Objective: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC).Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. Methods:In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers. Results:The study cohort comprised 311 patients with epilepsy with a median age of 11.3 (0-72) years (235 children and adolescents, 76 adults). Therapy with CBD was off-label in 91.3% of cases due to age, epilepsy subtype, lack of adjunct therapy with clobazam, and/or higher dose applied. CBD titration regimens were slower than recommended, with good tolerability of higher doses particularly in children. Of all patients, 36.9% experienced a reduction in seizure frequency of >50%, independent of their epilepsy subtype or clobazam co-medication. The median observation period was 15.8 months. About one third of all patients discontinued therapy within the observation period due to adverse effects or lack of efficacy. Adverse effects were reported frequently (46.9%).Significance: Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children. These findings call for further trials for an extended approval of CBD for other epilepsy subtypes and for children <2 years of age.

Dravet syndrome or severe myoclonic epilepsy in infancy (SMEI) is an epileptic syndrome characterised by refractory epilepsy and intellectual disability, typically presenting with febrile and afebrile generalised and unilateral clonic/tonic-clonic seizures in the first year of life and other types of seizures appearing later in the course of the disease. Five adult patients with SMEI and SCN1A mutations are reported, in which motor and behavioural abnormalities were outstanding symptoms. Bradykinesia, responding with latency, slow speaking with a thin voice, midface hypomimia and perseveration were distinctive features in all cases. These symptoms may be fit to define the adult phenotype of SMEI beyond seizure/epilepsy criteria. The motor and behavioural symptoms are discussed in the context of a possibly underlying frontal lobe/mesofrontal and cerebellar dysfunction.

Aim: Few studies have concerned anticonvulsive combination therapies in epilepsies resistant to established antiepileptic drugs in monotherapy. We sought to delineate the effects of zonisamidelevetiracetam comedication (ZNS+LEV) in adults with intellectual disabilities (ID). Material and Methods:Nine adult patients with drug resistant epilepsies and ID were treated in a routine outpatient setting with LEV or ZNS in combination with other anticonvulsants first and in a combination of both of them (ZNS+LEV) thereafter. Seizure frequency and behavioural effects were recorded in patients treated who approved to benefit from the combination of both substances but not when treated with only either of them. Results:The longitudinal follow up of individual cases of patients with difficult to treat epilepsies and intellectual disabilitiy (ID) suggests that the combination of ZNS and LEV may be an effective and well tolerated option, even if LEV or ZNS alone or in either other combinations had failed to reduce seizure frequency. Conclusions:These findings may not be generalized but request to perform further controlled studies on the efficacy and tolerability of the anticonvulsive therapy of ZNS in combination with LEV.

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