Cognitive and behavioral effects of antiepileptic drugs.

In managing epilepsy, drugs that offer the best seizure control to the patient should be used, but their influence on quality of life must also be considered. This must include any effects on mood and mental state, which should be minimal in order that these patients may achieve their full potential. Subtle behavioral and cognitive disadvantages may occur with anticonvulsant drug use. Behavioral changes with phenobarbital are both idiosyncratic and dose related. Carbamazepine and valproic acid can have adverse effects on mood and cognition, but do so less frequently than the other medications or combinations (Table 1). Cognitive dysfunction may relate to antiepileptic drug blood levels, but impairment of skills can occur in the nonintoxicated patient. Thus, office neurologic examinations are insufficient to detect these subtle mental impairments. Practical methods need to be developed to identify and monitor these problems so that in the future cognitive and behavioral dysfunction in epileptic patients can be minimized.

Glucose and perinatal hypoxic-ischemic brain damage in the rat.

Seven-day postnatal rats were rendered hyperglycemic by the SC injection of 50% glucose, following which they were exposed to hypoxia with 8% oxygen. The glucose-treated animals survived more than twice as long as saline-treated littermates. Other hyperglycemic and control rat pups were subjected to hypoxia-ischemia by unilateral common carotid artery occlusion combined with 2 hours of hypoxia. Neuropathologic analysis of recovered animals at 30 days of age showed that the brains of the glucose-treated animals were no more damaged than those of the saline controls (p greater than 0.05). The finding indicates that, unlike adults, glucose supplementation and its associated hyperglycemia in the immature rat does not increase the extent of hypoxic-ischemic brain damage.

Early predictors of one-year outcome for infants asphyxiated at birth.

This study attempted to identify within the first 48 hours of life those infants sustaining hypoxic-ischemic insults and destined to have neurodevelopmental abnormalities at one year of age. Neurological examination and cranial CT scan were quantitated to provide a post-asphyxia score and CT low-density index for each of 34 fullterm infants. The post-asphyxia score and CT infarction index were used to predict infants with normal and abnormal outcomes at one year of age, and both were valuable predictors of neurodevelopmental sequelae.

Occlusive vascular disease in asphyxiated newborn infants.

Six full-term severely asphyxiated newborn infants underwent evaluation with digital intravenous angiography. All infants were comatose and flaccid and had seizures, depressed brainstem function, and signs of intracranial hypertension. An initial brain CT scan revealed diffuse hypodensities and compressed ventricles. Follow-up noncontrast CT scans showed areas of increased attenuation. Digital intravenous angiography demonstrated venous sinus thrombosis in five infants, two of whom also had arterial thrombosis, and hypervascularity in the sixth infant. Our data document that occlusive vascular disease is a prominent feature of severe perinatal asphyxia.

Digital intravenous cerebral angiography in neonates.

Digital intravenous cerebral angiography was performed in 13 neonates. Injections were made either centrally into the right atrium or peripherally into a distal vein. Seven infants suffered from anoxia, one infant had clinical brain death, another had focal infarcts, and two had intracranial hemorrhage. One infant had an intracranial tumor and another had a neck tumor. Venous sinus thrombosis was seen in five of the seven anoxic infants. A total absence of intracranial arterial circulation was demonstrated in the clinically brain-dead infant. Vascularity and venous involvement by neoplasm were excellently delineated by this technique.

Arthrogryposis multiplex congenita in an infant with posterior agenesis of the corpus callosum.

A term male infant with arthrogryposis multiplex congenita and agenesis of the corpus callosum is described. Physical examination revealed multiplex dysmorphic features and fixed joints. A muscle biopsy showed type II fibers to be more than 12% smaller than type I fibers, consistent with the diagnosis of fiber type disproportion. The CT scan disclosed absence of the posterior corpus callosum and moderate atrophy of the cerebellar hemispheres. The pathogenetic mechanism for the muscle (and thus joint) abnormalities of this infant is discussed with respect to a central etiology.

Acute hyperammonemia in the young primate: physiologic and neuropathologic correlates.

Infusion-induced acute (less than or equal to 24 h) hyperammonemia to concentrations up to five times normal (0.19 +/- 0.03 versus 0.90 +/- 0.08 mM) was studied in eleven 6-9-month-old Macaca mulatta. The young primates developed a progressive reduction of consciousness that correlated in severity directly with the elevation of blood ammonia concentration. Hyperventilation, electroencephalographic slowing, occasional seizure activity, and, eventually, apneustic breathing also occurred. Intracranial pressure rose from 76 +/- 7 to 167 +/- 12 mmH2O. Arterial oxygen and blood pressure remained within normal limits. Neuropathologic examination showed early astrocytic changes, consisting primarily of swollen perikaryal cytoplasm and processes, and membranous whorls. The absence of neuronal pathology suggests that the acute, limited insult, as occurs in many of the childhood hyperammonemic syndromes, is fully reversible.