United States

Background and purpose: The implementation of acute stroke response protocols has resulted in a decrease in the time to diagnosis of acute stroke in children at select institutions, and this is essential for expanding access to hyperacute therapies. We aim to describe existing pediatric acute stroke response protocols in the United States and Canada to better understand how pediatric centers might implement such protocols within the context of institution-specific structures. Methods: We performed a survey-based study of pediatric stroke specialists focused on institutional acute stroke protocols. The survey queried: hospital demographics; child neurology and pediatric stroke demographics; acute stroke response; imaging; and hyperacute treatment. Results: Forty-seven surveys were analyzed. Most respondents practice at large, free-standing children&#39;s hospitals with moderate-sized neurology departments and at least one neurologist with expertise in pediatric stroke. The majority of institutions have an acute stroke pathway or protocol, and all but one of these include the activation of a stroke alert page. Most institutions cite magnetic resonance imaging as the preferred imaging modality and employ abbreviated magnetic resonance imaging protocols for acute stroke imaging. Most institutions also have either computed tomography- or magnetic resonance-based perfusion imaging available. At least one patient had been treated with intravenous tissue plasminogen activator and/or mechanical thrombectomy at the majority of institutions in the year prior to our survey. Conclusions: An acute stroke response protocol is utilized in at least 41 pediatric centers in the United States and Canada. Most acute stroke response teams are multidisciplinary, have annual experience providing intravenous tissue plasminogen activator and/or mechanical thrombectomy, and prefer abbreviated magnetic resonance imaging over computed tomography for stroke diagnosis. Further studies are needed to standardize practices of pediatric acute stroke diagnosis and hyperacute management.

IPSO 2021

Pediatric acute stroke response protocols

**[Download Full Agenda](https://drive.google.com/file/d/1Dm9lJyTfJrvd7-StaHFmUmhXC-J_UgTj/view?usp=sharing)**

Dear IPSO Virtual Conference Attendees:

Welcome to IPSO’s first-ever conference! We are delighted to bring together experts from <u>multiple disciplines</u> and <u>six continents</u> to provide a diverse perspective on pediatric cerebrovascular disease.  

A few quick words about what to expect.  Two important goals of this conference are to (1) foster a sense of community and (2) identify global priorities for our field. Hence, the program includes short presentations on an array of clinical controversies and dedicates more time to panel discussions with a live chat function so that everyone can participate. We are excited to announce IPSO is able to offer 8.75 CME units for the virtual conference. If you would like to claim CME credits, please email  <membership@internationalpediatricstroke.org>. 

We want to hear from you!  Planning for the [IPSO Founding Members’ Congress](https://internationalpediatricstroke.org/2022-congress/) in Vienna, April 24-26, 2022, will commence as soon as the Virtual Conference ends. Let us know your priorities through the live chat function, via email, or by submitting a symposium idea. Based on your input, the Scientific Program Committee will select the topics that we will address in greater depth when we meet again in the spring.

We hope you find the Virtual Conference both interesting and educational, and hope to see you in person in Vienna, or at another IPSO meeting in the future.  

Warm regards,

Heather Fullerton, IPSO President

Adam Kirton, IPSO Vice-President

Lori Jordan, IPSO Secretary & Treasurer


![](https://assets.underline.io/uploads/markdown_image/1/image/1c71a0aebc49947c923a7920d9f28857.jpg)



  
    
  


  



*Header Photo Credit: Helen Carlson, Ph.D, Alberta Children's Hospital*

To access IPSO 2021, you must pre-register for the conference.  Instructions on how to access the event will be provided directly to attendees and included on the IPSO 2021 conference website. [Register now](https://internationalpediatricstroke.org/2021-congress/registration/).

Welcome to the first IPSO Virtual Conference. The mission of the virtual conference is to unify the global community of professionals engaged in research and clinical care for children with cerebrovascular diseases, and chart a path forward for multinational, multidisciplinary efforts.  Please go here to access the virtual conference platform- <a href="https://underline.io/events/157/reception">Reception page</a>. 



Background and purpose: The implementation of acute stroke response protocols has resulted in a decrease in the time to diagnosis of acute stroke in children at select institutions, and this is essential for expanding access to hyperacute therapies. We aim to describe existing pediatric acute stroke response protocols in the United States and Canada to better understand how pediatric centers might implement such protocols within the context of institution-specific structures. Methods: We performed a survey-based study of pediatric stroke specialists focused on institutional acute stroke protocols. The survey queried: hospital demographics; child neurology and pediatric stroke demographics; acute stroke response; imaging; and hyperacute treatment. Results: Forty-seven surveys were analyzed. Most respondents practice at large, free-standing children's hospitals with moderate-sized neurology departments and at least one neurologist with expertise in pediatric stroke. The majority of institutions have an acute stroke pathway or protocol, and all but one of these include the activation of a stroke alert page. Most institutions cite magnetic resonance imaging as the preferred imaging modality and employ abbreviated magnetic resonance imaging protocols for acute stroke imaging. Most institutions also have either computed tomography- or magnetic resonance-based perfusion imaging available. At least one patient had been treated with intravenous tissue plasminogen activator and/or mechanical thrombectomy at the majority of institutions in the year prior to our survey. Conclusions: An acute stroke response protocol is utilized in at least 41 pediatric centers in the United States and Canada. Most acute stroke response teams are multidisciplinary, have annual experience providing intravenous tissue plasminogen activator and/or mechanical thrombectomy, and prefer abbreviated magnetic resonance imaging over computed tomography for stroke diagnosis. Further studies are needed to standardize practices of pediatric acute stroke diagnosis and hyperacute management.

poster

Objective Perinatal intracranial hemorrhage (pICH) is a rare event that occurs during the fetal/neonatal period with potentially devastating neurological outcome. However, the etiology of pICH is frequently hard to depict. We investigated the role of rare genetic variations in unexplained cases of pICH. Methods We performed whole-exome sequencing (WES) in fetuses and term neonates with otherwise unexplained pICH and their parents. Variant causality was determined according to the American College of Medical Genetics and Genomics (ACMG) criteria, consistency between suggested genes and phenotypes, and mode of inheritance. Results Twenty-six probands (25 families) were included in the study (9 with a prenatal diagnosis and 17 with a postnatal diagnosis). Intraventricular hemorrhage (IVH) was the most common type of hemorrhage (n = 16, 62%), followed by subpial (n = 4, 15%), subdural (n = 4, 15%), and parenchymal (n = 2, 8%) hemorrhage. Causative/likely causative variants were found in 4 subjects from 3 of the 25 families (12%) involving genes related to the brain microenvironment (COL4A1, COL4A2, and TREX-1). Additionally, potentially causative variants were detected in genes related to coagulation (GP1BA, F11, Von Willebrand factor [VWF], FGA, and F7; n = 4, 16%). A potential candidate gene for phenotypic expansion related to microtubular function (DNAH5) was identified in 1 case (4%). Fifty-five percent of the variants were inherited from an asymptomatic parent. Overall, these findings showed a monogenic cause for pICH in 12% to 32% of the families. Interpretation Our findings reveal a clinically significant diagnostic yield of WES in apparently idiopathic pICH and support the use of WES in the evaluation of these cases

Whole-exome sequencing analysis in antenatal and perinatal intracerebral hemorrhage

Introduction: Adenosine deaminase 2 (ADA2) deficiency is a rare genetic cause of pediatric cerebrovascular disease typically associated with polyarteritis nodosa-like multi-systemic vasculitis. Patients usually present with strokes around age 2, after presenting with a livedo reticularis rash, systemic signs of inflammation and immunodeficiency. We present a now 2-year-old female, who initially presented at 5 months of age, then showed recurrent cerebral infarcts at 8 months of age, after which she was found to have a compound heterozygous pathogenic mutation involving the ADA2 gene. We highlight the importance of identifying ADA2 mutations in recurrent idiopathic strokes even in infancy and despite lack of accompanying systemic features, given available preventative immunotherapies. Case: A previously healthy 5-month-old female initially presented with altered mental status without focal deficits and was found to have bi-thalamic infarcts with a non-yielding work up (vessel imaging, hypercoagulable studies, echocardiogram). She re-presented at 8 months of age with sudden left sided weakness with acute infarcts of the right corona radiata and internal capsule; early chronic infarcts of the right basal ganglia and the deep right periatrial white matter, likely representing a third ischemic event. Cerebral angiography was without signs of vasculitis. Whole exome sequencing sent given recurrent idiopathic strokes, identified a compound heterozygous pathogenic mutation in the ADA2 gene. She is maintained on etanercept with no recurrent infarcts but with residual mild left hemiparesis. Discussion: ADA2 deficiency represents a rare cause for pediatric stroke, but one that is easily identifiable with genetic testing and preventable with immunosuppression. With less than 75 reported cases, our patient is one of the youngest, and to our knowledge only to have ischemic strokes in the absence of systemic symptoms thus far. Consider early genetic testing for ADA2 mutations in infantile stoke, despite lack of systemic manifestations.

The Brain-Immune Connection: ADA2 deficiency is a preventable cause of pediatric stroke

Case description 16 years old female with JD was admitted for stroke with symptoms of sudden onset right-sided hemiparesis, diplopia, dysarthria & difficulty word finding. On examination,was alert, oriented & neurologically intact except dysarthric speech, ataxic gait, bilateral dysmetria & dysdiadokinesia. MRI brain showed patchy asymmetric areas of T2/FLAIR hyperintensities without diffusion restriction involving pons, bilateral middle cerebellar peduncles & hemispheres. Initially started on immunosuppressive therapy (Steroids, Methotrexate & Cellcept) with concerns for cerebral vasculitis but due to worsening symptoms, imaging findings further investigation revealed positive JC Virus in her CSF fluid. Thus diagnosed with PML. Subsequently was treated with plasmapheresis. After 6 months of treatment & rehab she continues to show improvement. She is now able to sit without support & her speech is more clear. Recent JC virus results show 333 copies/ml (down from 2,900 at time of diagnosis). Recent MRI shows some improvement as well. Discussion: Active replication of JC virus in the brain leads to the development of PML, characterized by focal areas of demyelination and necrosis of glial cells(3). Diagnosis of PML is based clinically, neuroimaging & detection of JC virus in CSF. Most commonly reported neurological features are mono- and hemiparesis (50%), apathy (46%), confusion (38%), visual disturbance (29%), and seizures (21%)(2). In the pediatric population less than 50 cases of PML have been reported related to AIDS & less than 10 cases with inherited immunodeficiency. To our knowledge this is the first PML case reported in a pediatric patient with Juvenile Dermatomyositis (JD) and subsequent immunosuppression(1). References: 1.ReAngelini L, et al. Progressive multifocal leukoencephalopathy in a child with hyperimmunoglobulin E recurrent infection syndrome and review of the literature. Neuropediatrics. 2001;32(5):250-255. doi:10.1055/s-2001-19119 2.Shitrit D, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Transpl Int. 2005;17(11):658-665. doi:10.1007/s00147-004-0779-3 3.Burke MT, et al. Progressive multifocal leukoencephalopathy with gastrointestinal disease in a pediatric kidney transplant recipient. Pediatr Transplant. 2013;17(5):E119-E124. doi:10.1111/petr.12107 Images: Asymmetric T2/FLAIR hyperintense signal within the right cerebellar peduncle the extensive cerebral hemisphere without evidence of diffusion restriction

Progressive multifocal leukoencephalopathy in a child with juvenile dermatomyositis presented as stroke

Introduction: Pediatric stroke is one of the leading causes of morbidity and mortality worldwide. Given the paucity of literature on etiology and presentation of childhood stroke in India, the clinico-etiological profile study would give better insights into understanding, treating and preventing childhood stroke among the Indian population. Methods: This is a Retro-prospective cohort study conducted at Narayana health city, Bangalore over a 6months period. 76 children in the age group of 0-18yrs diagnosed as arterial ischemic stroke clinically and radiologically, were included. Data was collected from hospital database and at OPD visits, analyzed and compared with available Indian and international data. Results: Our study found that most common causes for pediatric stroke were: cardio-embolic (28%), cryptogenic (27%), arteriopathy (17%) and infections (15%). There was a definite male preponderance (66%) and most of them presented at 0-5yrs age (52%). Clinically, common presenting features were hemiparesis (63%), seizures (53%), facial paresis (26%), encephalopathy (22%), fever (17%), headache (9%). 57% of patients had single cerebral hemispheric involvement. Multiple vascular territories were involved in 30%. Nine children had recurrence (11%) of which, four had Moya Moya Disease, two had cardioembolic stroke, one had vertebral artery dissection, one had propionic aciduria and one Prothrombin gene mutation. Most of them were managed conservatively (95%). Four children (7%) underwent interventions: STA-MCA bypass with EDAMS, vertebral artery coiling and 2 mechanical thrombectomy. Conclusions: Our study found the cardio-embolic phenomena as the commonest cause of AIS in India. Rarer causes of stroke were also identified. 27% remained cryptogenic despite exhaustive evaluation. A definite male preponderance was noted. Further multi-centric studies with larger sample size would confirm these findings and shed light on common causes, modes of diagnosis, preventive and curative treatment specific to Indian pediatric population.

A cohort study of clinical and etiological profile of arterial ischemic stroke among Indian pediatric population: A single center experience

The problem of a pediatric stroke has become relevant in recent decades. More than 50% of children with ischemic stroke are diagnosed with arteriopathy. Aim: assessment of the clinical features and course of arteriopathy in children diagnosed with arterial ischemic stroke (AIS). Materials: 72 patients with AIS, who were treated in Moscow primary pediatric stroke center from 2013 to 2018. Boys vs girls - 42 vs 30 (58,4%vs41,6%), the average age 7.6 years. The observation period was from 16 months to 5 years. Results: in 43 children out of 72 were diagnosed the arteriopathy. 30/43 showed signs of unilateral focal stenosis of the distal internal carotid artery (ICA) and / or the middle cerebral artery (CMA) and / or the anterior cerebral artery (PMA) with / without occlusion, The severity of stroke by PedNIHSS in average 7,3. CT was made: CT angiography 28 patients (from 7 days to 4 months from the onset of stroke (1 patient twice), 8 - direct catheter angiography. Arteriopathies in patients with focal cerebral artheropathy were divided: vasculitis- 3, progressive arteriopathy -4, dissection-3, transient cerebral arteriopathy (TCA)- 20. Dynamic MRI study (from 3 to 6 months) showed: a complete restoration of blood flow-5; increase of stenosis -4; decrease of stenosis - 11; without dynamics relatively acute period -3. MR-angiography after 9-12 months: full restoration of blood flow-9; reduction of stenosis (incomplete recovery) -7. Relapse of AIS was observed in 6 patients (11.6%)with artheriopathy during the follow-up period. Conclusion: Modern methods of neuroimaging have significantly improved the diagnosis of childhood stroke, clarifying the nature and extent of cerebral vascular lesions, including artheriopathy, which is very important in determining the management of children and adolescents.

Transient cerebral arteriopathy in children and adolescents, features of clinical manifestations and course

Objectives: The prevalence of cancer among children with ischemic stroke is unknown. This study sought to evaluate cancer-associated childhood ischemic stroke in a multinational pediatric stroke registry. Methods: Children between 29 days and 19 years of age with arterial ischemic stroke (AIS) and/or cerebral sinovenous thrombosis (CSVT) enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including types of cancer, stroke etiology, and stroke treatment were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests. Results: Remote or active cancer was present in 99 of 2968 children (3.3%) with AIS and 64 of 596 children (10.7%) with CSVT. Children with cancer were older than children without cancer in both the AIS (9.5 versus 5.7 years, p=0.0001) and CSVT groups (8.2 versus 6.3 years, p=0.014). Among children in whom cancer type was identified, 42 of 88 (48%) AIS cases had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 (78%) CSVT cases had hematologic malignancies and 8 (14%) had brain tumors. Primary causes most commonly reported in children with cancer-associated AIS included: arteriopathy (n=34, 62%), cardioembolic (n=9, 16%), prothrombotic state (n=4, 7%), and infection (n=4, 7%). The most frequently reported primary cause of CSVT in children with cancer was prothrombotic state (n=38, 83%). Children with cancer were less likely to receive any antithrombotic therapy for AIS (58 % v. 80%, p=0.007) and anticoagulation for CSVT (71% v. 87%, p=0.046), compared with children without cancer. Recurrent AIS (5% v. 2%, p=0.04) and CSVT (5% v. 1%, p=0.006) were more common among children with cancer. CONCLUSION: Cancer is an important risk factor for incident and recurrent childhood stroke. Although multiple risk factors for stroke were noted in children with cancer, presence of cerebral arteriopathy in children with AIS and prothrombotic state in children with CSVT appear to be the most significant underlying mechanisms contributing to increased risk for stroke in this population. Future research investigating the role of stroke prophylaxis in the high-risk subpopulations identified in this study are warranted.

Cancer-associated stroke in children: Results from the International Pediatric Stroke Study (IPSS)

Introduction: Immunomediated encephalitis has been studied with great interest in recent years. So far, etiology is not known, but it could be stowed by viral infections. Most cases have normal neuroimaging. Our patient presented an associated ischemic stroke. Since our patient presented the two pathologies, related in time, we wondered what the relationship between them might be. Clinical case: Patient of 2 years, without perinatological history to highlight, that after a febrile picture presents clonic focal crises of upper right limb, continuous, difficult to manage and ipsilateral hemiparesis. MRI shows ischemic stroke in the territory of the middle cerebral artery and left anterior choroid artery. A week it presents hemorrhagic reformation, with good evolution.At 30 days from the onset of symptoms, it presents sensory alteration and adds abnormal movements. Anti-NMDA encephalitis is confirmed: it had qualitative antibodies in Cerebrospinal Fluid and plasma. MRI chronic evolution of known injury. Electroencephalogram with typical pattern of anti-NMDA encephalitis. It required first- and second-line treatment. After 6 months, there is clinical improvement. At the moment the child is 7ys and go to regular school, he has a mild hemiparesis. Discussion: We wondered if there was any relationship between these two pathologies. Is it an ischemic stroke that has evolved into an NMDA anti-NMDA encephalitis or an anti-NMDA encephalitis that has had an associated ischemic brain injury? And although they seemed far away, they have several pathophysiological mechanisms that relate them. In both pathologies, the brain receptor involved in cell damage is GluN1 NMDA. We can't confirm theories with any complete tests.

Ischemic Stroke and immune encephalitis: Which came first?

Background Stroke is a recognised complication following congenital cardiac surgery. In 2017, RCPCH published a guideline outlining investigations to be performed in children with evidence of stroke. Objectives To determine adherence to the RCPCH Stroke Guideline in patients with evidence of stroke who had undergone congenital cardiac surgery. To perform a structured survey to explore reasons for non-adherence. Methods Records of all paediatric cardiac patients undergoing surgery between January 2014 and July 2020 were cross-referenced with patients recorded as having ischaemia on brain imaging. 34 patients were identified. 16 patients who died during admission were excluded. Records of the remaining 18 patients were examined to ascertain rates of adherence to the RCPCH's recommended investigations. Subsequently, a structured survey was conducted amongst paediatric intensive care doctors to explore reasons for non-adherence. Results Table 1 documents adherence to investigations recommended by the RCPCH. Of note, complete adherence was not achieved in any patients. Of 33 doctors surveyed, 10 (30%) were aware of the guideline. When asked how likely they were to use the term 'stroke' to describe focal ischaemia on imaging, 16 (48%) respondents stated they were likely/very likely, with 9 (27%) stating they would be unlikely/very unlikely. When asked about which laboratory investigations they would perform, various tests referenced in the guideline were mentioned, but no respondents mentioned iron, total iron binding capacity, plasma homocysteine, lipoprotein, 2GP1 or alpha galactosidase. Discussion Cardiac investigations and routine blood tests were performed as per guidelines on congenital cardiac surgery. Neurological imaging was generally performed in keeping with RCPCH guidelines. However, other investigations were performed on an ad-hoc basis. The survey results suggest that this may be due to a lack of awareness of both the stroke guideline and the significance of the laboratory tests. Furthermore, disparities in terminology may contribute to a lack of consideration of the stroke guideline. As a result of this audit, the RCPCH Stroke Guideline will be available through the NHS GG&C guidelines application. Education will be delivered to raise awareness, and a stroke checklist will be introduced.

Stroke post congenital cardiac surgery - Adherence to national guidelines and reasons for non-adherence

Last years there has been a tendency to increase the incidence of stroke in children, which may be associated with an improvement in the diagnosis of this pathology in the pediatric population. Aim. Analysis of the clinical synmptoms and the conformity of the diagnoses: guides (according to the ambulance) and the discharge one. Materials. From October 2018 to December 2019, 502 hospitalization in the Primary pediatric stroke center of Morozov Hospital by the Moscow Ambulance with diagnoses of arterial ischemic stroke (AIS), hemorrage stroke (HI) and transit ischemic attaсk (TIA) were analyzed. 48.8% boys and 51.2% girls were hospitalized. Results. Of 502 admissions, the directing diagnosis was TIA - 38.6%, AIS - 52,6%, HI - 8.8%. The symptoms were: headache -38.5%; dizziness - 25.5%, ataxia - 21.1%; sensory impairment - 10.6%, paresis - in 10%, speech impairment and visual impairment were detected in 9.6% and 5.4%, facial asymmetry - 6.2%, and seizures - 4%. In 30.7% patients, at the time of admission to the Center, there was no a neurological deficit. The average time from the onset of the first symptoms to hospitalization in the hospital was more 4 hours. Neuroimaging was performed in 54.8%. Computed tomography(CT)- 41.4%, magnetic resonance imaging (MRI) - 20.7% cases, in 7.9% both CT and MRI. AIS was confirmed in 11,2%, HI -9.1%. In confirmed AIS, the common symptoms were: paresis- 84.6%, ataxia- 84.6%; facial asymmetry- 61.5%; speech impairment and impaired sensitivity - 38.5%, respectively; visual impairment - 15.4%; nausea or vomiting and convulsions - 7.7%. In 84% patients, stroke was not confirmed. Conclusion Based on the analysis of the most frequent symptoms and "mistakes", the "Attention, stroke!" Scale was developed for ambulance doctors, which has been practiced since January 2020 in the Moscow Ambulance.

Early diagnostics of a stroke in children. Experience of Moscow primary pediatric stroke center and Moscow Ambulance

Introduction: Pediatric acute stroke is often misdiagnosed in the acute setting. Computed tomgraphy imaging has a low sensitivity and specificity for diagnoses in pediatric patients presenting with acute focal neurologic deficit. We established a collaborative protocol involving both the vascular neurology and pediatric neurology divisions in our institution for pediatric code stroke. Methods: Multidisciplinary meetings were held with the division of vascular neurology, endovascular surgery, child neurology, intensive care and emergency medicine to update our pediatric acute stroke protocol to prioritize magnetic resonance imaging over computed tomography. Educational lectures about pediatric acute stroke were given to the department of emergency medicine, division of vascular neurology, division of child neurology, and division of pediatric intensive care. Results: The protocol has been active for 18 months. There have been 20 pediatric code strokes. Magnetic resonance imaging was obtained first in 14 of 20 cases. The average time from code stroke to imaging in the emergency department was 60 minutes. The average time in the inpatient setting was 115 minutes. Final diagnosis was acute ischemic stroke in 3 patients. The other diagnoses were; RCVS (1), Methotrexate toxicity (1), Seizure (10), Metabolic (2), Migraine (1), Conversion (1), Bell's Palsy (1). 1 patient recieved tissue plasminogen activator and mechanical thrombectomy for basilar artery occlusion (Figures 1 and 2). Conclusions: Magnetic resonance imaging is a sensitive and specific first-line imaging choice in pediatric patients presenting with acute focal neurologic deficit. Multidisciplinary collaboration including both vascular and pediatric neurologists may improve diagnosis time for patients presenting with acute focal neurologic defict.

Pediatric acute stroke response protocols

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Whole-exome sequencing analysis in antenatal and perinatal intracerebral hemorrhage

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Ischemic Stroke and immune encephalitis: Which came first?

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Pediatric acute stroke response protocols

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Next from IPSO 2021

Whole-exome sequencing analysis in antenatal and perinatal intracerebral hemorrhage

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Ischemic Stroke and immune encephalitis: Which came first?

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PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES

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