ABSTRACT
Self-limited Focal Epilepsies of Childhood (SELFEs) are the most prevalent electroclinical syndromes in pediatric age, whose typical evolution, with age-dependent onset and remission, has allowed the ILAE Nosology and Definitions Working Group (2022) to define them as "Selflimited Focal Epilepsies of Childhood", thus establishing alert and exclusion criteria to standardize their diagnosis. These syndromes include: Self-limited Epilepsy with Centrotemporal Spikes (previously Rolandic Epilepsy), Self-limited Epilepsy with Autonomic Seizures (previously Panayiotopoulos Syndrome), Childhood Occipital Visual Epilepsy, (previously Gastaut Syndrome), and Photosensitive Occipital Lobe Epilepsy. Using the term "benign" to refer to them is no longer recommended, as this would ignore the comorbidities some individuals suffer. Also, the term "idiopathic" is now only used to refer to the syndromes classified as Idiopathic Generalized Epilepsies.
Las Epilepsias Focales Autolimitadas de la Infancia (SELFEs - siglas en inglés) son los síndromes electroclínicos más prevalentes en edad pediátrica, cuya evolución típica, con inicio y remisión dependientes de la edad, ha permitido que el Grupo de Trabajo de Nosología y Definiciones de la ILAE (2022) las defina como "Epilepsias focales autolimitadas de la infancia", estableciendo así, criterios de alerta y exclusión para estandarizar su diagnóstico. Dentro de estos síndromes se incluyen: la Epilepsia Autolimitada con Espigas Centrotemporales (previamente Epilepsia Rolándica), Epilepsia Autolimitada con Crisis Autonómicas. (previamente Síndrome de Panayiotopoulos), Epilepsia Visual Occipital Infantil (previamente Síndrome de Gastaut), y Epilepsia Fotosensible del Lóbulo occipital. Ya no se recomienda utilizar el término "benignas" para referirse a ellas, ya que esto haría caso omiso de las comorbilidades que padecen algunos individuos. Asimismo, el término "idiopático" sólo se utiliza ahora para denominar a los síndromes clasificados como Epilepsias Generalizadas Idiopáticas.
Subject(s)
Epilepsies, Partial , Epilepsy, Generalized , Lennox Gastaut Syndrome , Humans , Child , Epilepsies, Partial/diagnosis , Seizures/diagnosisABSTRACT
Cannabidiol oil (CBD) has been approved as an anti-seizure medication for the treatment of uncommon types of epilepsy, occurring in children: Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis Complex. There are few publications in relation to use the CBD in adult patients with focal drug-resistant epilepsy. The objective of this study was to evaluate the efficacy, tolerability, safety, and quality of life, of adjuvant treatment with CBD, in adult patients with drug-resistant focal epilepsy for at least 6 months. An open, observational, prospective cohort study was conducted using a before-after design (time series) in adult patients undergoing outpatient follow-up in a public hospital in Buenos Aires, Argentina. From a total of 44 patients, 5% of patients were seizure-free, 32% of patients reduced more than 80% of their seizures and 87% of patients reduced 50% of their monthly seizures. Eleven percent presented a decrease of less than 50% in seizure frequency. The average final dose was 335 mg/d orally administered. Thirty-four percent of patients reported mild adverse events and no patient reported severe adverse effects. At the end of the study, we found in most patients a significant improvement in the quality of life, in all the items evaluated. Adjuvant treatment with CBD in adult patients with drug-resistant focal epilepsy was effective, safe, well tolerated, and associated with a significant improvement in their quality of life.
Subject(s)
Cannabidiol , Drug Resistant Epilepsy , Epilepsies, Myoclonic , Epilepsies, Partial , Epilepsy , Lennox Gastaut Syndrome , Adult , Child , Humans , Anticonvulsants/adverse effects , Drug Resistant Epilepsy/drug therapy , Drug Resistant Epilepsy/chemically induced , Epilepsies, Myoclonic/drug therapy , Epilepsies, Partial/drug therapy , Epilepsies, Partial/chemically induced , Epilepsy/drug therapy , Lennox Gastaut Syndrome/drug therapy , Prospective Studies , Quality of LifeABSTRACT
Introducción: El síndrome de Lennox Gastaut se considera una encefalopatía epiléptica. Las anomalías epileptiformes en este síndrome contribuyen a la discapacidad intelectual gradual, a las comorbilidades psiquiátricas y alteraciones conductuales. En la práctica clínica aparecen atipicidades del síndrome, con focalización funcional cuyo tratamiento constituye un desafío. Objetivo: Describir la evolución clínica, cognitiva y calidad de vida en un caso con síndrome de Lennox Gastaut antes, y después del tratamiento quirúrgico. Presentación del caso: Paciente masculino de 16 años con síndrome de Lennox Gastaut. Se revisó la historia clínica y se tomaron en consideración, los resultados del video-electroencefalograma, de la resonancia magnética nuclear y de la tomografía computarizada por emisión de fotón único. Se evaluó, además, el proceder quirúrgico, la evaluación clínica y neuropsicológica. Se realizó una descripción cualitativa de la evolución del paciente a los 6 meses y al año de la intervención quirúrgica. Conclusiones: el paciente con síndrome de Lennox Gastaut presentó una evolución favorable después del tratamiento quirúrgico, lo cual se reflejó en una disminución en la frecuencia de las crisis. mejoría cognitiva, conductual y mejor calidad de vida(AU)
Introduction: Lennox Gastaut syndrome is considered an epileptic encephalopathy. Epileptiform abnormalities in this syndrome contribute to gradual intellectual disability, psychiatric comorbidities and behavioral disturbances. In clinical practice, atypicalities of the syndrome appear with functional focalization whose treatment constitutes a challenge. Objective: To describe the clinical and cognitive evolution and quality of life in a case with Lennox Gastaut syndrome before and after surgical treatment. Case presentation: A 16-year-old male patient with Lennox Gastaut syndrome. The clinical history was reviewed and the results of the video-electroencephalogram, nuclear magnetic resonance and single photon emission computed tomography were taken into consideration. The surgical procedure, clinical and neuropsychological evaluation were also evaluated. A qualitative description of the patient's evolution past 6 months and one year after surgery was prepared. Conclusions: the patient with Lennox Gastaut syndrome has a favorable evolution after surgical treatment, which is reflected in a decrease in seizure frequency, cognitive and behavioral improvement and better quality of life(AU)
Subject(s)
Humans , Male , Adolescent , Quality of Life , Brain Diseases/etiology , Clinical Evolution/methods , Epilepsy/surgery , Lennox Gastaut Syndrome/surgery , Intellectual Disability , NeuropsychologyABSTRACT
Uso de canabidiol (CDB) medicinal presente no óleo de canabis. Indicação: Tratamento de crianças portadoras de epilepsia refratária resistente a medicação e síndromes graves decorrentes. Pergunta: O uso do canabidiol em crianças com epilepsia resistente a medicamentos apresentaria diminuição na frequência de crises convulsivas? Objetivo: Investigar a eficácia e a segurança do canabidiol, em comparação a placebo, na manutenção da remissão em crianças com epilepsia refratária. Métodos: Revisão rápida de revisões sistemáticas, por meio de buscas bibliográficas realizadas nas bases PUBMED, SCOPUS, BVS, Cochrane Library. Foram utilizadas estratégias de buscas com vocabulário padronizado e avaliação da qualidade metodológica usando o checklist AMSTAR 2. Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade. O CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria (RR 1.69 [1.20 2.36]), para a síndrome de Lennox-Gastaut o RR foi 2.98 (IC 95%, 1.83 - 4.85) e para a síndrome de Dravet o RR foi 2.26 (IC 95% ,1.38 - 3.70). O CDB pode resultar em uma diminuição no apetite em dosagens maiores (RR = 2,10, IC 95% [0,964,62], embora não apresente diferença de efeito dos grupos comparadores. Conclusão: Duas revisões sistemáticas recentes o CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria e síndromes graves. Entretanto, existem poucos ensaios clínicos publicados na área
: Use of cannabidiol (CBD) present in cannabis oil. Indication: Treatment of children with drug-resistant refractory epilepsy and severe syndromes resulting. Question: Would the use of cannabidiol in children with drug-resistant epilepsy lead to a decrease in seizure frequency? Objective: to investigate the efficacy and safety of cannabidiol, compared to placebos, in maintaining remission in children with refractory epilepsy. Methods: Rapid review of systematic reviews, through a bibliographical search carried out in the PUBMED, SCOPUS, BVS, Cochrane Library databases. Predefined search strategies were followed, and the methodological quality of the included studies was evaluated using the AMSTAR 2 tool. Results: Two systematic reviews were selected, which met the eligibility criteria. CBD when compared to placebo reduce 50% of seizures for refractory epilepsy (RR 1.69, IC 95% [1.20 2.36]), for Lennox-Gastaut Syndrome the RR was foi 2.98 (IC 95%, 1.83 - 4.85) and for Dravet Syndrome o RR FOI 2.26 (IC 95% ,1.38 - 3.70). CBD may result in appetite decrease using high doses (RR = 2.10, 95% IC [0.96 4.62], with no statistical difference. Conclusion: Two recent systematics, CBD, when compared to placebo, presented 50% of seizures for refractory epilepsy and severe syndromes. However, there are few clinical trials published in the area
Subject(s)
Male , Female , Child, Preschool , Child , Cannabidiol/therapeutic use , Drug Resistant Epilepsy/drug therapy , Dronabinol/therapeutic use , Cannabinoids/therapeutic use , Efficacy , Lennox Gastaut Syndrome/drug therapy , AnticonvulsantsABSTRACT
Tecnologia: Felbamato. Indicação: Tratamento de epilepsia refratária. Pergunta: O Felbamato é mais eficaz e seguro comparado a anticonvulsivantes disponíveis no Sistema Único de Saúde (SUS) em pacientes com epilepsia refratária? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: O felbamato não demonstrou ser uma opção mais benéfica que os demais medicamentos disponíveis no SUS no tratamento de epilepsia refratária a medicamentos. Salienta-se que a maior parte das evidências eram de baixa certeza
Technology: Felbamate. Indication: Treatment of refractory epilepsy. Question: Is felbamate more effective and safer compared to anticonvulsants available in Brazilian Public Health System in patients with refractory epilepsy? Methods: A rapid review of evidence (overview) of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Two systematic reviews that met the inclusion criteria were selected. Conclusion: Felbamate did not prove to be a more beneficial option than the other drugs available in the Brazilian Public Health System in the treatment of drug-refractory epilepsy. It should be noted that most of the evidence was of low certainty
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Seizures/drug therapy , Drug Resistant Epilepsy/therapy , Anticonvulsants/therapeutic use , Comparative Effectiveness Research , Lennox Gastaut SyndromeABSTRACT
INTRODUCTION: The aim of this study was to extend our knowledge of the genetic background of Argentinean pediatric patients with developmental and epileptic encephalopathy (DEE) applying a next generation sequencing (NGS) panel. METHODS: Thirty one patients with DEE were studied, including these phenotypes: Dravet syndrome (n:7), Dravet like syndrome (n:3), West syndrome (WS) (n:6), WS that evolved to Lennox-Gastaut syndrome (LGS) (n:4), epilepsy of infancy with migrating focal seizures (n:2), continuous spikes and waves during slow sleep evolving to LGS (n:1), LGS (n:1), myoclonic status in non-progressive encephalopathy (n:1), myoclonic atonic epilepsy (n:1), epileptic encephalopathy with multifocal spikes (n:1) and unclassified epileptic encephalopathy (n:4). Fifty-two genes frequently associated with DEE were studied by NGS in genomic DNA from peripheral blood. RESULTS: Relevant variants were detected in 12 cases; 6 novel pathogenic or likely pathogenic variants, 6 previously reported as pathogenic and 1 variant of unknown significance. Single-nucleotide heterozygous variants were identified in the SCN1A (5), GABRG2 (1), STXBP1 (2) genes, a mosaic variant in SCN2A (1) and a homozygous variant in SCN1B (1). Additionally, a heterozygous deletion involving the SCN1A, SCN2A and SCN3A genes (1), and the most frequent triplet repeat expansion in the ARX gene (1) were detected. DISCUSSION: Genetic diagnosis was made in 39% of patients. We emphasize the importance of considering mosaic variants, copy number variants and hereditary forms when designing and interpreting molecular studies, to optimize diagnosis and management of patients. Approximately 42% of the detected variants were novel, expanding the knowledge of the molecular basis of DEEs in Latin-American patients.
Introducción: El objetivo del estudio fue ampliar el conocimiento de las bases moleculares de las encefalopatías epilépticas y del desarrollo (EED) en pacientes pediátricos argentinos aplicando un panel de secuenciación de nueva generación (NGS). Métodos: Se analizaron 31 pacientes con los fenotipos clínicos de síndrome de Dravet (n:7), síndrome símil Dravet (n:3), síndrome de West (SW) (n:6), SW que evoluciona a síndrome de Lennox Gastaut (SLG)(N:4), epilepsia de la infancia con crisis focales migratorias (n:2), actividad de punta onda continua durante el sueño que evolucionan a SLG (n:1), SLG (n:1), encefalopatía no progresiva con estatus mioclónico (n:1), epilepsia mioclónica atónica (n:1), encefalopatía epiléptica con espigas multifocales (n:1) y encefalopatía epiléptica indeterminada (n:4). Se estudiaron los 52 genes más frecuentemente asociados a EED a través de NGS, en ADN extraído de sangre periférica. Resultados: Se identificaron variantes relevantes en 12 casos, de las cuales 5 fueron nuevas y 6 previamente reportadas como patogénicas o posiblemente patogénicas, mientras que una variante fue clasificada como de significado incierto. Variantes heterocigotas, de nucleótido único, se identificaron en los genes SCN1A (5), GABRG2 (1), STXBP1 (2), una variante en mosaico en SCN2A (1) y otra homocigota en SCN1B (1). Además, se detectó una deleción que involucra a los genes SCN1A, SCN2A y SCN3A (1) y la expansión de repeticiones de tripletes más frecuente en el gen ARX (1). Discusión: Se alcanzó el diagnóstico molecular en el 39% de los pacientes. Remarcamos la importancia de considerar variantes en mosaico, variantes en el número de copias y formas heredadas al momento de diseñar e interpretar los estudios moleculares, de tal forma de optimizar el diagnóstico y seguimiento de los pacientes con EED. Cabe destacar, que el 42% de las variantes detectadas fueron nuevas, ampliando nuestro conocimiento sobre las bases moleculares de las EED en población latino americana.
Subject(s)
Brain Diseases , Epilepsies, Myoclonic , Epilepsy , Lennox Gastaut Syndrome , Spasms, Infantile , Humans , Epilepsy/diagnosis , Epilepsies, Myoclonic/diagnosis , Brain Diseases/genetics , Lennox Gastaut Syndrome/diagnosis , Lennox Gastaut Syndrome/genetics , Spasms, Infantile/diagnosis , Spasms, Infantile/genetics , Phenotype , SeizuresABSTRACT
OBJECTIVE: The objective of this systematic review with meta-analysis was to evaluate the efficacy, safety, and short- and long-term tolerability of cannabidiol (CBD), as an adjunct treatment, in children and adults with Dravet syndrome (SD), Lennox-Gataut syndrome (LGS), or tuberous sclerosis complex (TSC), with inadequate control of seizures. METHODS: This systematic review was conducted through a search for scientific evidence in the Mediline/PubMed, Central Cochrane, and ClinicalTrials.gov databases until April 2022. Selected randomized clinical trials (RCTs) that presented the outcomes: reduction in the frequency of seizures and total seizures (all types), number of patients with a response greater than or equal to 50%, change in caregiver global impression of change (CGIC) (improvement ≥1 category on the initial scale), adverse events (AEs), and tolerability to treatment. This review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses. RESULTS: Notably, six RCTs were included, with a total of 1,034 patients with SD, LGS, and TSC, of which 3 were open-label extension RCTs. The meta-analysis of the studies showed that the use of CBD as compared with placebo, in patients with convulsive seizures refractory to the use of medications, reduces the frequency of seizures by 33%; increases the number of patients with a reduction ≥50% in the frequency of seizures by 20%; increases the number of patients with absence of seizures by 3%; improves the clinical impression evaluated by the caregiver or patient (S/CGIC) in 21%; increases total AEs by 12%; increases serious AE by 16%; increases the risk of treatment abandonment by 12%; and increases the number of patients with transaminase elevation (≥3 times the referral) by 15%. CONCLUSIONS: This systematic review, with meta-analysis, supports the use of CBD in the treatment of patients with seizures, originated in DS, LGS, and TSC, who are resistant to the common medications, presenting satisfactory benefits in reducing seizures and tolerable toxicity.
Subject(s)
Cannabidiol , Epilepsies, Myoclonic , Epilepsy , Lennox Gastaut Syndrome , Tuberous Sclerosis , Adult , Child , Humans , Anticonvulsants/therapeutic use , Anticonvulsants/adverse effects , Cannabidiol/therapeutic use , Cannabidiol/adverse effects , Epilepsies, Myoclonic/drug therapy , Epilepsies, Myoclonic/chemically induced , Lennox Gastaut Syndrome/drug therapy , Seizures/etiology , Seizures/chemically induced , Tuberous Sclerosis/complications , Tuberous Sclerosis/drug therapy , Tuberous Sclerosis/chemically inducedABSTRACT
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)
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Cannabidiol/therapeutic use , Treatment Outcome , Epilepsy/drug therapy , Medical Marijuana/therapeutic use , Lennox Gastaut Syndrome/drug therapy , Drug Resistant Epilepsy/drug therapy , Hospitals, Pediatric , Anticonvulsants/therapeutic use , Prospective Studies , Cohort StudiesABSTRACT
OBJECTIVE: The aim of this current report was to present a critical review of the use of cannabidiol (CBD) in the treatment of refractory epilepsies in the pediatric population. DATA SOURCE: Literature review was carried out in the Medline (PubMed), Cochrane, and Scientific Electronic Library Online (SciELO) databases with the descriptors "Cannabidiol" and "Epilepsy." The search was not limited by the date of publication, language, or study design. A total of 69 articles were included in the review. DATA SYNTHESIS: The efficacy of CBD in treating epileptic seizures has been confirmed by randomized controlled trials for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. The incidence of side effects reported in subjects of the studies is high. However, most studies indicate a good safety profile and tolerance to the drug, with most of the adverse effects being mild to moderate and transient. CONCLUSIONS: There is no consensus on the release of CBD as a therapeutic tool by the drug regulatory agencies worldwide. However, the use of CBD is promising since it has presented satisfactory results in crisis control in well-designed studies. In addition, this drug has a good safety and tolerance profile. However, further studies with a long follow-up period are needed to confirm its usefulness and the long-term safety in pediatric patients.
Subject(s)
Cannabidiol , Drug Resistant Epilepsy , Drug-Related Side Effects and Adverse Reactions , Epilepsy , Lennox Gastaut Syndrome , Anticonvulsants/therapeutic use , Cannabidiol/therapeutic use , Child , Drug Resistant Epilepsy/chemically induced , Drug Resistant Epilepsy/drug therapy , Epilepsy/chemically induced , Epilepsy/drug therapy , Humans , Lennox Gastaut Syndrome/drug therapyABSTRACT
Introducción: El síndrome de Lowe o síndrome oculocerebrorenal es un trastorno multisistémico. Es una enfermedad rara e infrecuente. Objetivo: Exponer un caso clínico típico, con fracaso renal controlado sin método dialítico y que de manera tardía en su adolescencia se diagnostica con síndrome de Lennox-Gastaut. Presentación caso: Adolescente masculino de 18 años nacido de un embarazo sin riesgo y parto por cesárea, macrofeto. Desde el nacimiento, con diagnóstico perinatal de catarata congénita y evolutivamente glaucoma bilateral con tratamiento conservador. A partir del primer año de vida padece de acidosis tubular y síndrome de Fanconi con evolución a una enfermedad renal crónica. Relacionado todo con retraso del desarrollo psicomotor, discapacidad intelectual, estereotipias, síntomas obsesivos compulsivos y depresión. De manera tardía, a los 10 años tuvo inicio de crisis epilépticas de varios tipos con predominio de las tónicas durante el sueño y en vigilia, frecuentes, con electroencefalograma característico de síndrome Lennox-Gastaut. Tuvo atención interdisciplinaria y evolución clínica estable hasta la edad adulta cumplida. El estudio molecular de ADN materno y del niño confirmaron la mutación c2224_2226 del GTA (exón 19), delección de valina en la posición 742 del cromosoma X del OCRL 1, que ratifica el síndrome de Lowe. Conclusiones: El Síndrome de Lowe, es un trastorno multisistémico, ligado al cromosoma X y frecuente en varones. Clínicamente se caracteriza por alteraciones oftalmológicas, renales y neurológicas(AU)
Introduction: Lowe syndrome or oculocerebrorenal syndrome is a multisystemic disorder. It's a rare and uncommon disease. Objective: Show a typical clinical case, with controlled renal failure without dialytic method and that late in the adolescence is diagnosed with Lennox-Gastaut syndrome. Case presentation: 18-year-old male adolescent born of a risk-free pregnancy and cesarean delivery, with macrosomia. From birth, he had a perinatal diagnosis of congenital cataract and evolutionarily bilateral glaucoma with conservative treatment. From the first year of life he suffers from tubular acidosis and Fanconi syndrome with an evolution to chronic kidney disease. All of these were related to delayed psychomotor development, intellectual disability, stereotypies, obsessive-compulsive symptoms and depression. Lately, at 10 years old, epileptic seizures of various types with predominance of tonic ones during sleep and wakefulness began; they were frequent, with characteristic electroencephalogram of Lennox-Gastaut syndrome. He had interdisciplinary care and stable clinical evolution into adulthood. The molecular study of the mother and child DNA confirmed the c2224_2226 mutation of GTA (exon 19), valine deletion at position 742 of the X chromosome of OCRL 1, which ratifies Lowe syndrome. Conclusion: Lowe Syndrome is a multisystemic disorder, linked to the X chromosome and common in males. Clinically, it is characterized by ophthalmological, renal and neurological alterations(AU)
Subject(s)
Humans , Male , Adolescent , Cataract/therapy , Rare Diseases/etiology , Renal Insufficiency, Chronic/therapy , Lennox Gastaut Syndrome/diagnosis , Oculocerebrorenal Syndrome/diagnosis , Electroencephalography/methodsABSTRACT
Introdução: A Síndrome de Lennox-Gastaut (SLG) é uma encefalopatia epiléptica grave na infância. Seu tratamento é complexo, principalmente devido à multiplicidade das crises epilépticas, o que favorece à ocorrência de lesões dentais Objetivo: O objetivo deste relato é apresentar o manejo clínico de um paciente com SLG, vítima de traumas recorrentes, discutir os achados dentais observados e o tratamento odontológico realizado. Relato do caso: Paciente L.H.D.L., do sexo masculino, com 15 anos de idade, apresentando grande acúmulo de biofilme dental, alto risco de cárie, fluorose leve e gengivite generalizada. Clinicamente foi possível observar fratura de esmalte dos dentes 12 e 14. Os dentes 21, 22, 32 e 42 estavam ausentes clinicamente, o que se confirmou radiograficamente. Além disso, notou-se giroversão de 180 graus do dente 11, com a face palatina voltada para a vestibular. O dente apresentou-se com leve alteração de cor, mas com resposta positiva aos testes de vitalidade. Resultados: Técnicas de manejo de comportamental, foram adotadas e orientações quanto à higiene bucal e dietéticas foram fornecidas tanto ao paciente quanto ao seu cuidador. Quatro sessões de profilaxia e aplicação tópica de flúor foram realizadas semanalmente. O tratamento endodôntico foi realizado no dente 12, seguido da restauração de resina composta do dente 12 e 14 e a restauração estética do dente 11 (girovertido). Por fim, foi realizada uma prótese adesiva para restaurar a estética da região de incisivo central superior. Apesar das dificuldades para tratar pacientes com SLG, no presente caso foi possível obter resultados funcionais e estéticos satisfatórios com um diagnóstico e tratamento cuidadoso, envolvendo uma equipe multiprofissional treinada no atendimento de pacientes com necessidades especiais. Conclusão: Pode-se concluir que o cirurgião dentista deve estar familiarizado com as possíveis manifestações bucais da SLG e realizar uma pesquisa criteriosa de sinais de traumatismo dental e, sempre que possível, solicitar um exame radiográfico para que traumatismos não identificados ao exame clínico não passem desapercebidos.
Introduction: Lennox-Gastaut Syndrome (LSG) is a severe childhood epileptic encephalopathy. Its treatment is complex, mainly due to the multiplicity of epileptic crises, which in turn favors the occurrence of dental injuries. Objective: The aim of this case report is to present the clinical management of a patient with LGS, victim of recurrent trauma, discuss the observed dental findings and the dental treatment. Case report: Patient L.H.D.L., male, 15 years old presenting high quantity of oral biofilm, mild fluorosis and generalized gingivitis. Clinically, it was possible to observe enamel fractures of teeth 12 and 14. Teeth 21, 22, 32 and 42 were clinically absent, which was confirmed radiographically. In addition, a 180-degree rotation of tooth 11 was noted, with the palate facing the buccal aspect. The tooth presented a slight change in color, but with a positive response to vitality tests. Results: Behavioral management techniques were adopted and guidelines on oral hygiene and diet were provided to both the patient and their caregiver. Four sessions of prophylaxis and topical application of fluoride were performed weekly. Endodontic treatment was performed on tooth 12, followed by aesthetic restoration of teeth 12 and 14 and esthetic restoration of tooth 11 (rotated). Finally, an adhesive prosthesis was performed to restore the esthetics of the upper central incisor region. Despite the difficulties of treating patients with LGS, in the present case it was possible to obtain satisfactory functional and aesthetic results with a careful diagnosis and treatment, involving a multidisciplinary team trained in the care of patients with special needs. Conclusion: It can be concluded that the dental surgeon must be aware with the possible oral manifestations of GLS and carry out a careful search for signs of dental trauma and, whenever possible, request a radiographic examination so that unidentified traumas on clinical examination do not pass unnoticed.
Subject(s)
Lennox Gastaut Syndrome , Oral Manifestations , Adolescent , Disabled Persons , Tooth InjuriesABSTRACT
OBJECTIVE: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. BACKGROUND: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. METHODS: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. RESULTS: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). CONCLUSIONS: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.
Subject(s)
Hispanic or Latino/genetics , Lennox Gastaut Syndrome/genetics , Membrane Proteins/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Spasms, Infantile/genetics , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Electroencephalography , Female , Hispanic or Latino/statistics & numerical data , Humans , Infant , Male , Puerto Rico , Retrospective Studies , Spasms, Infantile/physiopathology , Young AdultABSTRACT
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 â 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.
Subject(s)
Anticonvulsants/pharmacokinetics , Cannabidiol/pharmacokinetics , Drug Resistant Epilepsy/drug therapy , Epilepsies, Myoclonic/drug therapy , Lennox Gastaut Syndrome/drug therapy , Administration, Oral , Adolescent , Anticonvulsants/therapeutic use , Brain Diseases/drug therapy , Cannabidiol/therapeutic use , Child , Child, Preschool , Drug Interactions , Epileptic Syndromes/drug therapy , Female , Humans , Male , Oils , Thyroxine/adverse effectsABSTRACT
AIM: The aim of this study was to analyze electroclinical features of a group of patients with West syndrome (WS) who subsequently developed Lennox-Gastaut syndrome (LGS) during the transition between both syndromes. METHODS: A retrospective and descriptive study was conducted of a series of patients diagnosed with WS who developed LGS seen at Hospital de Pediatría Prof. Dr. JP Garrahan between January 2012 and January 2019. The medical charts of 170 patients with WS were analyzed. In 63 (37 %) of the children WS evolved to LGS. RESULTS: During the transition from WS to LGS four well-defined electroclinical patterns were recognized. The first corresponded to a group of patients with multiple seizure types, including epileptic spasms associated with multifocal paroxysms; the electroclinical pattern in second group showed mainly focal seizures associated with focal discharges in the EEG; the third group showed predominance of epileptic spasms and myoclonic seizures associated with diffuse spike-and-wave and polyspike-and-wave paroxysms; and the remaining group was characterized by a mixed electroclinical pattern including features of the other three groups. All patients had a neuropsychological deficit. Worsening of cognition and behavior was observed during the transition period in 11, 8, and 5 patients of groups 1, 3, and 4, respectively. CONCLUSION: Our study of the transition period from WS to LGS allowed us to recognize four well-defined electroclinical patterns. The early recognition of the different patterns could, in the future, support a more precocious prognostic evaluation.
Subject(s)
Epilepsies, Myoclonic/physiopathology , Intellectual Disability/physiopathology , Lennox Gastaut Syndrome/physiopathology , Spasms, Infantile/physiopathology , Child , Child, Preschool , Cognition/physiology , Electroencephalography/methods , Epilepsies, Myoclonic/complications , Female , Humans , Infant , Intellectual Disability/complications , Lennox Gastaut Syndrome/complications , Male , Retrospective Studies , Seizures/diagnosis , Spasms, Infantile/complicationsABSTRACT
OBJECTIVE: Here, we present a multicenter series of patients with developmental and epileptic encephalopathies (DEE) and related electroclinical patterns (REP) other than Lennox-Gastaut syndrome (LGS) who were treated with rufinamide as add-on therapy. METHODS: Medical records of 34 patients with DEE and REP other than LGS treated with add-on rufinamide seen at four pediatric neurology centers in Argentina between May 2014 and March 2019 were retrospectively analyzed. RESULTS: We evaluated 34 patients (18 males, 16 females), aged between 2 and 15â¯years with a mean and median age of 6 and 8â¯years, respectively. The children had different types of childhood-onset refractory DEE and REP other than LGS and were treated with rufinamide for a mean period of 20â¯months (range, 12-60â¯months). Twenty-two of 34 patients (64.5%) who received rufinamide as add-on therapy had a greater than 50% decrease in seizures, and two patients (5.8%) became seizure-free. Four patients (11.7%) had a 25-50% seizure reduction, while seizure frequency remained unchanged in four others (11.7%) and increased in two patients (5.8%). The final mean dosage of rufinamide was 31.5⯱â¯15.5â¯mg/kg per day (range, 19-75.4â¯mg/kg) if combined with valproic acid and of 35.4⯱â¯11.5â¯mg/kg per day (range, 8-60.5â¯mg/kg) without valproic acid. Adverse effects were recorded in nine patients (26.4%). A seizure increase was reported in two of 24 patients (7.3%). CONCLUSION: Rufinamide may be used as a treatment option in DEE and REP other than LGS.
Subject(s)
Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Lennox Gastaut Syndrome , Seizures/drug therapy , Triazoles/administration & dosage , Adolescent , Argentina/epidemiology , Child , Child, Preschool , Drug Therapy, Combination , Epilepsy/diagnosis , Epilepsy/epidemiology , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Seizures/diagnosis , Seizures/epidemiology , Valproic Acid/administration & dosageSubject(s)
Hypopigmentation/diagnostic imaging , Skin/diagnostic imaging , Brain/diagnostic imaging , Child, Preschool , Developmental Disabilities/complications , Developmental Disabilities/diagnostic imaging , Humans , Hypopigmentation/complications , Lennox Gastaut Syndrome/complications , Lennox Gastaut Syndrome/diagnostic imaging , Magnetic Resonance Imaging , Male , Neurocutaneous Syndromes/complications , Neurocutaneous Syndromes/diagnostic imagingABSTRACT
West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.
Subject(s)
Lennox Gastaut Syndrome/etiology , Spasms, Infantile/complications , Anticonvulsants/therapeutic use , Disease Progression , Electroencephalography , Female , Humans , Infant , Lennox Gastaut Syndrome/diagnosis , Lennox Gastaut Syndrome/drug therapy , Magnetic Resonance Imaging , Methylprednisolone/therapeutic use , Retrospective Studies , Spasms, Infantile/diagnosis , Spasms, Infantile/drug therapy , Syndrome , Vigabatrin/therapeutic useABSTRACT
El síndrome de West o espasmos infantiles, es una encefalopatía epiléptica clasificada como epilepsias y síndromes generalizados. Hay múltiples informes de la evolución de síndrome de West a síndrome de Lennox-Gastaut de un 25 hasta 60%, sin reconocerse una causa específica. Se ha comunicado que pueden ser solo una entidad epiléptica dependiente de la edad y que estaría en relación con el grado de inmadurez cerebral. En esta revisión retrospectiva de 130 casos de espasmos infantiles, solo 14 (10.7%) evolucionaron a Lennox-Gastaut. El haber recibido en todos los casos vigabatrina como tratamiento nos hace suponer que la baja incidencia podría estar relacionada con el uso de este fármaco. Dado que la vigabatrina tiene una acción gabaérgica y aumenta los niveles de ACTH podría explicar esta relación, pero esto deberá confirmarse con el mejor conocimiento de los mecanismos íntimos de estas graves encefalopatías.
West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.
Subject(s)
Humans , Female , Infant , Spasms, Infantile/complications , Lennox Gastaut Syndrome/etiology , Spasms, Infantile/diagnosis , Spasms, Infantile/drug therapy , Syndrome , Methylprednisolone/therapeutic use , Magnetic Resonance Imaging , Retrospective Studies , Disease Progression , Vigabatrin/therapeutic use , Electroencephalography , Lennox Gastaut Syndrome/diagnosis , Lennox Gastaut Syndrome/drug therapy , Anticonvulsants/therapeutic useABSTRACT
Doose and Lennox-Gastaut (syndromes) are rare generalized electroclinical affections of early infancy of variable prognosis which manifest with very diverse kinds of seizures. Very frequently, these types of epilepsy become drug resistant and finding reliable treatment results is very difficult. As a result of this, fighting against these syndromes becomes a long term (or endless) event for the little patient, the neurologist and the parents. A lot of Electroencephalographic (EEG) records are so accumulated during the child's life in order to monitor evolution and correlate it with medications. So, given a bunch of EEG, three questions arise: (a) On which year was the child healthier (less affected by seizures)? (b) Which area of the brain has been the most affected? (c) What is the status of the child with respect to others (which also have a bunch of EEG, each)? Answering these interrogations by traditional scrutinizing of the whole database becomes subjective, if not impossible. We propose to answer these questions objectively by means of time series entropies. We start with our modified version of the Multiscale Entropy (MSE) in order to generalize it as a Bivariate MSE (BMSE) and from them, we compute two indices. All were tested in a series of patients and coincide with medical conclusions. As far as we are concerned, our contribution is new.