The Beneficial Effect of Probiotics as an Adjuvant Treatment in Childhood Drug Resistant Epilepsy

Abstract Background Epilepsy is the most frequent chronic neurologic condition in children and every year >4.9 million people develop new-onset epilepsy. The foundation of treatment in epilepsy is drug therapy with anti- seizure medications (ASM). However, about one-third develop drug resistant epilepsy (DRE) due to inability to achieve seizure control despite the use of appropriate ASM. Recent studies indicate that gut dysfunction/dysbiosis is presumably involved in the pathogenesis of and susceptibility to epilepsy. The reconstruction of the intestinal microbiome through probiotic intervention has shown beneficial effects on DRE. Aim of the Work The aim of this study is to study safety and effectiveness of probiotics in controlling epileptic seizures in DRE patients by decreasing frequency and severity of seizures. Patients and Methods This study is a prospective study – Single arm Clinical Trial (Pilot study) conducted on 35 DRE patients at the neurology outpatient clinic, Pediatric Neurology Unit, Ain Shams University, from January to August, 2023, of which 14 (40%) dropped out due to socioeconomic reasons and non-compliance while 21 (60%) patients completed this clinical trial. All the results were calculated based on the 21 patient who completed the study. Patients were supplemented with probiotics for 4 months and assessed pre and post probiotics intake by the following tools: seizure assessment by Chalfont seizure severity scale, a blood sample taken to measure serum sCD14 as an inflammatory marker, an EEG was done and QOLIE-31 was used to asses quality of life. Probiotics (spores of antibiotic resistant Bacillus clausii; Enterogermina 2 Billion @ SANOFI) were used with the following doses daily for 4 months (as per SANOFI’s dose prescribtion): ages 1 year to 2 years: 1 vial per day, ages 2 years to 18 years: 2 vials per day. Results Our study included 21 participants; the median age at the time of the study was 11 years ranging from 2.5 to 15 years of age and the median age of onset of seizure was 7 ranging from 6 months to 12 years. The majority of participants were found to be female 15 (71.4%) and the rest were male 6 (28.4%). This clinical trial shows that probiotics could be a useful supplement in the treatment of DRE where 42.9% of our patients achieved the Therapeutic goal of reduction (≥50%) in the number of seizures & improvement in seizure severity (p-value < 0.001) and frequency (p-value < 0.005). Serum sCD14 levels were withdrawn as an inflammatory marker to understand the potential cause of the improvement in epileptic seizures and their levels were outstandingly improved between pre and post probiotics intake with p-value < 0.001. We also found that quality of life was significantly improved as measured by questionnaire QOLIE31 between pre and post probiotics intake in our patients in all its aspects with total score <0.001. We compared between our 2 main diagnoses (The GDD and Genetic epilepsy) and found that there was higher quality of life in the genetic group than the global developmental delay group with p-value < 0.001 mostly attributing this to the fact that most of the genetic patients had a higher starting point than their counterpart in their developmental history and other aspects. Our patients were also sub-divided into 2 groups based on the effectiveness of the probiotics in improving seizures frequency 50% or more and it was found that the effective group had a lower median age (7 years) than the non-effective group (12.5 years) delineating that younger age responds better to probiotics or management in general. Conclusion This study revealed that probiotics decrease the frequency and severity of seizures and improve the quality of life of drug resistant epilepsy patients. Since this is a pilot study and there are deficient data in this area, more studies are needed to evaluate the applicability, safety and the mechanism of action of probiotics.