Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life.

INTRODUCTION: Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. METHODS: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients' medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. RESULTS: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. CONCLUSIONS: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life.

[Use of benzodiazepines in prolonged seizures and status epilepticus in the community]. / Uso benzodiacepinas en crisis prolongadas y estado epiléptico en la comunidad.

Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.

[Predictive variables for mental retardation in a Pediatric Epilepsy Monitoring Unit. Neuropsychological assessment]. / Variables predictoras de retraso mental en una unidad de monitorización videoelectroencefalográfica pediátrica. Evaluación neuropsicológica.

AIM: We sought to describe the epidemiological and clinical data from our patients in the Pediatric Epilepsy Monitoring Unit (PEMU) of the Sant Joan de Deu Hospital of Barcelona, and determine the variables of risk for mental retardation. PATIENTS AND METHODS: A retrospective review of PEMU reports and hospital discharge summaries from March 2005 to December 2008 was conducted. The data from patients with intelligence quotient (IQ) estimated, older than 3 years of age and with epileptic electroencephalography (EEG) activity was analyzed in 158 patients (8.8 +/- 5.2 years; 55.1% boys). Of those pediatric patients, 63 had IQ less than 70 and 47 an IQ greater than or equal to 70. Intractable epilepsy was present in all of them. RESULTS: The percentage of the patients with mental retardation is significantly higher in patients with onset of epilepsy before 24 months (68.3%) than patients with later onset (27.7%). Onset of seizures, EEG findings and epilepsy etiology are significant risk factors for mental retardation. CONCLUSIONS: Early age at seizure, multifocal epilepsy and cryptogenic etiology are factors of worse prognosis to normal development of cognitive functions in pediatric intractable epilepsy.

[Angelman syndrome: physical characteristics and behavioural phenotype in 37 patients with confirmed genetic diagnosis]. / Síndrome de Angelman: características físicas y fenotipo conductual en 37 pacientes con diagnóstico genético confirmado.

INTRODUCTION: Angelman syndrome (AS) is characterised by mental retardation, ataxic gait, epilepsy, absence of language and a special series of physical traits behavioural phenotype. Its incidence is estimated as one in every 20,000 individuals. On the basis of discoveries made in molecular biology, patients can be classified as belonging to five types: deletion, paternal uniparental disomy (UPD), imprinting defects, mutation of the UBE3A ubiquitin protein ligase gene and unidentified mechanism (15% 20% of patients). Some studies report significant correlations between the phenotype and the genetic cause. PATIENTS AND METHODS: We reviewed, retrospectively, 37 patients suffering from AS with a positive genetic study and who had been controlled for at least two years in the Neurological Service at the Hospital Sant Joan de D u. Data was collected on physical characteristics, behavioural phenotype, type of communication, sleep disorders and the medication they needed, as well as epilepsy, start age, types of seizures, medication, schooling and social integration. RESULTS: 87% of cases were due to de novo deletion, 8% were caused by UPD, and 5% had their origins in imprinting defects. The average age of diagnosis was 6.5 years. The sleep disorders present in 48% of the patients required medication in 67% of cases, and 95% presented epilepsy. The most frequent seizures were myoclonic, tonic clonic and atonic. The electroencephalogram (EEG) was the characteristic found in the AS in 68%. The most effective treatment was afforded by valproate and clonazepam. CONCLUSIONS: As regards the phenotype, no differences were found according to the genetic alteration. The most effective treatment for the sleep disorders was melatonin. Epilepsy was an almost constant finding in our series, as was cognitive affectation. Lastly, it must be pointed out that educational and socio occupational integration is difficult for patients suffering from AS.

[A ketogenic diet: is this a valid alternative in refractory epilepsy]. / Dieta cetógena: ¿una alternativa válida en epilepsias refractarias?

INTRODUCTION: The ketogenic diet was first used in refractory epilepsy of childhood in the early 1920s. It was forgotten when new antiepileptic drugs were introduced, but recently has been used again. Although its efficacy in the treatment of epilepsy, in some patients, is beyond doubt, its mechanism of action is still not clear. There are three types of diet: the classical diet with a proportion of 4:1 of long chain fatty acids, with MCT oil and with modified MCT oil. OBJECTIVE: To present a protocol recently designed in our hospital. We include the type of diet, form of onset, subsequent follow up of complications, clinical and electroencephalographic response and side effects seen in the patients. PATIENTS AND METHODS: Introduction of the ketogenic diet with MCT oil in six patients aged between 2 and 11 years, with various types of epilepsy, all resistant to treatment, who had been unsuccessfully treated for 28 months in one case and between 4 and 6 months in the others. We evaluated the response on the criteria of Huttenlocher and Panic electroencephalograms. RESULTS: Two of the patients improved with good control of their disorder and the EEG became normal. No serious side effects were seen apart from gastrointestinal symptoms which improved when the quantity of MCT oil was reduced. CONCLUSIONS: In patients with drug resistant epilepsy it is convenient to have a guideline for treatment using a ketogenic diet. It is also useful to have a multi disciplinary team for management, follow up to detect late side effects and obtain the cooperation of the patient s family in following the protocol.

Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical course, neuropathology and brain lipid composition in this Gaucher disease variant.

Glucosylceramide lipidosis results from a defective lysosomal degradation of this glycolipid. Lipid degradation is controlled by two components, the enzyme beta-glucocerebrosidase and a sphingolipid activator protein. While most Gaucher cases are due to mutations within the gene that codes for the lysosomal enzyme, only two patients have been described with normal enzyme levels and mutations in the gene for the sphingolipid activator protein C (sap-C). Here we present the detailed neurological manifestations, neuropathological findings and brain lipid composition in one sap-C-deficient patient. The patient was an 8-year-old boy who presented with transient losses of consciousness, myoclonic jerks and generalized seizures resistant to all antiepileptic drugs. He developed progressive horizontal ophthalmoplegia, pyramidal and cerebellar signs, and died at the age of 15.5 years. Neuropathological studies demonstrated neuronal cell loss and neuronophagia, massive intraneuronal lipid storage and lack of perivascular Gaucher cells. Electron microscopy examination showed different types of storage including lipofuscin granules as well as the cytosomes with parallel arrays of bilayers that are assumed to be formed by stored lipids. General brain lipid composition did not show a remarkable increase or loss of any of the major lipid fractions but the glucosylceramide concentration in the cortex of several anatomical regions showed a striking increase. Fatty acid composition of the ceramide moiety clearly suggests that gangliosides are the main precursors in the cerebral cortex, while it implies an additional and distinct source in the cerebellum. Studying the phenotypic consequences of mutant sphingolipid activator proteins is critical to a better understanding of the physiological significance of these proteins.

[The Ohtahara's syndrome: a special form of age-dependent epilepsy]. / Síndrome de Ohtahara: una forma de epilepsia edad-dependiente.

The aim of this report is to review the clinical and the outcome data in four patients with Ohtahara syndrome at Sant Joan de Déu Hospital, Barcelona, following the same clinical and electroencephalografic criteria reported by the author. The etiology of this syndrome is unknown and plurifactorial. Investigation studies were negative except for the EEG and neuroimaging. MRI was performed in two children, and pachigyria was observed in one and mycropoligyria in the other. There were no response to cofactors, phenobarbital, vigabatrine and valproate. Therefore two patients underwent treatment with ACTH with no response in one and good response in the other. Two patients died at 2 and 6 months; other one was transferred to another center at 6 months-old and was lost at follow-up. The fourth patient, fourteen-month-old, is free of seizures with improvement of EEG register with important development retardation. We conclude that Ohtahara syndrome is a severe neonatal epilepsy with poor neurologic outcome; MRI detects often brain malformations as cortical dysplasia and a therapeutic trial of ACTH is indicated because the possibility of control of the seizures.

[Infantile spasms in children with Down's syndrome]. / Espasmos infantiles en niños con síndrome de Down.

Two hundred eighty six infants with Down syndrome have been studied. Infantile spasms have been identified in nine of them, in which background, EEG pattern and its evolution, modalities of treatment and its effects, neuroimaging and development course have been revised. None of these patients had either familiar or personal pathological antecedents. The pattern in the first EEG made was hypsarrhytmic in all cases except one which showed a multifocal paroxystical activity, with intermittent and bilateral bursts of spike-waves. The treatment first used was ACTH in four cases, valproate in three cases and phenobarbital in two cases (one of these associated with nitrazepam). The ACTH treatment was effective in seven infants, either was the first or the second choice. An infant in whom the first treatment with ACTH was not successful, responded to the association with valproate+clonazepam. One patient treated initially with phenobarbital+nitrazepam, having no response to different prescriptions, responded finally to the association of carbamacepin+vigabatrin. The first treatment with valproate or phenobarbital had no effect in all patients. The EEG pattern improved in all cases just after the treatment response. Normal tracing was found for a period of two months to three years. Cranial TC was performed to three infants showing one of them a discrete ventricular dilatation and periventricular calcifications that suggested tuberous sclerosis. It is important to point out that, although the good effect of therapy and EEG pattern normalization, the development is below what had been expected in children with Down syndrome. Behavioral problems have been found in seven (77.7%) of these children.(ABSTRACT TRUNCATED AT 250 WORDS)

[Episodes of apnea in an infant: unusual forms of epileptic seizures]. / Episodes d'apnée chez un nourrisson: formes inhabituelles de crises comitiales.

The authors report the observation of an infant who begins at the age of 7 months to present episodes of epileptic apnea with cyanosis, lost of consciousness, hypotony and sometimes ocular revulsion and distal myoclonia. From their onset there are several a day, more frequent during sleep than when awake. From the EEG point of view they are characterized by a 5-7 c/sec large and diffuse rhythm. The infant also presents epileptic myoclonias, tonic and partial seizures. She has a very slight evolutive encephalopathy, disclosed at the age of 4 months by a psychomotor retardation. No etiology has been proved. The CT scan shows during the evolution a cortico-subcortical atrophy. Every type of seizure was very resistant to different treatments. The apneas disappeared after ACTH therapy. The authors demonstrate the epileptic nature of these apneas which are very rarely observed after the neonatal period.

[Comb-like rhythm: an EEG pattern peculiar to leucinosis]. / "Ritmos en peine": un patrón EEG propio de la leucinosis.

EEG and clinical aspects of a newborn baby with maple syrup urine disease are presented. EEG shows in central areas "Comb-like rhytms" with pseudo-periodic background activity. These patterns seem peculiar to maple syrup urine disease according to Trottier et al. (1975). EEG findings may suggest screening for aminoacids.

[Considerations on neonatal epileptic encephalopathies apropos of a personal case]. / Considérations sur les encéphalopathies épileptiques néonatales à propos d'une observation personnelle.

Studies were done on a newborn with tonic status seizures beginning at 15 days old to his death at 3 months of age. The clinical features were: (1) important psychomotor retardation; (2) tonic seizures consisting of flexion or extension of the upper limbs and head, ocular revulsion, facial cyanosis and respiration troubles. The seizure mean duration was from 4 to 6 sec. The seizures appeared sometimes isolated, sometimes in bursts with an increasing frequency but not related to the nycthemeral cycle. In the EEG there appears a 'burst-suppression' pattern which persists continuously whether the patient was asleep or awake. The clinical and electroencephalographic findings suggest Ohtahara's syndrome. Some considerations are made about the clinical, electroencephalographic and aetiologic findings of the several epileptic encephalopathies with suppression bursts in the newborn.