[Complex febrile Seizures or Dravet syndrome?: Description of 3 case reports]. / ¿Crisis febriles complejas o síndrome de Dravet?: Descripción de 3 casos clínicos.

INTRODUCTION: Dravet syndrome (DS) is one of the most intractable forms of epilepsy that begins in infancy. This syndrome is characterized by beginning with complex febrile seizures (FS) in a healthy infant and progresses to refractory epilepsy with psychomotor regression. The detection of a SCN1A mutation encoding the sodium channel can confirm the diagnosis. OBJECTIVE: To report 3 confirmed cases of genetically DS. CASE REPORTS: We describe 3 girls diagnosed with complex FS that started when they were between 2 and 7 months old. FS were frequent, hemi generalized and myoclonic associated with recurrent febrile status epilepticus (SE). Despite FS and SE recurrence, the psychomotor development, electrophysiological studies and magnetic resonance imaging (MRI) of the brain were normal. After a year, they developed afebrile seizures progressing to refractory epilepsy with developmental regression. A molecular study detected SCN1A mutation confirming DS. The specific antiepileptic treatment and prevention of febrile episodes allowed partial control of epilepsy with some recovery of psychomotor skills. CONCLUSIONS: The high frequency complex FS associated with recurrent SE in a previously healthy infant should alert about the possibility of DS. Molecular diagnostics helps us to establish a drugs and non-drug therapies treatment, as well as long-term prognosis and genetic counseling.

Interactions between genetic admixture, ethnic identity, APOE genotype and dementia prevalence in an admixed Cuban sample; a cross-sectional population survey and nested case-control study.

BACKGROUND: The prevalence and incidence of dementia are low in Nigeria, but high among African-Americans. In these populations there is a high frequency of the risk-conferring APOE-e4 allele, but the risk ratio is less than in Europeans. In an admixed population of older Cubans we explored the effects of ethnic identity and genetic admixture on APOE genotype, its association with dementia, and dementia prevalence. METHODS: A cross-sectional catchment area survey of 2928 residents aged 65 and over, with a nested case-control study of individual admixture. Dementia diagnosis was established using 10/66 Dementia and DSM-IV criteria. APOE genotype was determined in 2520 participants, and genetic admixture in 235 dementia cases and 349 controls. RESULTS: Mean African admixture proportions were 5.8% for 'white', 28.6% for 'mixed' and 49.6% for 'black' ethnic identities. All three groups were substantially admixed with considerable overlap. African admixture was linearly related to number of APOE-e4 alleles. One or more APOE-e4 alleles was associated with dementia in 'white' and 'black' but not 'mixed' groups but neither this, nor the interaction between APOE-e4 and African admixture (PR 0.52, 95% CI 0.13-2.08) were statistically significant. Neither ethnic identity nor African admixture was associated with dementia prevalence when assessed separately. However, considering their joint effects African versus European admixture was independently associated with a higher prevalence, and 'mixed' or 'black' identity with a lower prevalence of dementia. CONCLUSIONS: APOE genotype is strongly associated with ancestry. Larger studies are needed to confirm whether the concentration of the high-risk allele in those with African ancestry is offset by an attenuation of its effect. Counter to our hypothesis, African admixture may be associated with higher risk of dementia. Although strongly correlated, effects of admixture and ethnic identity should be distinguished when assessing genetic and environmental contributions to disease risk in mixed ancestry populations.

[Peri-ictal electrocardiographic alterations in paediatric epilepsy patients. A prospective study]. / Alteraciones electrocardiográficas periictales en pacientes pediátricos con epilepsia. Un estudio prospectivo.

INTRODUCTION: Epileptic seizures can be associated with peri-ictal heart rhythm disorders and even sudden death (SUDEP). Few paediatric studies have been conducted on the subject. AIM: To determine heart rhythm disorders in paediatric patients with epilepsy who were studied with video-electroencephalogram (video-EEG). METHODS: Prospective, observational study in patients under 18 years of age admitted for video-EEG at the Hospital Clinico Red de Salud UC-Christus, Santiago, Chile. A neurological and cardiological evaluation and electrocardiogram (ECG) were performed, in addition to a Holter ECG simultaneously with the video-EEG. RESULTS: Twenty-five patients were studied, 12 with refractory epilepsies, 23/25 focal and 20 on polytherapy. Altogether 768 hours of video-EEG were recorded, including 281 seizures in 15 patients: 157 clinical and 103 generalised. There were no serious arrhythmias, only non-specific or probably benign disorders, mainly incomplete right bundle branch block in 11 patients, which were more frequent in refractory epilepsies (p<0.036). Heart rate variation occurred mainly in seizures >30 seconds. No patient presented SUDEP. CONCLUSIONS: This is the first prospective study, with a new technique, using video-EEG and Holter ECG simultaneously in paediatrics. Despite the high number of seizures and refractory patients, we found no serious heart rhythm disorders, consistent with the clinical evaluation. Right bundle branch block is considered a non-pathological cardiological finding, but was highly prevalent in our sample compared to the normal population, especially in refractory epilepsy. Given that this is a serious event in epilepsy, it is important to further investigate such studies to assess preventive measures.

TITLE: Alteraciones electrocardiográficas periictales en pacientes pediátricos con epilepsia. Un estudio prospectivo.Introducción. Las crisis epilépticas pueden asociarse a alteraciones del ritmo cardíaco periictales e incluso a muerte súbita (SUDEP). Existen escasos estudios pediátricos al respecto. Objetivo. Determinar las alteraciones del ritmo cardíaco en pacientes pediátricos con epilepsia estudiados con videoelectroencefalograma (video-EEG). Métodos. Estudio prospectivo, observacional, en pacientes menores de 18 años ingresados para video-EEG en el Hospital Clínico Red de Salud UC-Christus, Santiago, Chile. Se realizó una evaluación neurológica y cardiológica, electrocardiograma (ECG) y Holter ECG simultáneo al video-EEG. Resultados. Se estudió a 25 pacientes, 12 con epilepsias refractarias, 23/25 focales y 20 en tratamiento con politerapia. Se registraron 768 horas de video-EEG, incluyendo 281 crisis epilépticas en 15 pacientes: 157 clínicas y 103 generalizadas. No hubo arritmias graves; sólo alteraciones inespecíficas o probablemente benignas, principalmente bloqueo incompleto de la rama derecha en 11 pacientes, más frecuente en las epilepsias refractarias (p menor de 0,036). La variación de la frecuencia cardíaca ocurrió principalmente en crisis > 30 segundos. Ningún paciente ha presentado SUDEP. Conclusiones. Éste es el primer estudio prospectivo, con una nueva técnica, usando simultáneamente video-EEG y Holter ECG en pediatría. Pese al alto número de crisis y pacientes refractarios, no encontramos alteraciones graves del ritmo cardíaco, en concordancia con la evaluación clínica. El bloqueo de la rama derecha se considera un hallazgo cardiológico no patológico, pero tuvo una alta prevalencia en nuestra muestra, comparada con la población normal, especialmente en la epilepsia refractaria. Dado que la SUDEP es un evento grave en la epilepsia, es importante ahondar más en este tipo de estudios para evaluar medidas preventivas.

Presence of the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease. / Polimorfismo p.L456V, presencia en pacientes cubanos con diagnóstico clínico presuntivo de la enfermedad de Wilson.

INTRODUCTION AND AIMS: Wilson's disease is characterized by the accumulation of copper in different organs, mainly affecting the liver, brain, and cornea, and is caused by mutations in the ATP7B gene. More than 120 polymorphisms in the ATP7B gene have been reported in the medical literature. The aim of the present study was to identify the conformational changes in the exon 3 region of the ATP7B gene and detect the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease. MATERIAL AND METHODS: A descriptive study was conducted at the Centro Nacional de Genética Médica and the Instituto Nacional de Gastroenterología within the time frame of 2007-2012 and included 105 patients with a clinical diagnosis of Wilson's disease. DNA extraction was performed through the salting-out method and the fragment of interest was amplified using the polymerase chain reaction technique. The conformational shift changes in the exon 3 region and the presence of the p.L456V polymorphism were identified through the Single-Strand Conformation Polymorphism analysis. RESULTS: The so-called b and c conformational shift changes, corresponding to the p.L456V polymorphism in the heterozygous and homozygous states, respectively, were identified. The allelic frequency of the p.L456V polymorphism in the 105 Cuban patients that had a clinical diagnosis of Wilson's disease was 41% and liver-related symptoms were the most frequent in the patients with that polymorphism. CONCLUSION: The p.L456V polymorphism was identified in 64 Cuban patients clinically diagnosed with Wilson's disease, making future molecular study through indirect methods possible.

[The direct costs of epilepsy in a Chilean population]. / Costes directos de la epilepsia en una población chilena.

INTRODUCTION: Epilepsy Chilean prevalence is 17-21/1,000 inhabitants. In past years, there is concern for the high costs involved in its handling. AIM. To estimate the direct costs of treatment and handling in specific population with epilepsy. PATIENTS AND METHODS: It is a retrospective study, in 6 groups of people with epilepsy: recent diagnosis (RD), remission (R), occasional seizures (OS), active without resistance to drugs (AWRD), resistance to pharmacological treatment (RPT), and epilepsy surgery (S). Data and characteristics tabulation and economical study of each group were made, considering 1 year of treatment. A comparison was made between them and their average in relation to international data. RESULTS: 293 patients. 52% male. 76% adults. 25% students. 55% focal seizures. Costs per group: (USD/patient/year): RD, 443; R, 316; OS, 430; AWRD, 711; RPT, 946; S, 4,262. Direct average cost of treatment for epilepsy in this population: 615 USD/patient/year. CONCLUSIONS: When differentiating in groups of individuals with epilepsy, the highest average annual cost is in surgery and the lowest in remission. In all the groups, except for surgery one, the highest expense is in drugs (average 81%). In relation to other countries, our direct costs are 5 times lower than in some developed countries and 3.5 times higher than in other developing countries. This data is of interest to governmental and financial spheres, so to provide a better quality of life for people with epilepsy, lowering costs and fees for their treatment and contributing to epilepsy and surgery national programs.

Intractable epilepsy in vascular congenital hemiparesis: clinical features and surgical options.

Forty-one patients with vascular congenital hemiplegia and intractable epilepsy were reviewed. Most had severe hemiparesis, mental retardation, porencephaly, and focal epilepsy. Thirty-three were considered surgical candidates and 25 underwent surgery. Seizure freedom and significant seizure reduction were achieved in 12 of 13 patients after functional hemispherectomy, 4 of 6 after temporal lobectomy, 2 of 2 with extratemporal focal resections, 1 of 3 with corpus callosotomy, and 1 with porencephalic cyst drainage.

[Childhood epilepsy status in a university hospital: a descriptive study]. / Estado epiléptico infantil en unhospital universitario: estudio descriptivo.

INTRODUCTION: Epileptic status (ES) is a medical emergency with a high rate of morbidity and mortality. AIM. To produce a retrospective description of the ES that are seen in the paediatric population attended in our centre. PATIENTS AND METHODS: We surveyed the records of 41 patients who presented ES and were controlled in the child neurology department between December 1999 and June 2007. Depending on the type of seizures, the cases were classified as either convulsive ES (CES) or non-convulsive ES (NCES). They were divided into categories according their causation using the modified Hauser classification. Newborn infants were excluded. RESULTS: A total of 41 patients were analysed, 25 (60%) of whom were males. The mean age was 32 months. Fifty-one per cent of cases were CES and 49% were NCES. Acute symptomatic ES (ASES) was the most frequent, especially in those under 2 years of age. ES recurrence was found to be 42% and ASES stood out as the least recurrent. The mortality rate was 2%. CONCLUSIONS: There was no difference in the number of cases between CES and NCES, probably due to the use of continual electroencephalogram monitoring in hospitalised patients with impaired consciousness. Hypoxic-ischaemic events were the chief cause of ASES, and malformations of the central nervous system prevailed in those of a remote aetiology. The rate of recurrence was high and in such cases patients must be submitted to a strict follow-up, especially those with an underlying condition.

[Mitochondrial encephalomyopathy, lactic acidosis and features of cerebrovascular disorders]. / Encefalomiopatía mitocondrial, acidosis láctica y apariencia de accidentes vasculares cerebrales.

A 12 year old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) is reported. After a normal childhood, at 9 years of age she developed generalized and hemilateralized seizures. Posteriorly, these episodes became more frequent and were accompanied by headache, homonimous hemianopsia, ataxia, vomiting, photophobia, left hemiparesis, slurred speech and even convulsive status. Laboratory tests evidenced lactic acidosis, brain lucencies at CT Scan and ragged skeletal muscle fibers at muscle biopsy.

Relevance of the pH probe in sleep study analysis in infants.

BACKGROUND: To establish the relationship between sleep apnoea and gastro-oesophageal reflux in infants and describe the clinical, demographic and pHmetric profile and the characteristic of the sleep polysomnography with a pH probe. METHODS: A total of 102 consecutive patients were evaluated. Parents were requested to fill out a questionnaire about symptoms and previous therapy. Gastro-oesophageal reflux was considered abnormal when the percentage of time with pH less than 4 was higher than 4% of total sleep time. RESULTS: A total of 102 infants were enrolled, 53% males. Seventy-four per cent of the infants were full-term babies. At the moment of the polysomnography, the mean age of the sample was 2.6 months. Suspicion of apnoea was the most common clinical diagnosis prior to the study. Only two infants have abnormal electroencephalogram. Mild gastro-oesophageal reflux was seen in 37 (36%) infants, while 22 (21.5%) did not have any reflux episode, and the remaining 43 (42%) infants had reflux index in the pathologic range. Only one patient had an unequivocal temporal relationship between acid oesophageal reflux and respiratory pause with oxygen desaturation. DISCUSSION: Infants with history of apnoea or acute life threatening event frequently had gastro-oesophageal reflux episodes which did not correlated with respiratory events, suggesting that gastro-oesophageal reflux and apnoea often occur in the same infant as two separate events.

[Behavior disorder of the REM sleep in 2 documented cases with polysomnography]. / Trastorno conductual del sueño REM en dos casos documentados con polisomnografía.

We report a 69 years old male with a parkinsonian syndrome and a 50 years old female without neurological problems who showed violent behavior during REM sleep. Polysomnography showed that both bad tonic or phasic muscular activity during REM sleep and a REM sleep behavior disorder was diagnosed. Clonazepam was used in both, with good clinical response. This condition is frequently unrecognized and confused with nightmares, nocturnal delirium or other parasomnias.

Prevalence and importance of congenital cytomegalovirus infection in three different populations.

A Chilean population was compared to low-income and middle/upper-class populations in Birmingham, Ala., with regard to prevalence of congenital cytomegalovirus infection as well as the importance of this infection in neonatal deaths. In the highly seroimmune Chilean (98%) and low-income Birmingham (82%) groups, congenital infections occurred more often (1.7% and 1.9%, respectively) than in the less immune (56%) middle/upper-income group in Birmingham (0.6%). In 407 autopsies reviewed in Chile no neonatal deaths were attributed to cytomegalic inclusion disease, whereas in Birmingham cytomegalovirus was the cause of death in nine of 938 (1%) newborn infants. These findings further support the concept that, despite an apparent lack of protection against intrauterine transmission, maternal immunity reduces the risk of severe fetal infection.

[Neuroborreliosis in Chile. Report of a child probably infected by imported pets]. / Neuroborreliosis en Chile. Caso pediátrico de probable adquisición por mascotas importadas.

Lyme disease, caused by the spirochete Borrelia burgdorferi, has several clinical manifestations and is transmitted to man by tick bites. In Chile and Latin America, several cases have been reported, but none with immunoblot confirmation or isolation of the infecting organism. We report a 9 year old boy consulting with bilateral facial palsy, polyradiculoneuritis with tetraparesis and meningeal irritation. Cerebrospinal fluid analysis showed increased protein concentration without pleocytosis and negative viral or bacterial cultures. IgM antibodies against Borrelia burgdorferi, were positive by ELISA and were confirmed by immunoblot at the Reference Laboratory of the University of Connecticut. The child had a recent contact with hamsters brought from Germany. The substantiation of Lyme disease existence in Chile should prompt the search and isolation of the causal agent.

Alteraciones polisomnográficas en lactantes con reflujo gastroesofágico / Polysomnographic abnormalities in infants with gastroesophageal reflux

BACKGROUND: Infant apnea is a common problem that conveys significant burden to families and physicians. Its temporal relationship with gastroesophageal reflux (GER) is controversial. AIM: To establish whether infants with GER of different magnitude have a higher incidence of respiratory events than children without GER. PATIENTS AND METHODS: 146 consecutive patients were evaluated with polisomnography (PSG) and with an esophageal pH probe. Those infants without GER episodes or with an esophageal pH below 4.0 in less than 5 per cent of total sleep time were considered as physiologic GER (Group I), between 5-10 per cent as mild GER (Group II), and over 10 per cent as severe GER (Group III). These groups were evaluated for demographic and polysomnographic characteristics. RESULTS: There were no differences in the demographic and global PSG characteristics neither in oxymetry, heart rate or electroencephalographic abnormalities. Group III infants had a higher percentage of active sleep compared to infants of Group I (p < 0.05) and higher incidence of central pauses and apneas compared to infants of Group I (p < 0.05). CONCLUSIONS: The presence of severe GER may modify the sleep pattern in infants, increasing the percentage of active sleep. The presence of central pauses and apneas in infants with severe GER suggest an association between the inmaturity of the respiratory centers and the adaptation of the anti-reflux mechanisms.

Ventilacion mecanica en insuficiencia respiratoria de origen pulmonar. / Mechanical vantilation in respiratory insufficiency of pulmonary origin

Se efectua un analisis retrospectivo de fichas de ninos con insuficiencia respiratoria aguda (I.R.A.) de origen exclusivamente pulmonar que necesitan ventilacion mecanica (V.M.) durante el periodo de 1980 y 1981. Se encuentra un predominio de lactantes menores con antecedentes de prematurez y eutroficos en el momento de enfermar. La causa mas frecuente de I.R.A. fue la bronconeumonia, en general necesitaron V.M., por menos 7 dias y en promedio estuvieron hospitalizados por 36,6 dias. La mortalidad de nuestra serie fue de 23% y de los que no fallecen, la gran mayoria se encontraban asintomaticos en el momento del alta

Costes directos de la epilepsia en una población chilena / The direct costs of epilepsy in a chilean population

Introducción. La prevalencia de la epilepsia en Chile es de 17-21/1.000 habitantes. Últimamente ha habido preocupación por los costes en su diagnóstico y tratamiento. Objetivo. Calcular los costes directos del tratamiento de una determinada población chilena con epilepsia. Pacientes y métodos. Estudio retrospectivo en seis grupos de pacientes: diagnóstico reciente (DR), remisión (R), crisis ocasionales (CO), activos sin resistencia a fármacos (ASRF), resistencia al tratamiento con fármacos (RTF) y cirugía de la epilepsia (C). Se tabularon datos clínicos y económicos por grupo, considerando un año de tratamiento, además de su comparación entre ellos y su promedio respecto a datos internacionales. Resultados. Hubo 293 pacientes, 52% masculinos, 76% adultos, 25% estudiantes; 16% con trabajo estable; 55% con crisis focales. Los costes promedios por grupos, calculados en dólares estadounidenses (USD)/paciente/año, fueron los siguientes: DR, 443; R, 316; CO, 430; ASRF, 711; RTF, 946; C, 4.262. Conclusiones. El coste más elevado en cada grupo, excepto el quirúrgico, fueron fármacos, con un promedio de 81%. El coste directo promedio grupal fue de 615 USD/paciente/año. En los costes promedios anuales por grupos, el mayor es el de cirugía, y el menor, el de remisión, debido al menor uso de medicamentos, exámenes y consultas. Nuestros costes directos son 5 veces menores que algunos países desarrollados y 3,5 veces superiores que otras naciones en vía de desarrollo. Estos datos pueden contribuir a mejorar la calidad de vida de personas con epilepsias, optimizando costes y tarifas, ayudando a programas nacionales de epilepsia y cirugía de la epilepsia

Introduction. Epilepsy Chilean prevalence is 17-21/1,000 inhabitants. In past years, there is concern for the high costs involved in its handling. Aim. To estimate the direct costs of treatment and handling in specific population with epilepsy. Patients and methods. It is a retrospective study, in 6 groups of people with epilepsy: recent diagnosis (RD), remission (R), occasional seizures (OS), active without resistance to drugs (AWRD), resistance to pharmacological treatment (RPT), and epilepsy surgery (S). Data and characteristics tabulation and economical study of each group were made, considering 1 year of treatment. A comparison was made between them and their average in relation to international data. Results. 293 patients. 52% male. 76% adults. 25% students. 55% focal seizures. Costs per group: (USD/patient/year): RD, 443; R, 316; OS, 430; AWRD, 711; RPT, 946; S, 4,262. Direct average cost of treatment for epilepsy in this population: 615 USD/patient/year. Conclusions. When differentiating in groups of individuals with epilepsy, the highest average annual cost is in surgery and the lowest in remission. In all the groups, except for surgery one, the highest expense is in drugs (average 81%). In relation to other countries, our direct costs are 5 times lower than in some developed countries and 3.5 times higher than in other developing countries. This data is of interest to governmental and financial spheres, so to provide a better quality of life for people with epilepsy, lowering costs and fees for their treatment and contributing to epilepsy and surgery national programs

Sintomas hipoglicemicos en la enfermedad de Addison. / Hipoglicemic symptoms in Addison's disease

La enfermedad de Addison en el nino, es poco corriente. Se presenta el caso de un nino de 13 anos con Enfermedad de Addison, cuyo diagnostico se sospecho por presentar crisis hipoglicemicas y sintomas neuropsiquiatricos. El control del tratamiento con mineralocorticoides, se, efectuo midiendo la actividad de la renina plasmatica. Se considera de interes conocer las diferentes formas de presentacion de esta enfermedad, para evitar diagnosticos tardios y se analiza las ventajas del corticoide fluorado, como terapia de reemplazo mineralocorticoidea