Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ 9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB 1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT 1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies' approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures.

Objective: Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential. Methods: We retrospectively reviewed data from female patients with IGE, 13-50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation. Results: One hundred ninety-eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P < .001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P < .001) and the juvenile myoclonic epilepsy (JME) group (P < .001). Thirty-six (70.6%) of 51 patients who switched from VPA during follow-up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P < .001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch. Significance: Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age. |CERULLI IRELLI Et aL.

Limbic encephalitis (LE) is an autoimmune condition characterized by amnestic syndrome, psychiatric features and seizures. Early diagnosis and prompt treatment are crucial to avoid long-term sequelae, including psycho-cognitive deficits and persisting seizures.The aim of our study was to analyze the characteristics of 33 LE patients in order to identify possible prognostic factors associated with the development of chronic epilepsy. Methods: This is a retrospective cohort study including adult patients diagnosed with LE in the period 2010-2017 and followed up for ≥12 months. Demographics, seizure semiology, EEG pattern, MRI features, CSF/ serum findings were reviewed. Results: All 33 LE patients (19 M/14F, mean age 61.2 years) presented seizures. Thirty subjects had memory deficits; 22 presented behavioural/mood disorders. Serum and/or CSF auto-antibodies were detected in 12 patients. In 31 subjects brain MRI at onset showed typical alterations involving temporal lobes. All patients received immunotherapy. At follow-up, 13/33 had developed chronic epilepsy; predisposing factors included delay in diagnosis (p = .009), low seizure frequency at onset (p = .02), absence of amnestic syndrome (p = .02) and absence/rarity of inter-ictal epileptic discharges on EEG (p = .06). Conclusions: LE with paucisymptomatic electro-clinical presentation seemed to be associated to chronic epilepsy more than LE presenting with definite and severe "limbic syndrome".

No abstract

No abstract