Die VAD (Dissektion der A. vertebralis) ist eine häufige Ursache für eine seltene Erkrankung, den PCAIS (pädiatrischer arterieller ischämischer Schlaganfall im hinteren Kreislauf des Gehirns). Sie kann zu einer fortschreitenden Arteriopathie und rezidivierenden Schlaganfällen führen. Die Autoren geben einen Überblick über die charakteristischen Bildgebungsmerkmale und die optimierte Bildgebung der VAD und des assoziierten PCAIS.

Vertebral artery dissection (VAD) is a common cause of a rare condition, pediatric posterior circulation arterial ischemic stroke (PCAIS). VAD is clinically important due to the risk of multifocal and continuing infarcts from artery-to-artery thromboembolism, with the potential for occlusion of arteries that perfuse the brainstem. Early diagnosis is important, as recurrent stroke is a common effect of VAD in children. Although the relative efficacies of different treatment regimens for VAD in children remain unsettled, early initiation of treatment can mitigate the risk of delayed stroke. Clinical diagnosis of PCAIS may be delayed due to multiple factors, including nonspecific symptoms and the inability of younger patients to express symptoms. In fact, subacute or chronic infarcts are often present at initial imaging. Although the most common cause of isolated PCAIS is VAD, imaging of the cervical arteries has been historically underused in this setting. Cervical vascular imaging (MR angiography, CT angiography, and digital subtraction angiography) for VAD must be optimized to detect the sometimes subtle findings, which may be identified at initial or follow-up imaging. Osseous variants of the craniocervical junction and upper cervical spine and other extrinsic lesions that may directly injure the vertebral arteries or lead to altered biomechanics have been implicated in some cases. The authors review characteristic imaging features and optimized imaging of VAD and associated PCAIS and related clinical considerations. Identification of VAD has important implications for evaluation, treatment, and imaging follow-up, as this condition may result in progressive arteriopathy and recurrent stroke. © RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Cerebrovascular diseases attributed to coronavirus disease 2019 (COVID-19) are uncommon but can result in devastating outcomes. Pediatric acute ischemic strokes are themselves rare and with very few large vessel occlusion related acute ischemic strokes attributed to COVID-19 described in the literature as of date. COVID-19 pandemic has contributed to acute stroke care delays across the world and with pediatric endovascular therapy still in its infancy, it poses a great challenge in facilitating good outcomes in children presenting with acute ischemic strokes in the setting of COVID-19. We present a pediatric patient who underwent endovascular therapy for an internal carotid artery occlusion related acute ischemic stroke in the setting of active COVID-19 and had an excellent outcome thanks to a streamlined stroke pathway involving the vascular neurology, neuro-interventional, neurocritical care, and anesthesiology teams.

BACKGROUND:Neuropsychiatric symptoms and CSF cytokine, chemokine, and SARS-COV-2 antibody profiles are unknown in pediatric patients with COVID-19 or multisystem inflammatory syndrome (MIS-C), (NP-COVID-19). METHODS:Children at a single pediatric institution quaternary referral center with laboratory-confirmed COVID-19 or MIS-C and neuropsychiatric symptoms were included in this retrospective case series. Clinical symptoms, ancillary testing data, treatments and outcomes are described. Multiplexed electrochemiluminescence assays for cytokines, chemokines and SARS-CoV-2 antibodies were tested in the CSF NP-COVID-19 patients compared to five controls and were analyzed using the Student's t-test. RESULTS:Three of five NP-COVID-19 patients had psychiatric symptoms, and two patients had encephalopathy and seizures. All patients had full or near resolution of neuropsychiatric symptoms by discharge. One patient received intravenous steroids for treatment for psychiatric symptoms; 3/5 other patients received immunotherapy for MIS-C, including IVIG, high-dose steroids, anakinra, and tocilizumab. Pro-inflammatory chemokines, including MIG, MPC, MIP-1β, and TARC were significantly elevated in NP-COVID-19 patients compared to controls. Two of five patients had elevated CSF neurofilament light chain. CSF SARS-CoV-2 antibody titers to the full-length spike, receptor binding domain and N-terminal domain were significantly elevated. SARS-CoV-2 antibody titers strongly correlated with pro-inflammatory chemokines/cytokines, including IL-1β, IL-2, IL-8, TNF-α, and IFN-γ (P≤0.05 for all). CONCLUSIONS:A spectrum of neuropsychiatric clinical manifestations can occur in children with SARS-CoV-2 infection. CSF pro-inflammatory chemokines and SARS-CoV-2 antibodies may serve as biomarkers of SARS-CoV-2 mediated NP-COVID-19. Additional study is required to understand the pathophysiologic mechanisms of neuroinflammation in children with COVID-19 and MIS-C.

Introduction: Carotid web is a radiographic entity located in the posterior aspect of the origin of the internal carotid arteries, considered to be a pathologic equivalent to intimal fibromuscular dysplasia, and has been implicated in acute ischemic strokes. The mechanism underlying its development is unknown and it remains unclear if this lesion is congenital or acquired. The aim of our study was to determine the frequency of carotid webs in a pediatric population with acute ischemic stroke (AIS). Methods: A retrospective review of neck CTA, MRA, or DSA images in a pediatric population with acute ischemic stroke was performed to determine the occurrence of carotid webs. Two fellowship-trained neurointerventionists performed independent vascular imaging review. Results: We identified forty-seven cases of childhood acute ischemic stroke (55% male; median age, 9 years). Congenital heart disease, sickle cell disease, infection, and recent head/neck trauma were the most common risk factors. Eight of the ischemic stroke cases were located in multiple vascular territories. Neck arterial imaging was undertaken in twenty-four patients. No carotid webs were detected in the studied pediatric stroke population. (The correlation coefficient for the determination of webs was Kappa = 1.00; p < 0.001). Conclusion: This study failed to find evidence that carotid webs are congenital. More studies are needed for a better understanding of carotid web origin, natural evolution, and the potential implications for treatment.

Demyelinating, inflammatory, and autoimmune conditions have been implicated as pediatric stroke mimics. 1 DeLaroche A.M. Sivaswamy L. Farooqi A. Kannikeswaran N. Pediatric stroke and its mimics: limitations of a pediatric stroke clinical Pathway. Pediatr Neurol. 2018; 80: 35-41 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Anti-myelin oligodendrocyte glycoprotein-associated disorder (MOG-AD) has not yet been identified as a pediatric stroke mimic. MOG-AD is a distinct entity with varying clinical demyelinating diseases due to anti-MOG antibodies (MOG-ab). 2 Reindl M. Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019; 15: 89-102 Crossref PubMed Scopus (162) Google Scholar ,3 Chen Q. Zhao G. Huang Y. et al. Clinical characteristics of pediatric optic neuritis with myelin oligodendrocyte glycoprotein seropositive: a cohort study. Pediatr Neurol. 2018; 83: 42-49 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Here we describe a patient who presented with acute-onset hemiparesis and respiratory failure with positive MOG-ab.

We would like to thank Budhram et al. for their interest in our report, “A Stroke Mimic: Anti-MOG Antibody-Associated Disorder Presenting as Acute Hemiparesis.” 1 Tutmaher M.S. Chen D.F. Hallman-Cooper J. Holt P.J. Philbrook B. Gombolay G.Y. A stroke mimic: anti-MOG antibody-associated disorder presenting as acute hemiparesis. Pediatr Neurol. 2020; 108: 123-125 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar As the authors pointed out, 2 Budhram A. Mirian A. Flanagan E.P. Unilateral cortical FLAIR-hyperintense lesions in anti-MOG encephalitis with seizures (FLAMES): an under-recognized entity. Pediatr Neurol. 2020; 110: 99-100 Abstract Full Text Full Text PDF Scopus (1) Google Scholar our patient resembles other cases that have been termed unilateral cortical FLAMES (FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures). 3 Budhram A. Mirian A. Le C. Hosseini-Moghaddam S.M. Sharma M. Nicolle M.W. Unilateral cortical FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES): characterization of a distinct clinico-radiographic syndrome. J Neurol. 2019; 266: 2481-2487 Crossref PubMed Scopus (85) Google Scholar In the initial description of unilateral cortical FLAMES, two pediatric patients were included in the literature review, one of whom did present with hemiparesis and lethargy. Moreover, a subset of adult patients also presented with hemiparesis. 3 Budhram A. Mirian A. Le C. Hosseini-Moghaddam S.M. Sharma M. Nicolle M.W. Unilateral cortical FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES): characterization of a distinct clinico-radiographic syndrome. J Neurol. 2019; 266: 2481-2487 Crossref PubMed Scopus (85) Google Scholar Our patient may represent a subset of patients with unilateral cortical FLAMES. Our goal was to highlight that anti-MOG antibody-associated disease can present as acute hemiparesis and we agree with the authors that this should be taken into consideration by both pediatric and adult neurologists. Unilateral Cortical Fluid-Attenuated Inversion Recovery–Hyperintense Lesions in Anti-Myelin Oligodendrocyte Glycoprotein–Associated Encephalitis With Seizures (FLAMES): An Under-recognized EntityPediatric NeurologyVol. 110PreviewWe read with interest the article by Tutmaher et al.1 They report an 11-year-old girl with acute-onset right hemiparesis concerning for stroke. Brain magnetic resonance imaging revealed mild left frontoparietal cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) hyperintensity. She was ultimately diagnosed with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)–associated disease (MOGAD). MOGAD is a recently recognized subset of central nervous system inflammatory demyelinating diseases, to which children and young adults seem particularly predisposed. Full-Text PDF

Background and Purpose— Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods— We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results— Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46–2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29–2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40–2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37–0.93), but the frequency of identified cardiac abnormalities was similar in both groups (P=0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08–0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55–8.09). Conclusions— Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.

A 2 month old child with a large hemispheric tumor; after subtotal resection, pathology showed pilomyxoid astrocytoma with BRAFV600E mutation by immunohistochemistry and pyrosequencing. He had multiple episodes of radiographic and clinical progression. Over the course of 5 years, therapy included carboplatin, TPCV, velban, and immunotherapy. Vemurafenib and dabrafenib were administered with no response. MRI showed rapid tumor progression in the brain with spinal dissemination and significant clinical deterioration. Patient underwent tumor debulking and pathology confirmed a high grade astrocytoma, without BRAF V600E mutation, but with a novel BEND4-NTRK2 fusion by molecular genetic testing. He underwent whole brain radiation of 33 Gy in 16 fractions and boost to primary tumor bed to a total dose of 43 Gy. No radiation was given to the spine. One month later, patient started compassionate treatment with entrectinib, a novel, CNS-active, TRK inhibitor, at 400 mg/m2/day. MRI obtained after 28 days on treatment demonstrated significant radiographic regression, with rapid improvement in clinical symptoms. His dose was then increased to 550 mg/m2/day. After 2 additional cycles, the tumor continues to decrease in size in the brain and a spine MRI demonstrated complete response despite no radiation to the spine. Toxicities included Grade 1 ALT, cholesterol and peripheral edema. In summary, we report the case of a refractory BRAF V600E mutated low grade glioma transformed into a high grade with a novel BEND4-NTRK2 fusion, and profound radiographic and clinical response to entrectinib.

SummaryPrevious reports have identified SLC6A1 variants in patients with generalized epilepsies, such as myoclonic‐atonic epilepsy and childhood absence epilepsy. However, to date, none of the identified SLC6A1 variants has been functionally tested for an effect on GAT‐1 transporter activity. The purpose of this study was to determine the incidence of SLC6A1 variants in 460 unselected epilepsy patients and to evaluate the impact of the identified variants on γ‐aminobutyric acid (GABA)transport. Targeted resequencing was used to screen 460 unselected epilepsy patients for variants in SLC6A1. Five missense variants, one in‐frame deletion, one nonsense variant, and one intronic splice‐site variant were identified, representing a 1.7% diagnostic yield. Using a [3H]‐GABA transport assay, the seven identified exonic variants were found to reduce GABA transport activity. A minigene splicing assay revealed that the splice‐site variant disrupted canonical splicing of exon 9 in the mRNA transcript, leading to premature protein truncation. These findings demonstrate that SLC6A1 is an important contributor to childhood epilepsy and that reduced GAT‐1 function is a common consequence of epilepsy‐causing SLC6A1 variants.

OBJECTIVE To provide access to cannabidiol (CBD) for children with medication resistant epilepsy (MRE) and evaluate CBD as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in seizure frequency. BACKGROUND The State of Georgia desires to provide children with MRE access to CBD and contribute to the scientific literature on CBD. DESIGN/METHODS This multi-center study for MRE patients 1 to 18 years of age at time of enrollment consists of 8 week baseline, titration, and treatment periods with CBD up to a 25 mg/kg/day dosage. Treatment will be provided for 52 weeks. The patient or caregiver records seizure frequency and drug compliance into an innovative electronic diary application. Statistical analyses were calculated for relevant median overall seizure frequency reduction from baseline. RESULTS As of 9/30/2015, total enrollment was 46 patients, of which, 20 [average age 9.6 yrs, range 1 to 17 yrs, male (n=11)], received at least 8-weeks of treatment for the analysis below. The common underlying causes of epilepsy were cryptogenic (n=10; 50[percnt]) and cortical dysplasia (n=5; 26[percnt]). The average number of concomitant AEDs was 3 (range= 2-5). Four patients had a history of epilepsy surgery (i.e. corpus callosotomy, cortical resection). After eight weeks of treatment, 95[percnt] of patients experienced seizure frequency reduction from baseline. Overall, reduction in total seizure frequency for all patients was 51[percnt] with a 48[percnt] reduction in all types of major seizures (tonic, atonic, and generalized tonic clonic). Adverse events in 10[percnt] of patients (n=2) included somnolence (n=1), ataxia (n=1), and vomiting (n=2). One patient withdrew primarily due to lack of efficacy. No related Serious Adverse Events (SAEs) were reported. CONCLUSIONS These results show that CBD may be a promising treatment for MRE and is generally well-tolerated in doses up to 25mg/kg/day. FUNDING State of Georgia IMP provided by GW Pharma

Purpose: To evaluate the efficacy, tolerability, and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures. Patients and methods: Children meeting enrollment criteria (n = 54) received a confirmatory 24-h ambulatory electroencephalogram (EEG) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose (10.2 mg/kg) was reached. Seizure freedom was assessed by diary review and clinic hyperventilation (clinic HV) and then confirmed by EEG with hyperventilation (HV/EEG). Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase (n = 30). Diary, clinic HV, and HV/EEG data were supplemented with 24-h ambulatory EEG at baseline and the ends of the Escalation and Maintenance Phases. Health outcome assessments were completed at screening and at the end of the Maintenance Phase. Results: By the end of the Escalation Phase, seizure-free rates (responders) were 59% by seizure diary (n = 51), 56% by HV/EEG (n = 54) (primary endpoint), and 49% by 24-h ambulatory EEG (n = 49). During the Maintenance Phase, 89% (week 24) and 86% (week 32) remained seizure free by diary (n = 28), 78% by clinic HV (n = 27), and 81% by 24-h ambulatory EEG (n = 26). Seizure freedom was first observed beginning at the fifth week of the Escalation Phase. The most frequent adverse events were headache and cough. Health outcome scores were either improved or unchanged at the end of the Maintenance Phase.