Impaired glymphatic system revealed by DTI-ALPS in cerebral palsy due to periventricular leukomalacia: relation with brain lesion burden and hand dysfunction.

PURPOSE: Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL. METHODS: We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP. RESULTS: There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect. CONCLUSION: This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.

Dystonia in individuals with spastic cerebral palsy and isolated periventricular leukomalacia.

AIM: To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI). METHOD: This was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non-PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists. RESULTS: Eighty-five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4-26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level. INTERPRETATION: Dystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI. WHAT THIS PAPER ADDS: Individuals with spastic cerebral palsy and isolated periventricular leukomalacia on magnetic resonance imaging commonly display dystonia. Common sites of dystonia are in the fingers and hip adductors.

Predictors of Risk for Cerebral Palsy: A Review.

PURPOSE: To identify the earliest predictors of risk for diagnosis of cerebral palsy (CP). METHODS: A comprehensive literature search was conducted using various databases. The publications were reviewed to identify risk factors for CP from conception to early infancy. Studies were critically appraised with Joanna Briggs Institute guidelines for quality appraisal and evaluated for risk of bias using the Agency for Health Care Research and Quality guidelines. RESULTS: The initial search yielded 129 studies and 20 studies were included. Forty-seven risk factors for CP were extracted of which several were duplicate terms. The significant risk factors found to be indicative of CP were low birth weight (<1500 g), birth at less than 28 weeks of gestational age, periventricular leukomalacia, grade 3 or 4 intraventricular hemorrhage, preeclampsia, prematurity, an Apgar score of less than 4 at the first minute, birth asphyxia, preterm premature rupture of membrane, and absent fidgety movements. CONCLUSION: Twenty-three factors were consistently reported as predictors of CP.

Gait features of dystonia in cerebral palsy.

AIM: To determine the features cited by motor phenotyping experts when identifying dystonia in people with cerebral palsy (CP). METHOD: Dystonia identification in CP, particularly when comorbid with spasticity, can be difficult. The dystonia diagnostic criterion standard remains subjective visual identification by expert consensus. For this qualitative study, we conducted an inductive thematic analysis of consensus-building discussions between three pediatric movement disorder physicians as they identified the presence or absence of dystonia in gait videos of 40 participants with spastic CP and periventricular leukomalacia. RESULTS: Unanimous consensus about the presence or absence of dystonia was achieved for 34 out of 40 videos. Two main themes were present during consensus-building discussions as videos were evaluated for dystonia: (1) unilateral leg or foot adduction that was variable over time, and (2) difficulty in identifying dystonia. Codes contributing to the first theme were more likely to be cited by a discussant when they felt dystonia was present (as opposed to absent) in a video (χ2 test, p=0.004). DISCUSSION: These results describe the gait features cited by experts during consensus-building discussion as they identify dystonia in ambulatory people with CP. Qualitative thematic analysis of these discussions could help codify the subjective process of dystonia diagnosis.

Vojta Therapy in Neuromotor Development of Pediatrics Patients with Periventricular Leukomalacia: Case Series.

Background and Objectives: Vojta therapy is used by physiotherapists and is based on stimulation through peripheral pressure that leads to the activation of involuntary motor response patterns, thus triggering patterns of reflex locomotion, hence also called reflex locomotion therapy. Objective: To analyze the changes produced by Vojta therapy in the evolution of infant motor development in patients with maturational delay due to periventricular leukomalacia. Materials and methods: One session of Vojta Therapy per week for eleven months, patients' neuromotor development was evaluated through the Denver II Test and the Baleys Scale. Results: A clinically significant increase in the development of the patients is observed. Conclusions: Neuromotor development seems to generate an adequate progression in the motor area.

Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age.

OBJECTIVE: The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. STUDY DESIGN: We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. RESULTS: Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. CONCLUSION: DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

Development of the quality of reaching in infants with cerebral palsy: a kinematic study.

AIM: To assess development of reaching and head stability in infants at very high risk (VHR-infants) of cerebral palsy (CP) who did and did not develop CP. METHOD: This explorative longitudinal study assessed the kinematics of reaching and head sway in sitting in 37 VHR-infants (18 CP) one to four times between 4.7 months and 22.6 months corrected age. Developmental trajectories were calculated using linear mixed effect models. Motor function was evaluated with the Infant Motor Profile (IMP) around 13 months corrected age. RESULTS: Throughout infancy, VHR-infants with CP had a worse reaching quality than infants without CP, reflected for example by more movement units (factor 1.52, 95% CI 1.16-1.99) and smaller transport movement units (factor 1.86, 95% CI 1.20-2.90). Total head sway of infants with and without CP was similar, but infants with CP used more head movement units to achieve stability. The rate of developmental change in infants with and without CP was similar. Around 13 months, head control and reaching quality were interrelated; both were associated with IMP-scores. INTERPRETATION: Infants with CP showed a worse kinematic reaching quality and head stability throughout infancy from early age onwards than VHR-infants without CP, implying that kinematically they do not grow into a deficit, but exhibit deficits from early infancy on. WHAT THIS PAPER ADDS: Reaching quality improves throughout infancy in all infants at high risk (VHR-infants). Infants with cerebral palsy (CP) show a worse reaching quality than VHR-infants without CP. Infants with CP achieve head stability differently from infants without CP. Infants with CP exhibit kinematic reaching problems from early age onwards.

Motor and cognitive outcome after specific early lesions of the brain - a systematic review.

The aim of this systematic review was to study motor and cognitive outcome in infants with severe early brain lesions and to evaluate effects of side of the lesion, sex, and social economic status on outcome. A literature search was performed using the databases Pubmed and Embase. Included studies involved infants with either cystic periventricular leukomalacia (cPVL), preterm, or term stroke (i.e. parenchymal lesion of the brain). Outcome was expressed as cerebral palsy (CP) and intellectual disability (mental retardation). Median prevalence rates of CP after cPVL, preterm, and term stroke were 86%, 71%, and 29% respectively; of intellectual disability 50%, 27%, and 33%. Most infants with cPVL developed bilateral CP, those with term stroke unilateral CP, whereas after preterm stroke bilateral and unilateral CP occurred equally often. Information on the effects of sex and social economic status on outcome after specific brain lesions was very limited. Our findings show that the risk for CP is high after cPVL, moderate after preterm stroke, and lowest after term stroke. The risk for intellectual disability after an early brain lesion is lower than that for CP. Predicting outcome at individual level remains difficult; new imaging techniques may improve predicting developmental trajectories.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

The whole spectrum of cystic periventricular leukomalacia of the preterm infant: results from a large consecutive case series.

PURPOSE: The purpose of this study is to describe features of cystic periventricular leukomalacia (PVL) in a large consecutive cohort study including long-term neurodevelopmental follow-up. METHODS: We performed a retrospective single-centre cohort study including all preterm infants ≤35 weeks of gestational age with PVL diagnosed by ultrasound scans (US) from a tertiary care university hospital between 1988 and 2012. RESULTS: The majority of 160 consecutively diagnosed cases had a gestational age between 28 and 32 weeks (60.6%), and male sex was predominant (60.6%). The most common associated clinical findings included respiratory distress syndrome, preterm premature rupture of the membranes, and chorioamnionitis (57.5, 49.4, and 39.4%, respectively). Infants presented with apnoeas in 66.3 and neonatal seizures in 23.1%. Any kind of respiratory support was present in 75.0%. Associated low-grade intraventricular haemorrhage was evident in 33.1, high-grade haemorrhage in 9.4%. Cysts were located on both hemispheres in 75% and PVL grades 3 and 4 were predominant (75.6%). Neurodevelopmental follow-up of 146 cases at a median age of 72 months revealed normal development in 11.0, mental retardation in 50.0, and cerebral palsy in 83.6%. Visual impairment was diagnosed in 21.9% and hearing impairment in one case. A quarter of cases (27.4%) developed seizure disorders. Outcome data were significantly better in unilateral compared to bilateral PVL. CONCLUSIONS: Long-term neurodevelopmental outcome of bilateral PVL always was adverse and different from unilateral PVL. The latter might be negatively influenced by associated intra- and periventricular haemorrhages.

Initial Resuscitation at Delivery and Short Term Neonatal Outcomes in Very-Low-Birth-Weight Infants.

Survival of very-low-birth-weight infants (VLBWI) depends on professional perinatal management that begins at delivery. Korean Neonatal Network data on neonatal resuscitation management and initial care of VLBWI of less than 33 weeks gestation born from January 2013 to June 2014 were reviewed to investigate the current practice of neonatal resuscitation in Korea. Antenatal data, perinatal data, and short-term morbidities were analyzed. Out of 2,132 neonates, 91.7% needed resuscitation at birth, chest compression was performed on only 104 infants (5.4%) and epinephrine was administered to 80 infants (4.1%). Infants who received cardiac compression and/or epinephrine administration at birth (DR-CPR) were significantly more acidotic (P < 0.001) and hypothermic (P < 0.001) than those who only needed positive pressure ventilation (PPV). On logistic regression, DR-CPR resulted in greater early mortality of less than 7 days (OR, 5.64; 95% CI 3.25-9.77) increased intraventricular hemorrhage ≥ grade 3 (OR, 2.71; 95% CI 1.57-4.68), periventricular leukomalacia (OR, 2.94; 95% CI 1.72-5.01), and necrotizing enterocolitis (OR, 2.12; 95% CI 1.15-3.91) compared with those infants who needed only PPV. Meticulous and aggressive management of infants who needed DR-CPR at birth and quality improvement of the delivery room management will result in reduced morbidities and early death for the vulnerable VLBWI.

[Cognitive and linguistic abilities of a boy with PVL showing relatively higher VIQ compared to PIQ].

In this study, we investigated the cognitive processing and language abilities of a 13-year-old boy with moderate periventricular leukomalacia (PVL), spastic diplegia and exotropia who had discrepant scores in the verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) in the Wechsler Intelligence Scale for Children, third edition (VIQ; 82 > PIQ; under 40). In the Kaufman Assessment Battery for Children and Das-Naglieri Cognitive Assessment System, his performance was poor at simultaneous processing compared to sequential processing. He could not copy three-dimensional figures, and he could place only two out of eight blocks correctly in the second level models of Benton three-dimensional block construction test, showing visuospatial impairment typical of patients with PVL. Despite the relatively high score in VIQ, there was a gap among the scores of the subtests in the Illinois Test of Psycholinguistic Abilities. He tended to get low scores in tests that required visual abilities. In addition, there was also an impairment in reading fluency tested by the Diagnostic Criteria and Medical Guideline for Specific Developmental Disorders. He was much less fluent in reading syllables, words or sentences (6.0 SD or more compared to 12-year-old boys). The relatively higher score in VIQ superficially suggests adequate language ability. However, in the present study, precise investigation revealed some discrepancies even within the field of language. Thus, defining stronger and weaker points of a patient is important in order to determine optimal medical or educational approaches.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy.

INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy.

Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial.

AIM: The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. METHOD: Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10 years 10 months, SD 2 years 10 months; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher's exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. RESULTS: All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. INTERPRETATION: Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated.

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

AIM: The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. METHOD: In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. RESULTS: Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). INTERPRETATION: Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions.

Cerebral ischemia or intrauterine inflammation promotes differentiation of oligodendroglial precursors in preterm ovine fetuses: possible cellular basis for white matter injury.

White matter injury in premature infants is known to be major cause of long-term neurocognitive disability, but the pathogenic mechanism remains unclear, hampering our ability to develop preventions. Periventricular leukomalacia is a severe form of white matter injury. In the present study, we explored the effects of cerebral ischemia and/or intrauterine inflammation on the development of oligodendroglia in the cerebral white matter using chronically instrumented fetal sheep. Each fetus received one of three insults: hemorrhage, inflammation and their combination. In the hemorrhage group, 40% of the fetoplacental blood volume was acutely withdrawn, and 24 hours after removal, the blood was returned to the fetus. The inflammation group received intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin and thus suffered from necrotizing funisitis and chorioamnionitis. The inflammatory hemorrhage group underwent acute hemorrhage under the inflammatory state. The sham group received no insults. Importantly, periventricular leukomalacia was not detected in the sham and the inflammation groups. Differentiating oligodendroglia at various developmental stages were identified by immunohistochemical analysis with specific antibodies. No difference in the density of oligodendroglial progenitors was detected among the four groups, whereas oligodendroglial precursors were significantly reduced in the three insult groups, compared to sham control. Moreover, the density of immature oligodendroglia was higher in the inflammation group and the inflammatory hemorrhage group, while the density of mature oligodendroglia was highest in the hemorrhage group. We propose that cerebral ischemia or intrauterine inflammation induces the differentiation of oligodendroglial precursors in preterm fetuses, eventually resulting in their exhaustion.

[Influence of neonatal diseases and treatments on the development of cerebral palsy in preterm infant].

OBJECTIVE: To investigated the risk factors of cerebral palsy development in preterm infants. METHODS: This study included 203 preterm infants (gestation age < 37 weeks) diagnosed with cerebral palsy (CP) and 220 preterm infants without cerebral palsy or any other severe neurological disorders during April 2005 to August 2011. The risk factors in the development of cerebral palsy, including the diseases of premature infants and the treatments in neonatal period, were analyzed by multiple logistic regression analysis. RESULTS: Multivariate logistic analysis for the risk factors associated with cerebral palsy in neonatal period found significant differences in the occurrence of periventricular leukomalacia (PVL, OR = 39.87, P < 0.05), hypoxia-ischemic encephalopathy (HIE, OR = 4.24, P < 0.05), hypoglycemia of neonatal (OR = 2.18, P < 0.05), neonatal hyperbilirubinemia (OR = 1.72, P < 0.05), continuous positive airway pressure (CPAP, OR = 0.21, P < 0.05). CONCLUSION: The factors including PLV, HIE, hypoglycemia, and neonatal jaundice may increase the risk in the development of CP in preterm infant, while CPAP may decrease the risk of cerebral palsy.

A screening method for visual attention disabilities in cerebral palsy with periventricular leukomalacia.

PURPOSE: Patients with periventricular leukomalacia (PVL) have been reported to have a variety of complications; however, whether these involve impaired visual attention disabilities remains unclear. Therefore, this study aimed to investigate the presence or absence and degree of visual attention disabilities in patients with PVL and propose a screening test that would allow anyone to check for visual attention disabilities easily. METHODS: The study participants were 14 patients with PVL and seven controls with dyskinetic cerebral palsy. All participants performed three types of visual attention tasks: spatial attention tasks, feature-based attention tasks, and object-based attention tasks. The participants also performed counting tasks to determine how many squares of the same size and color could be counted (up to nine). Receiver operating characteristic analysis was used to calculate cutoff values, with disability as the objective variable and the value of the counting task as the explanatory variable. RESULTS: The results revealed that patients with PVL often had visual attention disabilities, as indicated by a significant reduction in tasks requiring divided attention. Visual attention disabilities could be detected by a score of ≤8 in the square counting task. CONCLUSIONS: These findings suggest that family members and teachers of patients with PVL can easily screen for visual attention disabilities at home and school to improve mobility precautions in patients with this disability.

Bradykinesia assessment in children with cerebral palsy and periventricular leukomalacia.

OBJECTIVE: To analyse the motor phenotype with a focus on bradykinesia in children with Cerebral Palsy (CP) in the setting of periventricular leukomalacia (PVL). METHODOLOGY: Analysis of a cohort of 25 children with CP and PVL. The Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS) were used to classify the severity of motor function. Spasticity was rated using the Modified Ashworth Scale (MAS), dystonia was rated using the Burke-Fahn-Marsden Scale (BFMS), and bradykinesia was rated using the Unified Parkinson's disease rating scale (UPDRS). All patients were video-recorded following a standard protocol. RESULTS: Bradykinesia was observed in 96% of patients. It was noted mainly in the limbs, and it was moderate-to-severe in the legs and mild-to-moderate in the arms. Bradykinesia correlated with functional level, as classified by GMFCS and MACS; also with dystonia, as rated by BFMS but did not correlate with a measure of spasticity (MAS). CONCLUSIONS: This study confirms the existence of bradykinesia in patients with CP in the setting of PVL. Bradykinesia and dystonia appear to be important interrelated factors influencing the level of gross and fine motor skills in patients with PVL.