Vigabatrina comparado con hormona adrenocorticotrópica para el tratamiento de espasmos infantiles y Síndrome de West / Vigabatrin compared with adrenocorticotropic hormone for the treatment of infantile spasms and West Syndrome

OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.

OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.

Epilepsy and Neurodevelopmental Outcomes in a Cohort of West Syndrome Beyond Two Years of Age

Objective To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS). Methods This cross-sectional study was initiated after approval from Institutional Ethics Committee. A follow-up cohort of 114 children (aged?2 y) diagnosed and treated for WS at the authors' center were assessed in-person for epilepsy and neurodevelopmental outcomes using Vineland Social Maturity Scale - Malin’s adaptation for Indian children. Subsequently, age at onset, lead-time-to-treatment, etiology, and response to any of the standard therapies were analyzed as possible predictors of these outcomes. Results Of 114 children (mean age: 55±32 mo, 91 boys), structural etiology was the predominant underlying etiology (79.8%) for WS. At 2 y of age, 64% had ongoing seizures. At the last follow-up, 76% had social quotient<55, and 39% had cerebral palsy (spastic quadriparesis in 21%). An underlying structural etiology was associated with ongoing seizures [OR (95% CI) 3.5 (1.4–9); p=0.008] at 2 y of age and poor developmental outcomes [OR (95% CI): 3.3 (1.3–8.9); p=0.016]. Complete cessation of spasms with the standard therapy was signifcantly associated with better seizure control [OR (95% CI): 5.4 (2.3–13); p<0.001] and neurodevelopmental outcome [OR (95% CI): 5.2 (1.8–14.9); p<0.001]. Conclusion The majority of children with WS have a poor neurodevelopmental outcome and epilepsy control on follow-up. The underlying etiology and response to initial standard therapy for epileptic spasms have a prognostic role in predicting the neurological outcome in these patients on follow-up.

Research progress of copy number variations associated with infantile spasms / 中华实用儿科临床杂志

Infantile spasms (ISs) is an age-dependent epileptic encephalopathy, which is highly associated with cognitive impairment, autism spectrum disorder and developmental delay.At present, inheritance patterns, including chromosomal abnormalities, copy number variations (CNVs), and monogenic diseases have been found to correlated with the etiology of ISs.Among them, CNVs or structural chromosome rearrangements are of great significance in the pathogenesis of ISs.This article aims to review the research progress of CNVs and ISs, thus providing references for further clarifying the molecular mechanism and genetic basis of ISs.

West syndrome: clinic etiological profile, and response to treatment in Western India

Background: Information on the profile of infants with West syndrome in developing countries is limited. This study was done to determine clinico-etiological profile and clinical response of infantile spasms to various medications in children with west syndrome in a developing country.Methods: It was a retrospective cohort study from January 2017-january 2020 done in a tertiary care hospital in western India. Records of 39 children with west syndrome who visited this pediatric neurology division during study period were analysed. 6 were excluded in view of incomplete data. Detailed history, examination, investigations and medications given were noted. Follow up records were assessed to look for long term control of spasms, relapse rates after cessation, or progression to other seizure types.Results: Mean age at onset of infantile spasms was found to be 8.12 months (1 - 36 months).' Mean lag time to treatment was 5.35 months. Etiology was found in 69.7% children with perinatal causes being most common. With oral prednisolone, 54.5% had complete cessation of spasms, and with ACTH also 54.5% had complete spasm cessation. Favourable clinical response at 6 months follow up was found in 8 (47.05%) of the 17 children. Surprisingly, lag time (p=0.381) and symptomatic etiology (p=1.00) did not have any significant impact on outcome.Conclusions: This study highlights the developing country perspective of west syndrome. Increased lag time, different etiological profile and poor outcome are the challenges. High dose prednisolone is a good first line alternative treatment option in resource poor settings.

A Study to Evaluate the Clinical Profile of Patients with West Syndrome

Background: West Syndrome is an epilepsy syndromecomprising the triad of infantile spasms, an interictalelectroencephalogram (EEG) pattern termed hypsarrhythmiaand neurological regression. The aim of the present study tostudy the clinical profile of patients with West Syndrome.Materials and Methods: The present study was conductedamong 100 patients at B. J. Wadia Hospital for children, atertiary care teaching hospital at Parel, Mumbai over a periodof 18-24 months. Complete history was taken. Based onetiology West syndrome was classified as symptomatic (knownetiology) or cryptogenic (unknown etiology). Following tests willbe used to find correlation between different parameters withthe above outcome – one-way ANNOVA, unpaired t- test,Mean Whitney test, chi-square test and Kruskal Wallis.Results: In the present study total number of patients studiedincluded in the study were 100.The mean age at which patientswith infantile spasms presented to our hospital was 8.9 monthswhile the age of onset of spasms were 6 months. Male: Femaleratio was 3.5:1. Etiology of West syndrome was identified in74% children (Symptomatic) and 26% remained cryptogenicand idiopathic. The etiology of infantile spasms commonestbeing birth asphyxia (HIE) ;4 patients had history of meningitisin neonatal period; 2 were diagnosed with tuberous sclerosisand 4 with some brain deformity based on neuroimaging; and 1with TORCH infection. Frequency distribution of behaviourabnormalities and other evolving seizure types (over the followup years) among the patients was less.Conclusion: Our study concluded that Symptomatic WestSyndrome was the most common type, hypoxic ischaemicencephalopathy being the commonest etiology of it.

Síndrome de Proteus y síndrome de West en lactante femenina / Proteus Syndrome and West Syndrome in female infant

Introducción: El síndrome de Proteus es un raro síndrome hamartomoso congenito con manifestaciones neuroectodérmicas, de carácter progresivo y grado de severidad variable. Objetivo: Presentar un caso clínico donde se combinan dismorfias faciales, crecimiento excesivo de una hemicara, macrocráneo y manifestaciones neurológicas. Presentación del caso: lactante de 10 meses, femenina, con antecedentes de embarazo de riesgo, hija de madre adolescente, con exposición fetal a tabaco, marihuana y alcohol; nació con macrocefalia, dismorfia facial con hemihipertrofia derecha y nevó hiperpigmentado que comenzó con espasmos infantiles desde el primer mes vida y se diagnosticó síndrome west de etiología estructural con hemimegancefalia derecha. Cumple los criterios clínicos de síndrome de Proteus y tuvo una respuesta favorable con control de los espasmos, mejoría de la hipsarritmia y del desarrollo psicomotor, con tratamiento combinado de hormona adenocorticotrópica y vigabatrina. Conclusiones: el síndrome de Proteus se caracteriza por crecimiento exagerado en varios tejidos (epidérmico, conectivo, óseo, adiposo y endotelial) durante la embriogénesis, por lo que las manifestaciones clínicas suelen ser evidentes desde el nacimiento o en los primeros años de vida, se relaciona con un grupo de casos con malformaciones del sistema nervioso central y síndrome de West(AU)

Introduction: Proteus syndrome is a rare congenital hamartoma syndrome with neuroectodermal manifestations of progressive kind and a degree of variable severity. Objective: To present a clinical case where facial diysmorphias, the excessive growth of a hemicara, a macro-skull, and neurological manifestations are combined. Case presentation: A 10-month-old female infant with a history of risky pregnancy, daughter of a teenage mother, with fetal exposure to tobacco, marijuana and alcohol. She was born with macrocephaly, facial dysmorphia with right hemihypertrophy, hyperpigmented nevus that started with infantile spasms from the first month of life; and West syndrome of structural etiology with right hemimegalencephaly was diagnosed. The patient meets the clinical criteria of Proteus syndrome and she had a favorable response to the combined treatment of adrenocorticotropic hormone and Vigabatrin with control of spasms, improvement of hypsarrhythmia and psychomotor development. Conclusions: Proteus syndrome is characterized by exaggerated growth in various tissues (epidermal, connective, bone, adipose and endothelial) during embryogenesis, so that clinical manifestations are usually evident from birth or in the first years of life. It is related with a group of cases with malformations of the central nervous system and West syndrome(AU)

Efectos Adversos del Tratamiento con Vigabatrina en Síndrome de West: reporte de 2 casos / Adverse Effects of Vigabatrin Use for West Syndrome treatment: a report of 2 Clinical Cases

El síndrome de West (SW) es un síndrome epiléptico de la infancia temprana. Dentro de los fármacos de primera línea utilizados para su tratamiento se encuentran la hormona adrenocorticotropa (ACTH) y Vigabatrina. Estudios sugieren igual efectividad en el uso a largo plazo de ambos para controlar el SW. En Chile, el uso de Vigabatrina ha aumentado dada su mayor disponibilidad, facilidad de uso y menor costo. Se describen 2 casos clínicos presentando complicaciones agudas infrecuentes secundarias a su uso. Ambos pacientes con antecedentes de SW y trisomía 21. Primer caso: Lactante de 11 meses que inicia tratamiento con 100 mg/kg/día de Vigabatrina a los 7 meses, aumentando a 150 mg/kg/día por mala respuesta. Evolucionó con un síndrome extrapiramidal, con alteraciones radiológicas características. Segundo caso: Lactante de 7 meses, que tras iniciar tratamiento con vigabatrina (100 mg/kg/día) desarrolla rash facial sugerente de hipersensibilidad a fármacos antiepilépticos (FAEs), sin compromiso mucoso ni alteraciones sistémicas. Ambas regresan a su basal luego de suspensión o disminución de dosis del medicamento. Destaca la importancia de la monitorización de efectos adversos en el uso de FAEs y atender la aparición de reacciones poco conocidas. Las alteraciones imagenológicas por Vigabatrina son conocidas, no así el síndrome extrapiramidal asociado (primer caso). Por otra parte, las reacciones cutáneas están ampliamente descritas para múltiples FAEs, pero no para Vigabatrina (segundo caso). Dado el uso frecuente de Vigabatrina para tratar SW y otras epilepsias, es fundamental conocer y manejar reacciones adversas poco conocidas como las aquí presentadas. Palabras claves: Síndrome de West, Síndrome de Down, espasmos infantiles, vigabatrina, reacciones adversas, toxicidad, alergia, rash.

West Syndrome is an epileptic syndrome which typically presents in early childhood. In regard to treatment, the first line includes adrenocorticotropic hormone (ACTH) and Vigabatrin. Studies suggest similar response in the long term to both treatments. In Chile, Vigabatrin is being used more frequently as it is more available, of easier administration and lower cost. We present in the following report 2 clinical cases that presented acute infrequent complications secondary to its use in patients with both Down and West Syndrome. First case: 11-month-old infant who was initially treated with 100mg/kg/day of Vigabatrin at 7 months of age and increased to 150mg/kg/day due to lack of response. She evolved with an extrapyramidal syndrome with radiological manifestations. The second case: 7-month old toddler who initiated treatment with 100mg/kg/day of Vigabatrin and developed a facial rash, suggestive of hypersensitivity to antiepileptic drugs, with no mucosal or systemic involvement. Both patients returned to their previous condition shortly after Vigabatrin was decreased or discontinued. We emphasize the importance of the early monitorization of adverse effects in the use of antiepileptic drugs and awareness of less common reactions. Radiological findings associated with the use of Vigabatrin are well known, but not the clinical evolution with symptomatic extrapyramidal symptoms, as in the first case. Allergic reactions to the use of antiepileptic drugs have also been reported to several drugs, but not to Vigabatrin (second case). As Vigabatrin is being used more frequently to treat WS and other epilepsies it is important to know and manage uncommon adverse reactions as the ones presented in this report. Keywords: West Syndrome, Down Syndrome, infantile spasms, vigabatrin, adverse reactions, toxicity, allergy, rash

Lennox-Gastaut Syndrome in Mitochondrial Disease

PURPOSE: Previous studies have shown that neurologic symptoms are dominant in patients with mitochondrial diseases, and most of these patients have seizure-related disorders. The epileptic classification of these patients as Lennox-Gastaut syndrome (LGS) is as high as 25%. This study aimed to investigate the clinical manifestations, diagnoses, treatments, and epilepsy in LGS, which is associated with mitochondrial disease. MATERIALS AND METHODS: A retrospective study was conducted on 372 patients who were diagnosed with mitochondrial disease between 2006 and 2016. Of these 372 patients, 40 patients diagnosed with LGS were selected, and they were classified into two groups based on the history of West syndrome. Patient characteristics were reviewed, and associations between clinical factors and outcomes after the treatment were analyzed. RESULTS: The proportion of individuals with mitochondrial disease with LGS with a history of West syndrome was 32.5%. Among the patients with mitochondrial disease with LGS, neonatal seizure (p=0.029), seizure as the first symptom (p=0.018), and generalized paroxysmal fast activity frequency on electroencephalogram (p=0.018) in the group with a history of West syndrome were statistically significantly high. The first symptom onset (0.6±0.4 yrs vs. 1.6±0.9 yrs, p=0.003) and first seizure onset (0.9±0.7 yrs vs. 3.9±3.1 yrs, p < 0.001) were significantly faster in patients with a history of West syndrome. CONCLUSION: Close monitoring of the medical condition and early intervention might improve the prognosis of individuals with mitochondrial disease with LGS and a history of West syndrome.

Síndrome transicional: del síndrome de West al síndrome de Lennox-Gastaut / Transional syndrome: from West to Lennox-Gastaut syndromes

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.

Incontinencia pigmenti y manifestaciones neurológicas / Incontinentia pigmenti and neurological manifestations

Introducción: la incontinencia pigmenti es una genodermatosis rara ligada al cromosoma X, afecta al sexo femenino y tiene diferentes expresiones clínicas en una misma familia. Presentación del caso: preescolar de 20 meses de edad, con antecedente familiar de incontinencia pigmenti, que presentó lesiones típicas en la piel desde la primera semana de vida, de aspectos lineales, vesículo-costro-ampollosas, verrucosas, y luego hiperpigmentadas, en diferentes fases y múltiples brotes. Comienza desde el primer mes de vida con crisis epilépticas que evoluciona a una encefalopatía de West, con buena respuesta a la vigabatrina y control de los espasmos infantiles. Conclusiones: la incontinencia pigmenti se caracteriza por afectar, de forma variable, a los tejidos derivados del neuroectodermo, la piel y otras faneras, ojos y el sistema nervioso central, provoca daño multisistémico. Las lesiones de la piel son las más significativas desde el nacimiento, y la biopsia de piel confirma el diagnóstico(AU)

Introduction: incontinentia pigmenti is a rare genodermatosis linked to the X chromosome. It affects the female sex and has different clinical manifestations in the same family. Case presentation: a 20-month-old infant with a family history of incontinentia pigmenti, who from the first week of life presented typical lesions on the skin of linear, vesicular-crust-bullous, warty, and then hyperpigmented aspects, in different phases and multiple outbreaks. From the first month of life, the patient presented epileptic seizures that evolved to West encephalopathy, with good response to vigabatrin and control of infantile spasms. Conclusions: incontinentia pigmenti is characterized by affecting, in a variable way, the tissues derived from the neuroectoderm, the skin and other skin´s structures, the eyes and the central nervous system causing multisystem damage. Skin lesions are the most significant since birth, and skin biopsy confirms the diagnosis(AU)

Age-Based Characteristics of West Syndrome in Patients with Mitochondrial Disease / 대한소아신경학회지

PURPOSE: West syndrome is a severe form of age-specific epilepsy that typically affects infants younger than 2 years of age with mitochondrial disease. We aimed to examine age-specific characteristics of the syndrome in these patients. METHODS: We retrospectively analyzed 54 patients with West syndrome diagnosed with mitochondrial disease between March 2006 and March 2016. We compared treatment strategies and diagnostic and clinical variables between patients with early-onset ( < 6 months of age) and late-onset (≥6 months of age) seizures. RESULTS: Seizure was the first symptom in 30 (90.9%) and 13 (65%) patients of the early-onset and late-onset groups, respectively (P=0.046). Delayed development was observed in 3 (9.1%) and 7 (35%) patients of the early-onset and late-onset groups, respectively (P=0.023). Lactate levels were normal in 17 patients (55%) of the early-onset group and 5 (25%) of the late-onset group (P=0.036), while initial brain magnetic resonance imaging (MRI) findings were normal in 23 (67.6%) and 8 (40%) patients of the early-onset and late-onset groups, respectively. Final MRI findings were abnormal in 32 patients (94.1%) of the early-onset group and 18 (90%) of the late-onset group (P=0.036). Although ketogenic diets reduced seizure frequency in both groups, the difference was not significant. CONCLUSION: There is no significant difference in epilepsy-related variables when patients are divided based on a cut-off age of 6 months. However, differences in the first symptom at onset and MRI findings were observed. Although lactate levels were not of significant diagnostic value in the early-onset group, they may be in the late-onset group.

Hipoplasia pontocerebelosa secundaria a deleción en el gen CASK: Caso clínico / Pontocerebellar hypoplasia secondary to CASK gene deletion: Case report

Introducción: La hipoplasia pontocerebelosa (HPC) es la reducción del tamaño del cerebelo y la protuberancia secundaria a una alteración en su desarrollo, pudiendo ser provocado por enfermedades neurodegenerativas de causa genética, de las que se conocen 10 subtipos (PCH 1-10), malformaciones corticales, enfermedades metabólicas y enfermedades genéticas. Objetivo: Presentar el caso de una niña con microcefalia, HPC y Síndrome de West, en que el estudio genético permitió llegar al diagnóstico de una deleción en el cromosoma X. Caso clínico: Lactante de 7 meses al diagnóstico, sin antecedentes familiares ni obstétricos de interés, perímetro cefálico (PC) al nacimiento en -1.5 desviaciones estándar (DE). Evolucionó con escasa progresión ponderal y estancamiento del crecimiento del PC, retraso del desarrollo psicomotor, caracterizado por ausencia de fijación de la mirada e hipotonía con reflejos osteotendinosos conservados, y epilepsia refractaria. En los potenciales evocados auditivos se demostró compromiso de las vías pontomesencefálicas y en las neuroimágenes HPC. El estudio genético Array de Hibridación Genómica Comparada (aCGH) demostró deleción parcial heterocigota en el cromosoma X, afectando al gen CASK. Conclusiones: Ante el amplio diagnóstico diferencial que plantea las HPC, las nuevas técnicas citogenéticas han permitido mejorar la clasificación y en algunos casos establecer su etiología, pudiendo ofrecer en estos casos un adecuado asesoramiento genético a las familias.

Introduction: Pontocerebellar hypoplasia (PCH) is a reduction of the size of the cerebellum and pons secondary to an alteration in its development, and can be caused by neurodegenerative diseases of genetic origin, of which there are known 10 subtypes (PCH 1-10), cortical malformations, metabolic and genetic diseases. Objective: To present the case of a child with microcephaly, PCH and West syndrome, in which the genetic study allowed to make the diagnosis of a deletion on chromosome X. Case report: This is a female infant of 7-month at diagnosis, without family or obstetric history of interest, head circumference at birth -1.5 standard deviations (SD). She had little weight and growth in head circumference progression. In addition, physical examination revealed no fixating gaze, hypotonia with preserved deep tendon reflexes. Progressively developed refractary seizures. Brainsteam Auditory Evoked Potential demonstrated involvement of pontomesencefphalic ways and neuroimaging Pontocerebellar hypoplasia. The genetic study (aCGH) showed heterozygous deletion on the X chromosome, affecting the CASK gene. Conclusions: Given the wide differential diagnosis proposed at the PCH, new cytogenetic techniques have improved the classification of HPC and in some cases establish their etiology, so in these cases can provide appropriate genetic counseling to families.

Oral findings in West syndrome ­ A Case Report / Achados bucais na síndrome de West- Relato de um caso

West syndrome is a severe form of epilepsy syndrome which is characterized by a triad of infantile spasms, characteristic EEG findings (Hypsarrhythmia) and developmental delay. Minimal literature is available on dental findings of West syndrome. This case report presents an eight year old male child with cryptogenic form of West syndrome having a history of multiple clusters of infantile spasms. Orodental manifestations of west syndrome have been described and its dental management has been discussed in this report. (AU)

A síndrome de West é uma forma severa da síndrome de epilepsia que é caracterizada pela tríade de espasmos infantil, achados EEG (hipsarritimia) e atraso no desenvolvimento. A literatura disponível é escassa a respeito dos achados dentais e manejo da síndrome de West. Este caso relata uma criança de 8 anos de idade, masculino com a forma criptogênica da síndrome de West com história de múltiplos episódios de espasmos infantis e achados dentais típicos. O tratamento odontológico do caso é discutido e mediadas preventivas e tratamento da síndrome de West é descrito. (AU)

Clinical features and gene mutations analysis in 62 children with early - onset epileptic encephalopathy of un-known causes / 中华实用儿科临床杂志

Objective To study the clinical features and gene mutations of early - onset epileptic encephalo-pathy(EOEE)of unknown causes and to identify pathogenic mutations of EOEE by next generation sequencing. Methods The clinical data of 62 cases diagnosed with unexplained EOEE between June 2013 and June 2015 were ob-tained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy - related genes,and Sanger sequencing was performed to verify the results and confirm the source of the parents,further to identify suspected pathogenic mutations of EOEE. Results Among 62 cases with unex-plained EOEE,37 cases(61% )were diagnosed as non - specific EOEE,17 cases(27% )with West syndrome,6 ca-ses(10% )with Dravet syndrome,1 case(1% )with Ohtahara syndrome,1 case(1% )with early myoclonic epileptic encephalopathy. The pathogenic mutations were not detected among 17 cases with West syndrome and the early myoclonic epileptic encephalopathy. Among 37 cases with non - specific EOEE,suspected pathogenic mutations were detected in 7 cases. Three cases of missense mutations for PCDH19 gene,1 case of frame - shift mutation and 1 case of splice site mutation for CDKL5 gene,1 case of denovo nonsense mutation for KCNQ2 gene,and 1 case of missense muta-tion for GRIN2A gene were detected. Among 6 children with Dravet syndrome,2 cases of frame - shift mutations and 1 case of missense mutation for SCN1A gene were detected,of which 2 cases were of frame - shift mutations,1 case was denovo mutation,1 case of missense mutation for SCN1A gene and 1 case of missense mutation for SCN1A combined with SCN9A gene were detected. One case of denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 cases with clinical seizures were under control,and 40 cases were out of control. Conclusions The clinical pheno-types for children with unexplained EOEE were varied. SCN1A,SCN9A,STXBP1,PCDH19,CDKL5,KCNQ2 and GRIN2A genes detected in China are in accordance with those reported internationally and some gene sites are denovo mutations which have not been reported. The SCN9A gene may be the new pathogenic mutation for Dravet syndrome. And the KCNQ2 gene nonsense mutation may be the lethal mutation.

Perinatal brain lesions and epilepsy: prematurity and cerebral hypoxia evolving with west syndrome / Lesões cerebrais perinatais e epilepsia: prematuridade e hipóxia cerebral evoluindo com Síndrome de West / Lesiones cerebrales perinatales y epilepsia: prematuridad e hipoxia cerebral evolucionando con Síndrome de West

Introduction: West syndrome (WS) is the most frequent epileptic encephalopathy in the first year of life and is strongly correlated with prenatal and perinatal brain injury. Objective: To analyze the relationship between prematurity and birth asphyxia (cerebral hypoxia) with WS. Methods: This is an observational and cross-sectional study. All the patients with WS treated at Pediatric Neurology Service of Pequeno Príncipe Children?s Hospital from January 2010 to January 2015 were analyzed. The patients underwent magnetic resonance imaging (MRI) of the brain and electroen- cephalogram (EEG). Results: Thirty-eight patients with WS, 23 (60.53%) females; ages ranging from 9 to 27 months (±16.6 months). Twenty (52.63%) patients had a history of hypoxia/anoxia perinatal, 8 (21.05%) were premature, 8 (21.05%) had brain malformations, 4 (10.53%) had Down syndrome, 4 (10.53%) had tuberous sclerosis, and 2 (5.26%) had no comorbidities. MRI showed: 9 (23.68%) multi-cystic encephalomalacia, 4 (10.53%) periventricular leukomalacia, 4 (10.53%) periventricular leukomalacia with cerebral atrophy, 4 (10.53%) periventricular nodules, 3 (7.89%) brain atrophy, 2 (5.26%) pachygyria associated with agenesis of corpus callosum, one (2.63%) agenesis of the corpus callosum, one (2.63%) right frontal dysplasia, one (2.63%) left frontal dysplasia, one (2.63%) right frontoparietal dysplasia, one (2.63%) left frontoparietal dysplasia, and one (2.63%) pachygyria. Conclusion: The history of hypoxia/anoxia perinatal and prematurity is very frequent in WS. Improved care during pregnancy and childbirth is very important to reduce perinatal brain injury, premature birth, and neurological morbidity.

Introdução: A síndrome de West (SW) é a mais frequente encefalopatia epiléptica do primeiro ano de vida e está fortemente relacionada com lesões cerebrais pré-natais e perinatais. Objetivo: Analisar a relação entre prematuridade e asfixia perinatal (hipóxia cerebral) e SW. Métodos: Este é um estudo observacional e transversal. Todos os pacientes com SW tratados no Serviço de Neurologia Pediátrica do Hospital Infantil Pequeno Príncipe entre janeiro de 2010 e janeiro de 2015 foram analisados. Os pacientes foram submetidos a ressonância magnética (RM) do encéfalo e eletroencefalograma (EEG). Resultados: Trinta e oito pacientes com SW, 23 (60,53%) do sexo feminino; idade entre 9 a 27 meses (±16,6 meses). Vinte (52,63%) pacientes tinham história de hipóxia/anóxia perinatal, 8 (21,05%) eram prematuros, 8 (21,05%) tinham malformações cerebrais, 4 (10,53%) tinham síndrome de Down, 4 (10,53%) tinham esclerose tuberosa e 2 (5,26%) não apresentavam nenhuma comorbidade. A RM mostrou: 9 (23,68%) casos de encefalomalácia multicística, 4 (10,53%) leucomalácia periventricular, 4 (10,53%) leucomalácia periventricular com atrofia cerebral, 4 (10,53%) nódulos periventriculares, 3 (7,89%) atrofia cerebral, 2 (5,26%) paquigiria associada à atrofia de corpo caloso, um (2,63%) agenesia de corpo caloso, um (2,63%) displasia frontal direita, um (2,63%) displasia frontal esquerda, um (2,63%) displasia frontoparietal direita, um (2,63%) displasia frontoparietal esquerda e um (2,63%) paquigiria. Conclusão: A história de hipóxia/anóxia perinatal e prematuridade é muito frequente na SW. A melhora dos cuidados durante a gestação e o parto é muito importante para reduzir lesões cerebrais perinatais, nascimentos prematuros e consequentemente, a morbidade neurológica.

Introducción: El síndrome de West (SW) es la más frecuente encefalopatía epiléptica del primer año de vida y está fuertemente relacionado con lesiones cerebrales prenatales y perinatales. Objetivo: Analizar la relación entre prematuridad y asfixia perinatal (hipoxia cerebral) y SW. Métodos: Este es un estudio observacional y transversal. Fueron analizados todos los pacientes con SW tratados en el Servicio de Neurología Pediátrica del Hospital Infantil Pequeno Príncipe entre enero de 2010 y enero de 2015. Los pacientes fueron sometidos a resonancia magnética (RM) del encéfalo y electroence- falograma (EEG). Resultados: Treinta y ocho pacientes con SW, 23 (60,53%) del sexo femenino; edad entre 9 a 27 meses (±16,6 meses). Veinte (52,63%) pacientes tenían historia de hipoxia/anoxia perinatal, 8 (21,05%) eran prematuros, 8 (21,05%) tenían malformaciones cerebrales, 4 (10,53%) tenían síndrome de Down, 4 (10,53%) tenían esclerosis tuberosa y 2 (5,26%) no presentaban ninguna comorbilidad. La RM mostró: 9 (23,68%) casos de encefalomalacia multiquística, 4 (10,53%) con leucomalacia periventricular, 4 (10,53%) con leucomalacia periventricular con atrofia cerebral, 4 (10,53%) con nódulos periventriculares, 3 (7,89%) con atrofia cerebral, 2 (5,26%) con paquigiria asociada a la atrofia de cuerpo calloso, uno (2,63%) con agenesia de cuerpo calloso, uno (2,63%) con displasia frontal derecha, uno (2,63%) con displasia frontal izquierda, uno (2,63%) con displasia frontoparietal derecha, uno (2,63%) con displasia frontoparietal izquierda y uno (2,63%) con paquigiria. Conclusión: La historia de hipoxia/anoxia perinatal y prematuridad es muy frecuente en SW. La mejora de los cuidados durante la gestación y el parto es muy importante para reducir lesiones cerebrales perinatales, nacimientos prematuros y consiguientemente, la morbilidad neurológica.

Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice / Desenvolvimentos recentes na genética das encefalopatias epilépticas da infância: impacto na prática clínica

Recent advances in molecular genetics led to the discovery of several genes for childhood epileptic encephalopathies (CEEs). As the knowledge about the genes associated with this group of disorders develops, it becomes evident that CEEs present a number of specific genetic characteristics, which will influence the use of molecular testing for clinical purposes. Among these, there are the presence of marked genetic heterogeneity and the high frequency of de novo mutations. Therefore, the main objectives of this review paper are to present and discuss current knowledge regarding i) new genetic findings in CEEs, ii) phenotype-genotype correlations in different forms of CEEs; and, most importantly, iii) the impact of these new findings in clinical practice. Accompanying this text we have included a comprehensive table, containing the list of genes currently known to be involved in the etiology of CEEs.

Os avanços recentes em genética molecular permitiram a descoberta de vários genes para encefalopatias epilépticas da infância (EEIs). À medida que o conhecimento sobre os genes associados a este grupo de doenças se desenvolve, torna-se evidente que as EEIs apresentam uma série de características genéticas específicas, o que influencia o uso do teste molecular para fins clínicos. Entre as EEIs, há a presença de acentuada heterogeneidade genética e alta frequência de mutações de novo. Assim, os principais objetivos deste trabalho de revisão são apresentar e discutir o conhecimento atual a respeito de i) novas descobertas em genética molecular das EEIs, ii) correlações fenótipo-genótipo nas diferentes formas de EEIs; e, mais importante, iii) o impacto desses novos achados genéticos na prática clínica. Acompanhando o texto, incluímos uma tabela contendo a lista de genes conhecidos atualmente como envolvidos na etiologia da EEIs.

El electroencefalograma en el síndrome de West y otras entidades clínicas relacionadas / Electroencephalogram in the West syndrome and other related clinical entities

Se realiza una revisión de las características electroencefalográficas de los espasmos infantiles, espasmos epilépticos o síndrome de West, y otras entidades relacionadas con este. Se enfatiza en los patrones más frecuentes, fundamentalmente en los 2 tipos de hipsarritmia: clásica y periódica o fragmentada, observados en el síndrome anteriormente mencionado. Se comenta en relación con el trazado de suppression-burst o paroxismos-supresión, y su correlación con los síndromes de Ohtahara, y Aicardi y Goutières, descritos respectivamente en 1976 y 1978. Se aclara que estos 2 patrones no son exclusivos de estos síndromes, y pueden ser observados en otras entidades en el neonato, como la encefalopatía anóxica isquémica, la meningitis neonatal bacteriana y trastornos metabólicos, entre otros.

A review was made on the encephalographic characteristics of infantile spasms, epileptic spasms, or West syndrome, and other related entities. Emphasis was made on the most frequent patterns, mainly the two types of hypsarrhythmia, classical and periodic, and fragmented, which are observed in this syndrome. Likewise, comments were made on the suppression-burst or burst-suppression tracing and its correlation with Ohtahara, and Aicardi and Goutières syndromes that were described in 1976 and 1978, respectively. It was clarified that these two patterns are not exclusive of these syndromes and may be also observed in other illnesses affecting the neonates such as anoxic-ischemic encephalopathy, neonatal bacterial meningitis and metabolic disorders, among others.

Síndrome de West,experiencia con una serie de casos con acceso al tratamiento de primera línea, en Lima / West Syndrome, experience in a case series with access to first line medication, in Lima

Objetivos: Describirlas características clínicas de una serie de pacientes con Síndrome de West(SW) con acceso a la medicación de primera línea. Material y métodos: Estudio retrospectivo observacional, de niños con SW que fueron atendidos entre 1996 y2014. Resultados: Se incluyeron 37 casos, con una promedio de inicio de espasmos de 6,4 meses, con predominio del sexo masculino (75,7%), la mayoría procedentes de Lima. La etiología más frecuente fue secundaria (83,8%),como prenatales, malformaciones cerebrales, Esclerosis Tuberosa, Síndrome de Down y causas perinatales. El SW fue controlado en 67,6% de los casos; Vigabatrina o ACTH fueron efectivas en 20/32 (62,5%). Dos pacientes fueron controlados con levetiracetam, uno con topiramato, uno con lamotrigina, y uno con cirugía. El patrón electroencefalográfico de hipsarritmia fue predominante 24/37 (64,9%). La comorbilidad neurológica fue muy frecuente (97.3%) y fue degrado leve sólo en 7/37 (18,9%). Dos pacientes fallecieron. Conclusiones: En esta serie el SW fue de causa secundaria y se controló eficientemente con vigabatrina o ACTH, por tanto, se recomienda incluir estos medicamentos en el petitorio nacional.

Objectives: To describe the clinical characteristics of a seriesof patients with West Syndrome (WS) with access to first line medication. Material and Methods: Retrospective observational study of children treated between 1996 and 2014. Results: 37 cases were included, with an average starting age of 6.4 months, predominantly males (75.7%), the majority was from Lima. The most common etiology was secondary (83.8%), as prenatal, brain malformations, Tuberous Sclerosis, Down syndrome and perinatal causes. The WS was controlled in 67.6% of the cases; Vigabatrinand ACTH were effective in 20/32 (62.5%). Two patients were controlled with Levetiracetam, one with Topitamate, one with Lamotrigine and one with surgery. Hypsarrhythmia was the predominant electroencephalographic pattern 23/37 (64.9%). Neurologic comorbidities were very frequent (97.3%) and they were mild only in 7/37 (18.9%). Two patients passed away. Conclusions: In this series, the WS had a secondary cause and was efficiently controlled with Vigabatrin or ACTH, therefore, we recommend their inclusion in the national request.

The application of the sample entropy evaluation for the ketogenic diet in infantile spasms / 中华实用儿科临床杂志

Objective To evaluate clinical efficacy and electroencephalogram(EEG)changes quantitatively after the ketogenic diet (KD) by single sample entropy (SampEn) in the treatment of infantile spasms (IS),and to learn the quantitative relationship between the clinical efficacy and EEG.Methods Patients diagnosed as IS were enrolled and started KD in Shenzhen Children's Hospital from April 2010 to December 2013.The SampEn of EEG data in these patients before and after treatment with KD were analyzed.Patients were classified as seizure-free group and non-seizure-free group according to the therapeutic responsiveness to KD.The SampEn findings from two groups were compared to explore the effect of KD on EEG and its related factors.Results Among 35 patients,more than 2 months of treatment,10 cases were seizure free,25 cases still had seizures.SampEn was 0.377 ± 0.246 before treatment,and 0.725 ± 0.405 after treatment in all patients,there was significant difference (Z =-4.351,P =0.000).SampEn was 0.342 ± 0.277 before treatment,and 0.929 ± 0.379 after treatment in seizure free group,there was significant difference between 2 groups(Z =-3.371,P =0.001).While SampEn was 0.391 ± 0.237 before treatment,and 0.643 ± 0.393 after treatment in non-seizure free group,there was a significant difference between 2 groups(Z =-3.371,P =0.001).The mental and motor development was improved after KD with improvement rate were 56％ (14/25 cases) and 70％ (7/10 cases),respectively,but there was no statistical difference(P =0.704).Conclusions No matter seizures are controlled or not,KD can increase the complexity of electrical activity in the brain,which was more obvious in the seizure-free group.Intellectual and movement development can be improved in patients with KD.

Impacto del Síndrome de West en pacientes del Hospital del Niño Manuel Ascencio Villarroel / Impact of West Syndrome in Patients from Manuel Ascencio Villarroel's Children Hospital

El síndrome de West es una encefalopatía epiléptica pediátrica dependiente de la edad caracterizada por la tríada clásica de: espasmos epilépticos, patrón hipsarrítmico y retraso mental. Se inicia en la mayoría de los pacientes durante el 1er año de vida, con una incidencia entre los 3 y 12 meses de edad. Presenta varias etiologías: criptogénica, idiopática y sintomática. El objetivo de la investigación es describir la presentación clínica del Síndrome de West en nuestro medio, el diagnóstico y el tratamiento empleado. El estudio realizado es de tipo observacional y de corte transversal. El universo comprende 377 pacientes menores de 2 años con Epilepsia que acudieron al consultorio de Neurología Pediátrica del Hospital del Niño Manuel Ascencio Villarroel del Complejo Hospitalario Viedma de Cochabamba-Bolivia, del 1ero de enero de 2010 a 31 de diciembre de 2013. La Muestra son los 12 pacientes que fueron diagnosticados con Síndrome de West. En los resultados se destaca: que los 12 pacientes cumplían con la triada clásica de la enfermedad, siendo el 100% sintomático, correspondiendo al género femenino 8 y 4 al masculino. La edad en la que se hizo el diagnóstico con mayor frecuencia fue de 9 a 12 meses. Se realizó una evaluación de los antecedentes perinatales y neonatales entre los que se destacan: 5 casos con embarazo pre término y 6 casos con asfixia perinatal. Se realizaron pruebas diagnósticas complementarias con: tomografía axial computarizada y electroencefalograma. Se concluye que la presentación clínica del Síndrome de West en nuestro medio es sintomática en los 12 casos encontrados, el diagnostico se basó en la clínica y exámenes complementarios. El tratamiento principalmente empleado es el ácido valproico, debido a que la Hormona Adenocorticotrópica no está disponible en nuestro país.

West syndrome is a pediatric epileptic encephalopathy dependent on age characterized by the classic triad of epileptic spasms and mental retardation hypsarrhythmic pattern. It begins in most patients during the 1 st year of life, with an incidence between 3 and 12 months of age. Presents various etiologies: cryptogenic, idiopathic and symptomatic. The aim of the research is to describe the clinical presentation of West syndrome the diagnosis and treatment used. The study is descriptive and cross-sectional.The universe comprises 377 patients younger than 2 years with epilepsy who attended the clinic of Pediatric Neurology Children's Hospital Manuel AscencioVillarroelViedma Hospital in Cochabamba, Bolivia, January 1, 2010 to December 31,2013. The shows are the 12 patients who were diagnosed with West syndrome. In the results emerged: the 12 patients met the classic triad of the disease, with 100% symptomatic, corresponding to 8 and 4 female to male. The age at which the diagnosis is most often made was 9 to 12 months. 5 cases with preterm pregnancy and 6 cases with perinatal asphyxia:evaluation of prenatal and neonatal history including highlights was performed. Computed tomography and electroencephalogram: Additional diagnostic tests were performed. It is concluded that the clinical presentation of West syndrome in our country is symptomatic in 12 cases found, the diagnosis was based on clinical and complementary examinations. Treatment is mainly used valproic acid because the adrenocorticotropic hormone is not available in our country.