Vocabulary comprehension in adults with fragile X syndrome (FXS).

BACKGROUND: Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS: This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS: Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS: Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential.

Optic nerve heads in pediatric African Americans using retinal tomography.

PURPOSE: To characterize optic nerve head (ONH) parameters including symmetry between the eyes in healthy African American children using the Heidelberg retinal tomograph II, and to determine if there are associations between these parameters and age, refractive error, or gender. METHODS: The ONHs of 146 African American children aged 6 to 17 years without ocular disease were imaged with the Heidelberg retinal tomograph II. Mean values for 11 ONH parameters were determined as was their relationship to age, gender, and refractive error. Interocular symmetry of the parameters was determined. RESULTS: The mean (+/-standard deviation) disc area, rim area, and cup area were 2.18 +/- 0.57 mm2, 1.63 +/- 0.40 mm2, and 0.52 +/- 0.37 mm2, respectively. The mean linear cup-to-disc (C/D) ratio was 0.45 +/- 0.15, and mean cup depth was 0.22 +/- 0.10 mm. The mean retinal nerve fiber layer thickness was 0.26 +/- 0.07 mm. The ONH parameters were not related to age or refractive error. With the exception of the C/D area ratio and linear C/D ratio, which were greater in boys than in girls, ONH parameters were not related to gender. Most parameters were strongly correlated between the right and left eyes. The average interocular differences in disc area, cup area, rim area, linear C/D ratio, and mean retinal nerve fiber layer thickness were 0.09 +/- 0.31 mm2, 0.04 +/- 0.22 mm2, 0.06 +/- 0.40 mm2, 0.02 +/- 0.11, and 0.00 +/- 0.06 mm2, respectively. CONCLUSIONS: ONH parameters were not related to age and refractive error, and only C/D area ratio and linear C/D ratio were greater in boys than girls in a clinical sample of African American children. These measures of normative ONH parameters and range of interocular differences may be helpful in clinical pediatric eye care to facilitate identification of African American children with abnormal optic discs.

Polypharmacy and the lack of oculo-visual complaints from those with mental illness and dual diagnosis.

BACKGROUND: Individuals with mental illness (MI) and intellectual disability (ID) are characterized as dually diagnosed (DD). These individuals are known to have numerous systemic and oculo-visual anomalies. This comorbidity of conditions should elicit frequent oculo-visual complaints from these patients during the initial review of systems. A search of MedLine yielded one article that was published on oculo-visual symptomology/pain associated with MI and DD. This report appears to be the first to assess the frequency of these symptoms within these 2 unique populations. METHODS: A retrospective analysis of all medical records for patients (N = 202) evaluated at the Neumann Association (NA) Developmental Disabilities Service of the Illinois Eye Institute was completed. Only the records of patients who had either MI or DD and who were prescribed antipsychotics, antidepressants, anticonvulsants, or tranquilizers/anxiolytics were used for our analysis. Upon record review, 89.9% of MI and 59.4% of DD individuals met the above subject criteria. We determined the frequency of ocular anomalies, drugs taken, and complaints reported by patients during the initial review of systems. RESULTS: The most common documented side effects for the targeted drug types were decreased or blurred vision (near or far), visual hallucinations, decreased accommodation, and eyelid/conjunctiva irregularities. In our sample, the most frequent ocular anomalies encountered were astigmatism (50% MI and 37.84% DD), myopia (60.71% MI and 62.16% DD), presbyopia (35.71% MI and 37.84%DD), and blepharitis (32.14% MI and 32.43%DD). Additionally, the most frequently encountered complaints were no complaints (45.16% MI and 46.84% DD), blurry vision (17.74% MI and 17.72% DD), and need new glasses (11.29% MI and 17.72% DD). CONCLUSIONS: It has been established that MI and DD populations exhibit a higher incidence of oculo-visual anomalies (uncorrected refractive error, binocular vision anomalies, ocular pathology) than noted in the general population. They are also typically taking 1 or more neuropsychotropic medications that are frequently associated with undesirable visual side effects. Individuals with MI and DD should report numerous complaints associated with the medications they take and the oculo-visual anomalies they exhibit during the initial case history and the review of systems. The data from this study suggest that this is not the case and that only about 50% of those who should have complaints actually report them.

Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial.

A Phase II, 4-week randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome (FXS). After baseline screening, subjects with FXS (n = 49) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period. Cognitive and behavioral outcome measures were administered prior to treatment, at the end of treatment, and 2 weeks posttreatment. There were minimal side effects, no significant changes in safety parameters, and no serious adverse events. There was a 12.5% frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash. There was also no significant improvement in memory, the primary outcome measure, or in secondary measures of language, attention/executive function, behavior, and overall functioning in CX516-treated subjects compared to placebo. This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population, yet some were too difficult or variable. Adult subjects with FXS were able to complete an intensive clinical trial, and some valid outcome measures were identified for future FXS trial design. Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS.