Pathogenesis, neuroimaging and management in children with cerebral palsy born preterm

Abstract

With advances in obstetric and perinatal management, the incidence of intraventricular hemorrhage in premature infants has declined, while periventricular leukomalacia remains a significant concern. It is now known that brain injury in children born preterm also involves neuronal-axonal disease in supratentorial and infratentorial structures. The developing brain is especially vulnerable to white matter (WM) injury from 23 to 34 weeks gestation when blood vessels serving the periventricular WM are immature. Oligodendrocyte progenitors, which are beginning to form myelin during this time, are susceptible to attack from oxygen free radicals, glutamate, and inflammatory cytokines. Advances in imaging techniques such as diffusion tensor imaging provide a more complete picture of the location and extent of injury. Effective management of children born preterm with cerebral palsy is predicated on an understanding of sequential links from etiological antecedents to brain neuropathology as revealed with neuroimaging techniques to clinical phenotypes, toward focused interventions with measurable outcomes.

Motor, sensory and executive function brain networks in children with unilateral cerebral palsy

“…A limitation of the tensor model is its inability to resolve crossing fibres in complex white matter populations 32 , which has significant ramifications for the accuracy of tractography derived diffusivity measures. This presents a significant challenge in dMRI studies as it has been estimated that crossing fibres are present in at least two-thirds of brain voxels with FA > 0.2 91 . Within these anatomical locations, the clinical interpretation of diffusivity measures is difficult, as voxels containing highly organised crossed white matter networks can exhibit paradoxical reduced anisotropy 32 .…”

“…Although dMRI studies play a useful role in clinical management of CP 91 , the full potential of this technology remains largely in the research domain. When sMRI is already indicated, adding dMRI sequences to the scan will add only a few minutes to the overall scan time.…”

Automated injury segmentation to assist in the treatment of children with cerebral palsy

“…Several imaging technologies are used to assess CP [Accardo et al, 2004;Bosanquet et al, 2013], including computed tomography, cranial ultrasonography and magnetic resonance imaging (MRI). Of these modalities, MRI is favoured as ultrasound is limited by acoustic windows, computed tomography involves ionising radiation, and both lack soft tissue contrast important for brain imaging [Hoon and Vasconcellos Faria, 2010]. Although alternate modalities, including functional and diffusion MRI, can provide complementary information on brain structure and function [Heeger and Ress, 2002;Madden et al, 2009], structural MRI remains most widely used in clinical practice, detecting injury in approximately 85% of children with CP [Korzeniewski et al, 2008;.…”

“…This will facilitate injury detection in young children and neonates who might not show visible signs of motor or cognitive impairment, and enables interventions to be implemented earlier in life. Studies in the literature have found qualitative MR findings to be a strong predictor of the pathogenesis of CP [Palmer, 2004;de Vries et al, 2011] that can be used to assess neuro-developmental risk [Ashwal et al, 2004;Mathur and Inder, 2009], and predict neurological deficits [Arnfield et al, 2013;Hoon and Vasconcellos Faria, 2010;.…”

“…There is a marked increase in lateral ventricle volume amongst children with CP [Grant and Barkovich, 1997;Sööt et al, 2008]. Enlarged ventricles are an indirect measure for loss in WM due to brain injury [Hoon and Vasconcellos Faria, 2010], and has been correlated with motor and cognitive impairment [Melhem et al, 2000]. The assessment of this secondary lesion is described in Chapter 5 of this thesis.…”