Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Functional Gains in Children With Spastic Hemiplegia Following a Tendon Achilles Lengthening Using Computerized Adaptive Testing-A Pilot Study.

PURPOSE: This pilot study evaluated the outcomes of tendon Achilles lengthening in 12 children (mean age: 11.2 years) with spastic hemiplegia. METHODS: Cerebral Palsy Computer Adaptive Tests, the timed up-and-go, the Gross Motor Function Measure, the Gillette Functional Assessment Questionnaire, and the Pediatric Outcomes Data Collection Instrument were administered at baseline and at 6, 12, and 24 months postsurgery. RESULTS: Significant improvement at the latest follow-up (12-24 months following surgery) was seen in all domains of the Cerebral Palsy Computer Adaptive Test: activity (P = .017), lower extremity (P = .005), global (P = .005), pain (P = .005), and fatigue (P = .028), as well as in the Gross Motor Function Measure-D domain (P = .02) and the mobility domain of the Pediatric Outcomes Data Collection Instrument (P = .04). CONCLUSION: These findings indicate that the tendon Achilles lengthening improved functional outcome in these children as measured by tests of physical function, walking speed, and activity performance.

Subliminal (latent) processing of pain and its evolution to conscious awareness.

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, reorganization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions.

Pain and spinal cord imaging measures in children with demyelinating disease.

Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI) and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1) pediatric demyelinating conditions affecting the spinal cord; (2) their distinguishing features; and (3) current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

Inter- and intra-rater reliability of diffusion tensor imaging parameters in the normal pediatric spinal cord.

AIM: To assess inter- and intra-rater reliability (agreement) between two region of interest (ROI) methods in pediatric spinal cord diffusion tensor imaging (DTI). METHODS: Inner-Field-of-View DTI data previously acquired from ten pediatric healthy subjects (mean age = 12.10 years) was used to assess for reliability. ROIs were drawn by two neuroradiologists on each subject data twice within a 3-mo interval. ROIs were placed on axial B0 maps along the cervical spine using free-hand and fixed-size ROIs. Agreement analyses for fractional anisotropy (FA), axial diffusivity, radial diffusivity and mean diffusivity were performed using intra-class-correlation (ICC) and Cronbach's alpha statistical methods. RESULTS: Inter- and intra-rater agreement between the two ROI methods showed moderate (ICC = 0.5) to strong (ICC = 0.84). There were significant differences between raters in the number of pixels selected using free-hand ROIs (P < 0.05). However, no significant differences were observed in DTI parameter values. FA showed highest variability in ICC values (0.10-0.87). Cronbach's alpha showed moderate-high values for raters and ROI methods. CONCLUSION: The study showed that high reproducibility in spinal cord DTI can be achieved, and demonstrated the importance of setting detailed methodology for post-processing DTI data, specifically the placement of ROIs.

An investigation of motion correction algorithms for pediatric spinal cord DTI in healthy subjects and patients with spinal cord injury.

Patient and physiological motion can cause artifacts in DTI of the spinal cord which can impact image quality and diffusion indices. The purpose of this investigation was to determine a reliable motion correction method for pediatric spinal cord DTI and show effects of motion correction on DTI parameters in healthy subjects and patients with spinal cord injury. Ten healthy subjects and ten subjects with spinal cord injury were scanned using a 3T scanner. Images were acquired with an inner field-of-view DTI sequence covering cervical spine levels C1 to C7. Images were corrected for motion using two types of transformation (rigid and affine) and three cost functions. Corrected images and transformations were examined qualitatively and quantitatively using in-house developed code. Fractional anisotropy (FA) and mean diffusivity (MD) indices were calculated and tested for statistical significance pre- and post- motion correction. Images corrected using rigid methods showed improvements in image quality, while affine methods frequently showed residual distortions in corrected images. Blinded evaluation of pre and post correction images showed significant improvement in cord homogeneity and edge conspicuity in corrected images (p<0.0001). The average FA changes were statistically significant (p<0.0001) in the spinal cord injury group, while healthy subjects showed less FA change and were not significant. In both healthy subjects and subjects with spinal cord injury, quantitative and qualitative analysis showed the rigid scaled-least-squares registration technique to be the most reliable and effective in improving image quality.

Neuromuscular scoliosis in children with spinal cord injury.

BACKGROUND: The prevalence of neuromuscular scoliosis in children with spinal cord injury (SCI) is high. Published reports suggest that age at time of injury is the most important determinant. No studies have evaluated neurological characteristics using standardized methods to determine if they are strong predictors of scoliosis. OBJECTIVE: To test the hypothesis that neurological level, motor score, and injury severity are strong predictors of neuromuscular scoliosis. METHODS: Two hundred seventeen children were evaluated using the testing guidelines of the International Standards for Neurological Classification of Spinal Cord Injury. Cobb angles were calculated from plain radiographs as a measure of scoliosis. Multivariate analysis with statistical selection was used to determine predictors of worst Cobb angle and spinal fusion. The odds of having a spine fusion for subjects with at least 2-year follow-up and injured prior to (n=16) and after (n=91) 12 years of age were calculated. RESULTS: The hypothesis was not supported. Although there was a very high prevalence (100%) of scoliosis in the study sample, age at time of injury was the only predictor of worst curve (P < .0001) and spine fusion (P < .007). The calculated odds ratio demonstrated that children injured <12 years were 3.7 times more likely to have a spine fusion (95% CI, 0.31-44.64). CONCLUSION: There is a very high prevalence of neuromuscular scoliosis in pediatric SCI. Neurological level, motor level, and severity of injury are not strong predictors. Age is the only predictor of worst curve and spine fusion.

Diffusion tensor imaging in pediatric spinal cord injury: preliminary examination of reliability and clinical correlation.

STUDY DESIGN: The design was a nonexperimental, repeated measures design. OBJECTIVE: To examine the reliability of repeated diffusion tensor imaging (DTI) values of the pediatric cord and to compare DTI values with values obtained on the clinical examination and findings from conventional magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: DTI quantifies the diffusion of water molecules in directions parallel and transverse to the plane of neuronal axons. The unique characteristic architecture of the spinal cord allows DTI to examine the white matter and potentially separate white matter from gray matter and assess structural damage of the cord. METHODS: Ten youths with cervical spinal cord injury (SCI) were evaluated using the International Standards for Neurological Classification of SCI (ISNCSCI) and had 2 scans using a 3.0T Siemens Verio MR scanner. The imaging protocol consisted of conventional sagittal fast spin echo T1- and T2-weighted scans, axial fast spin echo T2-weighted scans, and axial DTI acquisition. Intraclass correlation coefficient (ICC) and 95% confidence interval were calculated for mean, axial, and radial diffusivity (MD, AD, RD, respectively) and fractional anisotropy (FA). Relationships among DTI, MRI, and ISNCSCI were evaluated using Spearman correlation coefficients (rs) and differences were tested using Cohen's method. RESULTS: There was moderate-to-strong reliability (ICC = 0.75-0.95) for MD, AD, and RD for all spinal levels. Reliability for FA for mid-C4 and between C5-C6 and C7-T1 was moderate (ICC = 0.75-0.80). Diffusivity values demonstrated moderate-to-good negative relationships (rs = -0.30 to -0.59), with 4 ISNCSCI values. FA values had a moderate-to-good (rs = 0.33-0.53) positive relationship, with 5 ISNCSCI values. Compared with MRI, DTI values had significantly stronger correlations (P ≤ 0.0001) with the majority of ISNCSCI values. CONCLUSION: DTI values had good-to-strong reliability on repeated scans and moderate-to-good concurrent validity with clinical scores. When compared with conventional MRI, DTI values had statistically stronger correlations with the majority of values from the clinical examination.

Diffusion tensor imaging in pediatric transverse myelitis: a case study.

Transverse myelitis is diagnosed based on the presence of spinal cord inflammation and the absence of infection to the central nervous system. In support of these criteria, patients undergo lumbar puncture to determine Cerebrospinal Fluid (CSF) pleocytosis and un-enhanced or Gadolinium-enhanced spinal Magnetic Resonance Imaging (MRI). We present the case of an 11~year-old previously healthy male who underwent a series of lab tests and MRI scans before a definite diagnosis of transverse myelitis four years prior to this study. The patient still shows deficits at the C4 cord level according to International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, however, his MRI results are negative, and his Diffusion Tensor Imaging (DTI) results are close to values reported in healthy subjects.