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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.

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.

Background Risk factors for pediatric stroke are poorly understood and require study to improve prevention. Total cholesterol and triglyceride values peak to near-adult levels before puberty, a period of increased stroke incidence. The role of lipids in childhood arterial ischemic stroke has been minimally investigated. Methods We performed a cross-sectional analysis of lipid and Lp(a) concentrations in children with arterial ischemic stroke in the International Pediatric Stroke Study to compare the prevalence of dyslipidemia and high- or low-ranking lipid values in our dataset with reported population values. We analyzed sex, body mass index, race, ethnicity, family history, and stroke risk factors for associations with dyslipidemia, high non–high-density lipoprotein cholesterol, and hypertriglyceridemia. Results Compared with the National Health and Nutrition Examination Survey, a higher proportion of children ≥5 years with arterial ischemic stroke had dyslipidemia (38.4% versus 21%), high total cholesterol (10.6% versus 7.4%), high non–high-density lipoprotein cholesterol (23.1% versus 8.4%), and low high-density lipoprotein cholesterol (39.8% versus 13.4%). The lipid values that corresponded to one standard deviation above the mean (84th percentile) in multiple published national studies generally corresponded to a lower ranking percentile in children aged five years or older with arterial ischemic stroke. Dyslipidemia was more likely associated with an underweight, overweight, or obese body mass index compared with a healthy weight. Ethnic background and an acute systemic illness were also associated with abnormal lipids. Conclusions Dyslipidemia and hypertriglyceridemia may be more prevalent in children with arterial ischemic stroke compared with stroke-free children.

Background/ Issue: Epidemiologically, pediatric strokes are rare; therefore, index of suspicion is low and many cases are not recognized early enough to qualify for acute treatment. With this small patient population, many regions have yet to develop protocols and policies for acute pediatric stroke response. In the District of Columbia, MedStar Georgetown University Hospital (MGUH) is the only Joint Commission Accredited Comprehensive Stroke Center with a pediatric intensive care unit. Purpose: The purpose of our program was to develop institutional protocols for pediatric stroke patients who are candidates for hyper-acute treatment. Protocols focused on pediatric patients who presented through our emergency department or were transferred from other facilities within the time window for acute treatment. The protocols were established to ensure a clear process for physicians and staff to follow. Methods: An interdisciplinary group met to discuss modification of our current Adult Ischemic Stroke Code Protocol needed for a coordinated approach to pediatric stroke patients. The team members included the Stroke Coordinator, Stroke Nurse Navigator, Stroke Nurse Practitioner, Pediatric Neurologist, Medical Director of the Pediatric ICU, Manager of the Pediatric ICU, Pediatric Anesthesia, Medical Director of the Stroke Program, and the Emergency Department Team. Results: The interdisciplinary team was able to adapt a protocol using the Adult Ischemic Stroke Code Protocol. Key differences between the adult and pediatric stroke code work-flow consisted of including pediatric neurologists early in the decision process, pediatric nurses to assist with monitoring children, and pediatric anesthesia for assistance with imaging and/or endovascular intervention. The order sets were adjusted to include weight- based calculations for medications, age-based monitoring parameters, and specific pediatric needs. Conclusion: It is possible to develop a Pediatric Stroke Code Protocol based on the Adult Ischemic Stroke Code Protocol to include all modifications appropriate for pediatric care and still maintain the rapid work-flow that everyone is familiar with. It is essential to include all key stakeholders to ensure a smooth and safe process.

Background Pediatric cerebral sinovenous thrombosis is a treatable cause of brain injury, acute symptomatic seizures, and remote epilepsy. Our objective was to prospectively study epilepsy and outcomes in neonates and children one year after cerebral sinovenous thrombosis diagnosis. Methods Patients with cerebral sinovenous thrombosis were enrolled prospectively from 21 international sites through the Seizures in Pediatric Stroke Study. Clinical data, including acute symptomatic seizures and cerebral sinovenous thrombosis risk factors, were collected at diagnosis. A neuroradiologist who was unaware of the diagnosis reviewed acute imaging. At one year, outcomes including seizure recurrence, epilepsy diagnosis, antiepileptic drug use, and modified Engel score were collected. Outcomes were assessed using the modified Rankin score and the King's Outcome Scale for Childhood Head Injury. Results Twenty-four participants with cerebral sinovenous thrombosis were enrolled (67% male, 21% neonates). Headache was the most common presenting symptom in non-neonates (47%, nine of 19). Nine (37.5%) presented with acute symptomatic seizures. Six (25%; 95% confidence interval, 10% to 47%) developed epilepsy by one-year follow-up. No clinical predictors associated with epilepsy were identified. King's Outcome Scale for Childhood Head Injury and modified Rankin scores at one year were favorable in 71%. Half of the patients who developed epilepsy (three of six) did not have infarcts, hemorrhage, or seizures identified during the acute hospitalization. Conclusion Our study provides a prospective estimate that epilepsy occurs in approximately one-quarter of patients by one year after diagnosis of cerebral sinovenous thrombosis. Later epilepsy can develop in the absence of acute seizures or parenchymal injury associated with the acute presentation.

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. 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. 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

Background: The NIH stroke scale (NIHSS) is a standardized scale for evaluation of severity in stroke patient, and is utilized in adults with acute stroke to select patients for urgent intervention. A modified NIHSS has been validated for use in children (PedNIHSS). As pediatric stroke is rare, the PedNIHSS is not used frequently, and physicians are less familiar with the administration. Hence, this scale is used inconsistently, scoring can be less accurate, and important information is lost. We developed a smart-phone app for facilitated administration and recording of PedNIHSS in pediatrics. Methods: The PedNIHSS-App was built using the cross-platform software-developed environment Xamarin. Throughout development] validation and testing was performed with neurology colleagues. Feedbacks were collected from six pediatric neurologists for optimization. A web-based testing version was available during development. Results: Administration of the NIHSS stroke scale involves scoring 11 items of neurologic function. Administration of the PedNIHSS in children requires specific age-appropriate modification for testing and scoring. In the newly-developed PedNIHSSApp each item appears on a single page with clear explanations for administration and immediate scoring. Cartoons have been developed for visual instruction. Anonymously-recorded scoring -with no concerns for violation of confidentiality and/or dissemination of protected medical information- can be saved with a time stamp or sent via password-protected email. Conclusion: The user friendly, easy-to-use PedNIHSS App will facilitate accurate acquisition of PedNIHSS in children with acute stroke, particularly in situations when time is critical and standardized tools can support decision-making. Additionally, the easy to use PedNIHSS App will support increased data acquisition and therefore facilitate future outcome studies in pediatric stroke.

Background: Pediatric stroke is a rare but important cause of mortality and morbidity in this population. Endovascular therapy up to 24 hours after symptoms onset is beneficial in adults LVO acute ischemic stroke (AIS), but no safety or efficacy data of this approach is available for patients Methods and Results: We present three pediatric AIS cases (age 15-17) treated at GUH and WVU with endovascular techniques using extended time-window with selection based on perfusion criteria. Case 1 : 17 year old patient with history of Ebstein’s anomaly presented the day after a cardiac catheterization procedure with right hemiparesis and aphasia (NIHSS = 22). CTP identified left proximal ICA occlusion (ASPECTS score 7). Using the Penumbra device successful clot retrieval was achieved at 9:19 hours from onset. She was found to have a venous clot and right-to-left shunt from an atrial septal defect. 3 months mRS was 1. Case 2 : 17 y.o. female with 2 weeks history of intermittent right arm numbness presented with left hemiparesis and hemi-sensory loss (NIHSS 12). ER arrival time was 18:43 hours from the onset of sensory symptoms. CTP demonstrated complete right M1 occlusion secondary to right sub-clavian thrombus (ASPECTS score 8). Using the Solitaire stent retriever, recanalization was obtained at 20:05 hours after clinical onset. 3 months mRS was 1. Case 3 : 15 y.o female with Down syndrome, recently started on BCP woke up with right hemiparesis and aphasia (NIHSS = 22). MR perfusion demonstrated a distal M1/M2 clot with a large mismatch in the left MCA territory. Using a stent retriever device complete recanalization was obtained at 14:46 hours from the last time she was well. On the day of discharge her NIHSS was 7. Complete recanalization (TICI 3) was obtained in all three patients. No complications were observed during or following the procedure. NIHSS before and after the procedure improved by 11-to-17 points. Conclusions: A controlled study regarding endovascular approach in pediatric stroke is unlikely to occur. Therefore, case series must be reported in order to understand the safety of this approach. Strict patient selection and a team approach involving multiple pediatric and adult expertise are needed for a pediatric AIS response that includes endovascular intervention.

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., Highlights • Graph theory used to study global impact of long term sickle cell disease on brain. • EEG and fMRI results compared to study spatial and temporal impact of disease. • More severe patients have less clustering and efficiency. • Small world values correlated with past hospitalizations, linking results to pain.

ObjectiveTo 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).MethodsFrom 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.ResultsAt 12 ± 3 months after stroke, 320 children had documented outcome measurements, including 15 who had died. In univariate analysis, very low income (p = 0.004). In multivariable analysis, including adjustment for stroke etiology, this association persisted (OR 3.17, 95% CI 1.18–8.47, p = 0.02). Income did not correlate with receiving rehabilitation services at 1 year after stroke; however, quality and quantity of services were not assessed.ConclusionsIn a large, multinational, prospective cohort of children with AIS, low income was associated with worse neurologic outcomes compared to higher income levels. This difference was not explained by stroke type, neurologic comorbidities, or reported use of rehabilitation services. The root causes of this disparity are not clear and warrant further investigation.

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.

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. J. MAGN. RESON. IMAGING 2015.

Introduction: Endovascular therapy (ET) for pediatric stroke has been described through case reports and series. Hypothesis: We aimed to determine how pediatric stroke neurologists practice regarding ET, and institutional readiness for this therapy. Methods: A link to a REDCap survey was emailed to the members of the International Pediatric Stroke Study (IPSS), which includes 58 centers and approximately 150 investigators, requesting responses from physicians who manage acute stroke. Results: We received 42 responses, with 12 countries represented. Most respondents were pediatric neurologists (n=33), with a median 10 years of experience treating pediatric stroke (SD 6.8). Fourteen (33%) had never recommended/performed ET, 10 (24%) had treated 1-2 patients, and 17 (40%) had treated 3-10 patients. All but one respondent would consider ET in a child. The mean minimum age for consideration of ET was 3 years (range 2-12 years), however most (n=27) had no set minimum age. Most used a time-window of 6 (33%) or 8 (24%) hours for anterior circulation stroke, though 38% had no set time window. Only 7 respondents reported a minimum NIHSS (median NIHSS 6, range 4-15), with the remainder reporting that deficits needed to be significant or the decision would dependent on the clinical scenario. The institutional analyses included only the responses of the 25 IPSS principal investigators to ensure just one response per institution. Fifty-six percent reported that ET would be performed at a children’s hospitals, 36% at an adjacent hospital, and 4% reported that ET would be performed off-site, with 67% responding that patients would need to travel > 10 miles. Only 3 reported working with interventional neuroradiologists who primarily or exclusively treated children, however 22 (88%) worked with adult interventional neuroradiologists comfortable treating children. Twenty (80%) reported having institutional ET guidelines in place or in development. Conclusions: Pediatric stroke neurologists were largely willing to consider ET, though many had limited experience. With varied clinician expertise and hospital settings, consensus-based guidelines would need to include minimum requirements for institutions to perform ET.

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.

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 + 4 years, 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 30 min. 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.

Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Childhood enuresis is a common occurrence, affecting 7-20% of children[1, 2]. While more frequently cases of enuresis have ties to behavioral, psychiatric[3] and genetic[4] predispositions, less common causes, including neurologic conditions, should not be overlooked. Given the association of neurologic problems with enuresis, the importance of thorough neurologic evaluation cannot be underestimated, as findings could suggest a neurologic etiology, particularly in cases refractory to traditional management. We present three pediatric cases of enuresis related to neurologic disorders in order to illustrate the importance of a high index of suspicion for neurological causes and a thorough neurologic history and examination in the evaluation of enuresis. In the cases presented, while all underlying diagnoses were promptly recognized by specialists, symptoms and signs were overlooked during general examination by nonspecialist.

Introduction: Lower socioeconomic status (SES) is associated with poorer outcome after adult stroke. In a large cohort of children with arterial ischemic stroke (AIS), we determined 12-month neurological outcome and tested the hypothesis that SES is a determinant of outcome in children. Methods: From 2009-2014, the Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS (29 days-18 years) at 37 international centers, including 3 in lower and middle income (LAMI) countries. Outcome was assessed at 12 months via the recurrence and recovery questionnaire (RRQ) parental report of the pediatric stroke outcome measure (PSOM). Poor outcome was defined as a PSOM of ≥1. Results: Of 355 children, outcome was available for 310 (87%) at a median of 12 months (IQR 11-13). Ten children died prior to hospital discharge and 4 by 12 months. Outcomes improved from discharge to 12 months (Figure). Of 23 cases in LAMI countries, 88% had an income $100,000). Other markers of SES (maternal education level and rural/suburban/urban residence) also did not predict outcome. Independent predictors of poor outcome included moderate (OR 4.6, 95% CI 2.0, 11) or severe (OR 21, 95% CI 7.1, 60) neurological deficits at discharge (compared to no deficits) and recurrent stroke (OR 3.5, 95% CI 1.5, 8.3). Conclusion: Outcomes after childhood stroke may be worse in LAMI countries, although we were underpowered to study this subgroup. Within non-LAMI countries, SES does not appear to impact outcome in children, unlike reports in adults, perhaps reflecting better access to rehabilitation services in the pediatric population.

Author(s): Fox, Christine K; Mackay, Mark T; Dowling, Michael M; Pergami, Paola; Titomanlio, Luigi; Deveber, Gabrielle; SIPS Investigators | Abstract: AimTo determine epilepsy risk factors after pediatric stroke.MethodA 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.ResultsAmong 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).InterpretationPediatric 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.

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.

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.

INTRODUCTION: The benefit of pharmacologic augmentation of stroke recovery remains unclear. As post-stroke motor recovery depends on training-dependent plasticity, we wanted to test the effect of these drugs on the excitability of primary motor cortex (M1), kinematic and psychophysical measures. METHODS: Nine able-bodied individuals (4 males) participated in 4 test sessions at least 1 week apart during which they were administered one oral dose of 4 different medications: placebo (P), amphetamine 10mg (A), methylphenidate 20mg (M), carbidopa/levodopa 25/100mg (D). We used transcranial magnetic stimulation (TMS) to measure the effects of the different drugs on M1 excitability. Motor evoked potentials (MEP) were elicited using TMS at intensities of 35-80% of maximum stimulator output. The Boltzmann function was calculated for MEP amplitudes and compared across the 4 drug conditions. The effects of the drugs on psychophysics and movement kinematics were captured by a 2d accelerometer mounted on the dorsum of the hand. We measured the reaction time and the peak acceleration and dispersion of directions of auditory paced ballistic wrist extension movements. RESULTS: Comparison of the 4 different equations for the Boltzmann sigmoid curve where R max represents the maximum MEP amplitude; k, the slope of the curve; and S50, the intensity that produced half of the maximum MEP amplitude revealed significant differences between drug conditions. Compared to P, A led to a significant decrease in the maximum MEP amplitude (p= 0.00015), while D increased it (p=0.013). The other two parameters were similar to placebo. M had no effect on any of the three parameters. The different drugs had no statistically significant effect on the kinematic measures or reaction time. CONCLUSIONS: These results indicate that the neuromodulatory effect of drugs on M1 excitability differs, which may point to different mechanisms mediating the beneficial effects of these drugs on functional recovery after stroke. It would also support the notion that the beneficial effect of the drugs on recovery is likely due to improved kinematics or psychophysics of executions during training.

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) (6 males, 3 females; gestational age range, 36-40 weeks; mean gestational age, 37.8 weeks) and eleven healthy-born infants (10 males, 1 female; gestational age range, 36-40 weeks; mean gestational age, 38.4 weeks) on a 3T scanner. For manual ROI labeling, eight ROIs were drawn freehand for each subject. 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. 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. Sensitivity (manual: 0.71, TBSS: 0.69), specificity (manual and TBSS: 0.72), and standard error (manual: 0.009, TBSS: 0.007) were comparable. Conclusions: Manual ROI labeling and TBSS are comparable methods of diffusion analysis to detect group differences in FA in the neonatal brain

A 13-month-old female presented to the emergency department with acute neurological deficit. Her parents stated that she had awoken that morning at approximately 6:30 am only looking to the right, with left-sided mouth droop, and weakness on the left side. They reported that the child hit her head earlier that same evening after falling backwards against the wall. She did not lose consciousness and was acting normal after the incident, until bed-time, around 8:30 PM. She was recovering from an upper respiratory infection (URI) and had appeared very pale over the previous couple of weeks.

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.

We report the difference existing between two clinical syndromes: Spiller's syndrome is caused by a complete involvement of the medial hemimedulla, while Déjérine's syndrome is determined by lesions restricted to the anterior portion of the medial hemimedulla and is characterized by hypoglossal nerve palsy and contralateral hemiparesis.

Using circular dichroism, fluorescence, and infrared spectroscopies, we studied the secondary structure of purified hamster PrP C in the presence of the mild, nonionic detergent octylglucoside. Under these native conditions, PrP C displayed an unexpectedly high β-sheet component, intermediate between the values previously reported for PrP Sc and an isoform of PrP C isolated in a zwitterionic detergent. The structure of PrP C appeared to depend strongly on the detergent and/or phase. Switching from octylglucoside to zwitterion 3–14 drastically modified PrP secondary structure by increasing the α-helix while abolishing the β-sheet component. In contrast, the conformation of PrP C in zwitterion was highly stable, since reverting to octylglucoside did not restore the original native structure. These and other results show that native PrP C in octylglucoside has some of the conformational characteristics that make the protein susceptible to conversion into PrP Sc . Most importantly, this is the first study to demonstrate the intrinsic plasticity of the full-length native PrP C isolated from animal brains.

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.

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.)

Motor learning results in changes of movement representation in primary motor cortex (M1) a process involving long-term potentiation (LTP). Pairing motor training with repetitive transcranial magnetic stimulation (rTMS) of M1 enhances the formation of a motor memory. Here we determined the effect of pairing M1 stimulation and the execution of training movements at different times and frequencies on the formation of a motor memory.Formation of a motor memory was defined as increases in motor evoked potentials (MEP) of the training agonist (extensor carpi ulnaris muscle, ECU) and increases in peak acceleration of the trained movements that last more than 60min. Training consisted of auditory-paced ballistic wrist extension movements (30min, 0.5Hz) paired with 0.1, 0.25 or 0.5Hz subthreshold rTMS. The rTMS pulse was applied at either the onset, 100ms prior to or 300ms after the onset of training movement related increases in electromyographic (EMG) activity of ECU. This was compared to a Sham condition.Only 0.1Hz rTMS applied at the onset of the training related increase in ECU-EMG activity resulted in increases in MEP amplitudes and peak acceleration when compared to the Sham.The formation of motor memory is enhanced above the naïve level by co-administration of low frequency rTMS at the time of execution of training movements.These results indicate the importance of time and frequency of rTMS in these settings and should be considered in the design of rehabilitation treatment strategies using rTMS.

A fundamental step in the pathogenesis of spongiform encephalopathies (prion diseases) is the conversion of the cellular isoform of prion protein (PrPC) into the infectious form (scrapie isoform, PrPSc), apparently by a conformational mechanism. Comparison of the native secondary and tertiary structures of both proteins is essential to elucidate the molecular basis of this transformation. To obtain sufficient quantities of native-like PrPC, we have developed a semipreparative method to purify PrPC from hamster brains. PrPC was solubilized from purified synaptosomal and microsomal membranes by the nonionic detergent n-octyl- beta-glucopyranoside; the soluble fraction was loaded at pH 7.5 onto a semipreparative cation-exchange TSK-SP-5PW (HPLC) column. The fractions eluted by linear NaCl gradient and enriched for PrPC were sequentially purified using an immobilized ion-affinity HPLC column charged by Co2+, followed by wheat germ agglutinin (WGA)-affinity HPLC or size-exclusion HPLC (SE-HPLC) using a TSK G3000SW column. More than 95% purity was achieved after SE-HPLC as estimated by quantitative densitometry of the silver-stained SDS-PAGE gel; the recovery of total brain PrPC was >/=8%. The purified PrPC was a monomer with an intact N-terminus, and with a Stoke's radius of 26 A, corresponding to that expected from the molecular weight for a native protein. The presence of the native-like conformation was further verified by peptide mapping after limited trypsin proteolysis, and by the apparent unfolding in guanidine hydrochloride, as detected by SE-HPLC.

To investigate the impact of anticoagulation on short-term outcome (1 month) in neonates with cerebral sinovenous thrombosis, the authors conducted a retrospective chart review of neonates admitted to 2 tertiary hospitals over a 5- and 8-year period, respectively. Neonates with confirmed radiographic evidence of cerebral sinovenous thrombosis were included. Eighteen total patients treated with hydration only were identified. Approximately 50% of these neonates showed clot extension or other complications on follow-up imaging that were obtained within 72 hours with either magnetic resonance imaging or computed topography. Five neonates were treated with anticoagulation, and none of these patients developed new infarcts or hemorrhages. The results of this retrospective study suggest that anticoagulation is safe in neonates with cerebral sinovenous thrombosis. Early follow-up scans can help treatment decision. Larger studies are needed to develop standardized guidelines for the evaluation and treatment of neonatal cerebral sinovenous thrombosis.

According to the Koch postulates an infectious organism is the one that can be isolated from an host suffering from a disorder, can be propagated in laboratory, can cause the same disease when introduced in another host, and finally, can be re-isolated from the host itself. If we change the word "organism" with the word "protein" we have a quite exact description of prions. Prion related disorders are a very unique category of infectious diseases. The ethiology of the so-called prionoses is related to the conversion of a normal protein (PrP(C), the cellular isoform of the prion protein) into a pathological form (the scrapie isoform of the prion protein, PrP(Sc)) which is able to propagate. The striking difference between the two forms seems to consist in a conformational modification of a mainly alpha-helix structured PrP(C) into a mainly beta-sheet PrP(Sc). The latter forms amyloid-like fibrils which precipitate into insoluble aggregates leading to the neurodegenerative changes specific of Spongiform Encephalopathies. This review will focus on the structure of the prion proteins and on PrP(C) cellular cycle, and it will discuss some hypothesis about the protein biochemical function. Finally, the various molecular mechanisms proposed for the development of conformational modifications will be reviewed, i.e. how a protein can become infectious by simply changing its structure.

We used RNA fingerprinting by arbitrary primed PCR to identify genes whose expression is up-regulated in the brain of hamsters affected by prion disease. One gene implicated by RNA fingerprinting encoded the hamster homologue of protein nexin-I (PN-I), a serine proteinase inhibitor, and was further investigated by Northern blot analysis. PN-I mRNA levels were increased at pre-clinical stages (19 days after inoculation) and remained elevated when the spongiform encephalopathy was anatomopathologically and clinically evident (at 50 and 80 days). Future RNA screening conducted as illustrated may help to reveal a spectrum of genes relevant for the etiopathogenesis and/or diagnosis of prion disease.

Transfalcial and transtentorial herniation and the engagement of the cerebellar tonsils into the foramen magnum are well recognised consequences of increased intracranial pressure. They were discovered through both experimental findings carried out in the 19th century,1 and pathological and clinical experiences reported in the first decades of this century.2 Harvey Cushing (1869–1939) is usually acknowledged as the first clinician who, in 1902, correlated the clinical picture of neurological disturbances and cardiorespiratory failure with the herniation of the cerebellar tonsils into the foramen magnum.3 However, when in his book on pontocerebellar angle tumours Cushing made use of the notion of “cerebellar pressure cone”,4 he was employing a term first introduced into the English language by Collier,5 as Cushing himself acknowledged in an earlier article.6 Here we report on the observations of Pierre Marie (1853–1940) that bear on the same issue and antedate those of both Cushing and …

Various neurological disorders have been related to Streptococcus pyogenes infection. Only recently, and for the first time, it has been suggested that acute disseminated encephalitis may also complicate a streptococcal infection. The case reported in this paper seems to confirm this hypothesis.

Spongiform encephalopathies in humans and animals include fatal neurodegenerative disorders that can be sporadic, infectious, or inherited (1). Regardless of their origin, spongiform encephalopathies are all transmissible to an appropriate animal species (2), with the exception of fatal familial insomnia (FFI) (3), whose transmission is still unknown. The unique features of the infectious agent that causes spongiform encephalopathies prompted Prusiner (4) to coin the term prion to define a new category of pathogens. In Prusiner’s terminology, the etiologic definition is substituted for the neuropathologic one, and spongiform encephalopathies are called prion diseases. Considerable neuropathologic variability among this group of diseases has been described (5). Some forms are characterized by widespread spongiform changes, while others show mostly prion protein (PrP) amyloid deposition (5). Scrapie, a disease naturally occurring in sheep and goats, is the prototype of prion diseases and has been adapted to various experimental rodent species.

We report the case of a 34-year old patient who first complained of fever, confusion and transient ophthalmoplegia and then developed akinetic mutism, frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and electrophysiological data support a diagnosis of encephalitis lethargica. Magnetic resonance imaging showed hyperintensive lesions in various brain regions. The patient responded to corticosteroid treatment. Two years after the onset of the first clinical signs he had recovered completely and today, after 5 years, he shows no sign of disease.

A controversial entity, Eagle's syndrome, is reviewed. After an anatomical description of the maxillo-vertebro-pharyngeal region we summarize the causative, diagnostic and therapeutic aspects of the syndrome. Two different conditions are often reported as Eagle's syndrome: one characterized by dysphagia and unilateral pharyngeal pain radiating to the ear and worsened by swallowing; the other characterized by pain in the head and neck region due to compression of the neurovascular structure by an elongated styloid process. The latter also includes typical cranial neuralgias (such as glossopharyngeal neuralgia) and carotidynia. We believe that the term “Eagle's syndrome” is legitimate only in the first case and in those “atypical” painful head and neck conditions related to an elongated styloid process and relieved by styloidectomy. We believe Eagle's syndrome deserves consideration in the International Headache Classification.

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.

The spectroscopic characterization of protein secondary structure is often partially unreliable when samples are not extremely pure and abundant. This problem may be overcome by the combination of circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR). We used these methods to characterize the secondary structure of two proteins of neurobiological interest, calexcitin (CE) and the cellular isoform of prion protein (PrPC). Both proteins were purified with multiple chromatographic steps and were obtained in buffer with high purity (95%) and in low amount (approximately 2 micrograms). The samples were analyzed by circular dichroism (down to 184 or 182 nm), recovered, and deposited on films for infrared analysis. The spectral deconvolution from the two methods yielded secondary structures in good agreement with each other as well as with theoretical predictions based on amino acid sequence. The conformation of CE was found to be dependent on its concentration and on calcium binding. The secondary structure of cellular native PrP varied dramatically with the detergent used. In conclusion, the combination of CD and FT-IR analysis is suitable for the characterization of the conformational changes induced by ligand binding and/or by different solvent conditions when the protein of interest is only scarcely available. The methods used here provide valuable insights into the putative correlation between protein structure and activity.