Aicardi syndrome: a case report / Síndrome de Aicardi: relato de caso

Abstract Introduction: the Aicardi syndrome (SA) is characterized as a rare syndrome identified in the presence of three classic characteristics: corpus callosum agenesis, chorioretinal lacunaeand infantile spasms. Description: data collection involved information reported by the mother and the accompanying physiotherapist describing the patient's clinical history andmajor complications according to clinical evolution, treatment, and therapeutic response. At two months of age, the child presented a delayed neuropsychomotor development and infantile spasms.However,the diagnosis of the syndrome was only performed at six months of life, involving brain magnetic resonance imaging where corneal body agenesis was observed. A multidisciplinary treatment was assembledwith a neuropediatrician, a physiotherapist, a psychologist, a nutritionistand a speech therapist, besides drug treatment with baclofen and phenobarbital. Discussion: through the established treatment, the child displayedmotor gain, cervical control, improvement of the respiratory condition, and no need forhospital admissions;these outcomescharacterizea good clinical evolution associated with the physiotherapeutic intervention focused on prevention and minimization of respiratory alterationsthatare frequently associated with morbidity and mortality in these cases. The results obtained point out the fundamental role of multidisciplinary intervention in coping with this condition.

Resumo Introdução: a Síndrome de Aicardi (SA), caracteriza-se como uma síndrome rara identificada na presença das três características clássicas: agenesia de corpo caloso, lacunas coriorretinianas e espamos infantis. Descrição: a coleta de dados envolveu informações relatadas pela genitora e pelo fisioterapeuta acompanhante da paciente, descrevendo assim a história clínica da paciente, as principais complicações de acordo com a evolução clínica, o tratamento e resposta terapêutica. Aos dois meses de idade a criança apresentou atraso no desenvolvimento neuropsicomotor e espasmos infantis, porém o diagnóstico da síndrome foi realizado somente aos seis meses de vida envolvendo um exame de ressonância magnética de encéfalo onde foi observada agenesia de corpo caloso, iniciando-se tratamento multidisciplinar com neuropediatra, fisioterapeuta, psicólogo, nutricionista e fonoaudiólogo, além do tratamento medicamentoso com baclofeno e fenobarbital. Discussão: através do tratamento estabelecido, a criança obteve ganho motor, controle cervical, melhora da condição respiratória e sem internações hospitalares, caracterizando uma boa evolução associada particularmente à intervenção fisioterapêutica que teve enfoque na prevenção e minimização de alterações respiratórias frequentemente associadas à morbidades e mortalidade nestes casos. Os resultados obtidos apontam o papel fundamental da intervenção multidisciplinar para o enfrentamento desta condição.

Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes.

OBJECTIVE: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. METHODS: We included patients aged 1-30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. RESULTS: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9-85%) and week 48 (59.1% [n = 27], IQR: 14-86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ2(2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. SIGNIFICANCE: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies.

[Epileptic encephalopathies in infancy. How do we treat them? Does the aetiology influence the response to treatment?] / Encefalopatias epilepticas del lactante. Como las tratamos? Influye la etiologia en la respuesta al tratamiento?

INTRODUCTION: Resistance to treatments is a common feature of Ohtahara, Aicardi, West and Dravet syndromes, as well as malignant migrating epilepsy in infancy. AIMS: To update the therapeutic management and to analyse whether the aetiology somehow determines the treatment. DEVELOPMENT: Convulsive seizures in the first year of life may be due to a potentially treatable aetiology, which makes it essential to carry out a complete evaluation so as to be able to begin, as early as possible, the most suitable and the non-specific symptomatic treatments to control the seizures, which prevents or minimises their deleterious effects. Metabolic disease must be ruled out and it is also essential to try a therapeutic regimen of vitamins and cofactors, as well as antiepileptic drugs. In Ohtahara and Aicardi syndromes, the first-order treatment is phenobarbital and phenytoin, and the most commonly used second-order drugs are midazolam, levetiracetam, lidocaine and valproate. In West's syndrome, the first-order treatment consists of adrenocorticotropic hormone and vigabatrine for the case of tuberous sclerosis; if there is no response, other pharmaceuticals, a ketogenic diet and surgery must be considered. For Dravet's syndrome, the main treatment consists in valproate with clobazam and stiripentol, and as the second order, other drugs and a ketogenic diet should be considered. In epilepsy with migrating seizures, the most effective treatment is with bromides, stiripentol, clonazepam and levetiracetam. CONCLUSIONS: Today there is little consensus on the therapeutic approach to be able to establish specific indications. The aetiology has an influence on the treatment, both in cases in which a curative treatment exists (metabolic diseases) and in the symptomatic management with antiepileptic drugs or other treatments (ketogenic diet or surgery).

TITLE: Encefalopatias epilepticas del lactante. Como las tratamos? Influye la etiologia en la respuesta al tratamiento?Introduccion. La refractariedad es una caracteristica comun del tratamiento de los sindromes de Ohtahara, Aicardi, West, Dravet y epilepsia maligna del lactante con crisis migrantes. Objetivo. Actualizar el manejo terapeutico y analizar si la etiologia determina de alguna manera el tratamiento. Desarrollo. Las crisis convulsivas en el primer año de vida pueden deberse a una etiologia potencialmente tratable, por lo que es imperativo una completa evaluacion para instaurar de manera precoz el tratamiento adecuado y el sintomatico no especifico para el control de las crisis, que evite o minimice el efecto deletereo de estas. Es obligado hasta descartar metabolopatia y ensayar pauta de vitaminas y cofactores, ademas de antiepilepticos. En los sindromes de Ohtahara y Aicardi, la primera linea es fenobarbital y fenitoina, y en segunda linea, los mas habituales son midazolam, levetiracetam, lidocaina y valproato. En el sindrome de West, la primera linea la constituye la hormona adrenocorticotropa y la vigabatrina para el caso de esclerosis tuberosa; si no hay respuesta, considerar otros farmacos, dieta cetogenica y cirugia. Para el sindrome de Dravet, los principales son valproato con clobazam y estiripentol, y de segunda linea, considerar otros farmacos y dieta cetogenica. En la epilepsia con crisis migrantes, los mas eficaces son bromuros, estiripentol, clonacepam y levetiracetam. Conclusiones. Actualmente existe poco consenso en el abordaje terapeutico para establecer indicaciones taxativas. La etiologia influye en el tratamiento, tanto en el caso de disponer de tratamiento curativo (metabolopatias) como en el abordaje sintomatico con antiepilepticos u otros tratamientos (dieta cetogenica o cirugia).

Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.

Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx((GCG)10+7) mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies.

Bilaterally independent epileptic spasms in a case of Aicardi syndrome.

A girl with Aicardi syndrome was observed to have two distinct types of asymmetric epileptic spasms, as detected by ictal video-EEG recording at three months of age. When the two types of spasm concurred, they showed no mutual interactions based on either clinical or EEG aspects. This observation does not support the hypothesis that the brainstem always plays an initiating role in generating spasms. [Published with video sequences].

[Aicardi syndrome associated with severe congenital ptosis]. / Un syndrome d'Aicardi associé à un ptosis congénital sévère.

Aicardi syndrome is a rare neurodevelopmental disorder characterized by corpus callosum agenesis, chorioretinal lacunae and early-onset infantile spasms. We report a particular case of Aicardi syndrome characterized by the association of the classical triad of severe bilateral ptosis, pontocerebellar hypoplasia, and perisylvian polymicrogyria in a girl born to non-consanguineous parents, but whose mother suffered from idiopathic generalized epilepsy.