Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study.

BACKGROUND: Drug-resistant epilepsy (DRE) affects the development and quality of life of children and young adults. We analyzed the effectiveness and safety of purified CBD in this population. METHODS: A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018 to 2022 at five medical centers in Israel. RESULTS: The most common diagnosis was Lennox-Gastaut syndrome (37.4%) followed by Dravet syndrome (16.5%) and tuberous sclerosis complex (16.5%). Median purified CBD dose was 12.5 mg/kg (range 2.5 to 20.0), and median treatment duration was 9.0 months (range 0.5 to 48.0). Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had >50% reduction. Fifty-three patients (38.1%) had positive effects: improved alertness (31.7%), improved speech (10.1%), and achievement of new developmental milestones (2.2%). A multivariate linear model assessing predictive factors for seizure reduction demonstrated that patients previously treated with CBD oils, especially those with >50% seizure reduction on prior treatment, were also more likely to have a reduced seizure frequency while they were treated with purified CBD (P = 0.01, P < 0.0001). Development, diagnosis, age, purified CBD dose (0 to 10 mg/kg/day vs 10 to 20 mg/kg/day), and concomitant treatment with clobazam, valproic acid, or everolimus did not affect seizure reduction by purified CBD. The most common adverse events were irritability (20.9%) and drowsiness (12.9%). CONCLUSION: Purified CBD is well-tolerated and effective in reducing seizure frequency in children and young adults with DRE.

A combinatorial modulation of synaptic plasticity in the rat medial amygdala by oxytocin, urocortin3 and estrogen.

The medial nucleus of the amygdala (MeA) plays a pivotal role in a variety of mammalian social behaviors. Specifically, activity of the hypothalamic pro-social neuropeptide oxytocin in the MeA was shown to be crucial for social recognition memory. The MeA is also a hub of neuroendocrine activity and expresses a large number of receptors of neuropeptides and hormones. These include oxytocin receptor, estrogen receptor alpha and corticotropin-releasing factor (CRF) receptor type 2 (CRFR2). In a previous study we found that intracerebroventricular (ICV) oxytocin application to anesthetized rats promotes long-term depression (LTD) of the MeA response to electrical stimulation of its main sensory input, the accessory olfactory bulb (AOB). We also reported that this type of synaptic plasticity contributes to long-term social recognition memory. Here we used similar methodology to examine the possibility that various neuromodulators pose a combinatorial effect on synaptic plasticity in the MeA. We found that ICV administration of the CRF-related peptide urocortin3 fifteen minutes before oxytocin, caused long-term potentiation (LTP), via CRFR2 activation. Similarly, ICV administration of 17ß-estradiol forty-five minutes before oxytocin induced LTP, which was blocked by an antagonist of the estrogen receptors alpha and beta. Notably, none of these two neuromodulators had any effect on its own, suggesting that they both turn the oxytocin-mediated synaptic plasticity from LTD to LTP. Finally, we found that application of 17ß-estradiol, forty-five minutes before urocortin3 also caused LTP in the MeA response to AOB stimulation, even without oxytocin application. We suggest that the combinatorial modulation of the bidirectional synaptic plasticity in the AOB-MeA pathway by oxytocin, 17ß-estradiol and urocotin-3 serves to modify social information processing according to the animal's internal state.

Vegetative state outcomes improved over the last two decades.

OBJECTIVE: To describe late outcomes in patients with prolonged unawareness, and factors affecting them. DESIGN: A retrospective study of 154 patients with traumatic brain injury (TBI) and 52 with non-traumatic brain injury (NTBI), admitted for intensive care and consciousness rehabilitation (ICCR), in a vegetative state (VS) lasting over 1 month. RESULTS: Survival rate (67% total) was higher than in past studies carried out at the same facility (p < 0.01). Consciousness recovery rate (54% total) was higher in NTBI VS patients (p < 0.01) than in earlier cohorts, and similar in TBI VS patients, despite their older age than that of earlier cohorts. No meaningful differences were found in characteristics or in outcomes between the TBI and NTBI groups. Age, length of stay in ICCR, and hydrocephalus were found to affect survival (p < 0.001). Younger age, absence of hydrocephalus, and anti-Parkinsonian medication contributed to consciousness recovery after VS (p < 0.05). CONCLUSIONS: The present study demonstrated an improvement in survival and recovery of consciousness in VS patients over the last two decades, and similar outcomes for both TBI and NTBI VS. Outcomes suggest that acute medical care and ICCR have contributed to advances in VS care.