46
Bilateral Spastic Cerebral Palsy - Pathogenetic Aspects from MRI By 1. Krägeloh-Mann1, B. Hagberg2, D. Petersen3,]. Riethmüller1, E. Gut3 and R. Michaelis 1 Departments of INeuropediatrics and 3Neuroradiology, University of Tübingen and 2Department of Pediatrics II, University of Gothenburg
Thirty eight children with bilateral spastic cerebral palsy underwent MRI at the age of 5 years and more. Twenty nine showed correlates of periventricular leucomalacia, which were found especially in preterms (20 out of 21) but also in 9 of 15 fullterms without birth asphyxia. These findings suggest compromising events in the periand neonatal period especially in preterms and prenatal 3rd trimenon compromise in most of the fullterms without birth asphyxia. Keywords Brain damage - Cerebral palsy - MRI
Bilateral spastic cerebral palsy (CP) - the diplegie and tetraplegie syndromes pooled together - stands for more than 50 % of all CP. Recent epidemiology indicates a prevalence of 1 per thousand, two third born preterm (5, 8, 11). In addition, both preterm diplegia and tetraplegia tend to increase secondary to raised preterm survival (6). As distinction between the two subgroups today is less clear than ever, analysis of origins without artificial borderlines is wanted. For prevention and forensie purposes it is essential to reveal causes and time of causing events. The following two controversial hypothesis are discussed: 1. Brain damage is caused peri- and neonatally. Because of the higher vulnerability of the very immature brain, preterms are especially affected (5,10,11). 2. Brain damage is caused prenatally. Prenatally impaired infants are born preterm and better perinatal care improves survival (8, 9). This paper will add some new data and aspects to the questions raised on the basis of MRI-investigations.
From a cohort of 183 children with bilateral spastic CP, examined within an epidemiologie study in the region of Tübingen, up to now 38 joined the MRI-study. They were selected at random. Twenty-five were boys and 13 girls (mean age 11, range 5 to 18 years). Magnetic resonance imaging was performed with a 1.5 Tesla Magnetom (Siemens), Tlw (TR 600ms, TE 15ms) and T2w images (TR 2 100ms, TE 45 and 90 ms) were obtained in axial and coronal orientation. Results were analysed according to four groupings: 1) Born at term with perinatal asphyxia (Apgar score < 5 at 1 mine or 5 mine or need for immediate neonatal resuscitation; ventilation andlor convulsions during the first two days of life) (2). 2) Born at term without asphyxia. 3) Born at gestational age (GA) 32-37 weeks. 4) Born GA < 32 weeks.
Results
Group 1 includes two children so far. In both, MRI showed multicystic encephalopathy with sparing of infratentorial structures.
Group2 comprises 15 children. (a) Nine showed periventricular hyperintensity on T2w images adjacent to the body of the lateral ventricles (cella media region) as weIl as in the peritrigonal region and variable reduction of white matter in these areas (Fig. 1). (b) Six disclosed various results: Two showed migration defects (lissencephaly and schizencephaly), one a genetic defect of myelin formation, one disclosed thrombembolic defects affecting the motor cortex bilaterally and two children showed normal results.
Group 3
Received November 29,1991; accepted December 3,1991 Neuropediatrics 23 (1992) 46-48 © Hippokrates Verlag Stuttgart
comprises 10 children. (a) Nine showed reduced periventricular white matter and abnormal signal intensities (T2w) as in Group 2 (a). (b) One child was born by Cesarian section at GA 32 because of hydrocephalus due to Arnold Chiari malformation, there were no white matter abnormalities.
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Patients and methods Abstract
Fig. 1 MRI findings of PVL correlates: T1w images (Ieft) show slightly enlarged and irregularly shaped lateral ventricles and reduced white matter in the peritrigonal area; T2w images (right) show areas of increased signal in-
Discussion
Group 4
comprises 11 children. All disclosed periventricular abnormalities as described in Group 2 (a). Correlation with clinical findings and risk factors Spastic tetraplegia (according to ref. 4) was found in both children of Group 1, in three of Group 2 (b) and one each of Group 2 (a) and 3 (a). Spastic diplegia (according to ref. 4), thus, was especially correlated to periventricular white matter abnormalities (Table 2). Intraventricular hemorrhage had occurred during the neonatal period in five children of Group 4 and two children of Group 3 (a); hypotrophy at birth in five children of Group 2 (three in 2 [al, two in 2 [b]); bleeding during the first trimenon in four children of Group 4, three of Group 3 (a) and the one in Group 3 (b); bleeding during the 2nd and 3rd trimenon in two of Group 4 and the one in Group 3 (b).
Table 1 Group
MRI and clinical findings according to groups (see text). no.
I
MRI-findings
I
Di-
Tetraplegla
(1)
2
(2)
15
~ulticystiC encephalopathy (a) 9 PVL (b) 6 various (1 gen., 2 malform.)
(3)
10
(a) 9 PVL (b) 1 malformation
(4)
11
PVL
tensities in the periventricular area adjacent to the bodies and trigona of the lateral ventricles.
2
8 3 7 11
1
3 2 1
Gross brain development and neuronal migration refer to the first 20 to 24 weeks of gestation. Impairments then result in maldevelopments: Arnold-Chiari, Dandy-Walker and heterotopias, sehizeneephaly, lisseneephaly, paehygyria a. o. (13). From GA 24, myelination, glial and dendritie formation oeeur, the periventrieular struetures being partieularly vulnerable during the period GA 24-36. Very preterm born babies (GA 26-30) are those most disposed to germinal matrix bleeding, some developing periventrieular hemorrhagie infaretion and CP (12). Compromised moderately preterms (GA 31-36) are those who elassieally develop periventrieular leueomalaeias (PVL) (12). Hypoxie-isehemie eneephalopathy of the fullterm mainly affeets the hemispheres (multicystie ehanges), the basal ganglia ("status marmoratus") and/or parasagittal subcortieal struetures (1). The latter are those of special relevanee for severe bilateral spastie CP. MRI effeetively shows malformations ofthe brain as well as the ehronie pathologie eonsequenees of PVL and hypoxie-isehemie eneephalopathy (1, 2). Genetie, maldevelopmental and early prenatal origin before GA 24 was in our series found in only 4/38 patients, three born at term and one preterm (Cesarian seetion beeause of the malformation), thus being a minority in bilateral spastie CP. In all preterms - with the exeeption of one - there were eorrelates to PVL, suggesting damaging events peri- and neonatally. In fullterms without asphyxia, findings were heterogeneous, the majority (9 out of 15), however, also with PVL eorrelates. This indieates a prenatal 3rd trimenon fetal eompromise in the major proportion of eases. Although the series is a limited seetion of a larger and
47
Downloaded by: University of British Columbia. Copyrighted material.
Neuropediatrics 23 (1992)
Bilateral Spastic Cerebral Palsy - Pathogenetic Aspects/rom MRI
1. Krägeloh-Mann et al
Neuropediatrics 23 (1992)
population-based study, the high number oflesions correlated to PVL (29 out of 38) nevertheless indicates that this pathogenetic mechanism might be themajor cause of aH bilateral spastic CP. In our preterms, the MRI data are weH in accordance with other recent studies of preterm spastic diplegias, where periventricular myelin reduction and abnormal signal intensities on T2w images were found in all (7, 14). For fullterm CP cases with bilateral spastic syndromes we think our findings give a new perspective on origin and the indicated intrauterine timing of deranging fetal circulatory events. Such data from the literature have previously only scarcely been reported, then mainly scattered cases (7, 14).
References Barkovich, A. ]., C. L. Truwit: Brain damage from perinatal asphyxia: correlation of MR findings with gestational age. AJNR 11 (1990) 10871096 2 Finer, N. N., C. M. Robertson, R. T. Richards, L. E. Pinell, K. L. Peters: Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. Pediatrics 98 (1981) 112-11 7 3 Flodmark, 0., B. Lupton, D. Li, G. K. Stimac, E. H. Roland, A. HilI, M. F. Whitfield, M. G. Norman: MR imaging of periventricular leucomalacia in childhood. AJR 152 (1989) 583-590 4 Hagberg, B., G. Hagberg, 1. Olow: The changing panorama of cerebral palsy in Sweden 1954-70. I. Analysis of general changes. Acta Paediatr. Scand. 64 (1975) 187-192 5 Hagberg, B., G. Hagberg, 1. Olow, L. von Wendt: The changing panorama of cerebral palsy in Sweden. V. The birth year period 1979-82. Acta Paediatr. Scand. 78 (1989) 283-290 1
Hagberg, B., G. Hagberg, R. Zetterström: Decreasing perinatal mortality - increase in cerebral palsy mortality? Acta Paediatr. Scand. 78 (1989) 664-670 7 Koeda, T., 1. Suganuma, Y. Kohno, T. Takamatsu, T. Takeshita: MR imaging of spastic diplegia. Neuroradiology 32 (1990) 187-1990 8 Pharoah, P. O. D., T. Cooke, R. W.1. Cooke, L. Rosenbloom: Birthweight specific trends in cerebral palsy. Arch Dis Child 65 (1990) 602-606 9 Stanley, F.]., D. R. English: Prevalence of and risk factors for cerebral palsy in a total population cohort of low birthweight « 2000 g) infants. Dev. Med. Child. Neurol. 28 (1986) 559-568 lOStewart, A. L., E. O. R. Reynolds, A. P. Lipscomb: Outcome for infants of very low birthweight: survey of world literature. Lancet (1981) 10381040 11 Takeshita, K., Y. Ando, K. Ohtani, S. Takashima: Cerebral palsy in Tottori, Japan. Benefits and risks of progress in perinatal medicine. Neuroepidemiology 8 (1989) 184-192 12 Volpe,J.J.: Current concepts of brain injury in the premature infant. AJR 153 (1989) 243-251 13 Williams, R. 5.: Cerebral malformations arising in the first half of gestation. New York: Developmental Neurobiology, Evrard, P., Minkowski, A. Raven Press (1989) 11-20 14 Yokochi, K., K. Aiba, M. Horie, K. Inukai, S. Fujimoto, M. Kodama, K. Kodama: Magnetic resonance imaging in children with spastic diplegia: correlation with the severity of their motor and mental abnormality. Dev. Med. Child Neurol. 33 (1991) 18-25 6
Dr. Ingeborg Krägeloh-Mann
Department of Neuropediatrics Children's Hospital Frondsbergstr.23 D-7400 Tübingen
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48
Bilateral Spastic Cerebral Palsy - Pathogenetic Aspects from MRI By 1. Krägeloh-Mann1, B. Hagberg2, D. Petersen3,]. Riethmüller1, E. Gut3 and R. Michaelis 1 Departments of INeuropediatrics and 3Neuroradiology, University of Tübingen and 2Department of Pediatrics II, University of Gothenburg
Thirty eight children with bilateral spastic cerebral palsy underwent MRI at the age of 5 years and more. Twenty nine showed correlates of periventricular leucomalacia, which were found especially in preterms (20 out of 21) but also in 9 of 15 fullterms without birth asphyxia. These findings suggest compromising events in the periand neonatal period especially in preterms and prenatal 3rd trimenon compromise in most of the fullterms without birth asphyxia. Keywords Brain damage - Cerebral palsy - MRI
Bilateral spastic cerebral palsy (CP) - the diplegie and tetraplegie syndromes pooled together - stands for more than 50 % of all CP. Recent epidemiology indicates a prevalence of 1 per thousand, two third born preterm (5, 8, 11). In addition, both preterm diplegia and tetraplegia tend to increase secondary to raised preterm survival (6). As distinction between the two subgroups today is less clear than ever, analysis of origins without artificial borderlines is wanted. For prevention and forensie purposes it is essential to reveal causes and time of causing events. The following two controversial hypothesis are discussed: 1. Brain damage is caused peri- and neonatally. Because of the higher vulnerability of the very immature brain, preterms are especially affected (5,10,11). 2. Brain damage is caused prenatally. Prenatally impaired infants are born preterm and better perinatal care improves survival (8, 9). This paper will add some new data and aspects to the questions raised on the basis of MRI-investigations.
From a cohort of 183 children with bilateral spastic CP, examined within an epidemiologie study in the region of Tübingen, up to now 38 joined the MRI-study. They were selected at random. Twenty-five were boys and 13 girls (mean age 11, range 5 to 18 years). Magnetic resonance imaging was performed with a 1.5 Tesla Magnetom (Siemens), Tlw (TR 600ms, TE 15ms) and T2w images (TR 2 100ms, TE 45 and 90 ms) were obtained in axial and coronal orientation. Results were analysed according to four groupings: 1) Born at term with perinatal asphyxia (Apgar score < 5 at 1 mine or 5 mine or need for immediate neonatal resuscitation; ventilation andlor convulsions during the first two days of life) (2). 2) Born at term without asphyxia. 3) Born at gestational age (GA) 32-37 weeks. 4) Born GA < 32 weeks.
Results
Group 1 includes two children so far. In both, MRI showed multicystic encephalopathy with sparing of infratentorial structures.
Group2 comprises 15 children. (a) Nine showed periventricular hyperintensity on T2w images adjacent to the body of the lateral ventricles (cella media region) as weIl as in the peritrigonal region and variable reduction of white matter in these areas (Fig. 1). (b) Six disclosed various results: Two showed migration defects (lissencephaly and schizencephaly), one a genetic defect of myelin formation, one disclosed thrombembolic defects affecting the motor cortex bilaterally and two children showed normal results.
Group 3
Received November 29,1991; accepted December 3,1991 Neuropediatrics 23 (1992) 46-48 © Hippokrates Verlag Stuttgart
comprises 10 children. (a) Nine showed reduced periventricular white matter and abnormal signal intensities (T2w) as in Group 2 (a). (b) One child was born by Cesarian section at GA 32 because of hydrocephalus due to Arnold Chiari malformation, there were no white matter abnormalities.
Downloaded by: University of British Columbia. Copyrighted material.
Patients and methods Abstract
Fig. 1 MRI findings of PVL correlates: T1w images (Ieft) show slightly enlarged and irregularly shaped lateral ventricles and reduced white matter in the peritrigonal area; T2w images (right) show areas of increased signal in-
Discussion
Group 4
comprises 11 children. All disclosed periventricular abnormalities as described in Group 2 (a). Correlation with clinical findings and risk factors Spastic tetraplegia (according to ref. 4) was found in both children of Group 1, in three of Group 2 (b) and one each of Group 2 (a) and 3 (a). Spastic diplegia (according to ref. 4), thus, was especially correlated to periventricular white matter abnormalities (Table 2). Intraventricular hemorrhage had occurred during the neonatal period in five children of Group 4 and two children of Group 3 (a); hypotrophy at birth in five children of Group 2 (three in 2 [al, two in 2 [b]); bleeding during the first trimenon in four children of Group 4, three of Group 3 (a) and the one in Group 3 (b); bleeding during the 2nd and 3rd trimenon in two of Group 4 and the one in Group 3 (b).
Table 1 Group
MRI and clinical findings according to groups (see text). no.
I
MRI-findings
I
Di-
Tetraplegla
(1)
2
(2)
15
~ulticystiC encephalopathy (a) 9 PVL (b) 6 various (1 gen., 2 malform.)
(3)
10
(a) 9 PVL (b) 1 malformation
(4)
11
PVL
tensities in the periventricular area adjacent to the bodies and trigona of the lateral ventricles.
2
8 3 7 11
1
3 2 1
Gross brain development and neuronal migration refer to the first 20 to 24 weeks of gestation. Impairments then result in maldevelopments: Arnold-Chiari, Dandy-Walker and heterotopias, sehizeneephaly, lisseneephaly, paehygyria a. o. (13). From GA 24, myelination, glial and dendritie formation oeeur, the periventrieular struetures being partieularly vulnerable during the period GA 24-36. Very preterm born babies (GA 26-30) are those most disposed to germinal matrix bleeding, some developing periventrieular hemorrhagie infaretion and CP (12). Compromised moderately preterms (GA 31-36) are those who elassieally develop periventrieular leueomalaeias (PVL) (12). Hypoxie-isehemie eneephalopathy of the fullterm mainly affeets the hemispheres (multicystie ehanges), the basal ganglia ("status marmoratus") and/or parasagittal subcortieal struetures (1). The latter are those of special relevanee for severe bilateral spastie CP. MRI effeetively shows malformations ofthe brain as well as the ehronie pathologie eonsequenees of PVL and hypoxie-isehemie eneephalopathy (1, 2). Genetie, maldevelopmental and early prenatal origin before GA 24 was in our series found in only 4/38 patients, three born at term and one preterm (Cesarian seetion beeause of the malformation), thus being a minority in bilateral spastie CP. In all preterms - with the exeeption of one - there were eorrelates to PVL, suggesting damaging events peri- and neonatally. In fullterms without asphyxia, findings were heterogeneous, the majority (9 out of 15), however, also with PVL eorrelates. This indieates a prenatal 3rd trimenon fetal eompromise in the major proportion of eases. Although the series is a limited seetion of a larger and
47
Downloaded by: University of British Columbia. Copyrighted material.
Neuropediatrics 23 (1992)
Bilateral Spastic Cerebral Palsy - Pathogenetic Aspects/rom MRI
1. Krägeloh-Mann et al
Neuropediatrics 23 (1992)
population-based study, the high number oflesions correlated to PVL (29 out of 38) nevertheless indicates that this pathogenetic mechanism might be themajor cause of aH bilateral spastic CP. In our preterms, the MRI data are weH in accordance with other recent studies of preterm spastic diplegias, where periventricular myelin reduction and abnormal signal intensities on T2w images were found in all (7, 14). For fullterm CP cases with bilateral spastic syndromes we think our findings give a new perspective on origin and the indicated intrauterine timing of deranging fetal circulatory events. Such data from the literature have previously only scarcely been reported, then mainly scattered cases (7, 14).
References Barkovich, A. ]., C. L. Truwit: Brain damage from perinatal asphyxia: correlation of MR findings with gestational age. AJNR 11 (1990) 10871096 2 Finer, N. N., C. M. Robertson, R. T. Richards, L. E. Pinell, K. L. Peters: Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. Pediatrics 98 (1981) 112-11 7 3 Flodmark, 0., B. Lupton, D. Li, G. K. Stimac, E. H. Roland, A. HilI, M. F. Whitfield, M. G. Norman: MR imaging of periventricular leucomalacia in childhood. AJR 152 (1989) 583-590 4 Hagberg, B., G. Hagberg, 1. Olow: The changing panorama of cerebral palsy in Sweden 1954-70. I. Analysis of general changes. Acta Paediatr. Scand. 64 (1975) 187-192 5 Hagberg, B., G. Hagberg, 1. Olow, L. von Wendt: The changing panorama of cerebral palsy in Sweden. V. The birth year period 1979-82. Acta Paediatr. Scand. 78 (1989) 283-290 1
Hagberg, B., G. Hagberg, R. Zetterström: Decreasing perinatal mortality - increase in cerebral palsy mortality? Acta Paediatr. Scand. 78 (1989) 664-670 7 Koeda, T., 1. Suganuma, Y. Kohno, T. Takamatsu, T. Takeshita: MR imaging of spastic diplegia. Neuroradiology 32 (1990) 187-1990 8 Pharoah, P. O. D., T. Cooke, R. W.1. Cooke, L. Rosenbloom: Birthweight specific trends in cerebral palsy. Arch Dis Child 65 (1990) 602-606 9 Stanley, F.]., D. R. English: Prevalence of and risk factors for cerebral palsy in a total population cohort of low birthweight « 2000 g) infants. Dev. Med. Child. Neurol. 28 (1986) 559-568 lOStewart, A. L., E. O. R. Reynolds, A. P. Lipscomb: Outcome for infants of very low birthweight: survey of world literature. Lancet (1981) 10381040 11 Takeshita, K., Y. Ando, K. Ohtani, S. Takashima: Cerebral palsy in Tottori, Japan. Benefits and risks of progress in perinatal medicine. Neuroepidemiology 8 (1989) 184-192 12 Volpe,J.J.: Current concepts of brain injury in the premature infant. AJR 153 (1989) 243-251 13 Williams, R. 5.: Cerebral malformations arising in the first half of gestation. New York: Developmental Neurobiology, Evrard, P., Minkowski, A. Raven Press (1989) 11-20 14 Yokochi, K., K. Aiba, M. Horie, K. Inukai, S. Fujimoto, M. Kodama, K. Kodama: Magnetic resonance imaging in children with spastic diplegia: correlation with the severity of their motor and mental abnormality. Dev. Med. Child Neurol. 33 (1991) 18-25 6
Dr. Ingeborg Krägeloh-Mann
Department of Neuropediatrics Children's Hospital Frondsbergstr.23 D-7400 Tübingen
Downloaded by: University of British Columbia. Copyrighted material.
48
