[Intracranial hypotension syndrome in a pediatric patient with Marfan syndrome].

Intracranial hypotension syndrome (IHS) is attributed to reduced cerebrospinal fluid (CSF) pressure. It may be spontaneous or secondary to a history of trauma or systemic disease. We present the case of an 11-year-old boy, with medical history of Marfan syndrome, with orthostatic headache and persistent vomiting (12 hours) following a fall on the sacrococcygeal region. Magnetic resonance showed extradural fluid collections at dorsal and lumbosacral levels, compatible with CSF leak. The condition was resolved with treatment, but the patient had two new episodes during the follow-up period. Thus, an epidural blood patch was performed two years after the first episode. Although HIS is uncommon in children, it should be suspected in patients with orthostatic headache, particularly if the patient presents a connectivopathy. Few studies have assessed the management of HIS in paediatric age. The case presented here and the reviewed available literature provides further data for these type of cases.

Síndrome de hipotensión intracraneal en paciente pediátrico con síndrome de Marfan / Intracranial hypotension syndrome in a pediatric patient with Marfan syndrome

El síndrome de hipotensión intracraneal (SHI) es consecuencia del descenso de la presión de líquido cefalorraquídeo (LCR), espontáneo o secundario a antecedente traumático o enfermedad sistémica.Presentamos el caso de un niño de 11 años con cefalea ortostática y vómitos de 12 horas de evolución tras una caída sobre región sacrocoxígea; antecedente de síndrome de Marfan. La resonancia craneomedular mostró colecciones líquidas extradurales a nivel dorsal y lumbosacro compatibles con fístula de LCR. El cuadro se resolvió tras tratamiento, pero hubo dos nuevos episodios durante el seguimiento, por lo que se aplicó un parche hemático epidural a los dos años del inicio.Aunque el SHI es infrecuente en niños, debe sospecharse ante pacientes con cefalea ortostática, especialmente si existe patología favorecedora como enfermedades del tejido conectivo. Existe poca evidencia sobre el manejo en edad pediátrica, por lo que se presenta este caso y se realiza una revisión de la literatura.(AU)

Intracranial hypotension syndrome (IHS) is attributed to reduced cerebrospinal fluid (CSF) pressure. It may be spontaneous or secondary to a history of trauma or systemic disease. We present the case of an 11-year-old boy, with medical history of Marfan syndrome, with orthostatic headache and persistent vomiting (12 hours) following a fall on the sacrococcygeal region. Magnetic resonance showed extradural fluid collections at dorsal and lumbosacral levels, compatible with CSF leak. The condition was resolved with treatment, but the patient had two new episodes during the follow-up period. Thus, an epidural blood patch was performed two years after the first episode.Although HIS is uncommon in children, it should be suspected in patients with orthostatic headache, particularly if the patient presents a connectivopathy. Few studies have assessed the management of HIS in paediatric age. The case presented here and the reviewed available literature provides further data for these type of cases.(AU)

HiperCKemia persistente asintomática en edad pediátrica. Diagnóstico de miopatía central core sin biopsia muscular / Asymptomatic hyperCKemia in children. Central core disease with non-diagnostic muscle biopsy

INTRODUCCIÓN: la elevación persistente de creatinfosfoquinasa (CK) puede constituir la primera manifestación de una patología muscular subyacente. Su correcto abordaje permite un adecuado tratamiento precoz, asesoramiento familiar e información sobre su pronóstico y sus complicaciones. CASO CLÍNICO: niño de siete años, asintomático, con elevación de CK como hallazgo casual en una analítica de rutina, persistiendo en controles seriados. Exploración física normal. Tras un estudio metabólico completo normal, se solicita estudio genético dirigido a descartar distrofinopatías u otras miopatías. Se observa una mutación en el gen RYR1, c.9912C>A; p. (Cys3304*), variante probablemente patogénica compatible con miopatía congénita de cores centrales (#MIM11700). Ante un diagnóstico genético en paciente asintomático, se evita la realización de otras técnicas invasivas. CONCLUSIONES: la miopatía congénita de cores centrales es la patología neuromuscular congénita más frecuente. Se relaciona con la presencia de mutaciones en el gen RYR1 (90% de los pacientes). Pertenece a la familia de los canales liberadores de calcio iónico, cuyo papel es fundamental en el fenómeno de acoplamiento excitación-contracción muscular. Su diagnóstico clásico era la biopsia muscular. Está asociado a complicaciones como hipertermia maligna o rabdomiolisis

INTRODUCTION: persistently elevated serum creatine kinase levels may lean the first manifestation of an underlying neuromuscular disease. Its appropriate approach allows an adequate early treatment, a genetic counselling and information concerning complications and prognosis. CASE DESCRIPTION: our patient was an asymptomatic 7-year-old boy with persistent serum CK elevation. He had a normal physical examination. After a normal metabolic study, a specific genetic study for dystrophinopaties or other myopathies was requested. A variant of uncertain significance mutation [RYR1, c.9912C>A; p. (Cys3304*)] associated with central core disease (#MIM11700) was obtained. Before this genetic diagnosis the invasive testing was rejected. DISCUSSION: central core disease is the most frequent congenital neuromuscular disease. About 90% of cases are linked to RYR1 gene mutations. RYR1 protein is a part of macromolecular complex deputed to excitation-contraction coupling through Ca2+ channels. Its diagnosis is confirmed by histological examination. CCD is associated to malignant hyperthermia and rabdomiolisis susceptibility

Síndrome de duplicación MECP2 familiar / Familial MECP2 duplication síndrome

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Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

BACKGROUND: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. METHODS: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. FINDINGS: Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59). INTERPRETATION: The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. FUNDING: Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.

Neurofibromatosis 1 y cavernomatosis múltiple familiar en un lactante con sialorrea profusa episódica / Neurofibromatosis 1 and multiple familial cavernomatosis in an infant with episodic profuse sialorrhoea

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Neurofibromatosis tipo 1 y trastorno por déficit de atención. Nuestra experiencia actual / Neurofibromatosis type 1 and attention-deficit disorder. Our current experience

Introducción. Los pacientes con neurofibromatosis de tipo 1 (NF1) tienen una gran predisposición a desarrollar déficit de atención. El objetivo del estudio es determinar los pacientes controlados en nuestra sección de neuropediatría con NF1 y diagnóstico de trastorno por déficit de atención/hiperactividad (TDAH), valorando la adhesión y respuesta al tratamiento. Pacientes y métodos. Se identifica a los pacientes afectos de NF1 que siguen controlados entre el 31 de diciembre de 2015 y el 31 de junio de 2017, y de ellos, los que presentan diagnóstico de TDAH, revisando datos clínicos y de tratamiento. Resultados. Se ha controlado a 56 pacientes afectos de NF1, con una edad media de 9,83 ± 4,17 años. De ellos, 23 (41%) presentan diagnóstico clínico de TDAH, con una edad media de 7,53 ± 2,46 años en el momento del diagnóstico. El 48,8% de los niños en edad escolar está afecto de TDAH. Todos los pacientes menos uno recibieron tratamiento con estimulantes, con un tiempo medio de tratamiento de 3,85 ± 3,04 años. Continúan con el tratamiento 19 pacientes de los 22 tratados (86%). Once casos refieren una clara mejoría, y ocho, una mejoría moderada. Conclusiones. El TDAH es muy prevalente en niños con NF1. Se destaca la importancia de la identificación y el tratamiento del TDAH en niños afectos de NF1. Nuestra revisión muestra una buena adhesión al tratamiento con estimulantes, con mantenida buena respuesta en la mayor parte de los casos

Introduction. Patients with neurofibromatosis type 1 (NF1) have a high predisposition to develop attention-deficit disorder. The aim of this study is to determine the prevalence of NF1 patients with attention-deficit/hyperactivity disorder (ADHD) diagnosis attending our Child Neurology Department. We assess patient adherence and medical treatment outcomes. Patients and methods. Identification of patients with NF1 being followed up from December 31 2015 to June 31 2017 with ADHD diagnosis. Clinical and treatment data were collected. Results. 56 patients with NF1 were enrolled in the study with a mean age of 9.83 ± 4.17 years. 23 patients (41%) were diagnosed with ADHD, mean age at ADHD diagnosis of 7.53 ± 2.46 years. School-age children with ADHD represented 48.8% of cases. All but one of the children received treatment, mean duration of treatment was 3.85 ± 3.04 years. 19 out of 22 patients (86%) continue medical treatment. Positive effects were reported by eleven patients with a moderate response in eight patients. Conclusions. Prevalence of ADHD in patients with NF1 is high. Early diagnosis and treatment of ADHD in patients with NF1 is highlighted by this study. Our study reveals good patient adherence and medical treatment outcomes in most patients

Hipertensión intracraneal idiopática: experiencia en 25 años y protocolo de actuación / Idiopathic intracranial hypertension: Experience over 25 years and a management protocol

Introducción y objetivos: Se presenta nuestra experiencia en hipertensión intracraneal idiopática (HII) preimplantación y postimplantación de un protocolo específico de actuación. Material y métodos: Estudio descriptivo retrospectivo de los pacientes con diagnóstico de HII en 25 años (1990-2015), comparando los últimos 7 años (tras implantar protocolo) con los 18 previos. Resultados: De 18.865 pacientes valorados en 25 años, hay 54 casos de HII (29 lactantes y 25 niños mayores). Se comparan ambos periodos: 32 casos de 1990-2008 -publicados en An Pediatr (Barc). 2009;71:400-6- y 23 de 2008-2015. En el periodo posprotocolo, hubo 13 pacientes entre 3 y 10 meses (62% varones) con abombamiento transitorio de fontanela y 10 entre 2 y 14 años (50% varones) con papiledema. El 54% de los lactantes habían finalizado recientemente tratamiento corticoideo por bronquitis. En los mayores, un caso asoció trombosis de senos venosos por otomastoiditis, otro tratamiento corticoideo por angioma y otro tratamiento con hormona de crecimiento. Se hizo ecografía transfontanelar a todos los lactantes; TAC, RM y angioRM a todos los mayores, y punción lumbar a 2 lactantes (por sospecha de meningitis) y a todos los mayores. Todos los pacientes evolucionaron favorablemente; solo en 3 se instauró tratamiento. Una paciente recidivó. Discusión: Las características y la evolución de los pacientes son superponibles en todos los años. La HII suele tener un curso favorable, aunque puede tardar en resolverse en niños mayores y presentar graves repercusiones visuales, por lo que precisa estrecho control oftalmológico. Destacamos la utilidad del protocolo para facilitar la toma de decisiones diagnósticas, de seguimiento y tratamiento (AU)

Introduction: We present our experience on idiopathic intracranial hypertension (IIH), before and after the introduction of a specific diagnosis and management protocol. Method: A descriptive retrospective study was conducted on patients with IIH over a 25 year period (1990-2015), comparing the last 7 years (after introduction of the protocol) with the previous 18 years. Results: Among the 18,865 patients evaluated, there were 54 cases of IIH (29 infants and 25 children). A comparison was made between the two time periods: 32 cases in 1990-2008 -published in An Pediatr (Barc). 2009;71:400-6-, and 23 cases in 2008-2015. In post-protocol period, there were 13 patients aged between 3-10 months (62% males) with transient bulging fontanelle, and 10 aged between 2-14 years (50% males), with papilloedema. A total of 54% of infants had recently finished corticosteroid treatment for bronchitis. In the older children, there was one case associated with venous thrombosis caused by otomastoiditis, one case on corticosteroid treatment for angioma, and another case treated with growth hormone. Transfontanelle ultrasound was performed on all infants, and CT, MRI and angio-MRI was performed on every child. Lumbar puncture was performed on 2 infants in whom meningitis was suspected, and in all children. All patients progressed favourably, with treatment being started in 3 of them. One patient relapsed. Discussion: Characteristics and outcomes of patients overlap every year. IIH usually has a favourable outcome, although it may be longer in children than in infants. It can cause serious visual disturbances, so close ophthalmological control is necessary. The protocol is useful to ease diagnostic decisions, monitoring, and treatment (AU)

Estudio de las epilepsias según la edad de inicio, controladas durante 3 años en una unidad de neuropediatría de referencia regional / A study of epilepsy according to the age at onset and monitored for 3 years in a regional reference paediatric neurology unit

OBJETIVO: Estudio de las epilepsias según la edad de inicio de las crisis y la etiología, de los pacientes controlados en una unidad de neuropediatría durante 3 años. PACIENTES Y MÉTODOS: Estudio de cohortes históricas. Revisión de historias de niños con epilepsia de la base de datos de neuropediatría controlados del 1 de enero de 2008 al 31 de diciembre de 2010. RESULTADOS: De 4.595 ni˜nos atendidos en el periodo, se estableció el diagnóstico de epilepsia en 605 (13,17%), siendo 277 (45,79%) epilepsias sintomáticas, 156 (25,79%) idiopáticas y 172 (28,43%) criptogénicas. La epilepsia de ausencias y la epilepsia benigna de la infancia con paroxismos centrotemporales son los síndromes epilépticos idiopáticos con mayor prevalencia, y las encefalopatías prenatales las epilepsias sintomáticas más prevalentes. El 26,12% iniciaron su epilepsia el primer a˜no, siendo sintomáticas el 67,72%. Se han considerado refractarias el 25,29% de las epilepsias; el 42,46% asocia déficit cognitivo, el 26,45% afectación motora y el 9,92% trastorno del espectro autista, siendo más frecuentes a menor edad de inicio. CONCLUSIONES: La ausencia de una clasificación universalmente aceptada de los síndromes epilépticos dificulta trabajos como este, empezando por la terminología. Una clasificación útil es la etiológica, con 2 grupos: un gran grupo con las etiologías establecidas o síndromes genéticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiológico añade orientación pronóstica. El pronóstico de la epilepsia lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, siendo peor en general a más precoz inicio y en etiologías concretas

OBJECTIVE: A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. PATIENTS AND METHODS: Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. RESULTS: A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. CONCLUSIONS: The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies

[Idiopathic intracranial hypertension: Experience over 25 years and a management protocol]. / Hipertensión intracraneal idiopática: experiencia en 25 años y protocolo de actuación.

INTRODUCTION: We present our experience on idiopathic intracranial hypertension (IIH), before and after the introduction of a specific diagnosis and management protocol. METHOD: A descriptive retrospective study was conducted on patients with IIH over a 25year period (1990-2015), comparing the last 7years (after introduction of the protocol) with the previous 18years. RESULTS: Among the 18,865 patients evaluated, there were 54 cases of IIH (29 infants and 25 children). A comparison was made between the two time periods: 32 cases in 1990-2008 -published in An Pediatr (Barc). 2009;71:400-6-, and 23 cases in 2008-2015. In post-protocol period, there were 13 patients aged between 3-10months (62% males) with transient bulging fontanelle, and 10 aged between 2-14years (50% males), with papilloedema. A total of 54% of infants had recently finished corticosteroid treatment for bronchitis. In the older children, there was one case associated with venous thrombosis caused by otomastoiditis, one case on corticosteroid treatment for angioma, and another case treated with growth hormone. Transfontanelle ultrasound was performed on all infants, and CT, MRI and angio-MRI was performed on every child. Lumbar puncture was performed on 2 infants in whom meningitis was suspected, and in all children. All patients progressed favourably, with treatment being started in 3 of them. One patient relapsed. DISCUSSION: Characteristics and outcomes of patients overlap every year. IIH usually has a favourable outcome, although it may be longer in children than in infants. It can cause serious visual disturbances, so close ophthalmological control is necessary. The protocol is useful to ease diagnostic decisions, monitoring, and treatment.

[A study of epilepsy according to the age at onset and monitored for 3 years in a regional reference paediatric neurology unit]. / Estudio de las epilepsias según la edad de inicio, controladas durante 3 años en una unidad de neuropediatría de referencia regional.

OBJECTIVE: A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. PATIENTS AND METHODS: Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. RESULTS: A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. CONCLUSIONS: The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies.

Estudio descriptivo de las epilepsias no sintomáticas según la edad de inicio en una unidad de neuropediatría de referencia regional / A descriptive study of non-symptomatic epilepsy according to age at onset at a Neuropediatric Section of regional reference

Objetivo. Estudio descriptivo de las epilepsias no sintomáticas (idiopáticas y criptogénicas), según la edad de inicio, controladas en una unidad de neuropediatría de referencia regional durante tres años. Pacientes y métodos. Revisión de historias de niños con epilepsia no sintomática de la base de datos de neuropediatría controlados del 1 de enero de 2008 al 31 de diciembre de 2010. Resultados. De 4.595 niños atendidos en el período, se diagnosticaron de epilepsia 605 (13,17%), de las cuales 156 (25,79%) fueron idiopáticas, y 172 (28,43%), criptogénicas. La edad media de inicio del total fue de 4,78 años; 6,31 años en las idiopáticas y 5,43 años en las criptogénicas. El 26,12% del total de epilepsias se inició en el primer año. Las epilepsias idiopáticas predominan en el grupo de inicio de 6-10 años, y las criptogénicas, en el de 3-6 años. La epilepsia de ausencias y la epilepsia benigna de la infancia con paroxismos centrotemporales son los síndromes epilépticos idiopáticos más prevalentes. Conclusiones. Existen muchas diferencias de datos epidemiológicos publicados sobre epilepsia infantil por la dificultad que entraña un diagnóstico sindrómico en la edad pediátrica, debido a la variabilidad clínica y electroencefalográfica. La ausencia de una clasificación universalmente aceptada de los síndromes epilépticos dificulta comparaciones entre series. Todas las epilepsias son sintomáticas, puesto que tienen causa, sea genética o adquirida. Una clasificación útil es la etiológica, con dos grupos: un gran grupo con las etiologías establecidas o síndromes genéticos muy probables y otro de casos sin causa establecida. La edad de inicio orienta a determinadas etiologías (AU)

Aim. A descriptive study of non-symptomatic epilepsy (idiopathic and cryptogenic), according to age at onset, monitored at a Neuropediatric Section of regional reference over a period of three years. Patients and methods. A review of neuropediatric database medical records of children with non-symptomatic epilepsy supervised from Jan 1, 2008 till December 31, 2010. Results. Of the 4595 children attended during the period, 605 were diagnosed with epilepsy (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. The average age at onset of the total was 4.78 years: 6.31 years in idiopathic epilepsies and 5.43 years in cryptogenic epilepsies. 26.12% of all the epilepsies began in the first year of life. Idiopathic epilepsy predominates in the startup group of 6-10 years and cryptogenic epilepsy in 3-6 years. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent. Conclusions. Many differences exist among published epidemiological data on childhood epilepsy due to the difficulty of a syndromic diagnosis in children, caused by clinical and electroencephalographic variability. The absence of a universally accepted classification of epileptic syndromes makes it difficult to compare publications. All epilepsies are symptomatic as they have a cause, whether it be genetic or acquired. A useful classification would be etiological, with two groups: one large with established etiology or very likely genetic syndromes and another with no established cause. The age at onset indicates specific etiologies (AU)

Hipofisitis tuberculosa que mimetiza un síndrome de Tolosa-Hunt / Tuberculous hypophysitis mimicking Tolosa-Hunt syndrome

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GNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females.

BACKGROUND: De novo heterozygous mutations in the GNAO1 gene, encoding the Gα o subunit of G-proteins, are the cause of a severe neurodevelopmental disorder, featuring early infantile seizures, profound cognitive dysfunction and, occasionally, movement disorder (early infantile epileptic encephalopathy-17). METHODS: We report a further case of this association in a 20 month-old Spanish girl with neonatal-onset refractory seizures, progressive microcephaly, oral-lingual dyskinesia and nearly absent psychomotor development. We performed whole-exome sequencing, a computational structural analysis of the novel gene variant identified and reviewed the previously reported cases. RESULTS: Trio whole-exome-sequencing uncovered a de novo p.Leu199Pro GNAO1 mutation. Computational structural analysis indicates this novel variant adversely affects the stability of the G-protein heterotrimeric complex as a whole. Of note, our patient showed a sustained seizure reduction while on a ketogenic diet. CONCLUSIONS: With this observation, a total of twelve patients with GNAO1 encephalopathy have been reported. Oral-lingual dyskinesia and responsiveness of seizures to ketogenic diet are novel features. The distorted sex ratio (12/12 females) of the condition remains unexplained; a differential gender effect of the disruption of G-protein- mediated signal transduction on the developing brain can be hypothesized.

Expansión del triplete citosina-guanina-guanina: 3 casos de síndrome OMIM en una misma familia / Triplet expansion cytosine-guanine-guanine: Three cases of OMIM syndrome in the same family

Introducción: El aumento del número de repeticiones del triplete citosina-guanina-guanina (CGG), en el gen FMR1 es responsable de 3 síndromes OMIM con fenotipo clínico bien diferenciado: síndrome de X frágil (SXF) y 2 enfermedades en adultos portadores de la premutación (55-200 repeticiones CGG): insuficiencia ovárica primaria (FXPOI) y síndrome de temblor-ataxia (FXTAS) asociado al SXF. Observación clínica o métodos: Se estudió la mutación dinámica CGG del gen FMR1 en muestras de ADN de sangre periférica del caso índice y familiares de primer, segundo y tercer grado mediante TP-PCR, así como el porcentaje de metilación. Resultados: Se confirmó el diagnóstico del SXF en 3 pacientes (21,4%), 8 pacientes (57,1%) se encontraban en el rango de premutación, un paciente varón con mosaicismo premutación-mutación completa (7,1%) y 2 pacientes (14,3%) con estudio normal. De los 8 pacientes premutados, 3 presentaron FXPOI y un paciente varón FXTAS. Discusión: Nuestro estudio muestra la importancia de realizar un diagnóstico precoz del SXF y su consecuente estudio familiar y consejo genético, que permita identificar nuevos pacientes afectos o pacientes premutados con síndromes relacionados con el gen FMR1 (FXTAS, FXPOI) (AU)

Introduction: The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS. Clinical observation and methods: CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation. Results: Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS. Discussion: Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI) (AU)

[Prognosis of symptomatic epilepsies in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years]. / Pronostico de las epilepsias sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.

AIM: To analyze the factors involved in the prognosis of symptomatic epilepsies in relation to their age at onset, monitored at a neuropediatric section of regional reference over a period of three years. PATIENTS AND METHODS: Children diagnosed with symptomatic epilepsy, supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established at 605 (13.17%): 277 (45.79%) symptomatic epilepsies. Symptomatic etiology predomininates in epileptic patients that started below one year of age, 67.72%, and between 1-3 years, 61.39%. 37.54% of symptomatic epilepsy is refractory, 72.92% have cognitive impairment, 55.23% have motor impairment and 17.32% have autism spectrum disorder. The younger the patient, the higher the percentage of refractoriness and display of any neurological or associated development impact. Some etiologies have higher rates of refractoriness. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is overshadowed by refractoriness and associated neurodevelopmental disorders, which are generally worse at an earlier onset and in certain etiologies.

TITLE: Pronostico de las epilepsias sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias sintomaticas en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante tres años. Pacientes y metodos. Revision de los pacientes con diagnostico de epilepsia sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos y evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 277 (45,79%) son epilepsias sintomaticas. En los pacientes que iniciaron la epilepsia por debajo del año de vida predominan las de etiologia sintomatica (67,72%), y tambien entre 1-3 años (61,39%). El 37,54% de las epilepsias sintomaticas son refractarias, el 72,92% asocian un deficit cognitivo, el 55,23%, alguna afectacion motora, y el 17,32%, algun trastorno del espectro autista. A menor edad, mayor porcentaje de refractariedad y de presentar alguna repercusion neurologica o del desarrollo asociada. Algunas etiologias tienen mayores tasas de refractariedad. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz es el inicio y en etiologias concretas.

Pronóstico de las epilepsias sintomáticas según la edad de inicio, controladas durante tres años en una unidad de neuropediatría de referencia regional / Prognosis of symptomatic epilepsies in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years

Objetivo. Analizar los factores implicados en el pronóstico de las epilepsias sintomáticas en relación con su edad de inicio, controladas en una unidad de neuropediatría de referencia regional durante tres años. Pacientes y métodos. Revisión de los pacientes con diagnóstico de epilepsia sintomática, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiológicos, clínicos y evolutivos. Resultados. Del total de 4.595 niños atendidos en el período, se estableció el diagnóstico de epilepsia en 605 (13,17%), de las cuales 277 (45,79%) son epilepsias sintomáticas. En los pacientes que iniciaron la epilepsia por debajo del año de vida predominan las de etiología sintomática (67,72%), y también entre 1-3 años (61,39%). El 37,54% de las epilepsias sintomáticas son refractarias, el 72,92% asocian un déficit cognitivo, el 55,23%, alguna afectación motora, y el 17,32%, algún trastorno del espectro autista. A menor edad, mayor porcentaje de refractariedad y de presentar alguna repercusión neurológica o del desarrollo asociada. Algunas etiologías tienen mayores tasas de refractariedad. Conclusiones. Una clasificación útil de la epilepsia es la etiológica, con dos grupos: un gran grupo con las etiologías establecidas o síndromes genéticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiológico añade orientación pronóstica. El pronóstico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto más precoz es el inicio y en etiologías concretas (AU)

Aim. To analyze the factors involved in the prognosis of symptomatic epilepsies in relation to their age at onset, monitored at a neuropediatric section of regional reference over a period of three years. Patients and methods. Children diagnosed with symptomatic epilepsy, supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical and developmental data. Results. Of the 4595 children attended during the period, the diagnosis of epilepsy was established at 605 (13.17%): 277 (45.79%) symptomatic epilepsies. Symptomatic etiology predomininates in epileptic patients that started below one year of age, 67.72%, and between 1-3 years, 61.39%. 37.54% of symptomatic epilepsy is refractory, 72.92% have cognitive impairment, 55.23% have motor impairment and 17.32% have autism spectrum disorder. The younger the patient, the higher the percentage of refractoriness and display of any neurological or associated development impact. Some etiologies have higher rates of refractoriness. Conclusions. A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is overshadowed by refractoriness and associated neurodevelopmental disorders, which are generally worse at an earlier onset and in certain etiologies (AU)

[Prognosis of non-symptomatic epilepsy in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years]. / Pronóstico de las epilepsias no sintomáticas según la edad de inicio, controladas durante tres años en una unidad de neuropediatría de referencia regional.

AIM: To analyze the factors involved in the prognosis of non-symptomatic epilepsy (idiopathic and cryptogenic) in relation to their age of onset, monitored at a regional section of Neuropediatry reference over a period of three years. PATIENTS AND METHODS: Patients with diagnosis of non-symptomatic epilepsy supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical, complementary examinations and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established in 605 (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. 15.7% of cryptogenic epilepsies and 14.1% of idiopathic epilepsies are refractory to treatment. Some epileptic syndromes, such as reflex epilepsies, Dravet syndrome, Ohtahara syndrome or Lennox-Gastaut syndrome, have higher rates of drug resistance. 84.62% of idiopathic epilepsies and 79.77% of cryptogenic epilepsies present no other associated neurological disorder. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain etiologies.

TITLE: Pronostico de las epilepsias no sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias no sintomaticas (idiopaticas y criptogenicas) en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante un periodo de tres años. Pacientes y metodos. Analisis de los pacientes con diagnostico de epilepsia no sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos, examenes complementarios y datos evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 156 (25,79%) fueron epilepsias idiopaticas, y 172 (28,43%), criptogenicas. El 15,7% de las epilepsias criptogenicas y el 14,1% de las idiopaticas son refractarias al tratamiento. Algunos sindromes epilepticos, como las epilepsias reflejas, el sindrome de Dravet, el sindrome de Ohtahara o el sindrome de Lennox-Gastaut, tienen mayores tasas de farmacorresistencia. No presentan otra alteracion neurologica asociada el 84,62% de las epilepsias idiopaticas y el 79,77% de las epilepsias criptogenicas. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz sea el inicio y en etiologias concretas.

Pronóstico de las epilepsias no sintomáticas según la edad de inicio, controladas durante tres años en una unidad de neuropediatría de referencia regional / Prognosis of non-symptomatic epilepsy in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years

Objetivo. Analizar los factores implicados en el pronóstico de las epilepsias no sintomáticas (idiopáticas y criptogénicas) en relación con su edad de inicio, controladas en una unidad de neuropediatría de referencia regional durante un período de tres años. Pacientes y métodos. Análisis de los pacientes con diagnóstico de epilepsia no sintomática, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiológicos, clínicos, exámenes complementarios y datos evolutivos. Resultados. Del total de 4.595 niños atendidos en el período, se estableció el diagnóstico de epilepsia en 605 (13,17%), de las cuales 156 (25,79%) fueron epilepsias idiopáticas, y 172 (28,43%), criptogénicas. El 15,7% de las epilepsias criptogénicas y el 14,1% de las idiopáticas son refractarias al tratamiento. Algunos síndromes epilépticos, como las epilepsias reflejas, el síndrome de Dravet, el síndrome de Ohtahara o el síndrome de Lennox-Gastaut, tienen mayores tasas de farmacorresistencia. No presentan otra alteración neurológica asociada el 84,62% de las epilepsias idiopáticas y el 79,77% de las epilepsias criptogénicas. Conclusiones. Una clasificación útil de la epilepsia es la etiológica, con dos grupos: un gran grupo con las etiologías establecidas o síndromes genéticos muy probables y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiológico añade orientación pronóstica. El pronóstico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto más precoz sea el inicio y en etiologías concretas (AU)

Aim. To analyze the factors involved in the prognosis of non-symptomatic epilepsy (idiopathic and cryptogenic) in relation to their age of onset, monitored at a regional section of Neuropediatry reference over a period of three years. Patients and methods. Patients with diagnosis of non-symptomatic epilepsy supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical, complementary examinations and developmental data. Results. Of the 4595 children attended during the period, the diagnosis of epilepsy was established in 605 (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. 15.7% of cryptogenic epilepsies and 14.1% of idiopathic epilepsies are refractory to treatment. Some epileptic syndromes, such as reflex epilepsies, Dravet syndrome, Ohtahara syndrome or Lennox-Gastaut syndrome, have higher rates of drug resistance. 84.62% of idiopathic epilepsies and 79.77% of cryptogenic epilepsies present no other associated neurological disorder. Conclusions. A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain etiologies (AU)

[Triplet expansion cytosine-guanine-guanine: Three cases of OMIM syndrome in the same family]. / Expansión del triplete citosina-guanina-guanina: 3 casos de síndrome OMIM en una misma familia.

INTRODUCTION: The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS. CLINICAL OBSERVATION AND METHODS: CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation. RESULTS: Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS. DISCUSSION: Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI).