Central Motor Conduction Time and Diffusion Tensor Imaging metrics in children with complex motor disorders

Highlights

• Both measurement of Central Motor Conduction Time (CMCT) and Diffusion Weighted Imaging (DWI) may aid with the clinical assessment of children and young people with complex motor disorders.

• Diffusion Tensor Imaging (DTI) metrics in a group of children with complex motor disorders did not correlate with CMCT, nor were group wise differences in DTI metrics identified when children with normal and abnormal CMCT where compared.

• Children and young people with acquired dystonia were frequently found to have normal CMCT values.

Abstract

Objectives

To explore potential correlations between Diffusion Tensor Imaging (DTI) metrics and Central Motor Conduction Time (CMCT) in a cohort of children with complex motor disorders.

Methods

For a group of 49 children undergoing assessment for potential Deep Brain Stimulation (DBS) surgery, CMCT was derived from the latency of MEPs invoked by transcranial magnetic stimulation of the contralateral motor cortex and from peripheral conduction times. Tract-Based Spatial Statistics (TBSS) was used to compare Diffusion Tensor Imaging (DTI) metrics between children with normal and abnormal CMCT. TBSS was also used to look for correlations between these metrics and CMCT across the group.

Results

Median age at assessment was 9 years (range 3–19 years). For 14/49 children a diagnosis of primary dystonia had been made. No correlation could be found between DTI metrics and CMCT, with no difference in metrics found between children with normal and abnormal CMCT.

Conclusions

DTI metrics did not differ between children with normal and abnormal CMCT. Tissue properties determining CMCT may not be explained by existing DTI metrics.

Significance

DTI and CMCT measurements provide complementary information for the clinical assessment of children with complex motor disorders.

Introduction

Hypertonic motor disorders in childhood may arise from a diverse range of pathological processes, often affecting more than one motor region of the central nervous system. An important distinction to be made in clinical practise is the relative integrity of the corticospinal tract (CST) in children with hypertonic motor disorders, influencing understanding of the underlying disease process and, more importantly, the choice of clinical intervention (Lin, 2003, Lin, 2011, McClelland et al., 2011). Dystonia and spasticity are often seen coincidently in the child with pathological hypertonicity, particularly in the context of cerebral palsy (Sanger et al., 2003). Clinical evaluation of the child with hypertonia is challenging, and concerns exist that the relative contributions of dystonia and spasticity may be under- and over-estimated respectively (Lin, 2011). Transcranial Magnetic Brain Stimulation (TMS) is a well-established tool for probing the integrity of the CST, and has been used to demonstrate the maturation of Central Motor Conduction Time (CMCT) in children (Eyre et al., 1991, Koh and Eyre, 1988). Prolonged CMCT has been demonstrated in a number of disorders known to affect the CST, including stroke, Multiple Sclerosis (MS) and Motor Neuron Disease (MND) (Berardelli et al., 1991, Heald et al., 1993, Hess et al., 1986). We have previously reported our own experience of using CMCT as a clinical tool for assessing CST integrity in children with dystonia undergoing assessment for deep brain stimulation (DBS), demonstrating normal CMCT time in the majority of patients for whom structural Magnetic Resonance Imaging (MRI) would be suggestive of CST damage (McClelland et al., 2011).

In recent years Diffusion Tensor Imaging (DTI) has become widely used in the investigation of children with movement disorders. DTI exploits the fact that the diffusion of water has different characteristics within different types of brain tissue to provide information about the microstructure of the brain, potentially providing a window into the relationship between structure and function (Le Bihan et al., 2001). Diffusion which is unrestricted and equal in any direction is termed isotropic, whereas diffusion which is restricted more in one plane than another is termed anisotropic. For example, anisotropic diffusion is seen in white matter pathways because water diffuses relatively freely along the longitudinal axis of a coherent axonal bundle, compared with relatively restricted diffusion in a direction perpendicular to this. One commonly used parameter is Fractional Anisotropy (FA), a measure of the directionality of water movement with values from 0 to 1, higher values indicating greater directionality which in turn is thought to reflect the integrity of white matter pathways. DTI has considerably advanced our understanding of the pathophysiology in cerebral palsy, and in particular the relative contributions of disruptions to motor and sensory pathways (Scheck et al., 2012). In the context of MND correlations have been demonstrated between the severity of motor disability, increasing delay in CMCT and reduction in FA (Ellis et al., 1999, Iwata et al., 2008, Mitsumoto et al., 2007, Sach et al., 2004). Taken together, these and other studies raise the possibility that FA could potentially be used as a biomarker for CST integrity.

Only one reported study to date has investigated possible correlations between DTI metrics and CMCT in healthy subjects, finding no areas of correlation (Hübers et al., 2012). This study applied a voxelwise approach, utilising Tract Based Spatial Statistics (TBSS) (Smith et al., 2006) to explore possible relationships between DTI metrics and a number of TMS measures, concluding that FA alone may be a poor marker of the biophysical tissue properties underlying CMCT.

We aimed to explore the relationship between CMCT and DTI metrics in a sample of children with motor disorders undergoing assessment for DBS. We utilised a TBSS approach, including FA and other DTI metrics, namely Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (PD).