Perinatal stroke causes most hemiparetic cerebral palsy, resulting in lifelong disability. We have demonstrated the ability of robots to quantify sensory dysfunction in hemiparetic children but the relationship between such deficits and sensory tract structural connectivity has not been explored. It was aimed to characterize the relationship between the dorsal column medial lemniscus (DCML) pathway connectivity and proprioceptive dysfunction in children with perinatal stroke. Twenty-nine participants (6-19 years old) with MRI-classified, unilateral perinatal ischemic stroke (14 arterial, 15 venous), and upper extremity deficits were recruited from a population-based cohort and compared with 21 healthy controls. Diffusion tensor imaging (DTI) defined DCML tracts and five diffusion properties were quantified: fractional anisotropy (FA), mean, radial, and axial diffusivities (MD, RD, AD), and fiber count. A robotic exoskeleton (KINARM) tested upper limb proprioception in an augmented reality environment. Correlations between robotic measures and sensory tract diffusion parameters were evaluated. Lesioned hemisphere sensory tracts demonstrated lower FA and higher MD, RD, and AD compared with the non-dominant hemisphere of controls. Dominant (contralesional) hemisphere tracts were not different from controls. Both arterial and venous stroke groups demonstrated impairments in proprioception that correlated with lesioned hemisphere DCML tract diffusion properties. Sensory tract connectivity is altered in the lesioned hemisphere of hemiparetic children with perinatal stroke. A correlation between lesioned DCML tract diffusion properties and robotic proprioceptive measures suggests clinical relevance and a possible target for therapeutic intervention. Hum Brain Mapp 38:2424-2440, 2017. © 2017 Wiley Periodicals, Inc.

The biology of post-concussive symptoms is unclear. Symptoms are often increased during activities, and have been linked to decreased cerebrovascular reactivity and perfusion. The aim of this study was to examine cerebral blood flow (CBF) in children with different clinical recovery patterns following mild traumatic brain injury (mTBI). This was a prospective controlled cohort study of children with mTBI (ages 8 to 18 years) who were symptomatic with post-concussive symptoms at one month post-injury (symptomatic, n = 27) and children who had recovered quickly (asymptomatic, n = 24). Pseudo continuous arterial spin labeling magnetic resonance imaging (MRI) was used to quantify CBF. The mTBI groups were imaged at 40 days post-injury. Global and regional CBF were compared with healthy controls of similar age and sex but without a history of mTBI (n = 21). Seventy-two participants (mean age: 14.1 years) underwent neuroimaging. Significant differences in CBF were found: global CBF was higher in the symptomatic group and lower in the asymptomatic group compared with controls, (F(2,69) 9.734; p < 0.001). Post-injury symptom score could be predicted by pre-injury symptoms and CBF in presence of mTBI (adjusted R2 = 0.424; p < 0.001). Altered patterns of cerebral perfusion are seen following mTBI and are associated with the recovery trajectory. Symptomatic children have higher CBF. Children who “recovered” quickly, have decreased CBF suggesting that clinical recovery precedes the cerebral recovery. Further longitudinal studies are required to determine if these perfusion patterns continue to change over time.

Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP), resulting in life-long disability. In this study, we examined the relationship between robotic upper extremity motor impairment and corticospinal tract (CST) diffusion properties. Thirty-three children with unilateral perinatal ischemic stroke (17 arterial, 16 venous) and hemiparesis were recruited from a population-based research cohort. Bilateral CSTs were defined using diffusion tensor imaging (DTI) and four diffusion metrics were quantified: fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivities. Participants completed a visually guided reaching task using the KINARM robot to define 10 movement parameters including movement time and maximum speed. Twenty-six typically developing children underwent the same evaluations. Partial correlations assessed the relationship between robotic reaching and CST diffusion parameters. All diffusion properties of the lesioned CST differed from controls in the arterial group, whereas only FA was reduced in the venous group. Non-lesioned CST diffusion measures were similar between stroke groups and controls. Both stroke groups demonstrated impaired reaching performance. Multiple reaching parameters of the affected limb correlated with lesioned CST diffusion properties. Lower FA and higher MD were associated with greater movement time. Few correlations were observed between non-lesioned CST diffusion and unaffected limb function though FA was associated with reaction time (R = -0.39, p < .01). Diffusion properties of the lesioned CST are altered after perinatal stroke, the degree of which correlates with specific elements of visually guided reaching performance, suggesting specific relevance of CST structural connectivity to clinical motor function in hemiparetic children.

Perinatal stroke causes lifelong disability, particularly hemiparetic cerebral palsy. Arterial ischemic strokes (AIS) are large, cortical, and subcortical injuries acquired near birth due to acute occlusion of the middle cerebral artery. Periventricular venous infarctions (PVI) are smaller, subcortical strokes acquired prior to 34 weeks gestation involving injury to the periventricular white matter. Both stroke types can damage motor pathways, thus, we investigated resulting alterations in functional motor networks and probed function. We measured blood oxygen level dependent (BOLD) fluctuations at rest in 38 participants [10 arterial patients (age = 14.7 AE 4.1 years), 10 venous patients (age = 13.5 AE 3.7 years), and 18 typically developing controls (TDCs) (age = 15.3 AE 5.1 years)] and explored strength and laterality of functional connectivity in the motor network. Inclusion criteria included MRI-confirmed, unilateral perinatal stroke, symptomatic hemiparetic cerebral palsy, and 6-19 years old at time of imaging. Seed-based functional connectivity analyses measured temporal correlations in BOLD response over the whole brain using primary motor cortices as seeds. Laterality indices based on mean z-scores in lesioned and nonlesioned hemispheres explored laterality. In AIS patients, significant differences in both strength and laterality of motor network connections were observed compared with TDCs. In PVI patients, motor networks largely resembled those of healthy controls, albeit slightly weaker and asymmetric, despite subcortical damage and hemiparesis.Functional connectivity strengths were not related to motor outcome scores for either stroke group.This study serves as a foundation to better understand how resting-state fMRI can assess motor functional connectivity and potentially be applied to explore mechanisms of interventional therapies after perinatal stroke. K E Y W O R D Sperinatal stroke, functional connectivity, motor networks, resting-state fMRI, cerebral palsy, pediatric

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ObjectiveWe aimed to employ diffusion imaging connectome methods to explore network development in the contralesional hemisphere of children with perinatal stroke and its relationship to clinical function. We hypothesized alterations in global efficiency of the intact hemisphere would correlate with clinical disability.MethodsChildren with unilateral perinatal arterial (n = 26) or venous (n = 27) stroke and typically developing controls (n = 32) underwent 3T diffusion and T1 anatomical MRI and completed established motor assessments. A validated atlas co-registered to whole-brain tractography for each individual was used to estimate connectivity between 47 regions. Graph theory metrics (assortativity, hierarchical coefficient of regression, global and local efficiency, and small worldness) were calculated for the left hemisphere of controls and the intact contralesioned hemisphere of both stroke groups. Validated clinical motor assessments were then correlated with connectivity outcomes.ResultsGlobal efficiency was higher in arterial strokes compared to venous strokes (p < 0.001) and controls (p < 0.001) and was inversely associated with all motor assessments (all p < 0.012). Additional graph theory metrics including assortativity, hierarchical coefficient of regression, and local efficiency also demonstrated consistent differences in the intact hemisphere associated with clinical function.ConclusionsThe structural connectome of the contralesional hemisphere is altered after perinatal stroke and correlates with clinical function. Connectomics represents a powerful tool to understand whole brain developmental plasticity in children with disease-specific cerebral palsy.

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SUMMARYObjective: Cognitive rehabilitation (CR) is a well-researched therapeutic option for a variety of neurocognitive problems. Recently, CR has been proposed as an option for patients who experience cognitive difficulties following epilepsy surgery (ES). However, there is inconsistency in reporting the efficacy of CR in this population. We appraise existing evidence regarding CR approaches in patients undergoing resective ES and review effectiveness of specific CR strategies. Methods: A comprehensive literature search using MEDLINE, Embase, CINAHL, PsycINFO, and EBM Reviews (including the Cochrane database) identified studies in English published before September 2014, without age restriction, related to CR in patients who underwent resective ES. We included studies focused on patients who underwent ES and who received at least one type of cognitive rehabilitation. Results: Of 2,059 citations identified, four fulfilled eligibility criteria (n = 577), and all investigated the effectiveness of specific CR strategies in patients with either left or right temporal lobe resections. CR strategies used included internal compensatory strategies, external memory aids, psychoeducation, verbal and visual memory training, and exercises of attention and executive functions. None were randomized trials, and only one study involved standardized methods or described the procedures in detail. Evidence suggests that CR may contribute to improvements in aspects of verbal memory, with particular benefit of visual imagery techniques; CR aimed at verbal memory functions may be less effective for patients with hemispheric-dominant resections, and figural memory may not be improved by CR. Furthermore, CR may improve functional and life outcomes, but its timing does not appear to influence its effectiveness. Significance: We demonstrate that CR interventions are overwhelmingly under researched or underreported, and there is a need for a systematic evaluation of CR in this patient population. CR should be given greater attention after ES to determine its efficacy and role in the management of these patients.