Correlation of quantitative sensorimotor tractography with clinical grade of cerebral palsy.
ABSTRACT The purpose of this study was to determine whether tract-specific diffusion tensor imaging measures in somatosensory and motor pathways correlate with clinical grades as defined using the Gross Motor Function Classification System (GMFCS) in cerebral palsy (CP) children.
Quantitative diffusion tensor tractography was performed on 39 patients with spastic quadriparesis (mean age = 8 years) and 14 age/sex-matched controls. All patients were graded on the basis of GMFCS scale into grade II (n = 12), grade IV (n = 22), and grade V (n = 5) CP and quantitative analysis reconstruction of somatosensory and motor tracts performed.
Significant inverse correlation between clinical grade and fractional anisotropy (FA) was observed in both right and left motor and sensory tracts. A significant direct correlation of mean diffusivity values from both motor and sensory tracts was also observed with clinical grades. Successive decrease in FA values was observed in all tracts except for left motor tracts moving from age/sex-matched controls to grade V through grades II and IV.
We conclude that white matter tracts from both the somatosensory and the motor cortex play an important role in the pathophysiology of motor disability in patients with CP.
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ABSTRACT: The objective of the study was to determine whether constraint-induced movement therapy (CIMT) could lead to changes in diffusion tensor tractography (DTT) associated with clinical improvement in young children with unilateral cerebral palsy (CP). A standardized pediatric CIMT protocol (4weeks, 120h of constraint) was used on 10 children with unilateral CP who were younger than 5years. DTT was performed in five participants before and after the intervention. Clinical outcome was measured by using the Pediatric Motor Activity Log (PMAL), Quality of Upper Extremity Skills Test (QUEST), and self-care domain of the Pediatric Evaluation of Disability Inventory. In two patients, the affected corticospinal tract (CST) visible on pretreatment DTT became more prominent on posttreatment DTT. In one patient, the affected CST was not visible on pretreatment DTT, but was visible on posttreatment DTT. All the clinical outcomes significantly improved in the CIMT group compared with the control group. Changes in the PMAL how often scale (PMAL-HO) score significantly differed between the CIMT and control groups. Changes in the properties of the affected CST on DTT were accompanied with improved arm function after CIMT in the children with CP. CIMT might lead to CST reorganization in young children with CP.Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 03/2014; · 3.12 Impact Factor
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ABSTRACT: Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16-0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.NeuroImage: Clinical. 01/2014; 5.
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ABSTRACT: Although cerebral palsy (CP) is among the most common causes of physical disability in early childhood, we know little about the functional and structural changes of this disorder in the developing brain. Here, we investigated with three different neuroimaging modalities [magnetoencephalography (MEG), diffusion tensor imaging (DTI), and resting-state fMRI] whether spastic CP is associated with functional and anatomical abnormalities in the sensorimotor network. Ten children participated in the study: four with diplegic CP (DCP), three with hemiplegic CP (HCP), and three typically developing (TD) children. Somatosensory (SS)-evoked fields (SEFs) were recorded in response to pneumatic stimuli applied to digits D1, D3, and D5 of both hands. Several parameters of water diffusion were calculated from DTI between the thalamus and the pre-central and post-central gyri in both hemispheres. The sensorimotor resting-state networks (RSNs) were examined by using an independent component analysis method. Tactile stimulation of the fingers elicited the first prominent cortical response at ~50 ms, in all except one child, localized over the primary SS cortex (S1). In five CP children, abnormal somatotopic organization was observed in the affected (or more affected) hemisphere. Euclidean distances were markedly different between the two hemispheres in the HCP children, and between DCP and TD children for both hemispheres. DTI analysis revealed decreased fractional anisotropy and increased apparent diffusion coefficient for the thalamocortical pathways in the more affected compared to less affected hemisphere in CP children. Resting-state functional MRI results indicated absent and/or abnormal sensorimotor RSNs for children with HCP and DCP consistent with the severity and location of their lesions. Our findings suggest an abnormal SS processing mechanism in the sensorimotor network of children with CP possibly as a result of diminished thalamocortical projections.Frontiers in Human Neuroscience 09/2014; 8(725). · 2.90 Impact Factor
Correlation of Quantitative Sensori-Motor Tractography with Clinical Grade of Cerebral Palsy
R. Trivedi1, S. Agarwal2, V. Shah3, P. Goyal4, V. K. Paliwal5, R. K. Rathore2, and R. K. Gupta6
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, Delhi, India, 2Mathematics and Statistics, Indian Institute of Technology, Kanpur,
Uttar Pradesh, India, 33Pediatric Orthopedic Surgery unit, Bhargava Nursing Home, Lucknow, Uttar Pradesh, India, 4Anesthesiology, Sanjay Gandhi Post Graduate
Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, 5Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India,
6Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Cerebral palsy (CP) is the term used to describe a group of developmental disorders of movement and posture causing activity limitation or disability.
During brain maturation, pyramidal tract and the somatosensory radiation are susceptible to injury leading to neurological deficits, often resulting in the classic clinical
presentation of spastic diplegia/quadriplegia in children born preterm . Neuroimaging studies using conventional magnetic resonance imaging (MRI) have shown that
70 to 90 % of affected children have structural brain abnormalities . Serial DTI has been used to study the plasticity of the CST in spastic quadriparesis . In most
studies, DTI quantitative metrics have been obtained using region of interest (ROI) analysis. ROI based morphometric DTI analysis is limited to 2dimensions (D) and
does not reflect the whole fiber bundle. The information about the direction of diffusion encoded by the eigenvalues and eigenvectors of the diffusion tensor has been
used in DTI tractography to investigate the continuity of axonal orientation between voxels and thus to infer the paths of fiber tracts in 3D. In the present study, we
analyzed fractional anisotropy (FA) and mean diffusivity (MD) values in sensory and motor tracts in children with spastic quadriparesis and age/sex matched controls.
Our primary hypothesis was that both sensory and motor WM injury would correlate with clinical grade as defined using the Gross Motor Function Classification
Materials and Methods: The institutional research ethics committee approved the study. We examined 39 children (30 boys and 9 girls) CP who had spastic
quadriparesis (mean age of 9 years) and 14 age and sex-matched controls. All of the children participated in this study were born at term (>37 weeks gestational age)
and had no history of seizures. The diagnosis of CP was based on clinical observations. The major signs that collectively lead to the diagnosis of CP were: delayed
motor milestones, abnormal neurologic examination, persistence of primitive reflexes, and abnormal postural reactions. All patients were assessed by standard clinical
examination, video gait examination, GMFCS scale  and modified Ashworth scales (to measure spasticity). Patients were graded according to GMFCS scale. Out of
39 children, twelve children had CP with grade II, 22 children had grade IV CP, and remaining 5 children had grade V CP.
Whole brain conventional MRI (T2, T1 and FLAIR) and DTI were performed on a 1.5-Tesla GE MRI system. All imaging was performed in the axial plane
and had identical geometrical parameters: field of view (FOV) = 240 × 240 mm2, slice thickness = 3 mm, interslice gap = 0 and number of slices = 36.DTI data were
acquired using a single-shot echo-planar dual spin-echo sequence with ramp sampling. The diffusion tensor encoding used was a dodecahedral scheme with 10
uniformly distributed directions. Fiber assignment by continuous tracking (FACT) algorithm was used for reconstruction of fibers. The white matter fiber tracts were
generated as described in detail elsewhere (5). The central sulcus was identified and marked on sagittal surface image reconstructed by 3D surface rendering of b0
image stack. By using 3D cross connectivity between three planes central sulcus was displayed on axial images. Free hand ROIs were drawn on axial T2-weighted
image near the brain’s vertex on the precentral and postcentral gyri, and the fibers generated from those ROIs were defined as motor and somatosensory tracts,
Statistical analysis: Bivariate analysis of correlation was performed to study the relationship between the sensory and motor tract specific DTI measures and clinical
grade of CP with the assumption that there was no correlation between DTI measures and clinical grade (Ho=0). Alternatively, if a correlation of <0.001 is observed at
α=0.05 and 90% power of the test, the null hypothesis was rejected. One-way analysis of variance (ANOVA) with multiple comparisons using Bonferroni, Post Hoc test
was performed to evaluate the differences in tract specific DTI metrics among age/sex matched controls and patient groups in sensory and motor tracts. P values of ≤
0.05 were considered to be significant.
Results: Significant inverse correlation between clinical grade and FA values was observed in both right* and left** motor (*r=-0.497, p=0.001; **r=-0.504, p=0.001)
and sensory (*r=-0.621, p<0.001; **r=-0.693, p<0.001) tracts. Significant direct correlation between clinical grade and MD was observed only in left motor (r=0.368,
p=0.032) tracts. When we pooled MD values from right and left hemisphere, significant direct correlation was observed between MD and clinical grade in both motor
(r=0.342, p=0.004) and sensory (r=0.278, p=0.023) tracts.
Successive decrease in FA values was observed in right motor and right as well as left sensory tracts moving from controls to grade V through grade II and
IV (Fig. 2). Though, no successive change in MD values in motor as well as sensory tracts was observed moving from controls to grade V through grade II and IV (Fig.
4), all the patient groups showed increased MD values compared to controls in both motor and sensory tracts.
Fig.1: Demonstration of methodology used for motor (red) and sensory (blue) tracts reconstruction from 7-years-old control.
Fig.2: Bar graph shows differences of FA values in the motor and sensory pathways in control and patient groups. *Denotes the significance difference in patient
groups compared to controls. # Denotes the significant difference between patient groups.
Discussion: This study demonstrates the correlation between clinical grades and DTI measures in motor and sensory pathways in children with CP. In this study 11
(28%) patients showed normal imaging even though they shared similar clinical profile with children who were abnormal on conventional imaging. This data suggests
that conventional MRI is inadequate for the assessment of clinical grade. Significant inverse correlation of FA with clinical grades suggests that FA is a better measure
than conventional MRI for the assessment of clinical grade in these patients.
Correlation of FA with clinical grade was much stronger in sensory tracts than motor tracts, which suggest that sensory tracts are probably more damaged in
these patients and may play a role in the pathophysiology of motor disability in patients with CP. Instead of using an indirect approach to quantify sensory tracts i.e.
thalamic radiation, in this study we quantified DTI measure of sensory tracts generated from primary somatosensory cortex. In contrast to Hoon et al. we performed
quantitative DTT analysis of whole sensory and motor tracts in these patients. In this study we extend our understanding of the pathophysiology of CP in children with
spastic quadriparesis by showing that DTI measures in both motor and sensory pathways reflects the degree of motor deficits.
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349; 4) Palisano R, et al. Dev Med Child Neurol 1997; 39: 214-223; 5) Pediatric Research 2009 (Epub ahead of print); 6) Hoon Jr AH, et al. Dev Med Child Neurol
2009; 51: 697-704.