detail. RESULTS: Nowadays there are many CBD related products available in the market, Cannabis sativa and Cannabis indica are the plants used due to their strong therapeutic effects and also seizure control. Regulations regarding the use of raw marijuana, cannabis extracts, and cannabinoid-based drugs vary from place to place. Many studies have been generated on the efficacy of cannabinoid therapy in the treatment of epilepsy. This therapy in patients with Dravet syndrome and Lennox-Gaust syndrome results in a reduction in the frequency of motor and total seizures. The most commonly reported side effects of CBD are drowsiness, seizures and diarrhea, but the therapy is generally well tolerated.SUMMARY AND CONCLUSIONS: Many available studies support the efficacy of CBD as a treatment option to reduce seizure frequency in children with drug-resistant epilepsy, particularly in patients with Dravet and Lennox-Gastaut syndrome. However, there is a lack of reports on the use of CBD in the adult population, which may be an area for further research.

Closed-Loop Neuromodulation and Self-Perception in Clinical Treatment of Refractory Epilepsy

Background: Newer “closed-loop” neurostimulation devices in development could, in theory, induce changes to patients’ personalities and self-perceptions. Empirically, however, only limited data of patient and family experiences exist. Responsive neurostimulation (RNS) as a treatment for refractory epilepsy is the first approved and commercially available closed-loop brain stimulation system in clinical practice, presenting an opportunity to observe how conceptual neuroethical concerns manifest in clinical treatment. Methods: We conducted ethnographic research at a single academic medical center with an active RNS treatment program and collected data via direct observation of clinic visits and in-depth interviews with 12 patients and their caregivers. We used deductive and inductive analyses to identify the relationship between these devices and patient changes in personality and self-perception. Results: Participants generally did not attribute changes in patients’ personalities or self-perception to implantation of or stimulation using RNS. They did report that RNS affected patients’ experiences and conceptions of illness. In particular, the capacity to store and display electrophysiological data produced a common frame of reference and a shared vocabulary among patients and clinicians. Discussion: Empirical experiences of a clinical population being treated with closed-loop neuromodulation do not corroborate theoretical concerns about RNS devices described by neuroethicists and technology developers. However, closed-loop devices demonstrated an ability to change illness experiences. Even without altering identify and self-perception, they provided new cultural tools and metaphors for conceiving of epilepsy as an illness and of the process of diagnosis and treatment. These findings call attention to the need to situate neuroethical concerns in the broader contexts of patients’ illness experiences and social circumstances.