الفهرس 
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Abstract
Introduction:
E
pilepsy affects approximately 70 million individuals worldwide, significantly contributing to the global burden of neurological disorders. It is associated with an increased risk of comorbid conditions, including psychiatric disorders, cognitive disturbances, and migraine headaches, impacting the quality of life. Mortality among people with epilepsy (PWE) is three times higher, with significant causes including sudden unexpected death in epilepsy (SUDEP), status epilepticus, physical injuries, and drowning. SUDEP risk is substantially elevated in individuals with drug-resistant epilepsy (DRE), reaching 18 per 1000 cases.
Drug-resistant epilepsy is defined by the failure of adequate trials of two tolerated antiepileptic drugs (AEDs) to achieve sustained seizure freedom. Despite initial success rates with the first AED, subsequent medications yield lower efficacy, leaving 30-40% of PWE with DRE. Focal-onset seizures (FOS) are more likely to become drug-resistant, accounting for 60% of epilepsy cases in adults.
Cortical electrical stimulation, utilizing open-loop and closed-loop approaches, has shown promise in suppressing epileptiform activity. Responsive Neurostimulation (RNS), a closed-loop system approved in 2013, involves continuous monitoring of electrocorticographic activity to detect and respond to ictal patterns, potentially preventing or aborting seizures. Deep Brain Stimulation (DBS), approved by the FDA in 2018, modulates cortical excitability via an open-loop system, targeting deep brain structures to interrupt seizure propagation along neural networks.
Both RNS and DBS offer treatment options for medically refractory seizures, with RNS focusing on intracranial placement of electrodes connected to a stimulator, while DBS involves the implantation of electrodes into deep brain structures with a generator placed superficially. Long-term outcomes and comparative effectiveness studies are essential for elucidating the role of these neuromodulation techniques in managing drug-resistant epilepsy.
Methodology:
The study protocol adhered to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA).
Eligibility Criteria:
Included studies from Jan 2000 – Dec 2023 encompassing various study designs such as clinical trials, observational studies, and case series with at least 6 cases.
Excluded systematic reviews, technical notes, letters, comments, duplicates, unavailable full texts, or abstract-only articles.
Required studies to provide sufficient seizure reduction data and detailed outcomes data stratified by treatment durations and types of epilepsy.
Types of Participants:
Included subjects aged 18-70 years with focal onset seizures refractory to two or more antiepileptic drugs (AEDs), experiencing an average of three or more disabling seizures per month, and diagnosed with 1-2 epileptogenic foci.
Excluded individuals with major psychiatric illness, cognitive impairment, previous surgery for drug-resistant epilepsy (DRE), or other clinical diseases of the central nervous system.
Types of Intervention:
Investigated neuromodulation techniques for the treatment of drug-resistant focal epilepsy, including Responsive Neurostimulation (RNS) and Deep Brain Stimulation (DBS).
Types of Outcome Measures:
Evaluated over a follow-up period of 6 months to 5 years, including mean percentage decrease in seizure frequency or seizure freedom, neuropsychological outcomes, quality of life, safety and adverse effects, cost-effectiveness, and post-operative complications.
Results:
The results of the analysis comparing responsive neurostimulation (RNS) and deep brain stimulation (DBS) for the treatment of epilepsy are as follows:
1. Study selection: A total of seven studies for RNS and twelve studies for DBS were included in the analysis for follow-up years one, two, and three. However, data for years four and five were insufficient for comparison.
2. Seizure Reduction:
• At one year follow-up, RNS demonstrated a mean seizure reduction of 66.3%, while DBS achieved 58.4%.
• At two years, RNS showed a reduction of 56.0%, compared to 56.5% for DBS.
• At three years, RNS exhibited a reduction of 68.4%, while DBS had 63.8%.
3. Forest Plot Analysis:
• At one year follow-up, RNS showed a mean difference of 66.257% compared to 58.44% for DBS.
• At two years, the mean difference was 53.817% for RNS and 54.184% for DBS.
• At three years, RNS had a mean difference of 68.421% compared to 63.739% for DBS.
4. Neuropsychological Outcome and Quality of Life: Both RNS and DBS showed varying rates of improvement in neuropsychological outcomes and quality of life, ranging from 0% to 100%. However, due to the limited number of studies reporting these outcomes, definitive conclusions are challenging to draw.
5. Safety and Adverse Effects: Both RNS and DBS demonstrated safety concerns and adverse effects, including infections, therapeutic agent toxicity, lead revisions, and device removals. RNS appeared to have a relatively lower incidence of adverse events, while DBS had a higher incidence, including serious adverse events affecting ≥2.5% of implanted participants.
6. Post-operative Complications: Post-operative complications, including acute and chronic issues, were observed in both RNS and DBS studies. Infections were observed in both modalities, while other complications such as intracranial hemorrhage and lead fractures were specific to DBS.
In summary, while both RNS and DBS showed promising results in reducing seizures, RNS appeared to have a slightly better seizure reduction profile and a potentially lower incidence of adverse events. However, further research is needed to confirm these findings and to better understand the long-term outcomes and safety profiles of both modalities.