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Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil-based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3-19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9-6.2), 49.6 ng/mL (14.4-302.0), and 226.3 ng ⋅ h/mL (70.5-861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine-CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring., (© 2020 International League Against Epilepsy.)

Purpose: In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add-on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs)., Methods: Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow-up of 1.5-16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day., Key Findings: Since add-on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add-on of sulthiame. Twenty-one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days., Significance: We understand that sulthiame may be effective as add-on treatment in children with ESES syndrome., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management., Methods: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document., Results: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood., Conclusions: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.

Objectives: To characterize the electroclinical features and evolution of Panayiotopoulos Syndrome (PS)., Methods: Children with electroclinical criteria of PS were prospectively identified and followed-up clinically, and with sleep and awake EEGs between February 1990 and 2006., Results: We identified 192 patients with PS. In the same length of time 398 children with benign childhood epilepsy with centro-temporal spikes (BCECTS) were registered. PS had a peak age at onset of 5 years. Autonomic manifestations were one of the most common ictal event. Ictal deviation of the eyes and progression to generalized convulsions were also quite frequent. Approximately one third had partial status epilepticus. In all patients except five, the seizures occurred during sleep. One-third also had fits while awake. Sixteen children had concomitant symptoms of rolandic epilepsy and eight developed rolandic seizures after remission of PS seizures. Prognosis was excellent. Eighty-four (44.2%) had a single seizure, 79 (41.2%) had 2-5 fits, and 28 (14.6%) had frequent seizures., Conclusion: PS is less common than BCECTS, but is well defined and easily recognizable by clinical and EEG features, with autonomic manifestations as one of the most common ictal event.

Purpose: To emphasize that, in some patients, different atypical evolutions occur in the course of so-called benign focal epilepsies of childhood (BFEC) and to promote interest in finding clinical and/or electroencephalographic (EEG) clues to which patients might be prone to these risky evolutions., Methods: Twenty-six patients who started with the typical clinical and EEG features of benign childhood epilepsy with centrotemporal spikes (BCECTS) but who had reversible or persistent, serious epileptic events including status epilepticus and language, cognitive, or behavioral impairments were followed for

Purpose: Polymicrogyria (PMG) is often associated with symptomatic focal epilepsy and neurologic dysfunction. We investigated the clinical and laboratory features of a group of children with congenital hemiparesis, unilateral polymicrogyria on magnetic resonance imaging (MRI), and a peculiar epileptic syndrome., Methods: Twelve patients (seven girls and five boys) with a mean age of 7.8 years (range, 5-13 years) were studied. All patients underwent clinical evaluation, computed tomography (CT) and MRI scanning, and neuropsychological assessment at initial examination. Patients were followed up from 1 to 7 years (mean, 4.5 years)., Results: Partial motor seizures with secondary generalization with onset between age 1 and 6 years (mean age, 2 years) were recorded in all patients. The course of epilepsy was similar in all patients with development of atypical absences, negative myoclonus, and gait difficulties. EEG recording demonstrated continuous spike-wave or bilateral abnormality throughout. Frequent relapses of the atonic and myoclonic seizures were seen in seven patients. However, during follow-up, seven patients were seizure free, and the others have not developed this particular seizure pattern. A single case underwent cortical resection 23 months ago and has had no seizures since then. Mental retardation was mild in nine and moderate in three patients., Conclusions: Children with unilateral polymicrogyria may develop a syndrome of negative myoclonus seizures that appears to be age specific and responsive to antiepileptic drug (AED) treatment. Despite limited follow-up time, a good outcome was observed in most cases.

We report the fourth case of partial status epilepticus (SE) in benign epilepsy of childhood with rolandic spikes (BECRS). The child suffered long-lasting attacks involving the mouth and pharynx, clinically manifest as speech arrest, sialorrhea, and drooling. Both clinical and electroencephalogram (EEG) data were compatible with the diagnosis of BECRS. Only during SE was the clinical picture similar to that observed in the operculum or Foix-Chavany-Marie syndrome. SE remission was obtained with the usual antiepileptic drug therapy (diazepam, clobazam, valproate). EEG records showed additional patterns of continuous spike-waves during slow sleep and specific inhibition and blocking of interictal centrotemporal spikes by mouth and/or tongue voluntary movements.