Changes in the Clinical Spectrum of Cerebral Palsy over Two Decades in North India An Analysis of 1212 Cases

JOURNAL OF TROPICAL PEDIATRICS, VOL. 59, NO. 6, 2013 Changes in the Clinical Spectrum of Cerebral Palsy over Two Decades in North India An Analysis of 1212 Cases by Pratibha Singhi and Arushi Gahlot Saini Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India Correspondence: Prof. Pratibha Singhi, Chief Pediatric Neurology and Neurodevelopment, Advanced Pediatrics Centre, PGIMER, Chandigarh-160012, India. Tel: þ91-172-2755304/2746699, Fax: þ91-172-2744401/2745078, E-mail <doctorpratibhasinghi@gmail.com>. Summary Background: Clinical spectrum of cerebral palsy (CP) is different in developing and developed countries. We evaluated the clinical profile, etiological factors and co-morbidities of children with CP in North India, and compared with our previous study. Methods: 1212 children with CP registered in last 10 years in our rehabilitation center were compared with our previous study of 1000 children from same center. Results: Spastic quadriplegia is the commonest type of CP (51.5%) although lesser than previous decade (61%). Birth asphyxia remains the main (51.98%) etiological factor as earlier (45.3%). CP due to CNS infections decreased from 63.5% to 57.4%, due to bilirubin-encephalopathy remained same (30%). Speech problems (83.7%), microcephaly (64.27%), seizures (44.5%) and intellectual disability (38.61%) are common co-morbidities. Common neuroimaging findings include hypoxic-ischemic changes and periventricular leucomalacia. Conclusion: The spectrum of CP is evolving in the developing countries with an increase in diplegic and a decrease in quadriplegic CP. Key words: cerebral palsy, quadriplegia, asphyxia, intellectual disability, seizures Introduction Cerebral palsy (CP) is the commonest physical disability in childhood, occurring in 2 2.5/1000 births [1]. Originally reported by Little in 1861 as cerebral paresis, the term encompasses a group of disorders of development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of CP are often accompanied by disturbances of sensation, cognition, communication, perception, behavior or seizure disorders [2]. Although the brain injury in CP is non-progressive, the co-morbidities and the functional limitations change over time, affecting Acknowledgements P.S.: clinician-in-charge, plan of study, neurological assessment, reviews of electrophysiology data and neuroimaging, and review of manuscript and literature. A.G.S.: collection of data, neurological assessment, draft of manuscript and literature review the functioning and quality of life. Therefore, an understanding of the various types and the co-existent impairments of CP is imperative to physicians to assess the magnitude of problem, involve multidisciplinary care, introduce preventive measures, predict functional limitations and communicating the impact to the parents. Additionally, the clinical spectrum of CP in resource-poor, developing countries is different from that in the developed countries. The trend of increasing survival of preterm babies and advances in maternal and neonatal care in the developed world is not yet evident in most developing countries [3]. There is a paucity of clinical data in resource-poor settings, despite the fact that perinatal (e.g. asphyxia, sepsis) and postnatal causes such as meningitis, head trauma and hyperbilirubinemia contribute a large proportion of disease, a scenario very different from the developed countries where CP is more often related to prematurity and survival. Most reports of CP in resource-poor settings are either hospital or clinic based or include lesser number or narrower age-range of patients [4 8]. The other two ß The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 434 doi:10.1093/tropej/fmt035 Advance Access published on 19 June 2013

large studies were from Nigeria and our previous study from North India [3, 9]. This variation between low- and high-income countries might reflect the differences in etiology as well as in the populations identified. Hence, this study was aimed to evaluate the clinical profile, types and etiologies of CP, associated risk factors in Northern India as well as to ascertain the changes in the spectrum of CP in the last decade as compared to our previous experience from the same center [3]. Our study presents the comparative data of the largest number of patients from a single center identified through intensive neuro-pediatric follow-up and gives a perspective on CP in developing countries with emphasis on the burden of preventable causes and need for improved perinatal care. Such studies help in determining which services in resource-poor settings would contribute to improving the livelihoods of children with CP and their families. Methods The study included 1212 consecutive children with CP seen at The Rehabilitation Center for Disabled Children, Chandigarh from 2000 09. The center provides free of cost, comprehensive evaluation and intervention services to children with various types of disabilities brought from all over North India after referral from hospitals and practicing doctors, or directly from the community by parents. A detailed history including socio-demographic, family structure and birth details was elicited using a pre-structured proforma, followed by a complete physical, developmental and neurological examination. Assessment of intelligence/development quotient (IQ/DQ), ENT and ophthalmological evaluation were performed in all children. Informed consent was obtained from the care-givers and assent from the patients wherever applicable. CP was defined as a non-progressive disorder that manifests as motor and postural abnormality, and results from CNS insult sustained during the early period of brain development, usually defined as the first 3 or 5 years of life [10]. CP was classified using Swedish classification: spastic (quadriplegia, diplegia, hemiplegia), ataxic and dyskinetic (including athetoid, dystonic), hypotonic and mixed [11]. The etiological classification was: (i) congenital CP (prenatal and perinatal causes); (ii) acquired CP due to identifiable factors acquired after birth in a child born normally (such as CNS infection, neonatal jaundice, head injury, hypoglycemia, intracranial hemorrhage); (iii) mixed wherein both congenital and postnatal factors played a role. For birth asphyxia, Apgar scores when available, or the following criteria were used: (i) history of delayed cry >5 min after birth; (ii) baby turning blue and requiring oxygen therapy, with difficulty in respiration, lethargy and/or seizures within 72 h of birth. Clinical psychologists conducted psychometric tests and children were classified into mild (IQ ¼ 50 70), moderate (IQ ¼ 30 50) and severe (IQ ¼ <30) intellectual disability (ID). Children with definite history of >1 recurrent seizures were considered to have epilepsy. Behavioral problems were considered significant if they were severe enough to be perceived as problems by parents, or interfered with therapy, or education of the child. Hearing defects were objectively identified by brainstem evoked response (BSERA) or formal audiometry. Microcephaly was defined as head circumference <2 SD of normal for age and sex. Protein-energy malnutrition (PEM) was graded according to criteria proposed by the Indian Academy of Pediatrics (expressing weight of the child as percentage of the expected weight): normal (>80%); grade I (71% 80%); grade II (61% 70%); grade III (50% 60%), and grade IV (<50% of expected weight for age) [12]. Socio-economic status was ascertained using the modified Kuppuswamy s socio-economic status scale [13]. All children were evaluated by a pediatric neurologist (PS), and a team of therapists, and provided appropriate rehabilitation with periodic follow-up. Electroencephalography (EEG) and magnetic-resonance imaging (MRI) were done when relevant, and findings corroborated with the clinical findings. Statistical analysis Data were entered and descriptive statistics were calculated using SPSS 160 software package. Continuous data with normal distribution are presented as the mean and SD, whereas data with other distributions are presented as the median and range (minimum maximum). Inferential statistics were used for purposes of comparing findings from the previous study and the present study in order to determine if differences in findings were statistically significant. The level of significance was p ¼ 0.005. Results Socio-demographic characteristics From January 2000 to December 2009, 1212 children with CP were seen. There was a male preponderance (72.4%); majority of children were in the age group 1 2 years (38.9%) at the time of their first visit, 12.9% were <1 year, 33.2% between 2 and 5 years, 9.7% between 5 and 8 years and 5.4% were >8 years. Age of onset of problems noted by the parents ranged from birth to 8 years (mean 4.98 6.92 months). Mean delay in presentation to a rehabilitation center was 2.60 2.43 years. Most (68.9%) children were from lower socio-economic status. More than half (56.9%) of the children were firstborns, 28.4% second, 11.1% third and 3.6% were 4 in birth order. The presenting problems were Journal of Tropical Pediatrics Vol. 59, No. 6 435

developmental delay (88%), seizures (34.7%), other problems predominantly associated with gait and posture (22.8%), speech delay (9.5%), and behavior problems (5.9%). A contributory family history such as ID, convulsions or CP was found in 8.6% of cases. Types of CP Types of CP seen were: spastic 73% (885/1212), dyskinetic/athetoid 7% (85/1212), hypotonic/ataxic 11.2% (135/1212) and mixed 8.8% (107/1212). Out of spastic CP, quadriplegic was 51.5% (456/885), diplegic 34.5% (306/885) and hemiplegic 13.8% (123/884). The distribution of these types and comparison with our previous study has been shown in Fig. 1. As compared to our previous study, though spastic CP remains the commonest type of CP (70% 73%, p-value 0.11); diplegia has increased (22% 34.5%, p-value 0.0001) and quadriplegia has decreased (61% 51.5% p-value 0.0001) significantly. The change in hemiplegic CP (17% 13.8%, p-value 0.03) and dyskinetic CP (8.4% 7%, p-value 0.22) has not been very significant. The contribution of hypotonic and mixed CP has also changed significantly (7.7% 11.2%, p-value 0.006 and 13.9% 8.8%, p-value 0.0002, respectively). Perinatal problems Antenatal problems (Fig. 2) were reported in 30.4% of the mothers. 81% were institutional deliveries, 75.6% were term and 24.4% preterm (range 26 37 weeks), and prolonged duration of labor was reported in 13.6% of the cases. Most (75.9%) were vaginal deliveries, 20.5% were caesarean-section, 0.1% was breech, and 3.5% required instrumentation. Delayed cry was reported in half (51.2%) of the cases: 23.2% required physical stimulation alone, 25.4% also required oxygen. The predisposing neonatal factors are shown in Table 1. Etiology of CP Majority of the cases were congenital (59.8%); 22.4% had both congenital and postnatal causes. Of the 17.8% cases of acquired CP, 57.4% were due to CNS infections such as meningitis and encephalitis, 30% bilirubin-encephalopathy (usually secondary to Rh-incompatibility or G6PD deficiency), 7.4% late hemorrhagic disease of newborn or intracranial bleeds, and the rest were secondary to hypoglycemia and head injury. The various causes and their relationship to the type of CP are shown in Table 2. As compared to our previous study, the contribution of prematurity (13.2% 24.3%, p-value 0.0001), low birth weight (20.4% 37.87%, p-value 0.0001), neonatal jaundice (21.6% 35.14%, p-value 0.0001) and birth asphyxia (45.3% 51.98%, p-value 0.001) has increased significantly. FIG. 2. Antenatal problems reported in the mothers of children with CP. FIG. 1. Distribution of CP cases in the present and previous study. 436 Journal of Tropical Pediatrics Vol. 59, No. 6

Co-morbidities The co-morbidities are shown in Table 3, and their association with the type of CP is shown in Table 4. Most children (64.3%) had a head circumference <2 SD of normal. Formal IQ assessment was done in 54.5%; 28.9% had mild, 22.6% had moderate and 19.4% had severe ID. About half of cases (43%) were malnourished: PEM grade I 44.6%, grade II 33.7%, grade III 15.7% and grade IV 5.9% cases. The types of seizures are depicted in Fig. 3. EEG was done in 81% cases with seizures: generalized epileptiform discharges 37%, focal epileptiform activity 20.2%, hypsarrhythmia 7.2%, diffuse slowing 4% and normal 25%. These abnormalities were most commonly seen in children with quadriplegic followed by diplegic CP. Visual problems were seen in 46.7% of children. Of these, 60% had strabismus, 12% refractory errors, 11.1% optic atrophy, 6.7% nystagmus and 2.2% cataracts. Neuroimaging On neuroimaging, 87.88% (791/900) of children had abnormalities: hypoxic-ischemic changes (35.7%), periventricular leucomalacia (PVL) (13.4%), brain malformations (7.4%), non-specific cerebral atrophy (12.8%) and basal ganglia changes (5.8%). Other findings (11.5%) included delayed myelination, intracranial bleeds and hypoglycemic injury. Gray matter injury and cerebral atrophy was significantly TABLE 1 Neonatal factors predisposing to CP Congenital CP cases (n ¼ 1212) % Birth asphyxia 630 51.98 Low birth weight 459 37.87 Neonatal jaundice 426 35.14 Neonatal sepsis 371 30.6 Neonatal seizures 326 26.9 Prematurity 294 24.3 Twin-gestation 41 3.4 TABLE 2 The causes of CP and their relation to the types of CP CNS infection NNJ Head injury associated with spastic quadriplegia, PVL with spastic diplegia and basal ganglia changes were predominantly seen with dystonic CP. Discussion Our rehabilitation center has a large catchment area that includes most of the Northern India and provides services to both referred cases as well as children from the community. Spastic quadriplegia has been the commonest type of CP in developing countries (rates between 36% and 71%) whereas spastic diplegia (5% 47%) is commoner in the developed world [3 8, 14, 15]. It is likely that the higher rates of diplegia in high-income settings partly reflect better neonatal services and higher rates of premature survivors, whereas higher rates of spastic quadriplegia in low-income settings reflect increased perinatal and postnatal causality (e.g. asphyxia, meningitis) [1]. As compared to our previous study, though spastic CP remains the commonest type of CP; the proportion of diplegia has increased (22% 34.5%) whereas that of quadriplegia has decreased (61% 51.5%) over the last decade [3]. Mixed type (where children may have both spasticity and athetoid features) of CP forms an important group though its proportion has declined over the decade (13.9% 8.8%). Hypoglycemia TABLE 3 Associated problems in children with CP Problems n ¼ 1212 % Speech problems 1015 83.7 Microcephaly 779 64.27 Visual defect 567 46.7 Seizures 539 44.4 Malnutrition 522 43.06 Intellectual disability 468 38.61 Feeding problems 228 18.8 Hearing problems 169 13.9 Behavior problems 169 13.9 LHDN/bleed Congenital þ postnatal Total Spastic QP 274 (7.8) 67 (54) 1 (1.5) 4 (66.7) 2 (40) 5 (31.2) 103 (38) 456 (37.6) Spastic DP 198 (27.3) 23 (18.5) 4 (6.2) 0 (0) 1 (20) 2 (12.5) 78 (28.8) 306 (25.2) Spastic HP 77 (10.6) 19 (15.3) 1 (1.5) 1 (16.7) 1 (20) 8 (50) 16 (5.9) 123 (10.1) Dystonic 19 (2.6) 2 (1.6) 51 (78.5) 0 (0) 0 (0) 1 (6.2) 12 (4.4) 85 (7) Hypotonic 110 (15.2) 6 (4.8) 2 (3.1) 0 (0) 0 (0) 0 (0) 17 (6.3) 135 (11.1) Mixed 47 (6.5) 7 (5.6) 6 (9.2) 1 (16.7) 1 (20) 0 (0) 45 (16.6) 107 (8.8) Journal of Tropical Pediatrics Vol. 59, No. 6 437

There has been a rise in CP associated with prematurity (13.2% 24.3%), low birth weight (20.4% 37.87%) and twin-gestation (1.2% 3.4%) [3]. However, unlike the western figures, majority of children in both of our studies were term babies. Role of perinatal complications, particularly birth asphyxia has been implicated strongly in developing countries in 20% 46% of cases [3 4, 6, 9]. In our series, the contribution of birth asphyxia has increased from 45.3% to 51.98% even though the majority was term institutional deliveries. This possibly reflects the need for better perinatal care as well as delineating operational definitions to record birth asphyxia in resource-poor settings. CNS infections, neonatal septicemia, neonatal hypoglycemia, hyperbilirubinemia and vitamin-k deficiency-associated intracranial bleeds constitute important preventable causes of acquired CP in the developing world. An emerging cause of CP observed over the last decade (22.36%) is a combination of both congenital and postnatal factors which cause an additive insult to the growing brain. Extreme levels of hyperbilirubinemia have been causally linked with kernicterus causing permanent neurologic sequelae, including ID, choreo-athetoid CP, gaze palsies and sensorineural hearing loss, while more subtle deecits in motor function, attention and learning are attributable to moderate hyperbilirubinemia [16 17]. Even though there has been an improvement in neonatal services, hyperbilirubinemia continues to be an important cause of acquired CP over the last two decades (30%) [3]. Prevalence rates of CP have been used as outcome measures of obstetric practice and neonatal care and it was expected that improvement in these areas would result in lower rates of CP [18]. Nonetheless, Total Seizures TABLE 4 Associated problems in relation to types of CP Intellectual disability Speech Vision predisposing antenatal factors were found in onefourth of cases in our previous and present studies [3]. The reported contribution of pre-eclampsia has increased from 22% to 30% whereas that of antepartum hemorrhage reduced from 31% to 12%. A large number of mothers (18%) gave history of fever in the first trimester but tests for intra-uterine infections were negative in the babies. Increased use of fetal interventions such as instrument-assisted deliveries and caesarean-sections has also been implicated among the risk factors [19, 20]. The contribution of caesarean-section has almost doubled over the decade (9.9% 20.5%). The percentage of reported speech problems has increased as compared to the previous decade (9.5% vs. 7.8%) possibly because of the increased awareness of parents. However, speech problems were detected in a much higher proportion (83.7%) on examination. Children with quadriplegia continue to have the worst intellectual outcome. Epilepsy in children with CP is a frequent problem and is often severe and difficult to control, particularly in children with ID [21]. Seizures were found to be most common in children with quadriplegic CP, and least common in ataxic and athetoid types similar to our previous study [3]. Comparable incidence of myoclonic seizures and infantile spasms has been observed before [22, 23]. EEG abnormalities were most commonly seen in children with quadriplegic CP. Neuroimaging, particularly MRI, not only helps to define the etiology, pattern and severity of neuropathology in CP but also indicates the likely timing of injury. The American Academy of Neurology now recommends that all cases of CP of unknown origin should undergo neuroimaging [24]. In developed Hearing Behavior Malnutrition Microcephaly Feeding Spastic QP 456 257 178 404 253 76 71 216 350 103 (37.6) (56.35) (39.03) (39.8) (55.48) (45) (42) (47.36) (44.9) (45.2) Spastic DP 306 93 101 234 152 17 37 117 175 49 (25.2) (30.39) (33) (23.1) (49.67) (10.1) (21.9) (38.23) (22.5) (21.5) Spastic HP 123 68 56 84 38 5 13 32 52 3 (10.1) (55.28) (45.52) (8.3) (30.89) (3) (7.7) (26.01) (6.7) (1.3) Dystonic 85 25 34 78 26 30 16 39 46 20 (7) (29.41) (40) (7.7) (30.58) (17.8) (9.5) (45.88) (5.9) (8.8) Hypotonic 135 57 52 119 53 23 23 56 80 21 (11.1) (42.22) (38.51) (11.7) (39.25) (13.6) (13.6) (41.48) (10.3) (9.2) Mixed 107 39 47 96 45 18 9 62 76 32 (8.8) (36.44) (43.92) (9.5) (42.05) (10.7) (5.3) (57.94) (9.8) (14) Total 1212 539 468 1015 567 169 169 522 779 228 (100) (44.47) (38.61) (83.74) (46.78) (13.94) (13.94) (43.06) (64.27) (18.8) 438 Journal of Tropical Pediatrics Vol. 59, No. 6

FIG. 3. Types of seizures in children with CP. countries, the main findings include PVL or white matter injury (40% 60%), cortical and deep gray matter lesions (10% 20%), and brain malformations (10%) [25, 26]. Cerebral imaging abnormalities were found in 87.88% of our patients similar to the Western data [27 29]. In concordance to the predominant type of CP, HIE changes are most commonly seen in our setup whereas PVL is the most common neuropathology in developed world [27, 28]. Additionally, children with dyskinetic CP secondary to neonatal hyperbilirubinemia showed basal ganglia changes in the MRI. Limitation Our study was not community based; hence there is a chance of missing mild cases of CP which did not seek institutional care. Nevertheless, it is reasonably reflective of the types of cases seen in Northern India due to the large drainage area of our rehabilitation center and the patient profile including both referred cases as well as children from the community. Conclusion Term, quadriplegic CP is most common in our set up with a trend towards increase in the diplegic and decrease in the quadriplegic CP. Preventable factors such as birth asphyxia, CNS infections and hyperbilirubinemia remained unchanged and reflect the need for improvement in perinatal care. References 1. Gladstone M. A review of the incidence and prevalence, types and etiology of childhood cerebral palsy in resource-poor settings. Ann Trop Paediatr 2010;30: 181 96. 2. Bax M, Goldstein M, Rosenbaum P, et al. Proposed definition and classification of cerebral palsy. Dev Med Child Neurol 2005;47:571 6. 3. Singhi PD, Ray M, Suri G. Clinical spectrum of cerebral palsy in North India an analysis of 1,000 cases. J Trop Pediatr 2002;48:162 6. 4. Burton KJ, Allen S. A review of neurological disorders presenting at a paediatric neurology clinic and response to anticonvulsant therapy in Gambian children. Ann Trop Paediatr 2003;23:139 43. 5. Lagunju I, Okafor O. An analysis of disorders seen at the Paediatric Neurology Clinic, University College Hospital, Ibadan, Nigeria. West Afr J Med 2009;28: 328 32. 6. Belonwu RO, Gwarzo GD, Adeleke SI. Cerebral palsy in Kano, Nigeria a review. Niger J Med 2009;18: 186 9. 7. Karumuna JMS, Mgone CS. Cerebral palsy in Dar Es Salaam. Cent Afr J Med 1990;36:8 10. 8. Khan NZ, Ferdous S, Munir S, et al. Mortality of urban and rural young children with cerebral palsy in Bangladesh. Dev Med Child Neurol 1998;40: 749 53. 9. Nottidge VA, Okogbo ME. Cerebral palsy in Ibadan, Nigeria. Dev Med Child Neurol 1991;33:241 5. 10. Eicher PS, Batshaw ML. Cerebral palsy. Pediatr Clin North Am 1993;40:537 51. 11. Hagberg B, Hagberg G, Olow I, et al. The changing panorama of cerebral palsy in Sweden. V. The birth year period 1979-82. Acta Paediatr Scand 1989;78: 283 90. 12. Nutrition. Sub-committee of Indian Academy of Pediatrics. Classification of protein calorie malnutrition. Indian Pediatr 1972;9:360. 13. Mishra D, Singh HP. Kuppuswamy s socioeconomic status scale a revision. Indian J Pediatr 2003;70:273 4. 14. Andersen GL, Irgens LM, Haagaas I, et al. Cerebral palsy in Norway: prevalence, subtypes and severity. Eur J Paediatr Neurol 2008;12:4 13. 15. Himmelman K, Hagberg G, Uverbrandt P. The changing panorama of cerebral palsy in Sweden X. Prevalence and origin in the birth-year period 1999 2002. Acta Paediatr 2010;99:1337 43. 16. Scheidt PC, Graubard BI, Nelson KB, et al. Intelligence at six years in relation to neonatal bilirubin levels: follow-up of the National Institute of Child Health and Human Development Clinical Trial of Phototherapy. Pediatrics 1991;87:797 805. 17. Jangaard KA, Fell DB, Dodds L, et al. Outcomes in a population of healthy term and near-term infants with serum bilirubin levels of 325 micromol/l (19 mg/ dl) who were born in Nova Scotia, Canada, between 1994 and 2000. Pediatrics 2008;122:119 24. 18. Stanley FJ, Blair E. Why have we failed to reduce the frequency of cerebral palsy? Med J Aust 1991;154: 623 6. 19. Torfs CP, Van den Berg B, Oechsli FW, et al. Prenatal and perinatal factors in the etiology of cerebral palsy. J Pediatr 1990;116:615 9. 20. Powell TG, Pharoah PO, Cooke RW, et al. Cerebral palsy in low-birthweight infants. I. Spastic hemiplegia: associations with intrapartum stress. Dev Med Child Neurol 1988;30:11 8. 21. Singhi P, Jagirdar S, Khandelwal N, et al. Epilepsy in children with cerebral palsy. J Child Neurol 2003;18: 174 9. 22. Kaushik A, Agarwal RP, Sadhna. Association of cerebral palsy with epilepsy. J Indian Med Assoc 1997;95: 552 65. 23. Okumura A, Hayakawa F, Kato T, et al. Epilepsy in patients with spastic cerebral palsy: correlation with MRI findings at 5 years of age. Brain Dev 1999;21: 540 3. Journal of Tropical Pediatrics Vol. 59, No. 6 439

24. Ashwal S, Russman BS, Blasco PA, et al. Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2004;62:851 63. 25. Krageloh-Mann I, Horber V. The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review. Dev Med Child Neurol 2007;49:144 51. 26. Korzeniewski SJ, Birbeck G, DeLano MC, et al. A systematic review of neuroimaging for cerebral palsy. J Child Neurol 2008;23:216 27. 27. Bax M, Tydeman C, Flodmark O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA 2006;296:1602 8. 28. Robinson MN, Peake LJ, Ditchfield MR, et al. Magnetic resonance imaging findings in a populationbased cohort of children with cerebral palsy. Dev Med Child Neurol 2009;51:39 45. 29. Towsley K, Shevell MI, Dagenais L. Populationbased study of neuroimaging findings in children with cerebral palsy. Eur J Paediatr Neurol 2011;15: 29 35. 440 Journal of Tropical Pediatrics Vol. 59, No. 6