Uso del cannabis medicinal en niños con encefalopatías epilépticas farmacorresistentes. Experiencia en Hospital Garrahan / Use of medicinal cannabis in children with drug-resistant epileptic encephalopathies. Experience at Garrahan Hospital

Objetivo: Reportamos resultados sobre la efectividad, seguridad y tolerancia del cannabidiol como adyuvante terapéutico en pacientes pediátricos con encefalopatías epilépticas del desarrollo (EED) resistentes al tratamiento farmacológico y no farmacológico tras un seguimiento promedio de 20 meses. Métodos: Se realizó un estudio de cohorte prospectivo para evaluar la eficacia, la seguridad y la tolerancia del aceite de cannabis medicinal enriquecido con CBD añadido a los medicamentos anticonvulsivos estándar en niños con EED resistentes a los medicamentos atendidos en un único centro. Resultados: Entre octubre de 2018 y marzo de 2020, se incluyeron 59 pacientes. La edad media en el momento del inicio del protocolo fue de 10,5 años (rango, 2-17 años). La mediana de la duración del tratamiento fue de 20 meses (rango, 12-32). La mediana de edad en el momento de la primera convulsión fue de 8 meses (rango, 1 día - 10 años). Al final del seguimiento, el 78% de los niños tenía una disminución ≥ 50% en frecuencia de las crisis y el 47,5% tenía una disminución > 75%. Siete pacientes (11,9%) estaban libres de convulsiones. El número de crisis se redujo de una mediana de 305/mes a 90/mes, que supone una reducción media del 57% y una mediana del 71% (p < 0,0001). Los efectos adversos fueron en su mayoría leves o moderados. El CBD se interrumpió en 17 pacientes (28,8%) por falta de respuesta al tratamiento, aumento de la frecuencia de las convulsiones, intolerancia al fármaco o cumplimiento terapéutico insuficiente. Conclusión: En los niños con EED resistentes a los fármacos, el tratamiento a largo plazo del cannabis medicinal enriquecido con CBD como terapia adyuvante resultó ser seguro, bien tolerado y eficaz. Las reducciones sostenidas en la frecuencia de las convulsiones y la mejora de los aspectos de la vida diaria se observaron en comparación con nuestros preliminares (AU)

Objective: We report results on the effectiveness, safety, and tolerance of cannabidiol (CBD) as add-on therapy in children with developmental and epileptic encephalopathies (DEE) resistant to pharmacological and non-pharmacological treatment after a mean follow-up of 20 months. Methods: A prospective cohort study was conducted to evaluate the efficacy, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEEs seen at a single center. Results: Between October 2018 and March 2020, 59 patients were included. The median age at protocol initiation was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). The median age at the time of the first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a decrease ≥ 50% in seizure frequency and 47.5% had a decrease of > 75%. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, accounting for a mean reduction of 57% and a median of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, drug intolerance, or poor compliance. Conclusion: In children with drug-resistant DEE, long-term treatment with CBD-enriched medicinal cannabis as add-on therapy proved to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement in aspects of daily living were observed compared to our preliminary results (AU)

Vagus Nerve Stimulation in the Treatment of Dravet Syndrome / 罕见病研究

Dravet syndrome is a epileptic syndrome characterized by drug-resistant epilepsy occuring at childhood. It is often accompanied by status epilepticus and cognitive and language impairment appearing gradually as the disease progresses. The effect of antiepileptic drugs and resection epilepsy surgery on Dravet syndrome is poor although neuromodulation surgery, especially vagus nerve stimulation, is an effective and feasible treatment for Dravet syndrome. In this article we reported a case of Dravet syndrome treated with vagus nerve stimulation, relevant literature was reviewed and summarized at the same time. A total of 141 cases of Dravet treated by vagus nerve stimulation were collected, and the overall effective rate was 53.9%.

Lack of meaningful genotype-phenotype association in SCN1A-related infantile-onset epileptic encephalopathies

Background & Objective: SCN1A gene which encodes for sodium channel alpha 1 subunit has been found to be the most common mutated gene in patients with epilepsy. This study aims to characterize the SCN1A mutations as well as to describe genotype and phenotype association in children with SCN1Arelated infantile-onset epileptic encephalopathies in Malaysia. Methods: Children with infantile-onset epileptic encephalopathy mostly suspected to have Dravet syndrome who had mutational analysis for SCN1A gene from hospitals all over Malaysia were included in the study. Their epilepsy syndrome diagnosis was classified into severe myoclonic epilepsy in infancy and its variants. Polymerase chain reaction and bidirectional sequencing were used to identify SCN1A mutations. Results: A total of 38 children with heterozygous mutations were analysed, 22 (57.9%) of which were novel mutations. Truncated mutations were the most common mutation type (19, 50%). Other mutation types were missense mutations (14, 36.8%), splice site mutations (4, 10.5%) and in-frame deletion (1, 2.6%). The mean age of seizure onset was 4.7 months. Seizure following vaccination was observed in 26.3% of the children. All of them had drug resistant epilepsy. There was no significant association between the type of mutation with the syndromic diagnosis, age of seizure onset, tendency of the seizures to cluster or having status epilepticus, mean age when developmental delay was observed and response to various antiepileptic drugs. Conclusion: This study expands the spectrum of SCN1A mutations and proves the importance of SCN1A gene testing in diagnosing infantile-onset epileptic encephalopathies patients. Although, our study does not support any clinically meaningful genotype-phenotype association for SCN1A-related infantile-onset epileptic encephalopathies, the clinical characteristics of our cohort are similar to those that have been described in previous studies.

Newer Anti-epileptic Drugs.

Need and Purpose of review: A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children. Methods used for locating, selecting, extracting and synthesizing data: MEDLINE search (1966-2013) was performed using terms “newer anti-epileptic drugs”, “Oxcarbazepine”, vigabatrin”, topiramate”, “zonisamide”, “levetiracetam”, “lacosamide”, “rufinamide”, “stiripentol”, “retigabine”, “eslicarbazepine”, “brivaracetam”, “ganaxolone” and “perampanel” for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children. Main conclusions: Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine , levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.

Genetic contribution to early-onset epileptic encephalopathies / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.022