Being a disease of the brain, cerebral palsy is associated with physical brain abnormalities that can be seen using neuroimaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET). People with cerebral palsy tend to have decreased cerebral blood flow and smaller brains (smaller cortical volumes) in general than their non-cerebral palsied counterparts. Identification of the specific brain regions that have been affected can aid in the understanding of cognitive and motor impairments in the cerebral palsy patient and can also be useful in the detection of risk factors for and the early diagnosis of cerebral palsy.
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CONTEXT: Magnetic resonance imaging (MRI) findings have been reported for specific clinical cerebral palsy (CP) subgroups or lesion types but not in a large population of children with all CP subtypes. Further information about the causes of CP could help identify preventive strategies. OBJECTIVE: To investigate the correlates of CP in a population sample and compare clinical findings with information available from MRI brain studies. DESIGN AND SETTING: Cross-sectional, population-based investigative study conducted in 8 European study centers (North West London and North East London, England; Edinburgh, Scotland; Lisbon, Portugal; Dublin, Ireland; Stockholm, Sweden; Tübingen, Germany; and Helsinki, Finland). PARTICIPANTS: Five hundred eighty-five children with CP were identified who had been born between 1996 and 1999; 431 children were clinically assessed and 351 had a brain MRI scan. MAIN OUTCOME MEASURES: Standardized clinical examination results, parental questionnaire responses, MRI results, and obstetric, genetic, and metabolic data from medical records. RESULTS: Important findings include the high rate of infections reported by mothers during pregnancy (n = 158 [39.5%]). In addition, 235 children (54%) were born at term while 47 children (10.9%) were very preterm (<28 weeks). A high rate of twins was found, with 51 children (12%) known to be from a multiple pregnancy. Clinically, 26.2% of children had hemiplegia, 34.4% had diplegia, 18.6% had quadriplegia, 14.4% had dyskinesia, 3.9% had ataxia, and 2.6% had other types of CP. Brain MRI scans showed that white-matter damage of immaturity, including periventricular leukomalacia (PVL), was the most common finding (42.5%), followed by basal ganglia lesions (12.8%), cortical/subcortical lesions (9.4%), malformations (9.1%), focal infarcts (7.4%), and miscellaneous lesions (7.1%). Only 11.7% of these children had normal MRI findings. There were good correlations between the MRI and clinical findings. CONCLUSIONS: These MRI findings suggest that obstetric mishaps might have occurred in a small proportion of children with CP. A systematic approach to identifying and treating maternal infections needs to be developed. Multiple pregnancies should be monitored closely, and the causes of infant stroke need to be investigated further so preventive strategies can be formulated. All children with CP should have an MRI scan to provide information on the timing and extent of the lesion.
[Bax, M., Tydeman, C. & Flodmark, O. (2006). Clinical and MRI correlates of cerebral palsy: The European cerebral palsy study. The Journal of the American Medical Association, 296(13), 1602-8.]
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Periventricular leukomalacia (PVL) due to hypoxic-ischemic insult to the immature brain, chorioamnionitis and maternal infection are the major etiological factors of spastic type cerebral palsy (CP). Despite advances in preventing and treating certain causes of CP, the number of patients has remained essentially unchanged and the pathophysiological mechanisms related to motor dysfunction remain poorly understood. In this study, statistical parametric mapping (SPM) analysis of cerebral gamma-aminobutyric acid (GABA) receptor PET imaging using [18F]-fluoroflumazenil showed increased GABA(A) receptor binding in the bilateral motor and visual cortices in spastic diplegia (SD) type CP patients (n = 20) compared with normal controls (n = 10). As GABA(A) receptor signaling modulates biological perception and production of movement, complex motor skills and use-dependent plasticity in the motor cortex, increased GABA(A) receptor binding in the motor cortex might play a important role in poor motor control. Decreased GABA(A) receptor binding was seen in the brain stem in SD CP patients, which appears to be related to spastic symptom.
[Lee, J. D., Park, H. J., Park, E. S., Kim, D. G., Rha, D. W., Kim, E. Y., Kim, D. I., Kim, J. J., Yun, M., Ryu, Y. H., Lee, J., Jeong, J. M., Lee, D. S., Lee, M. C. & Park, C. I. (2007). Assessment of regional GABA(A) receptor binding using 18F-fluoroflumazenil positron emission tomography in spastic type cerebral palsy. Neuroimage, 34(1), 19-25.]
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We study the effect of acupuncture on brain activation patterns in children with cerebral palsy using functional magnetic resonance imaging (fMRI). fMRI of the whole brain was performed in 11 children with cerebral palsy and 10 healthy children during stimulation of a common acupoint in Traditional Medicine [Liv3 (Taichong)] on the left foot. We use both twisting and nontwisting methods with a blocked paradigm on a 2.0 Tesla MRI scanner. Functional data were analyzed by using Statistical Parametric Mapping software (SPM 99). Both signal increase and decrease in various regions of the brain were found in both groups of children. However, the pattern was different for the 2 groups, especially with decreases in signal regions. We suggest that the observed differences between children with cerebral palsy and healthy children with the stimulation of acupoint Liv3 might be due to blockage of the liver meridian in children with cerebral palsy.
[Wu, Y., Jin, Z., Li, K., Wong, V., Han, T. L., Zheng, H., Caspi, O., Liu, G., Zeng, Y. W. & Zou, L. P. (2007). Effect of acupuncture on the brain in children with spastic cerebral palsy using functional neuroimaging (FMRI). Journal of Child Neurology, 23(11), 1267-74.]
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Neuroimaging, particularly with magnetic resonance techniques, can provide insight into the pattern and severity of cerebral injury underlying cerebral palsy providing a neuroanatomic understanding of the motor and related deficits. Early identification of injury before the establishment of marked motor deficits provides an opportunity for neuroprotection. Neuroimaging provides a robust manner for early delineation of the risk and nature of cerebral palsy that an infant may face. In the future, imaging may provide more functional methods, including novel methods such as optical tomography, map regeneration, adaptation, and functional recovery.
[Shimony, J. S., Lawrence, R., Neil, J. J. & Inder, T. E. (2008). Imaging for diagnosis and treatment of cerebral palsy. Clinical Obstetrics and Gynecology, 51(4), 787-99.]
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Magnetic resonance imaging was used to show that children with quadriplegic cerebral palsy and unable to ambulate independently compared to typically developing children have a remarkably underdeveloped femoral midshaft as indicated by a very thin diameter, a very thin cortical wall, and very low strength estimates. INTRODUCTION: The femoral shaft is very susceptible to fracture in children with quadriplegic cerebral palsy (QCP); however, its structure and strength have not been evaluated. METHODS: The volume and width of the middle third of the femur (midfemur) and its cortical wall and medullary cavity were assessed in children with QCP and unable to ambulate independently and typically developing children (n = 10/group) using magnetic resonance imaging (MRI). Estimates of cross-sectional moment of inertia (CSMI), section modulus (Z), and polar moment of inertia (J) were also determined. RESULTS: Total volume of the midfemur and volume of its cortical wall and medullary cavity were substantially lower in children with QCP than controls (51-55%; p < 0.001). In addition, the total midfemur, its medullary cavity and the anterior, posterior, and lateral sections of its cortical wall were thinner (27-43%) in children with QCP (p < 0.001). The midfemur in children with QCP also had remarkably lower CSMI, Z, and J (60-71%; p < 0.001). CONCLUSIONS: Children with QCP who lack the ability to ambulate independently have midfemurs that are very thin with very thin cortical walls and very low estimated strength. The disparity can be detected using MRI.
[Modlesky, C. M., Kanoff, S. A., Johnson, D. L. Subramanian, P. & Miller, F. (2008). Evaluation of the femoral midshaft in children with cerebral palsy using magnetic resonance imaging. Osteoporosis International [Epublication ahead of print].]
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OBJECTIVE: Extremely preterm birth is associated with adverse neurodevelopmental sequelae. Head circumference has been used as a measure of brain growth. There are limited data relating head circumference to MRI. The purpose of this work was to establish the relationship between head circumference with brain MRI at term-equivalent age and to relate head circumference with neurodevelopmental outcome at 2 years. PATIENTS AND METHODS: Two hundred and twenty-seven preterm infants (birth weight of <1250 g or <30 weeks' gestation) were recruited. Head circumference was measured at birth, term, and 2 years' corrected age, and z scores were computed. Microcephaly was defined as a head circumference z score of less than -2 SDs for age and gender. MRI scans at term (n = 214) were graded for white and gray matter abnormalities, and segmented volumes were calculated for different tissue types. Outcome at 2 years' corrected age (n = 202) included scores on the Bayley Scales of Infant Development II. RESULTS: Microcephaly increased from 7.5% at term to 29.7% at 2 years. There was no significant relationship between head circumference and white or gray matter abnormalities on MRI. There was a strong correlation between head circumference and brain volume at term. At term, microcephalic infants had significantly decreased volumes for total brain tissue and most segmented volumes compared with infants with normal head circumference, but only deep nuclear gray matter volume remained significantly lower when adjusted for total intracranial volume. At 2 years, microcephaly was associated with poorer cognitive and motor development and an increased rate of cerebral palsy. CONCLUSIONS: Brain volume is a determinant of head size at term. Microcephaly is associated with a reduction of brain tissue volumes, especially deep nuclear gray matter, which suggests a selective vulnerability. Poor postnatal head growth in preterm infants becomes more evident by 2 years and is strongly associated with poor neurodevelopmental outcome and cerebral palsy.
[Cheong, J. L., Hunt, R. W., Anderson, P. J., Howard, K., Thompson, D. K., Wang, H. X., Bear, M. J., Inder, T. E. & Doyle, L. W. (2008). Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome. Pediatrics, 121(6), e1534-40.]
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The American Academy of Neurology now recommends that all cases of cerebral palsy of unknown origin undergo neuroimaging. Controversy surrounds this recommendation because of concerns about the adequacy of the supporting evidence. This article reviews the evidence provided by magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies in cerebral palsy and discusses the potential benefits of imaging, techniques in current use, and future directions, with a focus on improving etiologic understanding. Most (83%) children with cerebral palsy have abnormal neuroradiological findings, with white matter damage the most common abnormality. Combined gray and white matter abnormalities are more common among children with hemiplegia; isolated white matter abnormalities are more common with bilateral spasticity or athetosis, and with ataxia; isolated gray matter damage is the least common finding. About 10% of cerebral palsy is attributable to brain malformations, and 17% of cerebral palsy cases have no abnormality detectable by conventional MR or CT imaging. Although neuroimaging studies have increased our understanding of the abnormalities in brain development in cerebral palsy, they are less informative than they might be because of 4 common problems: (1) inappropriate assignment of etiology to morphologic findings, (2) inconsistent descriptions of radiologic findings, (3) uncertain relationship of pathologic findings to brain insult timing estimates, and (4) study designs that are not based on generalizable samples. Neuroimaging is not necessarily required for diagnosis of cerebral palsy because the disorder is based on clinical findings. The principal contribution of imaging is to the understanding of etiology and pathogenesis, including ruling in or out conditions that may have implications for genetic counseling, such as malformations. In the future, as more sophisticated imaging procedures are applied to cerebral palsy, specific morphologic findings may be linked to etiologic events or exposures, thus leading to potential pathways for prevention.
[Korzeniewski, S. J., Birbeck, G., DeLano, M. C., Potchen, M. J. & Paneth, N. (2008). A systematic review of neuroimaging for cerebral palsy. Journal of Child Neurology, 23(2), 216-27.]
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We carried out a morphometric analysis of acetabular dysplasia in patients with cerebral palsy requiring hip surgery using three-dimensional CT. We evaluated 54 hips in 27 patients. The contralateral normal hips of ten patients with unilateral Perthes' disease were used as a control group. The acetabular defects were assessed qualitatively as anterior, posterior or global. Quantitative assessments were made using three-directional acetabular indices (anterosuperior, superolateral and posterosuperior) and measured by multiplanar reformation, from which we calculated the acetabular volume.In the qualitative study, posterior defects were most common in the subluxation group whereas global defects predominated in the dislocation group. In the quantitative study, all acetabular indices in both the subluxation and dislocation groups were higher than those in the control group and the superolateral indices showed a tendency to elevation in the dislocation group. The acetabular volume was largest in the control group, smallest in the dislocation group, and intermediate between the two in the subluxation group.
[Chung, C. Y., Park, M. S., Choi, I. H., Cho, T. J., Yoo, W. J. & Lee, K. M. (2006). Morphometric analysis of acetabular dysplasia in cerebral palsy. The Journal of Bone and Joint Surgery [British], 88(2), 243-7.]
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We aimed to assess the efficacy of tongue and body acupuncture with clinical function and brain glucose metabolism in children with a severe type of cerebral palsy. Four children were recruited. The motor function belonged to grade 5 of the Gross Motor Function Measure (i.e., completely nonambulatory). Daily tongue and body acupuncture was applied for 5 days a week for 8 weeks. The Functional Independence Scale for Children (WeeFIM), Clinical Global Impression Scale (CGIS), and positron emission tomography of the brain with [18F]fluorodeoxyglucose (FDG) were performed at baseline and after acupuncture. None of the children had any significant change in the Functional Independence Scale for Children score, despite the fact that all mothers scored 3 on the Clinical Global Impression Scale (i.e., 25% in improvement) in overall function. The brain glucose metabolism, however, showed a >10% increase in the frontal, parietal, temporal, and occipital cortices and cerebellum. Thus, a short course of tongue and body acupuncture was shown to increase brain glucose metabolism, despite lacking any clinical functional improvement seen during the eight-week course, possibly owing to the severity of the motor dysfunction and the short duration of treatment. The objective increase in brain glucose metabolism might serve as a surrogate marker for assessing the subclinical efficacy of an alternative treatment before any objective clinical improvement is evident. A larger-scale study for different degrees of severity of cerebral palsy and an impairment model should be undertaken to correlate clinical with neurometabolic change.
[Wong, V. C., Sun, J. G. & Yeung, D. W. (2006). Pilot study of positron emission tomography (PET) brain glucose metabolism to assess the efficacy of tongue and body acupuncture in cerebral palsy. Journal of Child Neurology, 21(6), 456-62.]
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In this study, three patients with spastic diplegia were examined with magnetic resonance imaging (MRI) and positron emission tomography (PET), using the steady state technique with 15O. Two of them had untractable seizures and mental retardation. On MRI the cortical structures were normal; increased T2 signals in the periventricular white matter in the second patient were the main findings. PET scan showed in the two patients with a seizure disorder and mental retardation a large left cortical area of decreased regional blood flow and oxygen consumption during the interictal phase. The third patient without epileptic spells had a normal PET scan examination. It is concluded that the epileptic disorder in two of our cases is due to an additional cortical lesion, while the spastic diplegia is caused by subcortical white matter destruction.
[Kucukali, I., De Reuck, J., Decoo, D., Strijckmans, K., Goethals, P. & Lemahieu, I. (1995). Positron emission tomography in spastic diplegia. Clinical Neurology and Neurosurgery, 97(1), 28-31.]
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Hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the term newborn is the most common recognized cause of the subsequent motor deficits often grouped under the rubric "cerebral palsy." In order to provide insight into the basic nature and pathogenesis of the brain injury in such infants, we studied regional cerebral blood flow (CBF) by positron emission tomography (PET) in 17 asphyxiated term infants during the acute period of illness. A consistent and apparently unifying abnormality was observed, namely, a relative decrease in CBF to parasagittal regions, generally symmetrical and more marked posteriorly than anteriorly. Thus, parasagittal values for CBF were generally 25 to 50% lower than those for the sylvian cortex; in the normal or near normal infant, parasagittal values are only approximately 10% lower than those for the sylvian cortex. (Additional normal findings for regional CBF were 50% higher flows to the cerebral cortex than to the cerebral white matter and flows to the basal ganglia and thalamus at least as high as those to the cerebral cortex). That the relative deficit in CBF to parasagittal regions reflects tissue injury was indicated by the close topographic correlation on technetium brain scans in 3 patients of increased tissue uptake of radionuclide and the CBF abnormality. Moreover, the single patient studied at postmortem examination exhibited parasagittal ischemic cerebral injury that correlated well with the PET abnormality of regional CBF. The topography of the PET abnormality, i.e., the cerebrovascular watershed regions, suggests that the brain injury is basically ischemic and that the pathogenesis relates to impaired cerebral perfusion, perhaps secondary to systemic hypotension occurring in association with the perinatal asphyxia. Experimental data support this formulation.
[Volpe, J. J., Herscovitch, P. Perlman, J. M., Kreusser, k. L. & Raichle, M. E. (1985). Positron emission tomography in the asphyxiated term newborn: Parasagittal impairment of cerebral blood flow. Annals of Neurology, 17(3), 287-96.]
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The CT findings in 120 cerebral palsied children are analysed. The 72.5% positive findings are correlated with the clinical types, as well as the aetiological basis for the cerebral palsy. The spastic type, 83.3% of the total number of children, had the highest positive findings. The yield was increased in children with seizures (91.3%) and those in the postnatal group (90%), as well as those with birth trauma and neonatal asphyxia (94%). The findings were those of atrophy in 30.8%, hydrocephalus, in 10%, infarct in 11.6%, porencephaly in 8.3% and others. The atropic changes and their patterns are explained. Treatable lesions, such as tumour, hydrocephalus, subdural haematoma, porencephaly and hygroma were identified in 22.5% of cases. It is concluded that CT scan is definitely efficacious in the management of cerebral palsied children.
[Kolawole, T. M., Patel, P. J. & Mahdi, A. H. (1989). Computed tomographic (CT) scans in cerebral palsy (CP). Pediatric Radiology, 20(1-2), 23-7.]
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The authors used MRI to analyse retrospectively the brain images of patients with cerebral palsy (CP) to evaluate its the role in the assessment of brain abnormalities and injury, and the relationship of pre-, peri- and postnatal events to CP. 70 patients with CP aged two to 16 years who underwent MRI were divided into four groups: group 1 (26 patients) comprised subjects whose CP was considered to have been caused by neuronal migration disorders in the embryonal stage; group 2 (30 patients) contained subjects whose cause was vascular disorders; in group 3 patients (five) the cause was intra-uterine infection; and CP clearly attributable to birth asphyxia (group 4) was noted in only nine patients. The results indicate that CP of term infants is often the result of prenatal factors, and their MRI findings indicated migration and cerebral infarction. Brain MRI is an essential examination in identifying the factors causing brain damage in CP.
[Sugimoto, T., Woo, M., Nishida, N., Araki, A., Hara, T., Yasuhara, A., Kobayashi, Y. & Yamanouchi, Y. (1995). When do brain abnormalities in cerebral palsy occur? An MRI study. Developmental Medicine and Child Neurology, 37(4), 285-92.]
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