United States

Case description 16 years old female with JD was admitted for stroke with symptoms of sudden onset right-sided hemiparesis, diplopia, dysarthria &amp; difficulty word finding. On examination,was alert, oriented &amp; neurologically intact except dysarthric speech, ataxic gait, bilateral dysmetria &amp; dysdiadokinesia. MRI brain showed patchy asymmetric areas of T2/FLAIR hyperintensities without diffusion restriction involving pons, bilateral middle cerebellar peduncles &amp; hemispheres. Initially started on immunosuppressive therapy (Steroids, Methotrexate &amp; 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 &amp; rehab she continues to show improvement. She is now able to sit without support &amp; 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 &amp; 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 &amp; 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

IPSO 2021

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

other cerebrovascular disease

Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
The 2022 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. Log in at any time throughout the event to:
* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges and compete to win a $10,000 grand prize sponsored by Laurel Road.
 

#### Attend Live Forums
**Oct. 20, 6 — 7 p.m. Central**
 **How to plan a career in academic medicine** 
 Learn how to plan a career in academic medicine and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
 
 **Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/d5adb133dfc58eb0a6d469e9cedcd5d4.jpg)
Ricardo Correa, MD, EdD
![](https://assets.underline.io/uploads/markdown_image/1/image/5f9437ab87861538bf02b9ca7c0d926e.jpg)
Stuart M. Greenstein, MD
![](https://assets.underline.io/uploads/markdown_image/1/image/05b1b637c99286d558c371f8e8b185ce.jpg)
Stephanie Strohbeen, MD
 
 **Oct. 22, 11 a.m. — Noon Central**
 **How to get published**
 Learn tips to get your research published and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
 
 **Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/8ce6235e957d31cb5e6f9097cc6f6972.jpg)
Jessica Li, MD/PhD Candidate
![](https://assets.underline.io/uploads/markdown_image/1/image/9950ef2e0237f54cb3d8280334d42491.jpg)
Charles Lopresto, DO

### Sponsor
AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on Dec. 7 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use the link below to register for free if you have not already done so:**

https://www.ama-assn.org/about/events/ama-research-challenge

Registration Is Required

AMA Research Challenge 2022

Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


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

poster

**[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 multiple disciplines and six continents 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>.

Introduction: Moyamoya is a progressive steno-occlusive arteriopathy affecting the distal internal carotid artery and its branches. Associated to an underlying condition such as neurofibromatosis type 1 (MMS-NF1) or sickle cell disease (MMS-SCD), it is called moyamoya syndrome (MMS) while an isolated arteriopathy is referred to as moyamoya disease (MMD). It remains unknown whether the associated condition impacts its evolution. Objective: We hypothesize that MMD presents and evolves differently compared to MMS. Methods: We performed a single-center chart review of patients with moyamoya followed between 2003 and 2019. Clinical and radiographic features at diagnosis were obtained. Subsequent stroke or neurosurgery clinic visits were reviewed to identify ischemic event occurrence. Evidence of disease progression or new infarction was sought on follow up MRI studies. Group comparisons between children with MMD and MMS and between MMD and MMS subgroups (MMS-NF1 and MMS-SCD) were conducted using Pearson's Chi-squared, Fisher's Exact, Mann-Whitney U, or t test, as appropriate. Survival analysis by cerebral hemisphere using Cox regression were conducted to assess ischemic event occurrence, disease progression and silent infarction at follow-up. A false discovery rate (FDR) p-value adjustment for multiple comparisons with a q-value< 0.05 was applied. Results: One hundred and eleven patients were identified (MMD=49; MMS-NF=23; MMS-SCD=21). MMD presented more with TIA than MMS (22.45% vs MMS 4.84%, q=.02), while MMS-NF1 presented less with a stroke compared to the other groups (MMD 46.94% vs MMS-NF1 8.7% vs MMS-SCD 42.86%; q=0.0032). MMS-NF1 had more frequently unilateral disease (MMD 26.53% vs MMS-NF1 78.26% vs MMS-SCD 33.33%; q=.0003) and less infarcts (MMD 67.35% vs MMS-NF 26.09% vs MMS-SCD 80.95%; q=.0008) at diagnosis, while MMS-SCD were less likely to have an ivy sign (MMD67.35% vs MMS-NF1 52.17% vs MMS-SCD 9.52%, q=.0003). At follow-up, MMD patients were more likely to suffer another ischemic event compared to MMS patients (OR 1.92, p=.019), these events were mainly TIA (OR 2.5, p=.004). However, compared to the other groups, MMS-NF1 were less likely to have another TIA (OR 0.43, p=.045). Conclusion: MMS has varying phenotypes. MMS-NF1 tends to be unilateral with a lower burden of infarction at presentation, while an ivy sign is not a common feature of MM-SCD. Compared to MMS-SCD and MMD, MMS-NF1 is less likely to have further ischemic events.

Distinct clinical and radiographic presentation and evolution in childhood moyamoya syndrome

The symptoms of Cerebral Autosomal Disorder Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) do not typically manifest until midlife, but it has been diagnosed in a few children. Although she appeared healthy as a young child, BV had a heterozygous NOTCH3 gene mutation, and she experienced previously undetected strokes in the left frontal area. At 4 years 9 months, BV exhibited sudden onset aphasia and left hemiparesis, and she was found to have had acute ischemic strokes involving the right anterior cerebral artery (ACA) and left middle cerebral artery (MCA) territories. Extensive vascular disease involving the internal carotid arteries, right ACA, and left MCA was also observed. Within days, BV experienced new strokes in the right centrum semiovale, left interior frontal white matter, and right parietal lobe. She underwent encephaloduroarteriosynangiosis (EDAS) procedures in the left brain hemisphere at 5 years 0 months and in the right brain hemisphere at 5 years 3 months. BV experienced brain edema following the second procedure, and she was diagnosed with an acute ischemic stroke in the right MCA area affecting the majority of the temporal, parietal, and occipital lobes approximately 1 week following that procedure. BV had neuropsychological evaluations at 5 years 1 month, 5 years 10 months, and 7 years 1 month. At the time of her first evaluation, BV's visuospatial processing was average, but her verbal abilities were generally low average. She also exhibited severe inattention and impulsivity. After revascularization surgery and additional strokes, BV's language processing was stable, but her visuospatial processing had declined and was generally low average to mildly impaired. BV's cognitive functioning had remained generally stable with some areas of modest development at the time of her third neuropsychological evaluation at 7 years of age.

Neuropsychological function across time in a child with NOTCH3 mutation and CADASIL

Introduction: After sustaining brain injury, children have unique challenges to their activities of daily living compared to their healthy peers. These barriers are especially notable in the classroom, where a combination of physical, emotional, social, and cognitive skills is required to allow optimal performance. Medical staff and educational professionals share a common mandate to facilitate a child's best future. When injury interferes with a child's function, the achievement potential is threatened. Methods:This presentation is a review of return to school initiatives in place for children in the USA and medical provider utilization of these systems. We will present comparative models of educational inclusion services, identifying strengths and opportunities for expansion. Preliminary results from a survey of pediatric brain injury care providers will detail utilization of these services. Results: We describe a continuum of services divided into 4 discrete paradigms: brain injury-specific classroom, transitional school model, day rehabilitation program, and school outreach/community-based services. Programs vary dramatically in cost, payer, service coverage, and geographic availability. There is minimal data on efficacy and little agreement on endpoints to demonstrate successful intervention. A wide variation in access to and utilization of services is reflected in healthcare provider experience. Conclusions: There is a clear need to develop robust, available, and successful programs to return children to their education after brain injury.

 A review and survey of school inclusion after acquired brain injury

Background:Stroke is an important cause of mortality and morbidity in children. Aim:The aim of the study was to evaluate long-term neurological outcome in children with arterial ischemic stroke (AIS) and explore predictive factors that affect poor outcome. Patients:56 patients aged between one month and 17 years who were treated at M.Iashvili Children Central Hospital, Tbilisi, Georgia, with an onset of stroke from 2007 to 2017 were included. Methods:To explore predictive factors of outcome, the following data were collected: demographic characteristics, risk factors, the presenting signs, radiological features, and presence of stroke recurrence. Neurological status at discharge and long-term neurological outcome at least 1 year after stroke was evaluated according to Pediatric Stroke Outcome Measure (PSOM) subscale. Results: The reported outcome after childhood stroke was variable with long-term neurological deficits in one-third of patients (30.4%). The neurological outcome was worse in males, in patients with multiple stroke episodes, and in those with infractions involving a combination of cortical and subcortical areas. Conclusion:Pediatric AIS carries the risk of long-term morbidity, and neuroimaging has a predictive influence on outcome.

Predictors of neurological outcome of arterial ischemic stroke in children

Background: Perinatal stroke occurs secondary to a focal disruption of blood flow in the brain occurring between 20 weeks' gestation and the 28th day of life. Current literature has associated perinatal stroke with adverse attention outcomes. Despite this, when parents of children with perinatal stroke were surveyed, very few recalled conversations with their clinician regarding their child's attentional outcome. There is therefore a need to evaluate the University Hospital Southampton (UHS) neurodevelopmental protocol to follow up attention outcomes in perinatal stroke. Aims: Firstly to evaluate adherence to the UHS neurodevelopmental protocol. Secondly, to evaluate the use of neuroimaging data and clinical data regarding neonatal seizures and post-natal epilepsy to identify children at risk of attention difficulties. Methodology: We conducted a service evaluation to determine whether the attention problem score from the Child Behavior Checklist (CBCL), was available from the parent reported questionnaire administered at the 2-year follow-up appointment. Neuroimaging data were analysed to identify cortical, white matter, basal ganglia, and thalamic involvement and to quantify infarct size. Presence of neonatal seizures and post-natal epilepsy were extracted from clinical notes. Chi-square was used to compare proportions. Results: CBCL data were only available for 35/63 patients. Reasons for missing CBCL data included patients not attending follow up, not returning questionnaires and inadequate data handling meaning data were not stored correctly. 13/35 children had attention scores in the borderline or clinical range. Basal ganglia and thalamic involvement (p=0.015), neonatal seizures (p=0.028) and post-natal epilepsy (p=0.042) were associated with borderline or clinically significant attention scores. Post-natal epilepsy predicted the highest relative risk of adverse attention outcomes. Conclusion: These clinical predictors could be used to identify children at high risk for attention difficulties to encourage parental adherence to the neurodevelopmental protocol, ensuring a complete clinical dataset and providing information to enable appropriate therapy and education.

A service evaluation of the University Hospital Southampton neurodevelopmental protocol to follow up and identify attention outcomes in children with perinatal stroke

Introduction Neurogenesis occurs after perinatal brain injury as a result of gene expression changes. DNA methylation and demethylation is one mechanism by which gene expression is regulated. Recent work has elucidated a role for Gadd45 proteins in mediating gene demethylation. Hypothesis We hypothesize that Gadd45 is responsible for active demethylation after perinatal hypoxia/ischemia and promotes neurogenesis as part of the regenerative response to injury. Methods We induced perinatal HI in 10 day old C57BL/6 pups by ligation of the right common carotid artery followed by exposure to hypoxia (8% O2/92% N2) for 45 minutes. The pups were sacrificed at 4 or 24 hours for molecular biology or immunohistochemistry. We used quantitative RT-PCR to study gene expression of Gadd45 family and TET family proteins. We evaluated targeted gene methylation status with methylation specific PCR and in situ DNA modifications using immonhistochemistry. Neurogenesis was quantified by 5-ethinyl-2'-deoxyuridine (EdU) incorporation in wild type and Gadd45b knockout mice. Results Gadd45 family mRNA is rapidly upregulated by 14-fold in the subventricular zone (SVZ) by 4 hours following perinatal HI, and remains upregulated at 24 hours. Small transient increases in expression were seen for Gadd45a and Gadd45g at 4 hours. There is no significant change in the expression of TET mRNA. Preliminary suggest specific demethylation of the BDNF promoter by 24 hours. Immunohistochemistry revealed increased expression of 5-hydroxymethylcytosine specifically within the SVZ progenitor cells, and neurogenesis was reduced in Gadd45-/- mice. Conclusion Perinatal HI induces upregulation of Gadd45b, which may contribute to demethylation of growth promoting genes in the neurogenic niche, driving the neurogenic response to perinatal hypoxic-ischemic brain injury.

Gadd45b modulates neurogenesis following perinatal hypoxic-ischemic brain injury

Background and Aims: Subpial hemorrhages (sPH) were first described in infants in 1972, but they remain underrecognized on neuroimaging and the clinical implications of sPH are poorly understood. The aim of this study is to describe the etiologies, risk factors, clinical presentations, and imaging findings of sPH in neonates. Methods: Institutional Neonatal Intensive Care Unit database was queried for presence of sPH. All infants recorded to have intracranial hemorrhage on brain MRI were reviewed by a pediatric neuroradiologist. Through retrospective chart review, data on pregnancy/birth history, comorbidities, and clinical concerns that led to imaging were collected. Results: Twenty-six infants with sPH were identified: 13 (50%) were preterm, 11 (42%) had low birthweight. Comorbidities included hypoxic-ischemic encephalopathy (n=1, 42%), birth trauma (n=6, 23%), cardiopulmonary disease (n=6, 23%), coagulopathy (n=6, 23%), ventricular shunt (n=3, 12%), severe congenital brain anomalies (n=1, 4%), and chromosomal anomaly (n=1, 4%). MRI acquisition was at a median of 5 days of life (range 1 to 41 days). sPH frequently accompanied intraparenchymal (n=17, 65%), subdural (n=16, 62%), intraventricular (n=13, 50%), and subarachnoid hemorrhage (n=8, 31%). In addition, 7 children (27%) had ischemic stroke. All children with sPH had either another form of hemorrhage, ischemic stroke, or both. In addition, 9 patients (34%) had follow-up MRIs. Development of adjacent encephalomalacia was consistently demonstrated in children with large subpial hemorrhages. Sixteen infants with sPH (62%) had clinical and/or electrographic seizures. Conclusions: sPH are associated with multiple comorbid medical conditions, other types of intracranial hemorrhage, and ischemic strokes. Further studies to evaluate long-term clinical implications of subpial hemorrhages are needed.

A new kind of bleed: Subpial hemorrhages in the neonatal intensive care unit

Introduction: In children, perinatal stroke is the most common type. Long-term morbidities can be high, and include motor, cognitive and behavioral domains. While some studies point to poorer global, motor and adaptive outcomes in presumed perinatal compared to acute perinatal stroke, few have studied specific cognitive functions in a developmentally homogenous sample. We aimed to assess cognitive outcomes in a homogenous sample regarding age, time since injury, and development. We predicted that delay in diagnosis and hence intervention may have an impact on long-term cognitive outcome. Hypothesis: Preschoolers with presumed perinatal stroke demonstrate poorer cognitive function than those with acute neonatal stroke. Methods: Children age 4;0-5;11 years (n=63, Acute Perinatal=39, Presumed Perinatal=24) underwent comprehensive neuropsychological assessment as part of standard care. Cognitive function was assessed with age-appropriate standardized tests of general cognitive ability, language, visual-spatial, memory, and motor functions. Parents completed ratings of executive and behavioral function. Data from initial evaluations at a single time point were analyzed retrospectively. Cognitive and behavioral function of the overall sample were compared to population means, as well as between acute and presumed perinatal subgroups. Results: Compared to population means, the perinatal group demonstrated poorer processing speed, auditory memory, visual-spatial and visual-motor skills (pFDR<.01-.05), and increased problems with executive functions (pFDR<.01; flexibility, emerging metacognition) and adaptive skills reported by parents/teachers. Further, the presumed perinatal stroke group showed reduced verbal ability (knowledge, reasoning, naming), and processing speed than the acute perinatal group (ps<.01-.05). Stroke location and maternal education were significant contributors. Conclusions: Perinatal stroke causes diminished cognitive and behavioral function in preschoolers and kindergartners. We found cognitive differences (verbal, processing speed) in children with presumed versus acute perinatal stroke. Findings will be further explored for predictors of outcome in an ongoing study; they underscore the importance of early diagnosis and intervention to improve long-term cognitive and psychosocial function.

Cognitive outcomes in preschoolers with presumed vs. acute perinatal stroke

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.

Downloads

Next from IPSO 2021

Distinct clinical and radiographic presentation and evolution in childhood moyamoya syndrome

Similar lecture

How to Distinguish Creutzfeldt-Jakob Disease from Progressive Multifocal Leukoencephalopathy when the Cerebrospinal Fluid Fails

.css-70qvj9{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}Downloads

Next from IPSO 2021

Distinct clinical and radiographic presentation and evolution in childhood moyamoya syndrome

Similar lecture

How to Distinguish Creutzfeldt-Jakob Disease from Progressive Multifocal Leukoencephalopathy when the Cerebrospinal Fluid Fails

Downloads