Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain. / Cannabidiol para el tratamiento del síndrome de Lennox-Gastaut y del síndrome de Dravet: recomendaciones de expertos sobre su uso en la práctica clínica en España.

INTRODUCTION: Cannabidiol (CBD) is one of the main components of the cannabis plant that has demonstrated anti-epileptic seizure effect. Following its clinical development, in September 2019 the European Medicines Agency approved its indication for the adjunctive therapy of epileptic seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), combined with clobazam (CLB), in patients of 2 years of age and older. AIM: To establish recommendations on the use of plant-derived highly purified CBD on which Spanish experts have reached consensus for the treatment of epilepsy in patients with DS and LGS based on their clinical experience and the scientific evidence. DEVELOPMENT: Consensus meeting with the participation of four Spanish neurologists and neuropediatric who are experts in epilepsy secondary to DS and LGS and with clinical experience in the use and management of CBD. They discussed on several topics, including posology (starting dose, dose escalation schema), efficacy (assessment of outcomes and indications for treatment withdrawal), and safety (evaluation, drug-drug interactions, adverse events management). CONCLUSIONS: In order to optimise CBD treatment, a slow dose escalation (= 4 weeks) is recommended until the maximum recommended dose or the desire effect is reached. It is also recommended that the concomitant antiseizure medications (ASMs) be reduced in case of adverse events due to interactions, and that the treatment continues for at least 6 months if it is well tolerated. The efficacy and safety of CBD must be assessed individually, considering the benefits and risks for individual patients.

TITLE: Cannabidiol para el tratamiento del síndrome de Lennox-Gastaut y del síndrome de Dravet: recomendaciones de expertos sobre su uso en la práctica clínica en España.Introducción. El cannabidiol (CBD) es uno de los componentes principales de la planta del cannabis que ha demostrado efecto ante las crisis epilépticas. Tras su desarrollo clínico, obtuvo su aprobación por la Agencia Europea del Medicamento en septiembre de 2019 para el tratamiento de las crisis epilépticas asociadas con el síndrome de Lennox-Gastaut (SLG) y el síndrome de Dravet (SD), en combinación con el clobazam (CLB), en pacientes a partir de los dos años. Objetivo. Establecer unas recomendaciones de manejo del CBD derivado de la planta altamente purificado consensuadas por expertos españoles en el tratamiento de la epilepsia para su uso en pacientes con SD y SLG, basándose en su experiencia clínica y en la evidencia científica. Desarrollo. Reunión de consenso de un grupo de cuatro neurólogos y neuropediatras españoles expertos en el manejo de la epilepsia asociada al SD y el SLG y con experiencia clínica en el uso de CBD. Se debatió sobre diferentes áreas, incluyendo la posología (dosis de inicio, pauta de escalada), la eficacia (valoración de resultados e indicaciones para la suspensión del tratamiento) y la seguridad (evaluación, interacciones entre fármacos, manejo de efectos adversos). Conclusiones. Para optimizar el tratamiento con CBD, se recomienda una pauta lenta de escalada de dosis (de cuatro semanas o más) hasta alcanzar la dosis máxima recomendada o el efecto deseado, reducir los fármacos anticrisis epilépticas concomitantes si aparecen efectos adversos por interacciones y mantener el tratamiento al menos seis meses si se tolera. La eficacia y la seguridad del CBD deben evaluarse de forma individual, considerando el beneficio y el riesgo para cada paciente.

Transient posterior encephalopathy induced by chemotherapy in children.

The cases of three children, 16, 12, and 12 years of age, who suffered sudden confusional state and cortical blindness lasting 12 to 30 minutes while under treatment with high-dose methotrexate, cyclophosphamide, and dactinomycin for a lower limb osteosarcoma are reported. Transient neuropsychologic deficits arose after the acute phase of treatment: left hemispatial neglect and constructive apraxia (Patient 1); constructive apraxia (Patient 2); and constructive apraxia and alexia without aphasia (Patient 3). The three patients recovered completely from all their deficits within the time frame of 3 hours to 2 weeks. Arterial hypertension and hypomagnesemia were found during the acute phase in all patients. In Patients 2 and 3, magnetic resonance imaging revealed increased parieto-occipital T(2) signal involving gray and white matter. In Patients 1 and 2, HmPAO-SPECT revealed parieto-occipital hypoperfusion that resolved a few days later. The alterations detected by neuroimaging were concurrent with the appearance and disappearance of the clinical symptoms. Such transient acute episodes have been named occipital-parietal encephalopathy. On the basis of our clinical, laboratory, and neuroimaging findings, an explanation for the origin of this syndrome, a migrainelike mechanism, triggered by chemotherapy-induced hypomagnesemia, is proposed.