Sleep-dependent memory consolidation in the epilepsy monitoring unit: A pilot study.

OBJECTIVE: We sought to examine whether patients with focal epilepsy exhibit sleep dependent memory consolidation, whether memory retention rates correlated with particular aspects of sleep physiology, and how the process was affected by seizures. METHODS: We prospectively recruited patients with focal epilepsy and assessed declarative memory using a task consisting of 15 pairs of colored pictures on a 5×6 grid. Patients were tested 12h after training, once after 12h of wakefulness and once after 12h that included sleep. EMG chin electrodes were placed to enable sleep scoring. The number and density of sleep spindles were assessed using a wavelet-based algorithm. RESULTS: Eleven patients were analyzed age 21-56years. The percentage memory retention over 12h of wakefulness was 62.7% and over 12h which included sleep 83.6% (p=0.04). Performance on overnight testing correlated with the duration of slow wave sleep (SWS) (r=+0.63, p<0.05). Three patients had seizures during the day, and 3 had nocturnal seizures. Day-time seizures did not affect retention rates, while those patients who had night time seizures had a drop in retention from an average of 92% to 60.5%. CONCLUSIONS: There is evidence of sleep dependent memory consolidation in patients with epilepsy which mostly correlates with the amount of SWS. Our preliminary findings suggest that nocturnal seizures likely disrupt sleep dependent memory consolidation. SIGNIFICANCE: Findings highlight the importance of SWS in sleep dependent memory consolidation and the adverse impact of nocturnal seizures on this process.

Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures.

OBJECTIVES: In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED. METHODS: In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (≤1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability. RESULTS: Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05). CONCLUSIONS: Low-dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy.

Evaluation of aroA deletion mutant of Salmonella enterica subspecies enterica serovar Abortusequi for its vaccine candidate potential.

The present study on a defined deletion aroA mutant (B-26) of Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi) for residual virulence and safety in experimental model revealed that the virulence of the strain was at no difference in any of the cell assays (caprine alveolar macrophages, bovine alveolar macrophages, guinea pig blood mononuclear cells and horse blood mononuclear cells) than that of its parent virulence plasmid cured (S-787) and wild type (E-156) strains. The mutant did not cause any apparent illness in baby guinea pigs (15 days old), adult male and female guinea pigs and also not in pregnant (54-55 days of gestation) guinea pigs through oral (4.2 x 10(9) cfu/ animal) and intramuscular (im) routes (4.2 x 10(7) cfu/ animal). In pregnant females the mutant also induced abortion as its parent (E-156) though to lesser extent (33%) than the parent strain (100%) on inoculation through intravaginal (4.2 x 10(9) cfu/ animal) and intraperitoneal (4.2 x 10(7) cfu/ animal) routes. The babies born from mutant inoculated mothers survived better and were also resistant to intraperitoneal lethal challenge (7.82 x 10(9) cfu/ animal) with 100% protection. Female guinea pigs challenged after 135-165 days of inoculation with the mutant afforded 100% protection from abortion and mortality caused by lethal infection (7.82 x 10(9) cfu/ animal) of wild type S. enterica Abortusequi (E-156). The study revealed that aroA mutant (B-26) was safe through oral and im routes for immunization and afforded 100% protection against salmonellosis for more than 5.5 months in guinea pigs. Although immunization with aroA mutant in experimental model afforded good protection against abortion and mortality induced by S. Abortusequi, further studies are needed in horses to exploit the strain's vaccine potential in the natural host.