Pediatric Cerebral Venous Sinus Thrombosis Research Articles

Clinical Course and Visual Outcomes of Papilledema in Pediatric Cerebral Venous Sinus Thrombosis

Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening event with significant neurologic and visual morbidity. In this study, we report on the natural history and visual outcomes of papilledema in children with CVST. Retrospective case series. Patients with CVST evaluated by the Department of Ophthalmology between 2000 and 2023 were included. Records were reviewed for presence and course of papilledema, treatment, and final visual outcomes following papilledema resolution. The study included 35 patients with a mean age of 9 ± 5 years and 40% were female. The most common risk factors for CVST were infection (69%), dehydration (26%), and hypercoagulability (23%). 31 patients (89%) had papilledema. Of these patients, 9 (29%) had progression of papilledema despite treatment, 17 patients (55%) did not have progression, and 5 patients (16%) lacked follow-up records. Initial Frisén grade among all cases was 2 ± 1, and cases with progression reached a grade of 4 ± 1 between 10 and 32 days following initial identification. Most patients (97%) were treated with anticoagulation and 100% required acetazolamide and/or lumbar puncture. Among 26 patients with follow-up, papilledema resolved in 107 ± 128 days. Fifty-four percent of patients had permanent ophthalmic sequelae. An initial Frisén grade ≥3 (odds ratio 7.54, 95% confidence interval 6.53-8.70, P< .001) was significantly associated with eventual optic atrophy. Children with CVST are at high risk for ophthalmologic sequelae. Papilledema can progress despite appropriate therapy. Our results highlight the importance of ophthalmologic follow-up during treatment course to prevent irreversible vision loss.

Machine Learning Model for Predicting Mortality Risk in Pediatric Cerebral Venous Sinus Thrombosis

Introduction: Pediatric Cerebral Venous Sinus Thrombosis (CVST) is a rare but serious disorder with risk for neurologic sequelae and mortality. Prediction of health outcomes for risk stratification and tailored therapy is difficult based on available literature with single center studies and limited sample sizes. We sought to analyze the CVST data in Pediatric Health Information System (PHIS) database, a large, multicenter administrative database of pediatric inpatient data, to assess if supervised machine learning can assist in identifying pediatric CVST patients with increased risk of adverse outcomes. Methods: Patients 0 to 17 years of age with a diagnosis of CVST were identified in the PHIS database from 2011 to 2022. Demographic information, clinical characteristics, evaluation and management, and outcome data was extracted from diagnostic, imaging, procedure, and pharmaceutical billing codes. An XGBOOST model was fitted using 10-fold cross-validation with Bayesian optimization for hyperparameter tuning. The clinical parameters with values optimal for analysis from the “early era” (2011-2015) dataset were used to train for machine learning, and the test was applied to the “late era” (2016-2022) dataset. The final model was chosen based on the highest test set AUC score. The clinical parameters with significant SHAP values from the model were compared to published risk factors for mortality from an International Pediatric Stroke Study (IPSS) (RN Ichord, et al. Arch Dis Child 2015). Results: 6080 hospitalizations with CVST diagnosis (0.1% of all hospitalizations) were identified. The clinical parameters applied for machine learning included the following: age, gender, race, major complications (intracranial bleeding, hydrocephalus, coma), child opportunity index and ICU admission (Table 1.). The overall mortality rate at discharge was 4.2%. 2029 hospitalizations occurred in the early era and 4051 hospital admissions occurred in the late era. With the analyzable clinical parameters, the XGBOOST model could predict mortality with a probability of 0.7906. Of the clinical parameters used for machine learning (Figure 1), ICU admission, intracranial bleeding, hydrocephalus and coma had positive SHAP values indicating higher mortality risk prediction, whereas older age and being non-Hispanic white had negative SHAP values indicating lower mortality risk prediction. Similar risk associations for mortality were reported in the IPSS study, with patients with intracranial bleeding, younger age, and coma having higher mortality risk, consistent with our study finding. Conclusion: Our study in pediatric CVST, using machine learning, shows higher risk of mortality with ICU admission, and complications including intracranial bleeding, hydrocephalus, and coma; and lower risk of mortality with older age and non-Hispanic White status, which are consistent with IPSS study observations. Our study also illustrates how machine learning can be utilized by investigators to predict adverse clinical outcomes in pediatric CVST. In rare diseases which are difficult to study due to limited sample sizes like pediatric CVST, our study shows that data from large databases such as PHIS can be utilized for machine learning to predict health care outcomes, which can in turn inform future clinical practice to improve patient outcome.

Increased Neonatal Mortality and Increasing Rate of Cerebral Venous Sinus Thrombosis in Hospitalized Children: A Pediatric Health Information System Database Study

Introduction: Pediatric Cerebral Venous Sinus Thrombosis (CVST) poses risks of neurological sequelae and mortality, necessitating timely diagnosis and appropriate antithrombotic therapy. Limited sample sizes in previous studies have led to inconsistent treatment recommendations. To better understand pediatric CVST, we used the Pediatric Health Information System (PHIS) database to compare clinical features, treatment practices, and outcomes in neonates versus older children, and in different time periods, to analyze the influence of various parameters on healthcare outcomes. Methods: Deidentified, retrospective data of pediatric CVST was extracted from the large multi-center PHIS administrative database from January 1, 2011, to October 1, 2022. Diagnostic, imaging, procedure, and pharmaceutical billing codes were used to identify demographic information, clinical characteristics, management, and outcome. Multivariance analysis was performed on study parameters in neonates vs. older children (Table 1) and early (2011-2015) vs. late (2016-2022) study era (Table 2). Results: 6080 hospitalizations with CVST diagnosis (0.1% of all hospitalizations) were identified (61% male; median age 5 years; range 0-17 years). Median hospital stay was 8 days (IQR 4, 22), with 52% (N=3147) admitted to the intensive care unit (ICU). Overall mortality of all children was 4.2%. Neonates constituted 17.3% of the hospitalizations (N=1,054). Clinical features in neonates were less-often reported vs. older children more often had headache, hypertension, vomiting, papilledema and hemiparesis (p&amp;lt;0.001). Congenital heart disease/sepsis were common associated diagnoses in neonates vs. sinusitis/mastoiditis in older children (p&amp;lt;0.001). Neonates had a longer hospital stay (median 24 (IQR 11, 55), vs. 8 days (IQR 4, 17); p &amp;lt;0.001), but lower ICU admission (33.4% vs. 55.6%; p&amp;lt;0.001) and readmission rate (0% vs. 1.0%; p=0.002) when compared to older children. CT without contrast was used less often (33.4% vs. 55.1%; p &amp;lt; 0.001), and head ultrasound more often (76.3% vs. 8.0%; p &amp;lt; 0.001) for neonates vs. older children. Enoxaparin and unfractionated heparin (UFH) remained the primary treatments for CVST, with UFH utilized more often in neonates (71.6% vs. 59.2%; p&amp;lt;0.001). Direct oral anticoagulants (DOACs) were predominantly used in older children in limited numbers. Coma and hydrocephalus as complications were lower (0.7% vs. 5.6%, p&amp;lt;0.001 and 6.2% vs. 9.4%, p=0.001), and intracranial bleeding was (19.1% vs.7.0%, p&amp;lt;0.001) in neonates vs. older children. Neonates had increased mortality rate compared to older children (9.7% vs. 3.1%; p&amp;lt;0.001). The number of CVST admissions increased in the late (2016-2022) compared to the early study era (2011-2015) (0.11% vs. 0.08% of all admissions, p&amp;lt;0.001). Patient demographics, duration of hospital stay, ICU admission rates, clinical features, and imaging modalities remained similar in both groups. The use of bivalirudin, and DOACs was present in the late vs. none in the early era (p&amp;lt;0.001 except Dabigatran). Coma in the late (p&amp;lt;0.001) and brain infarct in the early study era (p&amp;lt;0.001) were more common complications. Both readmission rate (p=0.006) and hospital stay (p=0.006) were slightly higher in the late era. No statistically significant differences were found in mortality rate between the two eras (p= 0.226). Conclusion: Pediatric CVST is a serious disorder, with an overall mortality rate of 4.2% in our study. Neonates had distinct clinical features, associated diagnoses, and complications compared to older children. Predominantly UFH and rarely DOACs were administered in neonates. Neonates experienced longer hospital stay, and statistically significant higher mortality rate when compared to older children, consistent with prior studies. Newer anticoagulants were utilized increasingly in the late vs. early study era. Though readmission rate and hospital stay increased in the late era (not statistically significant), this did not translate into increased mortality. Increasing rate of hospitalizations in late compared to early study era is likely due to increasing medical complexity/technological advances in diagnosis/management of pediatric CVST. Future multi-center, prospective studies are needed to better address the increased neonatal mortality and improve overall care of pediatric CVST which is increasingly prevalent as seen in our study.

Neurosurgical outcomes of pediatric cerebral venous sinus thrombosis following acute mastoiditis: a systematic review and meta-analysis.

Neurosurgical outcomes are not well defined in the management of pediatric patients with cerebral venous sinus thrombosis (CVST) following acute mastoiditis. Specific notable sequelae are otogenic (otitic) hydrocephalus and CVST management. Correspondingly, the aim of this study was to integrate the currently published metadata to summarize these outcomes. Electronic searches were performed using the Ovid Embase, PubMed, Scopus, and Cochrane databases from inception to November 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort-level data were then abstracted for analysis for appropriate pediatric patients. Outcomes were pooled by random-effects meta-analyses of proportions where possible. Twenty-three study cohorts describing 312 pediatric patients with otogenic CVST were included. At a cohort level, the median patient age was 6 years among 181 boys (58%) and 131 girls (42%). Modeling indicated papilledema at presentation in 46% of cases (95% CI 30%-62%). Regarding management, antibiotics were applied universally in all cases, mastoidectomy or other otologic surgery was performed in 91% (95% CI 82%-98%), and prophylactic anticoagulation was administered in 86% (95% CI 75%-95%). There was only 1 case (0.3%) of postprocedural intracranial hemorrhage, and there were no deaths reported among all studies. Although diagnostic lumbar puncture was performed in 14% (95% CI 3%-28%) at presentation, clinical otogenic hydrocephalus was ultimately suspected in 31% (95% CI 14%-49%), and acetazolamide was given in 65% (95% CI 35%-91%) overall. There were 10 cases (3%) that proceeded to permanent CSF diversion in the form of ventricular shunting. At a median follow-up of 8 months among all studies, the venous sinus was completely recanalized in 67% (95% CI 53%-79%). Most CVSTs following acute mastoiditis will recanalize with the standard use of antibiotics, otologic surgery, and anticoagulation, with minimal symptomatic hemorrhage risk. However, an appreciable proportion of these patients will develop symptomatic otogenic hydrocephalus, and it is imperative that the appropriate surveillance and workup is performed to fully optimize patient outcomes long-term. The possible need for permanent CSF diversion should be recognized.

A case report of a pediatric cerebral venous sinus thrombosis after a head injury detected with nonenhanced CT and MRI imaging

A case report of a pediatric cerebral venous sinus thrombosis after a head injury detected with nonenhanced CT and MRI imaging

A Study on the Distinctive Clinical Profile and Thrombophilia in Pediatric Cerebral Venous Sinus Thrombosis.

ABSTRACTAim:The objective of the study was to systematically bring out the clinical presentations, neuro-imaging features, treatment given, and long-term outcomes of children with cerebral venous sinus thrombosis (CVST).Materials and Methods:Data were obtained by retrospective analysis of electronic records spanning 13 years, of children (<18 years) with a confirmed diagnosis of CVST based on magnetic resonance imaging of the brain and managed at a tertiary care children’s hospital in the UK.Results:Seventeen patients with pediatric CVST were identified over a 13-year study period, highlighting the uncommon prevalence of this entity. This study comprised 10 males and seven females. The age range at presentation was between 2 days and 17 years with a median age of 5.5 years. Headache was the commonest presenting symptom in 10 of 17 children and focal neurological signs were seen in 11 of 17 patients. Among risk factors, six patients had an antecedent infection of the ear/mastoid, three children had acute leukemia, and two patients had central venous catheters. Para-infectious CVST (seven of 17 patients) responded well to appropriate antibiotic therapy. Thrombophilia screens were available in 10 of 17 patients with noninfectious CVST and returned abnormal in four patients (two with Factor V Leiden mutations and one each with deficiency of protein C and anti-thrombin III). Anticoagulants were used in only six of 17 cases and were generally well tolerated. Follow-up data revealed, 11 of 17 patients had a complete recovery and four of 17 patients had residual neurological deficits. Two children died in the entire cohort.Conclusion:Pediatric CVST is uncommon and has a different spectrum from adults, with unique clinical triggers and thrombophilic states. Management varies significantly among clinicians, due to the paucity of trial evidence and also due to the heterogeneity of this condition in children.

Clinico-etiological factors, neuroimaging characteristics and outcome in pediatric cerebral venous sinus thrombosis

Background:Cerebral venous sinus thrombosis (CVST) is rare in children, increasingly being recognized of late due to advances in neuroimaging. The aim of the study was to describe the clinical, etiological, and imaging characteristics of CVST and its outcome in children.Study Design:A retrospective chart review of children with CVST in a tertiary hospital from January 2011 to December 2020.Results:Of the 35 patients enrolled, 26 (74.3%) patients were males. The mean age was 5.03 years with a range of 0.17–12 years. The common presenting symptoms were seizures in 18 (51.4%) followed by headache in 17 (48.6%), fever in 16 (45.7%), and vomiting in 15 (42.9%) children. Superior sagittal sinus was the commonest site of thrombus occlusion in 20 (57%), followed by transverse sinus in 18 (51.4%) patients. Multiple sinus involvement was noticed in one-half of the patients. The risk factors associated with CVST were head and neck infections in 15 (42.9%) children, inherited thrombophilia in 4 (11.6%), head trauma, iron deficiency anemia, leukemia with l-asparaginase therapy, acquired thrombophilia in 3 (8.6%) each, dehydration in 2 (5.7%), and dural arteriovenous fistula in one child. Two children (5.7%) died and one-third of the cohort had a poor outcome.Conclusions:Head and neck infections continue to be the common cause of CVST in children. Though mortality is low, CVST is associated with significant morbidity in children.

Clinical Characteristics and Outcomes of Pediatric Cerebral Venous Sinus Thrombosis: An Analysis of 30 Cases in China.

Background: Cerebral venous sinus thrombosis (CVST) in children is rare in a clinical setting. The aim of this study was to summarize the etiological, clinical, and imaging characteristics of CVST in children.Methods: We retrospectively analyzed the data of 30 patients with a diagnosis of CVST who were admitted to Children's Hospital of Fudan University from 2008 to 2018. The medical records, including clinical manifestations, laboratory data, neurological findings, treatment, and short-term prognosis were analyzed.Results: Etiologically, the causes of CVST were infection (7/30), tumor (3/30), nephritis or nephrotic syndrome (8/30), traumatic brain injury (1/30), and undefined disease (11/30). All 30 cases were diagnosed with CVST after a neuroimaging examination using brain magnetic resonance imaging (MRI) combined with magnetic angiography venography (MRV). With regard to short-term prognosis, all the patients were treated with anticoagulants, after which 26 cases improved.Conclusions: CVST patients do not typically present with specific clinical manifestations, which leads to a high rate of misdiagnosis and delayed therapy. Increased consideration and prompt MRV checkup plays a key role in achieving an accurate diagnosis. Overall, anticoagulation is a safe and effective treatment for CVST.

Clinical Spectrum and Outcome of Cerebral Venous Sinus Thrombosis in Children.

To determine clinical spectrum, neuroimaging finding and outcome of cerebral venous sinus thrombosis (CVST) in children. Descriptive and cross-sectional study. Department of Paediatric Neurology, Children's Hospital and Institute of Child Health, Lahore, from 2015 to 2016. Data was collected in a predesigned proforma by non-probability purposive sampling technique from all enrolled 32 patients fulfilling the inclusion criteria. We analysed descriptively the clinical presentation, neuroimaging findings, associated risk factors and outcome. Chi-square test was used to check the association between demographic variables and findings at five percent level of significance. Out of 32 patients enrolled, 75% (24) patients were male; median age was 2.5 years. Fever was found the most common presentation followed by headache and lethargy. Neuroimaging showed superior sagital sinus thrombosis in all (100%), while 25% (8) have additional thrombosis of internal cerebral veins. Ischemic infarction was found in 11 (35%), while hemorrhagic infarction was found in 9 (29%) patients. Death occurred in 6.25% of children. Infections were the common cause of CVST in children followed by anemia and dehydration. Mortality trend was low with earlier diagnosis and aggressive treatment. Anticoagulant treatment along with adequate hydration, antibiotics and correction of anemia can lead to a better outcome. A large local and regional prospective multicenter studies for pediatric cerebral venous sinus thrombosis is suggested to evaluate the risk factors and plan guidelines for managing this condition in children.

Diagnosing pediatric cerebral venous sinus thrombosis

Pediatric cerebral venous sinus thrombosis (CVST) is not an uncommon condition. It is a dreadful condition, which can be easily missed until we suspect on clinical grounds. Here, we present a case of pediatric CVST following kidney transplantation in a child and the challenges in diagnosing the condition.

Pediatric cerebral venous sinus thrombosis or compression in the setting of skull fractures from blunt head trauma.

OBJECTIVE Pediatric cerebral venous sinus thrombosis has been previously described in the setting of blunt head trauma; however, the population demographics, risk factors for thrombosis, and the risks and benefits of detection and treatment in this patient population are poorly defined. Furthermore, few reports differentiate between different forms of sinus pathology. A series of pediatric patients with skull fractures who underwent venous imaging and were diagnosed with intrinsic cerebral venous sinus thrombosis or extrinsic sinus compression is presented. METHODS The medical records of patients at 2 pediatric trauma centers were retrospectively reviewed. Patients who were evaluated for blunt head trauma from January 2003 to December 2013, diagnosed with a skull fracture, and underwent venous imaging were included. RESULTS Of 2224 pediatric patients with skull fractures following blunt trauma, 41 patients (2%) underwent venous imaging. Of these, 8 patients (20%) had intrinsic sinus thrombosis and 14 patients (34%) displayed extrinsic compression of a venous sinus. Three patients with intrinsic sinus thrombosis developed venous infarcts, and 2 of these patients were treated with anticoagulation. One patient with extrinsic sinus compression by a depressed skull fracture underwent surgical elevation of the fracture. All patients with sinus pathology were discharged to home or inpatient rehabilitation. Among patients who underwent follow-up imaging, the sinus pathology had resolved by 6 months postinjury in 80% of patients with intrinsic thrombosis as well as 80% of patients with extrinsic compression. All patients with intrinsic thrombosis or extrinsic compression had a Glasgow Outcome Scale score of 4 or 5 at their last follow-up. CONCLUSIONS In this series of pediatric trauma patients who underwent venous imaging for suspected thrombosis, the yield of detecting intrinsic thrombosis and/or extrinsic compression of a venous sinus was high. However, few patients developed venous hypertension or infarction and were subsequently treated with anticoagulation or surgical decompression of the sinus. Most had spontaneous resolution and good neurological outcomes without treatment. Therefore, in the setting of pediatric skull fractures after blunt injury, venous imaging is recommended when venous hypertension or infarction is suspected and anticoagulation is being considered. However, there is little indication for pervasive venous imaging after pediatric skull fractures, especially in light of the potential risks of CT venography or MR venography in the pediatric population and the unclear benefits of anticoagulation.

Acute Post-traumatic Pediatric Dural Venous Sinus Thrombosis: A Case Report

Pediatric cerebral venous sinus thrombosis (PDST) is seen frequently after ear problems, coagulation disorders, and acute gastroenteritis with dehydration. Etiology is uncommon after head injury and poses great challenge to manage it. Till today there is no proper guidelines to follow for such cases. We present a case of a 1-year-old girl with posttraumatic DST who was managed safely with anti-coagulation therapy (ACT), and had resolution of her signs and symptoms with radiological improvement within 5 days after ACT. This therapy can be used safely for PDST, and may reduce complications further along with hospital stay and expenses.