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.

Cerebral Arteriopathies of Childhood - Current Approaches.

Up to more than half of previously healthy children presenting with their first arterial ischemic stroke have a cerebral arteriopathy. Cerebral arteriopathies during childhood can be congenital, reflecting abnormal vessel development, or acquired when caused by disruption of vascular homeostasis. Distinguishing different types of cerebral arteriopathies in children can be challenging but of great clinical value as they may dictate different disease and treatment courses, and clinical and radiologic outcomes. Furthermore, children with stroke due to a specific arteriopathy exhibit distinctive features when compared to those with stroke due to other causes or a different type of arteriopathy. These features become crucial in the management of pediatric stroke by choosing appropriate diagnostic and treatment strategies. The objective of this article is to provide the reader with a comprehensive up-to-date review of the classification, symptoms, diagnosis, treatment, and outcome of cerebral arteriopathies in children.

A Web-based System to Assist With Etiology Differential Diagnosis in Children With Arterial Ischemic Stroke.

BACKGROUND AND PURPOSE: The diagnosis of childhood arteriopathy is complex. We present a Web-based, evidence-backed classification system to return the most likely cause(s) of a pediatric arterial ischemic stroke. This tool incorporates a decision-making algorithm that considers a patient's clinical and imaging features before returning a differential diagnosis, including the likelihood of various arteriopathy subtypes. METHODS: The Vascular Effects of Infection in Pediatric Stroke study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). Previously, a central panel of experts classified the stroke etiology. To create this tool, we used the 174 patients with definite arteriopathy and spontaneous cardioembolic stroke as the "derivation cohort" and the 34 with "possible" arteriopathy as the "test cohort." Using logistic regression models of clinical and imaging characteristics associated with each arteriopathy subtype in the derivation cohort, we built a decision framework that we integrated into a Web interface specifically designed to create a probabilistic differential diagnosis. We applied the Web-based tool to the "test cohort." RESULTS: The differential diagnosis returned by our tool was in complete agreement with the experts' opinions in 20.6% of patients. We observed a partial agreement in 41.2% of patients and an overlap in 29.4% of patients. The tool disagreed with the experts on the diagnoses of 3 patients (8.8%). CONCLUSIONS: Our tool yielded an overlapping differential diagnosis in most patients that defied definitive classification by experts. Although it needs to be validated in an independent cohort, it helps facilitate high-quality, and timely diagnoses of arteriopathy in pediatric patients.

Arterial Ischemic Stroke-Peculiarities of Clinical Presentation and Risk Factors in Indian Children.

There are not enough recent studies on arterial ischemic stroke (AIS) in Indian children. We retrospectively reviewed data on 95 children (69 boys), aged 3 months to 17 years, with AIS. Focal signs were noted in 84 (88%) with hemiparesis in 72 (76%). Diffuse signs were present in 33 (35%) with fever in 22 (23%), altered mental status in 20 (21%), and headache in 12 (13%). Seizures occurred in 29 (31%) children. Arteriopathy was observed in 57 (60%) children with mineralizing lenticulostriate vasculopathy (mLSV) in 22 (23%) being the most common, followed by moyamoya in 14 (15%), arterial dissection in 9 (10%), and focal cerebral arteriopathy (FCA) in 8 (8%). Preceding head/neck trauma was present in 27 (28%) children: 23 had minor head trauma (MHT), 3 neck trauma, and 1 unspecified. Other common risk factors (RFs) were iron deficiency in 10 children, homocysteinemia in 8 children, and tuberculous meningitis in 5 children. Complete or nearly complete recovery occurred in 42 (44%). Nine children developed epilepsy and five cognitive and language disability. Stroke recurrences occurred in nine children. Overall, arteriopathies accounted for majority of the cases of childhood AIS in our study with mLSV and moyamoya being the most frequent. Compared with data from Western countries, FCAs, postvaricella arteriopathy, and arterial dissections were less common. Of the nonarteriopathic RFs, MHT, iron deficiency, homocysteinemia, and neuroinfections were most frequent in our cohort in contrast to cardioembolic diseases and inherited procoagulant conditions, which are common in developed countries.

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study.

OBJECTIVE: To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. DESIGN: Population based cohort study. SETTING: Nationwide healthcare registers in Denmark and Norway. PARTICIPANTS: All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. MAIN OUTCOME MEASURES: Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. RESULTS: The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. CONCLUSIONS: Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Single Arm Access for Combined Transarterial and Transvenous Neurointerventional Procedures.

A concurrent arterial and venous access is routinely obtained for diagnosis and treatment of various neurovascular diseases. Traditionally, venous access is obtained by accessing the femoral vein or through direct internal jugular puncture. Although complication rates are low, life-threatening severe complications have been reported. Moreover, venous access can be challenging in large body habitus patients through these traditional routes. There is a growing trend of utilizing radial artery access for neuroendovascular procedures. Nevertheless, the use of upper limb veins in neurointerventional procedures is rare. We present 3 cases of the concurrent arterial and venous approach through the radial artery and cephalic or basilic vein of the forearm for diagnostic cerebral arteriography and venography. Radial access was obtained by using the standard technique, and venous access was obtained by cannulating cephalic or basilic vein using ultrasound guidance, and a 5F or 6F short sheath was placed. Venous angiography and catheterization of right and left internal jugular veins were then performed using a Simmons (SIM) 2 catheter alone or using 6F Envoy guide catheter coaxially over the SIM 2 catheter if an additional support for microcatheter was needed. Procedures were successfully completed with no adverse effects, and patients were discharged home the same day. We also describe the technique for the reformation of the SIM 2 catheter in the venous system for catheterization of right and left internal jugular veins through the arm access.

Cerebral venous sinus stenosis should not be neglected when cerebral artery stenosis is confirmed: a case report.

PURPOSE: Cerebral venous sinus stenosis (CVSS) is easily neglected in clinical setting due to its nonspecific symptoms. In patients with cerebral arterial stenosis (CAS), the symptoms caused by CVSS are often mistakenly thought of being attributed to CAS. In this case, we aimed to highlight the clinical manifestations and treatment strategies of CVSS comorbid with CAS. MATERIALS AND METHODS: We present an 83-year-old female who complained a series of nonspecific and non-focal neurological deficits such as tinnitus, head noise, dizziness, etc. She was initially diagnosed as CAS and underwent anti-CAS medication orally for over 2 years, whereas her symptoms were still aggravating. RESULTS: Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) displayed severe stenoses at bilateral sigmoid-transverse sinus conjunctions, and thus, the patient underwent intravenous stenting finally. Her aforementioned symptoms significantly attenuated after venous stenting and even disappeared gradually at 3-month, 6-month and 1-year follow-up. CONCLUSIONS: This paper revealed that cerebral venous outflow disturbance should not be overlooked when the nonspecific and non-focal neurological deficits could not be explained by cerebral artery disease. For this arteriovenous condition, intravenous stenting may be a feasible and effective way for symptoms relieving.

Review on the Diagnosis and Treatment of Reversible Cerebral Vasoconstriction Syndrome in Children and Adolescents.

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiologic diagnosis that affects children and adolescents, but it is much more frequently reported in adults. Clinically, patients present with severe and commonly recurrent thunderclap headaches. Typical precipitating triggers include vasoactive substances, serotonergic agents, and the postpartum period. There may be associated neurologic complications at presentation or in the weeks following, such as convexity subarachnoid hemorrhage, stroke, cerebral edema, cervical artery dissection (CeAD), and seizures. Angiographically, the cerebral arteries demonstrate segmental vasoconstriction and dilation, although imaging early in the clinical course may be normal. Work-up is performed to exclude intracranial disorders such as vasculitis, subarachnoid hemorrhage due to ruptured aneurysm, meningitis, and intracranial venous sinus thrombosis. Within 1 month of initial symptom onset, clinical symptoms such as severe headache have ceased, and within 3 months, the cerebral vasoconstriction is much improved or resolved. Management involves avoidance of precipitating triggers and potentially short-term pharmacotherapy with calcium channel blockers for patients with associated neurologic complications. Steroids are not recommended and may worsen the clinical outcome. Prognosis is excellent in the large majority of patients, and only 5% of patients experience a recurrence of RCVS.

Focal cerebral arteriopathy and childhood stroke.

PURPOSE OF REVIEW: Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischaemic stroke in a previously healthy child. Distinguishing between different subtypes of arteriopathy is challenging and has significant management implications. RECENT FINDINGS: Recent studies have helped to define the subtypes of focal cerebral arteriopathies and improved understanding of their clinical and radiological features. In addition, they have reported new evidence for the association between viral infection and inflammation in the pathogenesis of FCA and proposed new radiological, serum and cerebrospinal fluid biomarkers to guide diagnosis and management. There is limited evidence to guide treatment of FCA but a role for steroids and antiviral therapies have been reported. SUMMARY: Despite the recent advances there is a limited knowledge of the pathophysiology and outcomes following FCA. Research priorities include the identification of biomarkers to improve accuracy of initial diagnosis and predict progression, and interventional trials to determine best treatments to reduce stroke recurrence risk.

Arterial ischemic stroke in non-neonate children: Diagnostic and therapeutic specificities.

Pediatric arterial ischemic stroke (AIS) is a severe condition, with long-lasting devastating consequences on motor and cognitive abilities, academic and social inclusion, and global life projects. Awareness about initial symptoms, implementation of pediatric stroke code protocols using MRI first and only and adapted management in the acute phase, individually tailored recanalization treatment strategies, and multidisciplinary rehabilitation programs with specific goal-centered actions are the key elements to improve pediatric AIS management and outcomes. The main cause of pediatric AIS is focal cerebral arteriopathy, a condition with unilateral focal stenosis and time-limited course requiring specific management. Sickle cell disease and moyamoya angiopathy patients need adapted screening and therapeutics.

Clinical, imaging features and outcome in internal carotid artery versus middle cerebral artery disease.

BACKGROUND: Only a very few studies had compared the differences in topographic patterns of cerebral infarcts between middle cerebral artery (MCA) and internal carotid artery (ICA) disease. Besides, the comparison of clinical features and outcomes between MCA and ICA disease had rarely been reported. OBJECTIVES: To compare the clinical, imaging features and outcome of MCA versus ICA disease. METHODS: We prospectively enrolled 1172 patients with noncardiogenic ischemic stroke in ipsilateral ICA or MCA territory. Clinical, neuroradiologic and outcome of the two groups were compared in this observational cohort study. RESULTS: The ICA group more frequently presented with decreased alertness, gaze palsy, aphasia, and neglect than the MCA group at admission, and more often had higher National Institute of Health stroke scale score at admission and discharge. Meanwhile, the ICA group more frequently had multiple acute infarcts, watershed infarcts, territorial infarct, small cortical infarct, and responsible artery stenosis ≥70%. Whereas penetrating artery infarct and parent artery occluding penetrating artery was more often associated with MCA disease. The ICA group more frequently had inhospital complications of pneumonia and deep vein thrombosis, more often had disability at discharge, and had more recurrent ischemic stroke or transient ischemic attack in 1 Year. Multivariable logistic regression identified male (OR, 1.99; 95% CI, 1.30 to 3.05; P = 0.002), history of coronary heart disease (OR, 1.85; 95% CI, 1.03 to 3.32; P = 0.041), multiple acute infarcts (OR, 4.18; 95% CI, 2.07 to 8.45; P<0.0001), and territorial infarct (OR, 2.23; 95% CI, 1.52 to 3.27; P<0.0001) was more often associated with ICA territory disease. CONCLUSIONS: The clinical, radiologic characteristics and outcome are distinctively different between ICA and MCA disease. Compared to MCA disease, ICA disease has more serious clinical and radiologic manifestation, and poorer outcome.

Posterior reversible encephalopathy syndrome associated with reversible cerebral vasoconstriction syndrome in a patient presenting with postpartum eclampsia: A case report.

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction (RCVS) are rare neurological disorders with complex physiopathology which is not yet fully understood. We present here the case of a 31-year-old woman with a bi-amniotic bi-chorial pregnancy who developed immediate postpartum eclampsia after vaginal delivery, associated with RCVS and PRES. Although post-partum is a well-known precipitating factors for these diseases, to our knowledge, there are only few similar cases reported with the association of these syndromes. Repeated MRI scans were instrumental in the final diagnosis of RCVS associated with PRES, allowing us to give the patient the appropriate treatment. These two syndromes have similar symptoms but may have different treatments, thus highlighting the importance of a correct diagnosis.

A Clinical Paradigm for Classifying Neurologic Symptoms to Screen for Emergent Large Vessel Occlusions.

BACKGROUND: With newly-extended treatment windows for endovascular therapy in emergent large vessel occlusions, it is increasingly important to identify thrombectomy-eligible patients without overwhelming resources dedicated to acute stroke care. We devised a simple paradigm to classify patient's presenting neurologic symptoms to screen for large vessel occlusions. METHODS: We reviewed the presenting symptoms, imaging findings, and final diagnoses of consecutive emergency department stroke alert cases. Patients were classified based on their neurologic exams as focal objective, focal subjective, or nonfocal. Outcomes of final diagnoses of acute ischemic stroke and large vessel occlusions were compared across groups. Comparisons were made to other large vessel occlusion prediction scales. RESULTS: Of 521 patients, 342 (65.6%) were categorized as focal objective, 142 (27.2%) as focal subjective, and 37 (7.1%) as nonfocal. Ischemic stroke and large vessel occlusions were diagnosed in 114 (21.9%) and 27 (5.2%) of patients, respectively. Classification as focal objective significantly predicted stroke (odds ratio 3.77; 95% confidence interval 2.17-6.55) and captured all large vessel occlusions (P = .0001). The focal objective categorization was the only tool which achieved 100% sensitivity for large vessel occlusions (with a specificity of 36%) compared to other large vessel occlusion prediction tools. CONCLUSIONS: Patients who presented as stroke alerts without focal neurologic symptoms were unlikely to have large vessel occlusions. With high sensitivity, classifying patients' neurologic exams into focal objective versus subjective or nonfocal categories may serve as a useful tool to screen for large vessel occlusions and prevent unnecessary emergent workup in patients unlikely to be endovascular candidates.

Design, Application and Infield Validation of a Pre-Hospital Emergent Large Vessel Occlusion Screening Tool: Ventura Emergent Large Vessel Occlusion Score.

BACKGROUND: The outcome of endovascular treatment for emergent large vessel occlusion (ELVO) is dependent on timely recanalization. To identify ELVO in the field, we present a simplified score, which has been applied and validated in the field by emergency medical services (EMS). Methods and Analysis: Ventura ELVO Scale (VES) comprise of 4 components: Eye Deviation, Aphasia, Neglect, and Obtundation with score range 0-4. The score of greater than or equal to 1 will be considered as ELVO positive. A positive VES along with positive Cincinnati scale prompts ELVO activation. EMS then notify to neurointervention protocol at the receiving stroke center. The performance of VES was evaluated retrospectively. For statistical analysis, SAS version 9.4 was used and Fisher's modelling was used for the comparative analysis. RESULTS: Total 184 patients were included in the final analysis, 62 (33.7%) patients were called VES positive from the field. Out of 62, 36 (58%) patients had ELVO. The mean NIHSS on arrival was 16 in VES positive and 5 in VES negative patients. VES was 94.7% sensitive and 82.4% specific while the PPV and NPV of VES were 58.1% and 98.4%, respectively. It showed 84.9% accuracy. CONCLUSIONS: VES is an effective and simplified prehospital screening tool for detection of ELVO in the field. Its implementation can beat the target door to groin time to improve outcomes and in future it can be used for rerouting of ELVO patients to comprehensive stroke center.

Modeling Stroke Patient Transport for All Patients With Suspected Large-Vessel Occlusion.

Importance: Ischemic stroke with large-vessel occlusion can be treated with alteplase and/or endovascular therapy; however, the administration of each treatment is time sensitive. Objective: To identify the optimal triage and transport strategy: direct to the endovascular center (mothership) or immediate alteplase treatment followed by transfer to the endovascular center (drip and ship), for all patients with suspected large-vessel occlusion stroke. Design Setting, and Participants: This was a theoretical, conditional probability modeling study. Existing data from clinical trials of stroke treatment were used for model generation. The study was conducted from February 1, 2017, to March 1, 2018. Main Outcomes and Measures: The time-dependent efficacy of alteplase and endovascular therapy and the accuracy of large-vessel occlusion screening tools were modeled to estimate the probability of positive outcome (modified Rankin Scale score, 0-1 at 90 days) for both the drip-and-ship and mothership transport strategies. Based from onset to treatment, the strategy that estimates the greatest probability of excellent outcome is determined in several different scenarios. Results: The patient's travel time from both thrombolysis and endovascular therapy centers, speed of treatment, and positive predictive value of the screening tool affect whether the drip-and-ship or mothership strategy estimates best outcomes. With optimal treatment times (door-to-needle time: 30 minutes; door-in-door-out time: 50 minutes; door-to-groin-puncture time: 60 minutes [mothership], 30 minutes [drip and ship]), both options estimate similar outcomes when the centers are 60 minutes or less apart. However, with increasing travel time between the 2 centers (90 or 120 minutes), drip and ship is favored if the patient would have to travel past the thrombolysis center to reach the endovascular therapy center or if the patient would arrive outside the alteplase treatment time window in the mothership scenario. Holding other variables constant, if treatment times are slow at the thrombolysis center (door-to-needle time: 60 minutes; door-in-door-out time: 120 minutes), the area where mothership estimates the best outcomes expands, especially when the 2 centers are close together (60 minutes apart or less). The area where mothership estimates the best outcome also expands as the positive predictive value of the screening tool increases. Conclusions and Relevance: This study suggests that decision making for prehospital transport can be modeled using existing clinical trial data and that these models can be dynamically adapted to changing realities. Based on current median treatment times to realize the full benefit of endovascular therapy on a population level, the study findings suggest that delivery of the treatment should be regionally centralized. The study modeling suggests that transport decision making is context specific and the radius of superiority of the transport strategy changes based on treatment times at both centers, transport times, and the triaging tool used.

A non-traumatic, rapid-onset headache that is as dangerous as subarachnoid hemorrhage (SAH) seen in the emergency department.

A 36yo male with multiple non-traumatic, rapid-onset headaches had Emergency Department visits on days 3 and 10 after onset of symptoms. He is a social smoker and drinker. CT head imaging was negative. An MRI/MRA was obtained. The image represents multiple foci of vasoconstriction and dilation in medium and large cerebral vessels consistent with Reversible Cerebral Vasoconstriction Syndrome (RCVS). Multiple rapid-onset headaches and "string of beads" on MRA imaging are pathognomonic for RCVS, which has a 4:1 female to male ratio. Manifestations include the pure cephalic form, characterized by a headache; subarachnoid hemorrhage and cerebral infarction have also been reported. Vasoactive drugs and the post-partum period are recognized as common inciting events. Symptoms usually resolve in 3-6 months. Treatment with nimodipine, 1-2mg/kg/hr IV and/or 30-60mg PO QID orally over 4-8 weeks, has been reported to be effective.