[Predominant factors of neonatal encephalopathy: hypoxic and ischemia, a global problem]. / Factores predominantes de encefalopatía neonatal: hipoxia e isquemia, un problema global.

If a difficulty arises during birth, due to a maternal or fetal anomaly, acute or chronic, asphyxia of the fetal brain constitutes a greater risk, because it could result in the destruction of neurons and the possibility of evolving towards a Ischemic Hypoxic Encephalopathy with long -term sequelae. This review highlights the most recent scientific aspects but at the same time it offers an essential margin of knowledge regarding pathophysiology, diagnosis and treatment, as well as offering a perspective on the future of clinical care of ischemic hypoxic encephalopathy.

Si una dificultad sobreviene durante el nacimiento de un niño, por una anomalía materna o fetal, aguda o crónica, la asfixia del cerebro fetal constituye un riesgo mayor, porque ella podría dar como resultado la destrucción de las neuronas y la posibilidad de evolucionar hacia una encefalopatía hipóxico isquémica con secuelas a largo plazo. En esta revisión se resaltan los aspectos científicos más recientes pero a la vez se ofrece un margen de conocimiento imprescindible en cuant o a la patofisiología, diagnóstico y tratamiento, así como también se ofrece una perspectiva sobre el futuro de la atención clínica de la encefalopatía hipóxico isquémica.

Factores predominantes de encefalopatía neonatal: hipoxia e isquemia, un problema global / Predominant factors of neonatal encephalopathy: hypoxic and ischemia, a global problem

Si una dificultad sobreviene durante el nacimiento de un niño, por una anomalía materna o fetal, aguda o crónica, la asfixia del cerebro fetal constituye un riesgo mayor, porque ella podría dar como resultado la destrucción de las neuronas y la posibilidad de evolucionar hacia una encefalopatía hipóxico isquémica con secuelas a largo plazo. En esta revisión se resaltan los aspectos científicos más recientes pero a la vez se ofrece un margen de conocimiento imprescindible en cuanto a la patofisiología, diagnóstico y tratamiento, así como también se ofrece una perspectiva sobre el futuro de la atención clínica de la encefalopatía hipóxico isquémica.

If a difficulty arises during birth, due to a maternal or fetal anomaly, acute or chronic, asphyxia of the fetal brain constitutes a greater risk, because it could result in the destruction of neurons and the possibility of evolving towards a Ischemic Hypoxic Encephalopathy with long -term sequelae. This review highlights the most recent scientific aspects but at the same time it offers an essential margin of knowledge regarding pathophysiology, diagnosis and treatment, as well as offering a perspective on the future of clinical care of ischemic hypoxic encephalopathy.

[Neonatal hypoxic-ischemic encephalopathy]. / Encefalopatía hipóxica-isquémica neonatal.

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).

Encefalopatía hipóxica-isquémica neonatal / Neonatal hypoxic-ischemic encephalopathy

La encefalopatía hipóxica-isquémica es un síndrome bien definido que afecta a los recién nacidos a término debido a asfixia fetal al nacer. La incidencia es 1-8 de cada 1000 nacidos en países desarrollados y asciende hasta 25 cada 1000 nacidos en países en desarrollo. Las causas más frecuentes son desprendimiento de la placenta, prolapso del cordón umbilical y rotura uterina. El criterio diagnóstico incluye incapacidad parcial o total del recién nacido para llorar y respirar al ser estimulado que requiere ventilación asistida en la sala de partos, Apgar < 5 en 5 y 10 minutos, acidemia (pH ≤ 7 y/o déficit de bases ≥ 12 mmol/l), alteraciones del estado de vigilia/sueño, de los reflejos primitivos y estiramiento muscular y tono muscular. En la forma leve la recuperación es total en tres días y sin (o con mínimas) secuelas de neurodesarrollo. En las formas moderadas y graves existen déficits neurológicos permanentes y alteraciones del neurodesarrollo (48%), 27% mueren y 25% son normales. El EEG regular o amplitud integrada y la resonancia magnética y espectroscópica realizados entre las 24 y las 96 horas y los 7 y 21 días de nacido respectivamente tienen un gran valor diagnóstico y pronóstico. Se recomienda hipotermia corporal (33.5 °C por 72 horas) antes de las 6 horas de nacido en las formas moderadas y graves. El resultado es una disminución de la mortalidad (de 35% a 27%) y de la morbilidad (de 48% a 27%).

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).

Trastornos del sueño en niños y adolescentes con enfermedades neurológicas / Sleep disorders in children and adolescents with neurological diseases

Resumen Los trastornos del ciclo circadiano vigilia-sueño son primarios y secundarios. Los primarios o intrínsecos son menos frecuentes (31%) que los secundarios o extrínsecos pero más rápido diagnosticados y tratados (69%). Los primarios se deben a alteraciones intrínsecas anatómico y/o funcionales del ciclo circadiano sueño-vigilia. Su tratamiento está bien definido en caso de que exista. Los trastornos del sueño secundarios son alteraciones extrínsecas del sueño de origen adquirido cuyo diagnóstico de certeza es más clínico que polisomnográfico y su tratamiento dirigido a la condición asociada así como a la manifestación anormal onírica. Aunque las secundarias son más comunes que las primarias (69% contra 31%) se diagnostican y tratan menos que las primarias. Cuando no se diagnostican y tratan correctamente inducen problemas significativos emocionales, conductuales y cognoscitivos en niños y adolescentes comparados con aquellos sin tales sin trastornos del sueño. El propósito de esta revisión es que los pediatras generales, pediatras neurólogos y paidopsiquiatras tengan en mente la alta incidencia de los trastornos secundarios del sueño en niños con enfermedades neurológicas y que pregunten a los padres y pacientes sobre la calidad del sueño de sus hijos y realicen un diagnóstico y tratamiento precoz para evitar consecuencias en algunos casos fatales.

Abstract The disorders of the circadian cycle sleep-wake are primary and secondary. The primary or intrinsic are less frequent (31%) than the secondary or extrinsic but early diagnosed and treated (69%). The primary intrinsic alterations are due to anatomical and/or functional process circadian rhythm sleep-wake cycle. Its treatment is well defined in case it exists. The secondary sleep alterations are extrinsic and their diagnosis is more clinical than polysomnographic and its treatment directed to the associated condition as well as the manifestation abnormal sleep. Although the secondary are more common than the primary (69% vs. 31%) they are diagnosed and treated less than the primaries. When not properly diagnosed and treated induce significant problems with emotional, behavioral and cognitive changes in children and adolescents compared with those without sleep disorders. The purpose of this review is that the general pediatricians, pediatric neurologists and pediatric psychiatric bear in mind the high incidence of side effects of sleep disorders in children with neurological diseases and to ask parents and patients about the quality of sleep of their children and adolescents and make a diagnosis and early treatment to avoid fatal consequences in some cases.

[Metabolic myopathies]. / Miopatías metabólicas.

AIM: To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. DEVELOPMENT: These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (< 10 min) exercises. Those secondary to fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. CONCLUSIONS: The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

TITLE: Miopatias metabolicas.Objetivo. Revisar las miopatias metabolicas manifestadas solamente por crisis de mialgias, calambres y rigidez musculares con dificultad para contraer los musculos afectados y el examen neurologico normal entre las crisis en niños y adolescentes. Desarrollo. Estas miopatias metabolicas se deben a deficits enzimaticos heredados en forma autosomica recesiva del metabolismo de los carbohidratos y lipidos. El resultado final es una reduccion del trifosfato de adenosina principalmente a traves de la fosforilacion oxidativa mitocondrial con disminucion de la energia disponible para la contraccion muscular. Las secundarias a trastornos del metabolismo de los carbohidratos se producen por ejercicios de alta intensidad y breves (< 10 min) y las secundarias a trastornos de los lipidos, por ejercicios de baja intensidad y prolongados (> 10 min). Los deficits enzimaticos en el primer grupo son de miofosforilasa (glucogenosis V), fosfofructocinasa muscular (glucogenosis VII), fosfoglicerato mutasa 1 (glucogenosis X) y beta enolasa (glucogenosis XIII), y en el segundo, de carnitina palmitol transferasa tipo II y de acil-CoA deshidrogenasa de cadena muy larga. Conclusiones. Las caracteristicas diferenciales de los pacientes en cada grupo y dentro de cada grupo permitiran el diagnostico clinico presuntivo inicial en la mayoria y solicitar solamente los examenes necesarios para corroborar el diagnostico. El tratamiento de las crisis consiste en hidratacion, glucosa y alcalinizacion de la orina. Las medidas preventivas son evitar el tipo de ejercicio que induce las crisis y el ayuno. No existe cura o tratamiento especifico. El pronostico es bueno con la excepcion de casos raros de insuficiencia renal aguda debido a la elevacion sanguinea de la mioglobina producto de una rabdomiolisis grave.

[Juvenile myasthenia gravis]. / Miastenia gravis juvenil.

Juvenile myasthenia gravis is a chronic autoimmune disorder which occurs when serum antibodies combine with nicotinic acetylcholine receptors at the muscle membrane of the motor endplate imparing the neuromuscular transmission. It results in early muscle fatigability with progression to a complete paralysis during repetitive muscle contraction (movements) or steady muscle contraction (postures), and less common persistent paralysis at rest. The cranial nerves, mainly the one innervating the extraoccular and palpebral levator, are the most susceptible to permanent weakness and paralysis at rest. Initial clinical presentations are generalized, ocular and respiratory forms. The diagnosis is suspected through medical history of abnormal fatigability and corroborated by physical examination, repetitive nerve stimulation of an affected but not complete paralyzed muscle, correction of fatigability by the intravenous administration of acetylcholine esterase inhibitors, and by the presence of serum acetylcholine receptors antibodies (ACRA). The long term treatment is symptomatic (acetylcholine inhibitors) and etiopathogenic (immunosupresor drugs, plasmapheresis, intravenous gamma globulin and thymectomy. Spontaneous or post symptomatic and etiopathogenic treatment remissions occur from 1 to 10 years. Fatality is rare but children are at high risk during myasthenia crisis.

Miastenia gravis juvenil / Juvenile myasthenia gravis

La miastenia gravis juvenil (MGJ) es un trastorno crónico auto inmune en el cual existen anticuerpos séricos que al unirse a los receptores de acetilcolin nicotínicos de la membrana muscular de la placa motora alteran la transmisión neuromuscular. El resultado es fatiga muscular precoz con progresión a la parálisis durante estados de contracción muscular iterativos (movimientos) o sostenidos (posturas) y más raramente parálisis permanente durante el reposo. Los músculos inervados por los nervios craneales, especialmente los extraoculares y elevadores de los párpados, tienen más tendencia a la debilidad muscular persistente que los inervados por otros pares craneales y las extremidades. Las formas clínicas de presentación son generalizadas, oculares y respiratorias. El diagnóstico se sospecha mediante la anamnesia, la fatiga anormal se comprueba mediante el examen físico y la estimulación eléctrica iterativa del nervio que inerva al músculo afectado pero no paralizado. Se corrobora mediante la administración de inhibidores de la acetilcolin esterasa (IACE) que al aumentar la cantidad de acetilcolin en la hendidura sináptica, corrigen la fatiga o la debilidad muscular transitoriamente. Se hace el diagnóstico de certeza mediante la demostración sérica de anticuerpos contra los receptores de acetilcolin (ACRA). El tratamiento es a largo plazo sintomático con IACE y etiopatogénico con inmunosupresores, plasmaféresis, gamma globulina endovenosa y timectomía. El curso es crónico. La remisión espontánea o después de tratamiento sintomático o etiopatogénico ocurre entre 1-10 años respectivamente. La mortalidad es prácticamente nula aun durantes las crisis miastenias gracias a la educación de padres, pacientes y público en general sobre el tema, al desarrollo del sistema de respuesta rápida de auxilio domiciliario y las unidades de cuidados intensivos y el empleo de la ventilación asistida profiláctica, plasmaféresis y administración endovenosa de gamma globulina.

Juvenile myasthenia gravis is a chronic autoimmune disorder which occurs when serum antibodies combine with nicotinic acetylcholine receptors at the muscle membrane of the motor endplate imparing the neuromuscular transmission. It results in early muscle fatigability with progression to a complete paralysis during repetitive muscle contraction (movements) or steady muscle contraction (postures), and less common persistent paralysis at rest. The cranial nerves, mainly the one innervating the extraoccular and palpebral levator, are the most susceptible to permanent weakness and paralysis at rest. Initial clinical presentations are generalized, ocular and respiratory forms. The diagnosis is suspected through medical history of abnormal fatigability and corroborated by physical examination, repetitive nerve stimulation of an affected but not complete paralyzed muscle, correction of fatigability by the intravenous administration of acetylcholine esterase inhibitors, and by the presence of serum acetylcholine receptors antibodies (ACRA). The long term treatment is symptomatic (acetylcholine inhibitors) and etiopathogenic (immunosupresor drugs, plasmapheresis, intravenous gamma globulin and thymectomy. Spontaneous or post symptomatic and etiopathogenic treatment remissions occur from 1 to 10 years. Fatality is rare but children are at high risk during myasthenia crisis.

[Sleep disorders in the newborn]. / Enfermedades del sueño en el recién nacido.

Sleep disorders are classified in dyssomnias, parasomnias, sleep disorder associated with medical and psychiatric disorders and proposed sleep disorders. Only the parasomnias have been studied as such in the newborn period. The parasomnias that occur in this age group are infant sleep apnea, congenital central hypoventilation syndrome, sudden infant death syndrome, and benign neonatal sleep myoclonus. Infant sleep apnea includes three entities: (1) apnea of prematurity, (2), apparent life threatening episodes with apnea and (3) obstructive sleep apnea. Congenital central hypoventilation syndrome can be associated with other autonomic system illness, such as Hirschsprung disease (Haddad syndrome) and neuroblastoma. The implementation of the supine sleep position and smoking free homes has diminished the frequency of sudden infant death syndrome. Benign neonatal sleep myoclonus should be considered in all newborns with a normal exam between the episodes when they always occur during sleep. This entity may be mistaken for status epilepticus, because it is associated with increases in heart rate. Benzodiazepines prolongs the duration of the episodes.

[Medical and surgical indications of evoked potentials]. / Indicaciones médicas y quirúrgicas de los potenciales evocados.

Evoked potentials (EP) are more sensitive than specific, safe, objective and reproducible neurophysiologic techniques to assess integrity of peripheral and central sensory and motor pathways. The integrity of pathways are determined by measurement the latency of the recorded and digitally averaged electrical events elicited after adequate stimulation. EP are medically and surgically recommended in conditions in which the diagnoses, determination of neurological outcome in comatose and under anesthesia patients, and determination of the course and evaluation of treatment are uncertain with neurologic examination and other neurodiagnostic studies.

Fetal deformations: a risk factor for obstetrical brachial plexus palsy?

The purpose of this report is to discuss the association of brachial plexus palsy and congenital deformations. We reviewed all charts of patients less than 1 year of age with obstetrical brachial plexus palsy evaluated by one of the authors (IA) between January 1998 and October 2005 at Miami Children's Hospital Brachial Plexus Center. Of 158 patients with obstetrical brachial plexus palsy, 7 had deformations (4.4%). Deformations were present in 32% of patients delivered by cesarean section, but in only 2% of patients delivered vaginally. The deformations were ipsilateral, involving the chest in two patients, distal arms in two patients, proximal arm in one patient, ear in one patient, and the leg in one patient. All patients with deformations had unilateral Erb's palsies. None had a history of maternal uterine malformation. Two presumptive mechanisms of injury, one causing the deformation (compressive forces) and one causing brachial plexus palsy at the time of delivery (traction forces), were present in all cases. The higher incidence of deformation in patients with obstetrical brachial plexus palsy born by cesarean sections and the presence of two presumptive mechanisms in all of the cases presented here raises the possibility that fetal deformations are a risk factor for obstetrical brachial plexus palsy.

Intrauterine shoulder weakness and obstetric brachial plexus palsy.

Obstetrical brachial plexus injury occurs when the forces preventing the stretch of the brachial plexus are overcome by the forces stretching it. This report describes an 8-day-old male delivered by uncomplicated cesarean section with right obstetrical brachial plexus palsy and congenital arm atrophy. The patient had a history of decreased right arm movement detected by fetal ultrasound at 18 to 20 weeks of gestation. The purpose of this article is to report that stretching of brachial plexus at birth sufficient to produce a plexus injury may occur in a patient with a vulnerable plexus even in the absence of traction during delivery.

Bilateral decreased oxygenation during focal status epilepticus in a neonate with hemimegalencephaly.

Early surgical removal of a dysplastic hemisphere appears to be beneficial for neonates with hemimegalencephaly and medically resistant seizures. We analyzed the changes in the cerebral regional oxygen saturation index in a neonate with tuberous sclerosis and right hemimegalencephaly (1) during seven episodes of right hemisphere electroencephalographic status epilepticus with and without clinical manifestations and (2) after right hemispherectomy. The cerebral regional oxygen saturation index demonstrated marked fluctuations and progressive decline in both hemispheres during the episodes and normal values in the remaining hemisphere after surgery. We speculate that decreased oxygenation of the nonepileptic cerebral hemisphere in patients with hemimegalencephaly and medically resistant seizures can contribute to the production of global neurologic impairments in these patients and that the benefits of early hemispherectomy are due to the improved oxygenation of the nondysplastic hemisphere following surgery.

Opsoclonus: an early sign of neonatal herpes encephalitis.

Preferential involvement of certain central nervous systems areas by specific viruses provides a valuable guide to the selection of antiviral agents. We report a neonate that developed opsoclonus 7 days prior to the diagnosis of herpes simplex type 2 cerebellitis. The course of the opsoclonus paralleled the clinical course and radiologic evolution of the infection. The purpose of this report is to describe opsoclonus as a possible early sign of herpes simplex type 2 central nervous system infection.

Adolescents with muscular dystrophies.

The muscular dystrophies (MDs) are inherited or de novo gene mutation disorders of sarcolemma-associated proteins or nuclear membrane-associated proteins. They are manifested by progressive striated muscle weakness and wasting. Cardiac and central nervous system abnormalities may be present. MD phenotypes vary in terms of defective gene, mode of inheritance, age of onset, distribution of muscle involvement, and severity. Clinical diagnosis is confirmed by direct or indirect mutation analysis and gene product defect detection in frozen muscle samples by immunohistochemistry and Western blot. The majority of the adolescents with MD are already aware of the nature and course of their condition, which adds a significant psychosocial pathology to their physical disability. Management includes: (1). prevention of new cases by preconception counseling, prenatal testing, and neonatal screening; (2). prevention and treatment of skeletal deformities, cardiac and respiratory insufficiencies, and psychological and psychiatric disturbances; and (3). education, counseling, and support to patients, parents, siblings, caretakers, and teachers. Management is better achieved with a multidisciplinary approach. Although there is no cure, oral steroids may preserve transitorily acceptable muscle function. Despite the initial failure with myoblast transfer therapy, advances in molecular genetic and stem cell implants are promising.

Methemoglobinemia in an infant receiving nitric oxide after the use of eutectic mixture of local anesthetic.

High levels of methemoglobinemia can cause tissue hypoxia and cyanosis. We report the case of a 7-month-old girl with pulmonary dysplasia receiving inhaled nitric oxide who had cyanosis caused by methemoglobinemia after prolonged use of a eutectic mixture of local anesthetics cream.