Hamostaseologie 2023; 43(03): 188-195
DOI: 10.1055/a-1848-3649
Original Article

Laboratory Findings, Medical Imaging, and Clinical Outcome in Children with Cerebral Sinus Venous Thrombosis

Hannah Glonnegger*
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Nicole Glatthaar*
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Matthias Eckenweiler
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Michael Barth
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Markus Uhl
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Martin Büchsel
2   Institute of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
,
Barbara Zieger
1   Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Medical Centre - University of Freiburg, Baden-Württemberg, Germany
› Author Affiliations
Funding No funding was received for conducting this study.

Abstract

Introduction Cerebral sinus venous thrombosis (CSVT) is a rare disease, especially in children. Therefore, thrombophilia markers, risk factors, treatment strategy, and MRI, as well as clinical outcome need further investigation to support future diagnostic and therapeutic guidelines for children.

Methods We retrospectively identified all children with CSVT treated in our center between January 1, 2000, and December 31, 2015. Risk factors and laboratory findings were investigated. Furthermore, outcome and treatment satisfaction were evaluated using magnetic resonance imaging (MRI) analyses and a modified questionnaire.

Results All 43 patients, who agreed to participate, were treated with therapeutic levels of heparin; 86% of children had an increased risk for thromboembolic events upon onset of CSVT (acute disease: 58.1%, perinatal risk factors: 9.3%, medical intervention/immobility: 14%, chronic disease: 16.3%). Thrombophilia markers showed positive results (e.g., reduced values for protein C/S, factor-V–Leiden mutation) in 58% of children at the time of CSVT diagnosis but dropping to 20.9% over the course of the disease. Forty-two of 43 patients received MRI follow-ups and the outcome showed complete recanalization in 69% of the patients and partial recanalization in 31%. At the onset of CSVT, 88% of patients reported restrictions in everyday life due to CSVT; at follow-up this percentage declined to 18%. Satisfaction with the outcome among parents/patients according to the questionnaire was high with 1.7 (German school grades from 1 to 6).

Conclusions All 42 children with MRI follow-up demonstrated complete or partial recanalization under anticoagulation. This positive result underlines the need for future studies on anticoagulation to optimize therapy regimens of pediatric CSVT.

Author Contributions

N.G. and B.Z. initiated and developed the design of the study. N.G., B.Z., and all other authors were involved in writing and reading the manuscript. M.B. performed the laboratory testing and contributed to writing the manuscript. H.G. performed the final revision.

All authors finally approved the final manuscript.


Ethics Approval

Ethical approval was received from the local Ethics Committee of Freiburg.


Consent to Participate

Informed consent was obtained from all participants or legal guardians included in the study.


Consent for Publication

All participants or legal guardians were informed in written form about publication of anonymized data.


* Shared authorship.


Supplementary Material



Publication History

Received: 27 November 2021

Accepted: 22 August 2022

Article published online:
10 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Grunt S, Wingeier K, Wehrli E. et al; Swiss Neuropaediatric Stroke Registry. Cerebral sinus venous thrombosis in Swiss children. Dev Med Child Neurol 2010; 52 (12) 1145-1150
  • 2 Bruhn HD, Hach-Wunderle V, Schambeck CM, Scharf RE. Hämostaseologie für die Praxis: Sicher durch den klinischen Alltag. Stuttgart; 2011
  • 3 Penn A, Snyder CA. 1,3 Butadiene, a vapor phase component of environmental tobacco smoke, accelerates arteriosclerotic plaque development. Circulation 1996; 93 (03) 552-557
  • 4 Younkin DP. Diagnosis and treatment of ischemic pediatric stroke. Curr Neurol Neurosci Rep 2002; 2 (01) 18-24
  • 5 Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V. International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol 2011; 69 (01) 130-140
  • 6 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341 (08) 586-592
  • 7 Li C, Miao JK, Xu Y. et al. Prenatal, perinatal and neonatal risk factors for perinatal arterial ischaemic stroke: a systematic review and meta-analysis. Eur J Neurol 2017; 24 (08) 1006-1015
  • 8 Dentali F, Crowther M, Ageno W. Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood 2006; 107 (07) 2766-2773
  • 9 Portegies MLP, Koudstaal PJ, Ikram MA. Cerebrovascular disease. Handb Clin Neurol 2016; 138: 239-261
  • 10 Ciccone A, Citterio A. Cerebral venous thrombosis. Lancet 2001; 357 (9269): 1706-1707
  • 11 Pourhassan S, Sandmann W. Gefäßerkrankungen im Kindes- und Jugendalter. Vol. 108–126. Heidelberg: Springer Verlag; 2010
  • 12 Ferro JM, Aguiar de Sousa D. Cerebral venous thrombosis: an update. Curr Neurol Neurosci Rep 2019; 19 (10) 74
  • 13 Capecchi M, Abbattista M, Martinelli I. Cerebral venous sinus thrombosis. J Thromb Haemost 2018; 16 (10) 1918-1931
  • 14 Ghoneim A, Straiton J, Pollard C, Macdonald K, Jampana R. Imaging of cerebral venous thrombosis. Clin Radiol 2020; 75 (04) 254-264
  • 15 Kurnik K, Bidlingmaier C, Hütker S, Olivieri M. [Haemostatic disorders in children]. Hamostaseologie 2016; 36 (02) 109-125
  • 16 Ichord R. Cerebral sinovenous thrombosis. Front Pediatr 2017; 5: 163
  • 17 Andrew M, deVeber G. Pediatric Thromboembolism and Stroke Protocols. Vol. 1–12. London: BC Dekcer Inc. Hamilton; 1999
  • 18 Monagle P, Chan AKC, Goldenberg NA. et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e737S-e801S
  • 19 Bethell CD, Read D, Stein REK, Blumberg SJ, Wells N, Newacheck PW. Identifying children with special health care needs: development and evaluation of a short screening instrument. Ambul Pediatr 2002; 2 (01) 38-48
  • 20 Robert Koch Institut. KiGGS Welle 2- Gesundheitliche Lage von Kindern und Jugendlichen. J Health Monitor 2018; 3: 1-120
  • 21 Leroy-Matheron C, Duchemin J, Levent M, Gouault-Heilmann M. Genetic modulation of plasma protein S levels by two frequent dimorphisms in the PROS1 gene. Thromb Haemost 1999; 82 (03) 1088-1092
  • 22 Duchemin J, Gandrille S, Borgel D. et al. The Ser 460 to pro substitution of the protein S alpha (PROS1) gene is a frequent mutation associated with free protein S (type IIa) deficiency. Blood 1995; 86 (09) 3436-3443
  • 23 Vielhaber H, Ehrenforth S, Koch HG, Scharrer I, van der Werf N, Nowak-Göttl U. Cerebral venous sinus thrombosis in infancy and childhood: role of genetic and acquired risk factors of thrombophilia. Eur J Pediatr 1998; 157 (07) 555-560
  • 24 Sébire G, Tabarki B, Saunders DE. et al. Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain 2005; 128 (Pt 3): 477-489
  • 25 Kenet G, Waldman D, Lubetsky A. et al. Paediatric cerebral sinus vein thrombosis: a multi-center, case-controlled study. Thromb Haemost 2004; 92 (04) 713-718
  • 26 deVeber G, Andrew M, Adams C. et al; Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345 (06) 417-423
  • 27 Gunes HN, Cokal BG, Guler SK. et al. Clinical associations, biological risk factors and outcomes of cerebral venous sinus thrombosis. J Int Med Res 2016; 44 (06) 1454-1461
  • 28 Golomb MR, Fullerton HJ, Nowak-Gottl U, Deveber G. International Pediatric Stroke Study Group. Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study. Stroke 2009; 40 (01) 52-57