Effects of postnatal dexamethasone exposure on the developmental outcome of premature infants.

Extremely low birth weight premature infants are at risk for poor neurodevelopmental outcome. Postnatal dexamethasone has often been used in premature infants to prevent or treat bronchopulmonary dysplasia, and this drug is thought by some to affect neurodevelopmental outcome. We retrospectively examined the effect of this steroid on early neurodevelopment. Dexamethasone exposure was associated with an adverse outcome and was a stronger predictor of outcome than other accepted risk factors. If used, dexamethasone should be used in these high-risk infants for as short a period as possible.

Progressive dystonia masking ataxia in ataxia-telangiectasia.

A 10-year-old boy with ataxia-telangiectasia had severe progressive dystonic posturing that masked the ataxia until treatment relieved the dystonia. A younger sister had mor classical neurologic manifestations of the disease. However, both children had telangiectasia, immunologic abnormalities, and other features of ataxia-telangiectasia. The pathologic changes that have been found in the basal ganglia at autopsy and the occurrence of choreoathetosis, oculomotor disturbances, and now dystonia indicate that the function of the basal ganglia in patients with ataxia-telangiectasia is abnormal. Children who have basal ganglial abnormalities should be studied for ataxia-telangiectasia.

Clinical and morphometric analysis of the hypoplastic corpus callosum.

A total of 307 children were evaluated over a 3-year period in our neurogenetics clinic. Review of their medical records demonstrated 26 patients with diagnoses of anomalies of the corpus callosum. Morphometric analysis was performed on those 23 patients qualitatively assessed as having a hypoplastic (small, but morphologically intact) corpus callosum. Morphometric data were compared with clinical correlates for each patient. From these data, we conclude that the hypoplastic corpus callosum is not a normal variant of development but rather an indicator of a more fundamental abnormality of cerebral development.

Gastritis with valproate therapy.

We have identified ten children who developed gastritis after prolonged anticonvulsant therapy that included either valproic acid or divalproex sodium. Presenting symptoms were primarily feeding difficulties, including anorexia and refusal to eat. Vomiting was present in two thirds of the patients, with diarrhea, weight loss, and abdominal pain occurring less frequently. Occult blood in stool samples was a late development. All patients responded to therapy with H2-receptor antagonists, oral antacids, or both, with prolonged treatment often necessary to prevent relapse. Although gastrointestinal tract side effects are common with the initiation of valproate sodium therapy, feeding difficulties after long-term treatment are less common. Gastritis should be suspected in children receiving valproate therapy when feeding difficulties arise, particularly if the symptoms are persistent or recurrent.

Intracellular calcium accumulation in Duchenne dystrophy and other myopathies: a study of 567,000 muscle fibers in 114 biopsies.

Ultrastructural studies have shown plasmalemmal defects in a proportion of non-necrotic muscle fibers in Duchenne dystrophy, suggesting that intracellular calcium overloading may be an important mechanism of muscle fiber degeneration. To investigate this assumption, we studied the localization of calcium with the von Kóssa method, with alizarin red, and with glyoxalbis-(o-hydroxyanil) in serial, fresh-frozen sections of 114 biopsy specimens. The biopsy material included Duchenne dystrophy (24 cases), other dystrophies (27 cases), inflammatory myopathies (47 cases), and normal controls (11 cases). Counted in each specimen were every muscle fiber, the so-called large-dark fibers, and all calcium-positive fibers. Separate counts were made of the large-dark, necrotic, and other types of calcium-positive fibers. In Duchenne dystrophy, non-nectotic calcium-positive fibers occurred with a mean frequency of 4.83 percent. For all other groups, the corresponding value was 0.57 percent, with a range of 0.21 percent (normals) to 1.76 percent (scleroderma), p less than 0.001. Large-dark fibers were 12 times more common in Duchenne dystrophy than in all other cases. Forty-three percent of the fibers were calcium-positive in Duchenne dystrophy, whereas calcium-positive large-dark fibers were extremely rare in the other cases.

Asterixis associated with sodium valproate.

Intoxication with most anticonvulsants can produce asterixis. Asterixis rarely occurs with therapeutic serum anticonvulsant levels. We report two patients with asterixis who were taking valproic acid and had serum levels within the therapeutic range. Neither patient had clinical or laboratory evidence of hepatotoxicity. Only one other patient has been reported with valproate-associated asterixis in the absence of toxic serum drug levels or hepatotoxicity. Asterixis seems to be due to a central effect of the drug unrelated to hepatotoxicity or sedation.

Chronic ECHO type 5 virus meningoencephalitis in X-linked hypogammaglobulinemia: treatment with immune plasma.

A patient with X-linked hypogammaglobulinemia developed chronic meningoencephalitis. ECHO virus type 5 was repeatedly cultured from cerebrospinal fluid (CSF). Infusions of high-titer, specific plasma resulted in clinical improvement, but failed to eradicate the virus. After more intensive plasma infusions, the virus could not be cultured from the CSF. The patient died 8 months after institution of intensive therapy. The cause of death was unknown. Autopsy showed persistence of perivascular and meningeal inflammation. Specific anti-ECHO-virus-5 plasma was shown to be more effective in lowering CSF ECHO-virus titers than was plasma without anti-ECHO-virus antibody.

An adult-onset myopathy characterized by a double ring appearance of muscle fibers.

We report a 33-yr-old man with an unusual neuromuscular disorder characterized by progressive generalized weakness of 3 yr duration whose muscle biopsy showed a double ring appearance in most muscle fibers. This double ring appearance was due to a peripheral outer sarcoplasmic mass and an inner ring of annular myofibrils surrounding a core of normal longitudinally oriented myofibrils. Nerve conduction studies were normal. Electromyography showed fibrillations, positive waves, and increased brief duration, low amplitude, polyphasic potentials.

Cerebral infarction related to neck position in an adolescent.

A 16-year-old boy developed a left occipital lobe infarction after falling asleep with his head extended and rotated to the left. He was found to have an anomalous cerebrovascular system, in which the entire blood supply to the left occipital cortex derived from the right vertebral artery. It has been shown that vertebral artery flow can be compromised by physiologic degrees of extension of the neck and rotation of the head to the opposite side. To our knowledge, this is the only reported case of cerebral cortical infarction due to temporary arterial obstruction of the vertebral artery during physiologic hyperextension of the neck and rotation of the head. All previous cases attributed to this mechanism have been brainstem, cerebellar, or cervical spinal cord involvement with thrombosis of the vessel in question. Anomalies of the cerebrobasilar vascular system may place these individuals in jeopardy during otherwise harmless physical activities.

The neuroimaging findings in Sotos syndrome.

We reviewed the neuroimaging studies of 40 patients with classic Sotos syndrome. The studies consisted of CT scans only in 4 patients and one or more MRI scans in 36 patients. The diagnosis of Sotos syndrome was made using well-established clinical criteria. The neuroimaging studies of each patient were evaluated subjectively by visual inspection and the chief findings were tabulated and grouped into five categories: 1) ventricular abnormalities, 2) extracerebral fluid spaces, 3) midline abnormalities, 4) migrational abnormalities, and 5) others. The most common abnormality of the cerebral ventricles was prominence of the trigone (90%), followed by prominence of the occipital horns (75%) and ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were increased for age in 70% of the patients and the fluid spaces in the posterior fossa were increased in 70% also. A variety of midline abnormalities were noted but anomalies of the corpus callosum were almost universal. Gray matter heterotopias occurred in only 3 (8%) of 36 patients. Periventricular leukomalacia, presumably the result of prenatal or perinatal difficulties and unrelated to the basic condition, was the most common of the miscellaneous other abnormalities noted. The neuroimaging findings of Sotos syndrome are distinct enough to allow differentiation of this syndrome from other mental retardation syndromes with macrocephaly.

Volumetric neuroimaging in Usher syndrome: evidence of global involvement.

Usher syndrome is a group of genetic disorders consisting of congenital sensorineural hearing loss and retinitis pigmentosa of variable onset and severity depending on the genetic type. It was suggested that the psychosis of Usher syndrome might be secondary to a metabolic degeneration involving the brain more diffusely. There have been reports of focal and diffuse atrophic changes in the supratentorial brain as well as atrophy of some of the structures of the posterior fossa. We previously performed quantitative analysis of magnetic resonance imaging studies of 19 Usher syndrome patients (12 with type I and 7 with type II) looking at the cerebellum and various cerebellar components. We found atrophy of the cerebellum in both types and sparing of cerebellar vermis lobules I-V in type II Usher syndrome patients only. We now have studied another group of 19 patients (with some overlap in the patients studied from the previous report) with Usher syndrome (8 with type I, 11 with type II). We performed quantitative volumetric measurements of various brain structures compared to age- and sex-matched controls. We found a significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces. These data suggest that the disease process in Usher syndrome involves the entire brain and is not limited to the posterior fossa or auditory and visual systems.

Longitudinal head growth in developmentally normal preterm infants.

OBJECTIVE: To determine growth in head circumference from birth to 18 months of age in normal infants with low birth weight. METHODS: Healthy, appropriate-for-gestational-age, singleton, white infants weighing less than or equal to 2500 g at birth and with normal development at 18 months of age were included in this study. Serial measurements of head circumference (corrected for gestational age) from 450 eligible infants were compared with reference data for head circumference. RESULTS: Longitudinal measurements of head circumference for infants weighing more than 1000 g at birth were similar to reference data for term infants. Head measurements for infants weighing less than or equal to 1000 g at birth were notably smaller than the measurements in the reference data. A cubic spline curve drawn through the head circumference measurements between birth and age 18 months (corrected for gestational age) for infants weighing less than or equal to 1000 g at birth was significantly (P < .001) below the curve for infants weighing more than 1000 g at birth. At age 18 months, the mean difference in head circumference between the group weighing less than or equal to 1000 g at birth and the weights in the reference data was 1.6 cm (P < .01). (Data were analyzed with Wilcoxon's signed rank test.) CONCLUSIONS: These data show that head circumference grids are appropriate for observing head growth in infants with a birth weight more than 1000 g. However, head circumference growth for normal infants with birth weight less than or equal to 1000 g does not "catch up" with that of larger premature infants or term infants.

Dementia pugilistica and cavum septi pellucidi: born to box?

Described nearly 70 years ago as the 'punch drunk' syndrome, dementia pugilistica has recently received increasing attention in both the medical and lay press. The association between the finding of cavum septi pellucidi and dementia in old boxers was first described by Ferguson and Mawdsley in 1965. Since then it has commonly been listed as one of the features of this condition. We review the significance and the epidemiology of cavum septi pellucidi and present an alternative explantation for the association between this developmental anomaly of the brain and dementia pugilistica.

Wasp sting-associated cerebral infarction: a role for cerebrovascular sympathetic innervation.

A 38-year-old man, stung repeatedly by wasps on the left face and neck, had his left internal carotid artery occluded 2 days later. A mechanism for ischemic stroke involving the sympathetic innervation of cerebral vasculature is suggested.

Midazolam in the treatment of refractory neonatal seizures.

Midazolam, a potent short-acting benzodiazepine, is a safe and highly effective agent for the control of status epilepticus. Its efficacy in the control of neonatal seizures, however, has not been determined. Six neonates (aged 1-9 days; gestation, 30-41 weeks) developed seizures from a variety of causes. In each case, seizures persisted for > 12 h despite high-dose phenobarbital therapy with or without the addition of phenytoin. Midazolam was then administered by continuous intravenous infusion (0.1-0.4 mg/kg/h) for 1 to 3 days. Within 1 h of initiation of midazolam, seizures were controlled in all six neonates. Electroencephalographic seizures were abolished in four of six neonates; however, two neonates continued to have electrographic seizures (without clinical accompaniment) for a further 12 h. Blood pressure and pulse rate were not changed after the initiation of midazolam, and adverse reactions were not observed in any neonate. Because more than one third of all neonatal seizures are refractory to high-dose phenobarbital and phenytoin, midazolam administered by continuous intravenous infusion may be a valuable adjunctive therapy.

Acute and delayed cerebral infarction after wasp sting anaphylaxis.

A 52-year-old man developed a severe anaphylactic reaction after a wasp sting. Slurred speech and left hemiparesis were noted a few hours later. Three-and-one-half weeks later, he became acutely obtunded and quadriparetic. Angiographic studies demonstrated complete and near-complete occlusions of the right and left internal carotid arteries, respectively. A mechanism is suggested for delayed ischemic stroke after wasp sting anaphylaxis that involves cerebrovascular sympathetic innervation.

Size of the corpus callosum in cerebral palsy.

It has been suggested that the size of the corpus callosum may have diagnostic significance in cerebral palsy, although this relationship is incompletely defined. Ninety-one patients with cerebral palsy had been studied by magnetic resonance imaging in the 5-year period from 1990 to 1994. Fifty-seven of these 91 patients had a technically appropriate midsagittal magnetic resonance image for quantitative morphometric analysis. The ratio of the area of the corpus callosum to the area of the supratentorial brain was compared to published age- and gender-specific norms. Imaging findings were correlated with clinical history and cause of cerebral palsy. The corpus callosum was of normal size in 43 patients and more than 2 standard deviations below the mean in 14 patients. The causes for cerebral palsy included hypoxic ischemic encephalopathy (32), cerebral dysgenesis (8), and porencephalic strokes (6); the etiology could not be established in 11 patients. The size of the corpus callosum was highly correlated with the cause of cerebral palsy, such that all patients with cerebral dysgenesis had hypoplasia of the corpus callosum (one-sided z test, p < 0.0001). Conversely, the callosum was of normal size in 32 of 38 patients with hypoxic ischemic encephalopathy and porencephalic strokes. The presence of a hypoplastic corpus callosum is highly associated with cerebral dysgenesis as a cause for cerebral palsy.

Infantile spasms.

Infantile spasms are a seizure disorder in young infants with diverse etiologies, suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development. The prognosis for normal intellectual and neurologic development parallels that of the underlying etiology. Early and appropriate treatment with ACTH may lead to seizure control in a majority of patients. The treating physician must anticipate the side effects of this modality.

The floppy infant: recent advances in the understanding of disorders affecting the neuromuscular junction.

The clinician is often asked to evaluate the floppy infant. Numerous conditions that cause hypotonia in infancy are briefly outlined in this article. These conditions may affect the brain, spinal cord, or motor unit. Several disorders of neuromuscular transmission, including four distinct and recently described congenital myasthenic syndromes and infant botulism, are discussed thereafter.

Cerebral dysgenesis. An overview.

A significant portion of patients with neurodevelopmental abnormalities (mental retardation, learning disabilities, and so forth) have no definable cause for these problems. Mounting evidence suggests a substantial number of these idiopathic conditions have subtle abnormalities of brain development (cerebral dysgenesis) as the inherent pathophysiologic event. In this article the authors summarize normal and abnormal brain development, the diagnostic approach to idiopathic neurodevelopmental anomalies, and the new molecular genetic insights into the underlying causes of brain malformations.