Transient and Persistent Pain Induced Connectivity Alterations in Pediatric Complex Regional Pain Syndrome

Evaluation of pain-induced changes in functional connectivity was performed in pediatric complex regional pain syndrome (CRPS) patients. High field functional magnetic resonance imaging was done in the symptomatic painful state and at follow up in the asymptomatic pain free/recovered state. Two types of connectivity alterations were defined: (1) Transient increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb vs. unaffected limb in the CRPS state, but with normalized connectivity patterns in the recovered state; and (2) Persistent increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb as compared to the unaffected limb that persisted also in the recovered state (recovered affected limb versus recovered unaffected limb). The data support the notion that even after symptomatic recovery, alterations in brain systems persist, particularly in amygdala and basal ganglia systems. Connectivity analysis may provide a measure of temporal normalization of different circuits/regions when evaluating therapeutic interventions for this condition. The results add emphasis to the importance of early recognition and management in improving outcome of pediatric CRPS

Migraine in the Young Brain: Adolescents vs. Young Adults

Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result

Biological laterality and peripheral nerve DTI metrics

BACKGROUND AND PURPOSE: Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular). MATERIALS AND METHODS: We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed. RESULTS: A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles. CONCLUSION: For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients’ recovery and how we forecast pain chronification

DTI and MTR Measures of Nerve Fiber Integrity in Pediatric Patients With Ankle Injury

Acute peripheral nerve injury can lead to chronic neuropathic pain. Having a standardized, non-invasive method to evaluate pathological changes in a nerve following nerve injury would help with diagnostic and therapeutic assessments or interventions. The accurate evaluation of nerve fiber integrity after injury may provide insight into the extent of pathology and a patient's level of self-reported pain. The aim of this investigation was to evaluate the extent to which peripheral nerve integrity could be evaluated in an acute ankle injury cohort and how markers of nerve fiber integrity correlate with self-reported pain levels in afferent nerves. We recruited 39 pediatric participants with clinically defined neuropathic pain within 3 months of an ankle injury and 16 healthy controls. Participants underwent peripheral nerve MRI using diffusion tensor (DTI) and magnetization transfer imaging (MTI) of their injured and non-injured ankles. The imaging window was focused on the branching point of the sciatic nerve into the tibial and fibular division. Each participant completed the Pain Detection Questionnaire (PDQ). Findings demonstrated group differences in DTI and MTI in the sciatic, tibial and fibular nerve in the injured ankle relative to healthy control and contralateral non-injured nerve fibers. Only AD and RD from the injured fibular nerve correlated with PDQ scores which coincides with the inversion-dominant nature of this particular ankle injuruy cohort. Exploratory analyses highlight the potential remodeling stages of nerve injury from neuropathic pain. Future research should emphasize sub-acute time frames of injury to capture post-injury inflammation and nerve fiber recovery

Challenges of functional imaging research of pain in children

Functional imaging has revolutionized the neurosciences. In the pain field it has dramatically altered our understanding of how the brain undergoes significant functional, anatomical and chemical changes in patients with chronic pain. However, most studies have been performed in adults. Because functional imaging is non-invasive and can be performed in awake individuals, applications in children have become more prevalent, but only recently in the pain field. Measures of changes in the brains of children have important implications in understanding neural plasticity in response to acute and chronic pain in the developing brain. Such findings may have implications for treatments in children affected by chronic pain and provide novel insights into chronic pain syndromes in adults. In this review we summarize this potential and discuss specific concerns related to the imaging of pain in children

Parenting, self-regulation, and treatment adherence in pediatric chronic headache: A self-determination theory perspective

This study examined parenting factors associated with children’s self-regulation and physician-rated treatment adherence using a self-determination theory framework in pediatric chronic headache. Participants were 58 children and adolescents (aged 10–17 years), who underwent initial and follow-up multidisciplinary evaluation at a headache clinic, and their mothers. Regression analyses showed that higher maternal autonomy support and structure were significantly related to children’s lower treatment-related reactance and higher adherence. Maternal controllingness had associations in the opposite directions. Children’s fear of pain was related to maternal controllingness. Results suggest the importance of parents’ provision of clear expectations and engaging children in treatment problem-solving and decision-making

Detailing neuroanatomical development in late childhood and early adolescence using NODDI

<div><p>Diffusion tensor imaging (DTI) studies have provided much evidence of white and subcortical gray matter changes during late childhood and early adolescence that suggest increasing myelination, axon density, and/or fiber coherence. Neurite orientation dispersion and density imaging (NODDI) can be used to further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional DTI. We used measures from NODDI and DTI to examine white and subcortical gray matter development in a group of 27 healthy participants aged 8–13 years. Neurite density index (NDI) was strongly correlated with age in nearly all regions, and was more strongly associated with age than fractional anisotropy (FA). No significant correlations were observed between orientation dispersion index (ODI) and age. This suggests that white matter and subcortical gray matter changes during late childhood and adolescence are dominated by changes in neurite density (i.e., axon density and myelination), rather than increasing coherence of axons. Within brain regions, FA was correlated with both ODI and NDI while mean diffusivity was only related to neurite density, providing further information about the structural variation across individuals. Data-driven clustering of the NODDI parameters showed that microstructural profiles varied along layers of white matter, but that that much of the white and subcortical gray matter matured in a similar manner. Clustering highlighted isolated brain regions with decreasing NDI values that were not apparent in region-of-interest analysis. Overall, these results help to more specifically understand patterns of white and gray matter development during late childhood and early adolescence.</p></div

Age- and sex-related differences in the presentation of paediatric migraine: A retrospective cohort study.

peer reviewedIntroduction Although migraine is a common headache complaint in children and adolescents there remains a significant gap in understanding the unique aspects of the disease in these age groups and their evolution with development. The aim of this retrospective cohort study was to identify migraine features that are influenced by age and sex. Methods The headache characteristics of 359 paediatric patients with a clinical diagnosis of migraine from a tertiary paediatric headache clinic were assessed. Patients retrospectively reported headache characteristics during a structured intake interview and clinical exam. Headache characteristics, description and associated symptoms were compared between children (age 12 years), and between male and female migraineurs. Results Several migraine features differed significantly with age and/or sex, including: (i) a marked change from a 1:1 sex ratio in children to a 2:1 predominance of girls in adolescents; (ii) a higher frequency of headache attacks per month in adolescents and female migraineurs; (iii) a higher proportion of adolescents endorsed a 'throbbing' pain quality; (iv) a higher proportion of children reporting nausea and vomiting; and (v) a higher proportion of adolescents, particularly female migraineurs, had a diagnosis of a co-morbid anxiety. Conclusion The presentation of migraine, both in terms of its headache characteristics and associated symptoms, appear to vary as a function of age and sex. Given that migraine symptoms have a neural basis, it is not surprising that during the key period of neurodevelopment from childhood to adolescence this may impact their presentation

Orientation density index (ODI) trajectories in white (A, B) and grey (C) matter volumes-of-interest.

<p>No correlations between ODI and age were significant; non-significant best-fits are shown as dotted lines. CST: corticospinal tract; ILF/SLF: inferior/superior longitudinal fasciculus; UNC: uncinate fasciculus; ATR: anterior thalamic radiation; CNG: cingulum; FMAJ: forceps major; FMIN: forceps minor; AMYG: amygdala; CAUD: caudate; HIPP: hippocampus; PALL: pallidum; PUTA: putamen; THAL: thalamus.</p

Linear fitting results of NDI (neurite density) and ODI (orientation density) vs. age.

<p>Linear fitting results of NDI (neurite density) and ODI (orientation density) vs. age.</p