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The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: A systematic review
Abstract
The aim of this study was to show the role of magnetic resonance imaging (MRI) in elucidating the aetiology, or at least pathogenesis, of cerebral palsy (CP). A systematic review of studies using MRI in children with CP was performed according to pathogenetic patterns characterizing different timing periods of occurence of the lesions, and with respect to gestational age (term vs preterm) and CP subtypes. Out of the studies published since 1990 in English, six met all the inclusion criteria; they involved children with spastic and dyskinetic CP. Abnormal MRI was reported in 334 out of 388 (86%) patients and gave clues to pathogenesis in 83%. Fourteen studies met only part of the inclusion criteria and abnormal MRIs were reported even more frequently in these (91%; 930/1022). Periventricular white matter lesions were most frequent (56%) followed by cortical and deep grey matter lesions (18%); brain maldevelopments were rather rare, described in 9%. Brain maldevelopments and grey matter lesions were more often seen in term than in preterm-born children with CP (brain maldevelopments: 16% vs 2.5%; grey matter lesions: 33% vs 3.5%); periventricular white matter lesions occurred significantly more often in preterm than in term-born children (90% vs 20%). CP is mainly characterized by brain lesions which can be identified by MRI in around 75% of preterm infants; brain maldevelopments occur in around 10%.
... [1] Although neuro-imaging is not a prerequisite for the diagnosis of CP, it assists in determining the onset of the brain insult and possible aetiology. [1,[3][4][5] Both the American Academy of Neurology (AAN) and the 2017 NICE guidelines recommend that neuro-imaging should be done if the aetiology of CP is unknown. Magnetic resonance imaging (MRI) is the preferred diagnostic modality. ...
... [4] Neuro-imaging assists in defining different neuropathological patterns including congenital malformations and various destructive lesions of white and grey matter. [3,5,6] In a review by Krägeloh-Mann and Horber, the incidence of these pathogenic patterns was periventricular white matter injury (56%), deep grey matter injury (18%) and congenital malformations (9%). [5] Research has demonstrated an association between structural brain lesions and the CP motor subtype. ...
... [3,5,6] In a review by Krägeloh-Mann and Horber, the incidence of these pathogenic patterns was periventricular white matter injury (56%), deep grey matter injury (18%) and congenital malformations (9%). [5] Research has demonstrated an association between structural brain lesions and the CP motor subtype. [8][9][10] A systematic review by Franki et al. [11] published in 2020 concluded that more research is required to establish the relationship between structural brain pathology and functional outcome in CP. ...
Background. Cerebral palsy (CP) is a common cause of physical impairment in children. Brain magnetic resonance imaging (MRI) can define different neuropathological patterns of brain injury in CP. There are limited data available on MRI findings of children with CP in Africa. Objective. To describe the clinical characteristics, risk factors and MRI findings of children with CP attending a developmental clinic at a tertiary hospital in South Africa; and to assess possible associations between the clinical characteristics and pathogenic neuro-imaging patterns. Methods. This was a retrospective cross-sectional study. The cohort of 112 children was identified from the clinic’s REDcap database. Clinical information was obtained from existing medical records of the patients. Findings from brain MRI reports were classified according to the MRI classification system (MRICS) for CP. The MRI reports were rated independently by two study investigators. A descriptive analysis was conducted. Results. A total of 112 patient files and MRI brain reports were reviewed. Spastic CP was the most common type of CP (n=75%). The most common perinatal risk factors included prematurity (31%) and low birthweight (28%). Nineteen (17%) children acquired CP after the neonatal period. CP sub-type showed a significant association with functional motor impairment classified as per the gross motor function classification system (GMFCS), p<0.001. Predominant grey matter injury (PGMI) was the most common pathogenic MRI pattern identified (30%). The radiological findings (per MRICS) had a significant association with both the CP sub-type (p<0.005) and functional impairment according to the GMFCS (p<0.001). Conclusion. Standardised classification of neuro-imaging findings can assist in defining the pathogenesis and clinical manifestations of CP.
... Magnetic resonance imaging (MRI) is a non-invasive, radiation-free imaging technique widely used in the diagnosis of severe brain injury owing to its high sensitivity and specificity for detecting CE of different causes (17). However, there is no consensus on the timing of the MRI in predicting prognosis of CE. ...
... However, there is no consensus on the timing of the MRI in predicting prognosis of CE. For neonates with hypoxic-ischemic encephalopathy (HIE), the Guidelines of the American Academy of Neurology recommend MRI on postnatal days 2-8, while the Guidelines of the American College of Obstetricians and Gynecologists state that MRI should be performed in both early (1-4 days) and late (7-21 days) postnatal periods to obtain a more comprehensive assessment of injuries (15)(16)(17)(18). As CE is a dynamic process and a child's brain undergoes growth and development, it holds significant importance to conduct MRI scans during follow-up for children with severe brain injuries. ...
Purpose
To investigate the primary causes and clinical characteristics of cystic encephalomalacia (CE) in children.
Methods
The clinical data of 50 children who were admitted to our hospital due to CE between January 2008 and December 2020 were retrospectively reviewed. Their primary causes, clinical manifestations and cranial magnetic resonance imaging features were analyzed.
Results
Among all patients, 5 had prematurity, 19 had hypoxic-ischemic encephalopathy (HIE), 13 had intracranial infection, 14 had traumatic brain injury and hemorrhage, 4 had cerebral infarction, 2 had congenital genetic diseases, and 1 had hypoglycemia. The average time from primary disease onset to CE diagnosis was 70.1 ± 61.0 days. The clinical manifestations included speech or motor developmental delay ( n = 33), epilepsy ( n = 31), dystonia ( n = 27), limb paralysis ( n = 16), and visual or auditory impairment ( n = 5). Patients with HIE as the primary cause of CE had a significantly higher occurrence of dystonia, while a significantly higher incidence of paralysis was observed in those with cerebral infarction as the primary cause.
Conclusion
CE in children is mainly caused by HIE, intracranial infection, and cerebral hemorrhage. The major clinical manifestations included speech or motor developmental delay, epilepsy, and dystonia. Magnetic resonance imaging is an important tool for the diagnosis of CE.
... In the past, there was lack of evidence to support neuroimaging in the diagnostic work-up in CP (50),(51), even though in 2004 the American Academy of Neurology, in a Indeed, neuroimaging (MRI and/or CT) was able to identify abnormalities related to motor impairment in 80 to 88% of children with CP (52), (53), (54), (55). The variation observed in the distribution of findings between geographic cohorts is partly due to differences in the classification systems and methodologies. ...
... There is thus a strong indication for a more detailed investigation of some genetic or metabolic conditions (i.e., hereditary spastic paraplegias or ataxias, dopa-responsive dystonias, or other neurometabolic disorders) to identify certain treatable conditions associated with disturbed neuromotor development in cases where CP is suspected but the MRI is normal.Four imaging patterns are consistently reported as the most predictive ones; white matter injury-WMI (including cystic periventricular leukomalacia or periventricular hemorrhagic infarctions -56% of the cases), cortical and deep gray matter injury (including basal ganglia injuries, thalamic abnormalities, cortical defects, watershed injury [parasagittal injury], multicystic encephalomalacia, stroke or diencephalic lesions -18% of the cases), brain malformations (including lissencephaly, heterotopia, pachygyria, polymicrogyria, schizencephaly or hemimegalencephaly -9% of the cases), and miscellaneous findings (including unclassified to other patterns abnormalities such as haemorrhages, infection, ventricular enlargement, and tumors). In the previously mentioned 2014 Systematic Review(57), WMI was the most frequent imaging pattern among children with CP of all types (19 to 45% (up to 56% in other studies)), with the highest rate of WMI found in children with spastic subtypes and especially spastic diplegia (31%-60%)(54). GMI was associated with spastic quadriplegia (34%) and dyskinesia (21%), while focal insults with hemiplegia (24%). ...
This teaching review aims to provide an overview of the current approach to children with cerebral palsy (CP), retrieving the best available evidence and summarizing existing knowledge in the field of CP in children. We also highlight areas where more research is needed and novel strategies for diagnosing and treating cerebral palsy. CP includes a group of permanent disorders of movement and posture that cause activity limitation. Multiple risk factors, occurring preconceptionally, prenatally, perinatally, or postneonatally, are involved in the pathogenesis of CP, with the prenatal ones accounting for 80-90% of cases. Due to its heterogeneity, CP has various classifications, but usually is classified based on clinical findings and motor impairment. Standardized function classification systems have been developed to address inconsistencies in previous classifications. The combination of clinical assessment and validated predictive tools is recommended for an early diagnosis, which is important for early intervention and prevention of secondary impairments. The therapeutic regimen in CP involves prevention and management of the motor and associated problems. It includes the enhancement of motor performance, the enrichment of cognition and communication skills, the prevention of secondary impairments, and the support of parents and caregivers. The care of CP children demands a multidisciplinary approach focused on improving motor skills, reducing comorbidities, enhancing the quality of life, and prolonging survival.
... Diplegia affects both lower limbs signicantly more than the upper limbs, while trilegia indicates three limbs affected. Quadriplegia affects both upper and lower limbs, and the muscles of [5,6] the trunk, face, and mouth could also be affected. ...
... Inclusion criteria: Ÿ Children in the age group of 2-12 years diagnosed with cerebal palsy. Ÿ Children with moderate to severe impairment dened by gross motor functional [2,6,7] Ÿ Classication system who had been clinically diagnosed as cerebral palsy. International Journal of Scientific Research Exclusion criteria: Ÿ Children below the age of 2 years and above 12 years. ...
Introduction: Cerebal Palsy is the most common childhood physical disability representing a group of conditions with heterogenous symptoms that are characterized by decient motor control, spasticity, paralysis and other neurological disturbances that emerge before, during, or in a short time after birth. Methodology: A tertiary hospital based descriptive cross-sectional study among 73 subject of age group 2-12years diagnosed as cerebal palsy. The study was carried to nd the topographical and GMFCS pattern of Cerebal palsy in children. Results- Mean age of the patients was 5.2 ± 3.2 years (Range 2 to 12 years) with male to female ratio of 1.7:1. According to Topographical Pattern, 41.1% patients had spastic diplegia, 31.5% had spastic quadriplegia, 15% had spastic hemiplegia, 4.1% had dystonic type, 2.7% had ataxic type, 2.7% had hypotonic type and 2.7% had choreoathetoid or dyskinetic type of CP. As per GMFCS Pattern, 16.4% patients were in level III,47.9% were in level IV and 35.6% were in level 5 of GMCFS. Conclusion: Topographical classication is helpful in detecting the limb(s) affected. GMFC System is procient in determining in how and where a child is affected by CPand useful in ascertaining treatment protocols.
... Structural images included axial T2-weighted FSE, coronal 3D T1-weighted SPGR, coronal 3D T2-weighted SE, and 3D-TOF SPGR. Brain MRI studies were evaluated and categorized according to neuroradiological patterns described in the literature (for an extensive review of perinatal brain damage patterns, see [19,20]), the temporality of the lesion according to [21], and the classifications and levels of severity according to white and gray matter abnormality scales [22,23]. ...
... Additionally, non-cystic PVL was observed in the preterm groups. Our findings agree with those previously reported [21,43,44]. ...
Background:
Preterm birth is one of the world's critical health problems, with an incidence of 5% to 18% of living newborns according to various countries. White matter injuries due to preoligodendrocytes deficits cause hypomyelination in children born preterm. Preterm infants also have multiple neurodevelopmental sequelae due to prenatal and perinatal risk factors for brain damage. The purpose of this work was to explore the effects of the brain risk factors and MRI volumes and abnormalities on the posterior motor and cognitive development at 3 years of age.
Methods:
A total of 166 preterm infants were examined before 4 months and clinical and MRI evaluations were performed. MRI showed abnormal findings in 89% of the infants. Parents of all infants were invited to receive the Katona neurohabilitation treatment. The parents of 128 infants accepted and received Katona's neurohabilitation treatment. The remaining 38 infants did not receive treatment for a variety of reasons. At the three-year follow-up, Bayley's II Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) were compared between treated and untreated subjects.
Results:
The treated children had higher values of both indices than the untreated. Linear regression showed that the antecedents of placenta disorders and sepsis as well as volumes of the corpus callosum and of the left lateral ventricle significantly predicted both MDI and PDI, while Apgar < 7 and volume of the right lateral ventricle predicted the PDI.
Conclusions:
(1) The results indicate that preterm infants who received Katona's neurohabilitation procedure exhibited significantly better outcomes at 3 years of age compared to those who did not receive the treatment. (2) The presence of sepsis and the volumes of the corpus callosum and lateral ventricles at 3-4 months were significant predictors of the outcome at 3 years of age.
... CP is one of the most common causes of physical disability in children, and the majority of these children have impaired hand function that makes them experience difficulties in performing daily activities (3,4). It occurs in 2-3:1,000-1:2,500 live births (5,6). Depending on the timing of the lesion during fetal development, different types of lesions occur; cortical maldevelopments (first and second trimester of gestation), periventricular white matter (PVL) lesions (early third trimester) or cortical and subcortical lesions/ middle cerebral artery infarctions (MCA) (around term age). ...
... The following inclusion criteria were applied: (1) human participants with spastic CP; (2) mean age of the participants was not older than thirty years of age, since the focus of the study included children and young adults; (3) MRI imaging available; (4) assessment of somatosensory function; (5) published in English, Dutch, French or German; (6) original research papers (exclusion of study protocols, reviews and conference abstracts). ...
Background:
Objective: To identify and examine neural reorganization of the sensory network in terms of lesion type, somatotopic organization of the primary somatosensory area, and functional connectivity in relation to sensory function in children and young adults with cerebral palsy (CP).
Methods:
Design: systematic review, Prospero registration ID 342570. Data sources: PubMed; Cochrane; Web of Science; Embase; CINAHL and PEDro from inception to March 13, 2021. Eligibility criteria: All types of original studies, concerning sensory connectivity in relation to sensory outcome in patients with spastic CP, <30 years of age. No publication status or date restrictions were applied. Data extraction and synthesis: Two authors independently determined the eligibility of studies. Quality assessment was performed by a third author. Neuro-imaging/neurophysiological techniques, sensory outcomes and patient characteristics were extracted.
Results:
Children and young adults with periventricular leucomalacia (PVL) lesions have significantly better hand function and sensation scores than patients with cortical-subcortical/middle cerebral artery (MCA) lesions. Ipsilesional reorganization of the S1 (primary somatosensory cortex) area appears to be the primary compensation mechanism after a unilateral early brain lesion, regardless of the timing of the lesion. Interhemispheric reorganization of the sensory system after early brain lesions is rare and, when it occurs, poorly effective. Diffusion tractography shows a positive correlation between the ascending sensory tract (AST) diffusivity metrics of the more affected hemisphere and sensory test outcomes.
Discussion and conclusions:
Because of the large variability in study design, patient characteristics, neuroimaging/neurophysiological techniques and parameters as well as sensory assessment methods used, it is difficult to draw definite inferences on the relationship between the reorganization of the sensory network following early brain damage and sensory function in children and young adults with CP. In general, sensory function seems to be worse in cortical as opposed to white matter tract (PVL) lesions. International consensus on a clinically relevant sensory test battery is needed to enhance understanding of the intriguing compensatory mechanisms of sensory network following early brain damage and potential consequences for rehabilitation strategies.
Systematic review registration:
https://www.crd.york.ac.uk/prospero/.
... Diagnosing an individual with CP requires a multidisciplinary approach, including clinical observation, and usually radiological assessment of conventional structural brain magnetic resonance imaging (MRI), such as T1-and T2weighted images. These images are helpful in revealing the underlying cause of CP in the individual, such as periventricular leukomalacia, damage to deep grey matter, or cortical malformation, 3,4 and may have implications for further diagnostic examinations, such as genetic testing. Early conventional MRI is also used to aid in prognostication. ...
... In about 14% of the individuals clinically diagnosed with CP, no abnormalities on conventional MRI were found. 4 Interestingly, in the five studies in which, specifically, individuals diagnosed with CP without abnormalities on conventional MRI were compared with typically developing individuals, differences in structural and functional connectivity and network organization were observed. 30,31,48,52,53 However, in these individuals it often remains questionable whether the cause of the motor disorder is indeed CP, defined as a non-progressive disturbance that occurred in the developing brain, or rather another underlying (yet unidentified) metabolic or genetic disorder. ...
Aim
To explore altered structural and functional connectivity and network organization in cerebral palsy (CP), by clinical CP subtype (unilateral spastic, bilateral spastic, dyskinetic, and ataxic CP).
Method
PubMed and Embase databases were systematically searched. Extracted data included clinical characteristics, analyses, outcome measures, and results.
Results
Sixty‐five studies were included, of which 50 investigated structural connectivity, and 20 investigated functional connectivity using functional magnetic resonance imaging (14 studies) or electroencephalography (six studies). Five of the 50 studies of structural connectivity and one of 14 of functional connectivity investigated whole‐brain network organization. Most studies included patients with unilateral spastic CP; none included ataxic CP.
Interpretation
Differences in structural and functional connectivity were observed between investigated clinical CP subtypes and typically developing individuals on a wide variety of measures, including efferent, afferent, interhemispheric, and intrahemispheric connections. Directions for future research include extending knowledge in underrepresented CP subtypes and methodologies, evaluating the prognostic potential of specific connectivity and network measures in neonates, and understanding therapeutic effects on brain connectivity.
... After about 34 weeks of gestation, subcortical and cortical areas are the most vulnerable regions of the brain for hypoxic ischaemic insult and the resulting lesions include subcortical leucomalacia, multicystic encephalamalacia and gliosis. 17 Commonly observed in preterm infants and full-term children with suffocation, PVL is a significant manifestation of infant brain injuries. PVL is the main cause of infant mortality; patients who survive suffer from nervous system disorders and mental retardation later in life. ...
... There were 6.7% as miscellaneous group which does not fit in above groups. These findings are in accordance with the study done by Krägeloh-Mann et al. 17 Cortical malformation in our study was 10.6% which is comparable with the previous studies 23 of 10.6% cases, preterm were 13.2% and; 9.1% term babies. We also noted other significant finding. ...
... The time burdens associated with acquisition and analysis of sophisticated quantitative neuroimaging studies, however, limit clinical adoption. In contrast, categorical descriptions of the lesion pattern [45,46] are easily conducted in the clinic but offer limited precision. The semi-quantitative scale for classification of structural brain MRI (sqMRI) is a valid and reliable alternative that systematically assesses both the extent and the anatomical location of the brain lesion/s in people with CP [47,48]. ...
... European Journal of Paediatric Neurology38 (2022) [33][34][35][36][37][38][39][40][41][42][43][44][45][46] ...
Purpose
To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions.
Methods
The semi-quantitative scale for MRI (sqMRI) was scored for 101 children. Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling, numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores' laterality index. Verbal-language-related outcomes were compared between participants with left-sided versus bilateral brain lesions.
Results
Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables.
Conclusion
The laterality of early-life lesions influences the development of verbal cognitive functions.
... The time burdens associated with acquisition and analysis of sophisticated quantitative neuroimaging studies, however, limit clinical adoption. In contrast, categorical descriptions of the lesion pattern [45,46] are easily conducted in the clinic but offer limited precision. The semi-quantitative scale for classification of structural brain MRI (sqMRI) is a valid and reliable alternative that systematically assesses both the extent and the anatomical location of the brain lesion/s in people with CP [47,48]. ...
... European Journal of Paediatric Neurology38 (2022) [33][34][35][36][37][38][39][40][41][42][43][44][45][46] ...
Purpose: To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions.Methods: The semi-quantitative scale for MRI (sqMRI) was scored for 101 children.Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling,numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores’ laterality index. Verbal-language-related outcomes were compared between participants with left-sided versus bilateral brain lesions.Results: Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables.Conclusion: The laterality of early-life lesions influences the development of verbal cognitive functions.
... MRI is able to demonstrate and differentiate a variety of insults and anomalies that are responsible for cerebral palsy [10]. A previous study has reported that cerebral palsy is mainly featured with brain lesions that can be identified by MRI in around 75% of preterm infants [11]. MRI is a recommended technique in cerebral palsy children where the main presenting problem in cerebral palsy is decreased motor ability and the aetiology has not been established [12]. ...
Objective
This study focused on analyzing the clinical value and effect of magnetic resonance imaging plus computed tomography (MRCT) and CT in the clinical diagnosis of cerebral palsy in children.
Methods
From February 2021 to April 2023, 94 children diagnosed with cerebral palsy were selected from our hospital for study subjects. These patients were divided into CT and MRI groups, with CT examination given to the CT group and MRI examination given to the MRI group. The positive rate of the two examination methods in the diagnosis of cerebral palsy was compared, different imaging signs in two groups of children with cerebral palsy were compared, and the diagnostic test typing results between two groups were further analyzed.
Results
The diagnostic positivity rate of the children in the MRI group was 91.49%, which was significantly higher than that of the children in the CT group (70.21%) (P < 0.05). In both groups, encephalomalacia, bilateral frontal subdural effusions, and gray-white matter atrophy of the brain were the main signs, and the difference in the proportion of these three imaging signs between the two groups was not significant (P > 0.05). Differences between the two groups examined for cerebral palsy subtypes were not significant (P > 0.05).
Conclusion
The positive rate of pediatric cerebral palsy examined by MRI is higher than that of CT diagnosis, but the clinic should organically combine the two to further improve the detection validity and accuracy.
... In HICs, the sensitivity and specificity of abnormal MRI for cerebral palsy is approximately 90 % (125), and it can help in identifying the cause of cerebral palsy and timing of the insult (126,127). However, access to MRI is limited in LMICs, and the few studies using it to predict cerebral palsy have shown somewhat lower sensitivity but generally good specificity (128)(129)(130). ...
Background:
Ending preventable newborn deaths is an unfinished global health agenda. Infants surviving birth have a right to thrive and to reach their full developmental potential. The aim of this thesis was to evaluate methods for identification of infants in need of neonatal resuscitation and at risk of disability in low- and middle-income countries.
Paper I was an observational study conducted in Pokhara, Nepal, comparing the heart rate in the first 3 minutes in infants who were quietly breathing (n=54) versus crying (n=1155) immediately after birth. The median heart rate did not differ between the two groups, but both bradycardia and tachycardia were more common among non-crying but breathing newborns.
Paper II was a systematic review and meta-analysis of studies examining the incidence and outcomes of intrapartum-related neonatal encephalopathy in low- and middle-income countries. Altogether 53 articles were identified. The incidence ranged from 1.5 to 20.3 per 1000 live births (5 studies), the mean neonatal mortality was 19.3 % (45 studies, 3307 infants), and the incidence of combined outcome of death or moderate to severe disability at follow-up was 44.6 % (19 studies, 1595 children).
Paper III evaluated the feasibility of smartphone-aided remote General Movements Assessment for identification of children at risk of cerebral palsy in Kathmandu, Nepal. Children surviving birth asphyxia or neonatal seizures were filmed by parents using the NeuroMotion smartphone application at home at 3 months’ age. Altogether 31 children were enrolled, and 16 parents returned at least one video of approved technical quality. Usability of the app was good based on parental survey.
In Paper IV, individual (n=4) and group interviews (n=2) were conducted with ten mothers participating in the smartphone aided follow-up of their infants. The data were analysed using deductive qualitative content analysis. The remote follow-up was acceptable with support from the research assistants. Some participants would have preferred a face-to-face evaluation.
Conclusion:
Not crying at birth is a potential indicator for need of neonatal resuscitation. Infants who survive resuscitation are at risk of intrapartum-related neonatal encephalopathy, which has persistently high burden particularly in low-income countries. All survivors of encephalopathy need follow-up and smartphone-aided remote General Movements Assessment could complement the assessments in settings similar to Kathmandu.
... Regarding specific localization and etiopathogenetic pattern of brain lesions occurring in the immature brain (Krägeloh-Mann, 2004;Krägeloh-Mann & Cans, 2009;Krägeloh-Mann & Horber, 2007) the categorization is typically based on predominant pattern of damage, including: (a) cortical maldevelopments, occurring during the first 24 weeks of gestation and found in approximately 16 % of UCP cases; (b) periventricular white matter (PWM) lesions, commonly observed in preterm children, develop between 24 and 34 weeks of gestation and present in around 36 % of UCP children; (c) cortical and deep gray matter (CDGM) lesions, affecting cortical and subcortical areas, mostly occurring between 34 weeks of gestation and 28 days after birth, accounting for 31 % of UCP cases. Lesions that do not fit into these categories are usually classified as miscellaneous, comprising 7 % of UCP children. ...
Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.
... Cerebral palsy FLAIR Fluid-attenuated inversion recovery GMFM-66 Gross Motor Function Measure-66 MRI Magnetic resonance imaging MRICS MRI classification system sqMRI Semi-quantitative scale for classification of structural brain MRI TP time point TP1/2 Timepoint 1/2 T1w T1-weighted T2w T2-weighted score of increasing brain lesion load, ranging from 0 to 48. Brain lesion pattern was classified according to the presumed brain lesion timing using the Krägeloh-Mann classification [38,39]. ...
... Furthermore, the most important studies do not consider MRI which is the gold standard to define the diagnosis including minor brain lesions often missed at ultrasound [14,15]. Major brain lesions like cystic periventricular leukomalacia (PVL), germinal matrixintraventricular hemorrhage (GMH-IVH) complicated by periventricular hemorrhagic venous infraction (PVHI) or post-hemorrhagic ventricular distension (PHVD) and massive cerebellar hemorrhage (CBH) are strongly associated with important neurological impairment [16,17,18,19,20,21,22,23,24]. The role of minor lesions like low grade GMH-IVH, punctate white matter lesions (PWML) and micro CBH is still debated although some recent works seems to be associated with an impaired neurological development [25,26,27]. ...
Extrauterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very low birth weight (VLBW) preterms. We report a population of 288 patients with no or with low grade MRI lesions scanned at term equivalent age (TEA) born between 2012 and 2018. Griffiths mental development scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analysed. EUGR was defined for weigth z-score ˂10th percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point SDS from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p=0,01). EUGR at 6 months was associated with worse locomotor, personal-social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest to better invest on post-discharge nutritional, optimizing family nutritional education.
... 4,20,21 This is likely due to the predominance of grey matter injury or cortical malformation in children born at term, which is more likely to cause epilepsy compared to white matter injury observed in children born preterm. 22 These findings are in contradiction with previous studies that showed no impact of gestational age or preterm birth as a risk factor for epilepsy. 23,24 The frequency of epilepsy varies with the type of CP. ...
Aim
To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP).
Method
Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug‐responsive (n = 83) and drug‐resistant groups (n = 147) using logistic regression and hierarchical cluster analysis.
Results
Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug‐resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77–0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy.
Interpretation
Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment.
What this paper adds
Severe motor and non‐motor impairments in cerebral palsy (CP) increase epilepsy risk.
Epilepsy more likely resolves in bilateral spastic and milder CP impairments.
Epilepsy in CP often manifests at an early age with multiple seizure types and high drug resistance.
Children with a known genetic cause and CP epilepsy surgery group represent distinct clinical subgroups.
... Impairment of higher visual functions can be present with or without ophthalmological impairments [12,19,17,20]. Different brain lesions underlie the heterogeneous clinical spectrum of CP and this damage is often classified using a qualitative classification system based on structural MRI (sMRI) observations [21,22]. Based on the MRI classification system (MRICS), MRI outcomes can be categorized as brain maldevelopments, white matter (WM) lesions, grey matter (GM) lesions, miscellaneous abnormalities, or normal MRI [22]. ...
Abstract
Objective
The structure–function relation between magnetic resonance imaging (MRI) and visual impairment (VI) in children with cerebral palsy (CP) has not been fully unravelled. The present systematic review aims to summarize the relation between brain lesions on MRI and VI in children and adolescents with CP.
Methods
PubMed, Embase, Web of Science Core Collection, and Cochrane Database were systematically searched according to the PRISMA checklist. A total of 45 articles met the inclusion criteria.
Results
White matter lesions were most frequently associated with VI. Only 25 studies described lesions within specific structures, mainly in the optic radiations. Only four studies reported on the thalamus. 8.4% of children with CP showed no brain abnormalities on MRI. Diffusion-weighted MRI studies showed that decreased structural connectivity in the optic radiations, superior longitudinal fasciculus, posterior limb of the internal capsule, and occipital lobe is associated with more severe VI.
Conclusions
All types of brain lesions lead to visual dysfunctions, arguing for a comprehensive visual assessment in all children with CP. Whereas white matter damage is a well-known contributor, the exact contribution of specific visual structures requires further investigation, to enable early prediction, detection, and intervention.
... It has been recommended for many years to use MRI when diagnosing CP, even though CP remains a clinical diagnosis and MRI can be normal in a child with CP [3]. A systematic review from 2007 showed that the majority of MRIs gave clues to the pathogenesis of CP [14]. In a previous Australian study of children with CP, MRI patterns varied depending on parity, gestational age, level of neonatal care, Apgar score, and time to established respiration [15]. ...
Background
Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone.
Methods
The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3–11 months) and follow a subset of participants (n = 300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP.
Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method.
Discussion
Early screening for CP is increasingly possible and an interim diagnosis of “high risk of CP” is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis.
Trial registration
ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial.
... A diagnosis of CP is based upon clinical signs of motor disturbances and a history of known risk factors. Neuroimaging is also recommended to identify the brain injury, which is reported to be predictive of CP (3). CP is classified into subtypes based on the dominating motor function disturbances as well as which part of the body is affected, and confirmed at age five years (4). ...
The Norwegian Quality and Surveillance Registry for Cerebral Palsy (NorCP) has systematically collected data on individuals with cerebral palsy (CP) and been a driver of knowledge dissemination for over 20 years. NorCP data have increased the competence of health professionals in both the municipal and specialist healthcare services through publication of multiple scientific articles ranging from risk factors for CP to lifelong interventions, quality improvement projects, and training services. This has led to a streamlined process in the diagnosis and follow-up of children and youths with CP in Norway to ensure that they receive"the right treatment at the right time," regardless of where they live using evidence-based interventions based on needs that are revealed in the registrations.
NORSK SAMMENDRAG Norsk kvalitets- og oppfølgingsregister for cerebral parese (NorCP) har systematisk samlet inn data om personer med cerebral parese og vært en pådriver for kunnskapsformidling i over 20 år. NorCP data har økt kompetansen til helsepersonell i både kommune- og spesialisthelsetjenesten gjennom publisering av flerevitenskapelige artikler om risikofaktorer for CP til livslange intervensjoner, kvalitetsforbedringsprosjekter samt kurs og kompetansetjenester. Dette har ført til økt kvalitet på diagnostisering og oppfølging av barn ogunge med CP i Norge, som sikrer at de får «riktig behandling til rett tid», uansett hvor de bor i landet medbruk av evidensbaserte intervensjoner basert på behov som avdekkes ved registreringene.
... It has been recommended for many years to use MRI when diagnosing CP, even though CP remains a clinical diagnosis and MRI can be normal in a child with CP (3). A systematic review from 2007 showed that the majority of MRIs gave clues to the pathogenesis of CP (14). In a previous Australian study of children with CP, MRI patterns varied depending on parity, gestational age, level of neonatal care, Apgar score, and time to established respiration (15). ...
Background.
Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone.
Methods
The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3-11 months) and follow a subset of participants (n=300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP.
Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method.
Discussion
Early screening for CP is increasingly possible and an interim diagnosis of “high risk of CP” is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis.
Trial registration
ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial.
... suggests that the lesions were most likely caused by acute or chronic hypoxaemia late in pregnancy or at delivery. 12,27,31,32 Taking potential sentinel events into consideration, an overall interpretation of our results could be that an acute hypoxaemic event during delivery was in the causal pathway leading to dyskinetic CP in about 17% of the children. In some of these cases, a sentinel event may have added to already existing brain lesions, such as maldevelopments or white matter lesions. ...
Aim
To study the prevalence, birth, and clinical characteristics of children with dyskinetic cerebral palsy (CP) in Norway compared with spastic quadriplegic CP and other spastic CP subtypes.
Method
Data on children born from 1996 to 2015 were collected from the Norwegian Quality and Surveillance Registry for Cerebral Palsy and the Medical Birth Registry of Norway.
Results
One hundred and seventy (6.8%) children had dyskinetic CP. The birth prevalence decreased during 1996 to 2015 from 0.21 to 0.07 per 1000 livebirths (p < 0.001). Dyskinetic CP was more often associated with term/post‐term birth, and motor and associated impairments were more severe compared with spastic bilateral and unilateral CP, but less severe than spastic quadriplegic CP. On neuroimaging, grey matter injuries were most prevalent in dyskinetic CP (mainly basal ganglia/thalamus) and spastic quadriplegic CP (mainly cortico‐subcortical), white matter injuries in spastic bilateral, and white and grey matter injuries were equally common in spastic unilateral CP. Normal neuroimaging and brain maldevelopment were present in 25% of children with dyskinetic CP.
Interpretation
The decrease in birth prevalence of dyskinetic CP was probably due to improved antenatal and perinatal care. Potential sentinel events at term were more common in dyskinetic CP than other spastic CP subtypes. However, probable antenatal aetiologies were most prevalent. Motor and associated impairments were less severe in children with dyskinetic CP compared with spastic quadriplegic CP.
What this paper adds
Birth prevalence of those with dyskinetic and spastic bilateral cerebral palsy (CP) in Norway decreased between 1996 and 2015.
Potential sentinel events at term were more common in dyskinetic CP.
Nonetheless, probable antenatal aetiologies were most prevalent in dyskinetic CP.
Basal ganglia/thalamus lesions were more common in dyskinetic than spastic quadriplegic CP.
Motor and associated impairments were milder in dyskinetic than spastic quadriplegic CP.
... Brain lesion characteristics such as the lesion type, extent and location and the presence of bilateral lesions could provide additional information to the underlying mechanism of MM occurrence. The type of lesion, related to the timing of the lesion during gestation, can be classi ed into three categories: malformations (1st and 2nd trimesters of pregnancy), periventricular white matter lesion (PV, early 3rd trimester), and cortico-subcortical lesions (CSC, late 3rd trimester and around birth) 15 . Klingels et al (2016) demonstrated that malformations and PV lesions were related to more severe MM in the more-affected hand than other lesion types 6 . ...
Background. Mirror movements (MM) influence bimanual performance in children with unilateral cerebral palsy (uCP). Whilst MM are related to brain lesion characteristics and the corticospinal tract (CST) wiring pattern, the combined impact of these neurological factors remains unknown.
Methods. Forty-nine children with uCP (mean age 10y6mo) performed a repetitive squeezing task to quantify similarity (MM-similarity) and strength (MM-intensity) of the MM activity. We used MRI data to evaluate lesion type (periventricular white matter, N=30; cortico-subcortical, N=19), extent of ipsilesional damage, presence of bilateral lesions, and damage to basal ganglia, thalamus and corpus callosum. The CST wiring was assessed with Transcranial Magnetic Stimulation (17 CSTcontralateral, 16 CSTipsilateral, 16 CSTbilateral). Data was analyzed with regression analyses.
Results. In the more-affected hand, MM-similarity was higher with more damage to the corpus callosum. MM-intensity was higher in children with a CSTcontralateral wiring pattern with damage to the basal ganglia and thalamus. In the less-affected hand, MM-similarity was related with the interaction between lesion type and CST wiring pattern, with higher MM-similarity in children with cortico-subcortical lesions in the CSTcontralateral group. MM-intensity was higher with larger damage to the corpus callosum and unilateral lesions.
Conclusions. A complex combination of neurological factors influences MM characteristics, and the mechanisms differ between hands.
... Dahası, bu tür etkilenime sahip SP popülasyonu genel olarak etkilenmiş taraf üst ekstremitelerinde daha fazla olmak üzere hasarlı vücut taraflarında spastisite, kas kontraktürleri ve kas zayıflıklarını içeren motor bozukluk problemleri de yaşarlar (Baranello et al., 2016;Rose & McGill, 1998). Son olarak, beyinde meydana gelen lezyonun zamanı (doğumdan önce veya doğumdan sonraki erken dönemlerde), yeri, büyüklüğü, yapısal hasarın türü (yani beynin hatalı şekillenmesi, kortikal-subkortikal veya periventriküler lezyonlar) gibi faktörler normal gelişimi ve iyileşmeyi önemli derecede etkiler (Feys et al., 2010;Krägeloh-Mann & Horber, 2007). ...
... Brain lesion characteristics such as the lesion type, extent and location and the presence of bilateral lesions could provide additional information to the underlying mechanism of MM occurrence. The type of lesion, related to the timing of the lesion during gestation, can be classified into three categories: malformations (1st and 2nd trimesters of pregnancy), periventricular white matter lesion (PV, early 3rd trimester), and cortico-subcortical lesions (CSC, late 3rd trimester and around birth) 16 . Klingels et al. 6 demonstrated that malformations and PV lesions were related to more severe MM in the more-affected hand than other lesion types. ...
Mirror movements (MM) influence bimanual performance in children with unilateral cerebral palsy (uCP). Whilst MM are related to brain lesion characteristics and the corticospinal tract (CST) wiring pattern, the combined impact of these neurological factors remains unknown. Forty-nine children with uCP (mean age 10y6mo) performed a repetitive squeezing task to quantify similarity (MM-similarity) and strength (MM-intensity) of the MM activity. We used MRI data to evaluate lesion type (periventricular white matter, N = 30; cortico-subcortical, N = 19), extent of ipsilesional damage, presence of bilateral lesions, and damage to basal ganglia, thalamus and corpus callosum. The CST wiring was assessed with Transcranial Magnetic Stimulation (17 CSTcontralateral, 16 CSTipsilateral, 16 CSTbilateral). Data was analyzed with regression analyses. In the more-affected hand, MM-similarity and intensity were higher with CSTbilateral/ipsilateral. In the less-affected hand, MM-similarity was higher in children with (1) CSTcontra with CSC lesions, (2) CSTbilat/ipsi with PVL lesions and (3) CSTbilat/ipsi with unilateralized lesions. MM-intensity was higher with larger damage to the corpus callosum and unilateral lesions. A complex combination of neurological factors influences MM characteristics, and the mechanisms differ between hands.
... As CP is inherently a heterogeneous disorder, it is possible that differences in the type of insult and resultant structural damage contributed to differences within the somatosensory cortical responses between groups. While prior work has illustrated that some individuals with CP might not display abnormal MRI findings [58,59]. However, there is now a considerable literature showing that there are alterations in cortical volumes and morphometry (which are likely secondary in nature) in children with CP including in those where the predominant pathology appears to be in the white matter [60]. ...
Background
The brain-derived neurotrophic factor (BDNF) protein plays a prominent role in the capacity for neuroplastic change. However, a single nucleotide polymorphism at codon 66 of the BDNF gene results in significant reductions in neuroplastic change. Potentially, this polymorphism also contributes to the weaker somatosensory cortical activity that has been extensively reported in the neuroimaging literature on cerebral palsy (CP).
Aims
The primary objective of this study was to use magnetoencephalography (MEG) to probe if BDNF genotype affects the strength of the somatosensory-evoked cortical activity seen within individuals with CP.
Methods and Procedures
Twenty individuals with CP and eighteen neurotypical controls participated. Standardized low resolution brain electromagnetic tomography (sLORETA) was used to image the somatosensory cortical activity evoked by stimulation of the tibial nerve. BDNF genotypes were determined from saliva samples.
Outcomes and results
The somatosensory cortical activity was weaker in individuals with CP compared to healthy controls (P = 0.04). The individuals with a Val66Met or Met66Met BDNF polymorphism also showed a reduced response compared to the individuals without the polymorphism (P = 0.03), had higher GMFCS levels (P = 0.04), and decreased walking velocity (P = 0.05).
Conclusions and implications
These results convey that BDNF genotype influences the strength of the somatosensory activity and mobility in individuals with CP.
What this paper adds
Previous literature has extensively documented altered sensorimotor cortical activity in individuals with CP, which ultimately contributes to the clinical deficits in sensorimotor processing documented in this population. While some individuals with CP see vast improvements in their sensorimotor functioning following therapeutic intervention, others are clear non-responders. The underlying basis for this discrepancy is not well understood. Our study is the first to identify that a polymorphism at the gene that codes for brain derived neurotrophic factor (BDNF), a protein well-known to be involved in the capacity for neuroplastic change, may influence the altered sensorimotor cortical activity within this population. Potentially, individuals with CP that have a polymorphism at the BDNF gene may reflect those that have difficulties in achieving beneficial outcomes following intervention. Thus, these individuals may require different therapeutic approaches in order to stimulate neuroplastic change and get similar benefits from therapy as their neurotypical peers.
... We used GraphPad Prism version 9.2.0 (GraphPad Software, San Diego, CA, USA, www.graph pad.com) to perform descriptive statistics and Spearman's rank correlation coefficient, r s . We used RStudio version 1. 3 Descriptive statistics were obtained to investigate the percentage distribution of mirror movements. First, we examined the direction of mirror movements (i.e. more affected to less affected) with a Wilcoxon signed-rank test. ...
Aim
We systematically examined the relationship between mirror movements and brain lesion type, corticospinal tract (CST) organization, and hand function to determine the relevance between mirror movements, brain lesion, the CST pattern, and hand function in children with unilateral cerebral palsy (CP).
Method
Forty‐eight children (mean age 9y 9mo [SD 3y 3mo], range 6–18y; 30 males, 18 females) with unilateral CP participated. Mirror movements, brain lesion type, CST pattern identified by transcranial magnetic stimulation, and clinical outcomes were evaluated. Children performed four unilateral tasks: hand opening/closing, finger opposition, individuation, and finger ‘walking’. Mirror movements induced in the contralateral hand were scored using standardized criteria (scores 0–4 using the Woods and Teuber scale).
Results
We found that children with periventricular lesion may have stronger mirror movement scores induced in either hand than those with middle cerebral artery lesion (more affected hand: p=0.02; less affected hand: p<0.01). The highest mirror movement score a child exhibits across the tested tasks (i.e. scores of 3–4 using the Woods and Teuber scoring criteria) may potentially be an indicator of an ipsilateral CST connectivity pattern (p=0.03). Significant correlations were observed between higher mirror movement scores when performing hand opening/closing as well as finger walking and better unimanual dexterity (Spearman's rank correlation coefficient rs=0.44, p=0.002; rs=0.46, p=0.002 respectively).
Interpretation
Brain lesions may be predictive of the strength of mirror movements in either hand in children with unilateral CP. Our findings warrant further studies to extensively investigate the relationship between mirror movements and the underlying brain pathology.
What this paper adds
Brain lesion type may be predictive of mirror movement scores induced in either hand in children with unilateral cerebral palsy.
The highest mirror movement score a child exhibits across the tested tasks may indicate corticospinal tract connectivity pattern in children with unilateral cerebral palsy.
... Most of the subjects in our cohort (43/51, 84%) were born prematurely and 86% were diagnosed with Cerebral Palsy (CP). Moreover, the majority of them showed Periventricular Leukomalacia (PVL), sequelae of Intraventricular Hemorrhage (IVH) or periventricular hemorrhagic infarction in brain MRI (see Table 1 for further details), findings frequently associated with premature birth [31,44]. These data are in accordance with the current literature on CVI causes and associated conditions. ...
Cerebral Visual Impairment (CVI) has become the leading cause of children’s visual impairment in developed countries. Since CVI may negatively affect neuropsychomotor development, an early diagnosis and characterization become fundamental to define effective habilitation approaches. To date, there is a lack of standardized diagnostic methods to assess CVI in children, and the role of visual functions in children’s neuropsychological profiles has been poorly investigated. In the present paper, we aim to describe the clinical and neuropsychological profiles and to investigate the possible effects of visual functions on neuropsychological performance of a cohort of children diagnosed with CVI. Fifty-one children with CVI were included in our retrospective analysis (inclusion criteria: verbal IQ > 70 in Wechsler scales; absence of significant ocular involvement). For each participant, we collected data on neuropsychological assessment (i.e., cognitive, cognitive visual, and learning abilities), basic visual functions (e.g., Best Corrected Visual Acuity—BCVA, contrast sensitivity, and ocular motor abilities) and global development features (e.g., neurological signs and motor development delay) based on standardized tests, according to patients’ ages. The results showed that oculomotor dysfunction involving saccades and smooth pursuit may be a core symptom of CVI and might have a significant impact on cognitive visual and other neuropsychological abilities. Furthermore, visual acuity and contrast sensitivity may influence cognitive, cognitive visual, and academic performances. Our findings suggest the importance of a comprehensive assessment of both visual and neuropsychological functions in children when CVI is suspected, which is needed to provide a more comprehensive functional profile and define the best habilitation strategy to sustain functional vision.
... 6 In this study, the spastic diplegic form of CP is investigated, because it is frequent (29% of all CP's, 7 ) characterized by invalidating locomotor disorders and by a recurrent pattern of brain damage consisting of periventricular white-matter lesions. 8 Studies of locomotion in CP are almost entirely confined to gait. Several classifications of abnormal gait patterns in spastic diplegia are based on lower-limb joint angles on the sagittal plane while the subjects are walking in a straight line. ...
Goal-oriented locomotion (GOL) is a complex task integrating navigation and gait control. To our knowledge, this is the first study of GOL in subjects with Cerebral Palsy (CP). Thirteen subjects with spastic diplegia and 26 with typical development were enrolled in the study. Subjects performed a GOL task to reach luminous targets. Within-subject trajectory variability, maximal head deviation from trajectory and mean head anticipation over trajectory were analyzed. While all subjects showed gait impairment, only 8 of 13 subjects also showed navigation abnormalities as revealed by either: a) abnormal head orientation and trajectory formation, or b) abnormal head orientation with normal trajectory formation. Abnormal gait patterns do not account for and can be distinguished from navigation disorders in spastic diplegic CP. This distinction has important implications for novel rehabilitation methods that should specifically address navigation, not only gait.
... Each child's brain injury was visually classified by experienced pediatric neurologists (PVB and MD) from the 3D-T1 sequence into one of the three categories corresponding to the patterns of brain abnormalities predominantly associated with CP [20,30]. These three categories were: exclusive subcortical lesion (cystic periventricular leukomalacia or periventricular hemorrhagic infarctions), cortico-subcortical lesion (watershed ischemic injury, multicystic encephalomalacia, or stroke) or brain malformation (lissencephaly, pachygyria, polymicrogyria, or schizencephaly). ...
Objective
To develop an electrophysiological marker of proprioceptive spino-cortical tracts integrity based on corticokinematic coherence (CKC) in young children with unilateral cerebral palsy (UCP), in whom behavioral measures are not applicable.
Methods
Electroencephalography (EEG) signals from 12 children with UCP aged 19 to 57 months were recorded using 128-channel EEG caps while their fingers were moved at 2 Hz by an experimenter, in separate sessions for the affected and non-affected hands. The coherence between movement kinematics and EEG signals (i.e., CKC) was computed at the sensor and source (using a realistic head model) levels. Peaks of CKC obtained for the affected and non-affected hands were compared for location and strength. The relation between CKC strength on the lesion-side, the lesion-type (cortico-subcortical vs. subcortical) and the level of manual ability were studied with 2-way repeated-measures ANOVA.
Results
At the individual level, a significant CKC peak at the central area contralateral to the moved hand was found in all young children with their non-affected hand and in 8 out of 12 children with their affected hand. At the group level, CKC to the affected hand movements was weaker than CKC to the non-affected hand movements. This difference was influenced by the type of lesion, the effect being predominant in the subgroup (n = 5) with cortico-subcortical lesions.
Conclusion
CKC is measurable with EEG in young children with UCP and provides electrophysiological evidence for altered proprioceptive spino-cortical tracts on the lesioned brain hemisphere, particularly in children with cortico-subcortical lesions.
The treatment of spasticity is crucial for children whose central nervous systems (CNS) suffered damage at a young age. Spasticity is a disorder that develops because of numerous illnesses and pathophysiology, has a significant influence on patients' everyday lives, and necessitates family care. Discomfort brought on by spasticity feeds a vicious cycle of discomfort that makes the spasticity worse. Due to the fact that spasticity is a secondary pathology resulting from irreparably damaged CNS, treating it can have significant positive effects on children. Over the past ten years, there have been significant improvements in how spasticity is treated. The development of dorsal posterior rhizotomy contributed to the emergence of universal criteria for spasticity care. There does not appear to be a uniform or conventional selection process for patients who would be the best candidates for the treatment, nor is there a set postoperative therapy plan. This article explains how patients are chosen and treated with selective dorsal rhizotomy.
Introduction
Research using animal models suggests that intensive motor skill training in infants under 2 years old with cerebral palsy (CP) may significantly reduce, or even prevent, maladaptive neuroplastic changes following brain injury. However, the effects of such interventions to tentatively prevent secondary neurological damages have never been assessed in infants with CP. This study aims to determine the effect of the baby Hand and Arm Bimanual Intensive Therapy Including Lower Extremities (baby HABIT-ILE) in infants with unilateral CP, compared with a control intervention.
Methods and analysis
This randomised controlled trial will include 48 infants with unilateral CP aged (corrected if preterm) 6–18 months at the first assessment. They will be paired by age and by aetiology of the CP, and randomised into two groups (immediate and delayed). Assessments will be performed at baseline and at 1 month, 3 months and 6 months after baseline. The immediate group will receive 50 hours of baby HABIT-ILE intervention over 2 weeks, between first and second assessment, while the delayed group will continue their usual activities. This last group will receive baby HABIT-ILE intervention after the 3-month assessment. Primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes will include behavioural assessments for gross and fine motricity, visual–cognitive–language abilities as well as MRI and kinematics measures. Moreover, parents will determine and score child-relevant goals and fill out questionnaires of participation, daily activities and mobility.
Ethics and dissemination
Full ethical approval has been obtained by the Comité d’éthique Hospitalo-Facultaire/Université catholique de Louvain , Brussels (2013/01MAR/069 B403201316810g). The recommendations of the ethical board and the Belgian law of 7 May 2004 concerning human experiments will be followed. Parents will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.
Trial registration number
NCT04698395 . Registered on the International Clinical Trials Registry Platform (ICTRP) on 2 December 2020 and NIH Clinical Trials Registry on 6 January 2021. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT04698395?term=bleyenheuft&draw=1&rank=7 .
Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59–0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.
Background and Purpose
To define cystic patterns resulting from term hypoxic ischemic injury (HII) on delayed Magnetic Resonance Imaging (MRI) and determine associated HII patterns and lesions that reflect the severity of injury, from a database of African children with cerebral palsy.
Methods
Retrospective review of 1175 children with cerebral palsy due to term HII diagnosed on late MRI, identifying those with cystic changes. These were classified as multicystic or (multi‐) focal‐cystic, and were evaluated for associated injuries—thalami, basal ganglia, hippocampi, cerebellum, and presence of ulegyria.
Results
Three hundred and eighty‐eight of 1175 (33%) children had cystic encephalomalacia. Two hundred and seven of 388 (53.3%) had focal‐cystic and 181/388 (46.6%) had multicystic injury. The focal‐cystic group comprised 87.9% (182/207) with thalamic injury, 25.6% (53/207) with basal ganglia injury, and 15% (31/207) with cerebellar involvement. Basal‐ganglia‐thalamus (BGT) pattern was present in 43.9% (91/207) and ulegyria in 69.6% (144/207). In the multicystic group, 88.9% (161/181) had thalamic injury, 30.9% (56/181) had basal ganglia injury, and 21% (38/181) had cerebellar involvement. BGT pattern was observed in 29.8% (54/181) and ulegyria in 28.7%. (52/181). Significant associations ( p <.05) were found between multicystic injury and caudate/globus pallidus involvement, and between focal‐cystic pattern of injury and ulegyria.
Conclusions
Cystic encephalomalacia was seen in almost one‐third of patients with term HII imaged with delayed MRI, with a similar prevalence of focal‐cystic and multicystic injury. Multicystic injury was associated with caudate and globus pallidi involvement, typical of the BGT pattern of HII, whereas the focal‐cystic pattern was associated with ulegyria, typical of watershed injury.
Aim
To define the longitudinal trajectory of gastrocnemius muscle growth in 6‐ to 36‐month‐old children with and without spastic cerebral palsy (SCP) and to compare trajectories by levels of gross motor function (Gross Motor Function Classification System, GMFCS) and presumed brain‐lesion timing.
Method
Twenty typically developing children and 24 children with SCP (GMFCS levels I–II/III–IV = 15/9), were included (28/16 females/males; mean age at first scan 15.4 months [standard deviation 4.93, range 6.24–23.8]). Three‐dimensional freehand ultrasound was used to repeatedly assess muscle volume, length, and cross‐sectional area (CSA), resulting in 138 assessments (mean interval 7.9 months). Brain lesion timing was evaluated with magnetic resonance imaging classification. Linear mixed‐effects models defined growth rates, adjusted for GMFCS levels and presumed brain‐lesion timing.
Results
At age 12 months, children with SCP showed smaller morphological muscle size than typically developing children (5.8 mL vs 9.8 mL, p < 0.001), while subsequently no differences in muscle growth were found between children with and without SCP (muscle volume: 0.65 mL/month vs 0.74 mL/month). However, muscle volume and CSA growth rates were lower in children classified in GMFCS levels III and IV than typically developing children and those classified in GMFCS levels I and II, with differences ranging from −56% to −70% (p < 0.001).
Interpretation
Muscle growth is already hampered during infancy in SCP. Muscle size growth further reduces with decreasing functional levels, independently from the brain lesion. Early monitoring of muscle growth combined with early intervention is needed.
In this study, we examined whether epilepsy and drug-resistant epilepsy are associated with neuroimaging findings in children with cerebral palsy (CP).
Magnetic resonance imaging classification system (MRICS) proposed by Surveillance of Cerebral Palsy in Europe (SCPE) was used for classification of different MRI patterns in patients with cerebral palsy. We reviewed the brain MRI scans and medical records of children with CP who were followed-up in our clinic between 2019 and 2023. Patients were divided into three categories: CP without epilepsy, CP with controlled epilepsy and CP with DRE. MRI patterns were grouped as maldevelopments, predominant white matter injury, predominant gray matter injury, miscellaneous (delayed myelination, cerebral atrophy, cerebellar atrophy, brainstem lesions and calcifications, lesions that were not classified under any other group) and normal according to MRICS of the SCPE.
There were 325 CP patients. The most common MRI patterns were predominant white matter injury (47.6%) and gray matter injury (23.8%). There was a 1.5-fold reduction in the risk of epilepsy in patients with predominant white matter injury (OR = 1.54, 95% CI 1.23–1.94). In contrast, children in the miscellaneous group had significantly higher risks of epilepsy (p < 0.001), and we were able to determine that miscellaneous findings increased the risk by 1.8 times (OR = 1.77, 95% CI 1.47–2.12).
In conclusion, more than half of the children with CP had epilepsy, 40.7% of whom had DRE. On MRI, miscellaneous findings may indicate a poor prognosis for epilepsy, while predominant white matter injury may indicate a good outcome. Children with CP, especially those with miscellaneous findings on MRI, should be closely monitored for epilepsy development.
Cerebral palsy (CP), a neuromotor disorder characterized by prenatal brain lesions, leads to white matter alterations and sensorimotor deficits. However, the CP-related diffusion neuroimaging literature lacks rigorous and consensual methodology for preprocessing and analyzing data due to methodological challenges caused by the lesion extent. Advanced methods are available to reconstruct diffusion signals and can update current advances in CP. Our study demonstrates the feasibility of analyzing diffusion CP data using a standardized and open-source pipeline. Eight children with CP (8–12 years old) underwent a single diffusion magnetic resonance imaging (MRI) session on a 3T scanner (PAchieva 3.0T (TX), Philips Healthcare Medical Systems, Best, The Netherlands). Exclusion criteria were contraindication to MRI and claustrophobia. Anatomical and diffusion images were acquired. Data were corrected and analyzed using Tractoflow 2.3.0 version, an open-source and robust tool. The tracts were extracted with customized procedures based on existing atlases and freely accessed standardized libraries (ANTs, Scilpy). DTI, CSD, and NODDI metrics were computed for each tract. Despite lesion heterogeneity and size, we successfully reconstructed major pathways, except for a participant with a larger lesion. Our results highlight the feasibility of identifying and quantifying subtle white matter pathways. Ultimately, this will increase our understanding of the clinical symptoms to provide precision medicine and optimize rehabilitation.
Objective
To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups.
Method
We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger's test were used to investigate potential publication bias.
Results
Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%–41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%–51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%–34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP.
Conclusion
Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367766 , identifier CRD42022367766.
Background
Cerebral palsy is a nosological entity in which genetic diseases and other neurodevelopmental disorders are being included, which, despite presenting motor dysfunction, do not meet the criteria that define cerebral palsy as such. The aim of this study was to verify whether there are differences between cerebral palsy and other disorders or syndromes considered “related to cerebral palsy.”Method79 children with cerebral palsy and 65 children with pathologies apparently similar to cerebral palsy were assessed using the Gross Motor Function Classification System, the Manual Ability Classification System, the Communication Function Classification System, and the Bobath Foundation Scale.ResultsChildren with other pathologies presented higher overall deficit compared to the group with cerebral palsy, as well as greater problems in specific aspects of health, sensory-perception, autonomy, communication, and basic cognitive skills, while no intergroup differences were found with regard to motor functions. It was subsequently explored whether these functions were equally related to the cognitive-social sphere in the two groups, observing a greater relationship in the group with cerebral palsy.Conclusions
Cerebral palsy has a distinctive profile that differentiates it from other neurological disorders and syndromes, thereby questioning the trend to consider genetic and neurodevelopmental pathologies as cerebral palsy. The consequences of a correct diagnosis in the treatment of children have been considered.
Cerebral palsy (CP) consists of permanent disorders of the development of movement and posture that cause activity limitations. The various underlying etiologies for CP can be categorized broadly into prenatal causes, perinatal causes, and postnatal causes. CP is mostly a clinical diagnosis based on a child’s history and physical examination. However, different imaging modalities are now used to evaluate children with CP, including brain ultrasound, computed tomography, and magnetic resonance imaging. This chapter reviews the benefits and disadvantages of the different imaging techniques used to evaluate CP, and discusses in more detail the typical neuroimaging patterns of the different causes of CP.
Background
Public health indicators (PHIs) play an increasingly important role in health policy decision‐making. Although cerebral palsy (CP) is the commonest physical disability in children, its impact at population level has not been systematically measured so far.
Objectives
We aimed to propose six PHIs for CP designed to annually document the extent of CP and effectiveness of perinatal organisation, the burden of this condition, access to health services and preventive health strategies in the post‐neonatal period and to report on the latest updated estimations using population‐based data routinely collected by European CP registries.
Methods
The study included children with CP born between 2002 and 2011. Harmonised data (number of cases, functional profile, imaging) were extracted from the Surveillance of Cerebral Palsy in Europe (SCPE) database. Eligibility criteria for analyses were applied separately for each indicator by selecting registries, birth years and CP cases. Current estimates were based on the last 3 birth years, while trends were reported over a 10‐year period. All analyses were descriptive. Sensitivity analyses were carried out to examine the stability of the results using various thresholds of percentages of missing values.
Results
Analyses were performed on a total of 8621 children with CP from 12 to 17 SCPE registries. A decreasing prevalence of pre/perinatal CP overall, as well as in preterm and full‐term‐born children, was observed. The burden of the condition was strongly dependent on CP subtype and the presence of associated impairments. Access to brain imaging ranged from 80% to 100% depending on registries. The overall prevalence of post‐neonatally acquired CP was approximately 0.8 per 10,000 live births over the study period.
Conclusions
Population‐based CP registries can provide data that are relevant for generating key outcomes of interest at the population level, thus potentially contributing to improving public health policies for children with disabilities.
Due to their early brain lesion, children with unilateral spastic cerebral palsy (USCP) present important changes in brain gray and white matter, often manifested by perturbed sensorimotor functions. We predicted that type and side of the lesion could influence the microstructure of white matter tracts. Using diffusion tensor imaging in 40 children with USCP, we investigated optic radiation (OR) characteristics: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). First, we compared the OR of the lesional and non-lesional hemisphere. Then we evaluated the impact of the brain lesion type (periventricular or cortico-subcortical) and side in the differences observed in the lesional and non-lesional OR. Additionally, we examined the relationship between OR characteristics and performance of a visuospatial attention task. We observed alterations in the OR of children with USCP on the lesional hemisphere compared with the non-lesional hemisphere in the FA, MD and RD. These differences were influenced by the type of lesion and by the side of the lesion. A correlation was also observed between FA, MD and RD and the visuospatial assessment mainly in children with periventricular and right lesions. Our results indicate an important role of the timing and side of the lesion in the resulting features of these children’s OR and probably in the compensation resulting from neuroplastic changes.
La paralysie cérébrale (PC) regroupe un ensemble de troubles sensorimoteurs et est la conséquence d’une lésion cérébrale précoce. La PC de forme unilatérale spastique (PCU) représente 30% des individus avec PC. L’étude des marqueurs de la neuroplasticité pourrait favoriser la validation de thérapies motrices précoces en précisant leurs effets. L’électroencéphalographie (EEG) est utilisée pour investiguer le système cérébral sensorimoteur mais il existe peu d’études chez l’enfant avec PCU, encore moins en EEG haute densité (EEG-hd) qui permet une meilleure résolution spatiale. De plus, ces études se limitent à caractériser les modulations du rythme mu. L’objectif principal de cette thèse est donc de caractériser le fonctionnement du cortex sensorimoteur par EEG-hd chez le jeune enfant avec PCU en développant des paradigmes d’exploration du signal EEG destinés à étudier trois types de signaux électrophysiologiques considérés comme potentiellement intéressants : la cohérence cortico-cinématique (CKC), le rythme mu, et la connectivité fonctionnelle de repos. Dans un premier temps, une revue de la littérature a été effectuée à partir de 16 études observationnelles, et a montré que chez les individus adolescents avec PCU, le rythme mu est retrouvé chez presque tous les participants mais présente des schémas de modulation atypiques. Ensuite, la CKC a été analysée chez 12 enfants d’âge préscolaire avec PCU sur les hémisphères lésés et non lésés. Cette étude a montré que le traitement spino-cortical proprioceptif est altéré dans l'hémisphère lésé, particulièrement chez les enfants présentant des lésions cortico-sous-corticales. Enfin, les résultats préliminaires de la réactivité du rythme mu obtenus chez 7 enfants avec PCU ont montré une désynchronisation qui était supérieure sur l’hémisphère non-lésé dans la plupart des cas, ainsi que la quasi-absence de resynchronisation post-mouvement. En conclusion, le fonctionnement du cortex sensorimoteur peut être étudié précocement en EEG-hd chez l’enfant avec PCU. Des études complémentaires devront préciser la fiabilité test retest de ces signaux chez cette population, ainsi que l’apport de l’étude de la connectivité fonctionnelle de repos.
Cerebral palsy is the most common pediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the current study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed five minutes of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2–4 Hz), theta (5–7 Hz), alpha (8–12 Hz), beta (15–29 Hz), low gamma (30–59 Hz), and high gamma (60–90 Hz) frequency bands were computed. The resulting power spectral density maps were analyzed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma, and high gamma bands across the occipital, frontal, and secondary somatosensory cortical areas (all pFWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (p = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.
MR imaging in the term neonate with Hypoxic Ischaemic Encephalopathy
This is a PhD thesis by publication incorporating 8 previously published papers with a review of the literature and plans for future research
Recent neuroimaging studies allowed us to explore abnormal brain structures and interhemispheric connectivity in children with cerebral palsy (CP). Behavioral researchers have long reported that children with CP exhibit suboptimal performance in different cognitive domains (e.g., receptive and expressive language skills, reading, mental imagery, spatial processing, subitizing, math, and executive functions). However, there has been very limited cross-domain research involving these two areas of scientific inquiry. To stimulate such research, this perspective paper proposes some possible neurological mechanisms involved in the cognitive delays and impairments in children with CP. Additionally, the paper examines the ways motor and sensorimotor experience during the development of these neural substrates could enable more optimal development for children with CP. Understanding these developmental mechanisms could guide more effective interventions to promote the development of both sensorimotor and cognitive skills in children with CP.
The neurologic causes of foot and leg dysfunction are reviewed. Disorders causing foot and ankle pain, weakness, or other sensorimotor disturbances often cause difficulty with ambulation and prompt patients to seek medical evaluation. Physical signs and symptoms along with targeted diagnostic testing are needed to come to the correct diagnosis and treatment plan. An overview of peripheral nerve, muscle, and central nervous system disorders affecting the foot and leg are discussed.
Because of the availability of new knowledge about the neurobiology of developmental brain injury, information that epidemiology and modern brain imaging is providing, the availability of more precise measuring instruments of patient performance, and the increase in studies evaluating the efficacy of therapy for the consequences of injury, the need for reconsideration of the definition and classification of cerebral palsy (CP) has become evident. Pertinent material was reviewed at an international symposium participated in by selected leaders in the preclinical and clinical sciences. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, and health officials, and provide a common language for improved communication. With leadership and direction from an Executive Committee, panels utilized this information and have generated a revised Definition and Classification of Cerebral Palsy. The Executive Committee presents this revision and welcomes substantive comments about it.
To define neonatal pial middle cerebral artery infarction.
A retrospective study was made of neonates in whom focal arterial infarction had been detected ultrasonographically. A detailed study was made of cortical middle cerebral artery infarction subtypes.
Forty infarctions, with the exception of those in a posterior cerebral artery, were detected ultrasonographically over a period of 10 years. Most were confirmed by computed tomography or magnetic resonance imaging. Factor V Leiden heterozygosity was documented in three. The onset was probably antepartum in three, and associated with fetal distress before labour in one. There were 19 cases of cortical middle cerebral artery stroke. The truncal type (n=13) was more common than complete (n = 5) middle cerebral artery infarction. Of six infarcts in the anterior trunk, four were in term infants and five affected the right hemisphere. Clinical seizures were part of the anterior truncal presentation in three. One of these infants, with involvement of the primary motor area, developed a severe motor hemisyndrome. The Bayley Mental Developmental Index was above 80 in all of three infants tested with anterior truncal infarction. Of seven patients with posterior truncal infarction, six were at or near term. Six of these lesions were left sided. Clinical seizures were observed in three. A mild motor hemisyndrome developed in at least three of these infants due to involvement of parieto-temporal non-primary cortex.
Inability to differentiate between truncal and complete middle cerebral artery stroke is one of the explanations for the reported different outcomes. Severe motor hemisyndrome can be predicted from neonatal ultrasonography on the basis of primary motor cortex involvement. Clinical seizures were recognised in less than half of the patients with truncal infarction; left sided presentation was present in the posterior, but not the anterior truncal type of infarction. Asphyxia is a rare cause of focal arterial infarction.
It is not clear whether intrapartum asphyxia is an important factor in neonatal encephalopathy and seizures in term infants. Antenatal factors have been implicated, but there is no firm evidence that brain damage occurs in utero. This study examined the proposal that neonatal encephalopathy and early postnatal seizures, or both, are sequelae of early adverse antenatal events. Cerebral magnetic resonance imaging (MRI) or autopsy was carried out in 351 full-term infants having encephalopathy and/or seizures within 72 hours of birth. Infants with major congenital malformations or known chromosomal disorders were excluded. The 261 infants placed in group 1 had a diagnosis of neonatal encephalopathy, with or without seizures, as well as evidence of perinatal asphyxia. The 90 group 2 infants presented with seizures but failed to meet diagnostic criteria for encephalopathy. Cerebral MRI disclosed evidence of acutely evolving lesions not related to established injury or atrophy in 80% of group 1 infants. These lesions, which usually were bilateral, were consistent with a hypoxic-ischemic insult. In addition to white matter, abnormalities were found in the basal ganglia, thalamus, or cortex. Only 2 group 1 infants, fewer than 1% of the total, had evidence of established injury. Three of 21 autopsies showed, in addition to an acutely evolving lesion, very small foci of established gliosis in the periventricular white matter. Acute ischemic or hemorrhagic lesions were found in 69% of group 2 infants. Two infants (3%) had, in addition, changes of antenatal injury. Thirteen of the 28 remaining group 2 infants had MRI findings of a specific nonhyoxic-ischemic condition. The other 15 infants had normal scans. Seven of 10 infants with no specific diagnosis continued to have seizures. Antenatal risk factors that were significantly more frequent in infants having apparent antenatal lesion or disorders of genetic or neurometabolic origin included a family history of seizures or neurologic disorder, low birth weight, head circumference below the 10th percentile, and low maternal age. In this study, more than 90% of term infants with neonatal encephalopathy and/or early seizures had evidence of a perinatally acquired insult. Established brain injuries acquired before birth were quite infrequent. The findings do not rule out the change that antenatal (or genetic) factors could predispose some infants to perinatal brain injury.
Although cerebral palsy (CP) is the most common cause of motor deficiency in young children, it occurs in only a to 3 per 1000 live births. In order to monitor prevalence rates, especially within subgroups (birthweight, clinical type), it is necessary to study large populations. A network of GP surveys and registers was formed in 14 centres in eight countries across Europe. Differences in prevalence rates of GP in the centres prior to any work on harmonization of data are reported. The subsequent process to standardize the definition of CP, inclusion/exclusion criteria, classification, and description of children with CP is outlined. The consensus that was reached on these issues will make it possible to monitor trends in CP rate, to provide a framework for collaborative research, and a basis for services planning among European countries.
Information on the long-term development of larger series of children with non-progressive congenital ataxia (NPCA) is scarce. We have updated a personal cohort of subjects previously diagnosed as having NPCA. Children with brain malformations, acquired neurological illness, or defined syndromes were excluded. From 58 subjects, 34 were available for review (including three pairs of siblings). All our subjects had delayed motor and speech development. Truncal ataxia persisted but became less significant. Two subjects developed spasticity and three a focal dystonia. Epilepsy was a feature in 10 of the subjects. Cognitive impairment was present in 22 of 34 subjects. MRI was normal in 15 of 27. There were no obvious correlations between degree of motor delay, severity of ataxia, cognitive impairment, and neuroimaging. Although genetically and clinically not a homogeneous entity, NPCA is a helpful diagnostic label. Major problems arise in the majority of subjects related to cognitive impairment and less to neurological symptoms. Early individual prognosis is not possible from early developmental milestones', neurological signs, or neuroimaging.
Summary The Cerebral Palsy Register in eastern Denmark has collected cases using a uniform data sampling procedure since birth year 1979. We have investigated changes in the rate of cerebral palsy, related to gestational age, mortality and perinatal risk factors in children born 1983–90. The total cerebral palsy birth prevalence decreased from 3.0 in the birth year period 1983–86 to 2.4 per 1000 live births (P P P P Document Type: Research Article DOI: http://dx.doi.org/10.1046/j.1365-3016.2001.00354.x Affiliations: Department of Neonatology, The Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital, Denmark Publication date: July 1, 2001 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher In this Subject: Pediatrics , Public Health By this author: Topp, Monica ; Uldall, Peter ; Greisen, Gorm GA_googleFillSlot("Horizontal_banner_bottom");
Hypoxic ischemia is a common cause of damage to the fetal and neonatal brain. Although systemic and cerebrovascular physiologic factors play an important role in the initial phases of hypoxic-ischemic injuries, the intrinsic vulnerability of specific cell types and systems in the developing brain may be more important in determining the final pattern of damage and functional disability. Excitotoxicity, a term applied to the death of neurons and certain other cells caused by overstimulation of excitatory, mainly glutamate, neurotransmitter receptors, plays a critical role in these processes. Selected neuronal circuits as well as certain populations of glia such as immature periventricular oligodendroglia may die from excitotoxicity triggered by hypoxic ischemia. These patterns of neuropathologic vulnerability are associated with clinical syndromes of neurologic disability such as the extrapyramidal and spastic diplegia forms of cerebral palsy. The cascade of biochemical and histopathologic events triggered by hypoxic ischemia can extend for days to weeks after the insult is triggered, creating the potential for therapeutic interventions.Abbreviations: Ca2+, calcium; FD-glucose, fluorodeoxyglucose; HIE, hypoxic-ischemic encephalopathy; MR, magnetic resonance; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NMDA, N-methyl-d-aspartate a subtype of glutamate receptor; PET, positron emission tomography
Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal–fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1β, IL-6, IL-9, or tumor necrosis factor-α developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9–overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP. Ann Neurol 2000; 47:54–63
Twenty-seven MRI examinations from 17 children (7 females, 10 males) with bilateral lesions of the basal ganglia and thalamus, presenting over a period of 8 years, were reevaluated, and correlated with the type of cerebral palsy (CP) as well as motor and cognitive impairment. Children were between 1 year 6 months and 17 years old at last examination (mean 5 years 9 months). Brain damage had occurred as a consequence of birth asphyxia in nine patients and of neonatal shock in four patients. No adverse event could be identified in four children. In these, late prenatal compromise is assumed, as extensive screening (including MR spectroscopy in two patients) did not yield an underlying metabolic disorder. Three different degrees of MRI lesion patterns could be defined: a mild pattern (involvement of nucleus lentiformis and ventro-lateral thalamus only; n=7), an intermediate pattern (involvement of nucleus lentiformis, ventro-lateral thalamus, and pericentral region; n=3), and a severe pattern (involvement of nucleus lentiformis, entire thalamus, pericentral region, and hippocampus; n=7). This grading of MRI findings correlated significantly with the severity of both cognitive and motor impairment and type of CP. Normal cognitive development and mild motor delay was only seen with the mild pattern. All children developed CP: purely dyskinetic CP was only seen with the mild pattern, whereas the dyskinetic-spastic or spastic CP types could be seen in all three lesion patterns, with dyskinetic-spastic CP more related to the moderate, and purely spastic CP more related to the severe pattern.
Magnetic resonance imaging (MRI) findings for 34 children with spastic diplegia, examined between two and 10 years of age, were analysed. Dilatation of the trigone, atrophy of the peritrigonal white matter and prominent deep cortical sulci were seen. On T2‐weighted images, periventricular high‐intensity areas in the white matter adjacent to the trigones and bodies of the lateral ventricles were seen in many children. These MRI features may reflect the pathological changes of periventricular leukomalacia in children with spastic diplegia. Among the MRI findings, only the amount of white matter correlated with severity of disability: white matter reduction corresponded to the more severe motor disabilities.
RÉSUMÉ
Imagerie de résonance magnétique chez les enfants présentant une diplégie spastique: corrélation avec la gravité des anomalies mentales et motrices
Les données de l'imagerie de résonance magnétique (I.R.M.) chez 34 enfants atteints de diplégie spastique, examinés entre deux et dix ans d'ǎge, ont été analysées. La dilatation du trigone, l'atrophie de la substance blanche péritrigonale et des sillons corticaux saillants et profonds ont été observées. Sur les images de valeur T 2 , des aires périventricularies à forte densité dans la substance blanche voisine des trigones et des noyaux des ventricules latéraux ont été observées chez de nombreux enfants. Ces données I.R.M. peuvent traduire les modifications pathologiques de la leucomalacie périventriculaire chez les enfants atteints de diplégie spastique. Parmi les données I.R.M., seule la quantité de substance blanche était corrélée avec la gravité des incapacités: une réduction de la substance blanche correspondait aux plus graves des incapacités.
ZUSAMMENFASSUNG
MRI bei Kindern mit spastischer Diplegie: Gibt es eine Korrelation zur Schwere der motorischen und geistigen Behinderung?
Von 34 Kindern mit spastischer Diplegie, die mit zwei bis 10 Jahren untersucht worden waren, wurden die MRI Befunde analysiert. Man fand Trigonurndilatation, Atrophie der peritrigonalen weißen Substanz und sehr tiefe kortikale Sulci. Auf den T 2 ‐weighted images fanden sich bei vielen Kindern periventrikuläre Verdichtungszonen in der weißen Substanz, angrenzend an die Trigoni und die Seitenventrikel. Diese MRI Befunde spiegeln vielleicht die pathologischen Veränderungen der periventrikulären Leukomalazie bei Kindern mit spastischer Diplegie wider. Von den MRI Befunden korrelierte nur die Stärke der weißen Substanz mit der Schwere der Behinderung: eine Verminderung der weißen Substanz korrespondierte mit schweren motorischen Behinderungen.
RESUMEN
Imagen de Resonancia Magnética en niños con diplejia espástica: correlación con la gravedad de la anomalia motora y mental
Se analizaron los hallazgos de las Imágenes por Resonancia Magnetica (IRM) en 34 niños con diplegia espástica examinados entre dos y 10 años de edad. Se observaron dilataciones del trígono, atrofia de la substancia blanca peritrigonal y unos surcos corticales muy marcados. En las imágenes T 2 , en muchos niños se observaron areas periventriculares de alta densidad en la substancia blanca adyacente a los trígonos y a los cuerpos de los ventrículos cerebrales. Estas características de las IRM pueden reflejar los cambios patológicos de una leucomalacia periventricular en niños con diplejia espãstica. Entre los hallazgos de la IRM, solo la cantidad de substancia blanca estaba en correlación con la gravedad de la discapacidad: la reducción en la substancia blanca correspondia a unas alteraciones motoras más graves.
The authors report on the clinical examination and magnetic resonance imaging (MRI) of 41 children (29 term and 12 preterm) whose diagnosis of congenïtal hemiparesis was confirmed after the first year of life. Periventricular leukomalacia was the most predominant MRI finding (found in 15 term and eight preterm infants). The uniform pattern of lesions observed through MRI (without clear correlation with gestational age) suggests a common aetiopathogenesis in this subgroup. Comparison of these MR images with the periventricular leukomalacia observed in preterm children with spastic diplegia supports the thesis that ischaemia occurring between the 28th and 35th weeks of gestation could be the main cause.
RÉSUMÉ
Hémiparésie congénitale et leucomalacie périventricular: aspects pathogéniques à partir d'IRM Les auteurs rendent compte de l'examen clinique et des données IRM chez 41 enfants (29 nés a terme et 12 prématurés) chez qui un diagnostic d'hémiparésie congénitale avait été confirmé aprés l'àge d'un an. I.a leucomalacie périventriculaire avait été la donnée IRM la plus habituelle (trouvée chez 15 sujets nés a terme et huit prématurés). La distribution uniforme des lésions observées à l'IRM (sans corrélation évidente avec l'âge de gestation à la naissance) suggère une étiopathogcnie commune à ce sous‐groupe. La comparaison de ces IRM avec la leucomalacie périventriculaire observée chez les prematurés porteurs d'une diplegie spastique, est en faveur de la thése selon laquelle une ischémic sutvenam entre la 28éme et la 35cme semaine de gestation pourrait être la cause principale.
ZUSAMMENFASSUNG
Congenitale Hemiparese und periventrikuläre Leukomalazie: pathogenetische Aspekte der Kernspin‐Unlersuchung
Die Autoren berichten über klinische Untersuchungen und Kernspin (MR1) Befunde, bei 41 Kindern (29 reif‐ und 12 frühgeborene Kinder), bei denen die Diagnose der congenitalen Hemiparese nach dem ersten Lebensjahr bestätigt wurde. Der wichtigste MRI Befund war die periventrikuläre Leukomalazie (bei 15 reif‐ und acht frühgeborenen Kindern nachgewiesen). Das übereinstimmende Bild der Läsionen im MRI (ohne eindcutige Korrelation zum Gestationsalter) läßit eine gemeinsame Aetiopathogenese bei dieser Untergruppe vermuten. Der Vergleich dieser MRI Befunde mit der periventrikulären Leukomalazie bei Fruhgeborenen mit spastischer Diplegie spricht für die Hypothese, daß eine Ischämie in der Zeit von der 28. bis 35. Gestationswoche die Hauptursache sein könnte.
RESUMEN
Hemiparesia congenita y leucomalacia peri‐ventricular: aspectos patogénicos a partir de la IRM Los autores aportan los datos clinicos y de IRM dc 41 niños (29 a término y 12 pretérmino), en los que el diagnóstico de hemiparesia congénita fue confirmada después del primer año de vida. La leucomalacia periventricular era el hallaz. go por IRM mas predominante (fue confirmado en 15 a término y en ocho pretérmino). El partón uniforme de las lesiones observadas por la IRM (sin una clara correlación con la edad gestacional) sugiere que hay una etiopatogenia comiin en estc subgroupo. La comparación de estas imagenes por RM con la leucomalacia observada en niños pretermino con diplegia espástica, apoya la tesis de que la isquemia que tiene lugar entre las semanas 28 y 35 de gestateón puede ser la causa principal.
Eighteen children (eleven preterm birth and seven term birth) with clinical evidence of spastic diplegia (SD) were studied to clarify the differences of the lesions between preterm and term SD on MR imaging. All with preterm birth showed similar abnormalities of the periventricular white matter represented by high intensity in T2-weighted imaging and low intensity in T1 imaging. It seemed that the lesions were periventricular leukomalacia (PVL) and dysmyelination pathologically and correlated well clinically with spastic diplegia. SD with term birth group showed various lesions, two brain anomalies (schizencephaly and corpocephaly), one PVL, four showed no lesions. We suggested that SD with preterm birth is not only a clinical but also a pathological entity.
Half of the most severe cases of cerebral palsy (CP) survive to adulthood, but because this longevity is relatively recent, there is no empirical experience of their life expectancy past middle age. The last 2 decades have seen significant developments in the management of persons with CP, involving specialist services from an increasing number of disciplines that require coordination to maximize their effectiveness. This article provides an overview of CP. The author discusses definitions of CP, its epidemiology, pathologies, and range of possible clinical descriptions, and briefly touches on management and prevention.
Following agreement on definitions and classification, a central database was set up to include information on over 6000 children with cerebral palsy (CP) from 13 geographically defined populations in Europe. The overall rate for the period 1980 to 1990 was 2.08/1000 live births (95% CI 2.02 to 2.14). One in five children with CP (20.2%) was found to have a severe intellectual deficit and was unable to walk. Among babies born weighing less than 1500g, the rate of CP was more than 70 times higher compared with those weighing 2500g or more at birth. The rate of CP rose during the 1970s, but remained constant during the late 1980s. Future analyses will include data from children born in the 1990s. This collaborative work provides a powerful means of monitoring trends in birthweight-specific rates of CP and an infrastructure for research and service planning.
We used MR to retrospectively analyze the brains of patients suffering from cerebral palsy, our aim being to determine MR's role in the assessment of brain damage and the relationship of pre-, peri-, and post-natal events to cerebral palsy.
Forty patients (aged 1 month to 41 years) underwent MR scanning and findings were correlated with clinical histories in all cases.
Review of MR scans of 11 patients who had been born prematurely revealed findings of periventricular white matter damage, indicative of hypoxic-ischemic brain injury (82%), the chronology of which was difficult to determine. Among 29 patients who had been born at term, three major patterns emerged: (1), gyral anomalies, suggestive of polymicrogyria, consistent with mid-second trimester injury; (2), isolated periventricular leukomalacia reflecting late second- or early third-trimester injury; and (3), watershed cortical or deep gray nuclear damage, consistent with late third-trimester, perinatal or postnatal injury. In 16 (55%) of 29 patients born at term, MR findings of intrauterine brain damage were observed; in over half of these cases MR revealed developmental anomalies, which is nearly twice the rate reported in prior studies employing CT.
Our results support a growing consensus that cerebral palsy in term infants is often the result of prenatal factors, and less commonly related to the perinatal period.
The magnetic resonance findings in 22 children with athetotic cerebral palsy were studied. Sixteen had perinatal asphyxia, two had neonatal jaundice, and four had no association with predisposing conditions. In six of the children, symmetrical high intensity areas were found in both the thalamus and putamen in T2-weighted images. In five children they were seen only in the thalamus, and in another one only in the putamen. In six children, symmetrical periventricular high intensity areas were seen. In seven of the subjects, no abnormal magnetic resonance findings were seen. Magnetic resonance lesions, possibly caused by asphyxia, were found in the basal ganglia, thalamus and/or cerebral white matter in 14 of 16 children. Three children with lesions only in the cerebral white matter had mild motor abnormality, and six children with lesions in both the thalamus and putamen did not have mild abnormality.
One hundred neonates determined prospectively to be at risk for neurologic handicap underwent magnetic resonance imaging with a high-field (1.5 T) imager. Thirty-three demonstrated a total of 37 lesions consistent with hypoxic-ischemic encephalopathy, including periventricular leukomalacia (n = 12), basal ganglia hemorrhage (n = 5), multicystic encephalomalacia (n = 5), and focal parenchymal hemorrhage (n = 15). Diagnoses by ultrasonography and computed tomography were compared with those by magnetic resonance imaging in 29 and 17 infants, respectively. Ultrasonography agreed more frequently with magnetic resonance imaging than did computed tomography. Ultrasonography detected 79% of lesions demonstrated by magnetic resonance imaging whereas computed tomography detected only 41%. Periventricular leukomalacia was seen most often in preterm infants, basal ganglia hemorrhage and multicystic encephalomalacia primarily occurred in term infants, and focal parenchymal hemorrhage occurred at all gestational ages. Basal ganglia hemorrhage and multicystic encephalomalacia were strongly associated with histories of perinatal asphyxia, seizures, and early abnormal neurological status. All infants with basal ganglia hemorrhage (5/5) and multicystic encephalomalacia (5/5) and the majority with periventricular leukomalacia (9/12) and focal parenchymal hemorrhages (9/15) had developmental abnormalities at discharge.
The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project.
Eighteen children (eleven preterm birth and seven term birth) with clinical evidence of spastic diplegia (SD) were studied to clarify the differences of the lesions between preterm and term SD on MR imaging. All with preterm birth showed similar abnormalities of the periventricular white matter represented by high intensity in T2-weighted imaging and low intensity in T1 imaging. It seemed that the lesions were periventricular leukomalacia (PVL) and dysmyelination pathologically and correlated well clinically with spastic diplegia. SD with term birth group showed various lesions, two brain anomalies (schizencephaly and corpocephaly), one PVL, four showed no lesions. We suggested that SD with preterm birth is not only a clinical but also a pathological entity.
Improvements in combining obstetrics and neonatology led to a trend to intervene earlier in premature babies born before the 33rd week of gestational age. The enquiry that was carried out in 1985 in the Paris geographical region had as its objective to assess on the one part how many premature deliveries occurred between the 25th and 33rd week of amenorrhea and on the other hand what happened in the short term to the infants born from these pregnancies, i.e., their mortality; and for those who survived, their quality of life. The study was carried out on a representative sample of the deliveries in 1985 in the four departments of the Paris region--Paris and the three departments of the Petite Couronne--where half of all deliveries were assessed. The enquiry covered 53,430 deliveries for which the overall prematurity rate was 4.5%, and those deliveries that occurred before 33 weeks of gestational age constituted 1.0% (539 babies). Twenty children were lost for follow-up after a year. This was 4.9% of the live births and 6.3% of the live children who left the neonatology centres. At 2 years of age, the numbers that were not followed up were eventually 24, which was 5.8% of live births and 7.6% of those that left the centres of neonatology. The results show a very high rate of antepartum mortality but also of mortality during and after labour. Only 379 infants out of the 539 (70%) were transferred into special care baby units. By 1 year of age, the survivors were 57% of the total number of deliveries and 75% of the live births and 82% of those transferred to the special units. As far as concerned those that were live born, the survival rate at the age of 1 year varied considerably according to the duration of the pregnancy. The number of those that survived a pregnancy of less than 27 weeks was low (31%). It was, at 28 weeks, 53%. This is the age where births have to be registered. It reached 87% of the live births that occurred at 32 weeks. One has to point out that there is no statistically significant difference between 27 and 28 weeks of gestation. Whereas there is a significant difference (p less than 0.05) with those delivered at 29 weeks (75%). 80% of those 291 infants that were examined at 1 year of age were considered to be normal as far as psychomotor and sensorial behaviour was concerned.(ABSTRACT TRUNCATED AT 400 WORDS)
Cerebral arterial infarction is a more common cause of neonatal seizures than has been previously appreciated. In 50 full-term newborns with seizures studied, 7 had cerebral infarction which was the second most common definable cause of seizures. We describe these 7 full-term infants with cerebrovascular accidents who presented with focal or generalized seizures. Obstetrical histories were normal in 5 of these patients. Their neurological examinations demonstrated lethargy and generalized hypotonia. Electroencephalograms demonstrated focal abnormalities in 4 infants. Computed tomographic scans in the first week of life showed infarctions in 6 newborns and in another at age 6 months. Neonatal stroke should be considered as a cause of seizures in a full-term newborn in spite of a normal obstetrical history and a nonfocal neurological examination.
Cranial magnetic resonance imaging (MRI) was performed prospectively in 45 children (ages 3-27 months) with clinically documented motor delay to evaluate the ability of MRI to determine etiologic factors, to determine whether myelination correlated with motor delay, and whether the clinical category corresponded with the imaging findings. Of the 22 children diagnosed clinically as having major motor delay (i.e., cerebral palsy), 77% had magnetic resonance imaging abnormalities. In 23%, etiologic associations were established from MRI alone and in 32% a clinically suspected etiology was supported. No children had myelination delay as the sole abnormality. In 23 children with minor motor delay, only 17% had abnormal scans. Clearly, MRI provided useful information in the majority of children with cerebral palsy; therefore, a classification system is proposed in which MRI can be used in conjunction with clinical assessment to specify more precisely the etiologic factors in cerebral palsy.
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.
RÉSUMÉ
Quand les anomalies cérébrates de l'IMC survienncnt‐elles? Etude des IRM de 70 patients Les auteurs ont utilisé l'IRM pour analyser rétrospectivement les images cérébrales d' IMC, pour apprécier dans la genése, les anomalies et lésions cérébrales, et la relation avec des événcments pré‐, péri‐ et post nataux sur l' IMC 70 LM.C âgés de deux à 16 ans ayant bénéficié d' une IRM furent répartis en cjuatre groupes: le groupe 1 (26 patients) comprenait des sujels dont l' IMC était considéréé comme causée par un trouble de la migration neuronale durant le développcment embryologique; le groupe 2 (30 patients) comprenait des sujets chez qui était invoqué un trouble vasculaire; dans le groupe 3 (cinq patients), la cause était une infection intra‐utérine et une LM.C. manifestement atlribuable à une asphyxie à la naissance (groupe 4) ne Cut observée que pour neuf patients. Ces résultats indiquent que l'IMC d'enfants nés à terme est souvent le résultat de facteurs prénalaux, et leurs IRM indiquent alors un trouble de migration ou un infarctus cérébral. l' IRM est un examen essentiel pour identifier les facteurs causant le dommage cérábral dans l' IMC
ZUSAMMENFASSUNG
Wann treten llirnanomalicn bei Cerebralparese auf? Eine MRI sludie bei 70 Patienlen
Die Autoren haben retrospektiv die MRI Aufnahmcn von Patienten mil Cerebralparese (CP) analysicrt, urn ihre Bedeutung für die Beurteilung von Hirnänonialien und ‐verletzungen, sowie die Relatiun von prä‐ peri‐ und postnatalen Eintlüssen auf die CP zu untersuchen. 70 Patienten mit Cerebralparese. im Alter von zwei bis 16 Jahren, bei denen ein MRI gemacht worden war, wurden in vier Gruppen eingeteilt: Gruppe 1 unifaßte 26 Putienien, deren CP durch neuronale Migrationsstörungen im Umbryonalstadium bedingt war: Gruppe 2 hatte 30 Patienten, bei denen die Ur. sache für die CP Gefäßerkrankungen waren; Gruppe 3 umfaßte fünf Patienten, bei denen eine intrauterine Infektion vorlag; und in der Gruppe 4 waren neun Patienten. deren CP eindeutig auf eine Geburtsasphyxie zurückzuführen war. Die Hrgcbnissc zeigen, daß CP bei reifen Neugeborenen oft durch pränatule Faktoren bedingt ist und auf thren MRI Aufnahmen fanden sich Migration und Hirninfarkt. Das MRI des Gehirns ist eine wesentliche Untersuchung zur Differenzierung der Ursachen von Himschädigungen bei CP.
RESUMEN
Cuandu tienen lunar las anomalias cerebrates en la pardslisis cerebral? Estudio can IRM del cerebro de 70 pacientes
Los autores usaron la IRM para analizar restrospectivamente las imágenes cerebrates de pacientes con parálisis cerebral (PC) para evaluar su papel en la evaluación de las anomalías y lesiones cerebrales y las rclaciones de los acontccimientos pre‐ peri‐ y postnatales con la PC. 70 pacientes con PC de dos a 16 años de edad examinados con IRM, se dividieron en cuatro grupos: grupo 1 (25 pacientes), comprendió los sujetos cuya PC se consideró debida a alteraciones de la migración cerebral en el estadio embrionario; grupo 2 (30 pacientes), con sujetos cuya causa era vascular; grupo 3 (cinco) cuya causa era una infección intrauterina; y un grupo 4 en que la PC era claramente atribuible a una usfixia del parto (sólo en 9 casos). Los resultados indican que la PC en lactantcs a término es a menudo el resultado de factores prenatales y los hallazgos en sus IRM indican alteraciones en la migración e infarto cerebral. La IRM cerebral es una exploración esencial para identificar los factores causantes de una alteraeión cerebral.
MRI of the brain was performed on 56 children with bilateral spastic cerebral palsy (CP) at a mean age of 10.7 years. Specific pathology was found in 91 per cent; periventricular leukomalacia was present in 42 per cent of term‐ and H7 per cent of preterm‐born children. Parasagittal subeortico‐cortical injury, multicystie encephalomalacia and basal ganglia lesions were identified in 16 per cent, in all but one associated with severe peri‐/neonatal events at term or near term. Maldevelopment composed 9 per cent, all but one found in term‐born children. MRI morphology correlated strikingly with outcome. Periventricular leukomalacia was associated with more severe disability in term‐ than preterm‐born children.
RÉSUMÉ
Une forme spasticpie bilatérale: pathologic IRM el olivine. Analyse d' une série représentative de 56 cas
Une IRM du ccrveau a été effectuée chez 56 enfants IMC présentant une forme spastique bilatérale, á l'àge moyen de 10.7 ans. Une imagerie pathologique spécifique fut observée dans 91 pour cent des cas; une leucomalacie était présente chez 42 pour cent des enfants nés à terme et 87 pour cent des enfants nés prémalurément. Une lésion parasagittal sous‐cortico‐corticale. une encéphalomalacie multicystique el des lésions des noyaux gris furent identifyées dans 16 pour cent des cas, associées dans tous les cas sauf un, à des événements graves péri‐néonataux à terme ou près du term. Un mauvais développement fut trouvé dans neuf pour cent des cas. toujours sauf une fois, chez des enfants nés à terme. La morphologic IRM était corrélée de façon frappante avec le devenir. La leucomalacie périventriculairc était associée à une incapacité plus sévère chez. les enfants nés à terme, que chez les prématurés.
ZUSAMMENFASSUNG
Bilaterale spastischc Cercbralparvse: pathologische MRl‐Befunde und tlcrcn Ursachc. Analyse einer repräsenlativen Uniersuchungsreihe von 56 Fällen
Bei 56 Kinderen mit bilateraler spastischer Cerebralparese (CP) wurde im mittleren Alter von 10.7 Jahren ein MRI des Gehirns gemacht. 91 Prozent wiesen cine spezifische Pathologie auf; 42 Prozent der rcitgeborcnen Kinder und 87 Prozent der Frühgehorenen hatten eine periventrikuläre Leukomalazie. Parasagittal subcortico‐corticale Schädigungen, multizystische Enzephalomalazie und Läsionen der Basalganglien wurden bei 16 Prozent nachgewiesen und waren bei alien außer einem Patienten mit schweren peri‐ und/oder neonatalen Störungen in Verbindung zu bringen. Eine Fehlentwicklung fand sich in neun Prozent der Fälle. die alle außer einem zum Termin geboren worden waren. Die MRI‐Befunde korrelierten auffallend mit dem Outcome. Die periventrikuläre Leukumaiazic war bei den reifgeborenen Kindern mit schwcroren Behinderungen verbunden als bei den Frühgeborenen.
RESUMEN
Parálisis cerebral espástica bilateral: palologia IRM y arisen. Aná lists de una serie reprcsentativa de 56 casos
Se realizó una IRM cerebral en 56 niños con parálisis cerebral espastica bilateral (PC) con una edad de promedio de 10.7 años. Fn el 91 por ciento de los casos se halló una patología especifíca; la leucomalacia periventricular estaba presente en el 42 por ciento de los casos a término y en el 87 por ciento de los pretermino. En el 16 por ciento se identificó una lesión parasagital subcorticocortical. encefalomalacia multiquistica y lesiones en los ganglios basales, asociados en todos los casos menos uno con graves acontecimientos peri‐neonalales al término o cerca de él. Las alteraeiones de dcsarrollo comprendieron el 9 por ciento, todos los casos exeepto uno en niños a término. La morfología de la IRM se correlacionaba notableiuente con el curso. La leucomalacia periventricular estaba asociada a una mayor incapacidad en los niños a término, que en los pretérmino.
We have analyzed the MRI findings from the brains of 33 children with congenital hemiplegia. Referral of these children to our hospital was either because of neurological problems or a history of complicated birth. According to maturation-dependent pathophysiological mechanisms we have classified the lesions into the following five groups: 1. malformations/prenatal encephalo-clastic lesions, 2. periventricular leukomalacia or atrophy, 3. diencephalic lesions, 4. subcortical and cortical lesions, and 5. normal findings. Combination of lesions was not uncommon. The neuroradiologically most prominent and most expanded lesions determined the classification to the different groups. We detected malformations/encephalo-clastic lesions (Group 1) in 5 children; one of these children also presented additional lesions of Groups 2 and 3. Six children displayed periventricular leukomalacia (Group 2), and in one child in combination with diencephalic and subcortical lesions. Ten children exhibited diencephalic lesions (Group 3), in one case combined with periventricular leukomalacia. The MRI of seven children showed subcortical/cortical lesions (Group 4), in four cases extending into diencephalic structures. Two children had a combination of evenly matched periventricular, diencephalic and subcortical/cortical lesions, where it was impossible to define a principal lesion. Three children had normal MRI findings. Significantly, 8 of 33 children had bilateral lesions although presenting with hemiplegia. The large proportion of diencephalic lesions, not described in similar CT studies, and the small number of normal MRI findings show the value of MRI in evaluation of congenital hemiplegia. The ability to correlate, to some extent, neuroradiological findings of damage to developmental stage affords the conclusion that at least a third of the children in our series with congenital hemiplegia suffered prenatal damage.
Two-hundred fifty infants with high and no risk history transitory neurological findings (TNF) were examined during the first year of life. The neurological situation and the developmental progress were reconsidered in these children at 2.5-4.5 and 5-7 years of age. TNF were diagnosed mainly during the first two trimesters. Hyperirritability and asymmetries resolved to about 70% during the first half of the first year of life. In contrast, isolated central hypotonia resolved over a much longer period. No correlations of distinct types of TNF could be found with VLBW and LBW-infants, with fullterm infants, with birthweights, nor with risk factors. Children who developed spastic CP presented permanent hypertonia beside other specific neurological symptoms during the second half of the first year of life. Children with lasting non-spastic handicaps showed permanent hypotonia combined with other neurological abnormalities and symptoms of psychomotor retardation, which evolved also during the second half of the first year. From these results the question arises: which parts of TNF are essentially neurobiological findings indicating processes of transformation of the sensory motor system from non-intentional fetal to intentional motor behaviour of early infancy. TNF, then, should not longer be looked at as symptoms of pathological value only.
On the basis of MRI examinations in 88 neonates and infants with perinatal asphyxia, we defined 6 different patterns on T2-weighted images: pattern A--scattered hyperintensity of both hemispheres of the telencephalon with blurred border zones between cortex and white matter, indicating diffuse brain injury; pattern B--parasagittal hyperintensity extending into the corona radiata, corresponding to the watershed zones; pattern C--hyper- and hypointense lesions in thalamus and basal ganglia, which relate to haemorrhagic necrosis or iron deposition in these areas; pattern D--periventricular hyperintensity, mainly along the lateral ventricles, i.e. periventricular leukomalacia (PVL), originating from the matrix zone; pattern E--small multifocal lesions varying from hyper--to hypointense, interpreted as necrosis and haemorrhage; pattern F--periventricular centrifugal hypointense stripes in the centrum semiovale and deep white matter of the frontal and occipital lobes. Contrast was effectively inverted on T1-weighted images. Patterns A, B and C were found in 17%, 25% and 37% of patients, and patterns D, E and F in 19%, 17% and 35%, respectively. In 49 patients a combination of patterns was observed, but 30% of the initial images were normal. At follow-up, persistent abnormalities were seen in all children with patterns A and D, but in only 52% of those with pattern C. Myelination was retarded most often in patients with diffuse brain injury and PVL (patterns A and D).
Eighteen term infants with hypoxic ischaemic encephalopathy (HIE) were studied with serial magnetic resonance imaging of the brain for up to two months following birth. Important early findings included brain swelling, cortical highlighting, diffuse loss of grey/white differentiation and loss of signal in the posterior limb of the internal capsule (PLIC). These signs were easier to identify on T1-weighted spin echo or inversion recovery sequences than on T2-weighted spin echo sequences. Brain swelling was only seen in the first seven days and was present in all grades of HIE. All other signs persisted and were associated with the subsequent development of major structural changes in the brain. The exact pattern of injury was best identified after the first week of life once the signs of brain swelling had cleared.
This population-based study refers to 78 Swedish children with non-progressive ataxia from a total population of 3.1 million inhabitants. Inclusion criteria were ataxic gait without any signs of spasticity, dyssynergia, dysmetria and intention tremor. CT and/or MRI studies were available from 70 patients (90%). Infratentorial pathology was revealed in 27%, and findings were considered normal in 61%. If CT was normal, of recent date and of good quality, MRI did not add any new information. In half of the cases with pathological CT, however, MRI provided new information. The origin was considered prenatal in 45% (familial in 17%), perinatal in 4% and unclassifiable in 51%. 60% were mentally retarded; in the rest, cognitive development was near normal (18%) or normal (22%). Speech development was delayed in 88%, and 58% had visual dysfunction.
Coinciding with improved overall management of the very preterm infant, more techniques have become available to assess the neurological well-being of these high-risk infants. An overview is given of the different techniques which are now used in many neonatal intensive care units, and their value in predicting neurodevelopmental outcome is discussed. Attention is mainly focused on cranial ultrasound, electroencephalography and the different evoked potential modalities.
This seventh Swedish population-based cerebral palsy (CP) report comprises 216 children born between 1987 and 1990. The crude live birth prevalence was 2.36 per 1000, indicating a break in the continuous increase since 1970. Excluding 10 postnatally-derived cases, gestational-age specific prevalences were 80 for extremely, 54 for very and 8 for moderately preterms and 1.4 for term children per 1000. Birth weight-specific prevalences were 57 for birth weights < 1000 g, 68 for 1000-1499 g, 14 for 1500-2499 g and 1.4 for > or = 2500 g per 1000. The aetiology was considered prenatal in 8%, peri/neonatal in 54% and unclassifiable in 38% of preterms and 33, 28 and 39% of term children. Hemiplegic, diplegic and tetraplegic syndromes accounted for 22, 66 and 7% of preterms and 44, 29 and 10% of term children. Non-walking, mental retardation, epilepsy, severe visual impairment and infantile hydrocephalus were present in 39, 39, 26, 18 and 23% of preterms; and 38, 44, 36, 14 and 5% of term children, respectively. The entire series of 1408 cases born in 1954-90 revealed three distinct trend eras for preterms, clearly related to changes in perinatal care and shifts in type of CP manifestations.
The MR findings in patients with spastic diplegia were investigated and the role of MR imaging in assessing the extent of brain injury was evaluated.
39 male and 24 female patients (preterm/term 43/20) were imaged using a 0.5 T MR system.
The MR findings in term patients were quite different from those in preterm patients; 55% of the term patients showed normal and minimal changes on MR, whereas 90.7% of the 43 preterm children had periventricular leucomalacia. The deep cerebral white matter was the most frequently involved site. Objective measurements revealed significant reductions of the entire sagittal area of corpus callosum in diplegic patients in comparison with normal controls. The motor palsy severity correlated well with the extent of corpus callosum involvement.
The corpus callosum appears to be a sensitive marker site for the assessment of the extent of white matter injury.
To characterize the MR findings in children with spastic tetraplegia by gestational age at birth and perinatal history.
Thirty-four children, 19 boys and 15 girls, with spastic tetraplegia whose brain damage occurred in the prenatal or perinatal period were included in the study. Eighteen were born at term or later and 16 were premature. Axial proton density- and T2-weighted images and sagittal and coronal T1-weighted images were obtained on a 0.5-T MR imaging unit.
All patients had abnormal MR findings, with a high prevalence of congenital anomalies (62.5%) in term patients who had experienced no adverse perinatal events. Term patients who had suffered detrimental perinatal events had a wide variety of brain lesions. A high frequency (75%) of periventricular leukomalacia was characteristic of preterm patients.
MR imaging is useful for evaluating structural abnormalities in the brain and the extent of brain injury in patients with spastic tetraplegia.
The correlation between MRI findings and sensorimotor development was investigated in a group of 48 infants with bilateral spastic cerebral palsy (CP). The ages at MRI examination and cognitive assessment were fairly homogeneous (mean 15 months and 17 months, respectively). The following MRI parameters were scored: size of lateral ventricles, extension of white matter lesions and of white matter reduction, thinning of corpus callosum, presence and size of cystic areas, dimension of subarachnoid spaces and presence of cortical abnormalities. Cognitive assessment included Griffiths Developmental Scales and Uzgiris-Hunt Scales. The patients were subdivided into six classes according to intellectual level (DSM-III-R). For the whole group a highly significant correlation was found between all MRI parameters and the level of cognitive development. This result was probably due to the inclusion of 14 untestable, severely mentally retarded infants, who showed very severe MRI abnormalities. However, when the untestable infants were excluded from the analysis, it was the presence of cysts and the entity of white matter reduction that correlated with both Griffiths Scales and Uzgiris-Hunt Scales. These results indicate the clinical value of MRI findings and particularly of white matter abnormalities for early identification of sensorimotor impairment in infants with bilateral spastic CP.
Twenty-three infants with an infarct in the territory of the middle cerebral artery are reported. The diagnosis was made using cranial ultrasound in all, confirmed on postmortem in two cases and on MRI, performed during the neonatal period or in infancy, in 18 of the 20 survivors. Involvement of the main branch was present in 7 cases and three of these had a gestational age of less than 35 weeks. In the other 16 infants, involvement of a cortical branch or one or more of the lenticulostriate branches was present and all but three of these had a gestational age of 34 weeks or less. While involvement of the main branch was usually diagnosed on postnatal day 1 or 2 using ultrasound, involvement of the lenticulostriate branches was noted as a wedge-shaped echogenic lesion in the caudate nucleus, thalamus or putamen, between day 4 up till day 24, and at term age in one of the cases.
Neurodevelopmental outcome of those with involvement of the main branch was disappointing as all survivors developed a hemiplegia, associated with epilepsy in two; while so far only three of the other 16 infants developed cerebral palsy, one a hemiplegia and one athetoid cerebral palsy. Global delay was present in a further three cases.
Infarcts in the region of the middle cerebral artery can occur in both preterm as well as fullterm infants. Involvement of the main branch also occurred in infants with a gestational age below 35 weeks and resulted in the development of a hemiplegia in all survivors. Involvement of one of the other branches was especially common in preterm infants, who had a more favourable outcome.
As the lesion in the latter group was usually not present before the end of the first week, serial ultrasound up till term age is needed in order to identify these lesions.
The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. Eighty-one patients had diplegia, 45 had quadriplegia, and 26 had hemiplegia. Of patients with diplegia, 72 had periventricular leukomalacia (PVL) and very few had other types of lesions. In patients with quadriplegia, three main types of brain lesions were observed: PVL in 12 patients, term-type brain injury in 22, and brain anomaly in 10. In the 26 patients with hemiplegia, 17 had a unilateral lesion (rare in patients with diplegia and quadriplegia), and bilateral lesions were seen in seven others.
Brain injury in the premature infant is an extremely important problem, in part because of the large absolute number of infants affected yearly. The two principal brain lesions that underlie the neurological manifestations subsequently observed in premature infants are periventricular hemorrhagic infarction and periventricular leukomalacia. The emphases of this article are the neurology, neuropathology and pathogenesis of these two lesions. Recent work suggests that the ultimate goal, prevention of the lesions, is potentially achievable. Periventricular hemorrhagic infarction may be preventable by prevention of germinal matrix-intraventricular hemorrhage, and periventricular leukomalacia, by detection of impaired cerebrovascular autoregulation, prevention of impaired cerebral blood flow and interruption of the cascade to oligodendroglial cell death by such agents as free radical scavengers.
Information on the long-term development of larger series of children with non-progressive congenital ataxia (NPCA) is scarce. We have updated a personal cohort of subjects previously diagnosed as having NPCA. Children with brain malformations, acquired neurological illness, or defined syndromes were excluded. From 58 subjects, 34 were available for review (including three pairs of siblings). All our subjects had delayed motor and speech development. Truncal ataxia persisted but became less significant. Two subjects developed spasticity and three a focal dystonia. Epilepsy was a feature in 10 of the subjects. Cognitive impairment was present in 22 of 34 subjects. MRI was normal in 15 of 27. There were no obvious correlations between degree of motor delay, severity of ataxia, cognitive impairment, and neuroimaging. Although genetically and clinically not a homogeneous entity, NPCA is a helpful diagnostic label. Major problems arise in the majority of subjects related to cognitive impairment and less to neurological symptoms. Early individual prognosis is not possible from early developmental milestones, neurological signs, or neuroimaging.
To define the patterns of pathologic changes in cerebral palsy (CP) and to assess the etiology and time of brain damage, we reviewed the magnetic resonance images and clinical records of 86 pediatric CP patients seen over 8 years. Patients were divided into two groups, based on the gestational age at birth. The majority of CP patients (69) had spasticity. In the premature group (< 37 wk gestational age) n = 27), spastic diplegia (12 patients) and quadriplegia (8) were the major subtypes. In the term group (> or = 37 wk gestational age) ( n = 59), spastic hemiplegia (23) and quadriplegia (12) were most common. The other main clinical manifestations in the two groups were seizures (36) and mental retardation (15). Magnetic resonance (MR) imaging provided significant findings in 82 patients (95%). In the 27 patients born prematurely, MR imaging revealed periventricular leukomalacia (17), multicystic encephalomalacia (3), cortical and subcortical atrophy (4), migration disorders (2), and basal ganglia injury (1). Among the patients born at term, the MR imaging findings were more heterogeneous; they included cortical and subcortical atrophy (17), brain malformations (17), periventricular leukomalacia (6), multicystic encephalomalacia (5), porencephaly (4), hemiatrophy (3), delayed myelination (3), and none (4). MR imaging alone could define the time of brain insults in 73 of our 86 CP patients. Combined with clinical histories, MR imaging could help assess the time of insult in 93% of patients. The brain insults occurred prenatally in 34 of our patients, perinatally in 37, and postnatally in eight. The time of insult could not be determined in six patients. In the premature patients, the insult occurred most frequently perinatally (74%), whereas in the term group it occurred most frequently prenatally (54%). MR imaging was found to be very helpful in the evaluation of the various neuropathologic changes in CP, in the depiction of the etiology, and in the determination of the time of brain injury.
Magnetic resonance imagings of 91 children with hemiplegic cerebral palsy were analysed with the aim of clustering their features into fairly homogeneous forms. In addition, the different clinical patterns of each form were described. Four main types of lesion were distinguished: form 1 (13 cases), which comprised brain malformations, form 2 (41 subjects), which grouped abnormalities of the periventricular white matter, form 3 (27 children), which was represented by cortical-subcortical lesions, and form 4 (10 subjects), which grouped non-progressive postnatal brain injuries. None of the children had normal MRI and a high incidence of bilateral lesions was found, especially in form 2. A left motor involvement was prevalent in the sample and was noted in all but the third form. The severity of impairment was mainly moderate in forms 1 and 3, mild in the others. The upper limb was found to be more affected in all forms except the second one, which presented a greater involvement of the lower limb. Mental retardation occurred in about one-third of the children with forms 1 and 4, less often in the other two. Seizures occurred in about half of the children with forms 1 or 3, while the incidence was lower in forms 4 and 2. A strong correlation between the presence of seizures and mental retardation was observed. The results of this study show the importance of MRI in the evaluation of children with hemiplegic cerebral palsy.
Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal-fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1beta, IL-6, IL-9, or tumor necrosis factor-alpha developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9-overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP.
To determine the changes in the rates of survival, cranial ultrasound abnormalities and cerebral palsy in very low birthweight (VLBW) (birthweight 500-1499 g) infants between the early 1980s and the early 1990s.
A cohort study of consecutive VLBW live births in one tertiary perinatal hospital during two distinct eras was performed at The Royal Women's Hospital, Melbourne, a level-III perinatal centre. Consecutive VLBW infants born over the 18-month period from 1 October 1980 (n = 222), and over the 12-month period from 1 January 1992 (n = 202) were identified. The main outcome measures were the proportions of live births surviving to 5 years of age, rates of cranial ultrasound abnormalities, and rates of cerebral palsy at 5 years of age.
Over the 18 months from 1 October 1980, 68% (150/222) VLBW live births survived to 5 years of age. The survival rate rose substantially to 82% (165/202) during 1992 (odds ratio 2.1, 95% confidence interval 1.4-3.2). The survival rate increased over time more for those of 500-999 g birthweight than for those of 1000-1499 g birthweight. The rates of cerebroventricular haemorrhage (CVH) were similar inlive births and survivors from both eras, as were the rates of cerebral palsy (7.5% in 1980-82; 7.8% in 1992) in survivors seen at 5 years of age. The positive predictive value of CVH for cerebral palsy was low, but cystic periventricular leucomalacia was followed by cerebral palsy in seven of eight survivors from the 1992 cohort.
Despite the increasing survival rate with improvements in perinatal care, including more antenatal steroid therapy and the introduction of exogenous surfactant, the rates of CVH and of cerebral palsy in survivors have not diminished.
To review all cases of cerebral palsy (CP) that had magnetic resonance imaging (MRI) over a defined period of time.
The MRI brain scans of 42 children (12 premature, 30 full-term) with CP were studied. The scans were performed at the Royal Children's Hospital, Melbourne, between January 1995 and June 1996.
Abnormalities were found in 39 of the 42 scans. Five children had cortical malformations and three children had white matter hypoplasia, indicating insults during the second trimester of pregnancy. Twenty-one children had hypoxic-ischaemic lesions (eight premature, 13 full-term) with patterns of periventricular leucomalacia, subcortical lesions or cortical infarction indicating insults perinatally or in the third trimester. Only 10 children had scans that could not be categorized into these groups.
In this study sample of children with CP, MRI was useful in revealing underlying brain abnormalities, most of which were due to events in the third trimester or the perinatal period.
Three-dimensional MRI data sets were obtained from 12 young adult patients with congenital spastic hemiparesis caused by unilateral periventricular white matter lesions. The impact of these lesions on corticospinal projections to the upper and lower extremities was assessed on reconstructed semi-coronal planes following anatomical landmarks of somatotopic organization in the precentral gyrus and in the internal capsule: a more anterior plane running through the hand-knob of the precentral gyrus and the anterior portion of the posterior limb of the internal capsule representing projections to the upper extremity, and a more posterior plane running through the top of the precentral gyrus and the middle portion of the posterior limb of the internal capsule representing projections to the lower extremity. In addition, the total lesion extent was determined volumetrically, and Wallerian degeneration was assessed qualitatively in the internal capsule and quantitatively by measuring brainstem asymmetry. We found a strong correlation between motor dysfunction of the upper and lower limb and the lateral extent of the periventricular lesion measured on the respective semi-coronal planes. The total lesion volume and the degree of Wallerian degeneration correlated less strongly, both reaching statistical significance only with motor impairment of the hand.
Malformations of cerebral cortical development are common birth defects that can cause delayed development, epilepsy, focal neurologic deficits, and mental retardation. Rational classification of these disorders is essential for proper prognosis, genetic testing and counseling, and investigation of the underlying molecular causes. A rational approach to this classification is a framework based on whether these disorders are the result of abnormal cell proliferation or apoptosis, abnormal migration of immature neurons, or abnormal horizontal and radial orientation in the cortex. Superimposed on this framework are subclassifications that are based on topology of the malformation, associated central nervous system (CNS) or extra-CNS malformations, and results of molecular genetic testing. Characteristics that correlate with and enforce this system of classification can be identified by modern neuroimaging studies.