Pediatric Stroke Research Articles

Pediatric Cerebral Sinovenous Thrombosis and Risk for Epilepsy

BackgroundCerebral sinovenous thrombosis (CSVT) is a rare form of pediatric stroke with significant morbidity. We determined cumulative incidence and predictors of acute seizures, remote seizures, and epilepsy after pediatric CSVT. MethodsRetrospective analysis of 131 neonates and children with neuroimaging-confirmed CSVT enrolled between 2008 and 2020 from a single-center prospective consecutive cohort. Acute seizures occurred within 7 days of CSVT. Remote seizures occurred >7 days after CSVT. Epilepsy was defined as 2 or more remote seizures at least 24 hours apart. Survival methods determined the incidence of and risk factors for remote seizures and epilepsy. ResultsAcute seizures occurred in 14/33 neonates (42%) and 19/98 children (19%). Among children, hemorrhage predicted acute seizures (OR 6.6, 95% CI 1.9 to 22.4, P = 0.003). Remote seizures occurred in six neonates; five developed epilepsy. Remote seizures occurred in 14 children; 10 developed epilepsy. In neonates, 1- and 3-year epilepsy-free survival were 86% (95% CI 62% to 95%) and 66% (95% CI 32% to 87%). One- and 3-year epilepsy-free survival in children were 88% (95% CI 76% to 92%) and 84% (95% CI 59% to 86%). In multivariable analysis for children, acute seizures predicted epilepsy (HR 3.8, 95% CI 1.1-13.3, P = 0.039). In both cohorts, Pediatric Stroke Outcome Measure scores at last follow-up were worse in those with epilepsy compared to those without. ConclusionsAcute seizures occurred in approximately one quarter of our cohort and are an epilepsy risk factor in children with CSVT. Neonates and children with epilepsy had worse outcomes than those without.

Hemicraniectomia decompresiva en un paciente de 5 años con ataque cerebrovascular isquémico en el territorio de la arteria cerebral media derecha: presentación de caso clínico y revisión de la literatura

El ataque cerebrovascular (ACV) isquémico en la infancia es una entidad poco común que se ha venido incrementando en frecuencia y representa una patología de alto riesgo de eventos adversos en los niños; adicionalmente, es una patología de difícil manejo y con múltiples recurrencias. Los pacientes pediátricos que presentan esta clase de patología y que llegan al servicio de urgencias pediátricas son difíciles para establecer un diagnóstico e instaurar un manejo rápido, ya que esta entidad presenta múltiples diagnósticos diferenciales y por su baja incidencia no se tienen algoritmos claros y terapias rápidas y seguras para contrarrestar el compromiso neurológico severo del paciente. Esto se debe a que existen pocos estudios realizados en ACV pediátrico que describan el manejo médico adecuado o las intervenciones necesarias en esta patología, por lo cual no se tienen pautas claras para contrarrestar el evento agudo. Por lo tanto, se tienen intervenciones como trombectomía y la hemicraniectomia decompresiva, lo que lleva al paciente pediátrico a un riesgo mayor, pero tienen respuesta favorable en la mortalidad, con una recuperación favorable. Presentamos el caso clínico de un paciente pediátrico con ACV de territorio de arteria cerebral media derecha, su diagnóstico y tratamiento definitivo, con revisión de la literatura.

Tenecteplase in Acute Stroke: What About the Children?

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.

Predictors of neurocognitive outcome in pediatric ischemic and hemorrhagic stroke

ABSTRACT This clinical study examined the impact of eight predictors (age at stroke, stroke type, lesion size, lesion location, time since stroke, neurologic severity, seizures post-stroke, and socioeconomic status) on neurocognitive functioning following pediatric stroke. Youth with a history of pediatric ischemic or hemorrhagic stroke (n = 92, ages six to 25) underwent neuropsychological testing and caregivers completed parent-report questionnaires. Hospital records were accessed for medical history. Spline regressions, likelihood ratios, one-way analysis of variance, Welch’s t-tests, and simple linear regressions examined associations between predictors and neuropsychological outcome measures. Large lesions and lower socioeconomic status were associated with worse neurocognitive outcomes across most neurocognitive domains. Ischemic stroke was associated with worse outcome in attention and executive functioning compared to hemorrhagic stroke. Participants with seizures had more severe executive functioning impairments than participants without seizures. Youth with cortical-subcortical lesions scored lower on a few measures than youth with cortical or subcortical lesions. Neurologic severity predicted scores on few measures. No differences were found based on time since stroke, lesion laterality, or supra- versus infratentorial lesion. In conclusion, lesion size and socioeconomic status predict neurocognitive outcome following pediatric stroke. An improved understanding of predictors is valuable to clinicians who have responsibilities related to neuropsychological assessment and treatments for this population. Findings should inform clinical practice through enhanced appraisals of prognosis and the use of a biopsychosocial approach when conceptualizing neurocognitive outcome and setting up support services aimed at fostering optimal development for youth with stroke.

Grand challenges in pediatric stroke

SPECIALTY GRAND CHALLENGE article Front. Stroke, 19 May 2023Sec. Stroke in the Young Volume 2 - 2023 | https://doi.org/10.3389/fstro.2023.1204718

Establishing a pediatric acute stroke protocol: experience of a new pediatric stroke program and predictors of acute stroke.

Pediatric stroke is among the top 10 causes of death in pediatrics. Rapid recognition and treatment can improve outcomes in select patients, as evidenced by recent retrospective studies in pediatric thrombectomy. We established a collaborative protocol involving the vascular neurology and pediatric neurology division in our institution to rapidly diagnose and treat pediatric suspected stroke. We also prospectively collected data to attempt to identify predictors of acute stroke in pediatric patients. IRB approval was obtained to prospectively collect clinical data on pediatric code stroke activations based on timing metrics in resident-physician note templates. The protocol emphasized magnetic resonance imaging over computed tomography imaging when possible. We analyzed performance of the system with descriptive statistics. We then performed a Bayesian statistical analysis to search for predictors of pediatric stroke. There were 40 pediatric code strokes over the 2.5-year study period with a median age of 10.8 years old. 12 (30%) of patients had stroke, and 28 (70%) of code stroke patients were diagnosed with a stroke mimic. Median time from code stroke activation to completion of imaging confirming or ruling out stroke was 1 h. In the Bayesian analysis, altered mental status, hemiparesis, and vasculopathy history were associated with increased odds of stroke, though credible intervals were wide due to the small sample size. A trainee developed and initiated pediatric acute stroke protocol quickly implemented a hospital wide change in management that led to rapid diagnosis and triage of pediatric stroke and suspected stroke. No additional personnel or resources were needed for this change, and we encourage other hospitals and emergency departments to implement similar systems. Additionally, hemiparesis and altered mental status were predictors of stroke for pediatric acute stroke activation in our Bayesian statistical analysis. However credible intervals were wide due to the small sample size. Further multicenter data collection could more definitively analyze predictors of stroke, as well as the help in the creation of diagnostic tools for clinicians in the emergency setting.

Collateral circulation status-guided mechanical thrombectomy in pediatric stroke with an extended ghost infarct core: illustrative case.

Mechanical thrombectomy (MT) has been proved to be a highly effective therapy to treat acute ischemic stroke due to large vessel occlusion. Often, the ischemic core extent on baseline imaging is an important determinant for endovascular treatment eligibility. However, computed tomography (CT) perfusion (CTP) or diffusion-weighted imaging may overestimate the infarct core on admission and, consequently, smaller infarct lesions called "ghost infarct cores." A 4-year-old, previously healthy boy presented with acute-onset, right-sided weakness and aphasia. Fourteen hours after the onset of symptoms, the patient presented with a National Institutes of Health Stroke Scale (NIHSS) score of 22, and magnetic resonance angiography demonstrated a left middle cerebral artery occlusion. MT was not considered because of a large infarct core (infarct core volume: 52 mL; mismatch ratio 1.6 on CTP). However, multiphase CT angiography indicated good collateral circulation, which encouraged MT. Complete recanalization was achieved via MT at 16 hours after the onset of symptoms. The child's hemiparesis improved. Follow-up magnetic resonance imaging was nearly normal and showed that the baseline infarct lesion was reversible, in agreement with neurological improvement (NIHSS score 1). The selection of pediatric stroke with a delayed time window guided by good collateral circulation at baseline seems safe and efficacious, which suggests a promising value of vascular window.

Etiologies, mechanisms, and risk factors of ischemic stroke in a young Asian adult cohort

ObjectivesRisk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. Materials and methodsYoung AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). ResultsA total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. ConclusionsYoung adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.

Lipoprotein (a): Does It Play a Role in Pediatric Ischemic Stroke and Thrombosis?

The goal of this paper is to describe the current understanding of lipoprotein (a) (Lp(a)), clinical practice guidelines, and the potential pathophysiological mechanisms that appear to increase the risk of cardiovascular and thromboembolic events, specifically within the pediatric population. The proatherogenic and pro-thrombotic properties of Lp(a) may increase the risk of atherothrombotic disease. In adults, atherosclerotic plaques increase thrombotic risk, but antifibrinolytic and proinflammatory properties appear to have an important role in children. Although it is not well established in neonates, recent studies indicate the risk of incident thrombosis and ischemic stroke are approximately fourfold higher in children with elevated Lp(a) which also increases their risk of recurrent events. Despite this higher risk, Pediatric Lp(a) screening guidelines continue to vary among different medical societies and countries. The inconsistency is likely related to inconclusive evidence outside of observational studies and the lack of specific therapies for children with elevated levels. Additional research is needed to improve understanding of the pro-thrombotic mechanisms of Lp(a), appropriate screening guidelines for Lp(a) in the pediatric population, and to elucidate the short and long term effects of elevated Lp(a) on the risk of pediatric thrombosis and stroke.

Moyamoya disease presenting with tubular dysfunction in a child: pitfalls in diagnosing an atypical hyponatremic-hypertensive syndrome

BackgroundMoyamoya disease, a cause of pediatric stroke, has been shown to affect furthermore extra-cranial districts, mostly the kidney arterial site, resulting in steno-occlusive changes. Unilateral renal artery stenosis accounts for 8%-10% out of cases of renovascular hypertension in childhood, however it rarely underlies a hyponatremic-hypertensive syndrome (HHS).Case presentationWe describe an 18-month-old boy with a recent history of polyuria and polydipsia, who presented an acute febrile gastroenteritis with neurological impairment, severe dehydration, hyponatremia, hypokalemia, kidney tubular dysfunction, and elevated aldosterone and renin even with a normal blood pressure. Fluid and electrolytes correction was performed, with complete recovery. An abdominal ultrasound displayed a smaller right kidney. A brain magnetic resonance and an electroencephalogram did not show any relevant abnormalities. Five months later, the child experienced a left-side hemiparesis after a traumatic concussion, and a severe hypertension. A brain tomography documented a cerebral ischemia. Brain and kidney angiographic studies displayed puff of smoke findings of internal right carotid artery branches and a steno-occlusive pattern of right renal artery, respectively. Hence, moyamoya disease with HHS secondary to unilateral renal artery stenosis was diagnosed. After an unsuccessful antiplatelet and antihypertensive pharmacological treatment, the boy underwent a renal angioplasty and a cerebral STA-MCA bypass (direct superficial temporal artery-to-middle cerebral artery bypass), resulting in a significant improvement of both neurological and kidney disease.ConclusionsAlthough the association between unilateral renal artery stenosis and HHS has been previously shown, this is the first report of atypical HHS, with hypertension preceded by tubular dysfunction, recognized in the framework of moyamoya disease.

Seizures in Pediatric Moyamoya: Risk Factors and Functional Outcomes

BackgroundChildren with moyamoya arteriopathy are at high risk for stroke and seizures. Risk factors for seizures and the impact of seizures on neurological outcomes in children with moyamoya are unknown. MethodsThis is a single-center retrospective cohort study of children with moyamoya evaluated between 2003 and 2021. Functional outcome was assessed using the Pediatric Stroke Outcome Measure (PSOM). Associations between clinical variables and seizure occurrence were assessed using univariate and multivariable logistic regression. Associations between clinical variables and final PSOM score were assessed using ordinal logistic regression. ResultsEighty-four patients met inclusion criteria, and 34 (40%) children experienced seizure. Factors associated with seizures included moyamoya disease (vs syndrome; odds ratio [OR] 3.43, P = 0.008) and the presence of infarcts on baseline neuroimaging (OR 5.80, P = 0.002). Factors associated with decreased likelihood of experiencing seizures included older age at initial presentation (OR 0.82, P = 0.002) and asymptomatic (radiographic) presentation (OR 0.05, P = 0.006). Both older age at presentation (adjusted OR [AOR] 0.80, P = 0.004) and incidental radiographic presentation (AOR 0.06, P = 0.022) remained significant after adjusting for potential confounders. Seizures were associated with worse functional outcomes as assessed by the PSOM (regression coefficient 2.03, P < 0.001). This association remained significant after adjusting for potential confounders (adjusted regression coefficient 1.54, P = 0.025). ConclusionsYounger age and symptomatic presentation are associated with increased likelihood of seizures among children with moyamoya. Seizures are associated with worse functional outcomes. Prospective studies should clarify how seizures impact outcomes and how effective seizure treatment modifies this relationship.

Polish recommendations for diagnosis and therapy of paediatric stroke.

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

The Spectrum of Pediatric Infection-Associated Intracranial Arteriopathies and Acute Ischemic Stroke at 2 Eastern Indian Tertiary Care Centres.

Major and minor pediatric infections may cause intracranial arteriopathies, the long-term outcome of which we investigated and identified the factors influencing the progression/resolution of arteriopathies. We collected the clinical and radiological data of children aged 1 month-15 years who had ischemic stroke with definite arteriopathy following a recent febrile infection. Repeated neuroimaging was done over the next year to ascertain recurrent strokes and the progression and resolution of arteriopathies. The anterior circulation was more frequently affected (83.33%), predominantly involving the middle cerebral artery (41.67%), resolving in 20.84% of cases and progressing in 33.33% of cases. Lesions were commonly unilateral (54.17%) and stenotic (75%), resulting predominantly in cortical infarcts (45.83%), with hemiparesis being the most common neurodeficiency. Apart from tubercular meningitis patients, others had a good functional outcome. Lower age, minor infections, and unilateral arteriopathies had a significantly higher chance of resolution. Postviral arteriopathies had a significantly lower chance of progression compared with those following bacterial infections. Progressive and bilateral arteriopathies were significantly associated with worse outcomes and recurrent strokes.

Outcomes in infants with unprovoked venous thromboembolism: A retrospective cohort study

BackgroundAlthough children aged <1 year have a relatively high rate of venous thromboembolism (VTE) compared to older children, most have additional prothrombotic risk factors. Unprovoked VTE is rare, and little is known about this population, particularly the risk of recurrent VTE. ObjectivesWe aimed to determine the rate of recurrent VTE in infants with prior unprovoked VTE and evaluate long-term, end-organ outcomes for infants with renal and intracranial vein thrombosis. MethodsInfants <1 year of age with an unprovoked VTE between 2003 and 2021 at a single institution were included. Time to recurrent event and anticoagulation duration were summarized using the Kaplan-Meier estimator. Neurologic outcomes were summarized with the pediatric stroke outcome measure for infants with cerebral sinovenous, medullary, or cortical vein thrombosis. Kidney outcomes were summarized with estimated glomerular filtration rates for infants with renal vein thrombosis. Anticoagulation was summarized. ResultsForty infants with intracranial, renal, portal, and extremity VTE met the inclusion criteria and were followed for a median of 4.7 years (IQR, 2.1-8.5). Most VTE events occurred during the first month of life. There was 1 recurrent event in 237 person-years of follow-up (incidence rate, 4 per 1000 [95% CI, 0.6-29.9] person-years). In outpatient follow-up, 40% of infants with intracranial thrombosis met criteria for moderate or severe neurologic outcomes and two-thirds of infants with a prior renal vein thrombosis had abnormal kidney function (estimated glomerular filtration rate < 90 mL/min/1.73 m2). ConclusionThere is a low rate of recurrent VTE but significant end-organ morbidity in infants with unprovoked VTE.

Language and Cognitive Outcomes Following Ischemic Stroke in Children With Monolingual and Bilingual Exposure.

Aim: Although many children who experience ischemic stroke come from bilingual backgrounds, it is unclear whether bilingual exposure affects poststroke development. Our research evaluates bilingual and monolingual exposure on linguistic/cognitive development poststroke across 3 stroke-onset groups. Method: An institutional stroke registry and medical charts were used to gather data on 237 children across 3 stroke-onset groups: neonatal, <28 days; first-year, 28 days to 12 months; and childhood, 13 months to 18 years. The Pediatric Stroke Outcome Measure (PSOM), administered several times poststroke, was used to evaluate cognition and linguistic development. Results: Similar cognitive outcomes were observed across language groups. However, an interaction effect with stroke-onset group was observed, with monolinguals in the first-year group having worse productive language outcomes as compared to bilinguals. Interpretation: Overall, no detrimental effects of bilingualism were found on children's poststroke cognition and linguistic development. Our study suggests that a bilingual environment may facilitate language development in children poststroke.

Ischemic Cerebellar Stroke in a Young Patient with Neurofibromatosis Type 2, a Case Report (P12-5.026)

<h3>Objective:</h3> We present a case of brainstem ischemia in a young patient with neurofibromatosis 2 (NF2) and review the existing literature on similar cases, which together suggest a possible NF2-associated syndrome of which stroke neurologists and pediatric neurologists should be aware. <h3>Background:</h3> NF2 is a multifaceted disease characterized primarily by benign CNS tumors, especially meningiomas and vestibular schwannomas. There have been several cases of brainstem ischemic stroke in young NF2 patients reported in the literature. To date, there is no unified theory about the connection between NF2 and pediatric stroke. <h3>Design/Methods:</h3> We present a case of ischemia in the left cerebellar peduncle of a young patient with NF2, as well as a narrative review of the literature on previous cases. <h3>Results:</h3> The patient presented to the Emergency Department with left facial paresthesia and dizziness. Serial Magnetic Resonance Images (MRI’s) displayed an initial area of restricted diffusion in the left cerebellar peduncle with peripheral enhancement which did improve over several months, consistent with maturing infarct. <h3>Conclusions:</h3> Our case joins several others with similar presentations and findings, including pediatric patients for whom brainstem ischemia was the presenting symptom of NF2. The primary theory for the cause of brainstem ischemia in juvenile NF2 is a microvascular cause due to genetic deficiency of <i>neurofibromin 2</i>, a regulator of endothelial development, whose absence is likely to disrupt vascular homeostatic mechanisms. Multicenter studies with large NF2 cohorts are needed to better characterize this syndrome. Understanding brainstem ischemia in young NF2 patients will inform the development of treatment guidelines for such patients. <b>Disclosure:</b> An immediate family member of Mrs. Trautman has received personal compensation for serving as an employee of Hydro Extrusions. Mrs. Trautman has received personal compensation for serving as an employee of University of South Dakota. Dr. Sandhu has nothing to disclose.

Unvaccinated: An unrecognized risk factor for stroke (P14-5.030)

<h3>Objective:</h3> Review the under-recognized risk for childhood stroke for unvaccinated children. <h3>Background:</h3> Approximately thirty five percent of pediatric strokes may be attributed to focal cerebral arteriopathy (FCA). FCA is a unifocal and unilateral stenosis of a large intracranial artery of the anterior circulation. Cases have been associated with varicella infection in the year prior to stroke. Acute ischemic strokes caused by FCA have a 25% recurrence risk in one year and therefore need to be monitored closely. Literature suggests that patients with FCA may benefit from treatment with steroids, in addition to anti-thrombotic therapy, making early diagnosis essential for optimizing outcomes. We present a case of FCA in the setting of recent varicella infection. <h3>Design/Methods:</h3> n/a <h3>Results:</h3> A 14-year-old unvaccinated female presented to the emergency department with left facial droop, left hemiparesis and speech disturbance. Symptoms started four days prior, worsening on day of arrival. NIH Stroke Scale on presentation was 2 for aphasia. CT head was normal. MRI brain showed restricted diffusion involving the right internal capsule and deep grey matter. MRA showed right internal carotid artery narrowing. Given delayed presentation, she was out of the window for acute interventions and was transferred for higher level of care. History was notable for varicella 7 months ago and COVID-19 5 months ago. Vessel wall imaging showed narrowing in the right internal carotid and A1, consistent with FCA. Patient was started on pulse dose steroids and aspirin. <h3>Conclusions:</h3> We present a case arterial ischemic stroke secondary to FCA in a patient with history of varicella infection. Wild type varicella infection has been associated with FCA up to 12 months post-infection and under-vaccination is associated with over 8-fold increase in risk of childhood stroke. Incidence of strokes related to varicella infection has decreased with the availability of vaccinations, highlighting the importance of childhood vaccines. <b>Disclosure:</b> Dr. Gupta has nothing to disclose. Dr. Pearson has nothing to disclose.

Neurodevelopmental outcomes of neonatal posthemorrhagic hydrocephalus and psychological effects on the parents

BackgroundNeonatal posthemorrhagic hydrocephalus remains a common complication in preterm infants, with high rates of mortality and morbidity, placing parents at high risk of anxiety and depression. We sought to investigate the neurodevelopmental outcomes of infants with posthemorrhagic hydrocephalus who underwent surgery and the psychological effect on their parents.MethodsWe retrospectively analysed all infants with posthemorrhagic hydrocephalus born between 2014 and 2020 in the Children’s Hospital of Chongqing Medical University, China. The neurodevelopmental outcomes of 28 patients were evaluated by the Pediatric Stroke Outcome Measure score, and the psychological states of the parents of survivors were assessed by the Hospital Anxiety and Depression Scale.ResultsThe families of the 28 patients were followed up for a median duration of 3 years; 6 (21.4%) patients died within 6 months after discharge, 12 (42.9%) patients had moderate to severe dysfunction, and only 10 (35.7%) patients had good outcomes. Regarding the 22 parents of the survivors, 5 (22.7%) and 4 (18.2%) had borderline anxiety and depression symptoms, respectively. Two (9.1%) caregivers had exact anxiety and depression symptoms. Leukomalacia after intraventricular haemorrhage was associated with adverse neurological outcomes. The infants' histories of epileptic seizures during the neonatal period were associated with the anxiety of their parents.ConclusionThe overall outcome of posthemorrhagic hydrocephalus patients is unsatisfactory, and children with leukomalacia after haemorrhage tend to have poor outcomes. A history of epileptic seizures during the course of the disease may exacerbate the anxiety of the caregivers.

Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

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.

349 ZYX is a Novel Candidate Gene in Moyamoya Pathogenesis

INTRODUCTION: Moyamoya disease (MMD) is characterized by progressive bilateral stenosis in the proximal branches of the internal carotid arteries with compensatory angiogenesis. It is common in Japanese population; accounting for one fifth of pediatric stroke cases associated with arteriopathies. Although the etiology remains largely unknown, genetic factors have been implicated in the pathophysiology of MMD. METHODS: We performed gene-based mutational burden analysis using WES results of 23 MMD patients and a control cohort of 8380 Japanese individuals obtained from jMorp (8.3 kjpn). We performed a case-control analysis by comparing the enrichment of rare (Japanese minor allele frequency &lt;2.5e-4) and deleterious variants including loss of function (LoF) variants (stop gain, start loss, frameshift, splice acceptor and splice donor) and missense variants annotated as “deleterious” in MetaSVM (D-Mis). RESULTS: We identified ZYX gene, encoding a focal adhesion molecule Zyxin, top significantly enriched gene in MMD cohort (two tailed Fisher's P = 1.52E-5; OR 77.55 [95% CI 13.91–291.69]), with three individuals were found to carry a heterozygous LoF and two missense mutations in ZYX gene. ZYX expression was found above 96th percentile for an ‘arterial-enrichment ratio’ calculated using GtEX portal, suggesting its critical role in vascular cell types. CONCLUSIONS: In this study, we identified ZYX as a novel candidate gene in Moyamoya pathogenesis. Zyxin is a known focal adhesion molecule involved in mechanosensation in the vasculature, while its implication in MMD has not been previously reported.