Crisis con fiebre en el primer año de vida: ¿epilepsia del espectro Dravet? / Febrile seizures in the first year of life. Dravet spectrum epilepsy?

Introducción: El síndrome de Dravet se caracteriza por una epilepsia resistente a fármacos de inicio en el primer año de vida con crisis con fiebre, y posterior evolución con déficit cognitivo y epilepsia con múltiples tipos de crisis. Habitualmente se diagnosticaba en torno a los 3-4 años de vida, pero el mejor conocimiento de las características de las crisis en los últimos años y el hallazgo de la alteración genética causal más frecuente han permitido adelantar el diagnóstico. Pacientes y métodos: Se presenta una serie de 14 niños diagnosticados de síndrome de Dravet o epilepsia del espectro Dravet. A las características de las crisis ocurridas durante el primer año de vida en estos pacientes, se aplican una serie de criterios de riesgo para ver si es posible hacer el diagnóstico en dicho período de tiempo. Resultados: en el 100% de los niños de esta serie se podía sospechar el diagnóstico en el primer año de vida aplicando estos criterios. Además, el 79% cumplían ya los criterios de riesgo en la primera crisis. Conclusiones: Es posible obtener un índice alto de sospecha de síndrome de Dravet en el primer año de vida. Es esencial, por tanto, la difusión de los criterios clínicos que permiten la sospecha diagnóstica temprana y la distinción de crisis febriles de otro origen, y el establecimiento de un protocolo de recogida de datos para las crisis con fiebre en el primer año de vida(AU)

Introduction: Dravet syndrome is a drug resistant epilepsy which starts in the first year of life with febrile seizures, followed by cognitive impairment and epilepsy with multiple seizure types. Diagnosis has been typically made at the age of three to four years, but earlier diagnosis is now possible as clinical features are better recognised and molecular diagnosis is available. Patients and methods: We studied a series of 14 children with Dravet syndrome or Dravet spectrum epilepsy. A screening test, developed by other authors to distinguish the febrile seizures in Dravet syndrome from febrile seizures from other origin, was applied to the clinical features of the seizures occurring during the first year of life in our patients. Results: Clinical suspicion of Dravet spectrum epilepsy was possible in 100% of children in our series. Moreover, taking into consideration only the first seizure, 79% of patients scored sufficiently to detect Dravet syndrome. Conclusions: Dravet syndrome can be recognised during the first year of life. It is important that physicians are made aware of these clinical criteria capable to distinguish febrile seizures in Dravet syndrome from febrile seizures of other origin, and set up a protocol to collect appropriate data regarding febrile seizures occurring in the first year of life(AU)

[Febrile seizures in the first year of life: Dravet spectrum epilepsy?]. / Crisis con fiebre en el primer año de vida: ¿epilepsia del espectro Dravet?

INTRODUCTION: Dravet syndrome is a drug resistant epilepsy which starts in the first year of life with febrile seizures, followed by cognitive impairment and epilepsy with multiple seizure types. Diagnosis has been typically made at the age of three to four years, but earlier diagnosis is now possible as clinical features are better recognised and molecular diagnosis is available. PATIENTS AND METHODS: We studied a series of 14 children with Dravet syndrome or Dravet spectrum epilepsy. A screening test, developed by other authors to distinguish the febrile seizures in Dravet syndrome from febrile seizures from other origin, was applied to the clinical features of the seizures occurring during the first year of life in our patients. RESULTS: Clinical suspicion of Dravet spectrum epilepsy was possible in 100% of children in our series. Moreover, taking into consideration only the first seizure, 79% of patients scored sufficiently to detect Dravet syndrome. CONCLUSIONS: Dravet syndrome can be recognised during the first year of life. It is important that physicians are made aware of these clinical criteria capable to distinguish febrile seizures in Dravet syndrome from febrile seizures of other origin, and set up a protocol to collect appropriate data regarding febrile seizures occurring in the first year of life.

Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I / No disponible

La acidosis glutárica tipo I (AGTI) es un trastorno poco frecuente del metabolismo de los ácidos orgánicos consecuencia de un défi cit congénito de la enzima mitocondrial glutaril-CoA deshidrogenasa. Existe una alteración del metabolismo de los aminoácidos triptófano, lisina e hidroxilisina y se produce un aumento de los niveles de ácido glutárico que clínicamente se manifi esta con crisis distónicas agudas en niños de corta edad. La acumulación de ácido glutárico produce neurotoxicidad en los ganglios de la base y corteza fronto-temporal lo que puede causar distonía progresiva, hipotonía, disartria y crisis epilépticas. El diagnóstico precoz de esta enfermedad es crucial ya que la dieta y el tratamiento pueden alterar su historia natural. Presentamos los hallazgos neuroradiológicos de una adolescente de 16 años con AGTI que presentaba un síndrome distónico crónico. La RM demostró afectación del putamen de forma bilateral y de la sustancia blanca periventricular, además de atrofi a temporal en ambos hemisferios y ensanchamiento de ambas cisuras de Silvio

Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by defi ciency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging fi ndings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fi ssures

Manía en un adolescente con retraso mental grave y déficit visual: factores de riesgo y dificultad diagnóstica en trastornos del neurodesarrollo / Mania in an adolescent boy with severe mental retardation and visual deficit: risk factors and diagnostic difficulty in neurodevelopmental disorders

Introducción: Se han descrito episodios de manía-hipomanía en un 7% de los niños con déficit del neurodesarrollo. El retraso mental, motor y del lenguaje son factores de riesgo para enfermedad bipolar. Caso clínico: Describimos a un adolescente de 17 años con diplejía espástica por asfixia perinatal, retraso mental grave y déficit visual, sin historia psiquiátrica previa. Su padre padece enfermedad bipolar. Presenta, bruscamente, insomnio global de 8 días de duración, inquietud creciente, apatía y anhedonia. Mejora con lorazepam (1 mg), y trazodona (100 mg/día) en 3 meses, con remisión del cuadro. A los 12 meses presenta, de nuevo bruscamente, insomnio global de 14 días, logorrea e inquietud psicomotriz, por lo que se reinicia la administración de lorazepam y trazodona. Aparecen desorientación, alucinaciones y mayor inquietud. Mejora con olanzapina (2,5 mg/día). Persisten la agitación y las alucinaciones, que se alternan con apatía y anhedonia en un mismo día. Se inicia el tratamiento con valproato sódico intravenoso (16 mg/en 1 h), luego oral, con mejoría del cuadro en la primera semana tras el valproato oral (20 mg/kg/día). Hay un buen contacto con el medio y lenguaje coherente hasta 1,5 años tras el inicio de esta medicación. Discusión: El diagnóstico de manía es especialmente difícil en adolescentes con retraso motor, intelectual o déficit visual. La ciclación rápida, la carga genética y la respuesta a estabilizadores del humor apoyan el diagnóstico

Introduction: Mania-hypomania has been described in 7% of children with neurodevelopmental delay. Mental, motor and language retardation are all risk factors for bipolar disorder. Case report: We describe a 17-year-old boy with spastic diplegia, severe mental retardation, and visual deficit due to perinatal asphyxia, with no previous psychiatric history. His father has bipolar disorder. Our patient suddenly developed a first episode of global insomnia (lasting 8 days), prominent logorrhoea, psychomotor agitation, apathy and anhedonia. He improved with lorazepam (1 mg) and trazodone (100 mg/day) in 3 months, achieving complete remission of symptoms. Twelve months later, he suddenly developed global insomnia again (lasting 14 days) and restlessness. Lorazepam and trazodone were prescribed again. A few days later, he developed confusion, delusions and increased psychomotor agitation. The patient improved with olanzapine (2.5 mg/day), but his restlessness and delusions, which alternated with apathy and anhedonia in the same day, continued. Intravenous valproate (16 mg in 1 h) was started, followed by oral administration of oral valproate (20 mg/kg/day), with marked improvement of symptoms during the first week. He has been stable after 1,5 years of treatment with oral valproate monotherapy. Discussion: The diagnosis of mania is particularly difficult in adolescents with mental, motor and visual deficits. Rapid cycling, genetic factors and mood stabilizer response indicate a probable diagnosis of mania

[Specific disorders in the language development: neurobiological basis]. / Trastornos específicos del desarrollo del lenguaje: bases neurobiológicas.

Studies of twins, familial aggregates and particular phenotypic conditions have shown an inherited basis for some dysphasias or specific developmental language impairments (SLI). This predisposition is usually multifactorial but the analysis of some families allows to postulate an autosomal dominant transmission of deficits in specific modular aspects of linguistic competences. Moreover, neuroimaging studies have shown modifications of normal volumetric interhemispheric asymmetries, and in group of SLI with receptive prominent disorder coexist epileptiform activity in wakefulness and non-REM sleep EEG; in some of these cases, antiepileptic drugs, specially steroids, can significantly ameliorate the language processing. As many patients with SLI have a difficulty for discrimination of subtle temporal indices, a hypothesis can also be made of a dysfunction in various subcortical structures (thalamus, basal ganglia, cerebellum) modulating the cerebral cortex in phonological processing.

[Neurobiology of attention deficit-hyperactivity disorder]. / Neurobiología del trastorno de la atención e hipercinesia en el niño.

This is a review of current relevant evidences concerning the nature and pathophysiological mechanisms of attention deficit hyperactivity disorder (ADHD). From a neuropsychological point of view, clinical symptoms seem to arise from an early dysfunction of the executive system. Patients with ADHD have deficits in inhibitory control, cognitive flexibility, working memory and self-motivation, and all of them account for the attentional deficit in non automatic information processing. Decrease in prefrontal, caudate and pallidal structures, which sustain the executive function, have been found in neuroimaging volumetry. Cognitive evoked potentials obtained during attentional tasks have augmented latencies and abnormal topography. A dopaminergic deficit in the structures sustaining executive function is postulated from the results in experimental animal models and from functional neuroimaging studies in patients, and this seem to be the foundation of the favorable outcome with psychostimulants in correctly diagnosed patients. Psychopedagogic interventions are necessary to help the patient in order to get an optimal internal locus of control, which is necessary for attention and impulsiveness inhibition, and also for compensation of associated disorders.

Neuropsychological evaluation of children with intracranial tumors: impact of treatment modalities.

Antineoplastic treatment has a deleterious effect on intellectual functions, which is mainly attributable to radiotherapy. With the object of determining the neuropsychological disturbances associated with brain irradiation in the child, and to try to differentiate them from the effects caused by the other types of treatment (surgical and chemotherapy) as well as from the effects of the tumor itself, a cross-sectional study was carried out in 25 survivors of medial edge intracranial tumors. In order to monitor the effect of systemic chemotherapy on the cognitive functions, and the effect of prolonged absence from school, two control groups were formed, one made up of subjects treated with chemotherapy for extracranial tumors, and the other of patients with non-malignant chronic disease. Neuropsychological functions were measured using the Spanish version of the Wechsler scale, as well as the following tests: Spreen-Benton, ITPA and TALE scales, Yuste Memory Test, Thurstone Attention Test, and the Rey Complex Figure. In addition to a progressive decline found in the full scale intelligence quotient in children irradiated for intracranial tumors, variance analysis showed that these patients deteriorate mainly in visual attention and memory, but also significantly in verbal fluency and in the Performance Intelligence Quotient and all its subtests, when compared to the control groups. Visual attention and the Wechsler Picture Arrangement and Block Designs, were the tests whose decline correlated with the total radiation administered. The article relates this specific neuropsychological injury with the total brain irradiation dose but also with the structures located in the cone-down fields of irradiation to boost regions in the middle edge intracranial content.

[Gastroesophageal reflux in pediatric neurologic patients]. / Reflujo gastroesofágico en pacientes neurológicos pediátricos.

With the aim of evaluating the incidence of gastroesophageal reflux (GER) in neurologic pediatric patients with severe motor and/or psychiatric involvement, a retrospective study of 140 infants followed at the Neuropediatric Unit was realized. Forty-five patients (32.1%) had moderate to severe mental retardation (ms RR), 21 of these patients had associated tetraparetic cerebral palsy (T-CP). The rest of the infants presented variable degrees of neurologic involvement: 25 diplegic (D-CP), 27 hemiparetic (H-CP), 22 with slight mental retardation or borderline IQ without motor deficit (SMR), and 21 had attention deficit disorder with hyperactivity (ADD-H). The diagnosis of GER was based on clinical symptomatology and barium ingestion with fluoroscopy and/or esophagoscopy. GER was confirmed in 27 patients: 19 (90.5%) with T-CP, 6 (25%) with ms-MR and 2 (8%) with D-CP. The rest of the infants did not have GER. There was a very significant difference in the frequency of GER in the T-CP group with respect to the other groups (p < 0.001) and a significant difference in the ms-MR patients with respect to the other groups (p < 0.05). The treatment of GER was surgical in ten patients (37%), after failure of medical treatment in 8; exclusively medical treatment in 10 cases (37%) and postural and dietetic treatment in 7 (26%) patients. Good control of GER, resulting in an improvement in the quality of life, occurred in 90% of the patients treated surgically and only in 55% of the patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)

[Insulin resistance and clinical evolution in infantile myotonic dystrophy]. / Resistencia a la insulina y evolutividad clínica en la distrofia miotónica infantil.

We present the results of a 13 year follow-up of seventeen children with myotonic dystrophy, with the aim of better understanding the progression of this disease. We want to emphasize two basic aspects; first, the detection of myotonia with the use of EMG during the first five years of life when the clinical profile is suggestive of the disease, previous reports have stated that this sign appears relatively late in the disease process, and secondly, we want to point out that more than 50% of these patients showed insulin-resistance starting from the sixth year of life. This aspect of the disease has been well described in adult patients, but is practically absent in the pediatric literature. Hyperinsulinemic subjects demonstrated an intellectual quotient significantly lower than those subjects with normal insulin levels (p < 0.01). Basal insulin levels also had a predictive value in relation to the rest of the points n the insulin curve. The changes in insulin resistance are discussed in relation to cellular membrane changes present in myotonic dystrophy.

[Chronologic study of signs of myocardiopathy in progressive muscular dystrophy]. / Estudio cronológico de los signos de miocardiopatía en las distrofias musculares progresivas.

In order to analyze the evolution of cardiomyopathy in progressive muscular dystrophies, thirty-three patients (17 with Duchenne type, 11 with Becker type and 5 with the autosomal recessive type dystrophy) were studied retrospectively. Cardiac and systemic follow-up every 3-6 months was made in 29 patients. The electrocardiogram was the first test that became altered, followed by the echocardiogram and thoracic radiograph and finally heart failure manifestations. There was a direct correlation between age and the appearance of abnormal cardiac tests. Electrocardiographic alterations, in patients who were less than 12.5 years of age, were significantly more frequent in the group with Duchenne dystrophy that in the no-Duchenne group. In regards to the appearance of the echocardiographic and radiographic abnormalities, there were no significant differences between the two groups. However, we have noticed a trend towards a more frequent and earlier presentation of these abnormalities in the Duchenne's muscular dystrophy than in the no-Duchenne group.

Neuropsychological outcome of children after radiotherapy for intracranial tumours.

With the aim of determining the neuropsychological disturbances associated with cranial radiotherapy in the child, a cross-sectional study was carried out on 25 survivors of medial-edge intracranial tumours. Children irradiated for intracranial tumours experienced deterioration mainly in visual attention and memory, but also in verbal fluency, full-scale IQ, and performance IQ and all its subtests, compared with control groups. This deterioration progressed with time, finally involving at least abstract thought and verbal skills. The pattern of damage by irradiation varied according to the degree of brain maturity, therefore the younger the child at irradiation, the greater the decline in IQ and visual-constructive abilities, and the earlier the deterioration of visual memory and verbal skills.

[Alternating hemiplegia. Partial effectiveness of treatment with flunarizine]. / Hemiplejía alternante. Efectividad parcial del tratamiento con flunarizina.

A case of alternating hemiplegia in a young girl is presented. The partial benefits of treatment with a calcium antagonist Flunarizine in this patient and in those reported in literature are reviewed. The onset of the disease in this girl was at three months of age with several episodes that were diagnosed as seizures; afterwards she presented, besides, repeated attacks of hemiplegia involving both sides of her body in an alternating way each time with daily frequency and hours of days of duration accompanied of bad mood and irritability as well as autonomic disturbances, oculomotor abnormalities, acquired mental retardation and residual focal neurological abnormalities. After one year of treatment with a calcium-entry blocker: Flunarizine, there was a 30% reduction in the attacks frequency as well as in its severity and stop of the progression of mental retardation. So we report the consequence of precocious diagnosis and treatment of this not well known entity whose clinical signs resemble paroxistic vascular anomalies in the brainstem territory.

[Functional cerebral lateralization: neurobiology and clinical aspects in childhood]. / Lateralización funcional cerebral: neurobiología y clínica en la infancia.

Anatomical and functional evidences of cerebral hemispheric asymmetries are reviewed in reference to fetal life, infancy and childhood. In general, left hemisphere deals with linguistic-sequenced-analytic-logic-deductive cognitive processing, whereas the right hemisphere is involved in spatial-simultaneous-inductive-intuitive tasks; attention and interactional functions predominate on the right hemisphere, too. The clinical and technological means to diagnose the functional lateralization in individual patients are discussed. A critical review is made of abnormal lateralizations and interhemispheric supplencies in various neuropsychiatric conditions of childhood: learning disabilities, epilepsy, attention deficit disorder, mental deficiency with chromosomopathies and infantile autism.

[Asymmetric crying facies syndrome]. / Síndrome de facies asimétrica con el llanto.

We report four cases with syndrome of asymmetric crying facies, analyzing particularly the etiology, embryology, and incidence of the congenital hypoplasia of depressor anguli oris muscle. In one of the cases, with multiple malformations, the patient had an abnormal karyotype, 47,XX, +i(18p). We stress the high incidence of associations with congenital malformations (eight fold the general population) and more specifically with congenital heart disease, musculoskeletal, and genito-urinary defects. The diagnosis of MDAO agenesis is basically clinic, being as differential diagnosis the paralysis of the 7th cranial nerve, defining it with electrophysiological techniques.