Hypertriglyceridemia and cerebral venous thrombosis are well-recognized complications of asparaginase therapy for B-cell acute lymphoblastic leukemia. Hypertriglyceridemia has also been associated with an increased risk of thrombosis in conditions such as Behçet’s disease and has been implicated in a pediatric case of cerebral venous thrombosis, suggesting a possible link between hypertriglyceridemia and cerebral venous thrombosis. We present the case of a patient with acute delirium and amnesia, revealing a venous infarction caused by cerebral venous thrombosis of the sinus rectus. Classical causes, including hereditary thrombophilia, were excluded. Notably, the patient’s blood appeared lactescent at admission, and laboratory testing revealed severe hypertriglyceridemia. The patient improved significantly with heparin, dietary modifications, and ciprofibrate. This case suggests that severe hypertriglyceridemia should be considered as a potential trigger of cerebral venous thrombosis and that including a lipid panel in cerebral venous thrombosis work-ups could be considered, allowing subsequent specific therapeutic interventions.

This case report highlights brain imaging of 2 patients with a disease course suggestive of autoimmune glial fibrillary acidic protein astrocytopathy.

BACKGROUND AND PURPOSE:Prior studies highlighted the high diagnostic specificity (ranging from 92% to 100%) of clinical signs observed in functional neurological disorders (FNDs). However, these signs are rarely looked for by epileptologists when trying to distinguish between functional dissociative seizure (FDS) and epileptic seizure. The aim of this study was to determine the prevalence of inter-ictal clinical signs of FND in a cohort of patients with probable FDS. The secondary objective was to compare the prevalence of inter-ictal FND clinical signs in FDS patients with age- and gender-matched epileptic patients without FDS. METHODS:Patients diagnosed with FDS seen at two tertiary care centres and epileptic outpatients were included in the study. Each patient underwent a physical examination, searching for inter-ictal clinical signs of FND. RESULTS:In the FDS group, 79% of patients presented at least one sign of FND, compared to 16.6% of patients with epilepsy (p < 0.001). Moreover, 66.6% of FDS patients presented three or more FND signs, whereas only 4.1% of epileptic patients did (p < 0.001). The median number of FND clinical signs in the FDS group was four (SD 1.7; 5.5). Using the threshold of three signs or more, the specificity of detecting three or more FND signs was 83.3%, with a sensitivity of 79.2%. CONCLUSION:Inter-ictal clinical signs of FND are present in patients with FDS and should be looked for during neurological examination.

Introduction L’imagerie cérébrale par résonance magnétique peut mettre en évidence des lésions inflammatoires cérébrales en cas d’encéphalite et orienter vers une étiologie, selon la topographie et l’aspect de ces lésions. Observation Nous rapportons ici le cas de deux patients ayant présenté une méningo-encéphalo-myélite pour lesquels la réalisation de séquences avec injection de gadolinium en écho de spin a mis en évidence des prises de contraste des espaces péri-vasculaires diffuses, radiaires, évocatrices du diagnostic d’astrocytopathie à anti-GFAP. Ces lésions n’étaient pas visibles sur les séquences en écho de gradient. Les deux patients, âgés de 45 et 52 ans, ont présenté un tableau associant troubles cognitifs, ataxie proprioceptive, syndrome tétrapyramidal, troubles vésicosphinctériens, avec méningite lymphocytaire et synthèse intrathécale d’immunoglobulines. Le premier patient présentait également une papillite bilatérale. La recherche d’anticorps anti-GFAP était positive en immunofluorescence, mais pas sur cellules transfectées pour le patient 1. Elle était positive dans les deux modalités chez la patiente 2. Dans les deux cas, une IRM avec séquence injectée en écho de gradient avait été réalisée initialement et ne montrait pas d’anomalie. Un contrôle en écho de spin réalisé à l’arrivée des patients dans notre service (J+14 de la première imagerie pour le patient 1, J+19 pour la patiente 2) a mis en évidence des anomalies péri-vasculaires franches (Fig. 1). Discussion Les séquences en écho de gradient sont souvent utilisées, car elles offrent une bonne résolution anatomique et permettent la visualisation de la lumière des vaisseaux. Toutefois, les séquences en écho de spin offrent un meilleur contraste entre les lésions rehaussées et le parenchyme cérébral. Le délai de réalisation entre les IRM chez nos patients soulève la question d’un facteur confondant. Conclusion En cas de réalisation d’une IRM pour suspicion d’encéphalite, il nous semble pertinent de privilégier des séquences injectées en écho de spin, surtout si une astrocytopathie à anti-GFAP est suspectée.

BACKGROUND: Acute ischemic stroke is a neurologic emergency associated with severe disability and death. There is growing evidence that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acute stroke. By mechanical removal of the occluding thrombus from the patient's vasculature, endovascular thrombectomy enables the collection of thrombus material for immunohistologic analysis. The aim of our study was to strengthen the association of NET content in ischemic thrombi with clinical outcome and guide future therapeutics. METHODS: We performed an immunohistologic analysis of thrombi from 101 patients with acute ischemic stroke, focusing on the association between NET content and clinical and interventional indicators. RESULTS: NETs were present in every patient with acute ischemic stroke. Their abundance in thrombi was associated with interventional markers of thrombus stability. NET-rich thrombi were associated with unsuccessful recanalization (modified Thrombolysis in Cerebral Infarction <2B) and longer procedure time, and NET abundance in acute ischemic stroke thrombi was associated with outcomes evaluated by patients' postassessment National Institutes of Health Stroke Scale and modified Rankin Scale scores. CONCLUSION: These findings suggest that NET content is critically important to thrombus stability and clinical outcome in acute stroke. They should open new perspectives for innovative immunotherapy strategies based on neutrophil modulation.

Botulinum neurotoxin (BoNT) is a useful therapeutic option to treat dystonic manifestations. Data on its efficiency on dystonia associated with Parkinson's disease (PD) or atypical parkinsonism (AP) are scarce and no comparison of the efficiency of BoNT has been performed between these diseases and between the different localizations of dystonia in these pathologies. We retrospectively collected from patients' medical records the result of 611 BoNT injections in 63 dystonic parkinsonian patients (44 PD and 19 AP) using a self-reported clinical improvement scale and duration of effect. Using these data, we modeled the degree of improvement and its duration after BoNT treatment with a linear mixed model. This allowed us to assess the influence of clinical parameters on the reported treatment efficiency. On a scale from 0 to 100, patients with PD and AP, respectively, report a mean improvement of 69% and 55% after BoNT injection and it is similar regarding the different localizations of dystonia. Duration of effect is, however, longer in PD compared to AP (P = 0.023). Patients' demographic and clinical characteristics had no effect on the degree of improvement or duration of effect. Overall, our results support the use of BoNT in the various dystonic phenomena associated with degenerative parkinsonian syndromes. Shorter delays between injection sessions should be considered in AP compared to PD.Trial registration: This study was registered on Clinicaltrial.gov (NCT04948684).

La dystonie est un symptôme fréquent dans les syndromes parkinsoniens dégénératifs, à l'origine d'un handicap notable. Peu de données sont disponibles sur l'efficacité de la toxine botulique dans cette indication. Ce travail visait à modéliser l'efficacité de la toxine botulique sur les dystonies associées aux syndromes parkinsoniens dégénératifs et d'identifier d'éventuels paramètres influençant l'efficacité du traitement. Le bénéfice ressenti et la durée d'efficacité rapportés par auto-évaluation par les patients ont été recueillis rétrospectivement dans les dossiers médicaux des patients suivis pour un syndrome parkinsonien dégénératif et traités par toxine botulique dans le service de neurologie de l'Hôpital Avicenne. Un modèle linéaire mixte a été utilisé afin de modéliser ces paramètres d'efficacité chez les patients présentant une maladie de Parkinson idiopathique (MPI) et ceux présentant un syndrome parkinsonien atypique (SPA). Nous avons recueilli le résultat de 611 injections réalisées chez 63 patients (44 atteints d'une MPI et 19 d'un SPA). L'amélioration après traitement est similaire dans ces pathologies (MPI : 69 % vs SPA : 55 %; f2 = 0,069, p = 0,051). La durée d'amélioration est en revanche plus courte dans les SPA (6 vs 10 semaines dans la MPI; f2 = 0,110, p = 0,023). Les rétractions musculo-tendineuses réduisent l'efficacité et la durée d'amélioration (respectivement p < 0,001 et p = 0,008). Parmi les paramètres inclus dans la modélisation (âge, sexe, durée d'évolution de la pathologie, délai d'apparition de la dystonie, pathologie, localisation de la dystonie, numéro de session d'injection), aucun n'influe sur le degré d'amélioration obtenu après traitement par toxine botulique. Cela engage à considérer ce traitement indépendamment des caractéristiques cliniques du patient en cas de dystonie invalidante. L'amélioration des patients parkinsoniens dystoniques après injection de toxine botulique est notable. Le délai d'efficacité plus court dans les SPA doit faire privilégier des délais courts entre les injections.

Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. Results At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets—both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. Conclusions These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome. Graphic Abstract

HomeStrokeVol. 53, No. 10Bradykinin-Mediated Angioedema Following Tenecteplase Administration in an Acute Ischemic Stroke Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBBradykinin-Mediated Angioedema Following Tenecteplase Administration in an Acute Ischemic Stroke Arnaud Lapostolle, David Weisenburger-Lile, Marion Yger, Sonia Alamowitch and Olivier Fain Arnaud LapostolleArnaud Lapostolle Correspondence to: Arnaud Lapostolle, MD, AP-HP, Department of Neurology, Saint-Antoine Hospital, Paris, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-0736-8866 AP-HP, Department of Neurology, Saint-Antoine Hospital, Paris, France (A.L., M.Y.). , David Weisenburger-LileDavid Weisenburger-Lile Department of Neurology, Stroke Center, Foch Hospital, Suresnes, France (D.W.-L.). , Marion YgerMarion Yger AP-HP, Department of Neurology, Saint-Antoine Hospital, Paris, France (A.L., M.Y.). , Sonia AlamowitchSonia Alamowitch AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Hôpital Saint-Antoine, CRSA, INSERM, UMRS 938 Sorbonne Université, Paris, France STARE team, iCRIN, ICM, Paris, France (S.A.). and Olivier FainOlivier Fain Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France (O.F.). UPMC University Paris 06, Paris, France (O.F.). Sorbonne Universités, UPMC University Paris 06, INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Paris, France (O.F.). Originally published7 Sep 2022https://doi.org/10.1161/STROKEAHA.122.040052Stroke. 2022;53:e446–e447Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 7, 2022: Ahead of Print Key PointCare should be taken with tenecteplase and the use of C1 inhibitor concentrate should be considered if bradykinin-mediated angioedema occurs.An 81-year-old man treated with angiotensin-converting enzyme inhibitor was administered tenecteplase for a right posterior cerebral artery ischemia.In the following hour, lingual swelling and sudden oxygen desaturation were observed. The patient was diagnosed with angioedema and treated with C1 inhibitor concentrate alone, which resulted in rapid symptom improvement (Figure 1).Download figureDownload PowerPointFigure 1. Photographs of the 81-year-old patient. A, Lingual swelling developed after the injection of tenecteplase. B, Picture taken a few hours after administration of C1 inhibitor concentrate showing complete regression of angioedema.Histaminic and bradykinin-mediated angioedema are well-known sides effects of alteplase.1 Like alteplase, tenecteplase functions similarly to the natural tissue-type plasminogen activator, exerting its thrombolytic action by converting plasminogen entrapped in the thrombus to plasmin, the key effector of the fibrinolysis cascade. However, a backlash to the liberation of plasmin may be the activation of the plasma kallikrein-kinin system (plasma contact system) that leads to the generation of bradykinin.2C1 inhibitor concentrate inhibits factor XIIa and prevents the conversion of prekallikrein to kallikrein, thereby halting the formation of bradykinin (Figure 2).3Download figureDownload PowerPointFigure 2. Summary of the mechanism of reaction and treatment sites of C1 esterase inhibitor. ACE indicates angiotensin-converting enzyme.Article InformationSources of FundingNone.Disclosures Dr Lapostolle reports grants from Société Française Neurovasculaire. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page e447.Correspondence to: Arnaud Lapostolle, MD, AP-HP, Department of Neurology, Saint-Antoine Hospital, Paris, France. Email arnaud.lapostolle@aphp.frReferences1. Vigneron C, Lécluse A, Ronzière T, Bouillet L, Boccon-Gibod I, Gayet S, Doche E, Smadja D, Di Legge S, Dumont F, et al. Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.J Intern Med. 2019; 286:702–710. doi: 10.1111/joim.12962CrossrefGoogle Scholar2. Cicardi M, Zuraw BL. Angioedema due to bradykinin dysregulation.J Allergy Clin Immunol Pract. 2018; 6:1132–1141. doi: 10.1016/j.jaip.2018.04.022CrossrefMedlineGoogle Scholar3. Pahs L, Droege C, Kneale H, Pancioli A. A novel approach to the treatment of orolingual angioedema after tissue plasminogen activator administration.Ann Emerg Med. 2016; 68:345–348. doi: 10.1016/j.annemergmed.2016.02.019CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By (2023) Tenecteplase, Reactions Weekly, 10.1007/s40278-023-36374-8, 1949:1, (394-394) October 2022Vol 53, Issue 10 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.122.040052PMID: 36069184 Originally publishedSeptember 7, 2022 Keywordsangiotensin converting enzymetenecteplasekallikrein-kinin systemischemiabradykininPDF download Advertisement SubjectsIschemic Stroke

Abstract Background Emerging data based on analyses of peripheral and pulmonary immune responses to SARS-CoV-2 increasingly suggest that a dysregulated immune response underpins the development of severe disease in COVID-19 patients. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. Methods This longitudinal study compares study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2 – patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. Results At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets — both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide, an abnormality that was greater in superinfected than non-superinfected COVID-19 patients. Moreover, patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. Conclusions These data suggest that neutrophil exhaustion may play a central role in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.