Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.

BACKGROUND: Deficiency of aromatic L-amino acid decarboxylase (AADC) is associated with severe developmental delay, oculogyric crises (OGC), and autonomic dysfunction. Treatment with dopamine agonists and MAO inhibitors is beneficial, yet long-term prognosis is unclear. OBJECTIVE: To delineate the clinical and molecular spectrum of AADC deficiency, its management, and long-term follow-up. RESULTS: The authors present six patients with AADC deficiency and review seven cases from the literature. All patients showed reduced catecholamine metabolites and elevation of 3-O-methyldopa in CSF. Residual plasma AADC activity ranged from undetectable to 8% of normal. Mutational spectrum was heterogeneous. All patients presented with hypotonia, hypokinesia, OGC, and signs of autonomic dysfunction since early life. Diurnal fluctuation or improvement of symptoms after sleep were noted in half of the patients. Treatment response was variable. Two groups of patients were detected: Group I (five males) responded to treatment and made developmental progress. Group II (one male, five females) responded poorly to treatment, and often developed drug-induced dyskinesias. CONCLUSIONS: The molecular and clinical spectrum of AADC deficiency is heterogeneous. Two groups, one with predominant male sex and favorable response to treatment, and the other with predominant female sex and poor response to treatment, can be discerned.

Intracerebral aneurysms in human immunodeficiency virus infection: case report and literature review.

We describe a child with human immunodeficiency virus infection who presented with a large subarachnoid hemorrhage. She had multiple saccular and fusiform aneurysms in the proximal cerebral arterial circulation and no evidence of bacterial or fungal infection. The arteriopathy coincided with a high human immunodeficiency virus RNA load. Human immunodeficiency virus may cause cerebral arteriopathy with potentially life-threatening complications.

Dose-response effect of cocaine on newborn head circumference.

OBJECTIVE: To evaluate the relationship between head circumference, birth weight, and cocaine dose in healthy term and near-term newborns exposed to cocaine in utero. METHODS: We used radioimmune assay (RIAH) of cocaine metabolite in maternal hair to quantify third trimester cocaine exposure in 240 healthy newborn infants (gestational age: >36 weeks). Cocaine exposure was categorized into 3 levels: no exposure (n = 136), low cocaine exposure (n = 52; RIAH: 2-66 ng/10 mg hair), and high cocaine exposure (n = 52; RIAH: 81-4457 ng/10 mg hair). We collected information on maternal demographic characteristics, the pregnancy, and the use of substances through a structured interview and from the medical record. RESULTS: Means of birth weight, length, and head circumference of infants with high cocaine exposure differed significantly from those with low exposure and no exposure, but were similar between low exposure and no exposure. We used a multiple linear regression model to assess the association between newborn head circumference and cocaine level, adjusting for the effects of birth weight; gestational age; infant sex; and several maternal factors, including height, weight gain during pregnancy, syphilis during pregnancy, and the use of alcohol, cigarettes, marijuana, and opiates during pregnancy. Only birth weight, sex, and high cocaine exposure were significantly associated with newborn head circumference. The predicted head circumference deficit associated with high cocaine exposure (.44 cm) represents 34% of the unadjusted difference (1.28 cm) between mean head circumferences of infants in the high cocaine exposure and no exposure groups. CONCLUSION: Newborns exposed to a high level of cocaine in utero (RIAH: >81 ng/10 mg hair) exhibit asymmetric intrauterine growth retardation in which the head circumference is disproportionately smaller than would be predicted from the birth weight (head wasting). The deficit in head size associated with cocaine exposure may reflect the effects of a specific central nervous system insult that interferes with prenatal brain growth.

Dose-response effect of fetal cocaine exposure on newborn neurologic function.

BACKGROUND: Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. METHODS: Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores

Neurological correlates of fetal cocaine exposure.

Cocaine is a highly psychoactive substance with numerous effects that readily crosses the placenta, achieving variables levels in the fetus. Determining whether prenatal exposure to cocaine and its metabolites damages the developing human nervous system is hindered by the multiple intervening factors (confounders) that plague clinical settings, which warrant consideration in controlled studies. Prenatal cocaine exposure has been linked to numerous adverse neonatal outcomes, affecting fetal growth (i.e., low birth weight, intrauterine growth retardation, and small head size) and neurobehavior. These neurobehavior effects span the gamut from no abnormalities to impairments in arousal, neurological function, neurophysiological function, and state regulation. Strokes and possibly seizures are also noted. Dose-response effects of fetal cocaine exposure on fetal growth and neonatal neurobehavior are reported using quantitative methods of ascertainment. In early infancy, irritability and hypertonia are also described. Most cocaine associations are transient and resolve in infancy and early childhood. Whether such transient abnormalities place infants at increased risk for later neurodevelopmental impairments is not known. Controlled studies have found no cognitive differences related to prenatal cocaine exposure among toddlers or school age children, except as mediated through effects on head growth. Anecdotally, cocaine-exposed children seem to suffer from neurobehavioral abnormalities, but to date controlled studies have not established an association between cocaine and behavioral disorders, except for inattentiveness. Despite encouraging reports, the question of whether cocaine exerts long-term adverse effects on the developing human nervous system has not yet been resolved, largely because of the limitations of existing studies that rely on inadequate, mostly qualitative ascertainment of cocaine exposure as well as the dearth of studies in older children. Such methodological limitations may have compromised our ability to identify cocaine-exposed children at most risk.

Massive intracranial arachnoid cyst in a developmentally normal infant: case report and literature review.

Intracranial arachnoid cysts are developmental anomalies that are generally asymptomatic. We describe a 6-month-old boy with macrocephaly but normal neurological development who was found to have a rare, massive basal arachnoid cyst occupying most of the cranium and extending superiorly, causing significant shift due to mass effect. A cystoperitoneal shunt was placed, producing both a decrease in the arachnoid cyst dimensions and a concomitant reexpansion of parenchyma. After consideration of various management options, such a shunt system appears to offer a low risk of complications and a high likelihood of success.

Neurological correlates of fetal cocaine exposure: transient hypertonia of infancy and early childhood.

OBJECTIVE: To assess whether prenatal cocaine exposure has any long-term effects on neurodevelopment. DESIGN: A prospective cohort study with examiners blind to drug exposure and human immunodeficiency virus (HIV) status. SUBJECTS: Of 144 high-risk infants enrolled in a perinatal HIV neurodevelopmental study, 119 (83%) infants with both neurological and urine toxicology measures were followed up to age 24 months. METHODS: Neurological and developmental assessments were analyzed at 6-month intervals grouped according to the presence of cocaine in urine toxicology: 51 infants were cocaine-positive. Adjusted odds ratios (ORs) and 95% confidence interval (CI) were obtained by logistic regression equations that adjusted for perinatal variables, including measures of fetal growth, gestation, HIV status, and infant toxicology results. SETTING: Harlem Hospital Center from 1988 to 1992. RESULTS: At age 6 months, 21 of 51 (41%) cocaine-positive children exhibited hypertonia of any type (hypertonic tetraparesis, hypertonic diparesis, and hypertonic hemiparesis) compared with 17 of 68 (25%) cocaine-negative infants (OR = 2.1, CI = 1.0-4.6). Cocaine-positive infants were four times more likely to show hypertonic tetraparesis (HTP) than cocaine-negative infants (OR = 4.0; CI = 1.5-10.8). The association remained significant in multivariate analyses. Hypertonia, consistent with cerebral palsy, diminished over time in both groups. In 97% of affected infants hypertonia resolved by 24 months. Arm hypertonia abated first; leg hypertonia remained in some children up to age 18 months. No differences in development scores between cocaine-positive and cocaine-negative were noted at any age interval. However, among cocaine-positive infants those with early HTP showed significantly lower mean developmental scores at 6 and 12 month compared to infants without HTP. CONCLUSION: Cocaine positivity urine toxicology at birth is associated with hypertonia during infancy. Such cocaine-induced effects are usually symmetrical, transient, and the majority of exposed children outgrow hypertonia by 24 months of life. Among cocaine-positive infants, HTP may be a marker for later developmental impairments.

[The prevalence of markers for hepatitis A, B and C in a hospital in Mexico]. / Prevalencia de marcadores para hepatitis A, B y C en un hospital de México.

A prospective study was carried to determine the relative frequency of hepatitis A, B and C in patients with elevated liver enzymes (transaminases greater than two times normal) who had a viral hepatitis profile requested by their physicians between August of 1990 and July of 1992 in the Angeles Hospital in Mexico City. Prevalence of serological evidence of HBsAg and anti-hepatitis C antibodies was also studied in healthy blood donors seen at the hospital's blood bank during the same period. Among the 405 patients with elevated liver enzymes, 24.7 per cent had acute hepatitis A (positive anti-hepatitis A IgM), 7.9 per cent had active hepatitis B (positive HBsAg and/or HBcAb IgM) and 14.8 per cent had active or previous hepatitis C as evidenced by the presence of anti-hepatitis C antibodies. In blood donors the incidence of anti-hepatitis C and HBsAg was 0.61 and 0.32 per cent, respectively. A percentage of 46.2 of patients with anti-hepatitis C antibodies and transaminases greater than two-times normal had a past history of one or more blood transfusions. These data suggest that infection with the hepatitis C virus is more common than that caused by the B virus in both healthy blood donors, as well as in patients with hepatitis in this hospital.

Fetal effects.

The adverse effects of fetal drug exposures are well documented. Evidence for FAS, impaired intrauterine growth, birth defects, and mental retardation related to alcohol is compelling; evidence for alcohol-induced adverse behaviors and impaired speech is tenuous. Teratogenic, cognitive, or behavioral effects associated with prenatal exposure to marijuana, cigarettes, cocaine, or opiates have not been well established. The most convincing finding related to prenatal exposure to such substances is IUGR. Impaired fetal growth, especially of brain, may indirectly mediate drug effects on cognition. The abnormal neonatal neuro-behaviors described herein have no apparent impact on subsequent development. The development of opiate-exposed children, particularly those with withdrawal symptoms, however, appears to be more vulnerable to the adverse effects of an impoverished environment.

Neurologic findings in neonates with intrauterine cocaine exposure.

To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function, 30 term infants were evaluated prospectively: 14 cocaine-exposed and 16 unexposed. Cocaine-exposed infants had significantly lower mean birth weights, birth lengths, and head circumferences than urine-negative controls. Neurologic abnormalities among cocaine-exposed newborns included hypertonia of any type (86% vs 33%), axial hypertonia (79% vs 19%), plantar extension (46% vs 19%), and coarse tremor (57% vs 12%). The degree of hypertonia was sufficiently severe to warrant a diagnosis of "hypertonic tetraparesis" in 64% of cocaine-exposed and 12% of unexposed infants (P = .007). This diagnosis was highly correlated to small head size (r = 0.48; P = .01). Persistent tonic downward gaze was evident in two neurologically abnormal cocaine-exposed newborns. Gaze abnormalities improved slightly over the next 3 weeks of observation. One such infant re-evaluated at 6 months of age revealed resolution of tonic downward gaze and neurologic findings. We conclude that prenatal cocaine exposure is associated with tone and movement abnormalities in newborn infants.

Chronic ACTH treatment increases striatal dopamine D-2 receptor binding in developing rat brain.

ACTH has been reported to decrease elevated levels of dopamine metabolites in the CSF of patients with infantile spasms who respond clinically to ACTH therapy. To study the possible role of dopamine receptors in the effect of ACTH, we treated rat pups for thirty days with 40 IU/kg subcutaneously of porcine ACTH or with normal saline. Using 10 nM 3H-spiperone and sulpiride to determine nonspecific binding, specific binding of D-2 receptors increased significantly (46%) in the striata of ACTH-treated rats when compared to controls. No significant difference in specific binding was found in the nucleus accumbens. Protein concentration was significantly decreased by ACTH treatment. Saturation studies will be necessary to determine if the increase in dopamine receptor binding induced by a high dose of ACTH represents a change in receptor density or affinity. The effect of lower clinical doses of ACTH on dopamine receptors warrants study.