External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial.

BACKGROUND: External trigeminal nerve stimulation (ETNS) is an emergent, non-invasive neurostimulation therapy delivered bilaterally with adhesive skin electrodes. In previous studies, ETNS was associated to a decrease in seizure frequency in patients with focal drug-resistant epilepsy (DRE). OBJECTIVE: To determine the long-term efficacy and tolerability of ETNS in patients with focal DRE. Moreover, to explore whether its efficacy depends on the epileptogenic zone (frontal or temporal), and its impact on mood, cognitive function, quality of life, and trigeminal nerve excitability. METHODS: Forty consecutive patients with frontal or temporal DRE, unsuitable for surgery, were randomized to ETNS or usual medical treatment. Participants were evaluated at 3, 6 and 12 months for efficacy, side effects, mood scales, neuropsychological tests and trigeminal nerve excitability. RESULTS: Subjects had a median of 15 seizures per month and had tried a median of 12.5 antiepileptic drugs. At 12 months, percentage of responders was 50% in ETNS group and 0% in control group. Seizure frequency in ETNS group decreased by -43.5% from baseline. Temporal epilepsy subgroup responded better than frontal epilepsy subgroup (55.56% vs. 45.45%, respectively). Median stimulation intensity was 6.2 mA. ETNS improved quality of life, but not anxiety or depression. Long-term ETNS affected neither neuropsychological function, nor trigeminal nerve excitability. No relevant adverse events were observed. CONCLUSIONS: ETNS is an effective and well-tolerated therapy for focal DRE. Patients with temporal epilepsy showed a better response than those with frontal epilepsy. Future studies with larger populations may define its role compared to other neurostimulation techniques. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that ETNS reduces seizure frequency in patients with focal DRE.

Faecal phageome of healthy individuals: presence of antibiotic resistance genes and variations caused by ciprofloxacin treatment.

OBJECTIVES: Antimicrobial resistance genes (ARGs) can be transferred by means of mobile genetic elements, which play a critical role in the dissemination of resistance in the bacterial community. ARG transmission within mobile genetic elements has been reported in plasmids and transposons but less frequently in bacteriophages. Here, the bacteriophage fraction of seven human faecal samples was purified and deep-sequenced to detect the presence of ARGs in the phage particles. METHODS: Seven faecal samples (five from healthy individuals and two from a patient before and after receiving ciprofloxacin treatment) were used to extract phage DNA, which was purified and then sequenced in a MiSeq (Illumina). Generated reads were checked for quality and assembled, and then the generated contigs analysed with Kraken, PHASTER, VirSorter and Prokka. Some genes were also validated by quantitative PCR. RESULTS: Analysis of the purified phage DNA by Kraken identified from 4 to 266 viruses in the samples. The viral fraction corresponded mainly to the order Caudovirales, including phages from the Siphoviridae and Myoviridae families. Bacterial genes associated with antimicrobial resistance were detected in the viral DNA, as confirmed by quantitative PCR. Higher densities of ARG-carrying phage particles were observed in the post- versus pre-ciprofloxacin treatment sample. CONCLUSIONS: The finding of ARGs in phage particles supports the description of phages as mobile elements contributing to the dissemination of bacterial antibiotic resistance and suggests ciprofloxacin treatment may play a role in the release of ARG-carrying particles, thereby increasing resistance.