Evaluation

Common neurologic nonepileptic problems encountered in newborns are hyperexcitability in tremulous infants, nonepileptic cerebral manifestations of sepsis, cardiac disease, hypoxia, apnea of prematurity, and benign myoclonus. A rare condition seen in neonates is hyperekplexia. It is usually autosomally dominantly inherited and presents with exaggerated startle reactions to tactile stimuli over the face and trunk, resulting in tonic extension of the limbs, flexion of the head, and apnea. It is responsive to clonazepam.

The workup includes early assessment for treatable causes. Sepsis and metabolic derangements are frequent causes of neonatal seizures. The highest incidence of neonatal seizures is in infants with hypoxia/ischemia, sepsis, or hypoglycemia. Hereditary neonatal seizures ("fifth day fits") are autosomal dominant, variably expressed, and usually require chronic AEDs, often with a good outcome.

Complex hereditary metabolic disorders—e.g., urea cycle defects with hyperammonemia, maple syrup urine disease, and methylmalonic acidemia—usually become evident days or weeks after feedings with protein are initiated. Others may appear symptomatic in utero or soon after delivery—e.g., nonketotic hyperglycinemia, in which the mother reports fetal hiccoughs—and soon after birth the infant is flaccid, exhibiting myoclonic seizures. Seizures in these metabolic disorders are a signal of possibly significant CNS impairment.

Some of these disorders may be completely controlled or the effects may be reversed with appropriate dietary management (galactosemia and urea cycle defects) or coenzyme replacement (pyridoxine dependency, biotinidase deficiency, subtypes of folate, and vitamin B 12 responsive methylmalonic acidemia).

In evaluating an infant, the cause of the seizures may be readily apparent. Dysmorphic newborns could have a chromosomal defect (trisomy or deletion) or be identifiable only by the combination of unusual features (Cornelia de Lange syndrome). Neurocutaneous diseases infrequently cause seizures in newborns but are readily identifiable by certain signs, e.g., encephalotrigeminal hemangiomatosis in Sturge-Weber syndrome, or achromic patches in tuberous sclerosis. Cutaneous herpes with seizures is an indication that herpes simplex encephalitis is present. Chorioretinitis is a clear sign of intrauterine infection that could cause seizures (e.g., herpes, toxoplasmosis, cytomegalovirus, or rubella). Cerebral imaging is warranted in neonates to help define cerebral hemorrhage and structural abnormalities. Ultrasound may be sufficient for diagnosis in some cases, but MRI is the best study for migrational defects of the CNS (e.g., lissencephaly, heterotopia, and agenesis of the corpus callosum).

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