Download PDF
Thromb Haemost 2015; 113(06): 1270-1277
DOI: 10.1160/TH14-05-0431
Coagulation and Fibrinolysis
Schattauer GmbH

Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis

First report from the Italian Registry of Pediatric Thrombosis (R. I. T. I., Registro Italiano Trombosi Infantili)
Agnese Suppiej
1   Child Neurology Unit, Pediatric University Hospital of Padua, Padua, Italy
,
Chiara Gentilomo
2   Department of Pediatrics, Dell’Angelo Hospital, Venice, Italy
,
Paola Saracco
3   Pediatric Hematology and Oncology, University of Turin, Hospital Regina Margherita Turin, Italy
,
Stefano Sartori
1   Child Neurology Unit, Pediatric University Hospital of Padua, Padua, Italy
,
Manuela Agostini
4   Department of Pediatrics, University of Turin, Hospital Regina Margherita Turin, Italy
,
Rossana Bagna
4   Department of Pediatrics, University of Turin, Hospital Regina Margherita Turin, Italy
,
Bianca Bassi
5   Child Neuropsichiatry, University of Turin, Hospital Regina Margherita Turin, Italy
,
Paola Giordano
6   Pediatric Hematology and Oncology, University of Bari, Italy
,
Massimo Grassi
6   Pediatric Hematology and Oncology, University of Bari, Italy
,
Andrea Guzzetta
7   Department of Developmental Neurosciences, IRCCS Stella Maris, Pisa, Italy
,
Donatella Lasagni
9   Department of Hematology and Oncology and Transfusional Medicine, IRCCS Pediatric Hospital Bambin Gesù, Rome, Italy
,
Matteo Luciani
9   Department of Hematology and Oncology and Transfusional Medicine, IRCCS Pediatric Hospital Bambin Gesù, Rome, Italy
,
Angelo C. Molinari
10   Thrombosis and Hemostasis Unit, Department of Hematology and Oncology, IRCCS Giannina Gaslini, Genoa, Italy
,
Antonella Palmieri
11   Department of Pediatric Emergency, IRCCS Giannina Gaslini, Genoa, Italy
,
Maria Caterina Putti
12   Department of Oncology and Hematology, University Hospital of Padua, Padua, Italy
,
Luca Antonio Ramenghi
13   Neonatal Intensive Care Unit, IRCCS Gaslini Institute, Genoa, Italy
,
Lidia Luciana Rota
14   Cardiovascular Prevention Center, Humanitas Research Hospital, Milan, Italy
,
Domenico Sperlì
15   Pediatric Department, Annunziata Hospital, Cosenza, Italy
,
Anna Maria Laverda
1   Child Neurology Unit, Pediatric University Hospital of Padua, Padua, Italy
,
Paolo Simioni
16   Department of Medicine, Coagulation Diseases Unit, University of Padua Medical School, Padua, Italy
,
the Stroke working group of the R. I. T. I. (Registro Italiano Trombosi Infantili) › Author Affiliations
Further Information

Publication History

Received: 13 May 2014

Accepted after major revision: 14 January 2015

Publication Date:
22 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Data from large case series of children with cerebral thrombotic events are pivotal to improve prevention, early recognition and treatment of these conditions. The Italian Registry of Pediatric Thrombosis (R. I. T. I.) was established in 2007 by a multidisciplinary team, aiming for a better understanding of neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols. We analysed data relative to the paediatric cerebral thrombotic events of the R. I. T. I. which occurred between January 2007 and June 2012. In the study period, 79 arterial ischaemic stroke (AIS) events (49 in males) and 91 cerebral sinovenous thrombosis (CSVT) events (65 in males) were enrolled in the R. I. T. I. Mean age at onset was 4.5 years in AIS, and 7.1 years in CSVT. Most common modes of presentation were hemiparesis, seizures and speech disturbances in AIS, and headache, seizures and lethargy in CSVT. Most common etiologies were underlying chronic diseases, vasculopathy and cardiopathy in AIS, and underlying chronic diseases and infection in CSVT. Time to diagnosis exceeded 24 hours in 46 % AIS and 59 % CSVT. Overall data from the Italian Registry are in substantial agreement with those from the literature, despite small differences. Among these, a longer time to diagnosis compared to other registries and case series poses the accent to the need of an earlier recognition of paediatric cerebrovascular events in Italy, in order to enable prompt and effective treatment strategies.

Keywords

Thrombosis - AIS - CSVT - children - registry - Italy

 

  • References

  • 1 Steinlin M, Pfister I, Pavlovic J. et al. The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors. Neuropaediatrics 2005; 36: 90-97.
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Grunt S, Wingeier K, Wehrli E. et al. Cerebral sinus venous thrombosis in Swiss children. Dev Med Child Neurol 2010; 52: 1145-1150.
    CrossrefPubMedSearch in Google Scholar
  • 3 Martin C, von Elm E, El-Koussy M. et al. Delayed diagnosis of acute ischemic stroke in children - a registry-based study in Switzerland. Neuropaediatric Stroke Registry study group. Swiss Med Wkly 2011; 141: w13281.
    PubMedSearch in Google Scholar
  • 4 Bonduel M, Sciuccati G, Hepner M. et al. Arterial ischemic stroke and cerebral venous thrombosis in children: a 12-year Argentinean registry. Acta Haematol 2006; 115: 180-185.
    CrossrefPubMedSearch in Google Scholar
  • 5 deVeber G, Andrew M, Adams C. et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345: 417-423.
    CrossrefPubMedSearch in Google Scholar
  • 6 Sträter R, Kurnik K, Heller C. et al. Aspirin versus low-dose low-molecularweight heparin: antithrombotic therapy in paediatric ischemic stroke patients: a prospective follow-up study. Stroke 2001; 32: 2554-2558.
    CrossrefPubMedSearch in Google Scholar
  • 7 Sträter R, Becker S, von Eckardstein A. et al. Prospective assessment of risk factors for recurrent stroke during childhood--a 5-year follow-up study. Lancet 2002; 360: 1540-1545.
    CrossrefPubMedSearch in Google Scholar
  • 8 Heller C, Heinecke A, Junker R. et al. Cerebral venous thrombosis in children: a multifactorial origin. Circulation 2003; 108: 1362-1367.
    CrossrefPubMedSearch in Google Scholar
  • 9 Kenet G, Waldman D, Lubetsky A. et al. Paediatric cerebral sinus vein thrombosis. A multi-centre, case-controlled study. Thromb Haemost 2004; 92: 713-718.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Tuckuviene R, Christensen AL, Helgestad J. et al. Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis in Denmark 1994-2006: a nationwide population-based study. Acta Paediatr 2011; 100: 543-549.
    CrossrefPubMedSearch in Google Scholar
  • 11 Ganesan V, Prengler M, McShane MA. et al. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol 2003; 53: 167-173.
    CrossrefPubMedSearch in Google Scholar
  • 12 Amlie-Lefond C, deVeber G, Chan AK. et al. Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2009; 08: 530-536.
    CrossrefPubMedSearch in Google Scholar
  • 13 Amlie-Lefond C, Bernard TJ, Sébire G. et al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Paediatric Stroke Study. Circulation 2009; 119: 1417-1423.
    CrossrefPubMedSearch in Google Scholar
  • 14 Amlie-Lefond C, Chan AK, Kirton A. et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in paediatric stroke clinical trial. Neuroepidemiology 2009; 32: 279-286.
    CrossrefPubMedSearch in Google Scholar
  • 15 Golomb MR, Fullerton HJ, Nowak-Gottl U. et al. Male predominance in childhood ischemic stroke: findings from the international paediatric stroke study. Stroke 2009; 40: 52-57.
    CrossrefPubMedSearch in Google Scholar
  • 16 Goldenberg NA, Bernard TJ, Fullerton HJ. et al. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2009; 08: 1120-1127.
    CrossrefPubMedSearch in Google Scholar
  • 17 Mackay MT, Wiznitzer M, Benedict SL. et al. Arterial ischemic stroke risk factors: the International Paediatric Stroke Study. Ann Neurol 2011; 69: 130-140.
    CrossrefPubMedSearch in Google Scholar
  • 18 Golomb MR, MacGregor DL, Domi T. et al. Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. Ann Neurol 2001; 50: 163-168.
    CrossrefPubMedSearch in Google Scholar
  • 19 Suppiej A, Franzoi M, Gentilomo C. et al. High prevalence of inherited thrombophilia in 'presumed peri-neonatal' ischemic stroke. Eur J Haematol 2008; 80: 71-75.
    PubMedSearch in Google Scholar
  • 20 Simioni P. Who should be tested for thrombophilia?. Curr Opin Hematol 2006; 16: 337-343.
    PubMedSearch in Google Scholar
  • 21 Teksam M, Moharir M, Deveber G. et al. Frequency and topographic distribution of brain lesions in paediatric cerebral venous thrombosis. Am J Neuroradiol 2008; 29: 1961-1965.
    CrossrefPubMedSearch in Google Scholar
  • 22 Zafar A, Ali Z. Pattern of magnetic resonance imaging and magnetic resonance venography changes in cerebral venous sinus thrombosis. J Ayub Med Coll Abbottabad 2012; 24: 63-67.
    PubMedSearch in Google Scholar
  • 23 Dlamin N, Billinghurst L, Kirkham FJ. Cerebral venous sinus (sinovenous) thrombosis in children. Neurosurg Clin N Am 2010; 21: 511-527.
    CrossrefPubMedSearch in Google Scholar
  • 24 Sébire G, Fullerton H, Riou E. et al. Toward the definition of cerebral arteriopathies of childhood. Curr Opin Paediatr 2004; 16: 617-622.
    CrossrefPubMedSearch in Google Scholar
  • 25 Sébire G. Transient cerebral arteriopathy in childhood. Lancet 2006; 368: 8-10.
    CrossrefPubMedSearch in Google Scholar
  • 26 Danchaivijitr N, Cox TC, Saunders DE. et al. Evolution of cerebral arteriopathies in childhood arterial ischemic stroke. Ann Neurol 2006; 59: 620-626.
    CrossrefPubMedSearch in Google Scholar
  • 27 Centres for Disease Control and Prevention (CDC). Prehospital and hospital delays after stroke onset--United States, 2005-2006. Morb Mortal Wkly Rep 2007; 56: 474-478.
    PubMedSearch in Google Scholar
  • 28 Addo J, Ayis S, Leon J. et al. Delay in presentation after an acute stroke in a multiethnic population in South London: the South London Stroke Register. J Am Heart Assoc 2012; 01: e001685.
    PubMedSearch in Google Scholar
  • 29 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581-1587.
    CrossrefPubMedSearch in Google Scholar
  • 30 Intercollegiate Stroke Working Party. National clinical guideline for stroke, 4th edition.. London: Royal College of Physicians, 2012..
    PubMed
  • 31 Hacke W, Kaste M, Bluhmki E. et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359: 1317-1329.
    CrossrefPubMedSearch in Google Scholar
  • 32 Paediatric Stroke Working Group. Stroke in childhood: Clinical guidelines for diagnosis, management and rehabilitation. November 2004. www.rcplondon.ac.uk/pubs/books/childstroke/ (Accessed on January 14, 2011).
    PubMed
  • 33 Roach ES, Golomb MR, Adams R. et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008; 39: 2644-2691.
    CrossrefPubMedSearch in Google Scholar
  • 34 Monagle P, Chan AK, 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: e737S-e801S.
    CrossrefPubMedSearch in Google Scholar
  • 35 Guo XB, Guan S, Fan Y. et al. Local thrombolysis for severe cerebral venous sinus thrombosis. Am J Neuroradiol 2012; 33: 1187-1190.
    CrossrefPubMedSearch in Google Scholar
  • 36 Mohammadian R, Sohrabi B, Mansourizadeh R. et al. Treatment of progressive cerebral sinuses thrombosis with local thrombolysis. Interv Neuroradiol 2012; 18: 89-96.
    CrossrefPubMedSearch in Google Scholar
  • 37 Einhäupl K, Stam J, Bousser MG. et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol 2010; 17: 1229-1235.
    CrossrefPubMedSearch in Google Scholar
  • 38 Janjua N, Nasar A, Lynch JK. et al. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 2007; 38: 1850-1854.
    CrossrefPubMedSearch in Google Scholar
  • 39 Alshekhlee A, Geller T, Mehta S. et al. Thrombolysis for children with acute ischemic stroke: a perspective from the kids’ inpatient database. Paediatr Neurol 2013; 49: 313-318.
    CrossrefPubMedSearch in Google Scholar
  • 40 Mallick AA, Sharples PM, Calvert SE. et al. Cerebral venous sinus thrombosis: a case series including thrombolysis. Arch Dis Child 2009; 94: 790-794.
    CrossrefPubMedSearch in Google Scholar
  • 41 Kenet G, Kirkham F, Niederstadt T. et al. European Thromboses Study Group. Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study. Lancet Neurol 2007; 06: 595-603.
    CrossrefPubMedSearch in Google Scholar