Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

BACKGROUND: Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. AIM: To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. METHOD: Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. RESULTS: Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. CONCLUSION: Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity.

Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates.

Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV). Furthermore, a comprehensive neuropsychological battery and magnetic resonance imaging were assessed. The results show that PPVT-III gives limited information on cognitive performance and brain correlates, getting lower intelligence quotient scores. The WNV provides similar outcomes as RCPM, but cases with severe motor impairment were unable to perform it. Finally, the RCPM gives more comprehensive information on cognitive performance, comprising not only visual but also verbal functions. It is also sensitive to the structural state of the brain, being related to basal ganglia, thalamus and white matter areas such as superior longitudinal fasciculus. So, the RCPM may be considered a standardized easy-to-administer tool with great potential in both clinical and research fields of bilateral cerebral palsy.

Cortical thickness and behavior abnormalities in children born preterm.

AIM: To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. METHODS: We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). RESULTS: We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. INTERPRETATION: The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems.

Thalamic changes in a preterm sample with periventricular leukomalacia: correlation with white-matter integrity and cognitive outcome at school age.

INTRODUCTION: Thalamic abnormalities have been well documented in preterms with periventricular leukomalacia (PVL), although their contribution to long-term cognitive dysfunctions has not been thoroughly investigated. RESULTS: Significant differences between groups were observed for global thalamic volume. Neuropsychological assessments showed that preterms with PVL scored within the normal range, although significantly below controls in the full intelligence quotient and the specific cognitive domains of processing speed and working memory. Correlations of several thalamic regions with Working Memory Index and FIQ were found in the PVL group. Moreover, thalamic atrophy correlated with white-matter (WM) damage indexes (fractional anisotropy and radial diffusivity) assessed by diffusion tensor imaging. DISCUSSION: The findings suggest that thalamic damage is a common correlate of WM microstructural alterations and might be involved in the cognitive deficits seen in premature infants with PVL at school age. METHODS: We analyzed the impact of PVL-associated thalamic injury on cognitive status at school age and its correlation with WM integrity as measured by magnetic resonance imaging techniques. Thalamic volume and shape of 21 preterm children with PVL were compared with those of 11 preterm children of similar gestational age and birth weight with no evidence of focal WM abnormality.

Gray matter volume decrements in preterm children with periventricular leukomalacia.

Periventricular leukomalacia (PVL) is the prototypic lesion in the encephalopathy of prematurity. Although PVL is identified by targeting cerebral white matter (WM), neuropathological and MRI studies document gray matter (GM) loss in cortical and subcortical structures. This study aimed to investigate the distribution of GM changes in children with a history of premature birth and PVL. Voxel-based morphometry was used to examine regional GM abnormalities in 22 children with a history of preterm birth and PVL. Preterms with PVL were compared with 22 terms and 14 preterms without PVL of similar GA and birth weight. GM and WM global volumetric volumes were found to decrease in comparison with both control groups. Regional GM volume abnormalities were also found: compared with their term peers, preterm children with PVL showed several regions of GM reduction. Moreover, PVL differed from preterms without PVL in the medial temporal lobe bilaterally, thalamus bilaterally, and caudate nuclei bilaterally. In addition, in our preterm sample with PVL, birth weight showed a statistical significant correlation with decreased GM regions. In conclusion, the voxel-based morphometry methodology revealed that PVL per se does involve GM reductions.

Neuropsychologic impairment in bilateral cerebral palsy.

The lower-than-average cognitive performance of individuals with bilateral cerebral palsy found in previous studies does not always refer to an abnormal performance or clinically significant impairment. We aimed to establish the percentage of persons with bilateral cerebral palsy who present neuropsychologic impairment, and its relationship to perinatal data and motor signs. Forty children, adolescents, and adults (age range, 6-38 years; 15 females and 25 males) with bilateral cerebral palsy were neuropsychologically assessed. Vocabulary was impaired in 85% of participants, language comprehension in 13-48%, visuoperceptual abilities in 60%, visuospatial abilities in 90%, short-term memory in 21-58%, declarative memory in 47-67%, and praxis comprehension in 20%, with executive deficits in 58-74%. Perinatal data (intrauterine growth and birth weight) contributed to explaining memory impairment. Among cerebral palsy subtypes (spastic, mixed, and dyskinetic), forms of impairment differed only in short-term verbal memory. No persons with dyskinetic cerebral palsy experienced impairment in immediate memory or working visual memory. We conclude that visuospatial deficit is the most frequent impairment in people with bilateral cerebral palsy. Moreover, short-term memory impairment seems sensitive to perinatal complications, and differs among bilateral cerebral palsy subtypes.

Corpus callosum and prefrontal functions in adolescents with history of very preterm birth.

Very preterm (VPT) birth can account for thinning of the corpus callosum and poorer cognitive performance. Research findings about preterm and VPT adolescents usually describe a small posterior corpus callosum, although our research group has also found reductions of the anterior part, specifically the genu. The aim of the present study was to investigate the functional implications of this concrete reduction. Fifty-two VPT adolescents were compared with 52 adolescents born at term; there were no significant differences in age and gender, and socioeconomic status was similar between the groups. All participants underwent a magnetic resonance imaging (MRI) study and assessment of prefrontal functioning and vocabulary. The VPT group showed significant reductions of the genu, isthmus and splenium, as well as a significantly worse performance on category verbal fluency, executive functions, everyday memory and vocabulary. Although several parts of the corpus callosum correlated with some prefrontal functions, the genu was the part which principally explained these correlations. The subtest Vocabulary only correlated with the splenium. The relationship between genu and prefrontal functions and between splenium and vocabulary may be due to the fact that these parts of the corpus callosum connect prefrontal and posterior parietal cortex, respectively. The work presented here provides evidence of specific associations between reductions in the anterior corpus callosum (genu) and lower prefrontal functioning in VPT adolescents.

Gestational age at preterm birth in relation to corpus callosum and general cognitive outcome in adolescents.

Prematurity is associated with corpus callosum abnormalities and low general cognitive functioning. The present study explores the specific relationship between gestational age, corpus callosum, and intelligence quotient (IQ) in a sample of preterm-born adolescents. Sixty-four adolescents born at a gestational age of 36 weeks or less were divided into 4 groups attending to their gestational age (GA) (group 1, < or = 27; group 2, 28-30; group 3, 31-33; group 4, 34-36). These individuals were compared with 53 adolescents born at term and of similar age, gender, and sociocultural status. Individuals born at a gestational age of 27 or less (group 1) presented a generalized corpus callosum reduction in the posterior part (posterior midbody, isthmus, and splenium) as well as in the anterior part (anterior midbody and genu), a reduced total white-matter volume, and a low Full-Scale IQ. Group 2 (GA between 28 and 30) also showed a low IQ, but corpus callosum reduction was only found in the splenium, without total white-matter volume reductions. Group 3 (GA between 31 and 33) did not present differences in corpus callosum size or a reduced total white- matter volume, but they showed a low Full-Scale IQ. Group 4 (GA between 34 and 36) did not show a smaller corpus callosum or a lower general cognitive performance. Specific significant correlations were found between corpus callosum subregions and gestational age. These results suggest the importance of gestational age in prematurity in relation to brain structural and functional outcome. Premature babies born at a gestational age of 27 weeks or less are the target group for long-term corpus callosum and white-matter anomalies and for a low IQ.

Corpus callosum size and neuropsychologic impairment in adolescents who were born preterm.

Prematurity is associated with cerebral abnormalities that might account for poorer cognitive performance. The aim of our study was to investigate the correlations between corpus callosum reductions and neuropsychologic performance in adolescents who were born preterm. Twenty-five subjects born before 33 weeks' gestation were compared with 25 subjects born at term and of similar age, gender, and sociocultural status. All subjects underwent magnetic resonance imaging and neuropsychologic examinations. Premature subjects performed worse than controls in global cognitive functioning, verbal memory, and verbal fluency. Corpus callosum measurements showed a global reduction owing mainly to thinning in the splenium, posterior midbody, and genu. Corpus callosum size significantly correlated with gestational age, Wechsler Performance IQ, and memory performance. These results suggest that cerebral growth during infancy does not compensate for corpus callosum reduction and that this reduction reflects neuropsychologic deficit. The cognitive impairment can arise from the paucity of the complex interneuronal connections owing to fiber damage, particularly myelinated fibers.

Trastornos neuropsicológicos y del neurodesarrollo en el prematuro / Neuropsychological and neurodevelopmental deficiencies in prematurity

El niño prematuro presenta unas manifestaciones morfológicas y funcionales características de su propia inmadurez, que le predisponen a presentar una serie de complicaciones precoces o tardías, siendo la más frecuente la enfermedad de la membrana hialina que produce asfixia perinatal. Ésta puede generar hemorragias intraventriculares y periventriculares. Hay muy pocos estudios sobre la evolución posterior de estos sujetos. En cuanto al neurodesarrollo, los prematuros sin complicaciones presentan en la etapa neonatal una reducción de la sustancia gris cortical, un aumento de los ventrículos laterales y una afectación de la sustancia blanca que se hace más evidente en edades más avanzadas. A los 3-8 años principalmente se observa déficit en el coeficiente de inteligencia, y a los 14-15 se suma la lectura y el cálculo. Por otro lado el prematuro con complicaciones presenta dilatación ventricular, leucomalacia periventricular y atrofia de algunas estructuras subcorticales. En la infancia y a los 13 años se observan dificultades en el rendimiento cognitivo general y en algunas habilidades específicas como la memoria. Ante la escasez de datos, proponemos un estudio neuropsicológico y de neuroimagen exhaustivo y a largo plazo, que muestre las consecuencias de la prematuridad asociada o no a complicaciones (AU)

Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity.

Using optimized voxel-based morphometry (VBM), we compared the relationship between hippocampal and thalamic gray matter loss and memory impairment in 22 adolescents with history of prematurity (HP) and 22 normal controls. We observed significant differences between groups in verbal learning and verbal recognition, but not in visual memory. VBM analysis showed significant left hippocampal and bilateral thalamic reductions in HP subjects. Using stereological methods, we also observed a reduction in hippocampal volume, with left posterior predominance. We found correlations between left hippocampal gray matter reductions (assessed by VBM) and verbal memory (learning and percentage of memory loss) in the premature group. The stereological analysis showed a correlation between verbal learning and the left posterior hippocampus. Our results suggest that left hippocampal tissue loss may be responsible for memory impairment and is probably related to the learning disabilities that HP subjects present during schooling.

Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects.

In addition to the study of pathological conditions, magnetic resonance spectroscopy can provide useful information about brain-behavior relationships in normal subjects. Recently, there have been reports of correlations between N-acetylaspartate (NAA) values and cognitive functions in normal adults. We tested the possible specific relationship between the NAA/choline (Cho) ratio in the medial temporal lobe and memory performance in normal adolescents. The medial temporal NAA/Cho ratio was unrelated to age, gender and general intelligence but presented a clear correlation with several memory measures. In the regression analysis two memory variables (RAVLT learning and a face-name recognition task) explained 55.6% of NAA/Cho variance. We conclude that NAA values in the medial temporal lobe are related to memory abilities but not to global intelligence in normal adolescent subjects.

Memoria declarativa y procedimental en adolescentes con antecedentes de asfixia perinatal / Declarative and procedural memory in adolescents with antecedents of perinatal asphyxia

Los estudios neuropatologicos sobre asfixia perinatal han puesio de manifiesto una alta vulnerabilidad a las lesiones en el hipocampo y los ganglios basales. Esta afectación anatómica puede corresponderse a una alteración de la memoria declarativa y procedimental respectivamente. De acuerdo con esta hipótesis comparamos el rendimiento de diversas tareas de memoria en una muestra de 28 adolescentes con antecedentes de asfixia perinatal y 28 controles emparejados por edad, sexo y nivel sociocultural. Los resultados mostraron una alteración de la memoria declarativa verbal y visual en los sujetos con encefalopatía moderada, pero no en los leves. Sin embargo, no observamos diferencias significativas entre grupos en las tareas de aprendizaje procedimental. Los resultados sugieren una mayor vulnerabilidad del sistema hipocampal respecto al estriatal en la asfixia perinatal (AU)

Neuropathological studies of the cerebral consequences of perinatal asphyxia have shown the hippocampal and basal ganglia to be particularly vulnerable to injury. It has been suggested that neuroanatomical lesions of this kind may produce declarative and procedural memory deficits. To test this hypothesis we compared memory performance in 28 adolescents with antecedents of perinatal asphyxia and 28 controls matched for age, sex and sociocultural status. Results showed impairment in verbal and visual declarative memory in subjects with antecedents of moderate neonatal encephalopathy but not in subjects with mild encephalopathy. Procedural memory performance was similar in all groups. The results suggest that the hippocampal system is more vulnerable to perinatal asphyxia than the striatal system (AU)