Incidence of de novo malignancy and all-cause mortality among heart transplant recipients.

BACKGROUND: Heart transplant recipients develop cancer at two-times the rate compared to the general population. However, the incidence and mortality rates and the adjusted association between cancer and mortality remains unclear. METHODS: We estimated the incidence and mortality rates and the adjusted association between developing cancer (any, skin, hematologic, and solid tumor subtypes) and the all-cause mortality rates among adult heart transplant recipients from the Scientific Registry of Transplant Recipients from October 1, 1987, until June 28, 2020. RESULTS: Among 51,597 adult heart transplant recipients, 13,191 (25.6%) were diagnosed with de novo malignancy throughout the follow-up period. The cumulative incidence cancer at years 1, 5, 10, and 20 was 3%, 16.4%, 32.8%, and 56.6%, respectively. Among those with cancer, the cumulative mortality was 17.5%, 42.3%, 65%, and 91% at years 1, 5, 10, and 20, respectively. The incidence rate of any de novo malignancy was 38.7 cases per 1000 person-years and the mortality rate (for those with cancer) was 115.2 cases per 1000 person-years. Compared to those without cancer, those with cancer had a higher adjusted mortality association [HR: 2.14 (2.07, 2.21)]. The strongest associations were estimated for pancreatic [10.63 (8.34, 13.54)], leukemia [8.06 (4.33, 15.00)], and esophagus [6.94 (5.43, 8.87)] malignancies. The association between de novo malignancies and mortality was higher in the earlier years of follow-up. CONCLUSION: Compared to not developing cancer, those with de novo malignancy have a 2-fold higher mortality rate, on average. The strength of the association varies by cancer subtype and by follow-up time.

Magnetic Resonance Angiography Alone Is Insufficient for Diagnosis and Surgical Planning in Children With Moyamoya.

BACKGROUND: The gold standard for evaluation of the severity of moyamoya vasculopathy is the Suzuki grade determined with cerebral catheter angiography (CA). With greater use of magnetic resonance angiography (MRA) it is important to understand if MRA is truly comparable to CA. METHODS: Children with moyamoya were evaluated using the Suzuki score for CA and the modified MRA six-stage Suzuki score to describe the angiographic findings in moyamoya from initial narrowing of the distal internal carotid artery to the "puff of smoke" appearance of the lenticulostriate collaterals and finally to the disappearance of this network of collaterals. Using Cohen kappa we compared Suzuki grade based on CA with MRA in the same patients. RESULTS: A total of 27 children with moyamoya were reviewed. We calculated a weighted Cohen kappa of 0.49 (P < 0.0001), which is a moderate correlation. CONCLUSIONS: We suggest caution in the reliance on MRA for the diagnosis and evaluation of severity of moyamoya in children.

Yield of genetic evaluation in non-syndromic pediatric moyamoya patients.

PURPOSE: Few guidelines exist for genetic testing of patients with moyamoya arteriopathy. This study aims to characterize the yield of genetic testing of non-syndromic moyamoya patients given the current pre-test probability. METHODS: All pediatric moyamoya patients who received revascularization surgery at one institution between 2018 and 2022 were retrospectively reviewed. Patients with previously diagnosed moyamoya syndromes or therapeutic cranial radiation were excluded. RESULTS: Of 117 patients with moyamoya, 74 non-syndromic patients (44 females, 59%) were eligible. The median age at surgery was 8.1 years. Neurosurgeons referred 18 (24%) patients for neurogenetic evaluation. Eleven (61%) patients subsequently underwent genetic testing. Eight (73%) patients had available testing results. Five (62.5%) of these patients had developmental delay compared to 16 (22%) of the entire cohort. Six (75%) patients who underwent genetic testing were found to have at least one genetic variant. These results led to diagnosis of a new genetic disorder for 1 (12.5%) patient and screening recommendations for 2 (25%) patients. An RNF213 variant in one patient led to recommendations for family member screening and pulmonary hypertension screening. Another patient was diagnosed with CBL disorder and referred for cancer screening. The median age at surgery in patients with clinically actionable findings was 4.6 years compared to 9.2 years in those who were referred for genetic testing. All 3 patients who had an actionable finding had developmental delay. CONCLUSION: It may be beneficial to refer moyamoya patients under 5 for genetic screening given the high likelihood of discovering actionable mutations.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Prevention of postoperative stroke in pediatric moyamoya patients: a standardized perioperative care protocol.

OBJECTIVE: Perioperative stroke is a major complication of revascularization surgery in patients with moyamoya. Vomiting is common after neurosurgical procedures and may result in acute changes in intracranial pressure and cerebral blood flow. The authors instituted a standardized perioperative nausea and vomiting protocol for children with moyamoya undergoing indirect bypass surgery at their institution and analyzed its association with perioperative stroke. They hypothesized that instituting a standardized perioperative nausea and vomiting protocol would be associated with reduction in the number of perioperative strokes in children with moyamoya undergoing indirect bypass surgery. METHODS: The authors retrospectively reviewed consecutive cases of children and young adults with moyamoya who underwent indirect bypass surgery before and after implementation of a new perioperative nausea and vomiting protocol at a single institution. They compared the rate of strokes in the perioperative period (postoperative days 0 and 1) in the 31 months following implementation to 31 months prior to implementation using Fisher's exact test. RESULTS: The median ages pre- and postimplementation were 8.5 (IQR 4-12) years and 8.3 (IQR 5-15) years, respectively. There were no significant differences between the cohorts in disease severity or other potentially confounding factors. In the 31 months prior to initiation of the perioperative nausea and vomiting protocol, there were 5 strokes in 137 surgically treated hemispheres (3.6%). After initiation of the protocol, there were no strokes in 114 surgically treated hemispheres (p = 0.065). CONCLUSIONS: Instituting a standardized perioperative nausea and vomiting protocol was associated with reduction in perioperative strokes in children with moyamoya treated with indirect bypass surgery.

Cerebral Vasculopathy in Children with Neurofibromatosis Type 1.

Cerebrovascular abnormalities are a severe and often underrecognized complication of childhood neurofibromatosis type 1 (NF1). There are no prospective studies of cerebral vasculopathy in NF1; thus, the estimated frequency of vasculopathy varies between studies. The data is difficult to interpret due to the retrospective data collection and variability in whether imaging is done based on screening/surveillance or due to acute neurologic symptoms. The prevalent NF1-associated cerebral vasculopathy is moyamoya syndrome (MMS). Vascular changes can present without symptoms or with acute TIA or stroke-like symptoms or a range of progressive neurologic deficits. Advanced imaging may enhance sensitivity of neuroimaging in children. Medical and/or surgical interventions may prevent short- and long-term complications. Challenges for establishment of a screening protocol for cerebral vasculopathy in children with NF1 include the relatively large number of patients with NF1, the potential need for sedation to achieve quality imaging and the broad age range at time of detection for cerebral vascular changes. The goal of this review is to present the epidemiology, clinical presentation, imaging features and medical/surgical management of cerebral arteriopathies in children with NF1.

Autism Spectrum Disorder in Children With Perinatal Ischemic Stroke Varies by Stroke Type.

Background and Objectives: Perinatal stroke leads to significant morbidity over a child's lifetime, including diagnosis of various neurodevelopmental disorders. Specific studies examining the prevalence of autism spectrum disorder in children with perinatal stroke are scarce. Following the clinical observation of autism spectrum disorder in a pediatric referral stroke center, we evaluated the rate of autism spectrum disorder diagnosis after perinatal ischemic stroke, including analysis by subtypes of perinatal ischemic stroke. Methods: We retrospectively examined all children diagnosed with perinatal ischemic stroke, who were ≥18 months old at the time of last follow-up at a single institution from 2008 through 2021. We classified patients as having autism spectrum disorder if they were diagnosed by a neurologist, neuropsychologist, clinical psychologist, or developmental pediatrician. Multivariable logistic regression was performed to examine the association between ischemic stroke subtype and autism spectrum disorder. Results: Among 260 children with perinatal stroke, 19 children (7.3%) also had autism spectrum disorder. Children with perinatal venous stroke had 3-fold higher odds of autism spectrum disorder compared to those with perinatal arterial ischemic stroke (adjusted odds ratio: 3.01, 95% confidence interval: 1.07-8.47). Conclusion: In our perinatal ischemic stroke population, children with venous stroke had higher odds of autism spectrum disorder compared to those with arterial ischemic stroke alone. Prospective studies are needed to further investigate the role of perinatal stroke in autism spectrum disorder development.

Treatment Failure in Patient with Severe Mpox and Untreated HIV, Maryland, USA.

A 33-year-old man in Baltimore, Maryland, USA, with untreated HIV infection had a 74-day course of mpox with multiorgan system involvement and unique clinical findings. In this clinical experience combining 3 novel therapeutic regimens, this patient died from severe mpox in the context of untreated HIV and advanced immunodeficiency.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Diffusion-Weighted Magnetic Resonance Imaging Demonstrates White Matter Alterations in Watershed Regions in Children With Moyamoya Without Stroke or Silent Infarct.

BACKGROUND: Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) compared with controls, which raises concern for unrecognized white matter injury. Children with moyamoya have significantly lower FA and higher MD in their white matter compared with controls. However, it is unknown which white matter tracts are affected in children with moyamoya. METHODS: We present a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke or silent infarct compared with 25 controls. We analyzed dMRI data using unscented Kalman filter tractography and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, AD, and RD in each segmented white matter tract and combined white matter tracts found within the watershed region using analysis of variance. RESULTS: Age and sex were not significantly different between children with moyamoya and controls. Specific white matter tracts affected included inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, thalamofrontal, uncinate fasciculus, and arcuate fasciculus. Combined watershed region white matter tracts in children with moyamoya had significantly lower FA (-7.7% ± 3.2%, P = 0.02) and higher MD (4.8% ± 1.9%, P = 0.01) and RD (8.7% ± 2.8%, P = 0.002). CONCLUSIONS: Lower FA with higher MD and RD is concerning for unrecognized white matter injury. Affected tracts were located in watershed regions suggesting that the findings may be due to chronic hypoperfusion. These findings support the concern that children with moyamoya without overt stroke or silent infarction are sustaining ongoing injury to their white matter microstructure and provide practitioners with a noninvasive method of more accurately assessing disease burden in children with moyamoya.

Pediatric Moyamoya Syndrome Secondary to Tuberculous Meningitis: A Case Report.

Objectives: Tuberculosis is uncommon in the United States and a rare cause of meningitis in children with severe neurologic consequences. Tuberculous meningitis (TBM) is an even rarer cause of moyamoya syndrome with only a handful of cases previously reported. Methods: We report the case of a female patient who initially presented at 6 years of age with TBM and developed moyamoya syndrome requiring revascularization surgery. Results: She was found to have basilar meningeal enhancement and right basal ganglia infarcts. She was treated with 12 months of antituberculosis therapy and 12 months of enoxaparin and maintained on daily aspirin indefinitely. However, she developed recurrent headaches and transient ischemic attacks and was found to have progressive bilateral moyamoya arteriopathy. At age 11 years, she underwent bilateral pial synangiosis for the treatment of her moyamoya syndrome. Discussion: Moyamoya syndrome is a rare but serious sequalae of TBM and may be more common in pediatric patients. The risk of stroke may be mitigated by pial synangiosis or other revascularization surgeries in carefully selected patients.

Racial disparities in post-transplant stroke and mortality following stroke in adult cardiac transplant recipients in the United States.

Black heart transplant recipients have a higher mortality rate than white recipients 6-12 months after transplant. Whether there are racial disparities in post-transplant stroke incidence and all-cause mortality following post-transplant stroke among cardiac transplant recipients is unknown. Using a nationwide transplant registry, we assessed the association between race and incident post-transplant stroke using logistic regression and the association between race and mortality among adults who survived a post-transplant stroke using Cox proportional hazards regression. We found no evidence of an association between race and the odds of post-transplant stroke (OR = 1.00, 95% CI: 0.83-1.20). The median survival time of those with a post-transplant stroke in this cohort was 4.1 years (95% CI: 3.0, 5.4). There were 726 deaths among the 1139 patients with post-transplant stroke, including 127 deaths among 203 Black patients and 599 deaths among 936 white patients. Among post-transplant stroke survivors, Black transplant recipients experienced a 23% higher rate of mortality compared to white recipients (HR = 1.23, 95% CI: 1.00-1.52). This disparity is strongest in the period beyond the first 6 months and appears to be mediated by differences in the post-transplant setting of care between Black and white patients. The racial disparity in mortality outcomes was not evident in the past decade. The improved survival of Black patients in the recent decade may reflect overall protocol improvements for heart transplant recipients irrespective of race, such as advancements in surgical techniques and immediate postoperative care as well as increased awareness about reducing racial disparities.

Pediatric Moyamoya Biomarkers: Narrowing the Knowledge Gap.

Moyamoya is a progressive cerebrovascular disorder that leads to stenosis of the arteries in the distal internal carotid, proximal middle cerebral and proximal anterior cerebral arteries of the circle of Willis. Typically a network of collaterals form to bypass the stenosis and maintain cerebral blood flow. As moyamoya progresses it affects the anterior circulation more commonly than posterior circulation, and cerebral blood flow becomes increasingly reliant on external carotid supply. Children with moyamoya are at increased risk for ischemic symptoms including stroke and transient ischemic attacks (TIA). In addition, cognitive decline may occur over time, even in the absence of clinical stroke. Standard of care for stroke prevention in children with symptomatic moyamoya is revascularization surgery. Treatment of children with asymptomatic moyamoya with revascularization surgery however remains more controversial. Therefore, biomarkers are needed to assist with not only diagnosis but also with determining ischemic risk and identifying best surgical candidates. In this review we will discuss the current knowledge as well as gaps in research in relation to pediatric moyamoya biomarkers including neurologic presentation, cognitive, neuroimaging, genetic and biologic biomarkers of disease severity and ischemic risk.

Closing the Gap in Pediatric Hemorrhagic Stroke: A Systematic Review.

Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA). Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM). Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure. Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematoma >2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally).

Racial and Ethnic Disparities in Incidence and Prognosis of Perioperative Stroke Among Pediatric Cardiac Transplant Recipients.

Background In the general population, Black children have a higher incidence of stroke and all-cause mortality after stroke than White children. Beginning 6 months following cardiac transplantation, Black children have higher mortality than White children. However, whether there are racial and ethnic disparities in incidence and all-cause mortality following perioperative stroke among pediatric cardiac transplant recipients is unknown. Methods and Results Using the Scientific Registry of Transplant Recipients, we studied children who underwent their first heart transplant in the United States between January 1994 and September 2019. Using multivariable logistic regression, we assessed the association between race and ethnicity and perioperative stroke. We used multivariable piecewise Cox regression to examine the association between race and ethnicity and mortality among survivors of perioperative stroke. Among 8224 children who had a first cardiac transplant, 255 (3%) had a perioperative stroke. Black children had 32% lower odds of perioperative stroke compared with White children (adjusted odds ratio, 0.68 [95% CI, 0.46-0.996]). Following perioperative stroke, mortality rates were similar for Black and White children in the first 6 months (adjusted hazard ratio [HR], 0.99 [95% CI, 0.44-2.26]). However, Black children had a higher mortality rate than White children beyond 6 months (adjusted HR, 3.36 [95% CI, 1.22-9.22]). Conclusions Among pediatric cardiac transplant recipients, Black children have a lower incidence of perioperative stroke than White children. Among survivors of perioperative stroke, mortality is initially similar by race and ethnicity, but beyond 6 months, Black children have over a 3-fold higher mortality rate than White children. Identifying and intervening on potential differences in care is essential to addressing these disparities.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States.

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR = 1.13, 95% CI 0.96-1.32), mortality (aHR = 1.14, 95% CI 0.97-1.34), graft failure (aHR = 1.05, 95% CI 0.82-1.34) and acute rejection (aHR = 1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

Adverse effects of erenumab on cerebral proliferative angiopathy: A case report.

BACKGROUND: Cerebral proliferative angiopathy is a vascular malformation associated with compromised blood-brain barrier and with migraine-like headache. Treating blood-brain barrier-compromised patients with erenumab, an anti-calcitonin gene-related peptide receptor monoclonal antibody, may be risky. CASE: We describe a case of a 22-year-old chronic migraine patient with cerebral proliferative angiopathy who presented to our hospital in status epilepticus 2 d after his first dose of erenumab. Serial magnetic resonance imaging (MRI) studies demonstrated progressive areas of diffusion restriction including the brain tissue adjacent to the cerebral proliferative angiopathy, bilateral white matter and hippocampi. His 6-month post-presentation magnetic resonance imaging was notable for white matter injury, encephalomalacia surrounding cerebral proliferative angiopathy and bilateral hippocampal sclerosis. He remains clinically affected with residual symptoms, including refractory epilepsy and cognitive deficits. CONCLUSION: The evidence presented in this case supports further investigation into potential deleterious side effects of erenumab in patients with compromised blood-brain barrier, such as individuals with intracranial vascular malformations.

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

OBJECTIVE: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. METHODS: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. RESULTS: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. INTERPRETATION: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.

Prevalence of Symptoms of Anxiety, Depression, and Post-traumatic Stress Disorder in Parents and Children Following Pediatric Stroke.

Post-traumatic stress disorder (PTSD), anxiety, and depression are seen in parents and children following critical illness. Whether this exists in parents and children following pediatric stroke has not been thoroughly studied. We examined emotional outcomes in 54 mothers, 27 fathers, and 17 children with stroke. Parents of children 0-18 years and children 7-18 years who were within 2 years of stroke occurrence were asked to complete questionnaires to determine their emotional outcomes. Of participating mothers, 28% reported PTSD, 26% depression, and 4% anxiety; in fathers, 15% reported PTSD, 24% depression, and none reported anxiety. Further, children reported significant emotional difficulty, with 24% having depression, 14% anxiety, and 6% PTSD by self-report ratings. Maternal PTSD, anxiety and depression, and paternal anxiety were all negatively associated with the child's functional outcome. Clinically significant anxiety (based on clinical thresholds) was not found in fathers; however, continuous scores were still analyzed for association between subclinical anxiety and functional outcome, which revealed a statistically significant association between more reported symptoms and higher Recovery and Recurrence Questionnaire scores. Prevalence of PTSD and depression are greater in parents compared to the general population in this preliminary study.

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.