Cerebral Sinovenous Thrombosis Research Articles

Neonatal Cerebral Sinovenous Thrombosis: A Rare Case Report and Literature Review

Neonatal cerebral sinovenous thrombosis is a rare and potentially life-threatening disorder associated with various longterm neurological deficits. The pathogenesis of cerebral sinovenous thrombosis in neonates is still unclear. Many potential risk factors have been identified, such as gestational or delivery complications or neonatal comorbid conditions including dehydration, sepsis, or cardiac defects. A correct diagnosis is often delayed due to the subtle presentation of the disorder, leading to delayed treatment with poor outcomes. Herein, we report a preterm female neonate who was born only with the presentation of intrapartum maternal fever. Routine brain sonography showed intraventricular hemorrhage. In a further study, brain magnetic resonance imaging revealed neonatal multiple sinovenous thrombosis. To prevent potential thrombosis development and ameliorate possible thrombosis-related problems, the infant immediately received anticoagulation therapy. At the 3-month follow-up, developmental milestones were within the normal range, and the follow-up brain MRI scans also showed normal results. In conclusion, early recognition and proper treatment may yield a better prognosis for neonatal cerebral sinovenous thrombosis, especially when patients exhibit any possible risk factors, which should alert healthcare professionals.

Two years experience of a multidisciplinary approach for pediatric thrombosis in a tertiary referral center

Pediatrik tromboz epidemiyolojisi, patofizyolojisi ve tedavi oncelikleri nedeniyle eriskin tromboz yonetiminden cok farkli ozelliklere sahiptir. Tromboz teshisi konan cocuklar, multidisipliner bir ekip tarafindan tani, tedavi ve takip suresince degerlendirilmelidir. Burada pediatrik tromboz hastalarimizin yonetildigi 2 yillik multidisipliner tromboz konseyi deneyimimizi sunuyoruz. Kasim 2017-Agustos 2019 tarihleri arasinda 61 cocuk (95 basvuru) icin tromboz konseyi olgu sunumlarini ve konsey sonuclarini geriye donuk olarak inceledik. Degerlendirilen hastalarda erkek/kadin orani 1,54 saptandi, cocuklar ve adolesanlar cogunluktaydi. Hastalarin klinik ve radyolojik durumlarina gore tedavi ve profilaksi sureleri belirlendi. Olgularimiz icinde serebral arteriyel ve sinovenoz tromboz olgulari daha fazla idi. Kazanilmis risk faktorleri, kalitsal olanlardan daha fazla olup, infeksiyon ve Faktor VIII yuksekligi sik idi. Otuz dokuz hastaya (%64) farkli sureler boyunca K vitamini antagonistleri, aspirin veya LMVH ile primer veya sekonder profilaksi uygulandi. Pediatrik trombozda kanita dayali kilavuzlarin iyilestirilmesi icin tedavi ve profilaksi yonetimi uzerine daha fazla calismaya ihtiyac vardir. Multidisipliner tromboz konseyi komplike pediatrik trombozlu cocuk hastalarda hasta bakimini iyilestirebilir.

Abstract 51: The Incidence of Perinatal Stroke is 1:1200 Live Births: A Population-Based Study in Alberta Canada

Introduction: Perinatal stroke encompasses six cerebrovascular syndromes which occur between the 20 th week of gestation and the 28 th post-natal day. Morbidity is significant including motor, language, behavioral, and cognitive challenges, as well as epilepsy. Acute presentations include neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis (CSVT), and neonatal hemorrhagic stroke (NHS). Delayed presentations include arterial presumed perinatal ischemic stroke (APPIS), periventricular venous infarction (PVI), and presumed perinatal hemorrhagic stroke (PPHS). Inconsistent terminology and lack of population-based cohorts has limited accurate measurement of disease-specific perinatal stroke incidence. Our objective was to define the incidence of the subtypes of perinatal stroke using a population-based cohort. Methods: The Alberta Perinatal Stroke Project is a research cohort established in 2008 in Southern Alberta, Canada (population ~2.1 million). Leveraging universal health care at a single tertiary care pediatric center facilitated true population-based epidemiology. Patients included had neuroimaging-confirmed perinatal stroke. Case acquisition included exhaustive retrospective hospital and ICD code searches (1990-2008) and prospective enrollment from all NICU and neurology/stroke clinics (2008-2018). Live birth rate denominators were determined from the provincial census. Results: The overall incidence of perinatal stroke in Southern Alberta from 2008-2018 was 81 cases per 100,000 live births, or 1 case per approximately 1200 live births. The incidence of NAIS was 31 per 100,000 (~1/3000), APPIS was 11 per 100,000 (~1/9000), PVI was 18 per 100,000 (~1/5500), and CSVT was 10 per 100,000 (~1/9800). The incidence of NAIS increased after implementing prospective case identification, from 8.5 (95% CI 5.3-11.6) per 100,000 to 31 per 100,000 (95% CI 24.4-38.2), p<0.00001, the remainder of stroke subtypes were stable over time. Conclusions: The overall incidence of perinatal stroke in Southern Alberta is 1:1200 live births. Population-based sampling of disease-specific states may explain why this rate is much higher than previous estimates.

Role of platelet gene polymorphisms in ischemic pediatric stroke subtypes: a case-control study

AimTo assess the role of human platelet antigens (HPA), P-selectin gene (SELP) polymorphisms, and HPA and SELP haplotypes with factor V (FV) R506Q in ischemic pediatric stroke (IPS) subtypes: cerebral sinovenous thrombosis (CSVT), perinatal (PAIS), and childhood (CAIS) arterial ischemic stroke.MethodsThis case-control study enrolled 150 children with confirmed IPS and 150 age- and sex-matched controls. FV R506Q and HPA-1 were genotyped with CVD StripAssay®, HPA-2 and HPA-3 with real-time polymerase chain reaction, SELP S290N, V599L, and T715P with high resolution melting analysis, and SELP N562D with sequence-specific polymerase chain reaction.ResultsHPA-1b allele (odds ratio [OR] 2.75, 95% confidence interval [CI] 1.02-7.42, P = 0.048) and HPA-1a2a3b (OR 5.46, 95% CI 1.51-19.76, P = 0.011), HPA-1b2a3a (OR 7.00, 95% CI 1.25-39.13, P = 0.028), and HPA-1b2b3a (OR 11.39, 95% CI 1.39-92.95, P = 0.024) haplotypes increased the risk for CSVT. HPA-3b allele was significantly associated with 2-fold lower risk for PAIS (OR 0.49, 95% CI 0.26-0.89, P = 0.020) and CAIS (OR 0.47, 95% CI 0.26-0.86, P = 0.014) and non-significantly associated with increased risk for CSVT (OR 6.43, 95% CI 0.83-50.00, P = 0.022). HPA-1a2b3a haplotype was significantly associated with CAIS (OR 6.76, 95% CI 2.13-21.44, P = 0.001). The inclusion of FV R506Q in SELP haplotype analysis increased the risk for PAIS 4-fold in QNDVT carriers (OR 8.14, 95% CI 0.93-71.33, P = 0.060) compared with NDVT haplotype (OR 2.45, 95% CI 0.98-6.18, P = 0.058), but the result was not significant.ConclusionIndividual HPAs, and particularly HPA haplotypes, are involved in IPS subtypes pathogenesis. A possible risk-inducing synergistic effect of SELP haplotypes with FV R506Q is restricted to PAIS only.

Chapter 16 - Perinatal stroke

Perinatal stroke is a heterogeneous syndrome resulting from brain injury of vascular origin that occurs between 20 weeks of gestation and 28 days of postnatal life. The incidence of perinatal stroke is estimated to be between 1:1600 and 1:3000 live births (approximately 2500 children per year in the United States), though its actual incidence is difficult to estimate because it is likely underdiagnosed. Perinatal arterial ischemic stroke (PAIS) accounts for approximately 70% of cases of perinatal stroke. Cerebral sinovenous thrombosis, while less common, also accounts for a large proportion of the morbidity and mortality seen with perinatal stroke. Hemorrhagic stroke leads to disruption of neurologic function due to intracerebral hemorrhage that is nontraumatic in origin. While most cases of PAIS fall into one of these three categories, other patterns of injury should also be considered perinatal stroke. In some cases, the etiology of PAIS is not known but is idiopathic. This chapter will review the classification, risk factors, pathogenesis, clinical presentation, management, and long-term sequelae of perinatal stroke.

Bivalirudin anticoagulation to overcome heparin resistance in a neonate with cerebral sinovenus thrombosis.

: Anticoagulation in a neonate is a challenge and the availability of anticoagulant options is extremely limited. Here we describe the use of a direct thrombin inhibitor, bivalirudin, in a full-term neonate with symptomatic cerebral sinovenous thrombosis complicated by bilateral thalamic hemorrhagic stroke and intraventricular hemorrhage, who could not be effectively treated with sodium heparin due to heparin resistance (HR) and showed thrombosis regression after start of bivalirudin treatment, without worsening of the hemorrhage. While the use of bivalirudin in neonates has been previously described, the indication of cerebral sinovenous thrombosis and the setting of HR are unique.

Transient water-electrolyte disturbance after hemispherotomy in young infants with epileptic encephalopathy.

This study aimed to elucidate the clinical features of water-electrolyte disturbance (WED) as a sequela of hemispherotomy. We performed a retrospective chart review to identify the clinical features of diabetes insipidus (DI) as a complication in < 12-month-old patients who underwent hemispherectomy or hemispherotomy for severe epilepsy between 2007 and 2018. Central DI was diagnosed if a patient developed polyuria (urine output > 5mL/kg/h), abnormally high serum osmolality (> 300mOsm/kg), high serum sodium level (> 150mEq/L), either abnormally low urine specific gravity (< 1.005) or low urine osmolality (< 300mOsm/kg) or both, and effective control of polyuria with arginine vasopressin (AVP). The clinical course of post-hemispherotomy WED, complications other than WED, and seizure outcomes were analyzed. The review identified that 3 of 23 infants developed WED. All patients developed polyuria within 2days after surgery, with high serum osmolality and hypotonic urine; AVP was effective in treating these symptoms. The clinical course was compatible with central DI. Two patients subsequently developed hyponatremia in a biphasic or triphasic manner. All patients had multiple seizures that were probably related to WED. Two patients developed asymptomatic cerebral sinovenous thrombosis, possibly because of the surgical procedure and dehydration; anticoagulant treatment was provided. All patients were treated for WED for up to 2months and had no residual pituitary dysfunction. Systemic complications other than intracranial ones can occur in patients who have undergone hemispherotomy. Perioperative systemic management of young infants undergoing this procedure should include careful water and electrolyte balance monitoring.

Outcome Trajectories after Primary Perinatal Hemorrhagic Stroke

BackgroundPerinatal hemorrhagic stroke in late preterm and term neonates is understudied. We describe two-month and two-year neurological outcomes in a prospective cohort. MethodsNeonates ≥36 weeks’ gestation with spontaneous hemorrhagic stroke (parenchymal and intraventricular) presenting at age ≤28 days were enrolled between March 2007 and May 2015 at three tertiary pediatric centers. Hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis was excluded. The Pediatric Stroke Outcome Measure (PSOM) assessed outcomes. Wilcoxon signed-rank tests evaluated change over time. ResultsTwenty-six neonates were included (median age: 1 day, interquartile range [IQR] 0 to 16; median gestational age: 38.3 weeks, IQR 37.0 to 39.0). Hemorrhage was isolated intraventricular in seven (27%), isolated intraparenchymal in six (23%), and a combination in 10 (39%). Three neonates (12%) died during hospitalization; one died later due to cardiac disease. Among 22 survivors, outcomes were assessed at a median of 2.1 months (IQR 1.7 to 3.3) in 96% and 1.9 years (IQR 1.3 to 2.0) in 73%. Median PSOM scores were 0.0 (IQR 0.0 to 1.0) and 0.25 (IQR 0.0 to 1.3), respectively. At two years, 45% of patients had no or nonimpairing deficits (PSOM <1.0), 30% had mild deficits (PSOM 1.0 to 2.0), and 5% had moderate deficits (PSOM 2.5 to 4.5). Over time, 31% worsened and 6% improved. Although total PSOM scores did not change significantly (P = 0.08), language subscores worsened (P = 0.009). No child developed epilepsy. ConclusionsPerinatal hemorrhagic stroke survivors had favorable outcomes in early childhood; at two years moderate to severe deficits occurred in 5%. Language deficits may emerge over time, warranting close follow-up.

Risk Factors for Pediatric Cerebral Sinovenous Thrombosis: A Case-Control Study with Pediatric Neuroradiologist Case Validation

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) is a rare but serious disease process among all patients, with a slightly higher prevalence in pediatric patients. Despite its low frequency, CSVT represents the second most common type of venous thromboembolism (VTE) in children, next to deep vein thrombosis (DVT) of the limbs. Current literature lacks robust evidence on risk factors for CSVT, especially in the pediatric population. We sought to determine risk factors of CSVT in pediatric patients, via a single-institutional case-control study. METHODS: A case-control study was conducted at Johns Hopkins All Children's Hospital from patients admitted between March 31st 2006 and April 1st 2018. Cases were identified based on ICD-9 and ICD-10 codes and confirmed via electronic medical record (EMR) review and neuroradiologist confirmation of radiologic testing. Two controls were then randomly selected for each CSVT case, matched by month and year of admission. Clinical and demographic parameters were collected via abstraction from the EMR, including: age at admission, prior history of VTE, previous hospitalization within 30 days, head/neck surgery, other major surgery, congenital or acquired heart disease, dehydration, cancer, serious infection (included meningitis, sepsis, pneumonia, osteomyelitis, fungemia, pyelonephritis, head/neck infection, abscess involving anatomic sites other than skin or head/neck), prematurity, mechanical ventilation, chronic inflammatory disease, cystic fibrosis, nephrotic syndrome, obesity, and head/neck trauma. Associations between CSVT and putative risk factors were evaluated via logistic regression, using odds ratios (ORs) and 95% confidence intervals (95%CIs). Those risk factors with P-values &lt;0.1 in univariate logistic regression were included in adjusted (multivariate) logistic regression modeling; results of the latter employed a threshold of P&lt;0.05 for statistical significance. RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (and interquartile range in) age was 4.79 years (0.02-13.56 years) for cases and 5.58 years (1.16-10.78 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: presence of central venous catheter; serious infection; mechanical ventilation; chronic inflammatory disease; and head/neck trauma. In the multivariate model, mechanical ventilation (OR=9.01, 95%CI=2.19-37.02) and head/neck trauma (OR=11.52, 95% CI=2.63-50.41) remained independent, statistically-significant risk factors for CSVT. CONCLUSIONS: This single-institutional case-control study reveals that mechanical ventilation and head/neck trauma are independent risk factors for pediatric CSVT. These findings will be further investigated via the multicenter Children's Hospital-Acquired Thrombosis (CHAT) registry dataset, by which a risk model for CSVT in children will be further developed and validated, in order to inform future preventive strategies in pediatric patients at heightened risk of CSVT. Table Disclosures Goldenberg: NIH: Other: research support and salary support.

Cerebral Thrombosis As an Initial Presentation of Pediatric Acute Promyelocytic Leukemia

Disseminated intravascular coagulopathy and bleeding are common manifestations of acute promyelocytic leukemia(APL) which are both associated with significant mortality and morbidity. However APL related thrombosis is very rare and majority of the reported cases are adults in the literature. In the past 14 years, 14 cases with APL were found in our hospital database.There were 6 female and 8 male children with a mean age of 10.7±4.6 years (2-17y). Here, we report two pediatric APL case who presented with cerebral thrombosis at the initial presentation. 8/14(57%) had disseminated intravascular coagulation at the initial presentation and one patient had intracardiac and cerebral sinovenous thrombosis during the induction period. Case 1:A 13-year-old boy was admitted to our hospital with a complaint of headache for two days. His physical examination revealed a papilledema and cranial MRI did show sinovenous thrombosis. At the time of the evaluation his WBC count was found to be low and there were myeloid blasts on his peripheral smear,bone marrow aspiration was done and diagnosed as translocation t(15;17)positive APL. He remain in remission more than 4 years without any event however deceased after relapse. Case 2: A 8-year-old boy was admitted to our hospital with a complaint of right hemiparesis, there was a thrombotic occlusion of the left middle cerebral artery associated cerebral infarct on his MRI.His WBC was 5.9x109/l with 76% blasts and bone marrow aspiration and flow-cytometry were both compatible with APL. Patient died after 2 weeks of admission because of thrombosis and bleeding. The incidence of APL related thrombosis was 4.5 and 5.6% in two large adult cohorts. Both arterial and venous thrombosis may ocur in patients with APL. To the best of our knowledge there were limited number of pediatric APL case reports in the literature who presented with thrombosis. In our small group of pediatric APL patients 14% presented with thrombosis and the total number of thrombotic events were found to be 28% during the follow up. Disclosures No relevant conflicts of interest to declare.

Screening for paroxysmal nocturnal hemoglobinuria (PNH) in patients presenting with cerebral sinovenous thrombosis (CSVT): Results of a FLAER based flowcytometry study in Indian patients.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) may present with thrombosis at unusual sites, of which cerebral sinovenous thrombosis (CSVT) is one and screening for PNH is recommended in this condition. Though many patients diagnosed with PNH develop CSVT, it is unclear how many patients with PNH would present for the first time with thrombosis. We analysed the results of screening for PNH by flowcytometry in our patients with CSVT. The laboratory data of patients referred for thrombophilia and PNH testing in CSVT was examined to assess the frequency of PNH at presentation in these patients. FLAER and CD24 on granulocytes and FLAER and CD14 on monocytes respectively were used to screen the leucocytes for PNH by flowcytometry. The data for Protein C, S and Antithrombin deficiency, antiphospholipid antibodies and the Factor V Leiden mutation was examined and circumstantial risk factors were also assessed. Of the 180 cases of CSVT screened by flowcytometry for PNH, not a single case tested positive. Positivity for anti-phospholipid antibodies was the most common thrombophilic risk factor (5%). Pregnancy was the most common circumstantial risk factor. Our data on FLAER based flowcytometry in the North Indian population with CSVT suggests that PNH is not a common risk factor in our patients with thrombosis at this unusual site.

Seizures and Outcome One Year After Neonatal and Childhood Cerebral Sinovenous Thrombosis

BackgroundPediatric 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. MethodsPatients 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. ResultsTwenty-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. ConclusionOur 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.

Treatment and outcome of childhood cerebral sinovenous thrombosis.

To test our hypothesis that anticoagulation is associated with better neurologic outcomes in childhood cerebral sinovenous thrombosis (CSVT), we analyzed treatment and outcomes in a population of 410 children from the International Pediatric Stroke Study (IPSS). We included patients enrolled in the IPSS registry with a diagnosis of CSVT at age >28 days with radiologic confirmation, in isolation or with concomitant arterial ischemic stroke. The primary outcome was the neurologic status at discharge. We defined unfavorable outcome as severe neurologic impairment or death at discharge. The Pediatric Stroke Outcome Measure was used for long-term outcome in those with follow-up. Predictors of anticoagulation use and outcome were analyzed by logistic regression. Most children (95%) had identifiable risk factors, and 82% received anticoagulation. Shift analysis demonstrated better outcomes at discharge in children who were anticoagulated, and this persisted with longer-term outcomes. In multivariable analysis, anticoagulation was significantly associated with favorable outcomes (adjusted odds ratio [aOR] unfavorable 0.32, p = 0.007) whereas infarct was associated with unfavorable outcome (aOR unfavorable 6.71, p < 0.001). The trauma/intracranial surgery was associated with a lower odds of anticoagulation use (aOR 0.14, p < 0.001). Within the IPSS registry, children with risk factors of trauma or intracranial surgery were less likely to receive anticoagulation for CSVT. Anticoagulation was associated with a lower odds of severe neurologic impairment or death at hospital discharge, but this finding is limited and needs further confirmation in randomized, controlled, prospective studies.

Cause or Consequence: The Relationship Between Cerebral Venous Thrombosis and Idiopathic Intracranial Hypertension.

The aims of our study were to refer to the complex relationship between idiopathic intracranial hypertension (IIHT) and cerebral sinovenous thrombosis (CSVT), and to determine the differences and commonalities between the patients with and without CSVT in their etiology, along with documenting the uncertainties in concluding on the diagnosis and treatment of these patients. IIHT was diagnosed according to Dandy criteria, while CSVT was screened for by way of a cranial magnetic resonance imaging for all patients and cranial magnetic resonance venography only if the magnetic resonance imaging was nebulous or there was a family history. We retrospectively evaluated a total of 26 patients (9 of whom had CSVT) diagnosed with IIHT between 2014 and 2018. A total of 9 patients with concurrent CSVT were described as suffering from vascular IIHT, while the remaining 17 were described as suffering from other IIHT. Demographic characteristics were similar in both groups (mean age: 12 vs. 11; male/female ratio: 2/7 vs. 5/12 in vascular IIHT and other IIHT, respectively). Clinical findings, cerebrospinal fluid-opening pressure values, and pathologies of etiology were also similar (vitamin D deficiency: 66% vs. 52%; vitamin B12 deficiency: 11% vs. none; iron deficiency: 22% vs. 11%; obesity: 22% vs. 23%). A mixture of acetazolamide, topiramate, anticoagulant therapy, and acetylsalicylic acid were given according to the diagnoses. CSVT is a common clinical entity among the causes of IIHT, and it should be taken into consideration in this patient group. However, there is a need for a common guideline for laboratory and imaging methods to understand the etiopathogenesis of childhood IIHT and determine the patients at risk.

Perinatal Stroke

Perinatal strokes are a diverse but specific group of focal cerebrovascular injuries that occur early in brain development and affect an estimated 5 million people worldwide. The objective of this review is to describe the epidemiology, clinical presentations, pathophysiology, outcomes, and management for the 6 subtypes of perinatal stroke. Some perinatal strokes are symptomatic in the first days of life, typically with seizures, including neonatal arterial ischemic stroke, neonatal hemorrhagic stroke, and cerebral sinovenous thrombosis. The remaining subtypes present in the first year of life or later, usually with motor asymmetry and include arterial presumed perinatal ischemic stroke, presumed perinatal hemorrhagic stroke, and in utero periventricular venous infarction. The consequences of these injuries include cerebral palsy, epilepsy, and cognitive and behavioral challenges, in addition to the psychosocial impact on families. While there have been significant advances in understanding mechanisms of both injury and recovery, there is still a great deal to learn regarding causation and the optimization of outcomes.

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.

Incidence and features of thrombosis in children with inherited antithrombin deficiency.

Pediatric thromboembolism (≤18 years) is very rare (0.07-0.14/10,000/year) but may be more prevalent in children with severe thrombophilia (protein C, protein S or antithrombin deficiency). The aim of this study was to define the prevalence and clinical characteristics of pediatric thrombosis in subjects with inherited antithrombin deficiency. Our observational retrospective multicentric study from two countries recruited 968 patients of any age from 441 unrelated families with genetically, biochemically and functionally characterized antithrombin deficiency. Seventy-three subjects (7.5%) developed thrombosis before 19 years of age. Two high-risk periods for thrombosis were identified: adolescence (12-18 years, n=49) with thrombus localization (lower limb deep venous thrombosis or pulmonary embolism) and triggering factors common to adults (oral contraceptives, surgery or pregnancy); and the neonatal period (<30 days, n=15) with idiopathic thrombosis at unusual sites. The clinical evaluation of pediatric thrombosis in subjects with antithrombin deficiency revealed: i) a high prevalence of cerebral sinovenous thrombosis (n=13, 17.8%), mainly at young age (8 neonates and 4 children <6 years); ii) severe outcome with fatality in six cases (3 neonates, two of them homozygous for p.Leu131Phe). The majority of subjects (76.7%) carried quantitative type I deficiency. This retrospective analysis includes the largest cohort of subjects with inherited antithrombin deficiency so far and provides strong evidence for an increased risk of pediatric thrombosis associated with this thrombophilia (300-fold compared with the general population: 0.41%/year vs. 0.0014%/year, respectively). Our results support testing for antithrombin deficiency in children of affected families, particularly in case of type I deficiency.

Neurological complications in childhood nephrotic syndrome: A systematic review.

Nephrotic syndrome (NS) in childhood can be accompanied by serious neurological complications increasing the morbidity of disease. The study aimed to assess the spectrum of neurological complications in children with in terms of clinical presentation, contributory risk factors, and outcome. In this systematic review, we searched for articles in PubMed, providing individual patient-level data for any neurological complication in children and adolescents with primary NS, between January 1, 1990 and April 30, 2018. The search yielded 63 articles, involving 103 patients. Events occurred more frequently during nephrotic state relapses; 71.6% of cerebral thromboembolic (TE) events and 81.2% of posterior reversible encephalopathy (PRES) cases. Median duration of disease before a cerebral TE event was 3 months (IQR 0-27), and 18 months (IQR 1-37.5) for PRES. Among cases with TE, 73.1% presented with cerebral sinovenous thrombosis (CSVT), and 16.9% parenchymal lesions. 70% of patients had a risk factor for neurological complication including NS-associated thrombophilia, hypertension, and treatment with immunosuppressive agents. Outcome was favorable in 93.8% of the patients with PRES. In patients with cerebral TE outcome was favorable in 95.8% of the cases with CSVT only, and in 64.7% of the cases with parenchymal lesions. Neurological complications may occur in children with primary NS and risk factors during nephrotic state relapses. The outcome for PRES has been reported favorable. Outcome in cerebral TE events may differ by the presence of venous or artery infarct. Recognition of additional protrombotic state risk factors may help to lower the incidence of neurological complications.

Epidemiology of neonatal stroke: A population-based study.

The goal of this study was to obtain population-based data on the incidence, clinical presentation, management, imaging features, and long-term outcomes of patients with all types of neonatal stroke (NS). Full-term neonates with NS born between January 2007 and December 2013 were identified through the Nova Scotia Provincial Perinatal Follow-up Program Database. Perinatal data and neonatal course were reviewed. Neurodevelopmental outcomes were assessed at 18 and 36 months of age using standardized testing. Twenty-nine neonates with NS were identified during the study period, giving an incidence of 47 per 100,000 live births in Nova Scotia. Arterial ischemic stroke was the most common stroke type (76%), followed by neonatal hemorrhagic stroke (17%), then cerebral sinovenous thrombosis (7%). The majority of neonates presented with seizures (86%) on the first day of life (76%). At 36 months of age, 23 (79%) of the children had a normal outcome, while 3 (10%) were diagnosed with cerebral palsy (2 with neonatal arterial stroke and one with neonatal hemorrhagic stroke) and 3 (10%) had recurrent seizures (1 patient from each stroke subtype group). The incidence of NS in Nova Scotia is higher than what has been reported internationally in the literature. However, the neurodevelopmental outcomes at 3 years of age are better. Further studies are required to better understand the reasons for these findings.

Short-term neurological outcomes in ischemic and hemorrhagic pediatric stroke.

The aim of this study was to retrospectively assess short-term neurological outcomes in pediatric stroke with regard to patient characteristics. Children aged 28 days-18 years with arterial ischemic stroke (AIS), cerebral sinovenous thrombosis (CSVT), and hemorrhagic stroke (HS) between 2007 and 2013 were evaluated. Neurological findings in the first 3 months were accepted as short-term prognosis, and modified Rankin scale was used. A total of 33 patients (62%) with AIS, 12 (23%) with HS, and eight (15%) with CSVT were included. Moya moya syndrome was the most common new diagnosis in AIS. Stroke recurred in five (15%); and one AIS patient with posterior circulation infarct died (3%). Prognosis in AIS was favorable for 20 patients (61%) and poor for 13 patients (39%). Forty-two percent of HS were of vascular origin. Seven patients (70%) with HS had good prognosis and three (30%) had poor prognosis with no death. Homocysteine-related hypercoagulability was most frequently noted in the etiology of CSVT. Synchronous systemic thrombosis was observed in three CSVT patients (37.5%) and death occurred in two (25%). Prognosis was evaluated as favorable for three CSVT patients (37.5%) and poor for five (62.5%). For thrombophilia, thrombosis panel was performed fully in 83% of AIS and CSVT patients. Pediatric stroke is associated with a poor prognosis in a substantial number of patients in the short term, with CSVT having the worst prognosis. Detailed patient characteristics are listed not only for ischemic but also for hemorrhagic stroke; and a full thrombosis panel was achieved for most ischemic stroke patients.