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

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

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

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

Beyond the motor impairment in dyskinetic cerebral palsy: neuropsychological and connectome-based approach

[eng] The term cerebral palsy (CP) encompasses a group of disorders of movement and/or posture and of motor function due to a non-progressive injury, interference or abnormality in an immature or developing brain. These motor disorders are often accompanied by disturbances of sensation, perception, cognition, communication, behaviour or epilepsy, and it has been shown that these deficits may have a greater impact on the quality of life of these people than the motor impairment itself. Taking into account the classification of CP according to the type of motor involvement, dyskinetic CP is identified as a rare subtype (between 3% and 15% of all CP cases) characterized by abnormal patterns of posture and/or movement, accompanied by involuntary, uncontrolled, recurrent and, occasionally, stereotyped movements. This type of CP has been mainly associated with a perinatal hypoxic-ischemic event in children born at term or near term and in neonates with kernicterus. It has been shown that dyskinetic CP is one of the most disabling forms of CP, not only because of its association with greater motor impairment but also because of a greater presence and severity of associated deficits, such as speech and communication impairments. It should be noted that studies analysing this type of CP are still scarce, probably due to their lower frequency and greater severity. Cognitive and neuroimaging studies are specially rare, probably because most neuropsychological evaluations require manual dexterity and/or verbal responses, and neuroimaging studies involve the acquisition of MRI sequences in which the person must remain still. Therefore, the main goals of this thesis are: 1) to identify an objective measure of intelligence adequate for the great heterogeneity that exists in CP, 2) to describe the cognitive profile of a relatively large sample of people with dyskinetic CP, and 3) analyse the state of the cerebral white matter of this population through a connectome approach. To this end, a total of 52 subjects with dyskinetic CP and 52 typically-developing controls were included in the study and were administered a neuropsychological battery that included general cognitive performance (using the Raven’s progressive matrices - colour version, the Peabody picture vocabulary test and the Wechsler's nonverbal scale) and five specific cognitive domains (attention, visual perception, language, learning and memory and executive functioning). Finally, an structural MRI was acquired.[spa] La parálisis cerebral (PC) se define como un grupo de trastornos del movimiento y/o la postura y de la función motora debidos a una lesión, interferencia o anomalía no progresiva en un cerebro inmaduro o en desarrollo. Estos trastornos motores a menudo se acompañan de alteraciones sensoriales, de la percepción, de la cognición, de la comunicación, del comportamiento o de epilepsia, y se ha evidenciado que estos déficits pueden tener un mayor impacto sobre la calidad de vida que el propio déficit motor. Teniendo en cuenta la clasificación de la PC según el tipo de afectación motora se identifica que la PC discinética es un subtipo poco frecuente (entre el 3% y el 15% de todos los casos) que se caracteriza por patrones anormales de postura y/o movimiento, acompañados de movimientos involuntarios, descontrolados, recurrentes y, ocasionalmente, estereotipados. Este tipo de PC se ha asociado principalmente a procesos de hipoxia-isquemia en bebés nacidos a término o casi a término, y a la presencia de ictericia grave. Se ha evidenciado como la PC discinètica es más incapacitante que otros tipos de PC, no sólo por su asociación con una mayor afectación motriz sino también por una mayor presencia y gravedad de déficits asociados, como una mayor afectación del habla y de la comunicación. Cabe destacar que los estudios que han analizado este tipo de PC son todavía escasos, probablemente debido a su menor frecuencia y mayor gravedad. Especialmente escasos son los estudios cognitivos y de neuroimagen, ya que las pruebas neuropsicólogicas requieren de una destreza manual y/o de respuestas verbales y los estudios de neuroimagen implican la adquisición de secuencias de resonancia magnética en dónde la persona debe permanecer quieta. Es por ello que esta tesis tiene como objetivos principales: 1) identificar una medida objetiva de inteligencia adecuada para la gran heterogeneidad que existe en la PC, 2) describir el perfil cognitivo de una muestra relativamente amplia de personas con PC discinética, y 3) analizar el estado de la sustancia blanca cerebral de esta población mediante la técnica del conectoma. Para ello se incluyeron en el estudio un total de 52 sujetos con PC discinética y 52 sujetos control, a quienes se les administró una batería neuropsicólogica que evaluaba el rendimiento cognitivo general (mediante las Matrices progresivas de Raven - versión color, el Test de vocabulario en imágenes de Peabody - III y la Escala no verbal de aptitud intelectual de Wechsler) y cinco dominios cognitivos específicos (atención, visuopercepción, lenguaje, aprendizaje y memoria y función ejecutiva) y se les realizó un estudio de resonancia magnética estructural

Interventions with an Impact on Cognitive Functions in Cerebral Palsy: a Systematic Review

This systematic review aimed at investigating those interventions that impact on cognitive functioning in children and adults with cerebral palsy (CP). A systematic database search was conducted and twenty-eight studies suitable for inclusion were identified, of which only nine were randomized controlled trials (RCTs). Among all the studies included, ten were multimodal (cognitive and physical tasks), eleven physical, five cognitive, and two alternative and augmentative communication interventions. The evidence suggests that multi-modal and physical interventions improve general cognitive functioning. Multi-modal and cognitive interventions have an impact on visual perception. Both interventions, together with physical interventions have an effect on a specific executive function domain (inhibitory control), and only cognitive interventions improved other executive function domains such as working memory. However, no RCT assessed the effects of all executive function domains. Few studies have looked at interventions to improve memory and language, and there is a scarcity of long-term research. Future RCTs must be of higher quality and better account for age and sex differences, as well as the clinical heterogeneity of CP. To date, there is evidence that multi-modal, cognitive or physical interventions have an impact on general cognitive functioning, visual perception and executive functions in children with CP, which may support their cognitive development