A Retrospective Cohort Study of Combined Therapy in West Syndrome associated with Trisomy 21.

Background: West syndrome (WS) is a frequent epileptic encephalopathy associated with Down syndrome (DS). This study evaluated an outpatient protocol for WS in patients with DS who received vigabatrin (VGB) or VGB plus adrenocorticotrophic hormone. Methods: We analyzed infants treated in two neuropediatric centers from 2001-2021. We reviewed perinatal and familial history of epilepsy, spasm onset, treatment lag, electroencephalogram, neuroimaging, progression to epilepsy, and other neurological conditions. The outcomes were electroclinical resolution (ECR), relapses, and epilepsy progression. Results: Nineteen infants were included; 57.8% were male. The average spasm onset, follow-up, and treatment lag were 6.4 months, 8.15 years, and 2.33 months, respectively. Almost 74% had ECR after protocol intervention and minor epilepsy progression. Relapses occurred during combined therapy. Conclusions: The treatment protocol, especially combined therapy, was effective for WS in DS, impacting epilepsy progression and indicating the effectiveness of combined therapy to treat WS in patients with trisomy 21.

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.

Third case of Duchenne muscular dystrophy and West syndrome: Expanding the spectrum of the DMD neuropsychiatric phenotype.

Duchenne muscular dystrophy is an X-Linked neuromuscular disorder, and the most common muscular dystrophy. Neuropsychiatric phenotype associated to DMD gene mutations include now low IQ scores, epilepsy, autism, and attention deficit disorder. These have been observed with higher frequency in mutations that disrupt the short isoforms Dp71 and Dp140. West syndrome has been previously reported in two unrelated patients with Duchenne muscular dystrophy. Here, we report the third patient with West syndrome who had a novel hemizygous nonsense pathogenic variant in the exon 8 of the DMD gene c.811C>T, p.(Gln271*), suggesting West syndrome as part of the neuropsychiatric spectrum in Duchenne muscular dystrophy.

West syndrome: A study of 26 patients receiving short-term therapy.

OBJECTIVE: We describe the electroclinical characteristics of a series of 26 patients with idiopathic West syndrome (WS), who had an excellent response to treatment with vigabatrin (VGB) and corticosteroids alone or in combination. METHODS: Evaluating the records of 178 patients with WS studied at Garrahan Hospital, Niño Jesús Hospital, and Clínica San Lucas between January 2005 and June 2017, we selected 26 patients that met the inclusion criteria of idiopathic WS. The inclusion criteria for idiopathic WS were (1) no personal history of disease, (2) normal neurological examination and neurodevelopment, (3) symmetric spasms in clusters not preceded by any other type of seizure, (d) symmetric hypsarrhythmia, (e) normal electroencephalogram (EEG) background, e.g., normal sleep EEG pattern, (f) normal magnetic resonance imaging (MRI) recording, (g) normal neurometabolic and genetic studies, and (h) at least 2 years of follow-up. RESULTS: Fifteen boys and 11 girls met the inclusion criteria of idiopathic WS. The current age of the children ranges between 2 years 10 months and 12 years 10 months. Age at first epileptic spasms (ES) ranged from 4 to 11 months, with a mean age of 7 and a median of 7.5 months, respectively; ES were in clusters, bilateral and symmetrical in all cases. Spasms were flexor in nine (34.7%), mixed flexor-extensor in 15 (57.7%), and extensor in three (7.6%). In all patients the EEG showed typical pattern of hypsarrhythmia. CONCLUSION: These patients with idiopathic WS who have an excellent response to initial treatment should be treated for a short period of time with adrenocorticotropic hormone (ACTH) and VGB alone or in combination.

Neurological Development, Epilepsy, and the Pharmacotherapy Approach in Children with Congenital Zika Syndrome: Results from a Two-Year Follow-up Study.

Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant drugs, which in the long term are related to impairments in the child's neuropsychomotor development. Here, we describe the results from a two-year follow-up of a cohort of children diagnosed with CZS related to the growth of the head circumference and some neurological and motor outcomes, including the pharmacological approach, and its results in the treatment of epileptic seizures. This paper is part of a prospective cohort study carried out in the state of Mato Grosso Sul, Brazil, based on a Zika virus (ZIKV)-exposed child population. Our data were focused on the assessment of head circumference growth and some neurological and motor findings, including the description of seizure conditions and pharmacological management in two periods. Among the 11 children evaluated, 8 had severe microcephaly associated with motor impairment and/or epilepsy. Seven children were diagnosed with epilepsy. Of these, 3 had West syndrome. In four children with other forms of epilepsy, there was no pharmacological control.

Electroclinical pattern in the transition from West to Lennox-Gastaut syndrome.

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.

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

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

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.

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)

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)

Recognition of Infantile Spasms Is Often Delayed: The ASSIST Study.

OBJECTIVES: To characterize and quantify diagnostic and treatment delay among children with infantile spasms, and to estimate the developmental impact of this delay. STUDY DESIGN: In this cohort study, we surveyed the parents of 100 patients with infantile spasms about their experiences with diagnosis and treatment, and ascertained medical and sociodemographic factors potentially related to care of these infants. We specifically determined the latency to first visit an "effective provider," defined as a provider who identified infantile spasms, and prescribed an appropriate first-line treatment, namely adrenocorticotropic hormone, corticosteroids, or vigabatrin. Time to the first visit to an effective provider was evaluated using Cox proportional hazards regression. RESULTS: The median time from the onset of infantile spasms to first visit with an effective provider was 24.5 days. Only 29% of patients were evaluated by an effective provider within 1 week of infantile spasms onset. The time to first effective provider visit was associated with parental language preference, but with no other sociodemographic characteristics. Parents' suspicions that "something is wrong" were often discounted by healthcare providers, and survey respondents frequently reported that pediatricians and neurologists were unfamiliar with infantile spasms. CONCLUSION: This study demonstrates that substantial delay (ie, >1 week) in appropriate care is common, and suggests that the poor awareness of infantile spasms among healthcare providers is at least partly responsible for preventable and potentially significant delays in treatment.

Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone.

Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.

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)

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.

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(AU)

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 GoutiÞres 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(AU)

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.