Bozzola Elena

Bozzola Mauro

Calcaterra Valeria

Colafati Giovanna Stefania

Luciani Matteo

Villani A

Vittucci Annachiara

English

Bozzola et al. BMC Pediatrics 2014, 14:147http://www.biomedcentral.com/1471-2431/14/147CASE REPORT Open AccessMultiple cerebral sinus thromboses complicatingmeningococcal meningitis: a pediatric case reportElena Bozzola1*, Mauro Bozzola2, Giovanna Stefania Colafati3, Valeria Calcaterra2, Annachiara Vittucci1,Matteo Luciani4 and Alberto Villani1AbstractBackground: Cerebral venous sinus thrombosis (CVT) is a rare and potentially life-threatening condition in thepediatric population. The clinical presentation is frequently nonspecific; thus diagnosis is often delayed or missed.Case presentation: A previously healthy 8 month-old boy was diagnosed with meningococcal meningitis. At hospitaladmission, an urgent non contrast-enhanced computed tomography (CT) of the head and neck was performed withnormal results. Ceftriaxone was promptly started and the clinical condition of the patient improved. However, on the 7thday of hospitalization, the child suddenly manifested irritability and lethargy. An urgent contrast-enhanced CT of thehead and neck was immediately performed, revealing thrombosis of the superior sagittal, transverse and rectus sinuses.A thrombophilic evaluation was performed, revealing hyperhomocysteinemia and methylenetetrahydrofolate reductase(MTHFR) variants (C677T and A1298C).Conclusions: The causes of CVT may be categorized into three main groups: hypercoagulable states, conditions causingblood flow disturbances, and all causes of inflammation or infection. In this case report, we observed more than one riskfactor that predisposed the patient to CVT. Consequently, even if a causative factor is detected, a thrombophilic bloodevaluation should be performed. In fact, in case of a prothrombotic condition, the patient’s family should be advised thatprompt administration of anticoagulant is necessary in the event of situations that could lead to thrombosis. Finally, CVTmay be considered a possible complication of infection even when recent imaging results are normal. A prompt CVTdiagnosis is required to obtain a good outcome. Delayed diagnosis is mainly due to the rarity of the disease andphysicians’ unawareness of this type of complication.Keywords: Cerebral venous sinus thrombosis, Meningitis, Children, Thrombophilic evaluationBackgroundCerebral venous sinus thrombosis (CVT) is a rare, po-tentially life-threatening disorder that may have vital ormorbid consequences, such as motor dysfunction or vis-ual impairment. It predominantly affects adults in theirthird and fourth decades [1]. Even if high-quality epide-miologic studies are lacking, the available data suggestan incidence of 0.67 cases per 100,000 children per year.The prevalence of childhood CVT varies according toage; neonates are the most commonly affected [2-4].The signs and symptoms of CVT are frequently non-specific, often resulting in delayed or missed diagnosis[5]. In fact, CVT may present with a variety of signs and* Correspondence: elena.bozzola@opbg.net1Department of Pediatrics, Pediatric and Infectious Diseases Unit, BambinoGesù Children’s Hospital, IRCCS, Rome, ItalyFull list of author information is available at the end of the article© 2014 Bozzola et al.; licensee BioMed CentraCommons Attribution License (http://creativecreproduction in any medium, provided the orDedication waiver (http://creativecommons.orunless otherwise stated.symptoms, including irritability, headache, seizure, en-cephalopathy, papilledema, cranial nerve palsies, motorweakness and coma [6]. Studies suggest that promptdiagnosis and anticoagulant therapy may improve out-come in the majority of patients [2,4,7]. The causes ofCVT may be categorized into three main groups accord-ing to Virchow’s classification. The first group includesall hypercoagulable states. The second group consists ofconditions causing blood flow disturbances. Finally, thethird group comprises all causes of inflammation orinfection [8]. Among these, prothrombotic conditions,either genetic or acquired, malignancy, and head injuryare the most frequent causes. As regards infectiouscauses of CVT, these are responsible for only 6 to 12percent of cases [9]. Previous reports have cited sinusitis,otitis, and mastoiditis among the principal predisposingfactors. Although the frequency of septic thrombosis isl Ltd. This is an Open Access article distributed under the terms of the Creativeommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andiginal work is properly credited. The Creative Commons Public Domaing/publicdomain/zero/1.0/) applies to the data made available in this article,Bozzola et al. BMC Pediatrics 2014, 14:147 Page 2 of 4http://www.biomedcentral.com/1471-2431/14/147decreasing due to antibiotic development, recent studieshave demonstrated that CVT may be a complication ofmeningitis and sepsis in about 7% and 16% of cases,respectively [2,7,10].We describe the clinical case of a child with multiplesinovenous thromboses occurring after the diagnosis ofmeningococcal meningitis.Case presentationA previously healthy 8 month-old boy presented at theEmergency Department with high-grade fever, vomiting,and macular erythema of both upper limbs. No signsor symptoms of ear and upper respiratory infectionwere reported. Physical examination revealed a febrile,obtunded, and hypotonic child. Otoscopic findings aswell as throat examination were normal. Neck stiffnesswas noted. No neurological deficit or papilledema waspresent. Laboratory tests showed leukocytosis (27000/μL;normal value > 6000 and <17000/μL) and an increasedC-reactive protein (19,19 mg/dl; normal value below0,5 mg/dl). An urgent non-contrast computed tomog-raphy (CT) of the head and neck was performed, withnormal results. Bacterial meningitis was suspected and alumbar puncture confirmed the diagnosis. The cerebro-spinal fluid (CSF) was opalescent with 33900 white bloodcells, increased total protein (304,2 mg/dl) and normal glu-cose levels (37 mg/dl). Serum glucose level was also normal(106 mg/dl).The child received intravenous dexamethasone andceftriaxone as empiric treatment. Neisseria Meningitis Cwas confirmed in both blood and CSF cultures. Twodays later, the child’s condition improved, with feverresolution. Suddenly, seven days after hospital admis-sion, the child manifested irritability and lethargy. More-over, a bulging fontanel was noted at the physicalexamination. An urgent contrast-enhanced CT of thehead and neck was immediately performed and revealedthrombosis of the superior sagittal, transverse and rectussinuses (Figure 1). Heparin treatment was started inorder to recanalize the occluded sinuses and to preventthe propagation of thrombi. A thrombophilic evaluationwas performed which revealed hyperhomocysteinemiaand methylenetetrahydrofolate reductase (MTHFR) vari-ants (C677T and A1298C). One week later, a new CTrevealed a recanalization of the previously involved si-nuses, without parenchymal damage. Consequently, thepatient was discharged under treatment with subcutane-ous low molecular weight heparin (LMWH). At followup five months later, the child was in good clinical con-dition with normal magnetic resonance imaging (MRI)results (Figure 2). The anticoagulant therapy was discon-tinued, but the family was advised to administer antico-agulants in case of situations that could predispose tothrombosis.ConclusionsAccording to the literature, CVT may be caused by hy-percoagulable states, by conditions causing blood flowdisturbances, or by inflammation/infection [5]. In ourcase report, we observed more than one risk factor thatpredisposed to CVT. We speculate that the genetic pro-thrombotic condition predisposed to CVT, which wastriggered by a central nervous system infection. In fact,the CT scan was normal at both meningitis onset andpost-discharge follow-up. For this reason, thrombophilicevaluation should be encouraged in all children withCVT, independent of other established risk factors suchas meningitis, in order to identify children with in-creased risk factors for thrombophilia. Thrombophiliamay be defined as a high risk for thrombosis, which canbe either inherited or acquired. The percentage of patientswith CVT who have an identified risk factor for thrombo-philia varies significantly from study to study, from 33% to99% [11]. Moreover, there is no consensus as to whichbaseline studies should be included in a standard hyperco-agulability evaluation [12]. In one report, anticardiolipinantibody was the most common prothrombotic risk factor,while in another the homozygous MTHFR mutation wasthe most common [2,8]. A German study reported casesin which either elevated lipoprotein A or protein C defi-ciency was associated with CVT; in an American study,protein C and antithrombin III deficiencies were common[7,13]. Other potential procoagulant markers recently con-sidered in CVT include anemia, hyperhomocysteinemia,and factor VIII levels.In the event of a prothrombotic diagnosis, the patient’sfamily should be advised to administer drugs (antiplate-let or anticoagulant agents) in situations that could leadto thrombosis. In fact, patients recovering from CVT areat risk of recurrence or other thrombotic event [8]. Itshould be explained to patients that testing of their firstdegree relatives for heritable thrombophilia will allow thedetection of affected but asymptomatic family members.Because of its nonspecific presentation, diagnosis ofCVT may be delayed and even missed. Clinicians mustmaintain a high index of suspicion when treating anychild with an acute central nervous system infection andpresenting neurological signs and symptoms despite ad-ministration of appropriate therapy.Imaging should be considered to rule out intracranialcomplications. The currently available diagnostic toolsinclude head CT, MRI and MR venogram [4,6]. Of these,head CT is the most commonly performed examinationwhen sinus thrombosis is suspected [2]. Diagnostic sen-sitivity is increased with the addition of a postcontrast CT.The empty delta sign, a classic signature of CVT, is presenton post-contrast CT in 10% to 30% of cases. On head CTwith contrast, the empty delta sign may be seen as a tri-angular pattern of contrast enhancement surrounding aFigure 2 Axial T2w (a) and axial T1w images without (b) and with contrast (c), magnetic resonance venography (d) and sagittal T1wwith contrast (e).ac dbFigure 1 Head computed tomography images without (a,b) and with (c,d) contrast; axial (a,c) and reformatted sagittal (b,d) images.Note the empty delta sign (c, arrow).Bozzola et al. BMC Pediatrics 2014, 14:147 Page 3 of 4http://www.biomedcentral.com/1471-2431/14/147Bozzola et al. BMC Pediatrics 2014, 14:147 Page 4 of 4http://www.biomedcentral.com/1471-2431/14/147central region which lacks contrast enhancement in theposterior part of the superior sagittal sinus [2,4]. A densecord sign (hyperdense fresh blood clot) is seen on noncon-trast head CT in 1% to 5% of cases [4]. A previous normalresult, even if performed just a few days prior, should notinfluence the clinician’s decision to repeat the exam. Incase of CVT, follow-up imaging of the venous sinuses isgenerally performed in order to check thrombosis evolu-tion. The mainstay of CVT treatment is anticoagulationand supportive care. The purpose of anticoagulant therapyis to limit the propagation of an existing clot and toprevent the formation of further thrombi [2,4]. Previousstudies have reported encouraging data on the safetyof anticoagulation therapy in children with CVT andon improved cognitive outcome [2,7]. Although definitiveevidence of effectiveness is lacking, there is a generalconsensus that anticoagulation with unfractionated intra-venous heparin or subcutaneous LMWH is appropriatetreatment for acute CVT [14]. The treatment most usedfor infants and children is LMWH for 7–10 days (120-180 UI/kg twice a day in children up to 1 year of age, and100 UI/Kg twice a day in older patients) followed by oralanticoagulants or antiplatelets generally for 3–6 months[7]. Therapy is generally discontinued 6 months after theacute phase but may be prolonged after hematologicalevaluation depending on the patient’s age and clinicalcondition. Instructions to the family at patient’s dischargeinclude the necessity to continue anticoagulation afterthe acute phase in order to prevent CVT recurrence.Finally, CVT in children sometimes has a poor prog-nosis despite prompt diagnosis and therapy. Commonlyidentified morbidities include motor dysfunction, neuro-psychiatric disorders, visual impairment, pseudotumorcerebri, seizures, and headaches [4]. In our case, eventhough CVT involved multiple sinuses and the child wasaffected by both meningitis and sepsis, the prognosiswas good, with no sequelae at five months follow-up. Theearly diagnosis led to prompt therapy and consequentlyenabled a good neurodevelopmental outcome.ConsentWritten informed consent was obtained from the pa-tient’s mother for publication of these data and for theaccompanying images. A copy of the written consent isavailable for review by the Editor of this Journal.Competing interestsThe authors have no competing interests to declare.Authors’ contributionBE provided medical assistance to the patient and collected medicalinformation, BM and CV revised the literature, CGS supervised theneuroradiological examination included in the case report, LM supervisedthe hematological examination included in the case report, VA was involvedin the clinical follow-up of the patient, VA supervised the patient treatmentplan. All authors read and approved the final manuscript.AcknowledgementsThe authors are grateful to Mrs Jean Ringrose for revising the Englishlanguage of the paper.Author details1Department of Pediatrics, Pediatric and Infectious Diseases Unit, BambinoGesù Children’s Hospital, IRCCS, Rome, Italy. 2Fondazione IRCCS San MatteoPavia, Department of Internal Medicine, University of Pavia, Pavia, Italy.3Neuroradiology Unit, Department of Imaging, Bambino Gesù Children’sHospital, IRCCS, Rome, Italy. 4Department of Hematology, Oncology andTrasfusion Medicine, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.Received: 10 February 2014 Accepted: 27 May 2014Published: 13 June 2014References1. Algahtani HA, Aldarmahi AA: Cerebral sinus venus thrombosis.Neurosciences (Riyadh) 2014, 19(1):11–16.2. deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ, Camfield CS,David M, Humphreys P, Langevin P, MacDonald EA, Gillett J, Meaney B,Shevell M, Sinclair DB, Yager J, Canadian Pediatric Ischemic Stroke StudyGroup: Cerebral sinovenous thrombosis in children. N Engl J Med 2001,345(6):417–423.3. Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B,Cushman M, deVeber G, Ferro JM, Tsai FY, American Heart AssociationStroke Council and the Council on Epidemiology and Prevention: Diagnosisand management of cerebral venous thrombosis: a statement forhealthcare professionals from the American Heart Association/AmericanStroke Association. Stroke 2011, 42:1158.4. Carpenter J, Tsuchida T: Cerebral sinovenous thrombosis in children.Curr Neurol Neurosci Rep 2007, 7(2):139–146.5. Matar NE, Rassi SJ, Melkane AE, Haddad AC: Lateral sinus thrombosis inthe pediatric population: multiple presentations for a potentially lethaldisease. Pediatr Emerg Care 2009, 25(10):681–683.6. Hedlund GL: Cerebral sinovenous thrombosis in pediatric practice.Pediatr Radiol 2013, 43(2):173–188.7. Sébire G, Tabarki B, Saunders DE, Leroy I, Liesner R, Saint-Martin C, Husson B,Williams AN, Wade A, Kirkham FJ: Cerebral venous sinus thrombosis inchildren: risk factors, presentation, diagnosis and outcome. Brain 2005,128:477–489.8. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F: ISCVTInvestigators. Prognosis of cerebral vein and dural sinus thrombosis:results of the International Study on Cerebral Vein and Dural SinusThrombosis (ISCVT). Stroke 2004, 35:664.9. Carvalho KS, Bodensteiner JB, Connolly PJ, Garg BP: Cerebral venousthrombosis in children. J Child Neurol 2000, 16:574–580.10. Fitzgerald KC, Golomb MR: Neonatal Arterial Ischemic Stroke andSinovenous Thrombosis Associated With Meningitis. J Child Neurol 2007,22:818.11. Chan A, de Veber G: Prothrombotic disorders and ischemic stroke inchildren. Semin Pediatr Neurol 2000, 7:301–308.12. Mullins M, Grant P, Wang B, Gonzales RG, Schaefer PW: Parenchymalabnormalities associated with cerebral venous sinus thrombosis:assessment with diffusion-weighted MR imaging. Am J Neuroradiol 2004,25:1666–1675.13. Heller C, Heinecke A, Junker R, Knofler R, Kosch A, Kurnik K, Schobess R,von Eckardstein A, Strater R, Zieger B, Nowak-Gottl U, Childhood StrokeStudy Group: Cerebral venous thrombosis in children: a multifactorialorigin. Circulation 2003, 108:1362–1367.14. Coutinho JM, Stam J: How to treat cerebral venous and sinus thrombosis.J Thromb Haemost 2010, 8:877.doi:10.1186/1471-2431-14-147Cite this article as: Bozzola et al.: Multiple cerebral sinus thrombosescomplicating meningococcal meningitis: a pediatric case report. BMCPediatrics 2014 14:147.

Multiple cerebral sinus thromboses complicating meningococcal meningitis: a pediatric case report

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Multiple cerebral sinus thromboses complicating meningococcal meningitis: a pediatric case report

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