PEDIATRICS Vol. 118 No. 2 August 2006, pp. e379-e390 (doi:10.1542/peds.2005-1530)
ARTICLE |
Impact of Visual Impairment on Measures of Cognitive Function for Children With Congenital Toxoplasmosis: Implications for Compensatory Intervention Strategies
a Departments of Pediatrics and Psychiatry
b Health Studies
h Ophthalmology and Visual Sciences
i Ophthalmology, Medicine, Pediatrics, Infectious Disease, and Pathology, Committees on Immunology, Molecular Medicine, and Genetics, University of Chicago, Chicago, Illinois
c Department of Ophthalmology, Northwestern University Medical Center, Chicago, Illinois
d Department of Pediatrics, Division of Pediatric Infectious Diseases, Rush University Medical Center, Chicago, Illinois
e Department of Pediatric Neurology, Children's Memorial Hospital, Northwestern University, Chicago, Illinois
f Department of Mathematics and Statistics, Columbia University, New York, New York
g Department of Medicine, Division of Infectious Diseases, Stanford University and Palo Alto Medical Research Foundation, Palo Alto, California
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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OBJECTIVES. The purpose of this work was to determine whether visual impairment caused by toxoplasmic chorioretinitis is associated with impaired performance of specific tasks on standardized tests of cognitive function. If so, then we worked to determine whether there are patterns in these difficulties that provide a logical basis for development of measures of cognitive function independent of visual impairment and compensatory intervention strategies to facilitate learning for such children.
METHODS. Sixty-four children with congenital toxoplasmosis with intelligence quotient scores 
50 and visual acuity sufficient to cooperate with all of the intelligence quotient subscales had assessments of their vision, appearance of their retinas, and cognitive testing performed between 3.5 and 5 years of age. These evaluations took place between 1981 and 1998 as part of a longitudinal study to determine outcome of congenital toxoplasmosis. Children were evaluated at 3.5 or 5 (37 children) or both 3.5 and 5 (27 children) years of age. Cognitive function was measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised. Wechsler Preschool and Primary Scale of Intelligence-Revised scale scores were compared for children grouped as those children who had normal visual acuity in their best eye (group 1), and those who had impaired vision in their best eye (acuity <20/40) because of macular disease (group 2). Demographic characteristics were compared for children in the 2 groups. Test scores were compared between groups using all of the 3.5-year-old visits, all of the 5-year-old visits, and using each child's "last" visit (ie, using the 5-year-old test results when a child was tested at both 3.5 and 5 years of age or only at 5 years, otherwise using the 3.5-year-old test results). The results were similar and, therefore, only the results from the last analysis are reported here.
RESULTS. There were 48 children with normal visual acuity in their best eye (group 1) and 16 children with impaired vision because of macular involvement in their best eye (group 2). Ethnicity and socioeconomic scores were similar. There was a significantly greater proportion of males in group 2 compared with group 1 (81% vs 46%). There was no significant diminution in Wechsler Preschool and Primary Scale of Intelligence-Revised test scores between 3.5 and 5 years of age for the 27 children tested at both of these ages. Verbal intelligence quotient, performance intelligence quotient, full-scale intelligence quotient scores, and all of the scaled scores except arithmetic and block design were significantly lower for children in group 2 compared with group 1. The majority of the differences remained statistically significant or borderline significant after adjusting for gender. However, the difference in overall verbal scores does not remain statistically significant. Mean ± SD verbal (98 ± 20) and performance (95 ± 17) intelligence quotients were not significantly different for children in group 1. However, verbal (88 ± 13) and performance intelligence quotients (78 ± 17) were significantly different for children in group 2. For children in group 2, their lowest scale scores were in object assembly, geometric design, mazes, and picture completion, all timed tests that involved visual discrimination of linear forms with small intersecting lines. In the 2 scales scored that did not differ between groups 1 and 2, arithmetic and block design, timing and vision but not linear forms were components of the tasks. Children with monocular and binocular normal visual acuity did not differ in verbal, performance, or full-scale intelligence quotients or any of the subscale tests. Difficulty with sight or concomitant neurologic involvement also seemed to impact the ability to acquire information, comprehension skills, and vocabulary and performance in similarities testing. After controlling for gender, however, these differences were diminished, and there were no longer differences in overall verbal scores. As noted above, results were generally similar when all of the tests for 3.5-year-olds or 5-year-olds were analyzed separately. At the 3.5-year visit there were fewer significant differences between the 2 groups for the verbal components than at the 5-year visit.
CONCLUSIONS. In children with congenital toxoplasmosis and bilateral macular disease (group 2) because of toxoplasmic chorioretinitis, scaled scores were lowest on timed tests that require discrimination of fine intersecting lines. Although the severity of ocular and neurologic involvement is often congruent in children with congenital toxoplasmosis, ophthalmologic involvement seems to account for certain specific limitations on tests of cognitive function. Children with such visual impairment compensate with higher verbal skills, but their verbal scores are still less than those of children with normal vision, and in some cases significantly so, indicating that vision impairment might affect other aspects of cognitive testing. Patterns of difficulties noted in the subscales indicate that certain compensatory intervention strategies to facilitate learning and performance may be particularly helpful for children with these impairments. These patterns also provide a basis for the development of measures of cognitive function independent of visual impairment.
Key Words: congenital toxoplasmosis • T gondii • visual impairment • cognitive function
Abbreviations: Ig—immunoglobulin • DS—double-sandwich • AC/HS—differential agglutination • ELISA—enzyme-linked immunosorbent assay • WPPSI-R—Wechsler Preschool and Primary Scales of Intelligence-Revised • SES—socioeconomic scores • IQ—intelligence quotient • CI—confidence interval
Toxoplasma gondii is a common parasite, acquired by ingestion of material contaminated with T gondii oocysts excreted by cats or T gondii cysts in meat not cooked to "well done."1 T gondii has been estimated to infect 3000 infants born in the United States each year and to cause annual costs for care and lost productivity of between US $400 million and $8.8 billion.1,2
Toxoplasmic chorioretinitis is a major cause of loss of vision.1–10 Almost all congenitally infected individuals who are not treated in infancy develop retinal disease by adolescence.2–10 Progression and recurrences of chorioretinitis characterize this ophthalmologic disease.1,2 We have evaluated children with congenital toxoplasmosis in a standardized, prospective, and longitudinal manner.1,2,10–15 These children were either treated in utero and/or in the first year of life in the treatment arm or were older children whose infection was detected after the first year of life and who were, therefore, not treated during their first year.10
Although brain involvement and cognitive impairment secondary to congenital T gondii infection are well-recognized features of this illness,4 we hypothesized that some of what seemed to be difficulties with cognitive function in tests for such children was because of difficulties secondary to visual impairment rather than because of primary brain damage. Therefore, we analyzed cognitive test results examining 3 factors that might decrease performance because of poor visual acuity: linear forms with small intersecting lines, tests with time constraints (timed tests), and tests that require vision. We correlated these findings with whether there was normal visual acuity in their "best eye" or impaired vision because of toxoplasmosis chorioretinitis or chorioretinal scars in their best eye. We also looked at effects of normal monocular versus normal binocular visual acuity. The purpose of characterizing impact of vision on specific subscale results was to identify the specific characteristics of tasks that are difficult for children with impaired vision. If there were such patterns, and performance and verbal subscales did differ, the specific difficulties could then form a basis for the development of strategies to help children with toxoplasmic chorioretinitis compensate for the effect of their visual impairment on learning. We hypothesized that there would be a difference and then tested whether there is a difference between scores on verbal versus motor subscales of the developmental test that was more pronounced in children with either bilateral or unilateral macular scars.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Infants and Children
Sixty-four infants and children with congenital toxoplasmosis were referred to our study by their physicians. The institutional review board approved the study, and informed consent was obtained from parents or legal guardians. Inclusion criteria, methods to establish diagnosis, and methods for evaluation were as described previously.10
Criteria for Study Entry
Criteria for entry into the treatment trial included the presence of confirmed infection and an age of <2.5 months at referral. Infection was established by serologic evaluation performed by one of our researchers (J.R.), as described previously.1,10 In certain instances, serologic tests were conducted in the laboratory of Dr Philippe Thulliez (Institut de Puericulture, Paris, France) or the Massachusetts State Laboratory Institute (Jamaica Plain, Massachusetts). Specific immunoglobulin (Ig) G was measured with the Sabin-Feldman dye test. Specific IgM was measured with double-sandwich (DS) IgM enzyme-linked immunosorbent assay (ELISA), IgM immunosorbent agglutination assay, or both. IgM levels in the DS IgM ELISA >0.2 in neonates and >1.7 in adults were considered consistent with congenital infection and suggestive of recent infection, respectively. Lymphocyte stimulation studies, T gondii-specific IgA ELISA, Western blot, and differential agglutination test (AC/HS test) were performed in some instances, as described.1,10 Isolation of T gondii from white blood cells or placentas, fetal or newborn blood, and amniotic fluid were as described.7,8 Polymerase chain reaction for the T gondii B1 gene was performed on amniotic fluid or cerebrospinal fluid in certain instances.2,10 Infected children were identified prenatally, perinatally, or later. Maternal acquisition of T gondii during gestation was confirmed serologically by a fourfold rise in the titer in the Sabin-Feldman dye test or a T gondii-specific IgM level >1.7 in the DS IgM ELISA and with an acute pattern in the AC/HS test indicating recent maternal infection.
Congenital toxoplasmosis was established clinically and/or serologically on the basis of 1 of the following: presence of Toxoplasma-specific IgM or IgA in neonatal serum and/or in serum obtained during the first 4 months of life; presence of Toxoplasma-specific IgM in cerebrospinal fluid; relevant findings in maternal serum (Toxoplasma-specific IgM and/or AC/HS titers with an acute pattern or Sabin-Feldman dye test result of >300 IU) in conjunction with characteristic clinical findings of congenital toxoplasmosis, including retinochoroiditis, cerebral calcifications, and/or hydrocephalus; production of T gondii antibodies by the infant after disappearance of passively transferred maternal antibody; presence of Toxoplasma-specific antibodies (detected by Western blot) in infant's serum that were not present in the mother's serum; or presence of the T gondii B1 gene in amniotic fluid or cerebrospinal fluid (demonstrated by polymerase chain reaction). Congenital infection with cytomegalovirus was excluded by urine culture and/or serologic testing. Lack of development of antibodies to T gondii in serum from a small number of these children when treatment was discontinued may have been because of early initiation of treatment that eliminated tachyzoites before cysts formed.1
Children were either untreated during their first year of life (that is, before referral to our study group and, thus, called "historical patients") or treated during their first year of life. Treatment involved either a lower (treatment A) or higher (treatment C) dosage of pyrimethamine plus sulfadiazine and calcium leukovorin for 
1 year as described.1,10 Serologic, isolation, and polymerase chain reaction studies; serum pyrimethamine levels; and lymphocyte studies were performed in our laboratories as described (J.R. and R.M.).1,10,11
Evaluations
All of the treated infants and children were evaluated prospectively in the neonatal period and then again as they reach 1, 3.5, 5, 7.5, 10, 15, and 20 years of age.10 Untreated historical patients were evaluated when referred and thereafter at the same subsequent ages as the treated children. Ophthalmologic examinations were performed by the National Collaborative Study ophthalmologists (M.M., P.R., and M.K.); data sheets and narrative evaluations were prepared for each child at each examination. A standardized database was compiled including each evaluation for each child. Ophthalmologic evaluations included assessment of vision (fixation preference, Allen card testing, or Snellen chart reading) depending on the ages and capabilities of the child. No forced preferential looking tests were performed. Extraocular muscles and pupillary examinations were performed before cycloplegia. Patients' pupils were dilated with a combination of cyclopentolate hydrochloride 0.2% and phenylephrine hydrochloride 1% or cyclopentolate hydrochloride (0.5%, 1%, or 2%), phenylephrine hydrochloride (2.5%), and tropicamide (1%). After cycloplegia, all of the children had evaluations using slit-lamp examination, retinoscopy, and indirect ophthalmoscopy.
For the assessment of cognitive function used in the present analysis, the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) was performed at 3.5 and/or 5 years of age. Ophthalmologists, a developmental pediatrician, and a developmental psychologist reviewed the test materials to establish whether the subscale tests required vision, were time limited, or required discrimination of fine lines (Table 2). They defined a test as not requiring vision if a person could complete the subscale with eyes closed. They established whether a subscale test was timed or not timed based on whether a time limit is set to complete the subscale items. They determined whether the subtest included materials that required discrimination of fine lines (eg, a maze or a line drawing). Of the performance tasks, only block design did not require discrimination of fine lines. They also noted that of the performance tests, picture completion does not require fine motor skills.
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Evaluations were performed between 1981 and 1998. Developmental tests at 3.5 and 5 years of age were performed between 1984 and 1998.
Data Collection
A computerized database was compiled using 4th Dimension software (ACI US, Inc, Cupertino, CA). Specific eye manifestations, activity and location of chorioretinal scars, and factors that contributed to substantial visual impairment were characterized and analyzed. We defined periphery as any fundus location outside the major temporal arcades, not within 1 disk diameter of the optic nerve. An ophthalmologic severity score for each eye of each child, formulated to provide uniform means to characterize impact of the infection on vision, is as follows: normal vision, no lesions (0); normal vision, nonmacular lesions (1); normal vision, macular lesions (2); impaired vision, nonmacular lesions (3); impaired vision, macular lesions (4); impaired vision, inability to view posterior pole because of cataracts or another etiology (4.5); and no observable light perception (retinal detachment, grossly abnormal electroretinogram) (5).
For the purposes of the present analysis, 2 groups were constructed based on vision in the child's best eye (group 1): 0, normal vision, no lesions; 1, normal vision, nonmacular lesions; 2, normal vision, macular lesions; and (group 2) 4, impaired vision, macular lesions. Children with impaired vision because of nonmacular disease (3, impaired vision, nonmacular lesions) were not included in this analysis. Children with impaired vision and inability to view the posterior pole because of cataracts or another etiology (4.5) or no observable light perception (retinal detachment, grossly abnormal electroretinogram; 5) were also excluded from this analysis. Group 1 included children with normal vision in 1 or 2 eyes. This group was further divided into those with normal visual acuity bilaterally (group 1–0) and those with normal visual acuity unilaterally (group 1–1). Group 2 included children who had abnormal vision because of macular disease in both eyes (ie, in their best eye).
Socioeconomic scores (SES) were calculated according to Hollingshead Four Factor Index of Social Status.16 The Hollingshead Four Factor Socioeconomic Score includes educational level and occupations for both parents. WPPSI-R verbal, performance, and full-scale intelligence quotient (IQ) scores were analyzed in addition to each subscale score separately.
Statistical Analysis
Demographic characteristics were compared between groups 1 and 2 using 2-sample t tests for continuous variables and Pearson's 
2 tests or Fisher's exact tests, as appropriate, for categorical variables. The mean differences in scores between the 2 visits were calculated, and 95% confidence intervals (CIs) were constructed for those children with both the 3.5- and 5-year visits. Differences in scores between groups were assessed using 2-sample t tests assuming unequal variances. To control for the effect of gender on these differences, analysis of variance models, with group and gender as factors, were used. A group by gender interaction term was included but was dropped from the final model if not significant. Also, the association between visual acuity in the best eye, on the logMAR scale, and IQ scores was examined using Pearson correlation coefficients. Initially, results were analyzed by comparing all of the 3.5-year-old test results, all of the 5-year-old test results, and using each child's "last" visit (ie, using the 5-year-old test results when a child was tested at both 3.5 and 5 years of age or only at 5 years; otherwise using the 3.5-year-old test results). Conclusions were similar, and only the results from the last visit are analyzed and reported herein.
In addition, differences between verbal and performance IQ scores were examined using paired t tests within each group. These differences were then compared between groups 1 and 2 using a 2-sample t test. Because the performance IQ measure involved more visual tasks compared with the verbal IQ measure, this was used as a test of the hypothesis that there were different patterns of test performance between the children with and without visual impairment. Additional tests of this kind were performed with respect to specific subscales. For example, let yijs denote the response of subject i in group j on subscale s. The within-subject contrasts yijs – yijt were first formed, where s and t refer to 2 different subscales, and then compared between groups 1 and 2 using 2-sample t tests. Note that these tests are equivalent to a test of the "group x subscale" interaction term in a repeated-measures analysis of variance with group as a between-subjects factor and subscale as a within-subjects factor.
All of the data are summarized as mean ± SD unless otherwise noted. Statistical analyses were conducted using Stata, Version 8 (Stata Corp, College Station, TX).
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Characteristics of Children
Of the 64 children with congenital toxoplasmosis with full-scale IQ scores
50, there were 48 children with normal visual acuity in their best eye (group 1), and 16 children with impaired vision (<20/40) because of bilateral macular lesions (group 2). Twenty-seven children had testing at both the 3.5-year and 5-year visits, 18 had testing at only the 3.5-year visit, and 19 had testing at only the 5-year visit. Fifty (78%) of the 64 subjects were in the treated group. Ages were not significantly different between the groups (Table 1). SES were not significantly different between the groups, with the exception of those without bilateral macular disease who sought referral after the first year of life: they were of higher socioeconomic status than those in the treated group without bilateral macular disease. Ethnicity did not differ between the groups. However, the gender distribution was significantly different with group 1 being 46% male and group 2 being 81% male (P = .014). Geographic locations of the homes of these children are shown in Fig 1.
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Ophthalmologic Lesions
Representative peripheral and macular lesions are shown in Fig 2. A representative ophthalmologic data sheet is shown in Fig 3.
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Comparison of Test Results of Children Tested at 3.5 and 5 Years of Age
When scores of the 27 children tested at 3.5 and 5 years were compared (Fig 4), there was no significant diminution in IQ between 3.5 and 5 years of age.
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Comparison of Test Results for Children Who Have Normal Visual Acuity in Their Best Eye Versus Those Who Have Impaired Vision Because of Macular Involvement in Their Best Eye
Scores on verbal, performance, and full-scale IQs and on all of the subscales, except for arithmetic and block design, were significantly different between groups 1 and 2 (Table 2). In all of the comparisons of IQ and subscales, group 2 had lower scores than group 1. After adjusting for gender, the differences remained significant or borderline significant for performance and full-scale IQ and only 5 subscales (comprehension, mazes, picture completion, object assembly, and geometric design). Except for the picture completion subscale, there was no evidence for a group by gender interaction. Among females, group 1 (n = 26) scored on average 8.4 points higher on picture completion than did group 2 (n = 3). Among males, group 1 (n = 22) scored on average only 2.5 points higher than did group 2 (n = 13); however, these differences between groups reached statistical significance for both genders (P = .0091 and 0.037 for females and males, respectively). LogMAR visual acuity in the best eye was significantly associated with full-scale, performance, and verbal IQ scores with correlation coefficients of –0.57 (P < .0001), –0.59 (P < .0001), and –0.49 (P = .0001), respectively.
For children with visual impairment in the best eye (group 2), there was an average difference of 10 points between their performance and verbal IQ scores (P = .0042). Performance and verbal IQ scores did not differ for children with normal visual acuity in their best eye (group 1) or those with unilateral (group 1–1) or bilateral (group 1–0) normal visual acuity. See Table 3 and Fig 5. The difference between the 2 IQ scores, performance and verbal, was compared between groups 1 and 2 and did not reach statistical significance (P = .080), although the difference between IQ scores was 3 times greater in group 2 than in group 1.
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There is an important distinction in the skills required for picture completion, that is, it does not require fine motor skills. In contrast, all of the other performance subscale tests do require the use of one's hands. The picture completion subscale test is also dependent on the recognition of fine lines (Table 2). There is a large difference between groups 1 and 2 in the picture completion test. Thus, the difference identified in abilities in the picture completion test as opposed to the other performance subscale tests provides an important insight into the specific impact of visual difficulties for children with bilateral macular disease because of congenital toxoplasmosis.
The 4 lowest scores for children in group 2 were object assembly, geometric design, mazes, and picture completion, all tests requiring the recognition of fine lines. Block design was the best-preserved performance subscale and involves manipulating blocks of color to copy a design but not fine line recognition (Table 2). Object assembly involves putting together puzzles that are largely linear forms. Geometric design has thin lines in pictures where the child identifies the design that is the same as the one above and also copies the linear forms in a test booklet. The mazes subtest was the lowest mean subscale score. This subscale consists of completing mazes of linear forms with small intersecting lines. Picture completion requires the child to identify the incomplete part of the picture in linear representational drawings. Block design is the only subtest in which the results for group 1 and group 2 did not differ significantly (Table 2). When performance on the block design subscale was contrasted with each of the other subscales (object assembly, geometric design, mazes, and picture completion), there was a statistically significant difference between groups 1 and 2 for the block design versus picture completion contrast (Ps of .57, .31, .069, and .049, respectively). The average of the subscales involving fine lines was also contrasted with the average of the other 6 subscales, that is, block design plus the 5 verbal subscales, and a significant difference between groups 1 and 2 was found (P = .034). In all of the cases, group 2 exhibited more of a pronounced difference between these 2 distinct types of subscales than did group 1, indicating that fine line recognition might be important to address in any compensatory strategy. Children with visual impairment also performed more poorly on tests that had to be completed in a limited time (Table 2).
Results were similar when analyzed with all of the 3.5-year-olds or all of the 5-year-olds. However, the differences in many of the verbal tests were smaller when only the 3.5-year-olds were included.
Comparison of Test Results for Children Who Have Normal Unilateral Vision Versus Those Who Have Normal Binocular Vision
In verbal and performance IQ scores and all of the subscales, there were no significant differences between these 2 groups (P > .05; Table 2). There was also no significant difference between verbal and performance IQ scores in those children with normal monocular visual acuity (1–1) or in those with normal binocular visual acuity (1–0; P = .26 and P = .22, respectively; Table 3).
Analysis to Determine Whether Cognitive Function Is Different for Children With Unilateral Macular Disease (Group 1–1) Versus Those With Bilateral Macular Disease (Group 2)
Analysis of test results for children who have abnormal visual acuity in both eyes because of macular disease (group 2) compared with children with abnormal visual acuity in only 1 eye (group 1–1) demonstrated lower verbal IQ scores (88 ± 13 [range: 65–114] vs 99 ± 19 [range: 74–135]) but a greater difference in performance IQ scores (78 ± 17 [range: 51–115] vs 95 ± 18 [range: 66–126]). Subscales that differed significantly for children with bilateral as compared with children with unilateral macular disease included information, vocabulary, geometric design, mazes, and picture completion (Table 2).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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This study of the impact of impaired vision on measures of cognitive function in preschool children who have treated and untreated congenital toxoplasmosis provides unique data on the strengths and weaknesses in their cognitive profiles and factors which influence this performance. Children's IQ and subscale scores did not diminish significantly between 3.5 and 5 years of age (P > .05). These results contrast with earlier literature that demonstrated fall-off in IQ scores over time for untreated children or those treated for only 1 month.5
Whether our data were analyzed using (1) the last visit (primary analysis), (2) the 3.5-year visit only, or (3) the 5-year visit only, we found that bilateral impaired visual acuity impaired performance IQ scores disproportionately relative to verbal IQ scores. We had predicted that the subscales that require seeing figures with fine lines and that are timed would be affected by central retinal disease. Consonant with that prediction, we noted that scores on object assembly, geometric design, mazes, and picture completion were significantly impaired by bilateral macular disease. Despite requiring vision and being timed, the subscales of arithmetic and block design were not markedly different between those children with normal visual acuity in their best eye and those with impaired vision in their best eye, presumably because they did not require visual discrimination of fine lines, as in the other subscales (Table 2).
The subscales that consist entirely of test items made of fine lines and the overall performance IQ scale are the lowest for group 2. Group 2 (impaired vision in the best eye) compared with group 1 had significantly lower verbal, performance, and full-scale IQs and all of the subscales except arithmetic and block design. In the WPPSI-R, all of the scaled scores except comprehension have some items that require vision. All of the performance subscales and the verbal subscale of arithmetic are timed. Performance scales that contain items with fine lines are the lowest scale scores for group 2. This seems to indicate added difficulty with discrimination of fine lines above and beyond overall visual acuity and time limits for children with visual impairment. These tests are probably testing vernier visual acuity, that is, smallest detectable amount of misalignment of 2 line segments, like an Amsler Grid.
If the lower scores for the children with bilateral macular disease were attributed solely to brain damage, we would have expected verbal and performance IQ scores to diminish equally, but this was not the case. After adjusting for gender, there were no significant differences in scores between children with and without bilateral macular disease on verbal IQ and all of the subscales except comprehension, mazes, picture completion, object assembly, and geometric design (the last 2 being borderline significant). Before adjusting for gender, these subscales did differ significantly. All of the subscales require vision except for comprehension (Table 2). The fact that there was a significant difference between groups 1 and 2 on the comprehension subscale despite the fact that it does not formally involve vision does suggest that other unidentified factors may influence this subscale. Abilities of the children with bilateral visual impairment will be underestimated if all of the subscales of conventional IQ tests are used without considering their ability to visually discriminate the test materials. Furthermore, the highest subscale test for children in group 2 was vocabulary. The verbal subscale scores provide a more appropriate measure of their cognitive abilities, but impaired vision may also impact on the ease with which one can complete certain of these tests, as well as one's ability to acquire the information measured in these tests. Because the 4 subscales that required seeing linear forms (object assembly, geometric design, mazes, and picture completion) all show a significant difference for children with bilateral macular disease, this observation provides some guidance into ways to help the children with macular impairment in both eyes. In fact, when we compared the children's performance on these 4 subscales to their performance on the remaining subscales, group 2 had a significantly greater detriment on the scales involving linear forms than did group 1. Because development of reading skills greatly depends on perceiving lines, educational efforts should use techniques to help compensate for this weakness in perceiving linear forms. This "weakness in perceiving linear forms" may be equivalent to testing vernier visual acuity (ie, Amsler Grid). Vernier visual acuity is the most discriminating test of visual acuity. For group 2 children, the highest verbal mean score was in vocabulary. For group 1, the highest overall mean score was on the picture completion subscale. Using the strengths in vocabulary and short-term auditory memory to compensate may be another element of a good educational program. Unilateral macular involvement did not impact significantly or cause discrepant performance on any subscale scores. Although certain difficulties with test materials are attributable to visual impairment, it is not necessarily the case that all of the deficits noted can be entirely attributed to visual deficits and not to other underlying or concomitant neurologic deficits in the affected children. It is possible that some of those children with greater visual problems also have more significant neurologic deficits.
Our group of preschool children with congenital toxoplasmosis has demonstrated that, in the preschool years, they are able to maintain function on IQ testing. The children with normal vision in their best eye tested in the normal range. However, the children with bilateral visual impairment had lower scores, especially in subscales that required perceiving linear forms. This indicates a need to (1) consider compensatory strategies for this visual impairment as educational strategies are planned in schools, (2) maintain best-corrected visual acuity using spectacles and amblyopia therapy through regular periodic examinations by a pediatric ophthalmologist, and (3) perform periodic evaluations (where indicated) by a low-vision specialist to assess particular needs and suggest appropriate low-vision aids.
We began with the questions, "What are the specific problems that children with toxoplasmic chorioretinitis experience in test settings, and could a better understanding of these problems be translated into compensatory intervention strategies such that children can use these strategies to improve learning?" Some of the strategies and supportive materials that have been helpful to these and other older children specifically compensate for the vision deficits that we noted and include: hand-held magnifying devices for text, such as magnifying bars or bubbles; large print books; "talking" books; computer magnification of text; camera magnification of materials; removing time constraints for tests; opaque bars under lines of text; high-contrast colors in illustrative materials; sitting in front of the class in close enough proximity to easily view the chalk board; reading aloud to children so that fundamental information and vocabulary expand even if the children cannot accomplish specific visual tasks; and life skills and career counseling so that children appreciate the many career possibilities available to them and develop the skills needed to function independently despite visual limitations. These strategies seem to provide logical approaches, which have also been successful in assisting some of the older children in this study, to help children with toxoplasmic chorioretinitis compensate for specific difficulties because of their visual impairment. Active use of such strategies has resulted in remarkable achievements by some children who are college bound or already in college with bilateral macular toxoplasmic chorioretinal lesions.
It is important to note that we are analyzing this specific cohort of children with congenital toxoplasmosis and not testing children with other causes of visual impairment or other diseases that may impact on vision differently. Thus, our findings may or may not be generalizable to children with other clinical illnesses and/or with different types of visual deficits. Our work does raise the possibility that it may be important to determine whether there are similar findings for children with other diseases that affect vision and the macula. It will be of interest and important in the future to determine whether it is possible to extend our findings and generalize them to patients with other types and causes of visual impairment to develop interventions that would benefit not only patients with visual impairment because of toxoplasmosis but also visual impairment because of other causes.
We recognize that, in addition to global verbal and performance IQ measures, multiple subscales were compared between the 2 groups. This can inflate type I error rates, and we have not adjusted the P values presented in Tables 2 and 3 for multiple testing. However, the fact that group differences on the 3 global IQ measures were all significant and that the group differences on the subscales consistently showed a detriment to the bilaterally visually impaired group (although to varying degrees) makes it unlikely that the cited differences are spurious.
In this article we do not present analyses of these children assessing impact of their difficulties with vision over a lifetime or impact of correction of their specific structural deficits on their vision later in life. The work described is an analysis of children at early ages. We have not determined or defined herein whether it is feasible in each case to improve functional vision at these early ages or over time, either partially or completely. Our observations of some of these children who have reached older ages suggest that it is possible to improve functional vision for some children. The present study is an extensive analysis that demonstrated that difficulty in seeing all of the cognitive testing materials clearly is an important problem, even at early ages, for a subset of affected children, and that certain cognitive testing materials are evaluating vision as much as or more than cognition. This is a problem that needs to be addressed in correctly defining functional abilities in such children and so that those who work with them do not attribute all of their difficulties to cognitive impairment. These findings are also important in considering how one might try to help children with congenital toxoplasmosis and bilateral visual impairment compensate for deficits beginning at early ages. These findings presented herein have prompted our separate, ongoing analysis of efficacy of different compensatory strategies used over time to attempt to help such children (R. McLeod, N. Menon, A.G. Noble, P.L. Latkany, K. Boyer, N. Roizen, M. Msall et al, manuscript in preparation, 2006).
We have not focused on the additional impact of cognitive or motor deficits on functioning in these tests. Certainly the tests measure cognitive and motor function, as well as vision, when children can see the materials clearly. There also is an impact of this infection, which is destructive to fetal brain, as well as eyes, on subsequent intellectual function independent of the impact on vision, at least for some children. For example, we previously compared a small, initial subset of the infected children who had normal or near-normal IQs with uninfected children (ie, nearest age, same gender when possible, paired siblings, over the age of 5 years), tested with the same tests, in the same standardized setting. In this earlier work directly comparing developmental test results of infected children and their uninfected siblings, we noted an impact of this disease on cognitive function.13 Herein, we are only asking whether impairment in vision contributes to difficulty with the tests. Thus, for this present study, we concluded that the most informative comparisons would be those of abilities of children with congenital toxoplasmosis on specific subtests that relied on vision to varying degrees, comparing those with no eye disease or disease in 1 or both macula, as described. Our objective was to determine whether visual impairment caused by toxoplasmic chorioretinitis is associated with impaired performance of specific tasks and subscales on standardized tests of cognitive function. We then wanted to determine whether there are patterns in these difficulties that would provide a logical basis for development of measures of cognitive function that are independent of visual impairment and compensatory intervention strategies to facilitate learning for such children, and there are. Specifically, we found that infection that impairs vision bilaterally influences the tests most dependent on vision the most. Differences in specific areas of performance on the WPPSI-R are noted for the children with visual impairment and determined to be the result of the visual deficits. We found that differences between tests involving fine lines versus tests that did not were greater in the children with bilateral visual impairment. The degree of neurologic impairment may correlate with the degree of visual impairment, but the psychological testing did not reveal the same degree of verbal deficits as compared with selected deficits in the performance areas. This suggests that the performance deficits are related to more limited visual acuity.
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ACKNOWLEDGMENTS |
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This work was supported by R0I AI27530. Dr McLeod is the Jules and Doris Stein Research to Prevent Blindness Professor at the University of Chicago. Dr Mack is the recipient of the Research to Prevent Blindness Career Development Award at the University of Chicago.
The other authors and members of the Toxoplasmosis Study Group are: Michael Kipp, Peter Rabiah, Diana Chamot, Randee Estes, and Simone Cezar (Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL); Douglas Mack (Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL [Current Address: University of Colorado, Denver, CO]); Linda Pfiffner, Mark Stein, and Barbara Danis (Department of Psychiatry, University of Chicago, Chicago, IL [Current Address: University of California, San Francisco, CA]); Dushyant Patel (Department of Radiology, Michael Reese Hospital and Medical Center, Chicago, IL); Joyce Hopkins (Department of Psychology, Illinois Institute of Technology, Chicago, IL); Ellen Holfels (University of Chicago, Chicago, IL [Current Address: Stroger Hospital of Cook County, Chicago, IL]); Lazlo Stein (Department of Audiology, Northwestern University, Evanston IL [deceased]); Shawn Withers (Cermak Health Services of Cook County, Chicago, IL); Audrey Cameron (Department of Audiology, Mount Sinai Hospital, Chicago, IL); Jeanne Perkins (Department of Audiology, The University of Chicago, Chicago, IL); and Peter Heydemann (Department of Pediatrics and Neurology, Rush University Medical Center, Chicago, IL).
We thank the patients' families, their physicians, and the airlines who have assisted by providing complimentary transportation to Chicago. We thank E. Castro and L. Kallal for their assistance in preparation of this article.
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FOOTNOTES |
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Accepted Jan 31, 2006.
Address correspondence to Rima McLeod, MD, University of Chicago, AMBH S208, 5841 S Maryland Ave, Chicago, IL 60637. E-mail: rmcleod{at}midway.uchicago.edu; or Nancy Roizen, PhD, Children's Hosptial for Rehabilitation, The Cleveland Clinic, 2801 Martin Luther King, Jr. Dr, Cleveland, OH 44104-3865. E-mail: roizenn{at}ccf.orgroizenn@ccf.org
The authors have indicated they have no financial relationships relevant to this article to disclose.
Dr Roizen's current address is Children's Hospital for Rehabilitation, Cleveland Clinic, 2801 Martin Luther King Dr, Cleveland, OH 44104-3865.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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