Survey of practice patterns and preparedness for endovascular therapy in acute pediatric stroke.

PURPOSE: Endovascular therapy benefits selected adults with acute stroke while data are lacking for children. The purpose of this study was to assess physician practice and institutional preparedness for endovascular therapy in pediatric stroke. METHODS: A link to an anonymous online survey was sent to members of the International Pediatric Stroke Study (IPSS) group about physician experience with endovascular therapy, likelihood of treatment for provided clinical vignettes, and institutional readiness for the delivery of endovascular therapy to children. RESULTS: Thirty-one pediatric physicians with a mean of 11 years (SD 7.1) of experience responded. All but two would consider endovascular therapy in a child, and 20 (64.5%) had recommended endovascular therapy for a child in the preceding year. Most (n = 19, 67.9%) did not commit to an age minimum for endovascular therapy. Sixteen (57.1%) would consider treatment up to 24 h after symptom onset with 19 (67.9%) respondents reporting that their practice changed after the 2018 American Heart Association guidelines extended the time window for endovascular therapy in adults. Seventeen (60.7%) preferred imaging that included perfusion in children presenting beyond 6 h. Nineteen (70.4%) had institutional endovascular therapy criteria. Physicians in larger pediatric groups had more "likely to treat" responses on the clinical vignettes than physicians working in smaller groups (11.7 vs. 6.1, p < 0.05). CONCLUSION: Pediatric stroke physicians are largely willing to consider endovascular therapy with most changing their practice according to adult guidelines, though experience and selection criteria varied. These findings may help to inform consensus guidelines and clinical trial development.

Embolization of a traumatic arteriovenous fistula between the middle meningeal artery and middle meningeal vein in a child with pulsatile tinnitus.

Traumatic arteriovenous fistulas (AVFs) involving the middle meningeal artery (MMA) are uncommon lesions and rare in the pediatric population. An adolescent with headaches developed a bruit and a rhythmic "swooshing" noise in the left ear 9 weeks after a traumatic brain injury involving a left temporal bone fracture. An MRA of the brain demonstrated an enlarged left MMA and arterialized flow in the left middle meningeal vein (MMV), suggestive of an AVF. Cerebral angiography confirmed and characterized the left MMA-MMV fistula, which drained into the pterygoid plexus. The patient underwent transarterial coil embolization, with successful obliteration of the fistulous connection, and her tinnitus resolved. This case illustrates the importance of recognizing a post-traumatic AVF in a pediatric patient with pulsatile tinnitus, and that endovascular treatment by coil embolization is a safe and effective treatment option.

Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk.

AIM: To determine epilepsy risk factors after pediatric stroke. METHOD: A cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression. RESULTS: Among 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305). INTERPRETATION: Pediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner.

Comparing tract-based spatial statistics and manual region-of-Interest labeling as diffusion analysis methods to detect white matter abnormalities in infants with hypoxic-Ischemic encephalopathy.

PURPOSE: To compare manual region of interest (ROI) labeling and tract-based spatial statistics (TBSS) by their ability to detect group-wise differences in fractional anisotropy (FA) in the neonatal brain. MATERIALS AND METHODS: Diffusion-weighted data were obtained for nine infants with hypoxic-ischemic encephalopathy (HIE) (six males, three females; gestational age [GA] range, 36-40 weeks; mean GA, 37.8 weeks) and 11 healthy-control infants (10 males, 1 female; GA range, 36-40 weeks; mean GA, 38.4 weeks) at 3T. For manual ROI labeling, ROIs were drawn freehand for each subject in eight, clinically relevant brain regions. For TBSS, all FA data underwent an optimized, automated protocol for neonates. Each method was evaluated for detection of decreased FA in HIE infants, sensitivity, specificity, and variability. RESULTS: FA values from manual ROI and TBSS were strongly correlated (r = 0.94, P < 0.0001). Both methods found decreased FA in most ROIs for HIE infants. There was no significant interaction between method and group, indicating a similar ability to detect FA differences (F(1,19) = 0.599, P = 0.449). Sensitivity (manual: 0.709, TBSS: 0.694, 95% CI [-0.136, 0.163], P = 0.856), specificity (manual and TBSS: 0.716, 95% CI [-0.133, 0.133], P = 1), and standard error (manual: 0.009, TBSS: 0.007) were comparable. CONCLUSION: Manual ROI labeling and TBSS are comparable methods of diffusion analysis to detect group differences in FA in the neonatal brain.

Automated extraction and validation of children's gait parameters with the Kinect.

BACKGROUND: Gait analysis for therapy regimen prescription and monitoring requires patients to physically access clinics with specialized equipment. The timely availability of such infrastructure at the right frequency is especially important for small children. Besides being very costly, this is a challenge for many children living in rural areas. This is why this work develops a low-cost, portable, and automated approach for in-home gait analysis, based on the Microsoft Kinect. METHODS: A robust and efficient method for extracting gait parameters is introduced, which copes with the high variability of noisy Kinect skeleton tracking data experienced across the population of young children. This is achieved by temporally segmenting the data with an approach based on coupling a probabilistic matching of stride template models, learned offline, with the estimation of their global and local temporal scaling. A preliminary study conducted on healthy children between 2 and 4 years of age is performed to analyze the accuracy, precision, repeatability, and concurrent validity of the proposed method against the GAITRite when measuring several spatial and temporal children's gait parameters. RESULTS: The method has excellent accuracy and good precision, with segmenting temporal sequences of body joint locations into stride and step cycles. Also, the spatial and temporal gait parameters, estimated automatically, exhibit good concurrent validity with those provided by the GAITRite, as well as very good repeatability. In particular, on a range of nine gait parameters, the relative and absolute agreements were found to be good and excellent, and the overall agreements were found to be good and moderate. CONCLUSION: This work enables and validates the automated use of the Kinect for children's gait analysis in healthy subjects. In particular, the approach makes a step forward towards developing a low-cost, portable, parent-operated in-home tool for clinicians assisting young children.

Motor demand-dependent improvement in accuracy following low-frequency transcranial magnetic stimulation of left motor cortex.

The role of primary motor cortex (M1) in the control of voluntary movements is still unclear. In brain functional imaging studies of unilateral hand performance, bilateral M1 activation is inconsistently observed, and disruptions of M1 using repetitive transcranial magnetic stimulation (rTMS) lead to variable results in the hand motor performance. As the motor tasks differed qualitatively in these studies, it is conceivable that M1 contribution differs depending on the level of skillfulness. The objective of the present study was to determine whether M1 contribution to hand motor performance differed depending on the level of precision of the motor task. Here, we used low-frequency rTMS of left M1 to determine its effect on the performance of a pointing task that allows the parametric increase of the level of precision and thereby increase the level of required precision quantitatively. We found that low-frequency rTMS improved performance in both hands for the task with the highest demand on precision, whereas performance remained unchanged for the tasks with lower demands. These results suggest that the functional relevance of M1 activity for motor performance changes as a function of motor demand. The bilateral effect of rTMS to left M1 would also support the notion of M1 functions at a higher level in motor control by integrating afferent input from nonprimary motor areas.

Acute Pontine Ischemic Stroke in a Healthy Child With Intracranial Vasculopathy.

Here we report the case of a previously healthy 8-year-old boy who presented with altered mental status, right facial droop and right-sided hemiplegia the day after playing in an inflatable bouncer. No head trauma was reported by the patient nor witnessed by the parents. Urgent magnetic resonance imaging (MRI) demonstrated acute ischemic infarction in the left pons; computed tomographic angiography excluded arterial dissection but identified a small hyperdense filling defect in the basilar artery, later confirmed to be a calcification at the origin of a perforating artery. Pediatric National Institutes of Health (PedNIH) Stroke Scale score was 15. Infectious, inflammatory, hypercoagulable and additional vascular causes were excluded. Although the cause of the calcification remains obscure, we speculate that, similarly to mineralizing microangiopathy, a minor trauma led to stroke in this child. To our knowledge, mineralizing microangiopathy, the well-described entity affecting perforating arteries of the anterior circulation in young children leading to basal ganglia stroke following minor head traumas has not been described in the posterior circulation or in previously healthy school-age children.

Characteristics and Outcome in Children With Craniectomy Following Acute Ischemic Stroke in the International Pediatric Stroke Study.

The outcome of children with acute ischemic stroke treated with craniectomy has not been thoroughly examined. In adults, hemicraniectomy after middle cerebral artery territory stroke and posterior decompression after posterior circulation stroke has been shown to improve outcome. Pediatric cases of hemicraniectomy for middle cerebral artery stroke and posterior decompression following posterior circulation stroke suggest relatively good outcome. There are no published data in adults or children with craniectomy after cerebral sinovenous thrombosis. Our aim was to determine the outcome of children with acute ischemic stroke treated with craniectomy in the International Pediatric Stroke Study (IPSS). We included children enrolled who had a craniectomy following stroke presentation. Of 4294 patients in IPSS, 38 children (1%) were found to have craniectomy following an ischemic stroke. Of 38 craniectomy cases, 29 had anterior circulation strokes, 5 had posterior circulation strokes, and 4 had cerebral sinovenous thromboses. The mortality rate was 8%. Overall, children who have craniectomies have significant neurologic deficits. Prospective studies are needed to examine long-term morbidity following craniectomy.

Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease.

Sickle cell disease (SCD) is a hereditary blood disorder associated with many life-threatening comorbidities including cerebral stroke and chronic pain. The long-term effects of this disease may therefore affect the global brain network which is not clearly understood. We performed graph theory analysis of functional networks using non-invasive fMRI and high resolution EEG on thirty-one SCD patients and sixteen healthy controls. Resting state data were analyzed to determine differences between controls and patients with less severe and more severe sickle cell related pain. fMRI results showed that patients with higher pain severity had lower clustering coefficients and local efficiency. The neural network of the more severe patient group behaved like a random network when performing a targeted attack network analysis. EEG results showed the beta1 band had similar results to fMRI resting state data. Our data show that SCD affects the brain on a global level and that graph theory analysis can differentiate between patients with different levels of pain severity.

Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury.

OBJECTIVES: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. METHODS: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = 48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0-12, 12-36, and 36-60 h after birth) were collected, and neutrophil-to-lymphocyte ratio was calculated. RESULTS: Hypoxic-ischemic encephalopathy + total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body cooling) revealed that absolute lymphocyte count changes occurring at 0-12 h are likely due to disease progression, rather than total-body cooling treatment. CONCLUSION: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic-ischemic encephalopathy in neonates is warranted.

Socioeconomic determinants of outcome after childhood arterial ischemic stroke.

OBJECTIVE: To determine whether lower socioeconomic status (SES) is associated with worse 1-year neurologic outcomes and reduced access to rehabilitation services in children with arterial ischemic stroke (AIS). METHODS: From 2010 to 2014, the Vascular effects of Infection in Pediatric Stroke (VIPS) observational study prospectively enrolled and confirmed 355 children (age 29 days-18 years) with AIS at 37 international centers. SES markers measured via parental interview included annual household income (US dollars) at the time of enrollment, maternal education level, and rural/suburban/urban residence. Receipt of rehabilitation services was measured by parental report. Pediatric Stroke Outcome Measure scores were categorized as 0 to 1, 1.5 to 3, 3.5 to 6, and 6.5 to 10. Univariate and multivariable ordinal logistic regression models examined potential predictors of outcome. RESULTS: At 12 ± 3 months after stroke, 320 children had documented outcome measurements, including 15 who had died. In univariate analysis, very low income (

Classification of Normal and Pathological Gait in Young Children Based on Foot Pressure Data.

Human gait recognition, an active research topic in computer vision, is generally based on data obtained from images/videos. We applied computer vision technology to classify pathology-related changes in gait in young children using a foot-pressure database collected using the GAITRite walkway system. As foot positioning changes with children's development, we also investigated the possibility of age estimation based on this data. Our results demonstrate that the data collected by the GAITRite system can be used for normal/pathological gait classification. Combining age information and normal/pathological gait classification increases the accuracy of the classifier. This novel approach could support the development of an accurate, real-time, and economic measure of gait abnormalities in children, able to provide important feedback to clinicians regarding the effect of rehabilitation interventions, and to support targeted treatment modifications.

Effects of monoaminergic drugs on training-induced motor cortex plasticity in older adults.

Primary motor cortex (M1) plasticity is involved in motor learning and stroke motor recovery, and enhanced by increasing monoaminergic transmission. Age impacts these processes but there is a paucity of systematic studies on the effects of monoaminergic drugs in older adults. Here, in ten older adults (age 61+4years, 4 males), we determine the effects of a single oral dose of carbidopa/levodopa (DOPA), d-amphetamine (AMPH), methylphenidate (MEPH) and placebo (PLAC) on M1 excitability and motor training-induced M1 plasticity. M1 plasticity is defined as training related long lasting changes in M1 excitability and kinematics of the trained movement. At peak plasma level of the drugs, subjects trained wrist extension movements for 30min. Outcome measures were motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation at increasing intensity (stimulus response curve, SRC) and peak acceleration of the trained wrist extension movements. Measures were obtained before and after completion of training. The curve parameters plateau (MEPmax), inflection point, and slope were extracted from SRC. At baseline drugs had a differential effect on curve parameters, while kinematics remained unchanged. Training alone (PLAC) increased MEPmax but did not improve kinematics. Drugs affected training-related changes of the curve parameters differently, but did not enhance them or kinematics when compared to PLAC. The results demonstrate that in the older adults, MEPH, DOPA, or AMPH have differential effects on baseline M1 excitability and training-related M1 plasticity but fail to enhance them above the naïve level.

Gait parameters associated with balance in healthy 2- to 4-year-old children.

The use of validated measurements of gait and balance are crucial to establish baseline function and assess effectiveness of therapeutic interventions. Gait in children changes with motor development requiring frequent observations to effectively track progress. Standardized baseline spatiotemporal measurements and a greater understanding of the relationship between gait and balance would provide important feedback to clinicians regarding the effectiveness of rehabilitation and guide treatment modifications. 84 subjects (2.0-4.9 years) walked along the GAITRite(®), a walkway that records spatiotemporal parameters. The Pediatric Balance Scale (PBS) was administered to assess balance. Comparison of spatiotemporal parameter means between age groups showed trends associated with motor development similar to the ones described in the literature such as decreased cadence and increased step/stride length with increasing age. However, no significant differences in normalized spatiotemporal parameters were found between age groups. Age, leg length, cadence, step/stride length, step/stance time, and single/double support time showed significant correlation with balance scores. When the parameters were grouped into spatial, temporal, and age-related components using principal components analysis and included in a multiple regression model, they significantly predicted 51% of the balance score variance. Age-related components most strongly predicted balance outcomes. We suggest that balance can potentially be evaluated by assessment of spatial, temporal, and age-related characteristics of gait such as step length, cadence, and leg length. This suggests the possibility of developing new gait measurement technology that could provide functional assessment and track improvements during rehabilitation regimens. If the same model can be applied to monitor treatment efficacy in children with gait abnormalities remains to be addressed.

West Virginia University pediatric stroke registry: clinical description and risk factors identification in patients from a rural area.

PURPOSE: To develop an institutional pediatric stroke database at West Virginia University to support the classification and description of clinical and radiographic characteristics of pediatric stroke in children living in rural areas. METHODS: A custom-made database was developed using Microsoft Access to include specific query forms for data retrieval. Data were collected retrospectively from electronic medical record of pediatric patients with ischemic and hemorrhagic stroke, with emphasis on clinical presentation, risk factors, and neuroimaging studies between 2000 and 2012. RESULTS: In the children group, vasculitis and hypercoagulable disorders were identified less frequently than reported. In the neonate group, only extremely sick, symptomatic patents were acutely diagnosed with stroke. CONCLUSION: Patients with the most common risk factors for stroke (cardiac disease) were overrepresented. This suggests that in children receiving medical attention in rural areas less common risk factors for stroke might not be identified, increasing the risk recurrence. Increased index of suspicion is needed about pediatric stroke in rural areas, and early transfer to a tertiary care center for identification of risk factors is mandatory.

Can We Predict Functional Outcome in Neonates with Hypoxic Ischemic Encephalopathy by the Combination of Neuroimaging and Electroencephalography?

BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of mortality, morbidity, and long-term neurological deficits. Despite the availability of neuroimaging and neurophysiological testing, tools for accurate early diagnosis and prediction of developmental outcome are still lacking. The goal of this study was to determine if combined use of magnetic resonance imaging (MRI) and electroencephalography (EEG) findings could support outcome prediction. METHODS: We retrospectively reviewed records of 17 HIE neonates, classified brain MRI and EEG findings based on severity, and assessed clinical outcome up to 48 months. We determined the relation between MRI/EEG findings and clinical outcome. RESULTS: We demonstrated a significant relationship between MRI findings and clinical outcome (Fisher's exact test, p = 0.017). EEG provided no additional information about the outcome beyond that contained in the MRI score. The statistical model for outcome prediction based on random forests suggested that EEG readings at 24 hours and 72 hours could be important variables for outcome prediction, but this needs to be investigated further. CONCLUSION: Caution should be used when discussing prognosis for neonates with mild-to-moderate HIE based on early MR imaging and EEG findings. A robust, quantitative marker of HIE severity that allows for accurate prediction of long-term outcome, particularly for mild-to-moderate cases, is still needed.

Non-invasive serial casting to treat idiopathic toe walking in an 18-month old child.

BACKGROUND: Idiopathic toe walking is characterized by persistent toe walking in the absence of clinically diagnosed neuromuscular disease. Treatment options in children diagnosed with idiopathic toe walking include: observation, physical therapy, serial casting, or Achilles tendon (heel cord) lengthening surgery. OBJECTIVE: In this case report, we present a non-invasive serial casting protocol to treat severe and persistent toe walking in an 18-month old child, diagnosed as an idiopathic toe walker following neurological examination. METHODS: A series of below knee casts was used to provide a consistent stretch to the plantar flexor muscles. Upon removal of each set of casts, passive range of motion at the ankles was measured with a goniometer. RESULTS: Four sets of casts, each lasting approximately one week, increased passive ankle dorsiflexion to 10° of neutral and established a heel-toe walking gait. Improvements in ankle range of motion and gait were maintained upon repeated examinations at 3, 7, and 12 months post-casting. CONCLUSIONS: These results demonstrate that non-invasive procedures, such as serial casting, can be successful in very young children diagnosed as idiopathic toe walkers. Early identification and intervention for this diagnosis may eliminate the need for invasive surgeries and associated risks in this population.

Teaching Neuroimages: a pediatric patient with headache and neck stiffness.

A 14-year-old right-handed boy presented with sudden onset of severe headache and neck stiffness. Physical examination showed arm asymmetry with smaller size and muscle bulk (present since childhood) and increased deep tendon reflexes on the right, but normal strength. Brain CT and lumbar puncture ruled out subarachnoid hemorrhage or infection. MRI and angiography (figure) identified an unruptured type III spinal arteriovenous malformation at the C3-C4 level, supplied by the right vertebral artery.(1) Subtle physical examination findings can indicate underlying pathology and should not be overlooked in the proper context. Vascular studies should be considered for severe headache with negative initial workup.(2.)

Nocturnal headaches and pulsatile cranial mass: the tip of an iceberg.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) disorder is a newly defined hereditary disorder of the vasculature with typical defining features that include cutaneous capillary malformations associated with high-flow lesions in various other organ systems. Mutations on the RASA1 gene are reported to be associated with a variety of vascular malformations and present with a widely varying phenotype. PATIENT: A healthy 3 year old presented with acute onset of severe nocturnal headaches, nausea, and vomiting associated with a 2-cm pulsatile mass and prominent superficial veins on her forehead. Neuroimaging demonstrated a complex vascular malformation with multiple arteriovenous fistulae and cavernous angiomas present in multiple locations in the brain, but not in any other organ system. RESULTS: The patient was found to have a mutation of the RASA1 gene, which has not been previously described in the literature. CONCLUSIONS: This case describes a new RASA1 mutation with a phenotype that has not been previously described with a combination of pial fistulae and intracranial AV fistula in the absence of arteriovenous malformations.