Brain lesion scores obtained using a simple semi-quantitative scale from MR imaging are associated with motor function, communication and cognition in dyskinetic cerebral palsy

Purpose: To characterise brain lesions in dyskinetic cerebral palsy (DCP) using the semi-quantitative scale for structural MRI (sqMRI) and to investigate their relationship with motor, communication and cognitive function. Materials and methods: Thirty-nine participants (19 females, median age 21y) with DCP were assessed in terms of motor function, communication and a variety of cognitive domains. Whole-head magnetic resonance imaging (MRI) was performed including T1-MPRAGE, T2 turbo spin echo (axial plane), and fluid attenuated inversion recovery images (FLAIR). A child neurologist visually assessed images for brain lesions and scored these using the sqMRI. Ordinal, Poisson and binomial negative regression models identified which brain lesions accounted for clinical outcomes. Results: Brain lesions were most frequently located in the ventral posterior lateral thalamus and the frontal lobe. Gross (B = 0.180, p < .001; B = 0.658, p < .001) and fine (B = 0.136, p = .003; B = 0.540, p < .001) motor function were associated with global sqMRI score and parietal involvement. Communication functioning was associated with putamen involvement (B = 0.747, p < .028). Intellectual functioning was associated with global sqMRI score and posterior thalamus involvement (B = -0.018, p < .001; B = -0.192, p < .001). Selective attention was associated with global sqMRI score (B = -0.035, p < .001), parietal (B = -0.063, p = .023), and corpus callosum involvement (B = -0.448, p < .001). Visuospatial and visuoperceptive abilities were associated with global sqMRI score (B = -0.078, p = .007) and medial dorsal thalamus involvement (B = -0.139, p < .012), respectively. Conclusions: Key clinical outcomes in DCP are associated with specific observable brain lesions as indexed by a simple lesion scoring system that relies only on standard clinical MRI

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

Executive function and general intellectual functioning in dyskinetic cerebral palsy: comparison with spastic cerebral palsy and typically developing controls

Aim: To comprehensively describe intellectual and executive functioning (EF) in people with dyskinetic cerebral palsy (DCP), by comparing their performance with that of: 1) age and sex-matched typically developing controls (TDC); and 2) participants with spastic cerebral palsy (SCP) matched for age, sex, term/preterm and gross motor function classification system (GMFCS). Method: This cross sectional study was conducted by the University of Barcelona in collaboration with five institutions. Participants were people with DCP (n = 52; 24 females, median age 20.5 y: 5mo, interquartile range [IQR] = 13.75 y: 7mo; GMFCS I-V). As comparison groups, participants with SCP (n = 20; 10 females, median age = 20.5 y: 5.5mo, IQR = 13.75 y 9mo; GMFCS I-V) and TDC (n = 52; 24 females, median age = 20 y: 4mo, IQR = 12 y 7mo) were included. Intelligence and EF were assessed using common tests in all participants. Results: Both CP groups had lower intelligence than TDC and performed poorer in almost all EF tasks. Intelligence was higher in DCP than SCP (z = -2.51, p = 0.01). Participants with DCP also performed significantly better in goal-setting tasks (z = 2.27, p = 0.03) and information processing (z =-2.54, p = 0.01) than those with SCP. Conclusion: People with DCP present lower general intellectual functioning and poorer EF across multiple domains than typically developing controls. People with DCP have higher general intellectual functioning and better EF than people with SCP when levels of motor severity are similar

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Patients and methods: Thirty-three participants with dyskinetic CP (mean +/- SD age: 24.42 +/- 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. Results: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum). Conclusion: The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult

Proxy-reported quality of life in adolescents and adults with dyskinetic cerebral palsy is associated with executive functions and cortical thickness

Purpose: Quality of life (QOL) is a key outcome for people with cerebral palsy (CP), and executive functioning is an important predictor of QOL in other health-related conditions. Little is known about this association in CP or about its neural substrate. We aim to analyze the influence of executive functioning (including cognitive flexibility) as well as that of other psychological, motor, communication and socioeconomic variables on QOL and to identify neuroanatomical areas related to QOL in adolescents and adults with CP. Methods: Fifty subjects diagnosed with dyskinetic CP (mean age 25.96 years) were recruited. Their caregivers completed the primary caregiver proxy report version of the CP QOL-Teen questionnaire. Motor status, communication, IQ, four executive function domains, anxiety/depression and socioeconomic status were evaluated. Correlations and multiple linear regression models were used to relate CP QOL domains and total score to these variables. Thirty-six participants underwent an MRI assessment. Correlations were examined between cortical thickness and CP QOL total score and between cortical thickness and variables that might predict the CP QOL total score. Results: Executive functions predict scores in four domains of CP QOL (General well-being and participation, Communication and physical health, Family health and Feelings about functioning) in the regression model. Among the cognitive domains that comprise executive function, only cognitive flexibility measured in terms of performance on the Wisconsin card sorting test (WCST) predicts the CP QOL total score. Monthly income, fine motor functioning and communication ability predict scores on the domains Access to services and Family Health, Feelings about functioning and School well being, respectively. The clusters resulting from the correlation between cortical thickness and both CP QOL total score and WCST performance overlapped in the posterior cingulate and precuneus cortices. Conclusions: Cognitive flexibility predicts proxy report CP QOL-Teen total score in dyskinetic CP. This relationship has its anatomical correlate in the posterior cingulate and precuneus cortices

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

Whole-Brain Structural Connectivity in Dyskinetic Cerebral Palsy and Its Association With Motor and Cognitive Function

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system

Study protocol of a randomized controlled trial of home-based computerized executive function training for children with cerebral palsy

Background: Cerebral palsy (CP) is frequently associated with specific cognitive impairments, such as executive dysfunction which are related to participation and quality of life (QOL). The proposed study will examine whether a computerized executive function (EF) training programme could provide superior benefits for executive functioning, participation, QOL and brain plasticity, as compared to usual care. Methods: A single-blind randomized controlled trial (RCT) design will be performed. Thirty children with CP aged 8 to 12 years will participate in a home-based computerized multi-modal executive training programme (12 weeks, 5 days a week, 30 min a day training, total dose = 30 h). Thirty children with CP matched by age, sex, motor and intelligence quotient (IQ) will compose the waitlist group. Cognitive, behavioural, emotional, participation and QOL measures will be obtained at three time points: before, immediately after and 9 months after completing the training. Additionally, structural and functional (resting state) magnetic resonance images (MRI) will be obtained in a subsample of 15 children from each group. Outcomes between groups will be compared following standard principles for RCTs. Discussion: The study will test whether the cognitive training programme exerts a positive effect not only on neuropsychological and daily functioning of children with CP but also on other measures such as participation and QOL. We will also use brain MRI to test brain functional and structural changes after the intervention. If this on-line and home-based training programme proves effective, it could be a cost-effective intervention with short- and long-term effects on EF, participation or QOL in CP

Neuroimaging and executive function in dyskinetic cerebral palsy

[spa] INTRODUCCIÓN: La parálisis cerebral es una de las causas más frecuentes de discapacidad física en niños y supone una condición que persiste a lo largo de la vida (Krageloh-Mann & Cans, 2009). Concretamente, la prevalencia media mundial es de aproximadamente de 2 por cada 1000 nacidos vivos (Stavsky et al., 2017). El término parálisis cerebral incluye un grupo de trastornos permanentes del movimiento y / o postura y de la función motora debido a una afectación en el cerebro en desarrollado o inmaduro que pueden ir acompañados por diferentes comorbilidades (Rosenbaum et al., 2007; Surveillance of Cerebral Palsy in Europe, 2000). La parálisis cerebral es una condición heterogénea tanto en cuanto a etiología como en el tipo y gravedad de la afectación motriz. En este sentido, se considera útil categorizar a los individuos con parálisis cerebral en grupos para proporcionar un mayor nivel de detalle sobre las características y necesidades específicas de las diferentes personas (Surveillance of Cerebral Palsy in Europe, 2007). Los esquemas de clasificación tradicionales se han centrado principalmente en agrupar los casos según la distribución de las extremidades afectadas y el tipo predominante de tono o anormalidad del movimiento, lo que da lugar a tres grandes grupos de parálisis cerebral: el espástico, el discinetico y el atáxico (Platt, Krageloh‐Mann, & Cans, 2009). La presente tesis doctoral se centra en el estudio del segundo tipo más frecuente, la parálisis cerebral discinètica, que se caracteriza por movimientos involuntarios, descontrolados, recurrentes y, ocasionalmente, estereotipados. La resonancia magnética ha aumentado nuestra comprensión de la parálisis cerebral (Vandborg et al., 2015), pero mientras que la mayoría de los estudios se centran en la parálisis cerebral espástica, los estudios de neuroimagen centrados en la parálisis cerebral discinética son aun escasos. Tanto los procesos cognitivos globales como específicos pueden verse afectados en la parálisis cerebral y casi el 50% de la población de parálisis cerebral presenta un cociente intelectual por debajo de 70 (Novak, Hines, Goldsmith, & Barclay, 2012). La consideración de las funciones cognitivas es uno de los aspectos centrales en el estudio de la parálisis cerebral (Schiariti, Selb, Cieza, & O’Donnell, 2015) siendo la función ejecutiva de particular interés debido a su papel clave en la adquisición efectiva de nuevas habilidades, conocimiento y la aplicación de estas conocimiento en el día a día (Anderson & Ylvisaker, 2009). La asociacione entre la calidad de vida y la función ejecutiva se ha descrito en la población general y en otras condiciones neurológicas y psiquiátrica distintas a la parálisis cerebral (Barf, Post, Verhoef, Gooskens, & Prevo, 2010; Davis, 2010; Pattanayak, Sagar, & Mehta, 2012; Ritsner, 2007; Sherman, Slick, & Eyrl, 2006). Existe acuerdo en que la parálisis cerebral discinética presenta mayor gravedad motriz que otros tipos parálisis cerebral (Himmelmann et al., 2009). Sin embargo, existen pocos estudios que comparen las capacidades cognitivas entre este tipo de parálisis cerebral y otros subtipos y, de hecho, la mayoría de ellos no controla los resultados por el nivel de gravedad motriz. Ningún estudio hasta la fecha se ha enfocado específicamente en estudiar la función ejecutiva ni su asociación con las características de la estructura cerebral en este subtipo de parálisis cerebral. Las lesiones de los ganglios basales y el tálamo son especialmente frecuentes en personas con parálisis cerebral discinética (Bax, Tydeman, & Flodmark, 2006; Himmelmann, Ahlin, Jacobsson, Cans, & Thorsen, 2011) y dado que los circuitos fronto-estriatales juegan un papel crucial en el funcionamiento ejecutivo para las personas con un desarrollo normal (Bottcher, 2010; Krause et al., 2012), seria esperable encontrar este correlato anátomo-funcional en la parálisis cerebral discinética. Sin embargo, muy pocos trabajos han estudiado la relación entre la estructura cerebral y el funcionamiento ejecutivo en esta población. De hecho, no existe ningún estudio que analice esta relación en las personas con parálisis cerebral discinética (Weierink, Vermeulen, & Boyd, 2013). OBJETIVOS: El objetivo general de la tesis fue caracterizar el funcionamiento ejecutivo y el funcionamiento intelectual general y sus bases biológicas en imagen de resonancia magnética estructural convencional y de difusion en la parálisis cerebral discinética. Específicamente, en la presente tesis se formularon cuatro objetivos que han sido abordados mediante la realización de cuatro estudios. Primero, analizar el impacto de la función ejecutiva en la calidad de vida en personas con parálisis cerebral discinética (Estudio 1). El segundo objetivo fue identificar el perfil de funcionamiento ejecutivo e intelectual en las personas con parálisis cerebral discinética (Estudio 2). Tercero, identificar las alteraciones de la estructura cerebral en participantes con parálisis cerebral discinética (Estudio 3 y Estudio 4). Cuarto, investigar el correlato neural del funcionamiento ejecutivo e intelectual general en participantes con parálisis cerebral discinética (Estudio 3 y Estudio 4). RESULTADOS: En consecuencia, los principales hallazgos de los estudios son los siguientes. 1) Uno de los componentes de las funciones ejecutivas, la flexibilidad cognitiva, es un predictor importante de la calidad de vida en personas con parálisis cerebral discinética. 2) Las personas con parálisis cerebral discinética presentan dificultades tanto en el rendimiento intelectual general como en el funcionamiento ejecutivo. Sin embargo, las habilidades de planificación parecen ser similares a las de los controles con desarrollo normativo. Además, las personas con parálisis cerebral discinética muestran un mejor funcionamiento intelectual y ejecutivo que las personas con parálisis cerebral espástica, lo que indica una tendencia general hacia un mejor rendimiento cognitivo en lugar de un déficit disejecutivo específico. 3) Existen lesiones observables en la substancia blanca y gris, así como una reducción de la integridad de la substancia blanca en la parálisis cerebral discinética. Concretamente, las lesiones en el tálamo lateral posterior y en el lóbulo frontal son los más comunes en nuestra muestra de personas con parálisis cerebral discinética. Además, la pérdida en la integridad de la sustancia blanca en la parálisis cerebral discinética predomina en regiones posteriores subyacentes, principalmente en la corteza parietal. 4) El funcionamiento intelectual general está relacionado con la integridad de la substancia blanca en varias regiones cortico-corticales y cortico-subcorticales y con lesiones cerebrales observables principalmente del tálamo posterior. Las funciones ejecutivas se relacionaron con la microestructura de la sustancia blanca en regiones que contienen las vías fronto-corticales y cortico-subcorticales posteriores, así como con las lesiones cerebrales observables especialmente en el lóbulo parietal y de cuerpo calloso medio y posterior. Contrariamente a nuestra hipótesis, no se identificaron relaciones significativas entre la función ejecutiva y las vías fronto-estriatales. REFRENCIAS: Anderson, V., & Ylvisaker, M. (2009). Executive function and the frontal lobes: Themes for child development, brain insult and rehabilitation. Developmental Neurorehabilitation, 12(August), 253–254. https://doi.org/10.3109/17518420903086899 Barf, H. A., Post, M. W. M., Verhoef, M., Gooskens, R. H. J. M., & Prevo, A. J. H. (2010). Is cognitive functioning associated with subjective quality of life in young adults with spina bifida and hydrocephalus? Journal of Rehabilitation Medicine, 42(1), 56–9. https://doi.org/10.2340/16501977-0481 Bax, M., Tydeman, C., & Flodmark, O. (2006). Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. Jama, 296(13), 1602–8. https://doi.org/10.1001/jama.296.13.1602 Bottcher, L. (2010). Children with spastic cerebral palsy, their cognitive functioning, and social participation: a review. Child Neuropsychology : A Journal on Normal and Abnormal Development in Childhood and Adolescence, 16(3), 209–228. https://doi.org/10.1080/09297040903559630 Davis, J. (2010). The independent contribution of executive functions to health related quality of life in older women. BMC Geriatrics, 10(1), 16. Retrieved from http://www.biomedcentral.com/1471-2318/10/16 Himmelmann, K., Ahlin, K., Jacobsson, B., Cans, C., & Thorsen, P. (2011). Risk factors for cerebral palsy in children born at term. Acta Obstetricia et Gynecologica Scandinavica, 90(10), 1070–1081. https://doi.org/10.1111/j.1600-0412.2011.01217.x Himmelmann, K., McManus, V., Hagberg, G., Uvebrant, P., Krageloh-Mann, I., & Cans, C. (2009). Dyskinetic cerebral palsy in Europe: trends in prevalence and severity. Archives of Disease in Childhood, 94(12), 921–926. https://doi.org/10.1136/adc.2008.144014 Krageloh-Mann, I., & Cans, C. (2009). Cerebral palsy update. Brain & Development, 31(7), 537–544. https://doi.org/10.1016/j.braindev.2009.03.009 Krause, M., Mahant, N., Kotschet, K., Fung, V. S., Vagg, D., Wong, C. H., & Morris, J. G. L. (2012). Dysexecutive behaviour following deep brain lesions - Adifferent type of disconnection syndrome? Cortex, 48(1), 97–119. https://doi.org/10.1016/j.cortex.2011.03.014 Novak, I., Hines, M., Goldsmith, S., & Barclay, R. (2012). Clinical prognostic messages from a systematic review on cerebral palsy. Pediatrics, 130(5), e1285-312. https://doi.org/10.1542/peds.2012-0924 Pattanayak, R. D., Sagar, R., & Mehta, M. (2012). Neuropsychological performance in euthymic Indian patients with bipolar disorder type I: correlation between quality of life and global functioning. Psychiatry and Clinical Neurosciences, 66(7), 553–563. https://doi.org/10.1111/j.1440-1819.2012.02400.x Platt, M. J., Krageloh‐Mann, I., & Cans, C. (2009). Surveillance of cerebral palsy in Europe: reference and training manual. Medical Education, 43, 495–496. Ritsner, M. S. (2007). Predicting quality of life impairment in chronic schizophrenia from cognitive variables. Quality of Life Research, 16(6), 929–937. https://doi.org/10.1007/s11136-007-9195-3 Rosenbaum, P., Paneth, N., Leviton, A., Goldstein, M., Bax, M., Damiano, D., … Jacobsson, B. (2007). A report: the definition and classification of cerebral palsy April 2006. Developmental Medicine and Child Neurology. Supplement, 109, 8–14. Schiariti, V., Selb, M., Cieza, A., & O’Donnell, M. (2015). International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy: A consensus meeting. Developmental Medicine and Child Neurology, 57(2), 149–158. https://doi.org/10.1111/dmcn.12551 Sherman, E., Slick, D., & Eyrl, K. (2006). Executive dysfunction is a significant predictor of poor quality of life in children with epilepsy. Epilepsia, 47(11), 1936–1942. https://doi.org/10.1111/j.1528-1167.2006.00816.x Stavsky, M., Mor, O., Mastrolia, S. A., Greenbaum, S., Than, N. G., & Erez, O. (2017). Cerebral Palsy—Trends in Epidemiology and Recent Development in Prenatal Mechanisms of Disease, Treatment, and Prevention. Frontiers in Pediatrics, 5(February), 1–10. https://doi.org/10.3389/fped.2017.00021 Surveillance of Cerebral Palsy in Europe. (2000). Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers. Developmental Medicine & Child Neurology, 42(12), 816–824. https://doi.org/10.1111/j.1469-8749.2000.tb00695.x Surveillance of Cerebral Palsy in Europe. (2007). The definition and classification of cerebral palsy. Developmental Medicine & Child Neurology, 49(109), 1–44. https://doi.org/http://dx.doi.org/10.1111/j.1469-8749.2007.00001.x Vandborg, P. K., Hansen, B. M., Greisen, G., Mathiasen, R., Kasper, F., & Ebbesen, F. (2015). Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children: A Danish population-based study. Developmental Medicine and Child Neurology, 57(4), 378–384. https://doi.org/10.1111/dmcn.12603 Weierink, L., Vermeulen, R. J., & Boyd, R. N. (2013). Brain structure and executive functions in children with cerebral palsy: A systematic review. Research in Developmental Disabilities, 34(5), 1678–1688. https://doi.org/10.1016/j.ridd.2013.01.035[eng] Magnetic resonance imaging has increased our understanding of cerebral palsy [1] but most studies have focused on spastic cerebral palsy, whilst neuroimaging studies of dyskinetic cerebral palsy remain scarce. Global and specific cognitive processes may be affected in cerebral palsy, with almost 50% of the cerebral palsy population having an intellectual quotient below 70 [2]. Cognitive functions are considered one of the essential “Core Sets” in cerebral palsy [3], executive function being of particular interest because of its key role in the effective acquisition of new skills, knowledge, and the application of this knowledge in life [4]. Associations between quality of life and executive function have been described in the general population, in psychiatric conditions, and in neurological conditions other than cerebral palsy [5–9]. It is agreed that dyskinetic cerebral palsy is associated with poorer motor outcomes than other cerebral palsy types [10] but very few studies compare cognitive abilities in dyskinetic cerebral palsy with those of other cerebral palsy subtypes, particularly in groups with similar levels of motor ability. No study to date has specifically focused on executive function nor its association with brain magnetic resonance imaging characteristics in this cerebral palsy subtype. Basal ganglia and thalamus lesions are frequently described in people with dyskinetic cerebral palsy [11, 12] and fronto-striatal circuitry play a crucial role on executive functioning for typically developing people [13, 14]. However, there is a paucity of brain imaging studies focussing on executive functioning, with no studies including participants with dyskinetic cerebral palsy [15]. The overall aim of the thesis was to characterize executive functioning and general intellectual functioning and its biological bases in dyskinetic cerebral palsy, as measured by diffusion and structural magnetic resonance imaging. Specifically, the current thesis formulated the following four aims, which were accomplished through four studies. First, to analyse the impact of executive function on quality of life in people with dyskinetic cerebral palsy (Study 1). Second, to map executive and intellectual functioning in people with dyskinetic cerebral palsy (Study 2). Third, to identify brain structure alterations in participants with dyskinetic cerebral palsy (Study 3 and Study 4). Fourth, to investigate the neural correlate of executive and general intellectual functioning in participants with dyskinetic cerebral palsy (Study 3 and Study 4). The main findings of the studies are the following. (1) An executive function domain, cognitive flexibility, is an important driver of quality of life in people with dyskinetic cerebral palsy. (2) People with dyskinetic cerebral palsy present difficulties in both general intellectual and executive functioning but goal setting abilities are close to those in typically developing controls. Additionally, people with dyskinetic cerebral palsy display better intellectual and executive functioning than people with spastic cerebral palsy, indicating a general tendency towards a better cognitive level rather than a specific dysexecutive deficit. (3) Observable white and grey matter lesions as well as white matter integrity are involved in dyskinetic cerebral palsy. Specifically, posterior lateral thalamus and the frontal lobe lesions are the most common in our sample of people with dyskinetic cerebral palsy. In this sample, the loss in the integrity of the white matter predominantly appears outside of the frontal lobe, mainly in the parietal cortex. (4) General intellectual functioning is related to white matter integrity in several cortico-cortical and cortico-subcortical regions and with observable brain lesions particularly in the posterior thalamus. Executive functions were related with white matter microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways and with observable brain lesions particularly in the parietal lobe and the middle and posterior corpus callosum. Unexpectedly, neither in terms of white matter microstructure nor in terms of observable lesions, was there a significant relationship between executive function and the fronto-striatal pathways. References 1. Vandborg, P. K., Hansen, B. M., Greisen, G., Mathiasen, R., Kasper, F., & Ebbesen, F. (2015). Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children: A Danish population-based study. Developmental Medicine and Child Neurology, 57(4), 378–384. 2. Novak, I., Hines, M., Goldsmith, S., & Barclay, R. (2012). Clinical prognostic messages from a systematic review on cerebral palsy. Pediatrics. DOI:10.1542/peds.2012-0924 3. Schiariti, V., Selb, M., Cieza, A., & O’Donnell, M. (2015). 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Himmelmann, K., Ahlin, K., Jacobsson, B., Cans, C., & Thorsen, P. (2011). Risk factors for cerebral palsy in children born at term. Acta Obstetricia et Gynecologica Scandinavica, 90(10), 1070–1081. 13. Krause, M., Mahant, N., Kotschet, K., Fung, V. S., Vagg, D., Wong, C. H., & Morris, J. G. L. (2012). Dysexecutive behaviour following deep brain lesions – A different type of disconnection syndrome? Cortex, 48(1), 97–119. 14. Bottcher, L. (2010). Children with spastic cerebral palsy, their cognitive functioning, and social participation: a review. Child neuropsychology: A journal on normal and abnormal development in childhood and adolescence, 16(3), 209–228. 15. Weierink, L., Vermeulen, R. J., & Boyd, R. N. (2013). Brain structure and executive functions in children with cerebral palsy: A systematic review. Research in Developmental Disabilities, 34(5), 1678–1688

White matter microstructure and receptive vocabulary in children with cerebral palsy: The role of interhemispheric connectivity.

BackgroundCommunication and cognitive impairments are common impediments to participation and social functioning in children with cerebral palsy (CP). Bilateral language networks underlie the function of some high-level language-related cognitive functions.PurposeTo explore the association between receptive vocabulary and white-matter microstructure in the temporal lobes and the central part of the temporo-temporal bundles in children with CP.Materials and methods37 children with spastic motor type CP (mean age 9.6 years, 25 male) underwent a receptive vocabulary test (Peabody Picture Vocabulary Test, PPVT-IV) and 3T MRI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for the temporal lobes and the interhemispheric bundles traversing the splenium of the corpus callosum and the anterior commissure. Associations between microstructure and receptive vocabulary function were explored using univariable linear regression.ResultsPPVT-IV scores were significantly associated with mean white matter MD in the left temporal lobe, but not the right temporal lobe. There was no association between PPVT-IV and mean white matter FA in the temporal lobes. PPVT-IV scores were not significantly associated with the laterality of these diffusion tensor metrics. Within the corpus callosum, FA, but not MD of the temporo-temporal bundles was significantly associated with the PPVT-IV scores. Within the anterior commissure no equivalent relationship between diffusion metrics and PPVT-IV was found.ConclusionOur findings add further understanding to the pathophysiological basis underlying receptive vocabulary skills in children with CP that could extend to other patients with early brain damage. This study highlights the importance of interhemispheric connections for receptive vocabulary