Effects of coffee on driving performance during prolonged simulated highway driving.

RATIONALE: Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. OBJECTIVES: The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. METHODS: Non-sleep deprived healthy volunteers (n024) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. RESULTS: The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p00.024) and second hour (p00.019) after the break. Similarly, the standard deviation of speed (p0 0.024; p00.001), mental effort (p00.003; p00.023), and subjective sleepiness (p00.001; p00.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p00.004). CONCLUSIONS: These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving.

Eye manifestations of intrauterine infections.

The eye finding most characteristic of a prenatal, and therefore, congenital infection is a chorioretinal scar or an active chorioretinitis as can be seen in congenital toxoplasmosis, CMV, HSV, lymphocytic choriomeningitis virus, or varicella zoster infections. Congenital cataracts are suggestive, but less specific for congenital infection. They may be a relatively isolated finding in rubella, syphilis, varicella zoster, and Epstein-Barr virus infections. When they are present in congenital toxoplasmosis, HSV, and CMV, they are associated with extensive eye involvement. Other manifestations are less common as discussed above. The mechanism of action of these agents appears to be both a direct toxic and a teratogenic effect.

Congenital lymphocytic choriomeningitis virus infection: decade of rediscovery.

Lymphocytic choriomeningitis virus (LCMV) is an underdiagnosed fetal teratogen. This diagnosis should be considered for infants and children with unexplained hydrocephalus, micro- or macrocephaly, intracranial calcifications, chorioretinitis, and nonimmune hydrops. The immunofluorescent antibody test is the only reasonable, commercially available, screening diagnostic tool. The differential diagnosis of congenital LCMV infection includes toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, enteroviruses, human parvovirus B19 [corrected], and syphilis. The infection has also been misdiagnosed as various neurologic, ophthalmologic, and chromosomal syndromes. Further research, to determine the prevalence of this infection in human and rodent populations, and prospective studies, to delineate the clinical spectrum of congenital infection, are needed. The public and members of the medical profession should be made aware of the hazard that wild, pet, and laboratory rodents pose to pregnant women.

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital chorioretinitis.

PURPOSE: To elucidate the role and clinical spectrum of congenital lymphocytic choriomeningitis virus infection as a cause of chorioretinopathy, congenital hydrocephalus, and macrocephaly or microcephaly in the United States. METHODS: We performed complete ophthalmologic surveys of all residents at Misericordia, a home for the severely mentally retarded in Chicago, and prospectively evaluated all patients with chorioretinitis or chorioretinal scars during a 36-month period at Children's Memorial Hospital, also located in Chicago. Sera for patients demonstrating chorioretinal scars (a sign of intrauterine infection) were tested for Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus and lymphocytic choriomeningitis virus antibodies. RESULTS: Four of 95 patients examined at the home had chorioretinal scars, and two of these patients had normal T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers and dramatically elevated titers for lymphocytic choriomeningitis virus. Three of 14 cases of chorioretinitis at the hospital had normal T. gondii, rubella virus, cytomegalovirus, and herpes sim-plex virus titers and elevated lymphocytic choriomeningitis virus antibody titers. (A fourth case, diagnosed in 1996, was reported 2 years ago.) CONCLUSIONS: Lymphocytic choriomeningitis virus was responsible for visual loss in two of four children secondary to chorioretinitis in a population of severely retarded children. The six new cases of lymphocytic choriomeningitis virus chorioretinitis identified in these two populations over the last 3 years, compared with the total number ever reported in the United States (10 cases), suggests that lymphocytic choriomeningitis virus may be a more common cause of congenital chorioretinitis than previously believed. Because its consequences for visual and psychomotor development are devastating, we conclude that the workup for congenital chorioretinitis should include lymphocytic choriomeningitis virus serology, especially if T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers are negative.

Lymphocytic choriomeningitis virus chorioretinitis mimicking ocular toxoplasmosis in two otherwise normal children.

PURPOSE: To report unilateral macular lesions, mimicking toxoplasmic scars, in two children with serological evidence for lymphocytic choriomeningitis virus infection. METHODS: Case reports. RESULTS: Patients were 4 and 5 years old, with negative toxoplasma serologies and no sign of rubella, cytomegalovirus, or herpes simplex infection (TORCH evaluation). Lymphocytic choriomeningitis virus infection was detected in both cases by enzyme-linked immunosorbent assay and confirmed by Western immunoblotting. The modes of infection were unknown; no history of symptomatic systemic lymphocytic choriomeningitis virus infection was reported, and lymphocytic choriomeningitis virus serologies were negative in the mothers of the patients. Neurological examinations and brain magnetic resonance imaging were normal. CONCLUSION: Our observations suggest that chorioretinal scars can be an isolated manifestation of lymphocytic choriomeningitis virus infection.

Early diagnosis of Usher syndrome in children.

PURPOSE: To screen severe to profound, preverbal hearing-impaired children for Usher syndrome by ophthalmologic examinations, including electroretinographic testing. These patients are especially good candidates for early cochlear implants, which will improve listening and spoken language skills. METHODS: Consecutive patients over 2 years of age, given a diagnosis of severe to profound, preverbal hearing loss, were screened for Usher syndrome by a complete ophthalmologic examination including an electroretinogram. RESULTS: Five of 48 patients screened (10.4%) were diagnosed with Usher syndrome and received cochlear implants. CONCLUSION: All children with severe to profound, preverbal sensorineural hearing loss should be screened for Usher syndrome by ophthalmologic examination including electroretinogram.

Iridocorneal adhesions in patients with the Marfan syndrome.

Marfan syndrome is an autosomal dominant connective tissue disorder characterized by skeletal, cardiovascular, and ocular anomalies. Ectopia lentis is the most common ocular manifestation. We report an ocular sign not previously described in Marfan syndrome, iridocorneal adhesions secondary to anterior lens subluxation. Three patients with the Marfan syndrome had iridocorneal adhesions on slit-lamp examination. One patient developed adhesions following treatment with pilocarpine. She underwent pars plana vitrectomy and lensectomy in both eyes due to progression of the iridocorneal adhesions. Treatment with miotics rotates the lens-iris diaphragm anteriorly and may contribute to the formation of such adhesions. The two other patients remained stable and did not received lensectomy or vitrectomy. Careful slit-lamp examination of the anterior segment should be conducted in patients with dislocated lenses.

Childhood blindness and visual loss: an assessment at two institutions including a "new" cause.

PURPOSE: This study was initiated to investigate the causes of childhood blindness and visual impairment in the United States. We also sought a particular etiology--congenital lymphocytic choriomeningitis virus (LCMV)--which has been considered exceedingly rare, in a fixed target population of children, the severely mentally retarded. METHODS: We undertook a library-based study of the world literature to shed light on the causes of childhood blindness internationally and to put our data in context. We prospectively examined all consented children (159) at 2 institutions in the United States to determine their ocular status and the etiology of any visual loss present. One of the institutions is a school for the visually impaired (hereafter referred to as Location V), in which most of the students have normal mentation. The other is a home for severely mentally retarded, nonambulatory children (hereafter referred to as Location M). This institution was selected specifically to provide a sample of visual loss associated with severe retardation because the handful of cases of LCMV in the literature have been associated with severe central nervous system insults. Histories were obtained from records on site, and all children received a complete cyclopleged ophthalmic examination at their institution performed by the author. Patients at Location M with chorioretinal scars consistent with intrauterine infection (a possible sign of LCMV) had separate consents for blood drawing. Sera was obtained and sent for standard TORCHS titers, toxoplasmosis titers (Jack S. Remington, MD, Palo Alto, Calif), and ELISA testing for LCMV (Centers for Disease Control and Prevention, Atlanta, Ga). RESULTS: The diagnoses at Location V were varied and included retinopathy of prematurity (19.4%), optic atrophy (19.4%), retinitis pigmentosa (14.5%), optic nerve hypoplasia (12.9%), cataracts (8.1%), foveal hypoplasia (8.1%), persistent hyperplastic primary vitreous (4.8%), and microphthalmos (3.2%). The most common diagnosis at Location M was bilateral optic atrophy, which was found in 65% of the patients examined who had visual loss. Of these, the insults were most often congenital (42.6%), with birth trauma, prematurity, and genetics each responsible for about 15% of the optic atrophy. The second most common diagnosis was cortical visual impairment (24%), followed by chorioretinal scars (5%), which are strongly suggestive of intrauterine infection. Of 95 patients examined at Location M, 4 had chorioretinal scars. Two of these had dramatically elevated titers for LCMV, as did one of their mothers. One of the other 2 children died before serum could be drawn, and the fourth had negative titers for both TORCHS and LCMV. CONCLUSIONS: At both locations studied, visual loss was most often due to congenital insults, whether genetic or simply prenatal. The visual loss at Location V was twice as likely as that at Location M to be caused by a genetic disorder. The genetic disorders at Location V were more often isolated eye diseases, while those among the severely retarded at Location M were more generalized genetic disorders. Our study identified optic atrophy as a common diagnosis among the severely mentally retarded with vision loss, a finding that is supported by previous studies in other countries. In our population of severely retarded children, the target etiology of lymphocytic choriomeningitis virus was responsible for half the visual loss secondary to chorioretinitis from intrauterine infection. This is more common than would be predicted by the few cases previously described in the literature, and strongly suggests that LCMV may be a more common cause of visual loss than previously appreciated. We believe that serology for LCMV should be part of the workup for congenital chorioretinitis, especially if the TORCHS titers are negative, and that perhaps the mnemonic should be revised to "TORCHS + L." Childhood blindness and visual impairment are tragic and co

Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness.

X-linked congenital stationary night blindness (CSNB) is a recessive non-progressive retinal disorder characterized by night blindness, decreased visual acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X-linked CSNB have been proposed. Patients with complete CSNB show moderate to severe myopia, undetectable rod function and a normal cone response, whereas patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but measurable rod and cone function. The electrophysiological and psychophysical features of these clinical entities suggest a defect in retinal neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects the recently described genetic heterogeneity in which the locus for complete CSNB (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the CSNB2 minimal region was characterized and found to have similarity to voltage-gated L-type calcium channel alpha1-subunit genes. Mutation analysis of this new alpha1-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six different mutations that are all predicted to cause premature protein truncation. These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.

Cornea and iris changes in congenital ectropion uvea after trabeculotomy.

This article details a previously undescribed complication of trabeculotomy occurring in a patient with congenital ectropion uvea and discusses its possible association with an anterior chamber membrane. A 6-year-old boy with congenital ectropion uvea underwent trabeculotomy. After the trabeculotome was swept into the anterior chamber, multiple ovoid and round endothelial and posterior stromal opacities developed in the cornea, and new areas of iris surface irregularities appeared. This is the first reported case of corneal endothelial and iris changes occurring in a patient with congenital ectropion uvea after trabeculotomy without direct endothelial or iris contact from the trabeculotome. The exact cause of these changes is unknown.

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Resolution of intracranial calcifications in infants with treated congenital toxoplasmosis.

PURPOSE: To determine the natural history of intracranial calcifications in infants with treated congenital toxoplasmosis. MATERIALS AND METHODS: Between January 1982 and March 1994, cranial computed tomography was performed in 56 infants with treated congenital toxoplasmosis when they were newborns and approximately 1 year old. Locations and sizes of intracranial calcifications were noted. RESULTS: Forty newborns had intracranial calcifications. By 1 year of age, calcifications diminished or resolved in 30 (75%) and remained stable in 10 (25%) of these treated infants. Ten (33%) of the 30 infants whose calcifications diminished versus seven (70%) of the 10 infants with stable calcifications received less intensive antimicrobial treatment than the other treated infants. In contrast, a small number of infants who were untreated or treated 1 month or less had intracranial calcifications that increased or remained stable during their 1st year of life. CONCLUSION: Diminution or resolution of intracranial calcifications was an unexpected and remarkable finding in infants with treated, congenital toxoplasmosis, consonant with their improved neurologic functioning.