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.

Cerebellar ataxia and coenzyme Q10 deficiency.

The authors measured coenzyme Q10 (CoQ10) concentration in muscle biopsies from 135 patients with genetically undefined cerebellar ataxia. Thirteen patients with childhood-onset ataxia and cerebellar atrophy had markedly decreased levels of CoQ10. Associated symptoms included seizures, developmental delay, mental retardation, and pyramidal signs. These findings confirm the existence of an ataxic presentation of CoQ10 deficiency, which may be responsive to CoQ10 supplementation.

Death due to bioterrorism-related inhalational anthrax: report of 2 patients.

On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC. The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15. Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility. The cases of 2 postal workers who died of inhalational anthrax are reported here. Both patients had nonspecific prodromal illnesses. One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain. The other patient had a "flulike" illness associated with myalgias and malaise. Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation. Leukocytosis and hemoconcentration were noted in both cases prior to death. Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness. The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization. Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness. Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation. Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies.

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

[Zidovudine plus didanosine in HIV infected asymptomatic patients previously treated with zidovudine]. / Zidovudina más didanosina en pacientes asintomáticos infectados por VIH previamente tratados con zidovudina.

OBJECTIVE: To evaluate if the combination of AZT/ddl offered any advantages in surrogate markers among HIV infected asymptomatic patients previously treated with AZT for at least six months. METHODS: We used a prospective cohort of 269 asymptomatic HIV patients with CD4+ cell counts between 200 and 500 cells/microL. They were given didanosine (ddl 400 mg/d) in addition to AZT (500 mg/d) and had received AZT monotherapy for an average of 20 months. End points were progression to AIDS, death, or toxicity. RESULTS: Median CD4+ cell count at the start of the combination therapy was 339 cells/microL which increased at three months to 451 and subsequently declined at 6, 12 and 18 months of followup (medians of 392, 360, 307 cells/microL respectively). Five patients progressed to AIDS, six developed toxicity (myelosuppression, hepatitis or pancreatitis) and 26 had minor side effects that required only dose reduction. CONCLUSIONS: The addition of ddl to patients with prolonged ZDV monotherapy can be useful. CD4+ T cell counts showed a significant increase at 3 months with a gradual subsequent decline to below baseline at 18 months. Adverse effect of the drugs, although frequent, did not stop therapy in most patients.

The Girdlestone pseudarthrosis in the treatment of infected hip replacements.

The results of 78 resections of the head and neck of the femur (Girdlestone pseudarthrosis) in patients with infected hip replacements were studied. The mean follow-up was 5 years. At the time of the resection, gram-positive organisms were found in 53% of the cases, gram-negative in 33%, and in 12% there were mixed flora. The Girdlestone pseudarthrosis controlled the infection in 86% and achieved satisfactory relief of pain in 83%. The mean shortening of the limb was 4.1 cm and every patient needed some type of external walking aid. We found no correlation between the type of organisms and the persistence of infection, nor between shortening and the functional results. The Girdlestone pseudarthrosis is an acceptable method of controlling infection and relieving pain after infection of a total hip replacement.

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.

Prenatal cocaine exposure and school-age intelligence.

Assessments of the possible consequences of prenatal exposure to cocaine have been limited by lack of control for socio-demographic confounders and lack of follow-up into the school years. We evaluated intelligence at ages 6-9 years in 88 children from a cohort of 280 born between September 1, 1985 and August 31, 1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n = 96) births of comparable gender and birthweight. IQ scores did not differ between children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4, difference = 0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment for child height, head circumference and prior residence in a shelter or on the street, and for caregiver IQ and home environment (mean difference = 2.2 points, 95% CI-1.5, 5.8).

Low prevalences of HIV infection and sexually transmitted disease among female commercial sex workers in Mexico City.

OBJECTIVES: This study tried to determine human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevalences among female commercial sex workers in Mexico City. METHODS: A sampling frame was constructed that included bars, massage parlors, and street corners. RESULTS: Prevalences for Treponema pallidum, herpes simplex virus type 2, HIV, Neisseria gonorrhoeae, and Chlamydia trachomatis were 6.4%, 65%, 0.6%, 3.7%, and 11.1%, respectively. A significant association was found between higher STD frequencies and working at street sites. CONCLUSIONS: Most STD frequencies were lower in comparison with rates found for female sex workers in other countries. However, preventive programs against STD/ HIV are needed in this population.

Hepatitis B markers in men seeking human immunodeficiency virus antibody testing in Mexico City.

OBJECTIVES: To estimate the prevalence and associated risk factors of hepatitis B virus (HBV) serologic markers in 1,377 men with high-risk sexual behavior attending a center for human immunodeficiency virus (HIV) detection in Mexico City. METHODS: The study population consisted of all men who were tested for HIV from March to September, 1992. Study participants responded to a standardized questionnaire and provided a blood sample for serology. RESULTS: A total of 1.9% of the population were hepatitis B surface antigen (HBsAg) carriers, and there was a significant difference in HBsAg prevalence between HIV-negative (0.8%) and HIV-positive individuals (7.9%). Sexual preference was associated with HBsAg prevalence; only 0.3% of men who had female sexual partners exclusively were HBsAg carriers, compared with 4.8% of men who had male sexual partners exclusively. Prevalence of antibodies to hepatitis B core antigen (anti-HBc) was 15.4%. However, men who reported only female partners had a 4.6% prevalence, whereas men who had only male partners had a 30.4% prevalence. Logistic regression analysis demonstrated an association of anti-HBc prevalence with age, marital status, sexual preference, seropositivity for HIV, and antibodies to herpes simplex virus type 2. CONCLUSIONS: These data demonstrate that coinfection with HBV is common in the HIV-positive men studied. The highest prevalences of HBsAg and anti-HBc were observed among homosexual men. These results highlight the need to intensify safe-sex education campaigns and to promote hepatitis B vaccination especially among this population group.

[Seroprevalence of various viruses and sociodemographic characteristics of women seeking HIV screening]. / Seroprevalencias a diversos virus y características sociodemográficas en mujeres que buscan detectarse VIH.

OBJECTIVES: To study the seroprevalence of syphilis, herpes simplex-2, hepatitis B and HIV, and main sociodemographic characteristics and sexual behavior in women seeking testing for human immunodeficiency virus (HIV) in Mexico City. METHODOLOGY: A self-applied questionnaire was used in 454 women; and a blood sample was taken for the detection of markers for syphilis, herpes simplex virus-2 (HSV-2)), antibodies against core and surface antigens for hepatitis B virus (HBV), and ELISA and Western blot for HIV. RESULTS: Seroprevalences for antibodies against T. pallidum, HSV-2, HBV and HIV were 4.6%, 29.3%, 3.5% and 4.0%, respectively. Forty-six percent of the women were 20 to 29 years old; 70% reported complete junior high school or higher education level; 75% were sexually active; 56% reported at least one stable male sexual partner, 17% reported at least one occasional male sexual partner in the last three months, and 60% had had at least one sexual relation in the last three months; of these, only 18% (n = 82) reported the use of a condom as a preventive measure. Almost 30% of the HIV positive women had a history of blood transfusion, while less than 10% of the HIV negative women had received a transfusion. In addition, 10.6% said that one of their sexual partners was infected with HIV or had AIDS. CONCLUSIONS: Risks of HIV/STD transmission for this group of self-selected women were linked to blood transfusion, low education and, most important, the risk from male sexual partners who were HIV seropositive. It is expected that these results will contribute to the improvement and development of strategies for the control and prevention of STD among this population group, as well as the general population in Mexico.

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.

Toxoplasmosis of the central nervous system in patients with AIDS in Mexico.

Toxoplasmosis of the central nervous system (CNS) is the most common cause of intracerebral lesions in patients with AIDS. It is now standard clinical practice to treat empirically, based on clinical and radiographic findings, and to perform a biopsy of the lesion only in those patients who fail to have a clinical and radiographic response after two weeks of therapy. This study describes the presentation and response to therapy of central nervous system toxoplasmosis in patients with AIDS at a private practice in Mexico City. A retrospective chart and radiology review of all patients with AIDS treated empirically for toxoplasmosis between 1988 and 1993 was performed. A total of 177 patients with AIDS were seen, nine (5.1%) had toxoplasmosis. Patients with toxoplasmosis were males with a median age of 39 years (range 26 - 65). In two patients, toxoplamosis of the CNS was the initial manifestation of HIV infection, all others had a prior diagnosis of AIDS with a mean of 10 months between their first AIDS defining event and the diagnosis of toxoplasmosis. The median CD4+ T-cell count at the time of the diagnosis of toxoplamsosis was 78 cells/microL. Most patients had headache associated with other focal neurological symptoms such as hemiplegia (2), hemiparesis (2) or seizures (4). Only 4 out of 9 patients had fever as part of their initial clinical presentation. Serum IgG antibodies against Toxoplasma gondii were positive in 6 out of 7 patients tested, while IgM antibodies were negative in all patients. On imaging studies (Computerized Tomography or Magnetic Resonance Imaging), 4 patients had a single lesion while the rest had two or more lesions. Two patients were initially treated with pyrimethamine/sulfadiazine and were later changed to pyrimethamine/clindamycin, which was the treatment given from the beginning to all other patients. One patient died of an intralesional hemorrhage two weeks after the diagnosis despite adequate therapy. The probability of surviving 6 months after the diagnosis of toxoplasmosis was 60%. The findings of these authors are similar to those reported in other series where toxoplasmosis of the CNS is a late complication of HIV infection associated with a CD4+ cell count of < 100 cells/microL. However, survival was short in spite of a good response to therapy.