Current trends in epileptology: priorities, challenges, tasks and solutions

Within a field meeting of experts from the Russian branch of the League Against Epilepsy (RLAE), diagnostic and treatment aspects of epilepsy were discussed with the emphasis on the female population (girls, women of childbearing and older ages). All experts underscored the special features and unique needs of female patients with epilepsy. Experimental and clinical studies on efficacy and safety of traditional and novel antiepileptic drugs (AEDs) applied to women with epilepsy were discussed. It was commonly agreed that the new generation of AEDs did not yet find an appropriate place in the clinical practice, and that they were mainly used as add-on therapy in order to overcome drug resistance. The current use of AEDs in the treatment of epilepsy is, by large, not gender-specific and is not related enough to age, sociodemographic characteristics, and comorbid disorders. It should be noted that the new AEDs are addressed specifically to individual, socio-demographic, gender and clinical features of the patient. The potential of some AEDs (lamotrigine), in fact, remains underestimated by practitioners. Due to the current restrictions in using valproic acid, lamotrigine is the alternative medication for women with epilepsy. Having a balanced profile of efficacy and safety, lamotrigine is recommended as the first choice drug for initial therapy, as well as an alternative monotherapy for epilepsy in women.These data were presented at the Russian League Against Epilepsy (RLAE) on-site meeting “Epilepsy and Woman” 18 September 2019 (Ohrid, Makedonia)

Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations

Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10\ub73%) of 1381 pregnancies for valproate, 19 (6\ub75%) of 294 for phenobarbital, eight (6\ub74%) of 125 for phenytoin, 107 (5\ub75%) of 1957 for carbamazepine, six (3\ub79%) of 152 for topiramate, ten (3\ub70%) of 333 for oxcarbazepine, 74 (2\ub79%) of 2514 for lamotrigine, and 17 (2\ub78%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0\ub70140), lamotrigine (p=0\ub70145), phenobarbital (p=0\ub70390), and valproate (p<0\ub70001). After adjustment, multivariable analysis showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine and valproate as well as for phenobarbital at doses of more than 80 mg/day than for lamotrigine at doses of 325 mg/day or less. Valproate at doses of 650 mg/day or less was also associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250\u20134000 mg/day (odds ratio [OR] 2\ub743, 95% CI 1\ub730\u20134\ub755; p=0\ub70069). Carbamazepine at doses of more than 700 mg/day was associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250\u20134000 mg/day (OR 2\ub741, 95% CI 1\ub733\u20134\ub738; p=0\ub70055) and oxcarbazepine at doses of 75\u20134500 mg/day (2\ub737, 1\ub717\u20134\ub780; p=0\ub70169). Interpretation: Different antiepileptic drugs and dosages have different teratogenic risks. Risks of major congenital malformation associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the literature for offspring unexposed to antiepileptic drugs. These findings facilitate rational selection of these drugs, taking into account comparative risks associated with treatment alternatives. Data for topiramate and phenytoin should be interpreted cautiously because of the small number of exposures in this study. Funding: Bial, Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, UCB, the Netherlands Epilepsy Foundation, and Stockholm County Council