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.

Neonatal seizures; types, etiology and long term neurodevelopmental outcome at a tertiary care hospital

To study the types, etiology and long term neurodevelopmental outcome in neonates with seizures.A descriptive cross-sectional study. PNS Shifa Naval hospital Karachi from Jan 2011 to Feb 2014.Population: Ninety six neonates of either gender presented with seizures at NICU PNS Shifa Naval hospital Karachi were studied. Method: All neonates with seizures were evaluated. The seizures were classified according to the simiology. They were investigated according to NICU protocol to confirm the underlying diagnosis and timely management. The patients after discharge were regularly followed up for one year to assess the long term neurodevelopmental outcome. A total of 96 neonates with seizures were studied and it was observed that 60 [62.5%] were male babies and 56 [58.33%] were term with a male to female ratio of 1.6:1. Majority of the neonatal seizures were seen in 1stweek of life [85%]. The most common type of seizures was clonic 40 [41.67%] followed by subtle 20 [20.84%], mixed 16 [16.67%], tonic 10 [10.41%], myoclonic 5 [5.20%] and unclassified 5 [5.20%]. Antiepileptics were used in 82 [85.41%] patients. Phenobarbitone 49 [59.76%] was most commonly prescribed drug. The most common cause of seizures was birth asphyxia 48 [50%] followed by metabolic 16 [16.68%], sepsis 10 [10.41%], intracranial hemorrhage 6 [6.25%], bilirubin encephalopathy 4 [4.16%], inborn errors of metabolism 2 [2.08%], birth trauma 2 [2.08%] and unknown etiology 5 [5.20%]. 25 [26.04%] patients develop adverse neurodevelopmental outcome i.e. cerebral palsy with epilepsy 10 [40%] and cerebral palsy without epilepsy 05 [20%], developmental delay 10 [40%]. Mortality in the study was 12 [12.5%]. Clonic seizures are commonest in neonates apart from infants and children who have GTCS. The most common etiology of seizures in neonates is birth asphyxia. Phenobarbitone is still the most commonly prescribed antiepileptic. Quick assessment, timely diagnosis and aggressive management according to the etiology are necessary to prevent the morbidity and mortality associated with neonatal seizures. Long term neurodevelopmental outcome is worse in patients with birth asphyxia especially with low Apgar score at 5 minutes. Normal delivery and birth asphyxia were the major risk factors for cerebral palsy

female child with skin lesions and seizures case report of Incontinentia Pigmenti

Incontinentia Pigmenti [IP], [OMIM # 308300], is a rare X-linked dominant condition. It is a multisystemic disease with neuroectodermal findings involving the skin, eyes, hair, nails, teeth, and central nervous system. It is usually lethal in males; the disease has variable expression in an affected female. We report the case of a 6 month old girl who presented at Sultan Qaboos University Hospital, Oman, with neonatal seizures and hypopigemented/hyperpigmented skin lesions. She had multiple ophthalmic abnormalities and neurological manifestations which are discussed in this report

Cerebral MRI findings in neonatal tuberous sclerosis

Tuberous sclerosis [TS] is a developmental neuroectodermal disorder, affecting multiple organ systems. Most patients are diagnosed at the age of five years or later, Only recently, mutation analysis of TS Complex genes has enabled us make an early or even an antenatal diagnosis of the disease. Early onset with infantile seizures is mainly an ominous sign for an unfavorable outcome. MRI findings in older children and adults are well-known; however, only limited publications illustrate brain MRI findings in newborns. We present a female neonate with a positive family history, categorized as [definite TS.] On MRI of the brain, white matter lesions were depicted. MRI findings were correlated with published data on neonatal TS

Possíveis etiologias da Síndrome de West: avaliação de 95 pacientes / Possible etiologies of West syndrome: evaluation of 95 patients

OBJETIVO: Descrever as etiologias da síndrome de West (SW) em um grupo de crianças atendidas no ambiente de um centro de reabilitação. MÉTODO: Análise retrospectiva, avaliando-se os seguintes itens: gênero, idade por ocasião da definição do diagnóstico da SW e sua etiologia. Esta foi dividida em três categorias: sintomática, criptogênica e idiopática. Os casos sintomáticos foram divididos em pré, peri e pós-natais. RESULTADOS: Noventa e cinco pacientes foram incluídos, sendo 59 do gênero masculino (62 por cento). A idade do diagnóstico variou entre 1 e 24 meses, com média de 4,9 (±5,0) meses. Vinte e cinco casos foram considerados criptogênicos (26,3 por cento) e apenas um idiopático (1,1 por cento). Os demais foram classificados com sintomáticos (72,6 por cento), sendo predominantemente casos perinatais. CONCLUSÃO: Nossos achados se assemelham aos da literatura. Conforme se ampliam o conhecimento acerca da SW e os métodos complementares de diagnóstico, haverá tendência à diminuição dos casos hoje considerados criptogênicos ou idiopáticos.

OBJECTIVE: To describe the etiologies of West syndrome (WS) among children followed in a rehabilitation center. METHOD: Retrospective study with emphasis in the following items: gender, age at the diagnosis of WS and its etiology. The etiologies were divided into three categories: symptomatic, cryptogenic and idiopathic. Symptomatic cases were classified as follows: pre, post and perinatal. RESULTS: Ninety-five patients were included. Fifty-nine were boys (62 percent). Mean age at the diagnosis was 4.9 (±5.0) months. There were 25 cryptogenic (26.3 percent), one idiopathic (1.1 percent) and 69 (72.6 percent) symptomatic cases, most of them of perinatal origin. CONCLUSION: Our findings are in agreement with the literature. In the future, as our knowledge in the field of WS and its diagnostic methods increase, there will be a small number of cryptogenic and idiopathic cases.

Vigabatrina no tratamento da síndrome de West: avaliação clínica e eletrencefalográfica em 13 pacientes / Treatment of West syndrome with vigabatrin: clinical and electroencephalographic evaluation of 13 patients

Avaliamos a eficácia da vigabatrina (VGB) como monoterapia inicial para síndrome de West (SW), os seus efeitos colaterais e a evolução a curto prazo do eletrencefalograma (EEG), num estudo prospectivo, aberto e não controlado. A amostra foi de 13 lactentes atendidos entre outubro/2001 a setembro/2002 no ambulatório do IMIP ou em clínica privada. A dose média utilizada da VGB foi 118 mg/kg/dia. Houve supressão dos espasmos em 4 crianças (31 por cento), controle parcial em 3 (23 por cento), ausência de resposta em 5 (38 por cento) e piora em 1 (8 por cento). Dos 2 pacientes portadores de esclerose tuberosa, um ficou livre dos espasmos e o outro teve controle parcial. Efeitos colaterais ocorreram em 8 crianças (62 por cento) e consistiram de irritabilidade, insônia, sonolência e agitação, sendo todos toleráveis. Ocorreu desaparecimento da hipsarritmia no segundo EEG em 6 crianças (46 por cento), tendo 4 destas ficado livre dos espasmos. Nossos dados sugerem que a VGB é eficaz e bem tolerada como monoterapia inicial para a SW.

We evaluated the efficacy of vigabatrin (VGB) as a first drug to be used as monotherapy for West syndrome (WS), its side effects and correlations with the electroencephalogram (EEG). The sample consisted of 13 infants examined between October 2001 and September 2002 at IMIP ambulatory patientsÆ office or private clinic. Administration of vigabatrin was around 118 mg/kg/day. Suppression of spasms was obtained in 4 children (31 percent), partial control in 3 (23 percent), 5 of them did not present therapeutic response (38 percent) and just one (8 percent) got worse. On the two patients with tuberous sclerosis, one was seizure-free and in another there was partial control. Side effects happened in 8 children (62 percent) and consisted of irritability, insomnia, somnolence and agitation, and all of them have been well tolerated. The second EEG showed disappearance of hipsarrhythmia in 6 patients (46 percent). Four of these were seizure-free. We conclude that VGB is effective and well tolerated as initial monotherapy for WS.

A Case of Infantile Alexander Disease Accompanied by Infantile Spasms Diagnosed by DNA Analysis

Alexander disease (AD) is a rare leukodystrophy of the central nervous system of unknown etiology. AD is characterized by progressive failure of central myelination and the accumulation of Rosenthal fibers in astrocytes, and is inevitably lethal in nature. Symptomatically, AD is associated with leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in infants, and usually leads to death within the first decade. Its characteristic magnetic resonance imaging (MRI) findings have been described as demyelination predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene, coding for glial fibrillary acidic protein (GFAP), a principal astrocytic intermediate filament protein, have been shown to lead to AD. The disease can now be detected by genetic diagnosis. We report the Korean case of an 8-month-old male patient with AD. He was clinically characterized due to the presence of psychomotor retardation, megalencephaly, spasticity, and recurrent seizures including infantile spasms which is a remarkable presentation. Demyelination in the frontal lobe and in a portion of the temporal lobe was demonstrated by brain MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L mutation in the GFAP gene, involving the replacement of guanine with thymine.

Neuroimaging findings in children with infantile, spasms

The aim of the study was to document the neuroimaging findings of children with infantile spasms [IS] seen over a 3-year period. All children below the age of 4 years who presented to the Pediatric Department at the Northern Area Armed Forces Hospital, Hafr Al-Batin, Kingdom of Saudi Arabia from January 1, 1998 to December 31, 2000 with a history of seizures, atypical movements, psychomotor delay, flexor, extensor spasms or both were included in the study. Relevant birth, developmental and family history as well as information on the pattern of fits were documented. Investigations included complete blood count, serum electrolytes, liver function tests, screening for acquired and congenital metabolic disorders. The electroencephalogram, brain magnetic resonance imaging and computerized tomography scans were carried out routinely on all the children. There were a total of 30 Saudi children, 17 males and 13 females that fulfilled the criteria for evaluation of infantile spasms. The mean age was 10 months. The major causes of IS in this study were congenital brain lesions [40%] infections [20%], and birth trauma/asphyxia [16.7%]. The etiology was unknown in 6 [20%] cases. The neuroimaging pattern was dysgenesis [30%], brain atrophy [23.7%], infarctions/hemorrhage [10%] and hydrocephaly [10%]. In 8 cases [26.6%] the findings were normal. The neuroimaging findings in this study are comparable with observations in other studies carried out under different clinical settings and environment

Espasmos infantis: experiência em treze casos / Infantile spasms: experience in 13 cases

Os espasmos infantis são crises típicas da primeira infância e constituem patologia grave, com prognóstico sombrio. Apresentamos a experiência no tratamento de 13 casos novos atendidos no Serviço de Neurologia Infantil do Centro Geral de Pediatria FHEMIG de Belo Horizonte no ano de 1997, bem como revisão da literatura sobre o assunto. Após propedêutica adequada encontramos 12 casos considerados sintomáticos e 1 criptogenético. Todos os casos foram tratados com ACTH durante 6 semanas, associado a drogas antiepilépticas orais de manutenção em mono ou politerapia. Os resultados com o ACTH foram excelentes num momento inicial, com resposta completa em todos os casos e efeitos colaterais que não contra-indicaram o tratamento. Porém houve índice de recorrência de 55 por cento, sendo usada como droga de segunda linha a vigabatrina em 5 casos, com controle de 4 deles. Todos os casos apresentaram atraso do desenvolvimento neuropsicomotor.

Aspectos tomográficos da síndrome de West / CT scan findings on West's syndrome

No presente trabalho os autores relatam os achados tomográficos (TCC) de 34 crianças afetadas pela SW. Em 12 crianças (35,29 por cento) a TCC foi considerada normal; onze (32,35 por cento) apresentaram atrofia cerebral difusa; seis (17,64 por cento) mostraram sinais de atrofia cortical difusa; duas (5,88 por cento) apresentaram calcificações parenquimatosas cerebrais; numa criança (2,94 por cento) foi observada imagem de dilatação ventricular com formação cística intraventricular à direita; numa lactente (2,94 por cento) a TCC evidenciou agenesia do corpo caloso e cisto porencefálico à esquerda e, finalmente, noutra (2,94 por cento) o exame detectou apenas assimetria craniana. Os autores chamam a atenção para a importância do exame tomográfico do crânio como subsídio para o diagnóstico etiológico da SW

Encefalopatia con hipsarritmia sin espasmos infantiles / Infantile encephalopathy with hipsarritmia without spasms

Los niños con encelopatias cronicas pueden presentar retraso del desarrollo psicomotor y en algun momento de su evolucion, crisis de espasmos con tazado electroencefalografico hipsarritmico, constituyendo un sindrome de west sintomatico. Presentamos un analisis y seguimiento evolutivo de 9 niños que, si presentaron hipsarritmia, no sufrieron espasmos. Prevaleciendo en mujeres (8:1), la hipsarritmia comenzo en la mayoria de los pacientes (77.8 por ciento) antes de los meses. El factor etiologico fue, en todos los pacientes, un daño encefalico previo. Clinicamente los niños presentaron examen neurologico anormal, solo 6 niños presentaron convulciones y ninguno presento crisis de espasmos. Los electroencefalogramas mostraron algun tipo de hipsarritmia. Se evalua el resultado del tratamiento con ACTH instaurado. Resaltamos la existencia de hipsarritmia sin crisis de espasmos y destacamos que 3 niños de nuestra serie presentaron, como caracteristica propia distintiva, la ausencia de manifestaciones convulsivas

Síndrome de West secundario a cirugía cardíaca / West syndrome secondary to cardiac surgery

El síndrome de West puede presentarse como complicación de la cirugía cardíaca con cardioplejía y circulación extracorpórea. Presentamos una niña con diagnóstico de cardiopatía congénita que luego de la intervención quirúrgica, sin haber presentado signos de encefalopatía en el posquirúrgico inmediato, comenzó con crisis de espasmos infantiles e hipsarritmia, constituyendo un síndrome de West

Síndrome de West: estudio clínico, terapéutico, evolutivo / West Sindrome: clinic, therapeutic and evolutive study

Se analizaron 22 historias clínicas con diagnóstico de Síndrome de West, que ingresaron en las Clínicas Pediátricas "B" y "C" del Centro Hospitalario Pereira Rossell en el período de 2 años. Representaron el 9.5 por ciento de las epilepsias infantiles. El rango etario fue de 1 a 10 meses. La demora en el diagnóstico fue promedialmente de 1 mes. Las hipótesis diagnósticas iniciales fueron erróneas en el 72 por ciento de los niños. El 77 por ciento de los casos fueron de causa sintomática. El EEG inicial fue normal en el 9 por ciento de los niños. La terapéutica controló los espasmos infantiles en el 64 por ciento de los casos. El 80 por ciento de los niños presentaron secuelas. La ausencia de secuelas se asocian en forma significativa con West idiopáticos. Concluimos en la importancia de promover el diagnóstico y tratamiento precoz de esta entidad, pues del mismo dependerá el futuro de estos niños, especialmente los idiopáticos

Espasmo del sollozo / Breath holding spells in children

El espasmo del sollozo es una forma de síncope infantil. Su frecuencia en la población infantil es de 5 por ciento, y los afectados tienen una historia familiar positiva para dichos ataques. Su mayor incidencia es entre los seis y 18 meses, y los factores precipitantes son: golpes, frustración, miedo, sorpresa y enojo. El espasmo del sollozo se puede clasificar en cianótico, pálido e indeterminado. Las crisis cesan espontáneamente antes de la edad escolar. En el grupo cianótico, la respuesta a la compresión ocular es bradicardia o asístole breve; en cambio, en el grupo pálido la asístole cardiaca es más prolongada, con anormalidades electroencefalográficas sincrónicas. La diferenciación con epilepsia es importante. En el grupo pálido se puede usar atropina, pero en muchas ocasiones el tratamiento es innecesario

Encefalopatias epilépticas de la infancia / Epileptic encephalopathies in childhood

Se presenta una serie de 23 casos de encefalopatias epilepticas de la infancia, vistos en los consultorios externos de Neuropediatria del Hospital General Cayetano Heredia y Neurología del Hospital IPSS. Guillermo Almenara (Lima, Perú) entre Enero-1984 y Octubre-1988, con un seguimiento entre 6 meses y 4 años 6 meses para cada paciente. Del total, uno correspondió al síndrome de Ohtahara, 9 fueron West y 13 Lennox-Gastaut. Se revisan las características clínico electroencefalográfias de cada uno de los grupos y su evolución. Con relación al sindrome de Ohtahara llama la atención el buen pronóstico encontrado en este paciente; de los 9 West únicamente 2 evolucionaron para Lennox-Gastaut y de estos últimos ninguno tuvo antecedente de West y contrariamente a lo esperado y teniendo en cuenta los factores de riesgo para mal pronóstico, la mayor parte de nuestros pacientes tuvieron un buen control de crisis

Pesquisa etiológica en espasmos masivos / Etiologic research in massive spasms

Con el objeto de identificar un factor etiológico se aplicó un protocolo de estudio sistemático en 16 lactantes que presentaban espasmos masivos. En dos pacientes hubo antecedentes familiares relevantes, en tanto que cinco presentaron afecciones perinatales o postnatales graves. Diez niños presentaron retardo psicomotor y ocho otras crisis previo al inicio de EM. El examen físico reveló microcefalia, dismorfias, manchas hipopigmentadas de la piel, síndrome piramidal. Las técnicas de neuro-imagen demostraron hallazgos positivos en 9 casos, atrofia en 7, porencefalia en 3, calcificaciones en uno y agenesia del cuerpo calloso en uno. El laboratorio permitió el diagnóstico de dos casos con enfermedades metabólicas: hiperlactatemia y enfermedad de orina olor a jarabe de arce. Dos pacientes se catalogaron como criptogenéticos y 14 como sintomáticos. Entre los últimos en doce casos se identificó razonablemente una etiología. Este estudio enfatiza el valor de la búsqueda etiológica en EM, puesto que aporta el tratamiento específico y/o consejo genético en algunos pacientes