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Pediatric stroke: We need to look for it
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Revolutionary advancements in regenerative medicine have brought stem cell therapy to the forefront,
offering promising prospects for the regeneration of ischemic cardiac tissue. Yet, its full efficacy, safety, and
role in treating ischemic heart disease (IHD) remain limited. This literature review explores the intricate
mechanisms underlying stem cell therapy. Furthermore, we unravel the innovative approaches employed to
bolster stem cell survival, enhance differentiation, and seamlessly integrate them within the ischemic
cardiac tissue microenvironment.
Our comprehensive analysis uncovers how stem cells enhance cell survival, promote angiogenesis, and
modulate the immune response. Stem cell therapy harnesses a multifaceted mode of action, encompassing
paracrine effects and direct cell replacement. As our review progresses, we underscore the imperative for
standardized protocols, comprehensive preclinical and clinical studies, and careful regulatory
considerations. Lastly, we explore the integration of tissue engineering and genetic modifications,
envisioning a future where stem cell therapy reigns supreme in regenerative medicine
Background
Brain–computer interface (BCI) has been widely used for functional recovery after stroke. Understanding the brain mechanisms following BCI intervention to optimize BCI strategies is crucial for the benefit of stroke patients.
Methods
Forty-six patients with upper limb motor dysfunction after stroke were recruited and randomly divided into the control group or the BCI group. The primary outcome was measured by the assessment of Fugl–Meyer Assessment of Upper Extremity (FMA-UE). Meanwhile, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in all patients, followed by independent component analysis (ICA) to identify functionally connected brain networks. Finally, we assessed the topological efficiency of both groups using graph-theoretic analysis in these brain subnetworks.
Results
The FMA-UE score of the BCI group was significantly higher than that of the control group after treatment (p = 0.035). From the network topology analysis, we first identified seven subnetworks from the rs-fMRI data. In the following analysis of subnetwork properties, small-world properties including γ (p = 0.035) and σ (p = 0.031) within the visual network (VN) decreased in the BCI group. For the analysis of the dorsal attention network (DAN), significant differences were found in assortativity (p = 0.045) between the groups. Additionally, the improvement in FMA-UE was positively correlated with the assortativity of the dorsal attention network (R = 0.498, p = 0.011).
Conclusion
Brain–computer interface can promote the recovery of upper limbs after stroke by regulating VN and DAN. The correlation trend of weak intensity proves that functional recovery in stroke patients is likely to be related to the brain’s visuospatial processing ability, which can be used to optimize BCI strategies.
Clinical Trial Registration
The trial is registered in the Chinese Clinical Trial Registry, number ChiCTR2000034848. Registered 21 July 2020.
Background
There is little consensus on how lesion size impacts long-term cognitive outcome after pediatric arterial ischemic stroke (AIS). This study, therefore, compares two techniques to assessed lesion size in the chronic phase after AIS and determined their measurement agreement in relation to cognitive functions in patients after pediatric stroke.
Methods
Twenty-five patients after pediatric AIS were examined in the chronic phase (>2 years) after AIS in respect to intelligence, memory, executive functions, visuo-motor skills, motor abilities, and disease-specific outcome. Lesion size was measured using the ABC/2 formula and segmentation technique (3D Slicer). Correlation analysis determined the association between volumetry techniques and outcome measures in respect to long-term cognitive outcome.
Results
The measurements from the ABC/2 and segmentation technique were strongly correlated (r = 0.878, p < .001) and displayed agreement in particular for small lesions. Lesion size from both techniques was significantly correlated with disease-specific outcome (p < .001) and processing speed (p < .005) after controlling for age at stroke and multiple comparison.
Conclusion
The two techniques showed convergent validity and were both significantly correlated with long-term outcome after pediatric AIS. Compared to the time-consuming segmentation technique, ABC/2 facilitates clinical and research work as it requires relatively little time and is easy to apply.
Cerebral palsy (CP), the most common disability in childhood, is adevastating non-progressive ailment of the infants' brain with lifelongsequelae, e.g., spastic paresis, chronic pain, inability to walk, intellectualdisability, behavioral disorders, for which there is no cure at present.CP may develop after pediatric brain damage caused, e.g., by hypoxic-ischemia, periventricular leukomalacia, intracranial hemorrhage, hypoxic-ischemicencephalopathy, trauma, stroke, and infection. About 17 million peopleworldwide live with cerebral palsy as a result of pediatric brain damage.This reflects both the magnitude of the personal, medical, andsocioeconomic global burden of this brain disorder and the overt unmettherapeutic needs of the pediatric population.This review will focus on recent preclinical, clinical, and regulatorydevelopments in cell therapy for infantile cerebral palsy bytransplantation of cord blood derived mononuclear cells from bench tobedside. The body of evidence suggests that cord blood cell therapy ofcerebral palsy in the autologous setting is feasible, effective, and safe,however, adequately powered phase 3 trials are overdue.
https://mc.manuscriptcentral.com/jpmedJournal of Perinatal Medicine
https://www.researchgate.net/publication/365303033_2022_10_27_JPMed20220505_Accept_in_its_present_form [accessed Nov 11 2022].
Background and Objectives: The diagnostic value of thrombophilia remains unknown in young patients with patent foramen ovale (PFO) and stroke. In this study we hypothesized that inherited thrombophilias that lead to venous thrombosis are more prevalent in patients with PFO. Materials and Methods: The study included patients of the tertiary center Vilnius University Hospital Santaros Klinikos who had a cryptogenic ischemic stroke between the ages of 18 and 50 between the years 2008 and 2021. Transient ischemic attacks were excluded. Contrast-enhanced transcranial Doppler ultrasound and extensive laboratory testing were performed. Results: The study included 161 cryptogenic stroke patients (mean age 39.2 ± 7.6 years; 54% female), and a right-to-left shunt was found in 112 (69.6%). The mean time between stroke and thrombophilia testing was 210 days (median 98 days). In total, 61 (39.8%) patients were diagnosed with thrombophilia. The most common finding was hyperhomocysteinemia (26.7%), 14.3% of which were genetically confirmed. Two patients (1.2%) were diagnosed with factor V Leiden mutation, three patients (1.9%) with prothrombin G20210A mutation, one patient (0.6%) had a protein C mutation and one patient (0.6%)
had a protein S mutation. No antithrombin mutations were diagnosed in our study population. A total of 45.5% of patients with inherited thrombophilia had a right-to-left shunt, while 54.5% did not, p = 0.092. Personal thrombosis anamnesis was positive significantly more often in patients with antiphospholipid syndrome. Conclusions: The hypothesis of the study was rejected since inherited venous thrombophilia was not significantly more common in patients with PFO. Due to the rarity of thrombophilias in general, more research with a larger sample size is required to further verify our findings.
Background:
Children with severe motor impairment but intact cognition are deprived of fundamental human rights. Quadriplegic cerebral palsy is the most common scenario where rehabilitation options remain limited. Brain-computer interfaces (BCI) represent a potential solution, but pediatric populations have been neglected. Direct engagement of children and families could provide meaningful opportunities while informing program development. We describe a patient-centered, clinical, non-invasive pediatric BCI program.
Methods:
Eligible children were identified within a population-based, tertiary care children's hospital. Criteria included 1) age six to 18 years, 2) severe physical disability (non-ambulatory, minimal hand use), 3) severely limited speech, and 4) evidence of grade 1 cognitive capacity. After initial screening for BCI competency, participants attended regular sessions, attempting commercially available and customized systems to play computer games, control devices, and attempt communication.
Results:
We report the first 10 participants (median 11 years, range 6-16, 60% male). Over 334 hours of participation, there were no serious adverse events. BCI training was well tolerated, with favorable feedback from children and parents. All but one participant demonstrated the ability to perform BCI tasks. The majority performed well, using motor imagery based tasks for games and entertainment. Difficulties were most significant using P300, visual evoked potential based paradigms where maintenance of attention was challenging. Children and families expressed interest in continuing and informing program development.
Conclusions:
Patient-centered clinical BCI programs are feasible for children with severe disabilities. Carefully selected participants can often learn quickly to perform meaningful tasks on readily available systems. Patient and family motivation and engagement appear high.
Several studies have shown the positive clinical effect of brain computer interface (BCI) training for stroke rehabilitation. This study investigated the efficacy of the sensorimotor rhythm (SMR)-based BCI with audio-cue, motor observation and multisensory feedback for post-stroke rehabilitation. Furthermore, we discussed the interaction between training intensity and training duration in BCI training. Twenty-four stroke patients with severe upper limb (UL) motor deficits were randomly assigned to two groups: 2-week SMR-BCI training combined with conventional treatment (BCI Group, BG, n = 12) and 2-week conventional treatment without SMR-BCI intervention (Control Group, CG, n = 12). Motor function was measured using clinical measurement scales, including Fugl-Meyer Assessment-Upper Extremities (FMA-UE; primary outcome measure), Wolf Motor Functional Test (WMFT), and Modified Barthel Index (MBI), at baseline (Week 0), post-intervention (Week 2), and follow-up week (Week 4). EEG data from patients allocated to the BG was recorded at Week 0 and Week 2 and quantified by mu suppression means event-related desynchronization (ERD) in mu rhythm (8–12 Hz). All functional assessment scores (FMA-UE, WMFT, and MBI) significantly improved at Week 2 for both groups (p < 0.05). The BG had significantly higher FMA-UE and WMFT improvement at Week 4 compared to the CG. The mu suppression of bilateral hemisphere both had a positive trend with the motor function scores at Week 2. This study proposes a new effective SMR-BCI system and demonstrates that the SMR-BCI training with audio-cue, motor observation and multisensory feedback, together with conventional therapy may promote long-lasting UL motor improvement.
Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR2000041119].
OBJECTIVE
Ivy sign is a radiographic finding on FLAIR MRI sequences and is associated with slow cortical blood flow in moyamoya. Limited data exist on the utility of the ivy sign as a diagnostic and prognostic tool in pediatric patients, particularly outside of Asian populations. The authors aimed to investigate a modified grading scale with which to characterize the prevalence and extent of the ivy sign in children with moyamoya and evaluate its efficacy as a biomarker in predicting postoperative outcomes, including stroke risk.
METHODS
Pre- and postoperative clinical and radiographic data of all pediatric patients (21 years of age or younger) who underwent surgery for moyamoya disease or moyamoya syndrome at two major tertiary referral centers in the US and Israel, between July 2009 and August 2019, were retrospectively reviewed. Ivy sign scores were correlated to Suzuki stage, Matsushima grade, and postoperative stroke rate to quantify the diagnostic and prognostic utility of ivy sign.
RESULTS
A total of 171 hemispheres in 107 patients were included. The median age at the time of surgery was 9 years (range 3 months–21 years). The ivy sign was most frequently encountered in association with Suzuki stage III or IV disease in all vascular territories, including the anterior cerebral artery (53.7%), middle cerebral artery (56.3%), and posterior cerebral artery (47.5%) territories. Following surgical revascularization, 85% of hemispheres with Matsushima grade A demonstrated a concomitant, statistically significant reduction in ivy sign scores (OR 5.3, 95% CI 1.4–20.0; p = 0.013). Postoperatively, revascularized hemispheres that exhibited ivy sign score decreases had significantly lower rates of postoperative stroke (3.4%) compared with hemispheres that demonstrated no reversal of the ivy sign (16.1%) (OR 5.5, 95% CI 1.5–21.0; p = 0.008).
CONCLUSIONS
This is the largest study to date that focuses on the role of the ivy sign in pediatric moyamoya. These data demonstrate that the ivy sign was present in approximately half the pediatric patients with moyamoya with Suzuki stage III or IV disease, when blood flow was most unstable. The authors found that reversal of the ivy sign provided both radiographic and clinical utility as a prognostic biomarker postoperatively, given the statistically significant association with both better Matsushima grades and a fivefold reduction in postoperative stroke rates. These findings can help inform clinical decision-making, and they have particular value in the pediatric population, as the ability to minimize additional radiographic evaluations and tailor radiographic surveillance is requisite.
Adaptive recovery of cerebral perfusion after pediatric arterial ischemic stroke (AIS) is sought to be crucial for sustainable rehabilitation of cognitive functions. We therefore examined cerebral blood flow (CBF) in the chronic stage after stroke and its association with cognitive outcome in patients after pediatric AIS. This cross-sectional study investigated CBF and cognitive functions in 14 patients (age 13.5 ± 4.4 years) after pediatric AIS in the middle cerebral artery (time since AIS was at least 2 years prior to assessment) when compared with 36 healthy controls (aged 13.8 ± 4.3 years). Cognitive functions were assessed with neuropsychological tests, CBF was measured with arterial spin labeled imaging in the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA). Patients had significantly lower IQ scores and poorer cognitive functions compared to healthy controls (p < 0.026) but mean performance was within the normal range in all cognitive domains. Arterial spin labeled imaging revealed significantly lower CBF in the ipsilesional MCA and PCA in patients compared to healthy controls. Further, we found significantly higher interhemispheric perfusion imbalance in the MCA in patients compared to controls. Higher interhemispheric perfusion imbalance in the MCA was significantly associated with lower working memory performance. Our findings revealed that even years after a pediatric stroke in the MCA, reduced ipsilesional cerebral blood flow occurs in the MCA and PCA and that interhemispheric imbalance is associated with cognitive performance. Thus, our data suggest that cerebral hypoperfusion might underlie some of the variability observed in long-term outcome after pediatric stroke.
Background:
Pediatric arterial ischemic stroke (AIS), which was thought to be a rare disorder, is being increasingly recognized as an important cause of neurological morbidity, thanks to new advances in neuroimaging.
Objective:
The aim of this study was to review the main etiologies of stroke due to arteriopathy in children.
Methods:
Using a series of cases from our institution, we addressed its epidemiological aspects, physiopathology, imaging findings from CT, MR angiography, MR conventional sequences and MR DWI, and nuclear medicine findings.
Results:
Through discussion of the most recent classification for childhood AIS (Childhood AIS Standardized Classification and Diagnostic Evaluation, CASCADE), we propose a modified classification based on the anatomical site of disease, which includes vasculitis, varicella, arterial dissection, moyamoya, fibromuscular dysplasia, Takayasu's arteritis and genetic causes (such as ACTA-2 mutation, PHACE syndrome and ADA-2 deficiency). We have detailed each of these separately. Conclusions: Prompt recognition of AIS and thorough investigation for potential risk factors are crucial for a better outcome. In this scenario, neurovascular imaging plays an important role in diagnosing AIS and identifying children at high risk of recurrent stroke.
Aim
To identify clinical and radiological predictors of long‐term motor outcome after childhood‐onset arterial ischemic stroke (AIS) in the middle cerebral artery (MCA) territory.
Method
Medical records of 69 children (36 females, 33 males; median age at index AIS 3y 3mo, range: 1mo–16y) who presented to Great Ormond Street Hospital with first AIS in the MCA territory were reviewed retrospectively. Cases were categorized using the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE). Magnetic resonance imaging (MRI) and angiography were evaluated. An Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was calculated on MRI. The Recurrence and Recovery Questionnaire assessed motor outcome and was dichotomized into good/poor.
Results
Eventual motor outcome was good in 49 children and poor in 20. There were no acute radiological predictors of eventual motor outcome. At follow‐up, CASCADE 3A (i.e. moyamoya) and Wallerian degeneration were significantly associated with poor motor outcome. In the multivariate analysis, younger age and CASCADE 3A predicted poor motor outcome.
Interpretation
In the context of recommendations regarding unproven and potentially high‐risk hyperacute therapies for childhood AIS, prediction of outcome could usefully contribute to risk/benefit analysis. Unfortunately, paradigms used in adults, such as ASPECTS, are not useful in children in the acute/early subacute phase of AIS.
What this paper adds
Adult paradigms, such as the Alberta Stroke Program Early Computed Tomography Score system, are not useful for predicting outcome in children.
Younger children tend to have a poorer long‐term prognosis than older children.
Moyamoya is associated with poor prognosis.
Introduction:
Ischemic stroke is an important cause of death and long-term morbidity in children. Viral respiratory infections are emerging as important risk factors for ischemic stroke in this age group of patients. Direct action of virus against cerebral vessels, autoimmune reactivity, and an increased production of cytokines have all been advocated as main factors in determining ischemic stroke.
Case report:
We report the case of an EBV-induced ischemic stroke in a caucasian 2 year-old female. The cerebrospinal fluid samples showed positivity of polymerase chain reaction for EBV infection, also confirmed by pharyngeal swab culture. Increased levels of interleukin 6 and interleukin 1b were also detected in the cerebrospinal fluid. Discussion: EBV infection has been identified as an important cause of neurological involvement in children. Findings of increased levels of interleukin 6 and interleukin 1b in the cerebrospinal fluid of the child with EBV induced-ischemic stroke seems to validate the role of pro-inflammatory cytokines as crucial mediators of cerebral thrombus formation. Conclusions: We believe that this report can be useful to clarify some pathophysiological mechanisms related to ischemic stroke related to Epstein-Barr Virus (EBV) infection in children.
Arterial ischemic stroke (AIS) in children is a rare condition; its frequency is estimated at 0.58 to 7.9 new onsets in 100,000 children per year. The knowledge on risk factors, clinical outcomes and consequences of pediatric AIS is increasing. However, there are still many unknowns in the field. The aim of the study was to analyze the clinical presentation of pediatric AIS and its consequences according to the neuroimaging results and location of ischemia. The research was retrospective and observational. The analyzed group consisted of 75 AIS children (32 girls, 43 boys), whereby the age of the patients ranged from 9 months to 18 years at stroke onset. All the patients were diagnosed and treated in one tertiary center. The most frequent stroke subtype was total anterior circulation infarct (TACI) with most common ischemic focus location in temporal lobe and vascular pathology in middle cerebral artery (MCA). The location of ischemic focus in the brain correlated with post-stroke outcomes: intellectual delay and epilepsy, hemiparesis corresponded to the location of vascular pathology. A correlation found between ischemic lesion location and vascular pathology with post-stroke consequences in pediatric AIS may be important information and helpful in choosing proper early therapy. The expected results should lead to lesser severity of late post-stroke outcomes.
“Ivy sign” is a special imaging manifestation of moyamoya disease (MMD), which shows continuous linear or punctate high intensity along the cortical sulci and subarachnoid space on magnetic resonance images. Ivy sign was reported to reflect the development of compensatory collaterals, and to be closely related to hemodynamic changes and clinical symptoms, and to indicate the postoperative prognosis, in MMD patients. It is a unique and critical marker for MMD. However, due to the lack of consistent criteria, such as definition, grading, and identification standards, ivy sign has not received much attention. We undertook a comprehensive literature search and summarized the current situation regarding ivy sign in MMD in terms of baseline characteristics, detection methods, definition, regional division and distribution patterns, grading criterions, incidence, related factors, the mechanism of ivy sign, and the effects of treatments. We also provided related concerns raised and future prospects relevant to studies about ivy sign in MMD.
Context: Based on current literature, there is no consensus regarding the proper management of pediatric acute ischemic stroke (P-AIS); and there are lots of considerable controversies in this regard. Therefore, the current review was conducted to provide a more comprehensive discussion in this topic.
Evidence acquisition: The search was conducted using terms “pediatrics”, “stroke” and “recombinant tissue plasminogen activator” in PubMed database. English language papers on management of P-AIS published after 2000 were selected. A critical appraisal was performed in an expert panel to summarize the findings and make them applicable. Finally, the extracted data were categorized in subheadings and the manuscript was prepared.
Results: There are limited evidence on the topic; all extracted findings are categorized as follows: Etiology and the underlying diseases, clinical presentations, diagnosis, management (thrombolytic therapy and thrombectomy) and outcome.
Conclusion: It seems that although thrombolytic therapy is recommended in P-AIS, but since most of the cases are diagnosed outside the therapeutic window, this treatment is practically impossible, so they are candidate for mechanical interventions. On the other hand, proper device may not be available to fit the size of younger child's vasculature.
Pediatric access to exoskeletons lags far behind that of adults. In this article, we promote inclusiveness in exoskeleton robotics by identifying and addressing challenges and barriers to pediatric access to this potentially life-changing technology. We first present available exoskeleton solutions for upper and lower limbs and note the variability in the absence of these. Next, we query the possible reasons for this variability in access, explicitly focusing on children, who constitute a categorically vulnerable population, and also stand to benefit significantly from the use of this technology at this critical point in their physical and emotional growth. We propose the use of a life-based design approach as a way to address some of the design challenges and offer insights toward a resolution regarding market viability and implementation challenges. We conclude that the development of pediatric exoskeletons that allow for and ensure access to health-enhancing technology is a crucial aspect of the responsible provision of health care to all members of society. For children, the stakes are particularly high, given that this technology, when used at a critical phase of a child’s development, not only holds out the possibility of improving the quality of life but also can improve the long-term health prospects.
Similar to functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS) detects the changes of hemoglobin species inside the brain, but via differences in optical absorption. Within the near-infrared spectrum, light can penetrate biological tissues and be absorbed by chromophores, such as oxyhemoglobin and deoxyhemoglobin. What makes fNIRS more advantageous is its portability and potential for long-term monitoring. This paper reviews the basic mechanisms of fNIRS and its current clinical applications, the limitations toward more widespread clinical usage of fNIRS, and current efforts to improve the temporal and spatial resolution of fNIRS toward robust clinical usage within subjects. Oligochannel fNIRS is adequate for estimating global cerebral function and it has become an important tool in the critical care setting for evaluating cerebral oxygenation and autoregulation in patients with stroke and traumatic brain injury. When it comes to a more sophisticated utilization, spatial and temporal resolution becomes critical. Multichannel NIRS has improved the spatial resolution of fNIRS for brain mapping in certain task modalities, such as language mapping. However, averaging and group analysis are currently required, limiting its clinical use for monitoring and real-time event detection in individual subjects. Advances in signal processing have moved fNIRS toward individual clinical use for detecting certain types of seizures, assessing autonomic function and cortical spreading depression. However, its lack of accuracy and precision has been the major obstacle toward more sophisticated clinical use of fNIRS. The use of high-density whole head optode arrays, precise sensor locations relative to the head, anatomical co-registration, short-distance channels, and multi-dimensional signal processing can be combined to improve the sensitivity of fNIRS and increase its use as a wide-spread clinical tool for the robust assessment of brain function.
The introduction of robotic neurorehabilitation among the most recent technologies in pediatrics represents a new opportunity to treat pediatric patients. This study aims at evaluating the response of physiotherapists, patients and their parents to this new technology. The study considered the outcomes of technological innovation in physiotherapists (perception of the workload, satisfaction), as well as that in patients and their parents (quality of life, expectations, satisfaction) by comparing the answers to subjective questionnaires of those who made use of the new technology with those who used the traditional therapy. A total of 12 workers, 46 patients and 47 parents were enrolled in the study. Significant differences were recorded in the total workload score of physiotherapists who use the robotic technology compared with the traditional therapy (p < 0.001). Patients reported a higher quality of life and satisfaction after the use of the robotic neurorehabilitation therapy. The parents of patients undergoing the robotic therapy have moderately higher expectations and satisfaction than those undergoing the traditional therapy. In this pilot study, the robotic neurorehabilitation technique involved a significant increase in the patients’ and parents’ expectations. As it frequently happens in the introduction of new technologies, physiotherapists perceived a greater workload. Further studies are needed to verify the results achieved.
Background
The contralesional hemisphere compensation may play a critical role in the recovery of stroke when there is extensive damage to one hemisphere. There is little research on the treatment of hemiplegia by high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the contralesional cortex.
Objective
We conducted a 2-week randomized, sham-controlled, single-blind trial to determine whether high-frequency rTMS (HF-rTMS) over the contralesional motor cortex can improve motor function in severe stroke patients.
Methods
Forty-five patients with ischemic or hemorrhagic stroke in the middle cerebral artery territory were randomly assigned to treatment with 10 Hz rTMS (HF group), 1 Hz rTMS (LF group) or sham rTMS (sham group) applied over the contralesional motor cortex (M1) before physiotherapy daily for two weeks. The primary outcome was the change in the Fugl-Meyer Motor Assessment (FMA) Scale score from baseline to 2 weeks. The secondary endpoints included root mean square of surface electromyography (RMS-SEMG), Barthel Index (BI), and contralesional hemisphere cortical excitability.
Results
The HF group showed a more significant improvement in FMA score (p < .05), BI (p < .005), contralesional hemisphere cortical excitability and conductivity (p < .05), and RMS-SEMG of the key muscles (p < .05) compared with the LF group and sham group. There were no significant differences between the LF group and sham group. There was a positive correlation between cortical conductivity of the uninjured hemisphere and recovery of motor impairment (p= .039).
Conclusions
HF-rTMS over the contralesional cortex was superior to low-frequency rTMS and sham stimulation in promoting motor recovery in patients with severe hemiplegic stroke by acting on contralesional cortex plasticity.
Trial registration
Clinical trial registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn/showproj.aspx?proj=23264 (ChiCTR-IPR-17013580).
Objective
To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke.
Methods
We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with two‐year follow‐up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at two years by Pediatric Stroke Outcome Measure (PSOM). Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to two years as recovery (improved outcome), emerging deficit (worse outcome), or no change.
Results
Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates vs 48.8% of children at discharge compared to 8.0% vs 24.7% after two years. Predictors of poor outcome included age between 28 days and one year (compared to neonates, OR 3.58, p<0.05), underlying chronic disorder (OR 2.23, p<0.05), and involvement of both small and large vascular territories (OR 2.84, p<0.05). Recovery patterns differed, with emerging deficits more common in children under one year of age (p<0.05).
Interpretation
Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and one year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke.
This article is protected by copyright. All rights reserved.
Brain–computer interfaces (BCIs) allow control of various applications or external devices solely by brain activity, e.g., measured by electroencephalography during motor imagery. Many users are unable to modulate their brain activity sufficiently in order to control a BCI. Most of the studies have been focusing on improving the accuracy of BCI control through advances in signal processing and BCI protocol modification. However, some research suggests that motor skills and physiological factors may affect BCI performance as well. Previous studies have indicated that there is differential lateralization of hand movements’ neural representation in right- and left-handed individuals. However, the effects of handedness on sensorimotor rhythm (SMR) distribution and BCI control have not been investigated in detail yet. Our study aims to fill this gap, by comparing the SMR patterns during motor imagery and real-feedback BCI control in right- (N = 20) and left-handers (N = 20). The results of our study show that the lateralization of SMR during a motor imagery task differs according to handedness. Left-handers present lower accuracy during BCI performance (single session) and weaker SMR suppression in the alpha band (8–13 Hz) during mental simulation of left-hand movements. Consequently, to improve BCI control, the user’s training should take into account individual differences in hand dominance.
Brain computer interface (BCI)-based training is promising for the treatment of stroke patients with upper limb (UL) paralysis. However, most stroke patients receive comprehensive treatment that not only includes BCI, but also routine training. The purpose of this study was to investigate the topological alterations in brain functional networks following comprehensive treatment, including BCI training, in the subacute stage of stroke. Twenty-five hospitalized subacute stroke patients with moderate to severe UL paralysis were assigned to one of two groups: 4-week comprehensive treatment, including routine and BCI training (BCI group, BG, n = 14) and 4-week routine training without BCI support (control group, CG, n = 11). Functional UL assessments were performed before and after training, including, Fugl-Meyer Assessment-UL (FMA-UL), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). Neuroimaging assessment of functional connectivity (FC) in the BG was performed by resting state functional magnetic resonance imaging. After training, as compared with baseline, all clinical assessments (FMA-UL, ARAT, and WMFT) improved significantly (p < 0.05) in both groups. Meanwhile, better functional improvements were observed in FMA-UL (p < 0.05), ARAT (p < 0.05), and WMFT (p < 0.05) in the BG. Meanwhile, FC of the BG increased across the whole brain, including the temporal, parietal, and occipital lobes and subcortical regions. More importantly, increased inter-hemispheric FC between the somatosensory association cortex and putamen was strongly positively associated with UL motor function after training. Our findings demonstrate that comprehensive rehabilitation, including BCI training, can enhance UL motor function better than routine training for subacute stroke patients. The reorganization of brain functional networks topology in subacute stroke patients allows for increased coordination between the multi-sensory and motor-related cortex and the extrapyramidal system. Future long-term, longitudinal, controlled neuroimaging studies are needed to assess the effectiveness of BCI training as an approach to promote brain plasticity during the subacute stage of stroke.
Background
Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited.
Objective
To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations.
Methods
A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants.
Results
Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8–18.0). Populations included typical development (n = 118), perinatal stroke/cerebral palsy (n = 101), mild traumatic brain injury (n = 121) neuropsychiatric disorders (n = 37), and other (n = 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%.
Conclusions
Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.
Background and objectives:
Neonatal arterial ischemic stroke (NAIS) can lead to long-term neurological consequences such as cerebral palsy (CP). The aim of this study was to evaluate the predictive value of acute diffusion-weighted imaging (DWI) for CP by analyzing stroke volume next to brain structure involvement.
Methods:
We included 37 term-born infants with NAIS prospectively registered in a nationwide pediatric stroke registry. DWI was performed between 0 and 8 days (mean 3 days) after stroke manifestation. Participants were neurologically assessed at the age of 2 years. We calculated the stroke volume (in mm3) and the ratio of the stroke volume to the volume of the entire brain (relative stroke volume). The predictive value of the relative stroke volume was analyzed and an optimal threshold for classification of children with high- and low-rates of CP was calculated. Predictive value of brain structure involvements and the prevalence of CP in combinations of different brain structures was also assessed.
Results:
Sixteen children (43.2%) developed CP. Relative stroke volume significantly predicted CP (p < .001). Its optimal threshold for division into high- and low-rate of CP was 3.3%. The basal ganglia (OR 8.3, 95% CI 1.2-60.0) and basis pontis (OR 18.5, 95% CI 1.8-194.8) were independently associated with CP.
Conclusion:
In addition to determining the involvement of affected brain areas, the volumetric quantification of stroke volume allows accurate prediction of cerebral palsy in newborns with NAIS.
This paper presents a gamified motor imagery brain-computer interface (MI-BCI) training in immersive virtual reality. The aim of the proposed training method is to increase engagement, attention, and motivation in co-adaptive event-driven MI-BCI training. This was achieved using gamification, progressive increase of the training pace, and virtual reality design reinforcing body ownership transfer (embodiment) into the avatar. From the 20 healthy participants performing 6 runs of 2-class MI-BCI training (left/right hand), 19 were trained for a basic level of MI-BCI operation, with average peak accuracy in the session = 75.84%. This confirms the proposed training method succeeded in improvement of the MI-BCI skills; moreover, participants were leaving the session in high positive affect. Although the performance was not directly correlated to the degree of embodiment, subjective magnitude of the body ownership transfer illusion correlated with the ability to modulate the sensorimotor rhythm.
Tenecteplase is replacing alteplase as the fibrinolytic agent of choice for the acute management of ischemic stroke in many adult stroke centers due to practical and pharmacokinetic advantages in the setting of similar outcomes. Although thrombolytic use is increasing for acute childhood stroke, there is very limited experience with tenecteplase in children for any indication, and importantly, there are no data on safety, dosing, or efficacy of tenecteplase for childhood stroke. Changes in fibrinolytic capacity over childhood, pediatric pharmacological considerations such as age-specific differences in drug clearance and volume of distribution, and practical aspects of drug delivery such as availability in children's hospitals may impact decisions about transitioning from alteplase to tenecteplase for acute pediatric stroke treatment. Pediatric and adult neurologists should prepare institution-specific guidelines and organize prospective data collection.
Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.
Background and Aims: Although intravenous thrombolysis (IVT) represents standard-of-care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence-based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aimed to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry.
Methods: Weighted hospitalizations for pediatric (< 18 years of age) AIS patients were identified in the National Inpatient Sample during the period of 2001 to 2019. Complex samples statistical methods were performed to assess unadjusted and adjusted outcomes in patients treated with IVT or other medical management.
Results: Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT-treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n=15), and 71.9% (n=194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity-score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH [5.6% vs. 5.4%, p=0.931; adjusted odds ratio (aOR) 1.01, 95% confidence interval (CI) 0.48, 2.14, p=0.971], nor with favorable functional outcome (71.9% vs. 74.5%, p=0.489; aOR 0.88, 95% CI 0.60, 1.29, p=0.511) in comparison with other medical therapy.
Conclusions: Twenty years of population-level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation.
Patients with moyamoya arteriopathy are at high risk for developing ischemic stroke in the perioperative period. We sought to evaluate whether preoperative clinical and neuroimaging biomarkers are associated with postoperative stroke and transient ischemic attack in children with moyamoya following revascularization surgery. We performed a retrospective chart review of pediatric patients who underwent revascularization surgery for moyamoya in the last 15 years. Fifty-three patients who underwent 69 surgeries met the inclusion criteria. We recorded clinical predictors of stroke or transient ischemic attack within 7 days following surgery. We used Suzuki stage and Composite Cerebrovascular Stenosis Score to analyze neuroimaging. Significant risk factors for developing postoperative stroke or transient ischemic attack were younger age at surgery ( P = .004) and transient ischemic attack less than 1 month prior to surgery ( P < .001). Children under 5 and those with recent preoperative ischemic events should be the focus of investigation to evaluate modifiable risk factors and targeted interventions.
Congenital heart disease (CHD) is the most commonly reported birth defect in newborns. Neonates with CHD are more likely to be born prematurely, and a higher proportion of preterm neonates have CHD than their term counterparts. The implications of preterm birth on the cardiac and noncardiac organ systems are vast and require special management considerations. The feasibility of surgical interventions in preterm neonates is frequently limited by patient size and delicacy of immature cardiac tissues. Thus, special care must be taken when considering the appropriate timing and type of cardiac intervention. Despite improvements in neonatal cardiac surgical outcomes, preterm and early term gestational ages and low birthweight remain important risk factors for in-hospital mortality. Understanding the risks of early delivery of neonates with prenatally diagnosed CHD may help guide perioperative management in neonates who are born preterm. In this review, we will describe the risks and benefits of early delivery, postnatal cardiac and noncardiac evaluation and management, surgical considerations, overall outcomes, and future directions regarding optimization of perinatal evaluation and management of fetuses and preterm and early term neonates with CHD.
Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain–computer interfaces and robotics, all focused on improving outcomes after perinatal stroke.
Background and Purpose
Perinatal stroke is the leading cause of hemiparetic cerebral palsy resulting in lifelong disability for millions of people worldwide. Options for motor rehabilitation are limited, especially for the most severely affected children. Brain computer interfaces (BCIs) sample brain activity to allow users to control external devices. Functional electrical stimulation enhances motor recovery after stroke, and BCI-activated functional electrical stimulation was recently shown to improve upper extremity function in adult stroke. We aimed to determine the ability of children with perinatal stroke to operate a simple BCI.
Methods
Twenty-one children with magnetic resonance imaging–confirmed perinatal stroke (57% male, mean [SD] 13.5 [2.6] years, range 9–18) were compared with 24 typically developing controls (71% male, mean age [SD] 13.7 [3.7] years, range 6–18). Participants trained on a simple EEG-based BCI over 2 sessions (10 trials each) utilizing 2 different mental imagery strategies: (1) motor imagery (imagine opening and closing of hands) and (2) goal oriented (imagine effector object moving toward target) to complete 2 tasks: (1) drive a remote controlled car to a target and (2) move a computer cursor to a target. Primary outcome was Cohen Kappa with a score >0.40 suggesting BCI competence.
Results
BCI performance was comparable between stroke and control participants. Mean scores were 0.39 (0.18) for stroke versus 0.42 (0.18) for controls (t[42]=0.478, P =0.94). No difference in performance between venous (M=0.45, SD=0.29) and arterial (M=0.34, SD=0.22) stroke (t[82]=1.89, P =0.090) was observed. No effect of task or strategy was observed in the stroke participants. Over 90% of stroke participants demonstrated competency on at least one of the 4 task-strategy combinations.
Conclusions
Children with perinatal stroke can achieve proficiency in basic tasks using simple BCI systems. Future directions include exploration of BCI-functional electrical stimulation systems for rehabilitation for children with hemiparesis and other forms of cerebral palsy.
Endovascular therapies for acute childhood stroke remain controversial and little evidence exists to determine the minimum age and size cut-off for thrombectomy in children. Despite this, an increasing number of reports suggest feasibility of thrombectomy in at least some children by experienced operators. When compared with adults, technical modifications may be necessary in children owing to differences in vessel sizes, tolerance of blood loss, safety of contrast and radiation exposure, and differing stroke etiologies. We review critical considerations for neurologists and neurointerventionalists when treating pediatric stroke with endovascular therapies. We discuss technical factors that may limit feasibility of endovascular therapy, including size of the femoral and cervicocerebral arteries, which contributes to vasospasm risk. The risk of femoral vasospasm can be assessed by comparing catheter outer diameter with estimated femoral artery size, which can be estimated based on the child’s height. We review evidence supporting specific strategies to mitigate cervicocerebral arterial injury, including technique (stent retrieval vs direct aspiration) and device size selection. The importance of and strategies for minimizing blood loss, radiation exposure, and contrast administration are reviewed. Attention to these technical limitations is critical to delivering the safest possible care when thrombectomy is being considered for children with acute stroke.
Perinatal stroke (PS) causes hemiparetic cerebral palsy (CP) and lifelong disability. Compensatory changes in the nonlesioned hemisphere may mediate residual function and represent targets for neuromodulation. Region-based approaches may reveal relationships between cortical thickness of nonlesioned primary motor/sensory cortices and motor function. This study uses surface-based morphometry to explore cortical alterations in the nonlesioned hemisphere in children after perinatal stroke. Children aged 6-19 with MRI-confirmed unilateral perinatal stroke and CP underwent T1-weighted anatomical imaging. Participants were classified as arterial ischemic stroke (AIS; n=36), periventricular venous infarction (PVI; n=38), or typically developing controls (TDC; n=53). Group differences in cortical thickness (distance between grey/white matter boundary and pial surface), grey matter volume, gyrification and sulcal depth and relationships between these morphology metrics and validated measures of motor/executive function were explored. Group comparisons revealed less cortical thickness, greater gyrification, and greater surface area in the nonlesioned hemisphere in both AIS and PVI as compared to TDC. Greater volume and sulcal depth were observed in the nonlesioned hemisphere for AIS. The PVI group showed greater volume in the cingulate cortex and less volume in the precuneus relative to TDC. The AIS group showed more widespread differences than the PVI group in volume and other cortical surface parameters when compared with TDC. Only modest correlations were observed between morphometric changes and clinical function. We suggest that broad differences in structural developmental plasticity occur in the nonlesioned hemisphere after perinatal stroke, particularly the larger lesions seen with AIS, and may represent novel targets for therapeutic neuromodulation.
Purpose
Moyamoya disease and syndrome are progressive steno-occlusive cerebrovascular diseases that manifest clinically with ischemic episodes. There is evidence for the use of electroencephalography (EEG) in preoperative and long-term postoperative evaluation of these patients, as well as in the intraoperative period to monitor for changes correlated with perioperative ischemic events. However, the utility of EEG in the immediate post-procedure time period has not previously been described.
Methods
We review 6 patients who underwent pial synangiosis from 2017-2019. EEGs from the preoperative, intraoperative, and immediate postoperative period were evaluated, as well as clinical exam changes, and subsequent interventions.
Results
Six patients with postoperative EEG monitoring following pial synangiosis were included. EEG data was collected preoperatively, intraoperatively, and continuously postoperatively. Preoperatively, 5 of 6 patients had normal background activity on EEG, while 1 of 6 had hemispheric asymmetry. Three patients had new or worsening hemispheric intracerebral asymmetry on EEG during the immediate post-surgical period. Two of these had no clinical manifestations of ischemia, and one had transient left facial weakness. All three underwent blood pressure augmentation with improvement in the asymmetry on EEG, and clinical improvement in the symptomatic patient.
Conclusion
While widely accepted as a useful tool during the preoperative and intraoperative periods of workup and management of moyamoya disease and syndrome, we propose that the use of continuous EEG in the immediate postoperative period may have potential as a useful adjunct by both detecting early clinical and subclinical intracranial ischemia.
Background and Purpose
To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients.
Methods
We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome.
Results
Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome.
Conclusions
In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.
The use of mechanical thrombectomy for the treatment of acute childhood arterial ischemic stroke with large vessel occlusion is increasing, with mounting evidence for its feasibility and safety. Despite this emerging evidence, clear guidelines for patient selection, thrombectomy technique, and postprocedure care do not exist for the pediatric population. Due to unique features of stroke in children, neurologists and interventionalists must consider differences in patient size, anatomy, collateral vessels, imaging parameters, and expected outcomes that may impact appropriate patient selection and timing criteria. In addition, different causes of stroke and comorbidities in children must be considered and may alter the safety and efficacy of thrombectomy. To optimize the success of endovascular intervention in children, a multidisciplinary team should take into account these nuanced considerations when determining patient eligibility, developing a procedural approach, and formulating a postprocedure neurological monitoring and therapeutic plan.
Introduction:
Mechanical thrombectomy is standard treatment for large vessel occlusion (LVO) in adults. There are no randomized controlled trials for the pediatric population. We report our single-center experience with thrombectomy of LVO in a series of pediatric patients, and perform a review of the literature.
Methods:
Retrospective review of consecutive pediatric thrombectomy cases between 2011 and 2018. Demographic variables, imaging data, technical aspects and clinical outcome were recorded.
Results:
In a period of 7 years, 7 children were treated for LVO at our center. Median age was 13 (2-17), and median Ped-NIHSS was 15 (3-24), and the median ASPECTS was 8 (2-10). Five patients had cardiac disease, and 2 of them were under external cardiac assistance. Median time from onset of symptoms to beginning of treatment was 7h06m (2h58m-21h38m). Five patients had middle cerebral artery occlusions. Thrombectomy was performed using a stentriever in 3 patients, aspiration in 3 patients, and combined technique in 1 patient. Six patients had good recanalization (TICI 2 b/3). There were no immediate periprocedural complications. At 3 months, 4 patients (57%) were independent (mRS score <3). Two patients died, one after haemorrhagic transformation of an extensive MCA infarct, and one due to extensive brainstem ischemia in the setting of varicella vasculitis.
Discussion:
Selected pediatric patients with LVO may be treated with mechanical thrombectomy safely. In patients under external cardiac assistance and under anticoagulation, thrombectomy is the only alternative for treatment of LVO. A multidisciplinary approach in specialized pediatric stroke centers with trained neurointerventionalists are essential for good results.
Objective:
We 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.
Methods:
Children 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.
Results:
Global 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.
Conclusions:
The 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.
Background/objective
The prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer/tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry.
Methods
Children ages 29 days to <19 years with arterial ischemic stroke (AIS) and/or cerebral sinovenous thrombosis (CSVT) enrolled in the International Pediatric Stroke Study January 2003-June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests.
Results
Remote or active cancer/tumor was present in 99 of 2968 children (3.3%) with AIS and 64 of 596 children (10.7%) with CSVT. Among children in whom cancer type was identified, 42 of 88 (48%) AIS cases had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 (78%) CSVT cases had hematologic malignancies and 8 (14%) had brain tumors. Of 54 cancer-associated AIS cases with known cause, 34 (63%) were due to arteriopathy and 9 (17%) were due to cardioembolism. Of 46 cancer-associated CSVT cases with known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer/tumor were less likely to receive any antithrombotic therapy for AIS (58 % v. 80%, p=0.007) and anticoagulation for CSVT (71% v. 87%, p=0.046), compared with children without cancer. Recurrent AIS (5% v. 2%, p=0.04) and CSVT (5% v. 1%, p=0.006) were more common among children with cancer.
Conclusions
Cancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for pediatric cancer patients are needed.
Background
Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan.
Objective
These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD.
Methods
The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations.
Results
The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle– and high-income settings.
Conclusions
Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle–income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.
Objective
To test the hypothesis that the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is useful in determining outcomes after neonatal arterial ischemic stroke (NAIS), we assessed accuracy of the modified pediatric ASPECTS (pedASPECTS) to predict cerebral palsy (CP), neurologic impairment, and epilepsy.
Methods
Cross-sectional study included newborns with acute NAIS whose outcomes were assessed at ≥18 months after stroke. PedASPECTS accuracy to predict outcomes was determined by sensitivity, specificity, and receiver operator characteristic (ROC) curves, and correlation between pedASPECTS and infarct volume was determined by the Spearman correlation coefficient.
Results
Ninety-six children met the inclusion criteria. Median percentage infarct to supratentorial brain volume was 6.8% (interquartile range [IQR] 3.0%–14.3%). Median pedASPECTS was 7 (IQR 4–10). At a median age of 2.1 years, 35% developed CP, 43% had neurologic impairment, and 7% had epilepsy. Median pedASPECTS predicted outcomes of interest: CP (10, IQR 8–12) vs no CP (5, IQR 4–8) ( p < 0.0001), poor (9, IQR 7–12) vs good (6, IQR 4–8) neurologic outcomes ( p < 0.0001), and epilepsy (10, IQR 8–12) vs no epilepsy (7, IQR 4–10) ( p = 0.033). PedASPECTS accuracy was good for CP (ROC 0.811) and fair for neurologic impairment (ROC 0.760) and epilepsy (ROC 0.761). A pedASPECTS ≥8 had ≥69% sensitivity and ≥54% specificity for clinical outcomes. PedASPECTS correlated with infarct volume (Spearman rank 0.701, p < 0.0001).
Conclusions
This study provides Class II evidence that pedASPECTS has fair to good accuracy for predicting CP, neurologic impairment, and epilepsy after NAIS and correlates with infarct volume. PedASPECTS may assist with early identification of babies requiring close developmental surveillance.
Individuals with cerebral palsy can have weak and poorly coordinated ankle plantar flexor muscles that contribute to inefficient walking patterns. Previous studies attempting to improve plantar flexor function have had inconsistent effects on mobility, likely due to a lack of task-specificity. The goal of this study was to develop, validate, and test the feasibility and neuromuscular response of a novel wearable adaptive resistance platform to increase activity of the plantar flexors during the propulsive phase of gait. We recruited eight individuals with spastic cerebral palsy to walk with adaptive plantar flexor resistance provided from an untethered exoskeleton. The resistance system and protocol was safe and feasible for all of our participants. Controller validation demonstrated our ability to provide resistance that proportionally- and instantaneously-adapted to the biological ankle moment (R = 0.92 ± 0.04). Following acclimation to resistance (0.16 ± 0.02 Nm/kg), more-affected limbs exhibited a 45 ± 35% increase in plantar flexor activity (p = 0.02), a 26 ± 24% decrease in dorsiflexor activity (p < 0.05), and a 46 ± 25% decrease in co-contraction (tibialis anterior and soleus) (p = 0.02) during the stance phase. This adaptive resistance system warrants further investigation for use in a longitudinal intervention study.
Background:
Indirect bypass surgery is used to improve the hemodynamic status of the pediatric moyamoya disease (MMD). Symptomatic cerebral infarction during the early postoperative period may be the most frustrating complication.
Objective:
The purpose of this study is to investigate the factors associated with early post-operative symptomatic cerebral infarction.
Methods:
Between January 2000 and February 2014, we performed 1241 indirect bypass surgeries for 659 pediatric MMD patients. Symptomatic infarction during the early postoperative period was diagnosed in 63 operations of 61 patients.
Results:
The overall incidence of symptomatic cerebral infarction after indirect bypass surgery was 5.1 %. The median age of postoperative infarcted patients was 6 years (mean 6.4 years, range of 1 to 15 years). Performing of two craniotomies in single operation resulted in a higher rate of cerebral infarction. Moreover, young patients (under six years old) showed a relatively higher incidence than older patients. In a matched analysis, immediate postoperative hemoglobin levels of more than 13 g/dL was associated with decreased infarction risk (odd ratio=0.144, p=0.003). The mutation of the methylenetetrahydrofolate reductase (MTHFR) gene occurred in relatively high proportion of our infarction group.
Conclusion:
Postoperative symptomatic infarctions can occur despite a unified surgical method and formulaic perioperative management protocol. Patient-centered factors, such as the young age, genetic background of MTHFR and particular medical conditions including hyperthyroidism, renovascular hypertension and hemolytic uremic syndrome, as well as management related factors including two craniotomies and low immediate postoperative hemoglobin level could be risk factors for early postoperative symptomatic cerebral infarction.
p>In the article pre-published online on January 24, 2019 and published in the paper version of Haematologica [volume 104(8):1676-1681; doi:10.3324/haematol2018.211433] we have to correct: • that recurrent stroke occurred in 160/872 (instead of 160 / 880) children [page 1678, second column, line 6]. • the incidence rates of recurrent AIS with respect to the individual exposure time in years given in the abstract (page 1676, lines 16-18) and in the results section (page 1679, paragraph "prothrombotic risk factors", lines 38-40). As explained in the methods section, we calculated the absolute risk of AIS recurrence as incidence rates per 100 patient-years (%). According to the individual exposure times (years) to antithrombin, lipoprotein (a) and the presence of more than one prothrombotic risk factor the incidence rates calculated per 100 patient-years are presented in the table below {table presented}.</p