Response – Do white cells matter in white-matter damage?

We appreciate Crawford's critical reading of our recent paper [1xDo white cells matter in white matter damage?. Dammann, O. et al. Trends Neurosci. 2001; 24: 320–324Abstract | Full Text | Full Text PDF | PubMed | Scopus (52)See all References[1]. He offers a list of arguments supporting his view that periventricular leukomalacia (PVL) might not be the neuropathological substrate of prematurity-associated spastic diplegia. We would agree if PVL were the only form of white matter damage (WMD), and if spastic diplegia were the only form of cerebral palsy observed among infants born preterm.Crawford implies a deterministic, ‘if A then B’ view of the pathogenesis of WMD. We however, prefer a probabilistic view of ‘if A then the probability of B is higher than if not A’. The following are our point by point responses: first, there is reason to believe that damage to the optic radiation might be one of the factors that underlie the increased risk of reduced visual acuity among preterm infants without severe retinopathy of prematurity [2xReduced visual resolution acuity and cerebral white matter damage in very-low-birthweight infants. SanGiovanni, J.P. et al. Dev. Med. Child Neurol. 2000; 42: 809–815Crossref | PubMedSee all References[2]; second, we have offered the argument that protective factors might prevent disability even among those with WMD [3xBrain damage in preterm newborns: might enhancement of developmentally-regulated endogenous protection open a door for prevention?. Dammann, O. and Leviton, A. Pediatrics. 1999; 104: 541–550Crossref | PubMed | Scopus (86)See all References[3]; third, we do not hold that PVL covers all WMD. On the contrary, we believe that PVL is only the tip of the iceberg of earlier, more widespread damage to the cerebral white matter [4xMorphologic abnormalities in human infant cerebral white matter related to gestational and postnatal age. Leviton, A. and Gilles, F.H. Pediatr. Res. 1974; 8: 718–720Crossref | PubMedSee all References, 5xVentriculomegaly, delayed myelination, white matter hypoplasia, and ‘periventricular’ leukomalacia: how are they related?. Leviton, A. and Gilles, F. Pediatr. Neurol. 1996; 15: 127–136Abstract | Full Text PDF | PubMed | Scopus (136)See all References], which would certainly help explain the symmetry seen in diplegia and quadriplegia; and fourth, we agree that neuroimaging and clinical signs of WMD do not correlate perfectly [6xCharacteristics of cranial ultrasound white matter echolucencies that predict disability: a review. Holling, E.E. and Leviton, A. Dev. Med. Child Neurol. 1999; 41: 136–139Crossref | PubMed | Scopus (84)See all References[6].Following his four points, Crawford makes the additional statement that cytokine-induced WMD should also target sensory pathways, but appears to result in pure motor disability. The authors of the studies he quotes [7xNeurologic sequelae following interferon therapy of juvenile laryngeal papilloma. Vesikari, T. et al. Acta Paediatr. Scand. 1988; 77: 619–622Crossref | PubMedSee all References, 8xSuccessful treatment of infantile hemangiomas with interferon-alpha-2b. Chang, E. et al. J. Pediatr. Hematol. Oncol. 1997; 19: 237–244Crossref | PubMed | Scopus (148)See all References, 9xSpastic diplegia as a complication of interferon alpha-2a treatment of hemangiomas in infancy. Barlow, C.F. et al. J. Pediatr. 1998; 132: 527–530Abstract | Full Text | Full Text PDF | PubMed | Scopus (311)See all References] do not provide adequate detail to draw inferences about the sensory function of the children exposed to interferon-α who developed cerebral palsy. We think it is much too early to reject the idea that PVL might be both an oligopathy and an axonopathy [10xIs periventricular leukomalacia an axonopathy as well as an oligopathy?. Dammann, O. et al. Pediatr. Res. 2001; 49: 453–457Crossref | PubMedSee all References[10].